Tocilizumab Treatment in a Patient of Refractory Anti-EJ Positive ASyS: A Case Report.

Anti-synthetase syndrome (ASyS) is an autoimmune disease characterized by the presence of autoantibodies to aminoacyl-tRNA synthetases accompanied with various organ involvements, including the lung, joints, and skin. The ASyS-related interstitial lung disease (ILD) can be seen in the vast majority of patients. The extent of lung involvement has a significant impact on patient prognosis; the occurrence of rapid-progressive ILD could prominently increase mortality. The mainstay of treatment is prednisone in combination with conventional synthetic disease-modifying anti-rheumatic drugs or some biologic disease-modifying anti-rheumatic drugs (DMARDs). Tocilizumab (TCZ), a recombinant humanized anti-interleukin (IL)-6 receptor monoclonal antibody, has also been used to treat some systemic autoimmune rheumatic diseases associated with ILD. Although the most recent American College of Rheumatology (ACR) Guideline for the Treatment of Interstitial Lung Disease conditionally recommends against the use of TCZ as a treatment option for people with idiopathic inflammatory myopathy (IIM)-ILD progression despite initial ILD treatment, the treatment effect of TCZ in ASyS patients remains obscure, particularly for refractory cases with anti-non-Jo1 antibodies. This report describes a case of Chinese ASyS patients with anti-EJ-positive antibodies who presented with typical proximal muscle weakness, elevated creatine kinase, and ILD with non-specific interstitial pneumonia (NSIP) pattern, along with typical skin involvement such as mechanic's hand. The patients were resistant to various treatments, including rituximab (RTX), but benefited from TCZ. In this case, TCZ shows good therapeutic efficacy in a fatal acute exacerbation of ILD with a hyperinflammatory status, resulting in a relative remission of the disease flare and full preservation of lung function with a positive long-term treatment outcome.

Infections in newly diagnosed systemic lupus erythematosus patients with high disease activity: a retrospective cohort study / 中华风湿病学杂志

Objective:To determine the characteristics of hospitalized newly diagnosed systemic lupus erythematosus (SLE) patients with high disease activity, and identify the risk factors.Methods:Data from 194 newly diagnosed SLE patients at Shanghai Renji Hospital between May 2013 and December 2018 were collected retrospectively. All patients were followed up for 1 year or until death. Patients' demographic, clinical, and laboratory characteristics on admission and medication history were retrospectively collected as baseline data. Patients were divided into two groups, lupus patients with infection (51 cases) and lupus patients without infection (143 cases). The method of univariate analysis of data depended on the data distribution type. Variables that suggested association in the univariate analysis ( P<0.05) were entered into Cox regression model. Results:Among 194 patients with newly diagnosed SLE, 21 cases (11%) died and 51 cases (26%) were infected during 1-year follow-up. Regarding the infection site, 34 cases (67%) had lung infection, 9 cases (18%) had central nervous system infection and 9 cases (18%) had blood stream infection. Common bacteria were identified in 19 cases (45%), followed by fungal infection in 18 cases (43%) and mycobacterium infection in 7 cases (17%). Among the 51 patients with infection, 38 patients (75%) had infection within the first 3 months after diagnosis, and mortality in this group was significantly higher than that in the uninfected group (39%, 15/38 vs 2%, 3/143 , P<0.01). Comparing baseline parameters between patients with 3-month infection and without, significant differences ( P<0.05) were detected in age (≥40 years), systemic lupus erythematosus disease activity index (SLEDAI) score (>10 points), Systemic Lupus International Collaborating Clinic (SLICC)/American College of Rheumatology(ACR) systemic lupus erythematosus damage index (SDI) (≥1 point), pericardial effusion, nephritis, gastrointestinal vasculitis, diabetes, lymphocyte count <0.8×10 9/L platelet count <100×10 9/L, serum creatinine >104 mmol/L and serum globulin level <20 g/L. Finally, clinically meaningful candidate predictors were included in the Cox regression model and it showed that lymphocyte count <0.8×10 9/L, nephritis and gastrointestinal vasculitis were independently predictive for 3-month infection in new-onset lupus patients. Conclusion:Understanding disease spectrums and risk factors of infection in newly diagnosed SLE patients will help clinicians to manage those patients with infection effectively to achieve favorable prognosis.

