Prevalence and risk factors of osteoporosis in patients with ankylosing spondylitis: a 5-year follow-up study of 504 cases.

OBJECTIVES: The objective of this study was to assess the prevalence and risk factors of osteoporosis (OP) in patients with ankylosing spondylitis (AS). METHODS: Demographic and clinical data of 504 AS patients were collected. Bone mineral density (BMD) measurements of the lumbar spine, proximal femur and forearm were performed by dual-energy x-ray absorptiometry at baseline and follow-up. 106 cases of sex- and age-matched healthy volunteers were enrolled as normal controls. RESULTS: In contrast to normal controls, AS patients displayed a higher prevalence of both OP (9.7% vs. 0%) and osteopenia (57.5% vs. 34.9%). The prevalence of OP was significantly higher and the BMD were significantly lower in patients with elevated erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) than patients with normal ESR and CRP. Juvenile onset, morning stiffness lasting over 0.5 hours and elevated ESR levels were risk factors for bone loss at the lumbar spine; Male gender, older age, hip involvement and lack of regular treatment were risk factors for bone loss at the femur. 173 cases were followed up for 1 to 5 years, BMD changes per year at the lumbar spine, femur and forearm were 4.8%, 2.7%, and 2.6% respectively. There was no significant difference in annual BMD change between patients treated with or without low dose glucocorticoids (GCs). Hip involvement and persistent elevated ESR levels, but not GCs treatment, were associated with decreased BMD at both the lumbar spine and the femur during follow-up in longitudinal regression analysis. CONCLUSIONS: High disease activity and hip involvement are risk factors of bone loss in patients with AS. Low-dose GCs treatment in AS does not increase the risk of OP.

Ten years' experience with needle biopsy in the early diagnosis of sacroiliitis.

OBJECTIVE: To evaluate the usefulness of needle biopsy in the diagnosis of early sacroiliitis to improve the diagnostic level and outcome of ankylosing spondylitis (AS). METHODS: One hundred nine patients in whom early AS was highly suspected, but in whom only sacroiliitis of grade I or lower on radiography/computed tomography (CT) was seen, were recruited for study. CT-guided needle biopsy of the sacroiliac joints was performed, and the patients were followed up for 5-10 years. RESULTS: Of the 109 patients, magnetic resonance imaging (MRI) was used to confirm the presence or absence of sacroiliitis in 77 patients. Of these, 23 patients were determined to have sacroiliitis on MRI, and 54 had no sacroiliitis on MRI. Needle biopsy was performed on all 109 patients. Features of inflammation were found in 85 patients, which included all 23 patients with MRI evidence of sacroiliitis and 38 of the 54 patients without MRI evidence of sacroiliitis. No features of inflammation were found on needle biopsy in 24 of the patients, including the remaining 16 patients who did not have sacroiliitis on MRI. The sensitivity and specificity of MRI for the early diagnosis of sacroiliitis in these patients were 37.7% and 100%, respectively. Thirty-four patients with pathologic evidence of sacroiliitis were followed up for 5-10 years. At the study end point, 16 of these 34 patients continued to show grade I or lower changes on CT, and 18 had changes of grade II or higher. These 18 patients included 7 of the 8 patients with evidence of sacroiliitis on MRI and 6 of the 20 patients confirmed not to have MRI evidence of sacroiliitis at baseline. CONCLUSION: MRI, though of low sensitivity, is specific for the diagnosis of early sacroiliitis. Sacroiliitis can be detected earlier by needle biopsy than by MRI.

Burden of nonsteroidal anti-inflammatory and antiplatelet drug use in Asia: a multidisciplinary working party report.

