Immune checkpoint inhibitor-induced eosinophilic fasciitis: a case report and literature review / 中华内科杂志

A 58-year-old male patient with angioimmunoblastic T-cell lymphoma developed a rash and skin tightness on the face, limbs, and trunk together with joint stiffness and dysfunction after 6 months of treatment with the programmed cell death protein-1 inhibitor camrelizumab. Laboratory tests revealed progressive eosinophilia over 6 months, with the eosinophil count increasing from 0.07×10 9/L to 3.3×10 9/L. Magnetic resonance imaging showed thickened skin of both forearms, while T 2-weighted imaging showed markedly increased signal intensity within the myofascia. Skin biopsy of the right forearm showed thickened and fibrosed fascia and infiltration of inflammatory cells, including lymphocytes, plasma cells, and eosinophils. The patient was diagnosed with immune checkpoint inhibitor (ICI)-induced eosinophilic fasciitis (EF). After beginning treatment with methylprednisolone (40 mg daily), methotrexate (10 mg/week), and baricitinib (4 mg daily), his symptoms of skin tightness and joint dysfunction significantly improved within 1 month, and his peripheral blood eosinophil count decreased to 0.17×10 9/L. ICI-induced EF is a rare immune-related adverse reaction. To date, only 20 cases have been reported in published foreign literature, and their clinical characteristics are summarized here. The time from ICI treatment to EF was 12 (8,15) months, and the main clinical manifestations included skin involvement ( n=19), joint dysfunction ( n=11), myalgia/muscle weakness ( n=9), and peripheral eosinophilia ( n=16). After treatment, the clinical symptoms of EF improved in 17 patients, and eosinophil counts returned to normal after 3 (1,8) months. EF is a dysfunctional adverse response to ICI therapy. Tumor patients undergoing immunotherapy should be monitored for symptoms of EF. Early treatment is essential for preventing complications.

The characteristics of non-alcoholic fatty liver disease and its associated factors in patients with rheumatoid arthritis / 中华预防医学杂志

Objective: To investigate the characteristics of non-alcoholic fatty liver disease (NAFLD) and its associated factors in rheumatoid arthritis (RA) patients. Methods: This cross-sectional study recruited 385 RA patients [including 72 (18.7%) male and 313 (81.3%) female] who received abdominal sonographic examination from August 2015 to May 2021 at Department of Rheumatology, Sun Yat-Sen Memorial Hospital. There were 28 RA patients at 16-29 years old and 32, 80, 121, 99, 25 at 30-39, 40-49, 50-59, 60-69, ≥ 70 years old, respectively. Demographic and clinical data were collected including age, gender, history of alcohol consumption, disease duration, body mass index (BMI), waist circumference, blood pressure, RA disease activity indicators and previous medications. Logistic regression analyses were used to identify the associated factors of NAFLD in RA patients. Results: The prevalence of NAFLD was 24.2% (93/385) in RA patients, 26.3% (21/80) in 40-49 age group and 33.1% (40/121) in 50-59 age group. There were 22.1% (85/385) and 3.6% (14/385) RA patients with overweight and obese, in which the prevalence of NAFLD was 45.9% (39/85) and 78.6% (11/14) respectively, which was 2.6 folds and 4.5 folds that of RA patients with normal BMI. Although there was no significant difference of age, gender and RA disease activity indicators between RA patients with or without NAFLD, those with NAFLD had higher proportions of metabolic diseases including obese (11.8% vs. 1.0%), central obesity (47.3% vs. 16.8%), hypertension (45.2% vs. 29.8%) and type 2 diabetes mellitus (24.7% vs. 12.0%), consistent with higher levels of total cholesterol [(5.33±1.31) mmol/L vs. (4.73±1.12) mmol/L], triglyceride [(1.51±1.08) mmol/L vs. (0.98±0.54) mmol/L] and low-density lipoprotein cholesterol [(3.37±0.97) mmol/L vs. (2.97±0.78) mmol/L, all P<0.05]. Multivariate logistic regression analysis showed that BMI (OR=1.314) and triglyceride (OR=1.809) were the independent factors positively associated with NAFLD in RA patients. Conclusion: NAFLD is a common comorbidity in RA patients, especially in those with middle-aged, overweight or obese, which is associated with high BMI or high triglyceride. Screening and management of NAFLD in RA patients especially those with overweight, obese or dyslipidemia should be emphasized.

