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Objectives: We aimed to estimate the effectiveness and safety of iguratimod (IGU) monotherapy or in combination with methotrexate (MTX) in treating rheumatoid arthritis (RA) to provide an evidence-primarily-based foundation for clinical application.Methods: We conducted a systematic review of the meta-analysis using eight databases and two clinical trial websites searching for randomized controlled trials (RCTs) from conception to 15 March 2022, based on outcomes of patients with RA treated with IGU. The evidence quality assessment of primary outcomes was evaluated by the GRADE tool, and RevMan 5.3 and StataMP 14.0 were used to perform this research.Results: A total of 4302 patients with RA from 38 RCTs was included in this research. Pooled results demonstrated as follows: 1) Compared with methotrexate (MTX) alone, IGU alone was superior in improving ACR20 and DAS28-ESR, while having no significant difference in ACR50 and ACR70 [ACR20: (RR 1.15, 95% CI 1.05–1.27, p = 0.004); ACR50: (RR 0.97, 95% CI 0.66–1.44, p = 0.88); ACR70: (RR 0.92, 95% CI 0.45–1.90, p = 0.83); DAS28-ESR: mean difference (MD) −0.15, 95% CI −0.27 to −0.03, p = 0.01]. 2) Compared with MTX alone, IGU + MTX was more effective in improving ACR20, ACR50, ACR70, and DAS28-ESR. [ACR20: (RR 1.24, 95% CI 1.14–1.35, p < 0.00001); ACR50: (RR 1.96, 95% CI 1.62–2.39, p

Background: Extranodal natural killer/T-cell lymphoma (ENKTCL) has a unique treatment principle. However, the optimal combination of drugs along with radiotherapy (RT) is unknown. Design: Retrospective cohort study. Objectives: We screened multiple drug combinations to identify the most efficacious therapeutic combinations. Methods: We reviewed 3105 patients who received 40 chemotherapy regimens with different combinations of 9 drug classes and/or RT. Least absolute shrinkage and selection operator and multivariable Cox regression analyses were used to screen efficacious single drugs and identify optimal combinations for overall survival (OS). Inverse probability of treatment weighting (IPTW) and multivariable analyses were used to compare survival between treatment regimens. Results: Screening and validation revealed RT, asparaginase (ASP), and gemcitabine (GEM) to be the most efficacious single modality/drug. RT remained an important component of first-line treatment, whereas ASP was a fundamental drug of non-anthracycline (ANT)-based regimens. Addition of RT to non-ANT-based or ASP/GEM-based regimens, or addition of an ASP-drug into ANT-based or GEM/platinum-based regimens, improved 5-year OS significantly. Use of ASP/GEM-based regimens was associated with significantly higher 5-year OS (79.9%) compared with ASP/ANT-based (69.2%, p = 0.001), ASP/methotrexate-based (63.5%, p = 0.011), or ASP/not otherwise specified-based (63.2%, p

Abstract This study aimed to investigate the characteristics and prognosis of distant metastasis (DM) after primary treatment for early‐stage extranodal nasal‐type natural killer (NK)/T‐cell lymphoma (ENKTCL). A total of 1619 patients from the China Lymphoma Collaborative Group database were retrospectively reviewed. The cumulative incidence of DM was assessed using Fine and Gray's competing risk analysis. The correlation between DM sites was evaluated using phi coefficients, while DM sites were classified using hierarchical clustering. Regression analysis was used to assess the linear correlation between DM‐free survival (DMFS) and overall survival (OS). The 5‐year cumulative DM rate was 26.2%, with the highest annual hazard rate being in the first year (14.9%). The most frequent DM sites were the skin and soft tissues (SSTs, 32.4%) and distant lymph nodes (LNs, 31.3%). DM sites were categorized into four subgroups of distinct prognosis — distant LN, SST, extracutaneous site, and lymphoma‐associated hemophagocytic lymphohistiocytosis. SST or distant LN, solitary metastasis, and late‐onset DM demonstrated a relatively favorable prognosis. Contemporary chemotherapy significantly decreased DM rates and improved DMFS. Decreased DM rates were further associated with increased OS probabilities. Our findings improve the understanding of the variable clinical behaviors of early‐stage ENKTCL based on four distinct DM sites and thus provide guidance for future therapeutic decisions, metastatic surveillance, and translational trial design.