BACKGROUND & AIMS: We established a working group to examine the burden of atherothrombotic and musculoskeletal diseases in Asia and made recommendations for safer prescribing of nonsteroidal anti-inflammatory drugs (NSAIDs) and low-dose aspirin. METHODS: By using a modified Delphi process, consensus was reached among 12 multidisciplinary experts from Asia. Statements were developed by the steering committee after a literature review, modified, and then approved through 3 rounds of anonymous voting by using a 6-point scale from A+ (strongly agree) to D+ (strongly disagree). Agreement (A+/A) by ≥ 80% of panelists was defined a priori as consensus. RESULTS: We identified unique aspects of atherothrombotic and musculoskeletal diseases in Asia. Asia has a lower prevalence of degenerative arthritis and coronary artery disease than Western countries. The age-adjusted mortality of coronary artery disease is lower in Asia; cerebrovascular accident has higher mortality than coronary artery disease. Ischemia has replaced hemorrhage as the predominant pattern of cerebrovascular accident. Low-dose aspirin use is less prevalent in Asia than in Western countries. Traditional Chinese medicine and mucoprotective agents are commonly used in Asia, but their efficacy is not established. For Asian populations, little is known about complications of the lower gastrointestinal tract from use of NSAIDs and underutilization of gastroprotective agents. Our recommendations for preventing ulcer bleeding among users of these drugs who are at high risk for these complications were largely derived from Asian studies and are similar to Western guidelines. CONCLUSIONS: By using an evidence-based, multidisciplinary approach, we have identified unique aspects of musculoskeletal and atherothrombotic diseases and strategies for preventing NSAID-related and low-dose aspirin-related gastrointestinal toxicity in Asia.

Impact of Coronary Artery Anatomy in Arterial Switch Operation: In-hospital and Post-discharge Outcomes.

OBJECTIVE: The influence of the coronary artery anatomy on the prognosis of patients receiving an arterial switch operation (ASO) is currently controversial, and the risk factors for this operation may change in more complicated patients. This study aimed to investigate the influence of coronary artery anomalies on the in-hospital and post-discharge outcomes of ASO in patients with transposition of the great arteries (TGA) and Taussig-Bing anomaly (TBA). METHODS: We retrospectively reviewed 206 patients who underwent ASO from January 2007 to December 2019. The median age at operation was 33 [interquartile range (IQR): 20-71] days. Median follow-up time was 7.2 years (IQR: 4.0-10.3 years). RESULTS: Coronary anomalies were present in 86 patients (41.7%), with 9 (4.4%) of them having a single coronary artery. Additional coronary features included intramural courses in 5 (2.4%) patients, ostial stenosis in 1 (0.5%) patient, and accessory coronary artery orifices in 5 (2.4%) patients. There were 32 (15.5%) in-hospital deaths and 8 (4.6%) post-discharge deaths, yielding an overall survival of 81.3%, 80.7% and 79.9% at 1, 5 and 10 years, respectively. Mortality due to ASO has been drastically decreased since 2013. Patients with a single coronary artery had higher rate of in-hospital mortality, but this finding was not statistically significant. The earlier surgical era (OR: 2.756) and a longer cardiopulmonary bypass time (OR: 2.336) were significantly associated with in-hospital mortality, while coronary patterns were not. An intramural coronary artery (HR: 10.034) and a patient age of older than 1 year at the time of ASO (HR: 9.706) were independent predictors of post-discharge mortality. CONCLUSION: ASO remains the procedure of choice for TGA with coronary anomalies with acceptable in-hospital and post-discharge outcomes in terms of overall survival and freedom of reoperation. However, intramural coronary artery is an independent risk factor for post-discharge mortality. Timely surgery within the 1st year of life helps improve overall midterm survival of ASO.

The role of Smad7 in cutaneous wound healing.