The characteristics and associated factors of functional limitation in patients with rheumatoid arthritis / 中华内科杂志

Objective:To investigate the characteristics of functional limitation and associated factors in patients with rheumatoid arthritis (RA).Methods:Consecutive patients with RA were recruited from August 2015 to June 2019 at Department of Rheumatology, Sun Yat-Sen Memorial Hospital. Demographic and clinical characteristics including age, gender, erythrocyte sedimentation rate (ESR), visual analogue scale (VAS) of pain, clinical disease activity index (CDAI), modified total Sharp score were collected. Physical function was assessed by the Stanford health assessment questionnaire disability index (HAQ-DI).Ordered logistic regression was used to analyze the related factors of HAQ-DI.Results:A total of 643 RA patients were finally recruited including 114 males and 529 females with mean age (49.7±12.9) years. There were 399 (62.1%) patients having different degrees of functional limitation, who were classified as mild (293, 45.6%), moderate (73, 11.4%) and severe (33, 5.1%). The prevalence of functional limitation was positively correlated with age and disease activity. The most restricted activity was walking [43.5% (280/643)], followed by gripping [36.1% (232/643)], reaching [35.5% (228/643)], daily activities [33.4% (215/643)], hygiene [33.0% (212/643)], dressing and grooming [29.7% (191/643)] and arising [29.1% (187/643)], and the last eating [18.4% (118/643)]. Multivariate ordered logistic regression analysis showed that age ( OR=1.019, 95% CI 1.004-1.035),pain VAS ( OR=1.820, 95% CI 1.616-2.050), ESR ( OR=1.009, 95% CI 1.001-1.017), CDAI ( OR=1.080, 95% CI 1.059-1.102) and modified total Sharp score ( OR=1.010, 95% CI 1.004-1.015) were associated factors of functional limitation. Conclusion:The majority RA patients have functional limitation. Age, pain and active disease are independent associated factors. Therefore, target treatment and control of pain should be emphasized in RA patients.

The prevalence of hypertension and its associated factors in patients with rheumatoid arthritis / 中华风湿病学杂志

Objective:To investigate the prevalence of hypertension and its associated factors in rheumatoid arthritis (RA) patients.Methods:Consecutive Chinese patients with RA were recruited from August 2015 to September 2019 at Department of Rheumatology, Sun Yat-sen Memorial Hospital. Demo-graphic data and clinical data were collected including indicators of disease activity, functional assessment and radiographic assessment, comorbidities and previous medications. Logistic regression analysis was used to evaluate the related factors of hypertension in RA patients.Results:There were 674 RA patients recruited with 82.3%(555/674) female and mean age (50±13) years. The prevalence rate of hypertension was 32.9% (222/674), followed by dyslipidemia (9.9%, n=67), type 2 diabetes (8.8%, n=59), hyperuricemia (8.5%, n=43), fatty liver disease (8.0%, n=54), cardiovascular disease (6.2%, n=42) and chronic kidney disease (3.3%, n=22). Compared with those without hypertension, RA patients with hypertension had advanced age with longstanding disease duration, higher disease activity indicators, worse joint destruction, and higher proportions of comorbidities. Multivariate logistic regression analysis showed that comorbidities including hyperuricemia [ OR=1.977, 95% CI(1.002, 3.900)], dyslipidemia [ OR=1.903, 95% CI(1.102, 3.288)] and fatty liver disease [ OR=2.335, 95% CI(1.278, 4.265)] were risk factors of hypertension after adjustment for age and gender. Conclusion:Hyperten-sion is the most common comorbidity in RA patients which is associated with comor-bidities including hyperuricemia, dyslipidemia and fatty liver disease. Detection and management of hyperten-sion and other cardiovascular disease related comorbidities in RA patients should be emphasized.

