Ankle Swelling Research Articles

Clinical evaluation of the low-salt dietary interventions impact on arterial hypertension

Purpose . The estimation of low-salt dietary interventions impact on arterial hypertension clinical manifestation. Materials and methods . A randomized study was conducted with an intervention period of 4-weeks in 82 hypertensive subjects (52 women, 30 men) aged 47–76 years. All patients received baseline antihypertensive therapy with inadequate blood pressure (BP) control below 140/90 mm Hg. Patients were randomized on 2 groups, adjusted by age and sex. The first group included 41 subjects received standard recommendations for nutrition. Patients of the second group received a detailed explanation of the low-salt diet with indication on using low- salt supplement (consisting of 70 % NaCl, 30 % KCl) instead of the usual table salt. We analyzed the dynamics of BP, clinical signs, the data from the questionnaires, the frequency of urgent hypertensive cases, the frequency of patient’s re-visit to physicians regarding changes in antihypertensive treatment regimen during the observation period, data of objective examination. Results. According to the “office” measurements of BP, a general tendency to decrease the BP level in both groups has been noted. The diastolic BP level in the second clinical group was significantly lower than in the control group. The number of patients with “office” BP above 140/90 mmHg in the control group decreased by 27 %, in the second group – by 63.5 % (P < 0.0001). Intensive dietary interventions for salt reduction intake were associated with a significant reduction of the manifestation of ankle swelling (OR = 0.19; P = 0.0016). In the second group, hypertensive urgent cases were registered twice as less than in the control group (OR = 0.38; P = 0.11). The frequency of re-visit of the physician for the treatment correction has been noted in 48 % of first group patients and in 12 % in the second group (OR = 0.15, P < 0.001). Conclusions. Intensive low-salt dietary interventions have been associated with better blood pressure control in hypertensive patients received antihypertensive therapy. Low-sodium salt, enriched with 30 % potassium chloride, can be used as a supplement for effective control of blood pressure, helps to reduce ankle swelling manifestations and to lower the frequency of short-term re-visits to the physician for the correction of the antihypertensive treatment, compared with patients who accepted usual dietary recommendations.

4-(2-(4-chlorophenyl)-1-((4-chlorophenyl)amino)ethyl)benzene-1, 3-diol is a potential agent for gout therapy as a dual inhibitor of XOD and NLRP3

BackgoundGout is an inflammatory arthritis characterized by abrupt self-limiting attacks of inflammation caused by precipitation of monosodium urate crystals (MSU) in the joint. Both anti-hyperuricemia and anti-inflammation could be gout therapeutic strategies, whereas ideal drugs for gout treatment are deficient. Purpose4-(2-(4-chlorophenyl)-1-((4-chlorophenyl)amino)ethyl)benzene-1, 3-diol (CBED) was obtained from a cluster of deoxybenzoins derivatives synthesized by our research group with potent anti-hyperuricemic and anti-inflammatory activities, which was expected to be a dual inhibitor of xanthine oxidase (XOD) and NOD-like receptor protein 3 (NLRP3). This study aimed to investigate effects of CBED on XOD and NLRP3 in vitro, as well as the possible mechanisms by which CBED improved gout in vivo. MethodsAfter molecular docking detection, inhibitory effects of CBED on XOD and NLRP3 were evaluated in vitro. Subsequently, hyperuricemia and acute gouty arthritis animal models were established by potassium oxonate or MSU, respectively. After CBED treatment, serum uric acid levels, synovial interleukin (IL)-1β concentrations, hepatic XOD activities, as well as synovial morphological changes were examined. More importantly, synovial expressions of NLRP3 inflammasome components including NLRP3, apoptosis-associated speck-like protein (ASC) and caspase-1 in rats were analyzed by immunofluorescence and western blot. ResultsIn vitro, CBED obviously inhibited XOD activity with an IC50 value of 3.87 µM, moreover, it effectively inhibited MSU-induced NLRP3 inflammasome activation and IL-1β over-production in THP-1 cells. In addition, CBED dose-dependently decreased serum uric acid levels suppressed hepatic XOD activities in oxonate-induced hyperuricemic mice. On the other hand, CBED significantly improved MSU-induced ankle swelling and histopathological damage with elevated IL-1β. In addition, NLRP3 inflammasome activation could be blocked by CBED treatment in rats with acute gouty arthritis. Notbly, CBED exhibited no effects on all these indicators in normal animals, predicting its safety. ConclusionsCBED might serve as a dual XOD and NLRP3 inhibitor for treatment of gout.

