Continuation, reduction, or withdrawal of tofacitinib in patients with rheumatoid arthritis achieving sustained disease control: a multicenter, open-label, randomized controlled trial / 中华医学杂志(英文版)

BACKGROUND@#Rheumatoid arthritis (RA), a chronic systemic autoimmune disease, is characterized by synovitis and progressive damage to the bone and cartilage of the joints, leading to disability and reduced quality of life. This study was a randomized clinical trial comparing the outcomes between withdrawal and dose reduction of tofacitinib in patients with RA who achieved sustained disease control.@*METHODS@#The study was designed as a multicenter, open-label, randomized controlled trial. Eligible patients who were taking tofacitinib (5 mg twice daily) and had achieved sustained RA remission or low disease activity (disease activity score in 28 joints [DAS28] ≤3.2) for at least 3 months were enrolled at six centers in Shanghai, China. Patients were randomly assigned (1:1:1) to one of three treatment groups: continuation of tofacitinib (5 mg twice daily); reduction in tofacitinib dose (5 mg daily); and withdrawal of tofacitinib. Efficacy and safety were assessed up to 6 months.@*RESULTS@#Overall, 122 eligible patients were enrolled, with 41 in the continuation group, 42 in the dose-reduction group, and 39 in the withdrawal group. After 6 months, the percentage of patients with a DAS28-erythrocyte sedimentation rate (ESR) of <3.2 was significantly lower in the withdrawal group than that in the reduction and continuation groups (20.5%, 64.3%, and 95.1%, respectively; P  < 0.0001 for both comparisons). The average flare-free time was 5.8 months for the continuation group, 4.7 months for the dose reduction group, and 2.4 months for the withdrawal group.@*CONCLUSION@#Withdrawal of tofacitinib in patients with RA with stable disease control resulted in a rapid and significant loss of efficacy, while standard or reduced doses of tofacitinib maintained a favorable state.@*TRIAL REGISTRATION@#Chictr.org, ChiCTR2000039799.

Case reports and clinical analysis of 8 patients with primary Sj?gren's syndrome diagnosed as anti-synthase syndrome / 中华风湿病学杂志

Objective:Anti-synthase syndrome (ASS) is a rare autoimmune disease. To increase the understanding of the disease and reduce the rate of miss diagnosis.Methods:The clinical data of 8 patients with positive anti-synthase antibody afterprimary Sj?gren's syndrome (pSS) were retrospectively analyzed and descriptive statistical analysis was carried out.Results:The diagnosis of Sjogren's syndrome (SS) was in accordance with the revised European criteriaof SS issued by the US-Europe consensus Group in 2002 or the classification criteria of American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) SS in 2016, and the diagnostic ASS was in accordance with the diagnostic criteria of Conners in 2010 or Solomon in 2011. Eight(100%) patients had a history of interstitial lung disease, and 7 (88%) patients had fever (oral temperature >38.5 ℃). All patients were positive for anti-Ro-52 antibody, 4 patients were positive for anti-PL-7 antibody, 2 patients were positive for anti-EJ antibody, 1 patient was positive for both anti-PL-7 antibody and anti-EJ antibody, and 1 patient was positive for anti-PL-12.Conclusion:pSS patients with severe interstitial lung disease or high fever of unknown causes should be screened for anti-synthase antibodies and the possibility of ASS.

Systemic lupus erythematosus with primary sclerosing cholangitis / 中华风湿病学杂志

Objective:To investigate the clinical manifestations, laboratory and imaging features, treatment and prognosis of systemic lupus erythematosus (SLE) with primary sclerosing cholangitis (PSC).Methods:This is a retrospective case series study describing the clinical, laboratory and imaging manife-stations, treatment and prognosis of 3 SLE patients with PSC. The related literatures were reviewed.Results:In total, 10 patients were included. SLE with PSC, with an average age of (43±17) years old, was more common with hematological and renal involvement, jaundice and arthralgia, positive anti-double-stranded DNA (anti-dsDNA) antibody, hypocomplementemia, elevated erythrocyte sedimentation rate (ESR) and abnormal liver function with predominately elevated alkaline phosphatase (ALP). The classic magnetic resonance cholangio-pancreatography (MRCP) features of PSC include multifocal strictures, beading and areas of dilatation involving the intra- and/or extrahepatic bile ducts. The treatment included glucocorticosteroids, immunosup-pressants and ursodeoxycholic acid (UDCA), and some patients required biliary drainage. Most patients had a good prognosis.Conclusion:Although PSC is rare, attention should be paid to SLE patients with abnormal liver function, especially with elevated ALP, in order to differentiate from PSC.