Safety of the laparoscopic pancreaticoduodenectomy in 70 years of age or older patients / 中华消化外科杂志

Objective To investigate the safety of the laparoscopic pancreaticoduodenectomy (LPD) in 70 years of age or older patients.Methods The retrospective cohort study was conducted.The clinicopathological data of 40 patients (age ≥70 years old) who underwent pancreaticoduodenectomy in the West China Hospital of Sichuan University between January 2012 and December 2016 were collected.Twenty patients undergoing LPD were allocated into the LPD group,and 20 receiving open pancreaticoduodenectomy (OPD) who were selected by random number table during the same period were allocated into the OPD group.Observation indicators included:(1) intraoperative situations;(2) postoperative situations;(3) follow-up situation.Follow-up using outpatient examination and telephone interview was performed to detect the patients' survival after discharge and tumor recurrence and metastasis up to March 2017.Measurement data with normal distribution was represented as x±s,and comparison between groups were evaluated with the t test.Measurement data with skewed distribution were described as median (range) and comparison between groups was analyzed using the nonparametric test.Comparison of count data was analyzed using the chi-square test.Comparison of ranked data was analyzed by non parametric test.Results (1) Intraoperative situations:1 patient in the LPD group was converted to open surgery,with a conversive rate of 5.0％ (1/20).Operative time and volume of intraoperative blood loss were (463 ± 10) minutes,210.5 mL (152.5-300.0 mL) in the LPD group and (332± 25) minutes,420.0 mL (350.1-493.8 mL) in the OPD group,showing statistically significant differences between the 2 groups (t =5.48,Z =-3.98,P＜0.05).Cases with intraoperative blood transfusion and pylorus preservation were respectively 4,14 in the LPD group and 6,10 in the OPD group,showing no statistically significant difference between the 2 groups (x2=0.53,1.67,P＞0.05).The results of intraoperative rapid frozen pathological examination showed negative margin of the 40 patients.(2) Postoperative situations:cases in ICU,cases with postoperative analgesia,time for out-of-bed activity,time to anal exsufflation and time for intake were 17,7,(2.2±0.7)days,(4.2± 0.9)days,(4.8±0.7)days in the LPD group and 6,15,(3.6±0.8)days,(5.7±0.9)days,(7.1 ± 2.7)days in the OPD group,showing statistically significant differences between the 2 groups (x2 =12.34,6.47,t=-6.18,-6.55,-3.65,P＜0.05).Pancreatic fistula,delayed gastric emptying (Grade B),postoperative bleeding (Grade B),biliary fistula,pulmonary infection,intestinal obstruction,wound infection,reoperation and major complication were respectively detected in 2,3,1,1,3,1,0,2,3 patients of the LPD group and 2,4,1,1,4,1,2,3,4 in patients of the OPD group,showing no statistically significant difference between the 2 groups (x2 =0.00,0.17,0.00,0.00,0.17,0.00,2.11,0.23,0.17,P＞0.05).Results of postoperative pathological examination showed that duodenal adenocarcinoma,ampullary carcinoma,lower bile duct carcinoma,pancreatic ductal adenocarcinoma and pancreatic cystic tumor were respectively detected in 8,2,5,3,2 patients of the LPD group and 10,2,4,2,2 patients of the OPD group,showing no statistically significant difference between the 2 groups (x2 =0.53,P＞0.05).Duration of postoperative hospital stay in the LPD and OPD groups were (19± 13) days and (15±7) days,respectively,showing no statistically significant difference between the 2 groups (t =1.28,P＞ 0.05).Results of postoperative oncology showed that tumor diameter,number of lymph node dissected,number of positive lymph nodes,cases with negative margin,cases in T1N0M0,T2N0M0,T3N0M0,T3N1M0,T4N0M0,T4N1M0 of TNM staging were respectively (2.4±0.7)cm,15.4±2.3,2,20,2,7,8,2,1,0 in the LPD group and (2.8±0.9)cm,14.4±2.5,3,20,1,8,5,2,3,1 in the OPD group,with no statistically significant difference between the 2 groups (t =-1.64,1.32,x2 =0.23,0.00,Z =-0.69,P＞ 0.05).(3) Follow-up situation:1 patient died respectively in both groups within the postoperative 30 days.Thirty-eight patients were followed up for 1-26 months,with a median time of 14 months.During follow-up,2 patients had tumor recurrence and 1 died of myocardial infarction in the LPD group;3 had tumor recurrence and 1 died of tumor recurrence in the OPD group.Conclusion LPD in 70 years of age or older patients is not only safe and feasible,but also significantly reduce volume of intraoperative blood loss and demand of analgesia,as well as quickly resume normal diet and activities.