Diffuse Pigmented Villonodular Synovitis Around the Ankle.

Pigmented villonodular synovitis (PVNS) is a rare disorder around the ankle joint. The optimal treatment for diffuse-type PVNS is still controversial because of the high incidence of recurrence. We present the clinical features of our patients and review the current diagnostic and treatment modalities. Five patients with PVNS located around the ankle were surgically treated. In three patients, diffuse PVNS arose from the ankle joint, and in the other two it arose from the calcaneocuboid and intercuneiform joints. The average follow-up time after surgery was 2.9 years (range, 2-4.6 years). The average time between onset of pain and diagnosis of PVNS was 6.4 years (range, 4-10 years). Arthrotomic tumor resection was performed in all of the patients. In the three patients with ankle joint PVNS, both medial and lateral approaches were used. One patient experienced mild infection at the surgical site, but this healed conservatively. No tumor recurrences had occurred after minimum follow-up of 2 years, although mild pain persisted in the three patients with ankle PVNS. Diagnosis of diffuse PVNS is frequently delayed due to vague symptoms and variable growth patterns. Orthopedic clinicians should be aware of the existence of this lesion, and it should be suspected in patients with persistent ankle swelling. To prevent tumor recurrence, accurate evaluation of tumor location and careful operative planning are mandatory. A combined surgical approach involving medial and lateral incision is necessary to expose the entire joint cavity.

Increased hyperpolarized [1‐13C] lactate production in a model of joint inflammation is not accompanied by tissue acidosis as assessed using hyperpolarized 13C‐labelled bicarbonate

Arthritic conditions are a major source of chronic pain. Furthering our understanding of disease mechanisms creates the opportunity to develop more targeted therapeutics. In rheumatoid arthritis (RA), measurements of pH in human synovial fluid suggest that acidosis occurs, but that this is highly variable between individuals. Here we sought to determine if tissue acidosis occurs in a widely used rodent arthritis model: complete Freund's adjuvant (CFA)‐induced inflammation. CFA robustly evoked paw and ankle swelling, concomitant with worsening clinical scores over time. We used magnetic resonance spectroscopic imaging of hyperpolarized [1‐13C]pyruvate metabolism to demonstrate that CFA induces an increase in the lactate‐to‐pyruvate ratio. This increase is indicative of enhanced glycolysis and an increased lactate concentration, as has been observed in the synovial fluid from RA patients, and which was correlated with acidosis. We also measured the 13CO2/H13CO3 − ratio, in animals injected with hyperpolarized H13CO3 −, to estimate extracellular tissue pH and showed that despite the apparent increase in glycolytic activity in CFA‐induced inflammation there was no accompanying decrease in extracellular pH. The pH was 7.23 ± 0.06 in control paws and 7.32 ± 0.09 in inflamed paws. These results could explain why mice lacking acid‐sensing ion channel subunits 1, 2 and 3 do not display any changes in mechanical or thermal hyperalgesia in CFA‐induced inflammation.

Unilateral Plantar Erythema Nodosum in Sarcoidosis

A 32-year old male Caucasian patient presented with mild exertional dyspnea, pain and swelling of both ankles, and general malaise. On examination symmetrical arthritis of both ankles and a vivid nodular erythema with slight pain on pressure was detected on the sole of the right foot (A). A therapy with ibuprofen had not led to any improvement of symptoms. This article is protected by copyright. All rights reserved.

