Prediction of early progression of metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitor

Background:There are various alternative first-line therapeutic options besides tyrosine kinase inhibitors (TKIs) for metastatic renal cell carcinoma (mRCC). To inform therapeutic decision-making for such patients, this study aimed to identify predictive factors for resistance to TKI.Materials and methods:A total of 239 cases of mRCC patients who received first-line TKI therapy were retrospectively studied. Patients with a radiologic diagnosis of progressive disease within 3 months after initiating therapy were classified as primary refractory cases; the others were classified as non-primary refractory cases. The association between primary refractory cases and age, gender, pathology findings, serum c-reactive protein (CRP) level, metastatic organ status, and 6 parameters defined by the International Metastatic Renal Cell Carcinoma Database Consortium were analyzed.Results:Of 239 cases, 32 (13.3%) received a radiologic diagnosis of progressive disease within 3 months after initiating therapy. The rates of sarcomatoid differentiation, hypercalcemia, a serum CRP level of 0.3 mg/dL or higher, presence of liver metastasis, anemia, and time from diagnosis to treatment interval of less than a year were significantly higher in the primary refractory group. Multivariate analysis showed that sarcomatoid differentiation, hypercalcemia, a serum CRP level of 0.3 mg/dL or higher, and liver metastasis were independently associated with primary refractory disease. A risk-stratified model based upon the number of patients with these factors indicated rates of primary refractory disease of 4.0%, 10.1%, and 45.0% for patients with 0, 1, and 2 or more factors, respectively.Conclusions:Sarcomatoid differentiation, hypercalcemia, an elevated serum CRP level, and presence of liver metastasis were associated with primary refractory disease in mRCC patients receiving first-line TKI therapy. These results provide clinicians with useful information when selecting a first-line therapeutic option for mRCC patients.     

Leadless cardiac pacemaker implantations after infected pacemaker system removals in octogenarians

BackgroundManagement of pacemaker (PM) infections among advanced aged patients possesses particular clinical challenges due to higher rates of concurrent cardiovascular disease and medical comorbidities. Novel leadless cardiac pacemakers (LCPs) may provide new opportunities for better management options in this population, however, there is limited data especially in Asian populations to guide the decision making.MethodsWe reviewed 11 octogenarians (median age: 86 [minimum 82–maximum 90] years; male: 73%; median body mass index (BMI): 20.1 kg/m²) who received Micra Transcatheter Pacing System (Medtronic Inc, Minneapolis, MN) implantations following transvenous lead extractions (TLEs) for PM infections. ResultsAll patients had more than two medical comorbidities (average 3.7 comorbidities). The indications for LCP implantations were atrioventricular block in four patients, atrial fibrillation bradycardia in five, and sinus node dysfunction in two. Eight patients (73%) were bridged with temporary pacing using active fixation leads (median interval of 14.0 days), while one with severe dementia underwent a concomitant LCP implantation and TLE during the same procedure. Successful TLEs and LCP implantations were successfully accomplished in all without any complications. The median time from the TLE procedure to discharge was 22 days (minimum 7–maximum 136). All patients remained free of infections during a mean follow-up period of 17.2 ± 6.5 months.ConclusionsLCP implantations were safe and effective after removing the entire infectious PM system in all octogenarians. The novel LCP technology may offer an alternative option for considering a re-implantation strategy after transvenous PM infections in elderly patients, particularly those with severe frailty and PM dependency.

The incidence of cardiac pacemaker (PM) infections among patients with an advanced age has been increasing owing to the continually widening indications and growing number of generator replacements.^[1–3] In current clinical practice, there is a class l indication for removing all hardware in the case of a proven or suspected device infection, and after a recovery window, a new conventional PM is implanted in PM dependent patients.^[1,4,5] However, this management for the elderly population is one of the most sensitive issues, since they possess particular clinical challenges due to higher rates of concurrent cardiovascular disease and medical comorbidities.^[6–10]Recently, the implantation of a Micra Transcatheter Pacing System (Medtronic Inc, Minneapolis, MN) has emerged as a new option for PM re-implantations after the removal of infectious PMs.^[11–17] Without the use of leads and a device pocket, this leadless cardiac pacemaker (LCP) potentially reduces the risk of pocket infections and lead associated endocarditis.^[16,17] However, there have not been enough data supporting the feasibility of leadless PM implantations following the removal of infectious PMs in people with an older age, particularly in octogenarians. Furthermore, there has been no data regarding those therapeutic strategies in Asian populations who have a low body mass index (BMI) and are at a higher risk of a transvenous lead extraction (TLE) procedure. Therefore, in this case series, we sought to characterize the procedure for LCP implantations following TLEs of infected PMs in octogenarians at 2 Japanese high-volume centers.     