Abstract Background The gastrointestinal (GI) tract is the second most frequent extranasal involvement site for ENKTL. This study aimed to explore the clinicopathological features, treatment models, survival outcomes, and prognosis of gastrointestinal ENKTL (GI‐ENKTL). Methods The clinical data of GI‐ENKTL patients were extracted from the China Lymphoma Collaborative Group (CLCG) database and were analyzed retrospectively. Results A total of 30 patients were enrolled, with a male/female ratio of 4:1 and a median age of 42 years. Twenty‐nine patients received chemotherapy, of whom 15 patients received asparaginase‐based (ASP‐based) regimens. Moreover, seven received surgery and three received radiotherapy. The overall response an d complete remission rates were 50.0% and 30.0% for the whole cohort, 50.0% and 37.5% for patients treated with ASP‐based regimens, and 50.0% and 25.0% for those treated with non‐ASP‐based regimens, respectively. The median follow‐up was 12.9 months and the 1‐year overall survival rate was 40.0% for the whole cohort. For those patients in an early stage, ASP‐based regimens resulted in a superior 1‐year progression‐free survival rate compared to non‐ASP‐based regimens (100.0% vs. 36.0%, p = .07). However, ASP‐based regimens did not improve survival in patients at an advanced stage. Conclusion GI‐ENKTL still has a poor prognosis, even in the era of modern asparaginase‐based treatment strategies.

Survival from extranodal nasal-type NK/T-cell lymphoma (ENKTCL) has substantially improved over the last decade. However, there is little consensus as to whether a population of patients with ENKTCL can be considered “cured” of the disease. We aimed to evaluate the statistical “cure” of ENKTCL in the modern treatment era. This retrospective multicentric study reviewed the clinical data of 1,955 patients with ENKTCL treated with non-anthracycline-based chemotherapy and/or radiotherapy in the China Lymphoma Collaborative Group multicenter database between 2008 and 2016. A non-mixture cure model with incorporation of background mortality was fitted to estimate cure fractions, median survival times and cure time points. The relative survival curves attained plateau for the entire cohort and most subsets, indicating that the notion of cure was robust. The overall cure fraction was 71.9%. The median survival was 1.1 years in uncured patients. The cure time was 4.5 years, indicating that beyond this time, mortality in ENKTCL patients was statistically equivalent to that in the general population. Cure probability was associated with B symptoms, stage, performance status, lactate dehydrogenase, primary tumor invasion, and primary upper aerodigestive tract site. Elderly patients (>60 years) had a similar cure fraction to that of younger patients. The 5-year overall survival rate correlated well with the cure fraction across risk-stratified groups. Thus, statistical cure is possible in ENKTCL patients receiving current treatment strategies. Overall probability of cure is favorable, though it is affected by the presence of risk factors. These findings have a high potential impact on clinical practice and patients’ perspective.

Background: Occupational exposure to chromium compounds may result in adverse health effects. This study aims to investigate whether low-level hexavalent chromium (Cr(VI)) exposure can cause DNA damage in electroplating workers. Methods: 157 electroplating workers and 93 control subjects with no history of occupational exposure to chromium were recruited in Hangzhou, China. Chromium levels in erythrocytes were determined by graphite furnace atomic absorption spectrophotometer. DNA damage in peripheral lymphocytes was evaluated with the alkaline comet assay by three parameters: Olive tail moment, tail length and percent of DNA in the comet tail (tail DNA%). Urinary 8-OHdG levels were measured by ELISA. Results: Chromium concentration in erythrocytes was about two times higher in electroplating workers (median: 4.41 μg/L) than that in control subjects (1.54 μg/L, P < 0.001). The medians (range) of Olive tail moment, tail length and tail DNA% in exposed workers were 1.13 (0.14-6.77), 11.17 (3.46-52.19) and 3.69 (0.65-16.20), and were significantly higher than those in control subjects (0.14 (0.01-0.39), 3.26 (3.00-4.00) and 0.69 (0.04-2.74), P < 0.001). Urinary 8-OHdG concentration was 13.65 (3.08-66.30) μg/g creatinine in exposed workers and 8.31 (2.94-30.83) μg/g creatinine in control subjects (P < 0.001). The differences of urinary 8-OHdG levels, Olive tail moment, tail length and tail DNA% between these two groups remained significant (P < 0.001) even after stratification by potential confounding factors such as age, gender, and smoking status. Chromium exposure was found to be positively associated with chromium levels in erythrocytes, urinary 8-OHdG levels, Olive tail moment, tail length and tail DNA %. Positive dose-response associations were also found between chromium levels in erythrocytes and Olive tail moment, tail length and tail DNA%. Conclusion: The findings in this study indicated that there was detectable chromium exposure in electroplating workers. Low-level occupational chromium exposure induced DNA damage. [ABSTRACT FROM AUTHOR]

