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ID PMID Title PublicationDate abstract
25311252 Atypical focal forms of Whipple's disease seen by rheumatologists. 2015 Jan We report two atypical cases of focal Whipple's disease with rheumatic presenting symptoms. In one of these cases, the patient presented with chronic intermittent polyarthritis, systemic inflammation, and leukocytosis. Tests were positive for rheumatoid factor and anti-cyclic citrullinated peptide antibodies. There was no structural joint damage. Combined glucocorticoid and methotrexate therapy was only partially effective. Endocarditis requiring emergency valve replacement surgery occurred 4 years later. Evaluation of this event led to the diagnosis of Tropheryma whipplei infection responsible for both the endocarditis and the joint disease. The other patient presented with subacute inflammatory low back pain. His medical history was chiefly remarkable for intermittent inflammatory involvement of the wrists and right knee replacement surgery for osteoarthritis followed by a febrile effusion of the operated knee. Radiographs showed destructive lesions of the wrists. Magnetic resonance imaging findings suggested L2-L3 diskitis. A PCR assay on biopsy specimens from the disk lesions recovered T. whipplei, thus establishing the cause of the diskitis and previous joint manifestations. Combined doxycycline and hydroxychloroquine therapy was followed by full resolution of all clinical and laboratory abnormalities in both patients.
26295841 Transient synovitis of the hip: which investigations are truly useful? 2015 QUESTIONS UNDER STUDY/PRINCIPLES: To assess the usefulness of several laboratory and radiological investigations for the limping child with suspected transient synovitis of the hip. METHODS: The medical records of children admitted at our children's hospital for nontraumatic hip pain between 1999 and 2007 were retrospectively reviewed. During the study period, all children without a definite diagnosis after routine investigations in the emergency department were admitted and a specific work-up including antinuclear antibodies titre, rheumatoid factor, antistreptolysin O titre, Lyme disease serology and hip ultrasonography were obtained. Children were systematically re-evaluated 6 weeks after hospital discharge, with a clinical examination and radiological hip views. Patients were diagnosed with transient synovitis of the hip if an ultrasound-confirmed hip effusion was present at time of admission, complete resolution of symptoms occurred without any specific treatment, and no other pathology of the hip was identified during follow-up. RESULTS: A total of 417 cases without definite diagnosis were admitted and were submitted to a specific work-up. Transient synovitis of the hip was subsequently diagnosed in 383 patients, septic arthritis in 1 patient, and Lyme arthritis in 1 patient. Thirty-two patients remained without diagnosis. No rheumatological condition was found. CONCLUSION: Our results suggest that most investigations performed during the initial work-up in patients suspected transient synovitis of the hip are unnecessary and should routinely include only white blood cell count, C-reactive protein, erythrocyte sedimentation rate, and hip radiography and ultrasonography. No further investigations are necessary during follow-up for transient synovitis of the hip in asymptomatic children.
27621864 Characteristics of patients with pseudochylothorax-a systematic review. 2016 Aug BACKGROUND: Pseudochylothorax (PCT) (cholesterol pleurisy or chyliform effusion) is a cholesterol-rich pleural effusion (PE) that is commonly associated with chronic inflammatory disorders. Nevertheless, the characteristics of patients with PCT are poorly defined. METHODS: A systematic review was performed across two electronic databases searching for studies reporting clinical findings, PE characteristics, and the most effective treatment of PCT. Case descriptions and retrospective studies were included. RESULTS: The review consisted of 62 studies with a total of 104 patients. Median age was 58 years, the male/female ratio was 2.6/1, and in the 88.5% of cases the etiology was tuberculosis (TB) or rheumatoid arthritis (RA). PE was usually unilateral (88%) and occupied greater than one-third of the hemithorax (96.3%). There was no evidence of pleural thickening in 20.6% of patients, and 14 patients had a previous PE. The pleural fluid (PF) was an exudate, usually milky (94%) and with a predominance of lymphocytes (61.1%). The most sensitive tests to establish the diagnosis were the cholesterol/triglycerides ratio (CHOL/TG ratio) >1, and the presence of cholesterol crystals (97.4% and 89.7%, respectively). PF culture for TB was positive in the 34.1% of patients. Favorable outcomes with medical treatment, therapeutic thoracentesis, decortication/pleurectomy, pleurodesis, thoracic drainage and thoracoscopic drainage were achieved in 78.9%, 47.8%, 86.7%, 66.6%, 37.5% and 42.9%, respectively. CONCLUSIONS: PCT is usually tuberculous or rheumatoid, unilateral and the PF is a milky exudate. The presence of cholesterol crystals and a CHOL/TG ratio >1 are the most sensitive test for the diagnosis. The lack of pleural thickening does not rule out PCT. Treatment should be sequential, treating the underlying causes, and assessing the need for interventional techniques.