Chronic refractory wounds are generally caused by local tissue defects and necrosis, and they are characterized by delayed wound healing as well as high recurrence, which seriously affects life quality. However, effective therapeutics to treat wounds are currently unavailable. Therapy primarily aims to accelerate generation of granulation tissue and decrease recurrence. The pathogenesis of chronic refractory wounds is closely related to multiple complex signaling pathways and a series of cytokines. Among these signaling pathways, TGF-ß/Smad7 axis plays a critical role. Specifically, Smad7 is an antagonist of TGF-ß that inhibits activation of TGF-ß. Moreover, Smad7 promotes wound healing by regulating cytokines and controlling growth, differentiation and apoptosis of cells, which may be exploited to cure the disease. This review aims to reveal the exact functions and mechanisms of Smad7 in regulation of wound healing.

Associated risk factors of knee osteoarthritis: a population survey in Taiyuan, China.

BACKGROUND: Since knee osteoarthritis (KOA) is one of the common diseases, identification of its associated risk factors is of preventive significance. This investigation was designed to investigate the prevalence of KOA in Taiyuan, and identify the associated risk factors of KOA. METHODS: A population sample was surveyed of 2188 adults aged from 35 to 64 years, living in 6-story buildings without elevators. The protocol of Asia Pacific League of Associations for Rheumatology (APLAR) Community Oriented Program for Control of Rheumatic Diseases (COPCORD) core questionnaire was implemented. The data on knee pain and KOA were collected and analyzed. Variables such as sex, age, body mass index (BMI), waist circumference (WC), education level, and smoking history, were included in binary logistic regression model for further analysis. RESULTS: The prevalence rates of knee pain and KOA were 13.6% and 10.9%, respectively, significantly higher than those in Shantou of south China and similar to those in Beijing of north China. The prevalence of KOA was significantly higher in women than in men (18.3% versus 8.7% and 15.1% versus 6.3%), with a tendency of increase with age. The prevalence was increased more obviously in women after 40 years old and in men after 45 years old. BMI in KOA group was significantly higher than that in non-KOA group. Binary Logistic regression revealed that age, sex, and BMI were significantly associated with KOA, whereas no significant correlation was seen between KOA and other factors such as climbing stairs, WC, time length of occupation service, education level, smoking history and religious belief. CONCLUSION: Geography, age, sex, and BMI might be the risk factors of KOA, but climbing stairs, WC, time length of occupation service, education level, smoking history and religious belief are not correlated with KOA. Prevention of KOA should be initiated before the middle-age, especially in female adults, and weight control is necessary. Other factors might also contribute to the development of KOA, but further study is needed to elucidate the role of these factors.

[A cross-sectional population survey of knee osteoarthritis in Taiyuan region].

OBJECTIVE: Osteoarthritis (OA) of the knee is found to be one of the commonest rheumatic disorders. For prevention of knee OA, the risk factors for this condition should first be identified. METHODS: A population sample of 2188 adults aged 35 - 64 years, living in 6-story buildings without elevators, was surveyed from April to August 2005 in the urban of Taiyuan region, north China. Protocol of APLAR-COPCORD Core Questionnaire for identification of risk factors for knee OA was implemented. The positive respondents were examined simultaneously by rheumatologists. Lateral and anterior-posterior non-weight-bearing knee radiographs were arranged. Variables such as sex, age, body mass index (BMI), waist circumference, education level, and smoking et al, were included in binary logistic regression model for further analysis. RESULTS: Prevalence rate of knee pain and knee OA was 13.6% and 10.9% respectively, significantly higher than that in Shantou--in south of China and similar with Beijing--in north of China. Both of these prevalence was significantly higher in women than that in men (18.3% vs. 8.7% and 15.1% vs. 6.3%), and with a tendency of being increased with age. The prevalence rate of knee OA was increased more obviously in people after 40 years old in women and after 45 years old in men. BMI in knee OA group was significantly higher than that in non-knee OA group. Binary logistic regression revealed that age, sex, and BMI were significantly associated with knee OA. Whereas there were no significant association between the other factors such as climbing stairs, waist circumference, time length of occupation service, education level, smoking, as well as religious belief and knee OA. CONCLUSIONS: Geography, aging (aged > 40 years in woman and > 45 years in man, respectively), female, and overweight (BMI > or = 24 kg/m(2)) might be the associated risk factors of knee OA. No association between climbing stairs and knee OA was found. Prevention of knee OA should be initiated before the middle-aged, especially in female. Controlling body weight and avoiding obesity are important in preventing knee OA.