Standardized diagnosis and treatment of undifferentiated connective tissue disease and mixed connective tissue disease / 中华内科杂志

Undifferentiated connective tissue disease (CTD) usually refers to patients who are presented with certain symptoms and signs related to CTD, and positive serological evidence of autoimmune diseases but don′t fulfill any of the classification criteria for a certain CTD. Mixed CTD refers to patients who are presented with one or more clinical manifestations such as hand swelling, synovitis, myositis, Raynaud′s phenomenon, and acrosclerosis. Patients with mixed CTD always have high-titer anti-nuclear antibodies (ANA) of speckled pattern and high-titer anti-U 1 ribonuclear protein (RNP) antibody in serum, while with negative anti-Sm antibody. The update of diagnosis and treatment of undifferentiated CTD and mixed CTD lags behind other established CTD. There is a lack of evidence from randomized controlled trials or guidelines/recommendations on the treatment of undifferentiated CTD or mixed CTD. At present, the conventional therapy is mainly adopted according to the specific clinical manifestations of the disease. The standardized diagnosis and treatment of undifferentiated CTD and mixed CTD were drafted by the Chinese Rheumatology Association based on the previous guidelines and the progress of available evidence, so as to improve the management of these patients in China.

Skin sclerosis, hypertension and renal insufficiency: a report of one case with literture review / 中华风湿病学杂志

Objective:To improve the differential diagnosis of systemic sclerosis (SSc) with hypertension and renal insufficiency.Methods:The clinical characteristics, diagnosis and treatment of a SSc patient with hypertension and renal insufficiency were reported and discussed.Results:A middle-aged female patient with a history of SSc for 5 years, headache and gross hematuria for 10 days was admitted. Abrupt increase in blood pressure and creatinine, glomerular hematuria, proteinuria, low complement C3 and C4, positive antinuclear antibody (ANA), anti-dsDNA antibody and perinuclear antineutrophil cytoplasmic antibody (pANCA) were presented. Renal pathology showed lupus nephritis (LN) (type Ⅳ). After glucocorticoid pulse therapy, followed by cyclophosphamide, belimumab, and symptomatic treatment, the symptoms were relievedand lupus disease activity were decreased.Conclusion:For SSc patients with increased blood pressure and creatinine, the presence of other diseases should be considered in addition to scleroderma renal crisis. Renal biopsy and pathological examination should be performed to confirm the diagnosis and avoid misdiagnosis.

Case series of patients with cholesterol crystal embolism syndrome that mimics systemic vasculitis / 中华风湿病学杂志

Objective:To improve the awareness of cholesterol crystal embolism syndrome (CCE) inrheumatologists.Methods:The clinical characteristics of 40 Chinese CCE patients admitted to our department (one case) were summarize and in the literature (thirty-nine cases) were reviewed.Results:Among these 40 patients, 87.5%(35/40) were male and the mean age was (68±6) years. All patients suffered from athero-sclerosis and 87.5%(35/40) of them had precipitating factors such as endovascular intervention, vascular surgery, anticoagulant, or thrombolytic therapy. The clinical manifestations included renal insufficiency (90.0%, 36/40), blue toe syndrome (82.5%, 33/40), ulceration or gangrene (25.0%, 10/40), and livedo reticularis (15%, 6/40). Acute phase reactant was tested in 25 cases, of whom 84.0%(21/25) showed elevated C-reactive protein (CRP) and 56.0%(14/25) showed elevated erythrocyte sedimentation rate (ESR).Conclusion:Rheumatologists should be alert that CCE is one of the differential diagnosis of systemic vasculitis, especially for patients with severe atherosclerosis.

Clinical characteristics of 52 patients with eosinophilic granulomatosis with polyangiitis / 中华风湿病学杂志

