Hokkaido hospital

Rheumatoid arthritis (RA) frequently affects the joints of the hands, with joint space narrowing (JSN) representing an important early marker of structural damage. The semi-quantitative Sharp/van der Heijde (SvdH) scoring system is widely used in clinical practice but is inherently subjective and susceptible to observer variability. Moreover, the complex anatomy of the wrist and substantial overlap of carpal bones pose challenges for automated quantitative assessment of wrist JSN on routine radiographs. This study aimed to introduce a novel quantitative assessment perspective and to clinically validate an automated, compactness-related quantification framework for evaluating wrist JSN in RA. This study initially enrolled 51 patients with RA. After excluding one case with severe carpal fusion that precluded anatomical differentiation, 50 patients (44 females and 6 males) were included in the final analysis. The cohort had a mean age of 61 years (range: 21-82), a median symptom duration of 9 years (IQR: 1-32), and a median follow-up interval for bilateral hand radiographs of 1.06 years (IQR: 0.82-1.30). To quantify global wrist JSN, 10 compactness-related metrics were computed based on the spatial distribution of bone centroids extracted from carpal segmentation masks. These metrics were validated against the wrist JSN subscore of the SvdH score (SvdH-JSN_wrist) and the total Sharp score (TSS) as gold standards. Several distance-based metrics among the compactness-related metrics showed significant negative correlations with the wrist joint space narrowing subscore of the Sharp/van der Heijde score (SvdH-JSN_wrist). Specifically, mean-pairwise-distance (MPD), root-mean-square-radius (RMSR), and median-radius (R50) showed moderate to strong correlations (r = -0.52 to -0.63, all p≤0.0001) that were consistent at BL and FU. Correlations with TSS were weaker overall, with only R50 and its normalized form showing stable negative correlations (r = -0.40 to -0.43, p < 0.01). Longitudinal analyses showed limited correlations between metric changes and clinical score changes. The proposed automated compactness quantification framework enables objective and reliable assessment of wrist JSN on standard radiographs and complements conventional scoring systems by supporting automated and standardized evaluation of RA-related wrist structural changes.

Background and AimsOzanimod is a once-daily, oral, selective sphingosine 1-phosphate receptor 1 and 5 modulator. The objective of the randomized, phase 2/3 J-True North study (NCT03915769) was to assess the efficacy and safety of ozanimod in Japanese patients with moderately to severely active ulcerative colitis.MethodsIn the 12-week induction period (IP), patients were randomized 1:1:1 to receive placebo, ozanimod 0.46 mg, or ozanimod 0.92 mg. Patients who completed the IP with a clinical response at week (w) 12 were eligible to enter a 40-week maintenance period where they received the same treatment as they did in the IP. The primary endpoint was clinical response (complete Mayo score) at w12; clinical and mucosal secondary endpoints were assessed at w12 and w52.ResultsOf 198 patients randomized, 176 completed the IP. Of these patients, 97 entered and 77 completed the maintenance period. A significantly higher proportion of patients receiving ozanimod achieved clinical response at w12 versus placebo (ozanimod 0.46 mg: 52.9%, P = .0158; ozanimod 0.92 mg: 61.5%, P = .0006; vs placebo: 32.3%). Similar results were observed in the secondary endpoints where patients receiving ozanimod achieved higher rates of clinical remission, endoscopic improvement, and mucosal healing at w12 than those receiving placebo. Efficacy was maintained at w52 for all endpoints. Both doses of ozanimod were well tolerated, with no unexpected safety signals.ConclusionThis large-scale clinical trial demonstrated the efficacy and safety of once-daily oral ozanimod in Japanese patients with moderately to severely active ulcerative colitis. This is the first time that the efficacy and safety of ozanimod were verified in a large number of patients in Asia.

BackgroundOpioids are almost mandatorily used as analgesia for cancer pain and postoperative pain. Opioid analgesics frequently induce a side effect of nausea which is one of the most unpleasant symptoms. However, the incidence of nausea caused by opioids varies among individuals, and the genomic factors involved are still mostly unknown.Aims & ObjectivesWe aim to clarify the genetic background for individual differences in the occurrence of nausea during opioid administration.MethodsIncidence of nausea was investigated in 428 patients (HS) who received morphine for cancer pain treatment at Higashi-Sapporo Hospital and 806 patients (CIH) who underwent standby surgery under general anesthesia at Cancer Institute Hospital. Genomic DNA was purified from patients’ blood and whole genome genotyping was performed. Nine single nucleotide polymorphisms (SNPs) out of the top 20 SNPs strongly associated with nausea in genome-wide association analysis (GWA) of HS were found in the whole-genome genotyping data of CIH (Nishizawa et al., 2023). Out of these 9 SNPs, only TMEM132C rs7296262 SNP had been reported to be associated with suicide attempts in bipolar disorder subjects in a previous study (Willour et al., 2012). Thus, TMEM132C rs7296262 SNP was further analyzed for the association with nausea in HS and CIH by using SPSS software.ResultsTMEM132C rs7296262 SNP showed a significant association with nausea in HS and CIH (TT+TC vs CC, HS, p = 0.0001; CIH, p = 0.006). In HS, a higher incidence rate of nausea was observed in CC carriers compared to TT+TC carriers (TT+TC/CC (%) are shown: with nausea, 77/23; without nausea, 92/8), while in CIH, a higher incidence rate of nausea was observed in T-allele carriers (with nausea, 87/13; without nausea, 83/17).Discussion and ConclusionTMEM132C rs7296262 SNP was significantly associated with nausea during opioid use. The nausea-prone genotype of the rs7296262 SNP was reversed in HS and CIH. Opioids are used chronically for cancer pain, whereas opioids are used acutely during postoperative analgesia. The effect of TMEM132C rs7296262 SNP on nausea may be reversed between the chronic and acute phases of opioid use. The acute administration of morphine may cause an increase in central nervous system expression of substance P and upregulates functional expression of the NK-1 receptor in cortical neurons, while chronic opioid use may lead to long-term repeated activation of mu opioid receptors, resulting in opioid-induced bowel dysfunction that may be associated with nausea and/or vomiting (Howard et al., 2012). Thus, different effects of acute and chronic opioid use may relate to our reversed results on nausea after opioid use.ReferencesHoward S.S., et al. (2012) Opioid-induced nausea and vomiting. Ann Palliat Med. 1(2):121-129.Nishizawa D., et al, (2023) Genome-wide association study identifies novel candidate variants associated with postoperative nausea and vomiting. Cancers. 15(19), 4729.Willour V.L., et al. (2012) A genome wide association study of attempted suicide. Mol Psychiatry. 17(4): 433-444.