[Recognition and study of susceptible gene to ankylosing spondylitis].

To study the potential correlations between variances of TNFalpha gene and onset of ankylosing spondylitis in Chinese population, We scanned and analyzed the promoters of TNFalpha genes in 75 AS patients from south of China and found -850 T mutation allele frequency rather high (39.3%).By case-control study, the distribution of TT genotype is significantly higher in AS patients than that in normal subjects (10.7% VS 2.1%,P=0.003); Mutation T allele has a remarkable difference between AS group and normal control (72.2% vs 21.4%,P=2.729 x 10(-9)). The difference in distribution of TX genotype and non -TX genotype is also significant statistically between different genders(male: P=3.42 x 10(-9);female: P=0.001). The result suggests that this variation has a strong association with AS in males and females. No similar reports about the association between AS and the T mutation allele have been acquired. Therefore, our hypothesis can be supported by our results on the whole and the -850 C-->T mutation allele in the region on promoter of TNFalpha gene is likely one of susceptible genes to AS.

A long-term, observational cohort study on the safety of low-dose glucocorticoids in ankylosing spondylitis: adverse events and effects on bone mineral density, blood lipid and glucose levels and body mass index.

OBJECTIVES: This study aimed to investigate the risk of adverse events and effects on bone mineral density (BMD), blood lipid and glucose levels and body mass index (BMI) of low-dose glucocorticoid (GC) treatment in ankylosing spondylitis. DESIGN: We performed a retrospective, observational cohort study. Adverse effects were compared between GC users and non-GC users, and we analysed differences in the duration of GC exposure (no GC exposure, <6 months, 6 months to 2 years and >2 years). SETTING: Outpatient clinic in a tertiary general hospital in China, rheumatology follow-up visits over the past 30 years. PARTICIPANTS: We included 830 patients with ankylosing spondylitis who were followed up for at least 6 months without a previous history or current complications of active gastrointestinal problems, hypertension, psychiatric or mental problems, diabetes mellitus, tuberculosis and hepatitis. The median follow-up time was 1.6 years (range 0.5-15 years, a total of 1801 patient-years). RESULTS: A total of 555 (66.9%) patients were treated with low-dose GCs, and the median cumulative duration of GC therapy was 1.3 years (range 0.1-8.5 years). Dermatological incidents, including acne, bruisability and cutaneous infections, were the most common adverse events, with a cumulative incidence rate of 5.4% (22.2 events per 1000 patient-years), followed by a puffy and rounded face (1.6%), symptoms of weight gain (1.1%) and serious infections (1.0%). The rates of all other types of adverse events were less than 1%. The GC groups (GC users and non-GC users) and the duration of GC therapy were not associated with the frequency of low BMD, dyslipidaemia, hyperglycaemia or obesity (p<0.05). CONCLUSIONS: Adverse events during long-term treatment of low-dose GCs are limited. Low-dose GCs do not have an adverse effect on BMD, blood lipid and glucose levels and BMI.

Changes in the Prevalence of Rheumatic Diseases in Shantou, China, in the Past Three Decades: A COPCORD Study.