27481673 [Temporo-mandibular ankylosis]. 2016 Sep Ankylosis of the temporomandibular joint is defined as a permanent constriction of the jaws with less than 30mm mouth opening measured between the incisors, occurring because of bony, fibrous or fibro-osseous fusion. Resulting complications such as speech, chewing, swallowing impediment and deficient oral hygiene may occur. The overall incidence is decreasing but remains significant in some developing countries. The most frequent etiology in developed countries is the post-traumatic ankylosis occurring after condylar fracture. Other causes may be found: infection (decreasing since the advent of antibiotics), inflammation (rheumatoid arthritis and ankylosing spondylitis mainly) and congenital diseases (very rare). Management relies on surgery: resection of the ankylosis block in combination with bilateral coronoidectomy… The block resection may be offset by the interposition temporal fascia flap, a costochondral graft or a TMJ prosthesis according to the loss of height and to the impact on dental occlusion. Postoperative rehabilitation is essential and has to be started early, to be intense and prolonged. Poor rehabilitation is the main cause of ankylosis recurrence.
27592028 Are cytotoxic effector cells changes in peripheral blood of patients with Sjögren's syndr 2016 Dec Etiology of Sjögren's syndrome (SS) is still unknown, but there is strong evidence that certain pathogens of bacterial or viral origin can incite autoimmune response. The aim of this study was to quantitatively evaluate changes of the main cell populations (dendritic cells, natural killer, natural killer T and cytotoxic T lymphocytes) presumably participating in virus clearance in peripheral blood of patients with primary SS (pSS). In analyzing cytotoxic T lymphocytes (CTL) populations we observed alterations in the frequency of highly cytotoxic effector CD8(high)/57(+)/27(-)/45RA(+), less cytotoxic CD8(high)/57(-)/27(-)/45RA(+) effector cells and cytotoxic memory CD8(high)/57(+)/27(+)/45RA(-) effector cells. We found a decrease of conventional dendritic cells (cDC) population in peripheral blood of pSS patients. It is possible that, a decrease of effector CTL and cDC, accompanied by increase of transitory phenotype memory CTL in peripheral blood of pSS patients may be associated with viral etiopathogenesis of Sjögren's syndrome.