Objective:To analyze the clinical characteristics of patients with eosinophilic granulo-matosis with polyangiitis (EGPA) and improve the understanding of the disease.Methods:EGPA patients who fulfilled the 1990 American College of Rheumatology (ACR) classification criteria were recruited from Sun Yat-sen Memorial Hospital Sun Yat-sen University between December 2003 and April 2020. Their demographic characteristics, clinical manifestations, laboratory and auxiliary examinations were analyzed retrospectively. Mann-whitney U test and χ2 test were used for statistical analysis. Results:Among 52 EGPA patients, 34 (65.4%) were males and the median age at disease onset was 47(38-55) years. The median time from disease onset to diagnosis was 30(4-96) months. The most common initial symptoms were respiratory (61.5%) and nose/paranasal sinus (21.2%) involvement. The most common department for the first visit was respiratory medicine (53.8%), followed by rheumatology (11.5%). 44.2% EGPA patients were diagnosed by rheumatologists. The most common clinical manifestations were asthma (88.5%), nose/paranasal sinusitis (84.6%), pulmonary (76.9%) and nervous system (61.5%) in volvement. Eight(15.4%) patients were positive for antineutrophil cytoplasmic antibodies (ANCA). Patients with positive ANCA had lower incidence of asthma, but higher incidence of general symptoms especially arthralgia and renal involvement, elevated eosinophil count, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), Birmingham vasculitis activity score and vasculitis damage index than patients with negative ANCA (all P<0.05). 21.2%-34.6% EGPA patients had poor prognostic factors. Conclusion:Early diagnosis of EGPA is important. EGPA patients with positive ANCA may be more severe than patients with negative ANCA. The management should be a multi-disciplinary collaboration between rheumatologists and pulmonologists.

Patterns of tocilizumab use in clinical practice of rheumatoid arthritis: a multi-center, non-interventional study in China / 中华风湿病学杂志

Objective:To study the patterns of tocilizumab (TCZ) use, its efficacy and safety in patients with rheumatoid arthritis (RA) in routine clinical practice.Methods:A total of 407 patients with RA were enrolled from 23 centers and treated with TCZ within 8 weeks prior to the enrollment visit, and were followed for 6-month. The patterns of TCZ treatment at 6 months, the effectiveness and safety outcomes were recorded. Statistical analysis was performed using SAS version 9.4.Results:A total of 396 patients were included for analysis, in which 330 (83.3%) patients received TCZ combined with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), and 16.7%(66/396) received TCZ monotherapy. At baseline, TCZ was initiated in 56.6%(224/396) and 9.6%(38/396) of patients after failure of DMARDs and other biological agents (bDMARDs) respectively. During the 6-month follow-up period, the mean frequency of TCZ administration was (3.7±1.6), the mean TCZ dosage was (7.4±1.2) mg/kg, and the mean interval between doses was (40±13) days. 120(25.8%) patients were on TCZ treatment at the end of the study. Improvements in disease activity, systemic symptoms and patient report outcomes were observed at the end of the study. 22.7%(90/396) patients experienced at least one treatment related adverse event, and 8 patients experienced at least one serious adverse event.Conclusion:This study demonstrates that TCZ treatment is effective in patients with RA when being treated for 6 months with an acceptable safety profile. The duration of TCZ treatment needs to be extended.

Characteristics and clinical significance of body composition in gout patients / 中华内科杂志

Objective@#To investigate the characteristics of body composition (BC) in gout patients and its clinical significance.@*Methods@#Consecutive gout patients were recruited between August 2017 and December 2018. Demographic information, clinical characteristics and comorbidities were collected. BC was assessed by bioelectric impedance analysis including body fat percentage (BF%), trunk and limb BF%, appendicular skeletal muscle index. Overfat was defined by BF% ≥25% for male and ≥35% for female. The association between BC and serum uric acid (sUA) was evaluated by multiple linear regression.@*Results@#A total of 362 gout patients were recruited with median age 38 (30, 52) years, 96.1% (348/362) were male. Mean sUA was (551±133) μmol/L. The mean BF% was (25.8±6.4)% with 53.6%(194/362) patients overfat. Male gout patients with overfat showed more affected joints [4(2, 6) vs. 2(2, 5)], higher sUA [(576±126)μmol/L vs. (523±134) μmol/L], higher prevalence of dyslipidemia [70.1%(131/187) vs. 54.0%(87/161)], metabolic syndrome [60.8%(118/187) vs. 28.0%(47/161)], fatty liver [58.2%(113/187) vs. 35.1%(59/161)] and hypertension [44.4%(83/187) vs. 25.5%(41/161)] than male patients with normal fat (all P<0.05). Their BF%, trunk BF% and limb BF% were positively correlated with the numbers of affected joints, sUA, metabolic syndrome, fatty liver, and hypertension, respectively (r=0.154-0.435, all P<0.05). Multivariable linear regression suggested that BF% (β=4.29, P=0.020) and trunk BF% (β=9.11, P=0.007), but not limb BF%, were positively correlated with sUA.@*Conclusion@#Overfat is very common in gout patients. The proportion of trunk fat in male patients is positively correlated with sUA. When assessing obesity in gout patients clinically, body composition analysis should be performed simultaneously.