This study aimed to clarify changes in the prevalence of rheumatic diseases in Shantou, China, in the past 3 decades and validate whether stair-climbing is a risk factor for knee pain and knee osteoarthritis (KOA). The World Health Organization-International League Against Rheumatism Community Oriented Program for Control of Rheumatic Diseases (COPCORD) protocol was implemented. In all, 2337 adults living in buildings without elevators and 1719 adults living in buildings with elevators were surveyed. The prevalence of rheumatic pain at any site and in the knee was 15.7% and 10.2%, respectively; both types of pain had a significantly higher incidence in residents of buildings without elevators than was reported by people who lived in buildings with elevators (14.9% vs. 10.6% and 11.32% vs. 8.82%, respectively) (both P < 0.0001). The prevalence of rheumatic pain in the neck, lumbar spine, shoulder, elbow, and foot was 5.6%, 4.5%, 3.1%, 1.4%, and 1.8%, respectively; these findings were similar to the data from the 1987 rural survey, but were somewhat lower than data reported in the urban and suburban surveys of the 1990s, with the exception of neck and lumbar pain. The prevalence of KOA, gout, and fibromyalgia was 7.10%, 1.08%, and 0.07%, respectively, and their prevalence increased significantly compared with those in previous studies from the 20th century. There were no significant differences in the prevalence of rheumatoid arthritis (RA) (0.35%) or ankylosing spondylitis (AS) (0.31%) compared to that reported in prior surveys. The prevalence of KOA was higher in for residents of buildings without elevators than that in those who had access to elevators (16-64 years, 5.89% vs. 3.95%, P = 0.004; 16->85 years, 7.64% vs. 6.26%, P = 0.162). The prevalence of RA and AS remained stable, whereas that of KOA, gout, and fibromyalgia has increased significantly in Shantou, China, during the past 3 decades. Stair-climbing might be an important risk factor for knee pain and KOA.

Intrathecal gadolinium (gadopentetate dimeglumine) enhanced magnetic resonance myelography and cisternography: results of a multicenter study.

RATIONALE AND OBJECTIVES: This cooperative multicenter human study was designed to evaluate the safety, magnetic resonance (MR) imaging characteristics, and clinical response to a single gadolinium contrast agent: gadopentetate dimeglumine. MATERIAL AND METHODS: Ninety-five patients (age range: 1 month to 78 years; sex: 50 males, 45 females) were included in this prospective study. The patients presented clinically with a variety of cranial or spinal signs and symptoms for which an intrathecal contrast myelogram or cisternogram was requested by clinical staff. Via lumbar puncture (20-25 g needle), 3 to 5 mL/ml of cerebrospinal fluid were withdrawn and mixed with a single volume of 0.5 (n = 63), 0.7 (n = 13), 0.8 (n = 12), or 1.0 (n = 7) cc/mL of gadopentetate dimeglumine (Magnevist; Schering, Berlin, Germany). This was then injected into the subarachnoid space, and the needle was removed. Immediate and delayed (up to 96 hours) T1- and T2-weighted MR imaging was performed on super conductive, high-field (1.0-1.5 tesla) imaging units in two or three planes. All patients were hospitalized for an observation period of 24 hours following the procedure, and follow-up neurologic examinations were performed serially for 6 to 12 months afterward. RESULTS: No patient manifested gross behavioral changes, neurologic alterations, or seizure activity at any time following the procedure. Nineteen patients (20%) experienced postural postlumbar puncture headache, six patients had nausea (6%), and two patients had episodes of vomiting (2%), all which resolved within the first 24 hours of the lumbar puncture with conservative bed rest. CONCLUSION: This cooperative study demonstrates the general safety and feasibility of low dose (0.5-1.0 mL/ml) intrathecal gadopentetate dimeglumine administration. The potential useful clinical applications include the evaluation of obstructions and communications of the various subarachnoid spaces, spontaneous or traumatic/postsurgical craniospinal cerebrospinal fluid leaks, and subarachnoid space CSF flow and parenchymal CNS interstitial diffusion dynamics. This worldwide cooperative study seeks to progressively perform human studies for further definitive evaluation of the practical clinical applications, of the relationship of this technique to other imaging studies and modalities, and the long-term safety of the procedure in a larger number of subjects.

[Needle biopsy of spondyloarthropathy: pathological features and clinical significance].