The optimal combination and sequence of radiotherapy (RT) and chemotherapy (CT) for extranodal nasal-type natural killer/T-cell lymphoma (NKTCL) are not well-defined. The aim of this study was to create a risk-adapted therapeutic strategy for early-stage NKTCL. A total of 1273 early-stage patients from 10 institutions were reviewed. Patients received CT alone (n =170), RT alone (n = 253), RT followed by CT (n = 209), or CT followed by RT (n = 641). A comprehensive comparative study was performed using multivariable and propensity score-matched analyses. Early-stageNKTCLwasclassified as low risk or high risk based on 5 independent prognostic factors (stage, age, performance status, lactate dehydrogenase, primary tumor invasion). RT alone and RT with or without CT were more effective than CT alone (5-year overall survival [OS], 69.6% and 67.7% vs 33.9%, P < .001). For low-risk patients, RT alone achieved a favorable OS (88.8%); incorporation of induction or consolidation CT did not provide additional benefit (86.9% and 86.3%). For highrisk patients, RT followed by CT resulted in superior OS (72.2%) compared with induction CT and RT (58.3%, P = .004) or RT alone (59.6%, P = .017). After adjustment, similar significant differences in OS were still observed between treatment groups. New CT regimens provided limited benefit in early-stage NKTCL. Risk-adapted therapy involving RT alone for low-risk patients and RT consolidated by CT for high-risk patients is a viable, effective strategy for early-stage NKTCL. [ABSTRACT FROM AUTHOR]

Background & Aims: Growing evidence has shown that M2-PK is involved in cancer diagnosis and prognosis. The overall diagnostic accuracy of the pyruvate kinase isoenzyme type M2 (M2-PK) in biliary tract carcinoma (BTC) remains controversial. We performed a meta-analysis to evaluate the diagnostic value of M2-PK for BTC. Methods: The online PubMed, Cochrane, Web of Science, and Embase databases were searched for eligible studies published until August 8th, 2017. The Quality Assessment for Diagnostic Accuracy Studies 2 (QUADAS-2) was used to evaluate study quality. All statistical analyses were conducted with Stata 12.0. Results: We included 7 studies from 5 articles with 410 patients with BTC and 438 controls. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and AUC for M2-PK in the diagnosis of BTC were 0.79 (95%CI 0.70-0.86), 0.81 (95%CI 0.71-0.88), 4.1 (95%CI 2.5-6.8), 0.26 (95%CI 0.16-0.41), 17.159 (95%CI 5.468-54.071), and 0.87 (95%CI 0.83-0.89), respectively. The same indicators assessed for CA19-9 were as follows: 0.70 (95%CI 0.62-0.77), 0.71 (95%CI 0.45-0.87), 2.38 (95%CI 1.2-4.73), 0.43 (95%CI 0.34-0.53), 6.28 (95%CI 2.4-16.44) and 0.73 (95%CI 0.69-0.77), respectively. Additionally, the diagnostic value of M2-PK varied based on characteristics of golden methods and different cut-off values. Conclusions: This meta-analysis showed that M2-PK had a better diagnostic accuracy for BTC compared with CA19-9, with moderate diagnostic performance. However, prospective studies are required to confirm its diagnostic value. [ABSTRACT FROM AUTHOR]