27175675 Sjögren Sensory Neuronopathy (Sjögren Ganglionopathy): Long-Term Outcome and Treatment R 2016 May Primary Sjögren syndrome (SS) is an autoimmune disease mainly affecting the exocrine glands causing a sicca syndrome. Neurological manifestations are rarely seen in SS although they are debilitating. Peripheral neuropathies namely sensory axonal neuropathy and painful small fiber neuropathy are the most frequent neurological manifestations. Sensory neuronopathy (SN) is less frequently seen although leading to more severe handicap.The aim of the study was to analyze the clinical presentation and treatment efficacy in a series of SS-related SN.We retrospectively studied patients with SS fulfilling the American-European Classification Criteria and SN according to recent criteria. Studied variables were neurological findings, associated autoimmune diseases, biological profiles, nerve conduction and sensory/motor amplitudes study, treatments received, and outcomes. Handicap scores were studied at beginning and end of each treatment using the modified Rankin Scale (mRS).Thirteen patients were included (12 women, 1 man; median age 55 years at SN diagnosis) presenting with SN with a median follow-up of 3 years (range 2-17). In 11 patients, SN preceded or coincided with SS diagnosis. Most common neurological findings were ataxia and areflexia followed by paresthesia and pain. Lower limbs were more affected than upper limbs, neurological deficits were often symmetric and cranial nerves were affected in 3 patients. Seven patients were treated with corticosteroids, 7 with mycophenolate mofetil, 6 with hydroxychloroquine, 5 with intravenous immunoglobulins, 4 with cyclophosphamide, and 2 patients received other immunosuppressive drugs. At the beginning and at the end of follow-up, average mRS was 2.15 (median 2) and 2.38 (median 2), respectively.SS-related SN progression is heterogeneous but tends to be chronic, insidious, and debilitating despite treatment. From these data concerning a small number of patients, treatment strategies with corticosteroids in association with immunosuppressive drugs, namely mycophenolate mofetil, had positive results. In contrast, intravenous immunoglobulins had disappointing results.
26854251 Increased risk of concurrent gastroesophageal reflux disease among patients with Sjögren' 2016 Jun BACKGROUND: Little data is available on the risk of gastroesophageal reflux disease in patients diagnosed with Sjögren's syndrome. METHODS: We identified 4650 Sjögren's syndrome patients between 2000 and 2011 from the National Health Insurance Research Database. Each Sjögren's syndrome patient was matched to 4 controls based on age, sex, and index year, and all subjects were followed up from the index date to December 31, 2011. Cox proportional hazards regression model was used to estimate the risk of gastroesophageal reflux disease. RESULTS: The risk of gastroesophageal reflux disease for Sjögren's syndrome patients was 2.41-fold greater than that for the comparison cohort after adjusting for age, sex, and comorbidities. In age stratified analyses, the youngest Sjögren's syndrome cohort (age: 20-44years old) had the highest risk (HR=3.02; 95% CI=2.48-3.69) and the lowest risk at age ≥65years (HR=1.95; 95% CI=1.61-2.36). Regardless of in subjects with and without comorbidity, Sjögren's syndrome patients had a higher risk than the controls. Sjögren's syndrome subjects with ischemic heart disease, hyperlipidemia and renal disease had the highest risk for gastroesophageal reflux disease compared with the comparison cohort without those diseases (HR=7.67; 95% CI=5.32-11.1). CONCLUSION: Patients with Sjögren's syndrome have a significantly greater risk of developing subsequent gastroesophageal reflux disease than the general population.
26300591 Selected Aspects in the Pathogenesis of Autoimmune Diseases. 2015 Autoimmune processes can be found in physiological circumstances. However, they are quenched with properly functioning regulatory mechanisms and do not evolve into full-blown autoimmune diseases. Once developed, autoimmune diseases are characterized by signature clinical features, accompanied by sustained cellular and/or humoral immunological abnormalities. Genetic, environmental, and hormonal defects, as well as a quantitative and qualitative impairment of immunoregulatory functions, have been shown in parallel to the relative dominance of proinflammatory Th17 cells in many of these diseases. In this review we focus on the derailed balance between regulatory and Th17 cells in the pathogenesis of autoimmune diseases. Additionally, we depict a cytokine imbalance, which gives rise to a biased T-cell homeostasis. The assessment of Th17/Treg-cell ratio and the simultaneous quantitation of cytokines, may give a useful diagnostic tool in autoimmune diseases. We also depict the multifaceted role of dendritic cells, serving as antigen presenting cells, contributing to the development of the pathognomonic cytokine signature and promote cellular and humoral autoimmune responses. Finally we describe the function and role of extracellular vesicles in particular autoimmune diseases. Targeting these key players of disease progression in patients with autoimmune diseases by immunomodulating therapy may be beneficial in future therapeutic strategies.