OBJECTIVE: To study the pathological features of sacroiliitis, aiming at improving the early diagnosis of ankylosing spondylitis (AS). METHODS: CT guided needle biopsy of sacroiliac joint (SIJ) was performed in 96 cases of spondyloarthropathy (SpA) patients with 3 autopsy materials of non-SpA sacroiliac joints serving as control. Pathological features were studied by two independent observers. Clinical data were collected and analyzed. RESULTS: No pathological change was noticed in the control group. Among the 96 cases of SpA, pathological changes were found in 76 cases, including bone marrow inflammation, pannus formation, subchondral bony plate destruction, cartilage degeneration/erosion, synovitis, and enthesitis. The aforementioned first 4 findings were present in 45 cases of grade 0/I CT sacroiliitis. In the synovial specimens obtained, synovitis was seen in some cases of grade I and all of >/= grade II CT sacroiliitis,while no inflammatory change was noticed in all cases of grade 0 CT sacroiliitis. Frequency rate of cartilage erosion and ossification in grade 0/I CT sacroiliitis was the lowest in comparison with the other groups. Moreover, in cases of grade 0/I CT sacroiliitis, cartilage erosion only present at the bony plate side, while the joint cavity side was not affected. The inflammatory index was significantly lower in cases of grade IV CT sacroiliitis than that in the other groups. Enthesitis only presented in some cases of >/= grade II CT sacroiliitis. Among the 65 undifferentiated spondyloarthropathy patients, 45 were diagnosed as AS after SIJ pathological examination. The mean disease duration of these 45 cases was significantly shorter than that in cases of >/= grade II CT sacroiliitis. CONCLUSIONS: Inflammatory changes of SIJ did exist in cases of the < grade II CT sacroiliitis. Sacroiliitis probably initiated with bone marrow inflammation, followed by pannus formation, subchondral bony plate destruction, and cartilage degeneration/erosion, eventually leading to fibrosis, ossification and joint fusion. Synovitis and enthesitis were not the very early changes of sacroiliitis. Pathological examination was beneficial to the early diagnosis and differential diagnosis of ankylosing spondylitis.

Arylamine N-acetyltransferase polymorphisms in Han Chinese patients with ankylosing spondylitis and their correlation to the adverse drug reactions to sulfasalazine.

BACKGROUND: Polymorphisms of Arylamine N-acetyltransferase (NAT) that contribute to diverse susceptibilities of some autoimmune diseases are also linked to the metabolism of several drugs including sulfasalazine (SSZ). The aim of this study was to investigate the distribution of NAT polymorphisms in Han Chinese patients with ankylosing spondylitis (AS) and their correlation to sulfasalazine-induced adverse drug reactions (ADRs). METHODS: Arylamine N-acetyltransferase 1 (NAT1) and arylamine N-acetyltransferase 2 (NAT2) genotypes were determined in 266 AS patients who received SSZ treatment and 280 healthy controls. The correlation between NAT polymorphisms and SSZ-induced ADRs was analyzed. RESULTS: The co-occurrence frequency of NAT2 fast acetylator genotype and NAT1*10/NAT1*10 genotype was lower in AS patients than in controls. No positive correlations were detected between NAT polymorphisms and AS clinical features. The prevalence of SSZ-induced ADRs and drug withdrawal was 9.4% and 7.1%, respectively. The frequencies of overall ADRs, dose-related ADRs, and termination of drug treatment because of intolerance were higher in the NAT2 slow acetylator genotype carriers than in the fast-type carriers and in those with co-existence of NAT1 and NAT2 slow acetylator genotypes. Furthermore, the ADRs emerged earlier in the AS cases carrying both NAT1 and NAT2 slow acetylator genotypes. CONCLUSIONS: The prevalence of co-occurring NAT2 fast acetylator genotype and NAT1*10/NAT1*10 genotype was lower in AS patients than in controls. The NAT2 slow acetylator genotype and co-existing NAT1 and NAT2 slow acetylator genotypes appear to be associated with higher risks of SSZ-induced ADRs.