Clinical outcomes of first-line combination therapy with immune checkpoint inhibitor for metastatic non-clear cell renal cell carcinoma: a multi-institutional retrospective study in Japan

The version of record of this article, first published in International Journal of Clinical Oncology, is available online at Publisher’s website: https://doi.org/10.1007/s10147-024-02612-1.Background: In metastatic clear cell renal cell carcinoma (ccRCC), recent studies have shown promising efficacy of immune checkpoint inhibitor (ICI) combination therapy. However, there are insufficient evidences about clinical efficacy and safety of ICI combination therapy in metastatic non-ccRCC (nccRCC). Methods: We retrospectively investigated 44 patients treated with nivolumab plus ipilimumab (ICI + ICI group) or anti-PD-1/PD-L1 inhibitor plus tyrosine kinase inhibitors (TKI) (ICI + TKI group), and assessed clinical efficacy in both groups. Results: Of all patients, overall response rate and disease control rate for ICI combination treatments were 36.3% and 75%, respectively. The median progression-free survival (PFS) and overall survival (OS) was 8.8 and 23.9 months, respectively. Multivariate analysis revealed that the presence of liver metastasis significantly affected worse PFS and OS (p = 0.035 and p = 0.049). Importantly, PFS and OS seemed similar in ICI + ICI group and ICI + TKI group (p = 0.778 and p = 0.559). Although the discontinuation rate of the combination therapy due to adverse effects in patients aged ≥ 75 years was significantly higher compared to that in patients aged < 75 years (45% versus 12%, p = 0.017), there were no significant differences in PFS and OS between two groups (p = 0.290 and p = 0.257, respectively). Conclusion: This study confirms clinical benefit of ICI combination therapy for metastatic nccRCC patients in real-world settings. Furthermore, the effectiveness of combination therapy was comparable between patients aged < 75 and those ≥75 years with respect to clinical prognosis

Dysregulation of RNF213 promotes cerebral hypoperfusion

RNF213 is a susceptibility gene for moyamoya disease, yet its exact functions remain unclear. To evaluate the role of RNF213 in adaptation of cerebral blood flow (CBF) under cerebral hypoperfusion, we performed bilateral common carotid artery stenosis surgery using external microcoils on Rnf213 knockout (KO) and vascular endothelial cell-specific Rnf213 mutant (human p.R4810K orthologue) transgenic (EC-Tg) mice. Temporal CBF changes were measured by arterial spin-labelling magnetic resonance imaging. In the cortical area, no significant difference in CBF was found before surgery between the genotypes. Three of eight (37.5%) KO mice died after surgery but all wild-type and EC-Tg mice survived hypoperfusion. KO mice had a significantly more severe reduction in CBF on day 7 than wild-type mice (KO, 29.7% of baseline level; wild-type, 49.3%; p = 0.038), while CBF restoration on day 28 was significantly impaired in both KO (50.0%) and EC-Tg (56.1%) mice compared with wild-type mice (69.5%; p = 0.031 and 0.037, respectively). Changes in the subcortical area also showed the same tendency as the cortical area. Additionally, histological analysis demonstrated that angiogenesis was impaired in both EC-Tg and KO mice. These results are indicative of the essential role of RNF213 in the maintenance of CBF

Seismic Exploration Using Active Sources at Kuchierabujima Volcano, Southwest Japan

Seismic exploration using artificial sources was conducted at Kuchierabujima volcano, southwest Japan in November 2004 by 40 participants from 9 national universities andJapan Meteorological Agency to investigate the subsurface seismic structure. The exploration was the 11th joint experiment under the National Project for Prediction of Volcanic Eruptions. A total of 183 temporal stations equippedwith a 2 Hz vertical component seismometer (including 75 3component seismometers) and a portable data logger were deployed on Kuchierabu Island. Dynamite shots with charges of 10-115 kg were detonated at 19 locations, and seismic signals were successfully recorded. To reveal the P-wave velocity structure, 2955 arrival times of the first motion were picked from the seismograms, and 2187 were classified into ranks A and B. From the record sections and the arrival time data, characteristics reflecting the geological structure were identified. Refracted waves of 5 km/s were observed at stations＞5km from the shot points. Apparent velocities near the shot points depend on the surface geology around the shots. P-wave arrived earlier at stations near the summits. Strongly scattered waves were observed similarly near the summits

A rare form of out-of-hospital cardiopulmonary arrest due to spinal epidural arteriovenous fistula: A case report

