JAK inhibitors in systemic juvenile idiopathic arthritis

ObjectiveSystemic juvenile idiopathic arthritis (SJIA) is characterized by excessive and inappropriate production of proinflammatory cytokines. Janus kinase inhibitors (JAKi) can block the downstream pathway of many cytokines. The use of JAKi in SJIA or macrophage activation syndrome (MAS) has only been described in a limited number of case reports. In this study, we aimed to assess the efficacy and potential adverse effects of JAKi in SJIA patients.MethodsPatients with SJIA who received JAKi and underwent at least one assessment of efficacy and safety after JAKi initiation were eligible for this study. Data were collected retrospectively from inpatient or outpatient medical records at JAKi initiation, at 1, 3, 6, 9, and 12 months, after disease flare, after JAKi discontinuation, or at the last follow-up.ResultsTen patients with SJIA were included in the study. At the start of JAKi treatment, all patients presented with active disease; five showed variable adverse effects secondary to glucocorticoids. Seven patients received tofacitinib (one later switched to ruxolitinib). Of these, only two patients showed a complete response of persistent arthritis associated with tocilizumab; tofacitinib was used without a biological DMARD only in two patients, together with MTX, showing a partial response; three patients were nonresponders. Four patients with SJIA-related MAS or persistent hyperferritinemia were treated with ruxolitinib. Ruxolitinib allowed a good response on MAS parameters in three of them. All these four patients required an adjunction or switch to canakinumab later. The median decrease in the daily glucocorticoid dose between JAKi initiation and the last follow-up was 90.6% in patients with complete remission and 77.4% in other patients. Three patients discontinued glucocorticoid treatment after the introduction of JAKi. Severe adverse events, notably serious infection or thrombosis, were not observed during JAKi treatment.ConclusionJAKi may be an alternative or adjuvant agent for SJIA patients, especially in those with persistently active disease, glucocorticoid-related adverse reactions, or SJIA-MAS

Whole exome sequencing identifies frequent somatic mutations in cell-cell adhesion genes in chinese patients with lung squamous cell carcinoma

Lung squamous cell carcinoma (SQCC) accounts for about 30% of all lung cancer cases. Understanding of mutational landscape for this subtype of lung cancer in Chinese patients is currently limited. We performed whole exome sequencing in samples from 100 patients with lung SQCCs to search for somatic mutations and the subsequent target capture sequencing in another 98 samples for validation. We identified 20 significantly mutated genes, including TP53, CDH10, NFE2L2 and PTEN. Pathways with frequently mutated genes included those of cell-cell adhesion/Wnt/Hippo in 76%, oxidative stress response in 21%, and phosphatidylinositol-3-OH kinase in 36% of the tested tumor samples. Mutations of Chromatin regulatory factor genes were identified at a lower frequency. In functional assays, we observed that knockdown of CDH10 promoted cell proliferation, soft-agar colony formation, cell migration and cell invasion, and overexpression of CDH10 inhibited cell proliferation. This mutational landscape of lung SQCC in Chinese patients improves our current understanding of lung carcinogenesis, early diagnosis and personalized therapy

Clinical Features and Risk Factors of Kawasaki Disease Complicated with Deep Neck Space Involvement: A Summary of 38 Cases

Objective  To summarize the clinical characteristics and explore the risk factors of Kawasaki disease(KD) with deep neck space involvement(DNSI).  Methods  This study was a case-control study. We reviewed KD complicated with DNSI patients in Department of Rheumatology and Immunology of Shenzhen Children's Hospital from January 2018 to December 2020 as DNSI group. Meanwhile, children with KD withoutDNSI during this period were selected by systematic sampling at a ratio of 1∶7 as control group. The clinical characteristics were analyzed by Chi-square test and the Mann-Whitney test and risk factors of KD complicated with DNSI were analyzed by Logistic regression.  Results  A total of 38 children in the DNSI group who met the inclusion and exclusion criteria and 288 children in the control group were selected. In the DNSI group, 38 children (100%) had fever and cervical lymph node enlargement, and the cervical lymph node enlargement occurred within 5 days of onset; 30 patients (78.9%) had cervical lymph node pain and 25 patients suffered (65.8%) limited movement of neck. Compared with the control group, the clinical data of children in the DNSI group showed a variety of significant changes. In terms of clinical characteristics, the age of onset in the DNSI group was older, the hospital stay was longer and the proportions of cervical lymphadenopathy, cervical lymph node pain, limited neck movement and upper airway obstruction were all higher (all P < 0.05); in terms of laboratory tests, the neutrophil count and its percentage, C-reactive protein (CRP), ferritin (FER), total bile acid, total bilirubin, direct bilirubin, and globulin levels all increased, while platelet and lymphocyte counts and their percentages all decreased(all P < 0.05); in terms of coronary artery damage and treatment effect, the Kobayashi score, Sano score and the proportion of hormone therapy in the DNSI group all increased (all P < 0.05). Multivariate Logistic regression analysis showed that neck lymph node pain (OR=5.523, 95% CI: 1.443-21.141, P=0.013), limited cervical movement (OR=3.947, 95% CI: 1.044-14.928, P=0.043), higher CRP (OR=1.016, 95% CI: 1.002-1.030, P=0.024) and higher FER(OR=1.004, 95% CI: 1.001-1.006, P=0.002) were independent risk factors for KD combined with DNSI.  Conclusions  Most children with KD complicated with DNSI have clinical symptoms such as cervical lymph node enlargement, cervical lymph node pain, and limited cervical movement, and hematology shows that there is a high-intensity inflammatory response. For KD children with neck pain and limited cervical movement as the main clinical manifestations, accompanied by elevated serum CRP and FER, we should be alert to the possibility of DNSI

Barriers to community-based drug dependence treatment: implications for police roles, collaborations and performance indicators

ntroduction: Worldwide, people who use drugs (PWUD) are among the populations at highest risk for HIV infection. In China, PWUD are primarily sentenced to compulsory detainment centres, in which access to healthcare, including HIV treatment and prevention services, is limited or non-existent. In 2008, China's 2008 Anti-Drug Law encouraged the development and use of community-based drug dependence rehabilitation, yet there is limited evidence evaluating the efficacy and challenges of this model in China. In this study, we explore these challenges and describe how cooperation between law enforcement and health departments can meet the needs of PWUD. Methods: In 2015, we conducted semi-structured, in-depth interviews with all four staff members and 16 clients of the Ping An Centre No. 1 for community-based drug treatment, three local police officers and three officials from the local Centre for Disease Control. Interviews explored obstacles in implementing community-based drug dependence treatment and efforts to resolve these difficulties. Transcripts were coded and analyzed with qualitative data analysis software (MAXQDA 11). Results: We identified three challenges to community-based drug treatment at the Ping An Centre No. 1: (1) suboptimal coordination among parties involved, (2) a divergence in attitudes towards PWUD and harm reduction between law enforcement and health officials and (3) conflicting performance targets for police and health officials that undermine the shared goal of treatment. We also identified the take-home methadone maintenance treatment model at the Ping An Centre No. 1 as an example of an early successful collaboration between the police, the health department and PWUD. Conclusions: To overcome barriers to effective community-based drug treatment, we recommend aligning the goals of law enforcement and public health agencies towards health-based performance indicators. Furthermore, tensions between PWUD and police need to be addressed and trust between them fostered, using community-based treatment centres as mediators. The preliminary success of the take-home methadone maintenance treatment pilot can serve as an example of how collaboration with the police and other government agencies can meet the needs of PWUD and contribute to the success of community-based treatment