Characteristics and clinical significance of body composition in gout patients / 中华内科杂志

Objective To investigate the characteristics of body composition (BC) in gout patients and its clinical significance. Methods Consecutive gout patients were recruited between August 2017 and December 2018. Demographic information, clinical characteristics and comorbidities were collected. BC was assessed by bioelectric impedance analysis including body fat percentage (BF% ), trunk and limb BF%, appendicular skeletal muscle index. Overfat was defined by BF%≥25% for male and≥35% for female. The association between BC and serum uric acid (sUA) was evaluated by multiple linear regression. Results A total of 362 gout patients were recruited with median age 38 (30, 52) years, 96.1% (348/362) were male. Mean sUA was(551±133)μmol/L. The mean BF% was (25.8±6.4)% with 53.6%(194/362) patients overfat. Male gout patients with overfat showed more affected joints [4(2, 6) vs. 2(2, 5)], higher sUA [(576 ± 126)μmol/L vs. (523 ± 134) μmol/L], higher prevalence of dyslipidemia [70.1%(131/187) vs. 54.0%(87/161)], metabolic syndrome [60.8%(118/187) vs. 28.0%(47/161)], fatty liver [58.2%(113/187) vs. 35.1%(59/161)] and hypertension [44.4%(83/187) vs. 25.5%(41/161)] than male patients with normal fat (all P<0.05). Their BF% , trunk BF% and limb BF% were positively correlated with the numbers of affected joints, sUA, metabolic syndrome, fatty liver, and hypertension, respectively (r=0.154-0.435, all P<0.05). Multivariable linear regression suggested that BF% (β=4.29, P=0.020) and trunk BF% (β=9.11, P=0.007), but not limb BF% , were positively correlated with sUA. Conclusion Overfat is very common in gout patients. The proportion of trunk fat in male patients is positively correlated with sUA. When assessing obesity in gout patients clinically, body composition analysis should be performed simultaneously.

Characteristics of Uric Acid Excretion in Gout Patients with Obesity / 中山大学学报(医学科学版)

@#【Objective】To explore clinical manifestations and features of renal uric acid excretion in gout patients with obesity.【Methods】Totally 228 primary gout patients were enrolled and divided into three groups according to body mass index（BMI）. Clinical and fasting blood biochemical analysis data were collected. Indices of renal uric acid excretion were calculated according to 24 h urinary uric acid and urinary creatinine.【Results】The obese group（n = 44）was younger than overweight group（n = 88）and non-overweight group（n = 96）［43（32，57）years vs 55（45，65）years，58（45，67）years］，with earlier onset age［37（26，48）years vs 48（38，59）years］，higher serum uric acid［594（522，697）μmol/L vs 511（372，653）μmol/L］and had more hypercholesterolemia（56.8% vs 31.3%）and low density lipoproteinemia（59.1% vs 47.9%）compared with non-overweight group. The ratio of hypertriglyceridemia（43.5% and 37.5% vs 17.7%）and metabolic syndrome（50.0% and 36.4% vs 12.5%）in the overweight and obese group were both higher than non- overweight group. Fraction excretion of uric acid（FEUA）in obese group［5.5（3.6，7.4）% vs 7.0（5.2，9.8）%］was lower than non-overweight group，and the glomerular filtration load of uric acid［5.3（4.2，7.5）mg·min- 1 ·1.73 m- 2 vs 3.5（2.2，5.2）mg·min-1·1.73 m-2］in obese group was higher than that in non-overweight group（All P < 0.0167）. Multivariate regression analysis showed that overweight or obesity were negatively correlated with FEUA（All P < 0.05）.【Conclusion】High uric acid load of serum and glomerular filtration in gout patients with obesity may be due to the relative insufficiency of renal uric acid excretion.

