Janus kinase inhibitors vs. abatacept about safety and efficacy for patients with rheumatoid arthritis-associated interstitial lung disease: a retrospective nested case-control study.

BACKGROUND: Interstitial lung disease (ILD) related to rheumatoid arthritis (RA) is among the leading causes of death and an essential prognostic factor. There is only limited evidence for the safety of anti-rheumatic drugs for patients with RA-ILD. The aim of this study is to investigate the safety and efficacy of Janus kinase inhibitors (JAKis) by comparing it with abatacept (ABT) in patients with RA-ILD. METHODS: This single centre, retrospective nested case-control study enrolled patients with RA-ILD treated with JAKi or ABT. To determine the safety of the two drugs for existing ILD, we compared their drug persistency, incidence rates of pulmonary complications, and change of chest computed tomography (CT) image. For their efficacy as RA treatment, disease activity scores and prednisolone (PSL)-sparing effect were compared. We performed propensity score matching to match the groups' patient characteristics. RESULTS: We studied 71 patients with RA-ILD (ABT, n = 45; JAKi, n = 26). At baseline, the JAKi group had longer disease duration, longer duration of past bDMARD or JAKi use and higher usual interstitial pneumonia rate. After propensity score matching, no significant differences in patient characteristics were found between the two groups. No significant difference in the drug persistency rate for the first 2 years (ABT, 61.9%; JAKi, 42.8%; P = 0.256) was observed between the two matched groups. The incidence rate of pulmonary complications did not differ significantly between the two groups (P = 0.683). The CT score did not change after the treatment for the ABT group (Ground-glass opacities (GGO): P = 0.87; fibrosis: P = 0.78), while the GGO score significantly improved for the JAKi group (P = 0.03), although the number was limited (ABT: n = 7; JAKi: n = 8). The fibrosis score of the JAKi group did not change significantly.(P = 0.82). Regarding the efficacy for RA, a significant decrease in disease activity scores after the 1-year treatment was observed in both groups, and PSL dose was successfully tapered, although no significant differences were observed between the two drugs. CONCLUSIONS: JAKi is as safe and effective as ABT for patients with RA-ILD. JAKi can be a good treatment option for such patients.

Ultrasound and magnetic resonance image findings in a patient with a subungual abscess: A case report.

Subungual abscesses are rare, and information about them through imaging findings is lacking. Carbon dioxide laser drainage and antibiotics are effective treatment strategies for subungual abscesses. We report a case of a 47-year-old male healthcare worker with a subungual abscess that improved after manual drainage alone. Ultrasound and magnetic resonance images showed a tumor (with blood flow) between the nail plate and distal phalanx. Culture tests revealed Staphylococcus aureus. The patient's symptoms resolved quickly and the nail returned to normal after 4 months. This is possibly the first report of a subungual abscess with ultrasound and magnetic resonance imaging findings.

Effect of Recent Antirheumatic Drug on Features of Rheumatoid Arthritis-Associated Lymphoproliferative Disorders.

OBJECTIVE: In this study, we examine how advancements in novel antirheumatic drugs affect the clinicopathologic features of lymphoproliferative disorder (LPD) in patients with rheumatoid arthritis (RA). METHODS: In this multicenter study across 53 hospitals in Japan, we characterized patients with RA who developed LPDs and visited the hospitals between January 1999 and March 2021. The statistical tools used included Fisher's exact test, the Mann-Whitney U-test, the log-rank test, logistic regression analysis, and Cox proportional hazards models. RESULTS: Overall, 752 patients with RA-associated LPD (RA-LPD) and 770 with sporadic LPD were included in the study. We observed significant differences in the clinicopathologic features between patients with RA-LPD and those with sporadic LPD. Histopathological analysis revealed a high frequency of LPD-associated immunosuppressive conditions. Furthermore, patients with RA-LPD were evaluated based on the antirheumatic drugs administered. The methotrexate (MTX) plus tacrolimus and MTX plus tumor necrosis factor inhibitor (TNFi) groups had different affected site frequencies and histologic subtypes than the MTX-only group. Moreover, MTX and TNFi may synergistically affect susceptibility to Epstein-Barr virus infection. In case of antirheumatic drugs administered after LPD onset, tocilizumab (TCZ)-only therapy was associated with lower frequency of regrowth after spontaneous regression than other regimens. CONCLUSION: Antirheumatic drugs administered before LPD onset may influence the clinicopathologic features of RA-LPD, with patterns changing over time. Furthermore, TCZ-only regimens are recommended after LPD onset.

Traumatic renal artery occlusion treated with an endovascular stent--the limitations of surgical revascularization: report of a case.