Treatment with rituximab in 8 cases with systemic sclerosis / 中华风湿病学杂志

Objective:To observe the clinical efficacy and adverse reactions of rituximab in the treatment of systemic sclerosis (SSc).Methods:Eight SSc patients who received rituximab treatment in the Department of Rheumatology of Shanghai Ruijin Hospital from November 2016 to May 2020 were treated with rituximab at week 0, week 2, week 4, week 24 and week 48. The clinical symptoms and laboratory parameters were evaluated at baseline, week 4, week 24 and week 48 respectively. All data were analyzed by Wilcoxon test.Results:All the patients were diagnosed as diffuse SSc, including seven females and one male, with a median disease course of 2.5 years. At week 0, week 24 and week 48, the modified Rodnon skin scores (MRss) were 16.5 (11.8, 29.5) , 14.5 (9.5, 27) ( Z=0.841) and 10.5 (7, 24.3) ( Z=0.420) respectively, which were significantly improved as compared with the baseline ( P<0.05). The patients' self-scores were 60(50, 77.5), 52.5(41.3, 67.5)( Z=0.113) and 47.5(36.3, 57.5)( Z=0.474) respectively, which were significantly improved at week 24 and week 48, and the High Resolution CT (HRCT) scores at baseline and week 48 were 2.7(1.02, 3.7) and 1.6(0.65, 2.95)( Z=0.964) respectively, significantly improved after treatment ( P<0.05). The pulmonary aterial hypertension (PAH) values were 48(41, 58.5) mmHg and 47(38.5, 57) mmHg ( Z=0.315) respectively. There was no significant difference between the two groups. Clinical observation showed that the condition was improved and no adverse reaction occurred at the same time period. Conclusion:The improvement of skin sclerosis, pulmonary interstitial lesion and pulmonary artery pressure can be observed during the treatment with rituximab, which may be a new choice for the treatment of SSc. There is no serious adverse reaction during the treatment, and the patients are well tolerated and safe.

Fibrosis after damage to fat dome structure of skin of pig / 中华烧伤杂志

<p><b>OBJECTIVE</b>To observe the fibrosis of skin after damage to the fat dome structure in skin of pig.</p><p><b>METHODS</b>Totally 4 pieces of skin grafts of intermediate thickness in the size of 5 cm × 5 cm were obtained from both sides beside the spine of back in each of the 4 female red Duroc pigs with pedicle on one side with Humby knife performed by burn specialists, who were rich in clinical experience. These skin grafts were assigned as thin dermis group (TD). Pedicled tissue grafts in the size of 5 cm × 5 cm with the thickness of 1.5 mm were obtained within the wounds resulted from former incision with the same method mentioned above, and these tissue grafts were set as fat dome group (FD). The above-mentioned two groups of skin grafts were sutured back in situ immediately after completion of the former procedures. On post surgery day (PSD) 7, 14, and 21, 5 wounds were respectively selected according to the random number table for gross observation of the surgical areas. Tissue samples were obtained from corresponding surgical area deep to the deep fascia after gross observation at above-mentioned time points. Some of the tissue samples were used for observation of distribution of collagen fibers in the regions of operation of both groups of skin grafts with HE staining, and the breadth of fibrosis was measured; some of the tissue samples were used for observation of distribution of type I or III collagen fibers in the regions of incision of both two groups of skin grafts with Sirius red staining. Data were processed with two independent sample t test.</p><p><b>RESULTS</b>A little scab on the edge of wounds was observed on PSD 7; all the wounds were healed on PSD 14; a few hairs were observed growing in the surgical area on PSD 21. HE staining showed that traces of incision were observed in the superficial layer of dermis and at the junction between dermis and fat dome at each time point; profuse hyperplasia of collagen fibers with parallel and orderly arrangement were observed in the region of incision of skin grafts in groups TD and FD at each time point. The breadth of fibrosis of the region of incision of skin grafts was respectively (251 ± 31), (240 ± 3 7), and (342 ± 69) µm in group TD, (239 ± 36), (286 ± 61), and (332 ± 28) µm in group FD on PSD 7, 14, 21, without significantly statistical difference (with t values respectively 0.750, -1.971, and 0.375, P values above 0.05). Sirius red staining showed that large amount of type III collagen fibers and small amount of type I collagen fibers arranging parallelly were present in the region of incision of skin grafts in groups TD and FD at each time point.</p><p><b>CONCLUSIONS</b>Under the circumstances of relatively intact restoration of dermal tissue, no excessive fibrosis was observed after simple incisional injury of fat dome in skin of pig.</p>

Prognostic factors for diabetic foot ulcer / 中华创伤杂志

Objective To identify the factors related to prognosis of diabetic foot ulcer (DFU).Methods A total of 186 patients with type Ⅱ DFU from a single diabetic foot center was included in this prospective study.Follow-up of the final outcome (healing,major amputation or death) was made in 6 months.Influence of patient demographics and clinical data on outcome was detected using multivariate Logistic regression analysis.Results Follow-up was performed in 172 patients,of whom 147 were cured (55 cases cured after minor amputations),3 underwent major amputations,6 died,and 16 were not yet cured at the final follow-up.In multivariate Logistic regression analysis,the outcome was independently correlated with ischemia (P ＜0.01),infection (P ＜ 0.05),ulcer number (P ＜ 0.01) and peripheral neuropathy (P ＜ 0.05) ; the risk of poor outcome increased with ischemia [odds ratio (OR) =10.8],infection (OR =211.4),ulcer number (OR =39.5),and peripheral neuropathy (OR =181.1).Conclusion Prognosis of DFU is associated with ischemia,infection,ulcer number,and peripheral neuropathy.