Clinical characteristics and renal uric acid excretion in early-onset gout patients / 中华内科杂志

Objective To investigate clinical characteristics and renal uric acid excretion in early-onset gout patients.Methods Consecutive inpatients with primary gout were recruited between 2013 and 2017.The patients with gout onset younger than 30 were defined as early-onset group while the others were enrolled as control group.Clinical characteristics and uric acid (UA) indicators were compared between two groups.Results Among 202 recruited patients,the early-onset group included 36 patients (17.8％).Compared with control group,the early-onset group presented more patients with obesity [13 patients (36.1％) vs.22 patients (13.3％),P＜0.05],significantly higher serum UA level [(634± 124)μmol/L vs.(527± 169).μmol/L] and glomerular load of UA[(7.2±2.8)mg· min-1 · 1.73m-2 vs.(4.4±2.2)mg· min-1 · 1.73m-2] and estimated glomerular filtration rate (GFR) [(83±21)ml· min-1 · 1.73m-2 vs.(67±21)ml· min-1 · 1.73m-2] (all P＜ 0.05),lower fractional excretion of UA [4.4％ (3.4％,6.1％) vs.7.2％ (5.2％,9.6％),P＜0.05],whereas 24h urinary UA excretion was comparable [(2 788±882)l,μmol/1.73m2 vs.(2 645±1 140)μmol/1.73m2,P=0.274].Subgroup analysis of patients without chronic kidney disease showed significantly lower fractional excretion of UA in the early-onset group [4.5％(3.3％,6.1％) vs.6.7％ (5.1％,8.7％),P＜0.05].Logistic regression analysis showed that obesity (OR=3.25) and fractional excretion of UA less than 7％ (OR=9.01,all P＜0.05) were risk factors of gout early onset.Conclusion The gout patients with early-onset younger than 30 present high serum and glomerular load of uric acid which might be due to obesity and relative under-excretion of renal uric acid.

The reliability and validity of short form-36 questionnaire in patients with gout / 中华风湿病学杂志

Objective To investigate the reliability and validity of the medical outcomes by applying short form-36 (SF-36) in evaluating gout patients’ health related quality of life (HRQOL).Methods Gout patientswere enrolled between March 2016 and June 2016 in Foshan Hospital of Traditional Chinese Medicine.Patients completed the SF-36 questionnaire.Summary scores,physical component summary (PCS) and mental component summary (MCS) were calculated by summing factor-weighted scores across all 8 subscales,with factor weights derived from general population.The indicators of reliability and validity included internal consistency,test-retest reliability,structural and discriminant validity,ceiling and floor effect.Results Totally 306 patients were enrolled.The internal consistency test showed that the Cronbach α coefficients ranged from 0.782 to 0.822,and the test-retest reliability coefficients ranged from 0.720 to 0.986 (P＜0.01).Structural validity analysis showed that there were two items whose eigenvalues were greater than one with the cumulative contribution rate of 66.1％.The discriminant validity analysis found that patients with more numbers of tophi,higher frequency of flare,multi-arthrosis involved and more complications had less scores of PCS and MCS (P＜0.05).There was a high ceiling effect on physiological function and a higher ceiling and floor effect on role limitation and emotional function caused hy impaired physical health.Conclusion The SF-36 can be used for the assessment of HRQOL in Chinese gout patients but disease specific questionnaire are warranted.

Rosiglitazone inhibits osteoclastogenesis in rheumatoid arthritis by down-regulating RANKL expression and suppressing ERK phosphorylation / 中国病理生理杂志

AIM: To investigate the effects of rosiglitazone on fibroblast-like synoviocyte ( FLS )-induced osteoclastogenesis in rheumatoid arthritis ( RA) and the related mechanism.METHODS: RA-FLS were cocultured with peripheral blood monocytes from healthy volunteers in the presence of macrophage colony-stimulating factor ( M-CSF) and rosiglitazone.Osteoclasts were assayed by tartrate-resistant acid phosphatase ( TRAP) staining.Resorption lacunae area was identified by toluidine blue staining and quantified by image analysis software.The mRNA expression of RANKL and OPG was evaluated by real-time PCR, and the protein levels of RANKL, OPG, p-ERK, p-p38 and p-JNK were measured by Western blot.RESULTS:Compared with control group ( without rosiglitazone treatment) , rosiglitazone at concentration of 15 μmol/L significantly decreased the number of osteoclasts (P0.05 ) . CONCLUSION:Rosiglitazone inhibits RA-FLS-induced osteoclast formation and its resorption activity by down-regulating RANKL expression and ERK phosphorylation, suggesting that rosiglitazone may inhibit RA osteoclastogenesis and bone re-sorption.

