The risk of newly diagnosed cancer in patients with rheumatoid arthritis by TNF inhibitor use: a nationwide cohort study

Background : Tumor necrosis factor (TNF) inhibitors use in patients with rheumatoid arthritis (RA) has raised safety concerns about cancer risk, but study results remain controversial. This largest nationwide study to date compared cancer risk in TNF inhibitor users to non-biologic disease-modifying anti-rheumatic drug (nbDMARD) users in Korean patients with RA. Methods : Data on all the eligible patients diagnosed with RA between 2005 and 2016 were retrieved from the Korean National Health Information Database. The one-to-one matched patients consisted of the matched cohort. The risks for developing all-type and site-specific cancers were estimated using incidence and incidence rate (IR) per 1000 person-years. Adjusted hazard ratio (HR) and 95% confidence interval (CI) were estimated using a Cox regression model. Results : Of the 22,851 patients in the before matching cohort, 4592 patients were included in the matched cohort. Treatment with TNF inhibitors was consistently associated with a lower risk of cancer than in the nbDMARD cohort (IR per 1000 person-years, 6.5 vs. 15.6; adjusted HR, 0.379; 95% CI, 0.255–0.563). The adjusted HR (95% CI) was significantly lower in the TNF inhibitor cohort than the nbDMARD cohort for gastrointestinal cancer (0.432; 0.235–0.797), breast cancer (0.146; 0.045–0.474), and genitourinary cancer (0.220; 0.059–0.820). Conclusions : The use of TNF inhibitors was not associated with an increased risk of cancer development, and rather associated with a lower cancer incidence in Korean patients with RA. Cautious interpretation is needed not to oversimplify the study results as cancer-protective effects of TNF inhibitors. A further study linking claims and clinical data is needed to confirm our results.This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (grant number: HC17C0069

Clinical impacts of the concomitant use of L-asparaginase and total parenteral nutrition containing L-aspartic acid in patients with acute lymphoblastic leukemia

IntroductionL-asparaginase (ASNase) depletes L-asparagine and causes the death of leukemic cells, making it a mainstay for the treatment of acute lymphoblastic leukemia (ALL). However, ASNase's activity can be inhibited by L-aspartic acid (Asp), which competes for the same substrate and reduces the drug's efficacy. While many commercially used total parenteral nutrition (TPN) products contain Asp, it is unclear how the concomitant use of TPNs containing Asp (Asp-TPN) affects ALL patients treated with ASNase. This propensity-matched retrospective cohort study evaluated the clinical effects of the interaction between ASNase and Asp-TPN.MethodsThe study population included newly diagnosed adult Korean ALL patients who received VPDL induction therapy consisting of vincristine, prednisolone, daunorubicin, and Escherichia coli L-asparaginase between 2004 and 2021. Patients were divided into two groups based on their exposure to Asp-TPN: (1) Asp-TPN group and (2) control group. Data, including baseline characteristics, disease information, medication information, and laboratory data, were collected retrospectively. The primary outcomes for the effectiveness were overall and complete response rates. Relapse-free survival at six months and one year of treatment were also evaluated. The safety of both TPN and ASNase was evaluated by comparing liver function test levels between groups. A 1:1 propensity score matching analysis was conducted to minimize potential selection bias.ResultsThe analysis included a total of 112 ALL patients, and 34 of whom received Asp-TPN and ASNase concomitantly. After propensity score matching, 30 patients remained in each group. The concomitant use of Asp-TPN and ASNase did not affect the overall response rate (odds ratio [OR] 0.53; 95% confidence interval [CI] = 0.17–1.62) or the complete response rate (OR 0.86; 95% CI = 0.29–2.59) of the ASNase-including induction therapy. The concomitant use of Asp-TPN and ASNase also did not impact relapse-free survival (RFS) at six months and one year of treatment (OR 1.00; 95% CI = 0.36–2.78 and OR 1.24; 95% CI, 0.50–3.12, respectively). The peak levels of each liver function test (LFT) and the frequency of LFT elevations were evaluated during induction therapy and showed no difference between the two groups.ConclusionThere is no clear rationale for avoiding Asp-TPN in ASNase-treated patients

Food safety knowledge and practice by the stages of change model in school children

In this study, 342 grade 4-6 elementary school students in Gyeonggi-do were recruited to determine their readiness to change food safety behavior and to compare their food safety knowledge and practices by the stages of change. The subjects were divided into three stages of change; the percentage of stage 1 (precontemplation) was 10.1%, the percentage of stage 2 (contemplation and preparation) was 62.4%, and that of stage 3 (action and maintenance) was 27.5%. Food safety knowledge scores in stage 3 (4.55) or stage 2 (4.50) children were significantly higher than those in stage 1 children (4.17) (P < 0.05). The two food safety behavior items "hand washing practice" and "avoidance of harmful food" were significantly different among the three groups (P < 0.05). Stages of change were significantly and positively correlated with food safety knowledge and practice. Age was significantly and negatively correlated with the total food safety behavior score (r = -0.142, P < 0.05). The most influential factor on the stage of change was a mother's instruction about food safety (P < 0.01)

Increased Expression of Sodium Transporters in Rats Chronically Inhibited of Nitric Oxide Synthesis