27195488 A Point-Scoring System for the Clinical Diagnosis of Sjögren's Syndrome Based on Quantifi 2016 OBJECTIVE: To establish a point-scoring diagnostic system for Sjögren's syndrome (SS) based on quantified SPECT imaging of salivary gland, and evaluate its feasibility and performance compared with 2002 AECG criteria and 2012 ACR criteria. METHODS: 213 patients with suspected SS enrolled in this study. The related clinical data of all patients were collected. All patients were evaluated and grouped on a clinical basis and posttreatment follow-up by rheumatology specialists as the unified standard (SS group with 149 cases and nSS group with 64 cases). From SPECT imaging of salivary gland, Tmax, UImax, Ts and EFs were derived for bilateral parotid and submandibular glands, and compared between the groups. A point-scoring diagnostic system for SS was established based on the quantified SPECT imaging of salivary gland. We estimated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy for the new diagnostic system, compared with 2002 AECG criteria and 2012 ACR criteria. RESULTS: When 7.0 was used as the cut-off point, the sensitivity, specificity, PPV, NPV and accuracy for the new point-scoring system in diagnosing SS were 89.93% (134/149), 93.75% (60/64), 97.10% (134/138), 80.00% (60/75) and 91.08% (194/213), respectively. The new point-scoring diagnostic system based on quantified SPECT imaging of salivary gland keeps the specificity comparatively to 2002 AECG criteria and 2012 ACR criteria, but improves the sensitivity significantly (P<0.01). CONCLUSION: The new point-scoring diagnostic system for SS based on quantified SPECT imaging of salivary gland may be superior to 2002 AECG criteria and 2012 ACR criteria, with higher sensitivity and similar specificity in the diagnosis of SS. Additionally, it also has good feasibility in the clinical settings.
26933138 Interleukin-17 Impairs Salivary Tight Junction Integrity in Sjögren's Syndrome. 2016 Jul Sjögren's syndrome (SS) is an inflammatory autoimmune disease that causes secretory dysfunction of the salivary glands. It has been reported that proinflammatory cytokine interleukin-17 (IL-17) was elevated and tight junction (TJ) integrity disrupted in minor salivary glands from SS patients. However, whether the elevated IL-17 in SS affects TJ integrity and thereby alters the function of salivary gland is unknown. Here, by using nonobese diabetic (NOD) mice as SS model, we found that the stimulated salivary flow rate was significantly decreased in NOD mice. Lymphocyte infiltration was mainly observed in submandibular glands (SMGs), but not parotid glands (PGs), of NOD mice. IL-17 was significantly increased and mainly located in lymphocytic-infiltrating regions in SMGs but not detectable in PGs of NOD mice. Meanwhile, the epithelial barrier function was disrupted, as evidenced by an increased paracellular tracer clearance and an enlarged acinar TJ width in SMGs of NOD mice. Furthermore, claudin-1 and -3 were elevated especially at the basolateral membranes, whereas claudin-4, occludin, and zonula occludens-1 (ZO-1) were reduced in SMGs of NOD mice. Moreover, occludin and ZO-1 were dispersed into cytoplasm in SMGs of NOD mice. However, no change in the expression and distribution of TJ proteins was found in PGs. In vitro, IL-17 significantly decreased the levels and apical staining of claudin-4 and ZO-1 proteins in the cultured SMG tissues, as well as claudin-1, occludin, and ZO-1 in PG tissues. Moreover, IL-17 activated the phosphorylation of IκBα and p65 in SMG cells, whereas pretreatment with NF-κB inhibitor pyrrolidine dithiocarbamate suppressed the IL-17-induced downregulation of claudin-4 and ZO-1 in SMG tissues. Taken together, these findings indicate that IL-17 derived from infiltrating lymphocyte impairs the integrity of TJ barrier through NF-κB signaling pathway, and thus might contribute to salivary gland dysfunction in SS.