Efficacy of tocilizumab on disease activity and psychological state in patients with refractory rheumatoid arthritis / 中华风湿病学杂志

Objective To observe the efficacy and safety of tocilizumab on patients with refractory rheumatoid arthritis (RA).Methods Eighteen RA patients who were refractory to disease-modifying antirheumatic drugs (DMARDs) or tumor necrosis factor-α (TNF-α) antagonist were treated with tocilizumab were included into this study.Their clinical disease activity indices,Hospital Anxiety and Depression Scale (HADS)and safety were evaluated regularly.Statistical analysis was conducted with Mann-Whitney U test and x2 test.Results According to clinical disease activity index,44％(8/18) of patients reached treatment target 2 weeks after the first infusion of tocilizumab,and 78％ (14/18) reached treatment target after three infusions of tocilizumab.Fifty-six percent (10/18) of patients had anxiety and 22％ (4/18) had depressive symptoms at baseline.After three infusions of tocilizumab,6％(1/18) had anxiety symptoms and 11％(2/18) had depressive symptoms.The adverse effects included upper respiratory tract infection,aminotransferase elevation and neutropenia (3 patients,respectively).Conclusion Tocilizumab can rapidly and significantly improve the disease activity and psychological state with good tolerance and safety,which can be applied to Chinese refractory RA patients who failed with DMARDs or TNF-α antagonist.

Survey on doctor's screening practice and clinical management for hepatitis B virus infection in patients with rheumatoid arthritis / 中华风湿病学杂志

Objective To investigate doctor's screening practice for hepatitis B virus (HBV) infection before immunosuppressive therapy for rheumatoid arthritis (RA) patients and clinical management of RA patients with positive surface antigen of HBV (HBsAg).Methods One hundred fifty doctors who treated RA patients in daily clinic were survied with a modified American College of Rheumatology (ACR) questionnaire which was composed of demographic data and 10 multiple-choice questions.Step-forward logistic regression analysis was performed to find out the influencing factors,then receiver operator characteristic curve analysis and area under the curve were performed to confirm the influencing factors.Results One hundred and thirtytwo effective questionnaires were collected.Before immunosuppressive therapy,HBV screening rate in outpatients with RA was significandy lower than that in hospitalized patients (68.7％ vs 94.6％,x2=31.5,P＜0.01).Only 23.7％(31/131) of doctors considered antiviral treatment for all RA patients with positive HBsAg.One hundred and thirteen doctors had clinical experience of antiviral treatment,but only 30.1％(34/113) and 23.9％ (27/113) of these doctors chose entecavir or adefovir as the antiviral drug respectively,59.3％ (67/113) prescribed antiviral drug before or together with immunosuppressive therapy compared with 40.7％(46/113) after HBV reactivation.Only 20.4％(23/113) of doctors would sustain antiviral treatment until the termination of steroid or disease modifying antirheumatic drugs (DMARDs).During immunosuppressive therapy for HBsAg(+) RA patients,11.4％(15/132) and 30.3％(40/132) of doctors reported no regular monitoring of aminotransferase or HBV DNA respectively.Conclusion Our survey shows that HBV screening rate in outpatients with RA is low and low awareness of antiviral treatment for all RA patients with positive HBsAg,and lack of awareness of indication,choosing of antiviral drugs,initiation,monitoring and duration of antiviral treatment during immunosuppressive therapy.Further medical education on the associated information and importance to collaborate with hepatologists should be emphasized.