Antibodies to β2-glycoprotein I and clinical manifestations in patients with systemic lupus erythematosus

Objective. To investigate whether anticardiolipin antibodies (aCL) in patients with systemic lupus erythematosus (SLE) bind to β₂-glycoprotein I (β₂GPI), and to search for a relationship between the presence of IgG and/or IgM anti-β₂GPI antibody and clinical manifestations in SLE patients. Methods. IgG and IgM anti-β₂GPI in 308 Japanese SLE patients were measured using phospholipid-independent enzyme immunoassays. Relationships to clinical histories and to various laboratory data were examined. Results. The values of anti-β₂GPI and aCL, as measured by conventional enzyme immunoassay, showed a strong correlation, but the anti-β₂GPI assay was more useful in distinguishing β₂GPI-dependent aCL from β₂GPI-independent aCL. The presence of IgG anti-β₂GPI was associated with an increased frequency of a history of thrombosis. Comparisons of various laboratory data suggested that the titer of anti-β₂GPI may fluctuate with disease activity. Conclusion. The results suggest that pathogenic aCL is directed against structurally altered β₂GPI and that enzyme immunoassay for anti-β₂GPI may prove useful in evaluating the risk of thrombosis and monitoring the clinical course in patients with SLE.     

Nuclear FABP7 regulates cell proliferation of wild‐type IDH1 glioma through caveolae formation

Isocitrate dehydrogenase 1 (IDH1) is a key enzyme in cellular metabolism. IDH1 mutation (IDH1mut) is the most important genetic alteration in lower grade glioma, whereas glioblastoma (GB), the most common malignant brain tumor, often has wild‐type IDH1 (IDH1wt). Although there is no effective treatment yet for neither IDH1wt nor IDHmut GB, it is important to note that the survival span of IDH1wt GB patients is significantly shorter than those with IDH1mut GB. Thus, understanding IDH1wt GB biology and developing effective molecular‐targeted therapies is of paramount importance. Fatty acid‐binding protein 7 (FABP7) is highly expressed in GB, and its expression level is negatively correlated with survival in malignant glioma patients; however, the underlying mechanisms of FABP7 involvement in tumor proliferation are still unknown. In this study, we demonstrate that FABP7 is highly expressed and localized in nuclei in IDH1wt glioma. Wild‐type FABP7 (FABP7wt) overexpression in IDH1wt U87 cells increased cell proliferation rate, caveolin‐1 expression, and caveolae/caveosome formation. In addition, FABP7wt overexpression increased the levels of H3K27ac on the caveolin‐1 promoter through controlling the nuclear acetyl‐CoA level via the interaction with ACLY. Consistent results were obtained using a xenograft model transplanted with U87 cells overexpressing FABP7. Interestingly, in U87 cells with mutant FABP7 overexpression, both in vitro and in vivo phenotypes shown by FABP7wt overexpression were disrupted. Furthermore, IDH1wt patient GB showed upregulated caveolin‐1 expression, increased levels of histone acetylation, and increased levels of acetyl‐CoA compared with IDH1mut patient GB. Taken together, these data suggest that nuclear FABP7 is involved in cell proliferation of GB through caveolae function/formation regulated via epigenetic regulation of caveolin‐1, and this mechanism is critically important for IDH1wt tumor biology.     