Pattern, Precipitants and Short Term Outcome of Heart Failure Patients Managed at Federal Medical Centre Nguru, a Tertiary Health Centre in Yobe State Northeastern Nigeria

Heart Failure (HF) is a syndrome characterized by typical symptoms (e.g. breathlessness, ankle swelling and fatigue) that may be accompanied by signs (e.g. elevated jugular venous pressure, pulmonary crackles and peripheral oedema) caused by a structural and/or functional cardiac abnormality, resulting in a reduced cardiac output and/or elevated intracardiac pressures at rest or during stress. Clinical studies investigating the aetiological patterns of heart failure in Sub-Saharan Africa (SSA) revealed that hypertension, cardiomyopathy and rheumatic heart disease account for more than two-thirds of cardiac disease cases. The objective of this study therefore is to assess the pattern, precipitating factors and short term outcome of heart failure among patients admitted into our hospital. Method: The study was a prospective cross-sectional type conducted among in patients with heart failure in the medical ward of the hospital. Results: A total of three and fifty four (354) subjects were recruited into the study, comprising one hundred and twenty nine males (36.4%) and two hundred and twenty five (63.4%) females. Majority of the patients were admitted in NYHA functional class IV. This however improved to class II at discharge though few were discharged in NYHA class III. Heart failure secondary to progressive hypertensive heart disease was the most common (39.0%) followed by peripartum cardiomyopathy (22.6%) while idiopathic dilated cardiomyopathy (11.0%) and rheumatic heart disease (7.3%) were the third and fourth causes of heart failure respectively. The most common precipitating factor for heart failure in this study was chest infection (44.9%). In conclusion, the study revealed that progressive hypertensive heart disease was the leading cause of heart failure, followed by peripartum cardiomyopathy while idiopathic dilated cardiomyopathy and rheumatic heart disease were ranked third and fourth causes of heart failure respectively. Though myocardial infarction is on the increase, it was found to be the fifth cause of heart failure. The study also identified the following precipitants of heart failure in decreasing order of occurrence: chest infection, non-adherence to prescription, and urinary tract infection.

Medication Adherence Mediates the Relationship Between Heart Failure Symptoms and Cardiac Event-Free Survival in Patients With Heart Failure.

Heart failure (HF) symptoms such as dyspnea are common and may precipitate hospitalization. Medication nonadherence is presumed to be associated with symptom exacerbations, yet how HF symptoms, medication adherence, and hospitalization/death are related remains unclear. The aim of this study was to explore the relationships among HF symptoms, medication adherence, and cardiac event-free survival in patients with HF. At baseline, patient demographics, clinical data, and HF symptoms were collected in 219 patients with HF. Medication adherence was monitored using the Medication Event Monitoring System. Patients were followed for up to 3.5 years to collect hospitalization and survival data. Logistic regression and survival analyses were used for the analyses. Patients reporting dyspnea or ankle swelling were more likely to have poor medication adherence (P = .05). Poor medication adherence was associated with worse cardiac event-free survival (P = .006). In Cox regression, patients with HF symptoms had 2 times greater risk for a cardiac event than patients without HF symptoms (P = .042). Heart failure symptoms were not a significant predictor of cardiac event-free survival after entering medication adherence in the model (P = .091), indicating mediation. Medication adherence was associated with fewer HF symptoms and lower rates of hospitalization and death. It is important to develop interventions to improve medication adherence that may reduce HF symptoms and high hospitalization and mortality in patients with HF.

Implementing a Protocol to Improve Self-Care Behaviors in Adult Patients With Heart Failure.

Heart failure (HF) is a condition that affects millions of Americans and costs $30 billion to treat annually. HF is the cause for frequent hospitalizations. Self-care practices have been found to improve quality of life, decrease hospitalizations, and reduce treatment costs. Fifteen adult patients with a HF diagnosis ages 18 to 70 voluntarily participated in the implementation of a protocol aimed at improving self-care behaviors in patients with HF in a private cardiology practice located in a southeastern city. The project was a quality improvement design. A protocol was implemented using resources from the American Heart Association. Monitoring logs were provided to patients to record daily weights, sodium intake, blood pressure, and symptoms. Educational resources included information about medications and a list of valid HF websites. Participants were provided medication organizers and a two-liter container with which to monitor daily fluid intake. The written information and logs were compiled in red folders. Of the 15 participants, there were no hospital admissions or readmissions for HF during the implementation period. Leg and ankle swelling worsened; dyspnea improved; fewer participants felt like a burden to their family; HF knowledge improved. The findings indicate the feasibility of implementing the protocol throughout a private practice organization.

Comparative Studies of Different Extracts from Eucommia ulmoides Oliv. against Rheumatoid Arthritis in CIA Rats.