The present study was done to determine whether endogenous nitric oxide (NO) plays a role in the regulation of sodium transporters in the kidney. Male Sprague-Dawley rats were treated with NG-nitro-L-arginine methyl ester (L-NAME, 100 mg/L drinking water) for 4 weeks. Control rats were supplied with tap water without drugs. Expression of Na, K-ATPase, type 3 Na/H exchanger (NHE3), Na/K/2Cl cotransporter (BSC1), and thiazide-sensitive Na/Cl cotransporter (TSC) proteins was determined in the kidney by Western blot analysis. Catalytic activity of Na,K-ATPase was also determined. The treatment with L-NAME significantly and steadily increased the systemic blood pressure. Total and fractional excretion of urinary sodium decreased significantly, while creatinine clearance remained unaltered. Neither plasma renin activity nor aldosterone concentration was significantly altered. The α1 subunit expression and the catalytic activity of Na, K-ATPase were increased in the kidney. The expression of NHE3, BSC1 and TSC was also increased significantly. These results suggest that endogenously-derived NO exerts a tonic inhibitory effect on the expression of sodium transporters, including Na, K-ATPase, NHE3, BSC1, and TSC, in the kidney

Two-Dimensional ESPRIT-Like Shift-Invariant TOA Estimation Algorithm Using Multi-Band Chirp Signals Robust to Carrier Frequency Offset

In this paper, a two-dimensional (2-D) ESPRIT-like shift-invariant time-of-arrival (TOA) estimation (ELSITE) algorithm for multi-band chirp signals in the presence of a carrier frequency offset (CFO) is presented. For the shift invariant TOA estimation, the received signals must be transformed into a sinusoidal form. When the received signals are perturbed by a CFO, the frequency of the transformed sinusoids is also shifted such that the TOA estimation results are biased. The TOA-induced phase shift of the multi-band chirp signals is determined according to the parameters of the signal, while the CFO-induced phase shift is only proportional to the elapsed time. Based on this property, the proposed ELSITE algorithm achieves robust TOA estimation against CFO from the signal subspace of the stacked matrix. The root mean square error of the proposed algorithm was analyzed and verified in both an AWGN channel and a multipath channel with CFO via Monte-Carlo simulations. © 2002-2012 IEEE.

Effects of wearing knee-guards on skin pressure and skin blood flow during dynamic motions

The purpose of the present study was to explore the effects of wearing knee guards on skin blood flow and skin pressure during dynamic soccer motions. Twenty-one male subjects participated in the following two experimental conditions: wearing knee guards (KG) and no knee guards (Control). Subjects performed several consecutive soccer motions along with a standing position between each motion. Skin blood flow and skin pressure on the thigh, knee, and calf were monitored. The results showed that skin pressure had the greatest value in a sitting position for both the KG condition and Control, but the smallest during instep kicking and switching directions (P &lt; 0.001). The rear calf had the greatest skin pressure for the KG condition (P &lt; 0.001), while the side knee showed the greatest for the Control (P &lt; 0.001). Normalized skin blood flow based on values from their standing position was the greatest during the jump motion among the various soccer motions. Interestingly, skin blood flow decreased by wearing the knee guards on the front thigh and calf (r = - 0.859; r = - 0.835; P &lt; 0.001), while the blood flow increased on the side knee (r = 0.295, P &lt; 0.001). Subjects felt greater skin pressure sensation during the jump motion and switching directions than other soccer positions/motions (P &lt; 0.001). These results indicate that the knee guards result in relatively lighter pressure for dynamic motions (e.g., kick, switching directions, or jump) than for static positions (e.g., sitting or standing), and the skin blood flows for the thigh, knee, and calf are redistributed by wearing the knee guards, especially during jumping.N

Association of Tumor Necrosis Factor Inhibitors with the Risk of Nontuberculous Mycobacterial Infection in Patients with Rheumatoid Arthritis: A Nationwide Cohort Study

Tumor necrosis factor inhibitors (TNFi) are proposed as a risk factor for nontuberculous mycobacteria (NTM) infection. Limited research investigates NTM infection risk in rheumatoid arthritis (RA) patients treated with TNFi compared to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), considering other concurrent or prior non-TNFi antirheumatic drugs. We aimed to evaluate the NTM infection risk associated with TNFi using a real-world database. Patients with RA treated with TNFi or csDMARDs between 2005 and 2016 were identified utilizing the Korean National Health Insurance Service database. To minimize potential bias, we aligned the initiation year of csDMARDs for both TNFi and csDMARD users and tracked them from their respective treatment start dates. The association of TNFi with NTM infection risk was estimated in a one-to-one matched cohort using a multivariable conditional Cox regression analysis. In the matched cohort (n = 4556), the incidence rates of NTM infection were 2.47 and 3.66 per 1000 person-year in TNFi and csDMARD users. Compared to csDMARDs, TNFi did not increase the risk of NTM infection (adjusted hazard ratio (aHR) 0.517 (95% confidence interval, 0.205–1.301)). The TNFi use in RA patients was not associated with an increased risk of NTM infection compared to csDMARDs. Nevertheless, monitoring during TNFi treatment is crucial