Search

Objectives: To evaluate the efficacy and safety of first-line targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs) in patients with rheumatoid arthritis (RA) and chronic kidney disease (CKD)., Methods: This retrospective cohort study included 216 patients with RA prescribed their first tsDMARDs at two hospitals between 2013 and 2022. Dose reduction and contraindication guidelines for tsDMARDs according to kidney function were followed. The patients were categorised by kidney function and tsDMARD modality. The primary outcome was the 24-month drug retention rate, and the secondary outcomes were changes in the Disease Activity Score 28-C-reactive protein (DAS28-CRP) level, prednisolone dosage, and reasons for discontinuation., Results: The 24-month drug retention rates according to the estimated glomerular filtration rate (eGFR) (≥60, 30-60, or < 30 mL/min/1.73 m2) were as follows: all tsDMARDs (46.0, 44.1, 47.1%), tofacitinib (55.9, 53.3, 66.7%), baricitinib (64.2, 42.0%), and peficitinib (36.4, 44.1, 40.0%). Even in groups with lower kidney function, the drug retention rate was maintained (adjusted hazard ratio was 1.14 (95% confidence interval, 0.81-1.62), p= 0.45). Patients had a decreased DAS28-CRP (p< 0.01) and a reduced prednisolone dosage (p< 0.01) over the six-month period following tsDMARD initiation. The incidence of herpes zoster and deep vein thrombosis (DVT) was higher in the group with an eGFR <30 mL/min/1.73 m2, but not statistically significant., Conclusions: tsDMARDs have demonstrated efficacy and safety in patients with RA and CKD; however, clinicians should consider the potential for herpes zoster and DVT in patients with eGFR <30 mL/min/1.73 m2., (© The Author(s) 2025. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Exposure to cold environments is linked to cold-induced hypertension due to activated sympathetic nerve activity (SNA) and arterial baroreceptor reflex dysfunction. However, direct measurement of SNA during cold-induced hypertension and changes in baroreflex control of SNA remain unexplored., Methods: Chronically instrumented rats were exposed to cold temperatures (10 °C) over 4 days after a control period (24 °C), and renal and lumbar sympathetic nerve activities were simultaneously measured during cold-induced hypertension. Baroreflex curves for renal SNA (RSNA) and lumbar SNA and heart rate were generated by altering arterial pressure via a bolus intravenous infusion of vasoactive drugs., Results: RSNA increased immediately after cold exposure, increased progressively throughout the 4-day period, and remained high after the cold exposure ended. Cold exposure shifted the RSNA baroreflex curve to the right and upward, gradually increasing the upper plateau (maximum capacity of sympathetic drive). The upper plateau remained elevated even after the cold exposure ended. Conversely, cold exposure increased lumbar SNA, heart rate, and arterial pressure, which subsequently returned to control levels after the cold exposure ended. These data indicate that cold exposure increases the maximum capacity to drive renal SNA in a regionally different and time-dependent manner through cumulative effects., Conclusions: Four days of cold exposure resulted in reversible effects increasing arterial pressure via lumbar SNA and heart rate, alongside time-dependent cumulative effects on RSNA. This study provides direct evidence of a self-activating pathway for RSNA that is activated by cold exposure, thus initiating cold-induced hypertension.

The current study aimed to propose a method to directly measure right cervical vagal nerve activity (cVNA) alongside renal sympathetic nerve activity (RSNA) in conscious rats. The right cervical vagus nerve was surgically exposed and fitted with a bipolar electrode to record cVNA. A microcatheter was used to administer levobupivacaine to selectively block afferent cVNA. Upon levobupivacaine administration, cVNA reduced by 84%, enabling the exclusive assessment of efferent cVNA. Intravenous and intraperitoneal administration of cholecystokinin-8 (CCK-8) demonstrated that peripherally acting CCK-8 influences the central nervous system through afferent cVNA without affecting the RSNA or efferent cVNA. This technique can be highly applicable for quantifying the dynamic changes in the interaction between vagal and sympathetic nerve activities, thereby shedding light on their roles in maintaining homeostasis and developing autonomic dysfunction, as in obesity and diabetes.

Comprehensive genomic profiling (CGP) is increasingly used as a clinical laboratory test and being applied to cancer treatment; however, standardization and external quality assessments (EQA) have not been fully developed. This study performed cost-effective EQA and proficiency tests (PT) for CGP testing among multiple institutions those belong to the EQA working group of Japan Association for Clinical Laboratory Science (JACLS). This study revealed that preanalytical processes, such as derived nucleic acids (NA) extraction from formalin fixed paraffine embedded (FFPE) samples, are critical. First, EQA with extracted DNA from cell lines showed a detection rate of 100% (9 out of 9) in KRAS (c.38G > A; p.G13D), PIK3CA (p.H1047R), and B-Raf proto-oncogene, serine/threonine kinase (BRAF) (c.1799 T > A; p.V600E) in cases of > 10% variant allele frequency (VAF). However, BRAF (c.1799 T > A; p.V600E) detection decreased to 67% (6 out of 9) for a VAF of 4.9%. Second, when DNA was extracted from FFPE samples, pathogenic variants and variants with companion diagnostic indications were detected in all 10 participating laboratories. Each variant had < 20% VAFs on average (8.1-19.1%) and wide variability among laboratories was observed (relative standard deviation, 13-60%). Nonetheless, BRAF (c.1798&#95;1799delinsAA; p.V600K) of 8.1% VAF, EGFR (c.2235&#95;2249del; p.E746&#95;A750del) of 9.7% VAF, and EGFR (c.2254&#95;2277del; p.S752&#95;I759del) of 9.8% VAF were detected with 70% (7/10), 70% (7/10), and 60% (6/10) frequency, respectively. Therefore, 10% VAF in pre-analytic processing for DNA extraction from FFPE was critical for variant detection in CGP analysis. Further, incorrect results were reported in case independent variant calling of BRAF; c.1798&#95;1799delinsAA (p.V600K) was mistakenly interpreted as c.1798G > A, and c.1799 T > A was on the other strand. In conclusion, the EQA/PT among 10 institutes with common samples revealed the importance of VAF in pre-analysis and helped us understand the significance of the pipeline and common pitfalls usually ignored by the internal quality control in a single institute., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s).)