To compare efficacy of different extracts from Eucommia ulmoides Oliv. with both immune inflammation and joint destruction in collagen induced arthritis (CIA) rat model. Rats were divided into normal group (Nor), control group (CIA), TG group (treated with tripterygium glycoside), E70 group (treated with 70% ethanol extract from Eucommia ulmoides Oliv.), EA group (treated with ethyl acetate fraction from E70), and EN group (treated with n-butyl alcohol fraction from E70). All extracts from Eucommia ulmoides Oliv. could significantly inhibit ankle swelling, pathological manifestations, and cytokine levels in serum and spleen, by using foot volume measurement, H&E staining, ELISA, and RT-QPCR methods, respectively. All extracts could significantly inhibit rough joint surface and marginal osteophytes, improve RANKL/OPG ratio, and decrease MMP-9 expression, by using micro-CT and immunohistochemical staining. The activation of IKK/NF-κB signaling pathway was also inhibited by all extracts. In addition, ethyl acetate fraction from E70 presented better effect on RANKL/OPG system. This study identified effective extracts from Eucommia ulmoides Oliv. relieving immune inflammation and maintaining structural integrity of joints in CIA rats.

Compressive Stockings After Hindfoot and Ankle Surgery.

Swelling and pain are common after foot and ankle procedures. We hypothesized that compressive stockings (CS) treatment after hindfoot surgery would positively influence patient outcomes. We undertook this randomized controlled trial in 87 consecutive patients to analyze the clinical effect of CS after hindfoot and ankle surgery and evaluate CS-wearing compliance using sensors that were implanted into CS. Ankle swelling, pain status, quality of life (SF-36 score), and the American Orthopaedic Foot & Ankle Score (AOFAS) were set as the primary end points. The CS wearing time in hours and percentage were investigated as the secondary end points. All participants with CS (group I) were informed about the implanted sensor after the CS were taken off. A subgroup analysis of group I was performed to detect differences between patients with high vs low compliance. At 12 weeks, the results of ankle swelling (mean 234 mm in group I and 232 mm in group II), pain in the visual analog scale (1.7 group I vs 1.9 in group II), the SF-36 score (38 points in group I vs 30 points in group II), and the AOFAS score (a mean of 76 points in both groups) showed no statistical differences between the 2 groups. The mean wearing time was 136 (range, 0-470) hours, which corresponds to a compliance rate of 65%. Sixteen participants had high compliance (>80%, >170 hours), and 21 patients had low or noncompliance. The clinical results of patients with high wearing compliance were not significantly better compared to the results of patients with low compliance. CS therapy after ankle and hindfoot surgery was associated with a low wearing compliance and did not influence ankle swelling, function, pain, and the quality of life compared to the control group. Furthermore, the clinical results of patients with high compliance were not better compared to the results of patients with low or noncompliance wearing behavior. Level II, prospective randomized study of lower quality.

Gait training after spinal cord injury: safety, feasibility and gait function following 8 weeks of training with the exoskeletons from Ekso Bionics.

Prospective quasi-experimental study, pre- and post-design. Assess safety, feasibility, training characteristics and changes in gait function for persons with spinal cord injury (SCI) using the robotic exoskeletons from Ekso Bionics. Nine European rehabilitation centres. Robotic exoskeleton gait training, three times weekly over 8 weeks. Time upright, time walking and steps in the device (training characteristics) were recorded longitudinally. Gait and neurological function were measured by 10 Metre Walk Test (10 MWT), Timed Up and Go (TUG), Berg Balance Scale (BBS), Walking Index for Spinal Cord Injury (WISCI) II and Lower Extremity Motor Score (LEMS). Fifty-two participants completed the training protocol. Median age: 35.8 years (IQR 27.5-52.5), men/women: N = 36/16, neurological level of injury: C1-L2 and severity: AIS A-D (American Spinal Injury Association Impairment Scale). Time since injury (TSI) < 1 year, N = 25; > 1 year, N = 27. No serious adverse events occurred. Three participants dropped out following ankle swelling (overuse injury). Four participants sustained a Category II pressure ulcer at contact points with the device but completed the study and skin normalized. Training characteristics increased significantly for all subgroups. The number of participants with TSI < 1 year and gait function increased from 20 to 56% (P = 0.004) and 10MWT, TUG, BBS and LEMS results improved (P < 0.05). The number of participants with TSI > 1 year and gait function, increased from 41 to 44% and TUG and BBS results improved (P < 0.05). Exoskeleton training was generally safe and feasible in a heterogeneous sample of persons with SCI. Results indicate potential benefits on gait function and balance.