When renal artery occlusion occurs secondary to blunt trauma, the recovery rate of renal function after open revascularization is varied and far from satisfactory. Although the optimal treatment for this type of injury has not been established, percutaneous revascularization by endovascular stenting has recently been advocated for patients with unilateral renal artery occlusion. We herein report a case of blunt renal artery occlusion treated with an endovascular stent. After the placement of the stent, renal arteriography showed multiple nonflow-limiting contrast defects in the distal renal arteries, suggesting peripheral thrombosis. Although the duration of warm renal ischemia appears to be the crucial determinant of renal function, multiple thrombi in the distal renal arteries, which would be undetectable during open surgery, could also affect the functional outcome. The presence of these thrombi may explain the limited success of surgical revascularization in such cases.

Onsite medical rounds and fact-finding activities conducted by Nippon Medical School in Miyagi prefecture after the Great East Japan Earthquake 2011.

This report describes our onsite medical rounds and fact-finding activities conducted in the acute phase and medical relief work conducted in the subacute phase in Miyagi prefecture following the Great East Japan Earthquake and subsequent tsunami that occurred off northeastern Honshu on March 11, 2011. As part of the All-Japan Hospital Association medical team deployed to the disaster area, a Nippon Medical School team conducted fact-finding and onsite medical rounds and evaluated basic life and medical needs in the affected areas of Shiogama and Tagajo. We performed triage for more than 2,000 casualties, but in our medical rounds of hospitals, clinics, and nursing homes, we found no severely injured person but did find 1 case of hyperglycemia. We conducted medical rounds at evacuation shelters in Kesennuma City during the subacute phase of the disaster, from March 17 through June 1, as part of the Tokyo Medical Association medical teams deployed. Sixty-seven staff members (17 teams), including 46 physicians, 11 nurses, 3 pharmacists, and 1 clinical psychotherapist, joined this mission. Most patients complained of a worsening of symptoms of preexisting conditions, such as hypertension, respiratory problems, and diabetes, rather than of medical problems specifically related to the tsunami. In the acute phase of the disaster, the information infrastructure was decimated and we could not obtain enough information about conditions in the affected areas, such as how many persons were severely injured, how severely lifeline services had been damaged, and what was lacking. To start obtaining this information, we conducted medical rounds. This proved to be a good decision, as we found many injured persons in evacuation shelters without medication, communication devices, or transportation. Also, basic necessities for life, such as water and food, were lacking. We were able to evaluate these basic needs and inform local disaster headquarters of them. In Kesennuma City, we found that some evacuation shelters could not contact others even after 1 week after the earthquake. We realized from our experiences that, unlike our activities following more localized earthquake disasters, the first task following such large-scale disasters is to acquire information on basic life needs, including medication needs, and the number of persons requiring assistance. We must provide medical relief according to the unique characteristics of the disaster-affected areas as well as the specific nature of the disaster, in this case, a tsunami.

Mechanism of transition from xanthine dehydrogenase to xanthine oxidase: effect of guanidine-HCL or urea on the activity.

Mammalian xanthine oxidoreductase can be converted from the dehydrogenase to the oxidase form, either reversibly by formation of disulfide bridges or irreversibly by proteolytic cleavage within the xanthine oxidoreductase protein molecule. A tightly packed amino acid cluster stabilizes the dehydrogenase form, and disruption of this cluster is accompanied with rearrangement of the active site loop. Here, we show that the conversion occurs in the presence of guanidine-HCl or urea. We propose that xanthine dehydrogenase and oxidase are in a thermodynamic equilibrium that can be shifted by disruption of the amino acid cluster with a denaturant.

Systematic search for zinc-binding proteins in Escherichia coli.

A systematic search for Escherichia coli proteins with the zinc-binding activity was performed using the assay of radioactive Zn(II) binding to total E. coli proteins fractionated by two methods of two-dimensional gel electrophoresis. A total of 30-40 radioactive spots were identified, of which 14 have been assigned from N-terminal sequencing. In addition to five known zinc-binding proteins, nine zinc-binding proteins were newly identified including: acetate kinase (AckA), DnaK, serine hydroxymethyltransferase (GlyA), transketolase isozymes (TktA/TktB), translation elongation factor Ts (Tsf), ribosomal proteins L2 (RplB), L13 (RplM) and one of S15 (RpsO), S16 (RpsP) or S17 (RpsQ). Together with about 20 known zinc-binding proteins, the total number of zinc-binding proteins in E. coli increased up to more than 30 species (or more than 3% of about 1000 proteins expressed under laboratory culture conditions). The specificity and affinity of zinc-binding were analysed for some of the zinc-binding proteins.