Safety of the laparoscopic pancreaticoduodenectomy in 70 years of age or older patients / 中华消化外科杂志

Objective To investigate the safety of the laparoscopic pancreaticoduodenectomy (LPD) in 70 years of age or older patients.Methods The retrospective cohort study was conducted.The clinicopathological data of 40 patients (age ≥70 years old) who underwent pancreaticoduodenectomy in the West China Hospital of Sichuan University between January 2012 and December 2016 were collected.Twenty patients undergoing LPD were allocated into the LPD group,and 20 receiving open pancreaticoduodenectomy (OPD) who were selected by random number table during the same period were allocated into the OPD group.Observation indicators included:(1) intraoperative situations;(2) postoperative situations;(3) follow-up situation.Follow-up using outpatient examination and telephone interview was performed to detect the patients' survival after discharge and tumor recurrence and metastasis up to March 2017.Measurement data with normal distribution was represented as x±s,and comparison between groups were evaluated with the t test.Measurement data with skewed distribution were described as median (range) and comparison between groups was analyzed using the nonparametric test.Comparison of count data was analyzed using the chi-square test.Comparison of ranked data was analyzed by non parametric test.Results (1) Intraoperative situations:1 patient in the LPD group was converted to open surgery,with a conversive rate of 5.0％ (1/20).Operative time and volume of intraoperative blood loss were (463 ± 10) minutes,210.5 mL (152.5-300.0 mL) in the LPD group and (332± 25) minutes,420.0 mL (350.1-493.8 mL) in the OPD group,showing statistically significant differences between the 2 groups (t =5.48,Z =-3.98,P＜0.05).Cases with intraoperative blood transfusion and pylorus preservation were respectively 4,14 in the LPD group and 6,10 in the OPD group,showing no statistically significant difference between the 2 groups (x2=0.53,1.67,P＞0.05).The results of intraoperative rapid frozen pathological examination showed negative margin of the 40 patients.(2) Postoperative situations:cases in ICU,cases with postoperative analgesia,time for out-of-bed activity,time to anal exsufflation and time for intake were 17,7,(2.2±0.7)days,(4.2± 0.9)days,(4.8±0.7)days in the LPD group and 6,15,(3.6±0.8)days,(5.7±0.9)days,(7.1 ± 2.7)days in the OPD group,showing statistically significant differences between the 2 groups (x2 =12.34,6.47,t=-6.18,-6.55,-3.65,P＜0.05).Pancreatic fistula,delayed gastric emptying (Grade B),postoperative bleeding (Grade B),biliary fistula,pulmonary infection,intestinal obstruction,wound infection,reoperation and major complication were respectively detected in 2,3,1,1,3,1,0,2,3 patients of the LPD group and 2,4,1,1,4,1,2,3,4 in patients of the OPD group,showing no statistically significant difference between the 2 groups (x2 =0.00,0.17,0.00,0.00,0.17,0.00,2.11,0.23,0.17,P＞0.05).Results of postoperative pathological examination showed that duodenal adenocarcinoma,ampullary carcinoma,lower bile duct carcinoma,pancreatic ductal adenocarcinoma and pancreatic cystic tumor were respectively detected in 8,2,5,3,2 patients of the LPD group and 10,2,4,2,2 patients of the OPD group,showing no statistically significant difference between the 2 groups (x2 =0.53,P＞0.05).Duration of postoperative hospital stay in the LPD and OPD groups were (19± 13) days and (15±7) days,respectively,showing no statistically significant difference between the 2 groups (t =1.28,P＞ 0.05).Results of postoperative oncology showed that tumor diameter,number of lymph node dissected,number of positive lymph nodes,cases with negative margin,cases in T1N0M0,T2N0M0,T3N0M0,T3N1M0,T4N0M0,T4N1M0 of TNM staging were respectively (2.4±0.7)cm,15.4±2.3,2,20,2,7,8,2,1,0 in the LPD group and (2.8±0.9)cm,14.4±2.5,3,20,1,8,5,2,3,1 in the OPD group,with no statistically significant difference between the 2 groups (t =-1.64,1.32,x2 =0.23,0.00,Z =-0.69,P＞ 0.05).(3) Follow-up situation:1 patient died respectively in both groups within the postoperative 30 days.Thirty-eight patients were followed up for 1-26 months,with a median time of 14 months.During follow-up,2 patients had tumor recurrence and 1 died of myocardial infarction in the LPD group;3 had tumor recurrence and 1 died of tumor recurrence in the OPD group.Conclusion LPD in 70 years of age or older patients is not only safe and feasible,but also significantly reduce volume of intraoperative blood loss and demand of analgesia,as well as quickly resume normal diet and activities.