Primary Bone Lymphoma of the Talus: A Challenging Diagnosis

Diagnostic challenges are common in clinical practice and diagnostic or classification criteria for musculoskeletal conditions cannot overshadow clinical skills. We present the case of a young man who complained of prolonged articular pain and mild swelling of the right ankle in the absence of other remarkable data. Apparently fulfilling the Budapest diagnostic criteria for complex regional pain syndrome, the patient was treated accordingly, but the pain increased over time. Then the patient underwent an additional diagnostic workup including synovial and bone biopsies in 2 separate occasions with the second one demonstrating diffuse lymphoid infiltrate compatible with lymphoma. The conclusive diagnosis of primary diffuse large B-cell lymphoma of the talus was made and adequate treatment initiated. The diagnostic difficulties as well as the importance of a multidisciplinary approach for complex cases are highlighted in this report.

A Nurse Led Clinic’s contribution to Patient Education and Promoting Self-care in Heart Failure Patients: A Systematic Review

Introduction: Heart failure (HF) is a medical condition whereby the heart’s efficency is compromised. Typical symptoms include breathlessness, tiredness and ankle swelling and signs of increased heart rate, lung congestion or raised jugular venous pressure. It is confirmed by the presence of a structural or functional abnormality of the heart on echocardiograph. HF significantly affects the patient’s quality of life (QoL). HF is a major problem for society affecting 1-2% of adults in developed countries (Mosterd and Hoes 2007), in excess of 90,000 people in Ireland are affected (Corry et al. 2015). Background: The incidence and prevalence as well as high hospital admission rates, increase the cost of and burden of HF. Chronic disease management programmes developed nurse-led clinics and collaboration of the multi-disciplinary team (MDT) to improve HF guideline implementation and outcomes. Educating patients on the self-care skills and knowledge necessary to control symptoms and avoid hospitalisation, which include daily weight, symptom monitoring and seeking timely medical care for deterioration is vital. Self-care is the decisions and choice of behaviours by the individual in order to maintain life, healthy functioning and well-being (Reigel and Carlson 2002, Jaarsma et al. 2003). Cowie et al (2014) examined Acute HF in Europe and the USA recommending: Optimising care accross institutions, improving patient education/ support, providing equitable care, enhancing end of life care, and increasing HF prevention. Aim: To examine the evidence for the role of the nurse-led clinic in patient education on the outcomes of Self-Care and QoL for HF patients. Methodology: A search of the databases CINHAL, PubMed, Science Direct and Medline was conducted. Search criteria: Adult HF patients aged over 18years, attending Nurse-led HF clinics/ nurse managed HF care programmes, English language only, No geographical limit, Published 2006-2016. Inclusion Criteria: Original Research, Interventions delivered through nurse led clinics, patient education, self-care skills, health assessment, and referral to MDT. Grey literature- online reports x 2 and small unpublished local population study. Results: Sixty eight studies were identified spanning 12 countries, various components of disease management programmes such as goal setting & motivational interviewing, educational and self-care needs, barriers and facilitators. Characteristics included all classes of HF, group or individualised programmes. Themes identified included: learning needs; knowledge, symptom recognition, barriers to learning, self-care skills, role of social/ caregiver support and a therapeutic nurse/patient/relationship. Conclusion: The patient’s need to be connected is highlighted by the review. Quantitative measures of self-care tools and patient satisfaction are augmented by patient reported outcomes and rich qualitative data. Cognitive impairment and depression may interfere with learning, decision-making and perception of symptoms.. The evidence supports the need for individualised patient educational plans and management strategies. Lifestyle changes may include controlling or modifiying risk factors (Dickstein et al. 2008). Adherence to guidelines and supporting patient autonomy are also important. Patients must learn and understand the relevant self-care behaviour required (Stromberg 2005, McMurray et al. 2012), gain the necessary skills to act on deteriorating symptoms and ways of increasing activity adjusted to functional capacity and energy conservation. Through education adapted to patient’s needs and goals, Self-Care is promoted and quality of life is improved. Further research is needed into other factors that affect QoL screening and the use of nursing taxonomies.