Dynamic expression and significance of Bcl6 in fibroblast-like synoviocytes induced osteoclast differentiation and activation in rheumatoid arthritis / 中华风湿病学杂志

Objective To investigate the dynamic expression and significance of B cell lymphoma (Bcl) 6 in fibroblast-like synoviocytes (FLS) induced osteoclast differentiation and activation in rheumatoid arthritis (RA) patients.Methods RA-FLS were co-cultured with peripheral blood monocytes (PBMCs) from healthy volunteers in the medium containing M-CSF.Bcl6 protein and mRNA in osteoclasts and their precursors were determined by immunofluorescence and Real-time PCR at day 0,7,14 and 21,respectively.Osteoclasts were identified by tartrate-resistant acid phosphatase (TRAP) staining.Bone resorption activity of osteoclasts was determined by bone slices stained with toluidine blue.Kruskal-Wallis H and Bonferroni were used for statistical analysis.Results ① Immunofluorescence staining and TRAP staining showed that Bcl6 protein was mainly expressed in the nuclei of PBMCs.After co-cultured with RA-FLS for 7 days,some PBMCs differentiated into macrophages and a few differentiated to TRAP-positive multinucleated osteoclasts,and the total Bcl6 protein expression in osteoclasts and their precursors were increased.At day 14,the total Bcl6 protein expression was increased further.At day 21,the Bcl6 protein expression in nuclei of osteoclasts was decreased while PBMCs were differentiated into osteoclasts,and total Bcl6 protein expression was decreased.②Real-time PCR showed that Bcl6 mRNA expression in osteoclasts and their precursors at day 7 tended to increase than that at day 0 (x2=3.429,P＞0.05).At day 14 after co-cultured with RA-FLS,Bcl6 mRNA expression in osteoclasts and their precursors was significantly higher than that at day 0 (x2=5.333,P=0.045).At day 21,the expression of Bcl6 mRNA was significantly lower than that at day 14 (x2=6.023,P=0.038).Conclusion Bcl6 may be involved in osteoclast differentiation and activation,and may play a role in the inflammatory status in the process of differentiation from PBMCs to macrophages.Further studies are needed to establish the mechanisms.

Application of the modified team-based learning in internal medicine practice teaching for eight-year clinical students / 中华医学教育探索杂志

Targeting to improve clinical thinking and practice skill of interns, modified Team-based learning (TBL) based on seeing real patient was performed for interns from eight-year clinical medicine program. Teachers prepared the corresponding case material before the teaching and made teaching aids. And interns were mobilized and guided to preview and self-study in teams. During modi-fied TBL, in-class application of seeing real patient was performed to assess the effect of self-study in teams, besides individual test and team test deriving from traditional TBL. All teams were assigned one task of seeing real patient by drawing lots, and then finished the task, answered teachers' questions. And the students' performance was given comments and comprehensive scores by the judges. After the completion of teaching, the teaching effectiveness of the modified TBL was assessed from students' performance, their scores and their teaching evaluation. Practice shows that the modified TBL can not only attract students to engage in it, but also elevate their abilities of clinical thinking and practical skill. It can also cultivate their interpersonal ability.

Management window for patients with atrial fibrillation in community health center / 中华全科医师杂志

A management window model for patients with atrial fibrillation (AF) was established in Tilanqiao Community Health Service Center cooperated with tertiary hospitals.Patients were screened and treated in the community health service center,and a comprehensive management plan was conducted and patients were followed-up.A total of 105 patients with atrial fibrillation (97.2％) were effectively managed with an average follow-up of 10.6 months.The CHADS2 score ≥ 2 in 78 cases,including 11 cases with administration of warfarin (14.1％) and 26 cases with paroxysmal AF without transition to persistent atrial fibrillation.Compared to the data before management,the rate of taking aspirin and warfarin in managed patients was increased (all P ＜ 0.05),the international normalized ratio (INR) of patients receiving warfarin was improved (P ＜ 0.05) ; the ratio of receiving comprehensive treatment program,standardized treatment and health education were significantly increased (P ＜ 0.05) ; the awareness of the disease,treatment compliance and satisfaction of patients were improved significantly (all P ＜ 0.05).The results suggest that the management widow model is feasible and effective for management of patients with atrial fibrillation in community health service centers.