26564070 Acquired neurocutaneous disorders. 2015 A variety of neurologic diseases have cutaneous manifestations. These may precede, coincide with, or follow the neurologic findings. An array of autoimmune, genetic, and environmental factors play a role in expression and severity of the neurologic burden in these conditions. This chapter emphasizes congenital and genetic disorders, but we also discuss the pathophysiology and manifestation of various acquired neurocutaneous disorders with an emphasis Behcet's disease, dermatomyositis, Sjögren's syndrome, systemic lupus erythematosus, scleroderma, Parry-Romberg syndrome and Degos disease.
27909141 Developing a Risk-scoring Model for Ankylosing Spondylitis Based on a Combination of HLA-B 2016 Dec OBJECTIVE: To develop a genotype-based ankylosing spondylitis (AS) risk prediction model that is more sensitive and specific than HLA-B27 typing. METHODS: To develop the AS genetic risk scoring (AS-GRS) model, 648 individuals (285 cases and 363 controls) were examined for 5 copy number variants (CNV), 7 single-nucleotide polymorphisms (SNP), and an HLA-B27 marker by TaqMan assays. The AS-GRS model was developed using logistic regression and validated with a larger independent set (576 cases and 680 controls). RESULTS: Through logistic regression, we built the AS-GRS model consisting of 5 genetic components: HLA-B27, 3 CNV (1q32.2, 13q13.1, and 16p13.3), and 1 SNP (rs10865331). All significant associations of genetic factors in the model were replicated in the independent validation set. The discriminative ability of the AS-GRS model measured by the area under the curve was excellent: 0.976 (95% CI 0.96-0.99) in the model construction set and 0.951 (95% CI 0.94-0.96) in the validation set. The AS-GRS model showed higher specificity and accuracy than the HLA-B27-only model when the sensitivity was set to over 94%. When we categorized the individuals into quartiles based on the AS-GRS scores, OR of the 4 groups (low, intermediate-1, intermediate-2, and high risk) showed an increasing trend with the AS-GRS scores (r(2) = 0.950) and the highest risk group showed a 494× higher risk of AS than the lowest risk group (95% CI 237.3-1029.1). CONCLUSION: Our AS-GRS could be used to identify individuals at high risk for AS before major symptoms appear, which may improve the prognosis for them through early treatment.
26995659 Cytokine-induced STAT1 activation is increased in patients with primary Sjögren's syndrom 2016 Apr Limited data are available regarding the intracellular responses to different cytokines in primary Sjögren's syndrome (pSS). We studied the signal transducer and activator of transcription (STAT) activation profile in response to cytokine stimulations in peripheral blood mononuclear cells (PBMCs) from pSS patients by multicolor flow cytometry. The expression of the suppressors of cytokine signaling (SOCS), and interferon (IFN)-γ target genes in PBMCs was studied using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The induction of STAT1 phosphorylation in response to stimulation with IFN-α, IFN-γ or interleukin (IL)-6 was significantly increased in B cells and monocytes from pSS patients. Accordingly, the STAT1-mediated gene responses were significantly enhanced in PBMCs from pSS patients. Finally, the expression of SOCS1 and SOCS3 mRNA was increased in pSS patients. The results indicate increased sensitivity of immune cells from pSS patients to STAT1-activating signals, and may partly explain the IFN signature observed in pSS.