Effects of moxibustion on Treg/Th17 cell and its signal pathway in mice with rheumatoid arthritis

To observe the effects of moxibustion on Treg/Th17 imbalance and related signal pathway in mice with rheumatoid arthritis (RA), so as to explore the action mechanism of moxibustion on RA. Twenty-four DBA/1J male mice were randomly divided into a normal group, a model group, a sham moxibustion group and a moxibustion group, 6 mice in each one. RA model was induced by subcutaneous injection of typeⅡcollagen and adjuvant at tail in mice other than the normal group. The mice in the moxibustion group were treated with moxibustion at"Zusanli" (ST 36) and "Shenshu" (BL 23), 1 mg per cone, 6 cones per acupoint. The consecutive 6-day treatment was taken as one course, and totally 2 courses were given with an interval of 2 d between courses. The mice in the sham moxibustion group were treated with immobilization as the moxibustion group. The effects of moxibustion on joint swelling was evaluated by RA scale of collagen induced arthritis (CIA); the pathological changes of joint inflammation were observed by HE staining; the cell count of Th17 and Treg in spleen was analyzed by flow cytometry; the content of cytokine IL-1β, IL-6, IL-10, IL-17, IL-23, TGF-β and Galectin-9 were analyzed by ELISA; the mRNA and protein expression of Foxp3, Galectin-9, RORγt, CARMA1, NF-κB were analyzed by Real-time PCR and Western Blotting method. Ten to 12 d after the secondary immune, red and swelling of ankle joint, feet and toe joint were observed, indicating successful establishment of RA model. 15 d into moxibustion treatment, the joint swelling was improved in the moxibustion group and the sham moxibustion group, which was superior in the moxibustion group (P<0.05). As for pathological changes, compare with the normal group, the articular surface was rougher and synovial layer thinner in the model group, which was recovered to a certain extent in the sham moxibustion group; the articular surface was smooth and synovial layer was thicker in the moxibustion group, which was similar to the normal group. The results of flow cytometry test indicated the cell count of Treg in the model group was reduced but that of Th17 was increased than the normal group (both P<0.01); the moxibustion could increase significantly the cell count of Treg (P<0.05), but no effect was observed on Th17 (P>0.05). The results of ELISA test indicated the differences of increasing of IL-1β, IL-6, IL-17, IL-23, TGF-βas well as the reducing of IL-10 were not significant between the sham moxibustion group and the moxibustion group (all P>0.05); moxibustion treatment could increase the content of Galectin-9 which was reduced in RA mice (P<0.05). The results of RT-PCR and Western blotting test indicated the mRNA and protein expression of Foxp3, Galectin-9 were reduced in the model group (all P<0.01), which could be up-regulated by moxibustion treatment (P<0.05, P<0.01); the mRNA and protein expression of RORγt, CARMA1, NF-κB was increased (all P<0.01), which could be down-regulated by moxibustion treatment (P<0.05, P<0.01). Moxibustion could improve the swelling of joint and inflammatory reaction of joint synovial in RA mice; the mechanism may be related to the regulation of Treg cells number in spleen and the expression of Foxp3, Galectin-9, RORγt, CARMA1, NF-κB, mRNA and protein expression.

A case of painful ankle swelling: Cytomorphological clues and pitfalls.

A case of painful ankle swelling: Cytomorphological clues and pitfalls.

The tyrosine kinase inhibitor imatinib mesylate suppresses uric acid crystal-induced acute gouty arthritis in mice.