Clinical significance of aldosterone to renin ratio in screening primary aldosteronism / 中华内分泌代谢杂志

ObjectiveTo retrospectively analyse the data of patients with suspected primary aldosteronism (PA) during the last five years.The receiver operating characteristic (ROC) curve was used to evaluate the value of aldosterone to renin ratio (ARR) in screening primary aldosteronism.MethodsThe clinical data of ARR in supine and upright positions were collected in 590 patients with suspected during January 2006 to August 2010.There were 357 patients diagnosed as primary aldosteronism and 233 patients as essential hypertension among these patients.100 patients with suspected primary aldosteronism took the upright and random ARR during September 2010 to April 2011 ; Among these patients,29 patients were diagnosed as primary aldosteronism and 71 as cases of essential hypertension.ROC curve was made to retrospectively define the method and the cut-off value of the supine,upright or random ARR.ResultsThe area under the curve(AUC) of the supine ARR in the 590 patients who took the supine and upright ARR during January 2006 to August 2010 was 0.838 (0.805-0.867 ) and the AUC of the upright ARR was 0.873 (0.843-0.899 ).There was significant difference between these two AUC readings (P＜0.01 ).The AUC in the upright ARR of the 100 patients who took the upright and random ARR during Septeuder 2010 to April 2011 was 0.962 (0.928 -0.995 ) and the AUC of the random ARR was 0.944 (0.893-0.994 ).There was no significant difference between these two AUC readings (P＞0.05).The upright ARR cutoff value with 400 ( pg · ml-1 )/( ng· ml-1 · h 1 ) yielded a sensitivity of 91.9％ and a specificity of 64.2％ to diagnosis of PA.ConclusionUpright ARR value was more suitable in the screening test than supine ARR value.Random ARR showed similar effect as the upright ARR.In our research,under strict control of the drug,position and detection time,ARR value with 400 ( pg · ml-1 )/( ng· ml-1 · h-1 ) can be the cutoff point in screening the suspcctcd PA patients.

Progress in pharmaceutical treatment for adrenocotical carcinoma / 中华内分泌代谢杂志

Adrenocortical carcinoma (ACC) is a rare disease with poor prognosis.Patients usually present with signs of steroid hormone excess (e.g.Cushing's syndrome, Conn's syndrome, virilization) or an abdominal mass.In functional cases, Cushing's syndrome is the most frequent presentation.Mitotane is still the most important single drug for ACC treatment, and it plays a role in adjuvant therapy postoperatively as well as in advanced disease.In advanced ACC, a combination of mitotane with etoposide, doxorubicin, cisplatin or streptozotocin with mitotane may be used.Targeted therapies, such as insulin-like growth factor Ⅰ (IGF- Ⅰ)receptor inhibitor and multiple kinase inhibitors like sunitinib and sorafenib hold great promises.

Treatment of idiopathic hypogonadotropic hypogonadism with pulse infusion of gonadorelin via micro pump / 中华内分泌代谢杂志

Objective To explore the efficacy of pulse infusion of gonadorelin (LHRH) on the patients with idiopathic hypogonadotropic hypogonadism (IHH) via a micro infusion pump. Methods The protocol was designed as an open, self-controlled prospective study. 31 patients were enrolled and assigned to 3 groups: 23 males without gonadotropin-releasing hormone ( GnRH ) pulse ( group A), 2 males with GnRH pulse frequency insufficiency ( group B), and 6 females ( group C). All the subjects were admitted LHRH every 90 min via the micro infusion pump for 24 weeks. Sex hormones and related characteristics were compared before and after the treatment. Results After 24-weeks treatment, LH peak value reached ( 6. 92 ±5.66 ), ( 9. 55 ±0. 98 ), and ( 6. 93 ±4. 52 ) IU/L; and FSH peak value reached ( 7.44 ± 3. 80 ), ( 12. 85 ± 12. 80 ), and ( 7.38 ±4. 98 ) IU/L among 3 groups, respectively. The testosterone also reached ( 3.18± 1.81 ) and ( 5.78±4. 65 ) ng/ml in groups A and B ( all P＜0. 01 ). In groups A and B, the testis volumes were increased, seminal fluid production was found in 7 patients and spermatogenesis in 6 patients. In group C, uterus was enlarged 85.4%, as well as the ovaries of both sides. Menarche was reported in 5 patients. 19. 4% of the studied patients complained uncomfortable at the injection sites, all the symptoms were mild. Conclusion Pulse infusion of LHRH in IHH patients via a micro infusion pump is effective, while the medication system needs improving.

Investigation on translating relationship of hemoglobin A_1C and average glucose / 中国实用内科杂志

HbA1c measures chronic glycemia and is widely used to judge the adequacy of diabetic treatment and adjust therapy.According to ADAG study,the relationship between HbA1c and the calculated AG can be expressed as the linear regression:eAG(mg/dL)=28.7?HbA1c-46.7.ADA has adopted this equation on its website.In the same unit of measurement as used in self-monitoring blood glucose,eAG would facilitate the doctors to communicate with patients in the daily glucose control.