Benefits of robotically-assisted surgery for complex mitral valve repair

OBJECTIVESTo determine whether robotic mitral valve repair can be applied to more complex lesions compared with minimally invasive direct mitral valve repair through a right thoracotomy. Open in a separate windowMETHODSWe enrolled 335 patients over a 9-year period; 95% of the robotic surgeries were performed after experience performing direct mitral valve repair.RESULTSThe mean age in the robotic versus thoracotomy repair groups was 61 ± 14 vs 55 ± 11 years, respectively (P < 0.001); 97% vs 100% of the patients, respectively, had degenerative aetiologies. Repair complexity was simple in 106 (63%) vs 140 (84%), complex in 34 (20%) vs 20 (12%) and most complex in 29 (17%) vs 6 (4%) patients undergoing robotic versus thoracotomy repair, respectively. The average complexity score with robotic repair was significantly higher versus thoracotomy repair (P < 0.001). The robotic group underwent more chordal replacement using polytetrafluoroethylene and less resections. All patients underwent ring annuloplasty. Cross-clamp time did not differ between the groups, and no strokes or deaths occurred. More patients undergoing robotic repair underwent concomitant procedures versus the thoracotomy group (30% vs 14%, respectively; P < 0.001). The overall repair rate was 100%, with no early mortality or strokes in either group. Postoperative mean residual mitral regurgitation was 0.3 in both groups, and the mean pressure gradient through the mitral valve was 2.4 vs 2.7 mmHg (robotic versus thoracotomy repair, respectively; P = 0.031).CONCLUSIONSRobotic surgery can be applied to repair more complex mitral lesions, with excellent early outcomes.     

Creating an appropriate access for endovascular repair by replacing a dissected femoral artery in aortic dissection

Transfemoral endovascular repair has been widely accepted as an effective treatment for type B aortic dissection. However, if the dissection extends to the femoral artery, the transfemoral approach increases the risk of access complications. We describe a case of acute complicated type B aortic dissection involving the dissected bilateral femoral arteries. Successful endovascular repair without access complications was performed through an appropriate access route created by a femoral arterial conduit. We believe that this approach results in reliable cannulation of the true lumen and the reduction of the risk for intimal injury in aortic dissection with the dissected femoral artery.     

Zr- and Ce-doped Li6Y(BO3)3 electrolyte for all-solid-state lithium-ion battery

The ionic conductivity of Li₆Y(BO₃)₃ (LYBO) was enhanced by the substitution of tetravalent ions (Zr⁴⁺ and Ce⁴⁺) for Y³⁺ sites through the formation of vacancies at the Li sites, an increase in compact densification, and an increase in the Li⁺-ion conduction pathways in the LYBO phase. As a result, the ionic conductivity of Li_5.875Y_0.875Zr_0.1Ce_0.025(BO₃)₃ (ZC-LYBO) reached 1.7 × 10⁻⁵ S cm⁻¹ at 27 °C, which was about 5 orders of magnitude higher than that of undoped Li₆Y(BO₃)₃. ZC-LYBO possessed a large electrochemical window and was thermally stable after cosintering with a LiNi_1/3Mn_1/3Co_1/3O₂ (NMC) positive electrode. These characteristics facilitated good reversible capacities in all-solid-state batteries for both NMC positive electrodes and graphite negative electrodes via a simple cosintering process.

Ionic conductivity of Li₆Y(BO₃)₃ (LYBO) is enhanced by the substitution of tetravalent ions through an increase in the conduction pathways etc. Zr,Ce-doped LYBO can be used as an electrolyte for all-solid-state batteries via a cosintering process.     

School health promotion in South‐East Asia by Japan and partners

School health promotion in South‐East Asia has developed rapidly in recent years, and Japan has been one of the significant contributors to the reinforcement of school health promotion in the region. Starting from the Hashimoto Initiative on global parasite control, Japan advocated for international partnerships with several agencies for the development of school health programs in South‐East Asia. Through a strengthened collaboration with international organizations, countries such as the Lao PDR, Cambodia, the Philippines, and Thailand have created and implemented school health programs on nutrition, sanitation, and deworming, among others. In addition to school health program formulation and implementation, the expanded network in South‐East Asia led to more capable school health personnel, with many workers in the education and health sectors benefitting from the training programs jointly held by collaborating organizations.