Characteristics and prognosis of proliferative lupus nephritis with renal thrombotic microangiopathy / 中华风湿病学杂志

Objective Renal vascular injury,especially thrombotic microangiopathy (TMA),is an important prognostic factors in pat.ients with lupus nephritis.TMA is most likely to be associated with proliferative lupus nephritis.This single-center retrospective study was conducted in order to explore the characteristics and prognosis of patients with TMA associated with proliferative lupus nephritis.Methods From January 2013 to June 2016,146 hospitalized patients with lupus nephritis underwent renal biopsy in the Department of Rheumatology,South Campus,Ren Ji Hospital,of which 108 were proliferative nephritis including 32 with TMA and 76 without TMA.All the clinical records were collected.All data were analyzed by Graphpad 5.0 or SPSS 22.0 statistical software analysis.Nonparametric test,t test and Fisher test were used for comparison between the two groups.Predictors were analyzed by multiple factors regression analysis,survival curve was analyzed by Kaplan-Meire method.Results Patients with TMA were found to have higher levels of creatinine (Cr) [93.5 (69.0,179.8) μmol/L vs 73.0 (56.3,116.3) μmol/L,U=833,P=0.010 1],B-type brain natriuretic peptide (BNP) [177(93.2,619) pg/ml vs 87.5(28.5,255) pg/ml,U=765,P=0.004 6],24-hour urinary protein [4.98 (1.99,7.62) g vs 2.83 (1.71,4.38) g,U=875,P=0.022] and highersystemic lupus erythematosus disease activity index (SLEDAI) [16(13.25,18) vs 12(10.25,14),U=559,P＜0.000 1],as well as lower complement [C3:(0.37±0.15) g/L vs (0.52±0.20) g/L,t=3.713,P=0.000 3;C4:0.056 (0.035,0.140) g/L vs 0.088(0.053,0.167) g/L,U=912,P=0.047 9],albumin (Alb) [(24±6) g/L vs (28±6) g/L,t=3.416,P=0.000 9] and hemoglobin (Hb) [(88±19) g/L vs (99±21) g/L,t=2.627,P=0.015 7].They were more prone to hypertension [(24/32,75％) vs (35/76,46％),x2=7.613,P=0.006 4],had less glomerular sclerosis [0(0,0.038)％ vs 7(0,17)％,U=848,P=0.007 7] and higher acute score [16(14.25,19.75) vs 13(10,15),U=612,P＜0.000 1];while these patients received higher doses of corticosteroid therapy,and more patients were treated with cyclophosphamide for induction therapy.Multivariate regression analysis showed that Cr (OR =1.008,P=0.033) and SLEDAI (OR =1.272,P=0.003) scores might be predictors of TMA in patients with proliferative lupus nephritis.During follow up,6 and 2 patientsin two groups progressed to end-stage renal disease (ESRD),respectively (P=0.010 4).Univariate analysisfound that patients progressed to ESRD were more likely to have TMA[(6/8,75％) vs (23/85,27％),x2=7.831,P=0.010 4],and had more crescents[54.5(12,83.5)％ vs 20(6,41)％,U=183,P=0.032].Higher activity indices (AI) [(20±6) vs (14±4),t=3.489,P=0.000 7],Cr [286(214.5,395) μmol/L vs 76(59,115.5) μmol/L,U=19,P＜0.000 1] and BNP [456(192.3,1 060) vs 110(45.38,275.5),U=116.5,P=0.002 4],as well as lower Hb [(71±12) vs (97±19),t=3.776,P=0.000 3] and platelets (PLT) [(130±71)×109/L vs (196±76)×109/L,t=2.399,P=0.018 5] were observed in these patients.Conclusion This study has shown that patients with proliferative lupus nephritis with renal TMA have a higher level of Cr and more active disease state,requiring more aggressive immunosuppressive therapy and more likely to progress to ESRD.So renal TMA may be one of the risk factors of renal survival in these patients.