26785742 B-cell and T-cell quantification in minor salivary glands in primary Sjögren's syndrome: 2016 Jan 20 BACKGROUND: Evaluating lymphocytic infiltration of minor salivary gland biopsy in primary Sjögren's syndrome is challenging. We developed and evaluated a digital method for quantifying B and T lymphocytes in whole minor salivary gland biopsy slides. METHODS: Minor salivary gland biopsies were immunostained with anti-CD20/anti-CD3 antibodies using red/brown chromogens. Slides were digitised and spliced into mosaics of smaller JPEG format images in which red and brown pixels were counted. ImageJ Cell counter was used for validation. Agreement between the digital and manual methods was evaluated using Bland-Altman plots and the interclass correlation coefficient. External validation relied on the Chisholm-Mason, Tarpley, and focus-score methods. RESULTS: Of 62 minor salivary gland biopsy slides, 61.3 % had a Chisholm-Mason grade ≥ III or a focus score ≥1. The number of pixels correlated well with manual cell counts (r = 0.95 for red pixels vs. B cell count and r = 0.91 for brown pixels vs. T cell count). Interclass correlation coefficients between digital and manual counts were excellent (0.92 for B/T cells). B-cell proportion showed a significant positive correlation with the focus score (Spearman's coefficient 0.463, p < 0.0001). Median B-cell proportion was lower in minor salivary gland biopsies with Chisholm grades I-II (2.5 % (0.2-13.9)) than III-IV (30.0 % (15.5-45.2)) and increased with Tarpley's class (1, 2.2 % (0.2-6.6); 2, 27.2 % (13.0-38.9); and 3-4, 48.5 % (29.4-56.4); p < 0.001 for all comparisons). Minor salivary gland biopsy B-cell proportion was also significantly correlated with several markers of clinical and biological activity of the disease, especially with markers of systemic B-cell hyperactivation. CONCLUSION: The digital procedure proved accurate compared to the reference standard, producing reliable results for whole tissue sections. TRIAL REGISTRATION: ClinicalTrials.gov [ NCT00740948 ]. Registered 22 August 2008.
26065354 Effect of Oral Pilocarpine in Treating Severe Dry Eye in Patients With Sjögren Syndrome. 2015 Mar PURPOSE: The aim of this study is to evaluate the efficacy and safety of oral pilocarpine in treating severe dry eye unresponsive to conventional conservative treatment in patients with Sjögren syndrome. DESIGN: A prospective study. METHODS: Oral doses of pilocarpine were administered for at least 3 months to patients with Sjögren syndrome complicated by established dry eye of great severity unresponsive to conventional conservative treatment. RESULTS: Subjective eye symptoms (dry eye sensation and eye pain), fluorescein staining scores, rose Bengal staining scores, and tear film breakup time measurements improved significantly after 1 month and 3 months of oral treatment with pilocarpine, whereas no significant improvement was noted in Schirmer I testing. CONCLUSIONS: Oral administration of pilocarpine was useful in treating severe dry eye unresponsive to conventional conservative treatment in patients with Sjögren syndrome from the standpoint of efficacy and safety. Thus, we conclude that oral pilocarpine is effective as a new option in treating severe dry eye.
25701252 Potent and selective Bruton's tyrosine kinase inhibitors: discovery of GDC-0834. 2015 Mar 15 SAR studies focused on improving the pharmacokinetic (PK) properties of the previously reported potent and selective Btk inhibitor CGI-1746 (1) resulted in the clinical candidate GDC-0834 (2), which retained the potency and selectivity of CGI-1746, but with much improved PK in preclinical animal models. Structure based design efforts drove this work as modifications to 1 were investigated at both the solvent exposed region as well as 'H3 binding pocket'. However, in vitro metabolic evaluation of 2 revealed a non CYP-mediated metabolic process that was more prevalent in human than preclinical species (mouse, rat, dog, cyno), leading to a high-level of uncertainly in predicting human pharmacokinetics. Due to its promising potency, selectivity, and preclinical efficacy, a single dose IND was filed and 2 was taken in to a single dose phase I trial in healthy volunteers to quickly evaluate the human pharmacokinetics. In human, 2 was found to be highly labile at the exo-cyclic amide bond that links the tetrahydrobenzothiophene moiety to the central aniline ring, resulting in insufficient parent drug exposure. This information informed the back-up program and discovery of improved inhibitors.