Gouty arthritis is caused by the deposition of monosodium urate (MSU) crystals in joints. Despite many treatment options for gout, there is a substantial need for alternative treatments for patients unresponsive to current therapies. Tyrosine kinase inhibitors have demonstrated therapeutic benefit in experimental models of antibody-dependent arthritis and in rheumatoid arthritis in humans, but to date, the potential effects of such inhibitors on gouty arthritis has not been evaluated. Here we demonstrate that treatment with the tyrosine kinase inhibitor imatinib mesylate (imatinib) can suppress inflammation induced by injection of MSU crystals into subcutaneous air pouches or into the ankle joint of wild type mice. Moreover, imatinib treatment also largely abolished the lower levels of inflammation which developed in IL-1R1-/- or KitW-sh/W-sh mice, indicating that this drug can inhibit IL-1-independent pathways, as well as mast cell-independent pathways, contributing to pathology in this model. Imatinib treatment not only prevented ankle swelling and synovial inflammation when administered before MSU crystals but also diminished these features when administrated after the injection of MSU crystals, a therapeutic protocol more closely mimicking the clinical situation in which treatment occurs after the development of an acute gout flare. Finally, we also assessed the efficiency of local intra-articular injections of imatinib-loaded poly(lactic-co-glycolic acid) (PLGA) nanoparticles in this model of acute gout. Treatment with low doses of this long-acting imatinib:PLGA formulation was able to reduce ankle swelling in a therapeutic protocol. Altogether, these results raise the possibility that tyrosine kinase inhibitors might have utility in the treatment of acute gout in humans.

Treatment Outcomes of Buttress Plating for Posterior Pilon Fractures

Category: Ankle Introduction/Purpose: The purpose of current study was to retrospectively analyze the clinical outcomes of buttress plate treatment of posterior pilon fractures Methods: Between January 2005 and December 2009, 16 patients with posterior pilon fractures underwent buttress plate fixation. There were 11 males and 5 females and the mean age was 37.6 years (range, 23 to 62 years). Preoperative radiographs, CT scans and three dimensional reconstructions were used to evaluate the fracture patterns. On the basis of the extension of the fracture lines presented on the CT scans, a posterolateral approach or a combination of both posterolateral and posteromedial approaches were used to reduce and fixate the posterior malleolar fragments. Clinical and radiographic examinations were used for postoperative follow-up. The American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score and the Visual Analogue Scale (VAS) were used to evaluate the functional outcomes. Results: According to the CT scan images, the posterior pilon fractures were classified into 3 types. 14 patients were available for follow-up. The mean time of follow-up was 37.6 months (range, 16 to 52 months). The mean AOFAS score was 86.4 points (range, 70 to 98 points), and the mean VAS score was 1.4 points (range, 0 to 3 points). One patient was found with ankle joint swelling and long term walking discomfort at 2-year follow-up. Other patients received favorable functional outcomes. No hardware failure occurred. Conclusion: The clinical outcomes of buttress plate treatment of posterior pilon fractures were satisfactory. Buttress plating availed the patients to return to earlier weight-bearing and functional exercises.

Boldine isolated from Litsea cubeba inhibits bone resorption by suppressing the osteoclast differentiation in collagen-induced arthritis

ObjectiveTo investigate the effect of boldine isolated from Litsea cubeba on collagen-induced arthritis (CIA) rats and explore the molecular mechanism predicted by network pharmacology. Material and methodsCIA rats were orally administered with boldine. The bone destruction of paws was analyzed by histologic examination, tartrate-resistant acid phosphatase (TRACP) staining and micro-computed tomography. Prediction of signal pathway associated with boldine network molecules and CIA genes was applied by the network pharmacology analysis. The expressions of osteoprotegerin (OPG), receptor activator of nuclear factor-κB (RANK) and its ligand (RANKL) in the ankle were detected by immunohistochemistry. In vitro osteoclasts were cultured in the presence of variable doses of boldine and the RANK expressions were evaluated using Real-time polymerase chain reaction and western blot. ResultsBoldine reduced ankle swelling, alleviated pathological damage and significantly prevented bone destruction in CIA rats. Consistent with this, enzyme linked immunosorbent assay revealed boldine decreased serum TRACP5b levels and osteoclast number in the ankle region by TRACP staining from CIA rats. The network pharmacology analysis indicated that RANK signaling in osteoclasts was the most significant canonical pathway associated with boldine network molecules and CIA genes, which was verified by the increased expression of OPG, reduced expression of RANK, RANKL and RANKL/OPG in boldine-treated CIA rats. The in vitro study further confirmed that boldine inhibited osteoclastogenesis by inhibiting the RANKL/RANK signaling pathway. ConclusionTaken together, our study first indicates that boldine from Litsea cubeba suppresses osteoclastogenesis, improves bone destruction by down-regulating the OPG/RANKL/RANK signal pathway and may be a potential therapeutic agent for rheumatoid arthritis.