Background: A spinal arteriovenous fistula (AVF) can lead to cardiac arrest, but survival from out-of-hospital cardiac arrest (OHCA) has never been reported in the literature. Case presentation: An 84-year-old female called an ambulance because of sudden left hemiparesis. The emergency medical service crew found her in cardiac arrest. Upon hospital arrival, spontaneous circulation returned, and the patient was admitted to intensive care. She regained consciousness after targeted temperature management; however, no limb movements were observed. Since head computed tomography on arrival showed a high-density area at the cervical level, she underwent angiography, which revealed a spinal epidural AVF. Transarterial embolization of the AVF was performed. On day 70, the patient was transferred to a long-term care hospital under mechanical ventilation (cerebral performance category of 1 and modified Rankin Scale of 5). Conclusion: We reported a survival case of OHCA due to ruptured cervical epidural AVF. Optimal management for this condition requires further studies

Short-Range Spin Ordering near Room Temperature in Stoichiometric LuFe2O4

化学当量的なLuFe2O4において磁気秩序温度から300Kの間で短距離磁気秩序に関わる散漫散乱が観測されている。この散漫散乱を理解するためオークリッジ国立研究所のWAND2ビームラインにおいて磁場印加中の中性子回折実験を行ったところ短距離磁気秩序が発生する温度領域において磁場印加によってフェリ磁性秩序と同型の磁気ピーク構造が観測された。発表では磁化測定の結果も含め化学当量的なLuFe2O4の温度-磁場に依存する磁気秩序相について考察するMaterials Research Meeting 2021 (MRM2021

Effects of winter flooding on phosphorus dynamics in rice fields

Controlling phosphorous (P) loads from rice fields is important for the conservation of aquatic ecosystems, in part because P is relatively concentrated at its sources. Recently, winter flooding, by which irrigation water is maintained in rice fields during winter, has attracted much attention as a farming strategy for environmental conservation and biodiversity maintenance. However, the effects of winter flooding on nutrient cycles have received little research attention. We evaluated the effects of winter flooding on P loads in rice fields by performing laboratory experiments with soils from rice fields with/without winter flooding. These incubation experiments showed that total and soluble reactive P concentrations in surface solutions are decreased by winter flooding. This decrease may follow co-precipitation of P with iron, which may be dissolved from winter flooded soil and rapidly precipitates in solution. Periphyton, which may increase during winter flooding, may not contribute to this decrease because puddling resets periphyton quantities on surface soils. P loads from rice fields with winter flooding over 16 days after fertilization could be reduced by an average of 26% compared with those without winter flooding, indicating that winter flooding is a valuable strategy for reducing P loads in spring when high P loads occur.This research was supported by the RIHN Project (Grant No. D06-14200119) and JSPS KAKENHI Grant Number JP19K15723

Effects of autogenous bone graft on mass and quality of trabecular bone in Ti-6Al-4V spinal cage fabricated with electron beam melting

A spinal cage is one of the primary spinal devices used for the treatment of spinal diseases such as lumbar spondylolisthesis. Since it is set in the intervertebral space that causes instability to promote the fusion of the adjacent vertebral bodies, it requires the early induction of healthy bones. For this reason, in most cases, an autogenous bone extracted from the patient’s ilium is implanted in the interior of the cage to stimulate bone formation. However, collecting autogenous bone involves secondary surgery and several clinical problems such as pain in the part from which it is collected. Additionally, the effect of the autogenous bone graft itself has not been sufficiently studied yet. Moreover, the mechanical functions of trabecular bones in a vertebral body are governed by the anisotropic structure of the trabeculae and the preferential orientation of the apatite/collagen in a trabecula with respect to the principal stress. Despite this fact, after the implantation of the cage, the mass of the bones is evaluated with soft X-ray photography, which does not guarantee an accurate measurement of bone functions. In this study, the effect of the autogenous bone graft on the spinal cage was verified based on structural anisotropy of trabecular bones and the preferential orientation of apatite/collagen in a trabecula using sheep. The autogenous bone graft demonstrated a significant effect on the increase of bone mass and anisotropy of the trabecular structure. However, compared to the trabecular anisotropy of normal parts, the anisotropy of the trabecular structure and apatite c-axis orientation of the parts with autogenous bone graft were considerably lower, indicating a minimal effect of the autogenous bone graft. Therefore, it was suggested that early stabilization of the spinal cage requires another strategy that rapidly forms the unique hierarchical anisotropic structure of trabecular bones.Takahashi H., Ishimoto T., Inoue T., et al. Effects of autogenous bone graft on mass and quality of trabecular bone in Ti-6Al-4V spinal cage fabricated with electron beam melting. Materials Transactions 60, 144 (2019); https://doi.org/10.2320/matertrans.M2018329