27542719 Tibiotalocalcaneal arthrodesis with headless compression screws. 2016 Aug 19 BACKGROUND: Tibiotalocalcaneal arthrodesis with headless compression screws has not been previously reported. We hypothesized that these screws could be suitable for tibiotalocalcaneal arthrodesis because of their special design. This study aimed to evaluate the clinical outcomes of patients undergoing tibiotalocalcaneal arthrodesis with headless compression screws for the treatment of severe arthropathy of the ankle and subtalar joint. METHODS: From 2010 to 2015, 23 patients with severe ankle and subtalar arthropathy underwent tibiotalocalcaneal arthrodesis. All surgeries were completed by a senior surgeon in the same hospital. These patients were 18~76 years (mean 54.6 years) old; the duration of their disease was 9~38 months (mean 13.2 months). The study population included 12 males and 11 females; 12 patients underwent surgery on the left and 11 on the right. Indications for surgery included avascular necrosis of the talus (n = 14), severe posttraumatic arthritis (n = 4), osteoarthritis (n = 2), terminal tuberculous arthritis (n = 1), rheumatoid arthritis (n = 1) and Charcot neuroarthropathy (n = 1). A lateral oblique incision was performed to expose the subtalar joint, and an anteromedial longitudinal incision was used to expose the ankle joint. After the articular surfaces were removed, the tibia, talus and calcaneus were carefully aligned and fixed with two headless compression screws. Patients were followed up at 6 weeks and 3, 6 and 9 months after surgery; they were evaluated by Roles and Maudsley patient satisfaction scores, the American Orthopaedic Foot & Ankle Society (AOFAS) Ankle-Hindfoot Score, visual analogue scale (VAS) score and radiographic evaluation. RESULTS: Seventeen patients were studied, with a mean follow-up time of 6.5 months (range 5-24). The mean Roles and Maudsley patient satisfaction score was 1.41 at the last follow-up; most of the patients were satisfied with the surgery results. The mean preoperative AOFAS Ankle-Hindfoot Score was 29.6 (range 18-37), while the mean last follow-up AOFAS Ankle-Hindfoot Score was 68.5 (range 61-80). The VAS score for preoperative functional pain was 6.95 (range 3-10) compared to 1.56 (range 0-3) postoperatively (P < 0.001). The mean surgical duration was 57 (range 42-125) min. The mean time to union was 3.8 months (range 3-12 months); fusion of the ankle and subtalar joint was successful in all patients. One patient experienced delayed wound healing. CONCLUSIONS: Tibiotalocalcaneal arthrodesis with headless compression screws for the treatment of severe arthropathy of the ankle and subtalar joint is an effective treatment that is minimally invasive and is associated with a short operation time, high fusion rate, low incidence of complications and good postoperative recovery.
25704907 Visceral leishmaniasis mimicking systemic lupus erythematosus: Case series and a systemati 2015 Jun OBJECTIVE: Systemic lupus erythematosus (SLE) is an autoimmune disease that may present manifestations that resemble other diseases. Visceral leishmaniasis (VL) is a parasitic infection whose hallmarks may mimic SLE symptoms. Here, we report a case series and evaluate the published, scientific evidence of the relationship between SLE and VL infection. METHODS: To assess original studies reporting cases of VL-infected patients presenting manifestations that are capable of leading to inappropriate suspicions of SLE or mimicking an SLE flare, we performed an extensive search in several scientific databases (MEDLINE, LILACS, SciELO, and Scopus). Two authors independently screened all citations and abstracts identified by the search strategy to identify eligible studies. Secondary references were additionally obtained from the selected articles. RESULTS: The literature search identified 53 eligible studies, but only 17 articles met our criteria. Among these, 10 lupus patients with VL mimicking an SLE flare and 18 cases of VL leading to unappropriated suspicions of SLE were described. The most common manifestations in patients infected with VL were intermittent fever, pancytopenia, visceromegaly, and increased serum level of acute phase reactants. The most frequent autoantibodies were antinuclear antibodies, rheumatoid factor, and direct Coombs' test. CONCLUSION: In endemic areas for VL, the diagnosis of SLE or its exacerbation may be a clinical dilemma. Hepatosplenomegaly or isolated splenomegaly was identified in the majority of the reported cases where VL occurred, leading to unappropriated suspicions of SLE or mimicking an SLE flare. Furthermore, the lack of response to steroids, the normal levels of complement proteins C3 and C4, and the increased level of transaminases suggest a possible infectious origin.