Unusual acute lupus hemophagocytic syndrome \u2013 a test of diagnostic criteria: a case report

BackgroundHemophagocytic lymphohistiocytosis is an aggressive life-threatening syndrome of excessive immune activation. Hemophagocytic lymphohistiocytosis due to systemic lupus erythematosus is described as acute lupus hemophagocytic syndrome. Acute lupus hemophagocytic syndrome presenting with negative antinuclear antibody is uncommon.Case presentationA 57-year-old Sri Lankan woman presented with intermittent fever, weight loss, episodic confusion, and alopecia for 3 months. Investigations showed pancytopenia. Her erythrocyte sedimentation rate was 76 mm/hour and C-reactive protein was 2 mg/l. Septic screen was negative except for a positive sputum culture for Gram-negative coliforms. Chest X-ray was normal. Direct antiglobulin test was positive. Fever persisted with clinical worsening despite treatment with intravenous antibiotics. Antinuclear antibodies and double-stranded-deoxyribonucleic acid antibodies were negative. Bone marrow aspiration revealed features compatible with hemophagocytosis. Her serum ferritin and triglycerides were elevated. Diagnosis of hemophagocytic lymphohistiocytosis due to an evolving autoimmune disorder was made and she was treated with steroids. She showed a dramatic improvement and was discharged on oral steroids.After 6 months, while the steroids were being tapered she experienced oral ulcers, frothy urine, and ankle swelling and she was rehospitalized. Urine analysis revealed proteinuria with active sediment. Antinuclear antibodies and double-stranded-deoxyribonucleic acid antibodies were positive. Complement C3 and C4 were reduced. A renal biopsy revealed class IV-G lupus nephritis with immunofluorescence pattern consistent with systemic lupus erythematosus. Steroid dose was increased and mycophenolate mofetil was commenced. She improved.ConclusionsThis case showcases an uncommon presentation of acute lupus hemophagocytic syndrome with initial negative antinuclear antibody probably due to its cytokine-mediated pathogenesis. This is the first such reported case in South Asia to the best of our knowledge. According to the American College of Rheumatology criteria, our patient did not fulfill the criteria for systemic lupus erythematosus diagnosis for the initial hospitalization. But, according to the 2012 Systemic Lupus International Collaborating Clinics criteria, she did fulfill the criteria for systemic lupus erythematosus even in the first hospitalization which was subsequently proven with renal biopsy findings. This case confirms the increased sensitivity of Systemic Lupus International Collaborating Clinics criteria over American College of Rheumatology criteria in diagnosis of systemic lupus erythematosus.

Practical guidance on heart failure diagnosis and management in primary care: recent EPCCS recommendations.

Heart failure (HF) is a common and costly clinical syndrome, associated with significant morbidity and reduced life expectancy, affecting around 1–2% of adults in developed countries.1 Timely diagnosis is important to optimise evidence-based treatment opportunities, which delay mortality and improve symptoms, but the early stages of HF can be difficult to identify clinically. Primary care has a vital role in providing holistic, person-centred care from first symptoms to end of life. This article summarises the key aspects of HF management for general practice including new areas of diagnostics and drug therapy. HF is a clinical syndrome characterised by certain symptoms, and possibly signs, plus objective evidence of a structural or functional abnormality of the heart. The type of HF is determined according to left ventricular ejection fraction (LVEF), although the exact cut-point continues to be an area of debate.2 HF with reduced ejection fraction (HFrEF) is commonly defined as LVEF <40%. HF with preserved ejection fraction (HFpEF) is defined as LVEF ≥50% with evidence of diastolic dysfunction or structural cardiac changes.3 Recently, the European Society of Cardiology (ESC) added a third group, HF with midrange ejection fraction (HFmrEF), for the grey area between HFrEF and HFpEF.3 All three show reduced prognosis compared with the non-HF population. The classification is important for management: HFrEF has a strong evidence base for pharmacological intervention whereas the same treatments have not shown benefit in HFpEF.4 In both HFrEF and HFpEF, the heart fails to pump adequately, causing symptoms of fluid overload and cardiac stress, such as breathlessness, ankle swelling, and fatigue. These symptoms are common and can be associated …