27836732 Bone fracture nonunion rate decreases with increasing age: A prospective inception cohort 2017 Feb BACKGROUND: Fracture nonunion risk is related to severity of injury and type of treatment, yet fracture healing is not fully explained by these factors alone. We hypothesize that patient demographic factors assessable by the clinician at fracture presentation can predict nonunion. METHODS: A prospective cohort study design was used to examine ~2.5 million Medicare patients nationwide. Patients making fracture claims in the 5% Medicare Standard Analytic Files in 2011 were analyzed; continuous enrollment for 12months after fracture was required to capture the ICD-9-CM nonunion diagnosis code (733.82) or any procedure codes for nonunion repair. A stepwise regression analysis was used which dropped variables from analysis if they did not contribute sufficient explanatory power. In-sample predictive accuracy was assessed using a receiver operating characteristic (ROC) curve approach, and an out-of-sample comparison was drawn from the 2012 Medicare 5% SAF files. RESULTS: Overall, 47,437 Medicare patients had 56,492 fractures and 2.5% of fractures were nonunion. Patients with healed fracture (age 75.0±12.7SD) were older (p<0.0001) than patients with nonunion (age 69.2±13.4SD). The death rate among all Medicare beneficiaries was 4.8% per year, but fracture patients had an age- and sex-adjusted death rate of 11.0% (p<0.0001). Patients with fracture in 14 of 18 bones were significantly more likely to die within one year of fracture (p<0.0001). Stepwise regression yielded a predictive nonunion model with 26 significant explanatory variables (all, p≤0.003). Strength of this model was assessed using an area under the curve (AUC) calculation, and out-of-sample AUC=0.710. CONCLUSIONS: A logistic model predicted nonunion with reasonable accuracy (AUC=0.725). Within the Medicare population, nonunion patients were younger than patients who healed normally. Fracture was associated with increased risk of death within 1year of fracture (p<0.0001) in 14 different bones, confirming that geriatric fracture is a major public health issue. Comorbidities associated with increased risk of nonunion include past or current smoking, alcoholism, obesity or morbid obesity, osteoarthritis, rheumatoid arthritis, type II diabetes, and/or open fracture (all, multivariate p<0.001). Nonunion prediction requires knowledge of 26 patient variables but predictive accuracy is currently comparable to the Framingham cardiovascular risk prediction.
25837583 Factor-inhibiting HIF-1 (FIH-1) is required for human vascular endothelial cell survival. 2015 Jul Factor-inhibiting hypoxia-inducible factor (HIF)-1 (FIH-1) is an asparaginyl β-hydroxylase enzyme that was initially found to hydroxylate the HIF-α, preventing its transcriptional activity and leading to adaptive responses to hypoxia. More recently, other substrates, such as neurogenic locus notch homolog (Notch), have been found to be alternative FIH targets, but the biologic relevance of this regulation was never investigated. Given the key function of Notch in angiogenesis, we here investigate the role of FIH/Notch signaling in endothelial cells. We report that FIH-1 silencing in HUVECs results in reduced growth and increased apoptosis. The knockdown of FIH is associated with increased Notch2 activity, leading to enhanced expression of the Notch target hairy/enhancer-of-split related with YRPW motif protein 1 (Hey-1). Consistent with recent findings showing that Notch2 suppresses survivin (a key inhibitor of apoptosis), FIH targeting in HUVECs leads to selective repression of survivin in endothelial cells, thus promoting cell apoptosis and growth arrest. Our data support the concept that FIH-1 may interact with Notch2 and repress its activity, thereby playing a critical role in controlling the survival of vascular endothelial cells. These findings might pave the way toward novel, antiangiogenic strategies in disorders that are characterized by excessive vascular growth, such as cancer and rheumatoid arthritis.