Showing papers by "Kanazawa Medical University published in 2022"

Association of tumour burden with the efficacy of programmed cell death-1/programmed cell death ligand-1 inhibitors for treatment-naïve advanced non-small-cell lung cancer

Abstract: Tumour burden (TB) is implicated in resistance to programmed cell death-1/PD-L1 inhibitor (immune checkpoint inhibitor [ICI]) therapy. However, whether TB contributes to such resistance in non-small-cell lung cancer (NSCLC) has remained unknown.A total of 260 treatment-naïve patients with advanced NSCLC who started ICI monotherapy (ICI cohort), platinum-doublet therapy (Chemo cohort) or ICI and platinum-doublet therapy (ICI+Chemo cohort) as first-line treatment were consecutively included. TB was estimated on the basis of the sum of the diameters of measurable target lesions as per Response Evaluation Criteria in Solid Tumours. Progression-free survival (PFS) in the ICI cohort was evaluated as per TB as a preplanned primary objective, with the analysis based on propensity score-weighted survival curves and estimation of restricted mean survival time (RMST). The Chemo cohort served as a control to determine whether TB is predictive of ICI treatment outcomes. The ICI+Chemo cohort was exploratory. The relation of TB to tumour immune status was assessed by immune-related gene expression profiling (irGEP) of pretreatment tumour tissue.In the ICI cohort, patients with a low TB showed a significantly longer PFS than did those with a high TB (median, 17.9 vs 4.3 months; weighted hazard ratio, 0.32 [95% confidence interval, 0.19-0.53]). No such difference was apparent in the other cohorts. A significant difference in overall survival was also observed only in the ICI cohort. RMST-based analysis confirmed these results. The irGEP analysis implicated M2-type macrophages, angiogenesis and transforming growth factor-β as well as protumourigenic signalling pathways in ICI resistance conferred by a high TB.A high TB was associated with a poor outcome of ICI therapy for advanced NSCLC as a result of immunosuppressive phenotypes. Development of combination or novel treatment strategies for such disease is thus warranted.

Analysis of risk factors for postoperative complications in non-small cell lung cancer: comparison with the Japanese National Clinical Database risk calculator

Abstract: Although the risk calculator of the National Clinical Database (RC-NCD) has been widely used to predict the occurrence of mortality and major morbidity in Japan, it has not been demonstrated whether a correlation between the calculated RC-NCD risk score and the actual occurrence of mortality and severe morbidity exists.The clinical data of 585 patients who underwent pulmonary resection for non-small cell lung cancer were collected, and the risk factors for postoperative morbidity were analyzed to verify the validity of the RC-NCD.The coexistence of asthma (p = 0.02), nutrition lymphocyte ratio (p = 0.04), and pulmonary lobe (p < 0.01) were significant risk factors for postoperative morbidity in the present study, and the percent-predicted vital capacity (p < 0.01), pulmonary lobe (p = 0.03), and type of operative procedure (p = 0.01) were significant risk factors for severe postoperative morbidity. Furthermore, in patients received lobectomy, coexistence of asthma (p = 0.01) and pulmonary lobe (p < 0.01) were identified as significant risk factors for postoperative morbidity. Meanwhile, male sex (p = 0.01), high BMI (p < 0.01), low vital capacity (p = 0.04), and pulmonary lobe (p = 0.03) were identified as significant risk factors for severe postoperative morbidity.Given that the pulmonary lobe was a significant risk factor for postoperative morbidity in patients received pulmonary resection and for severe postoperative morbidity in patients received lobectomy, the RC-NCD for postoperative morbidity needs to be modified according to high-risk lobes.The Institutional Review Board of Kanazawa Medical University approved the protocol of this retrospective study (approval number: I392), and written informed consent was obtained from all patients.

Switching from blonanserin oral tablets/powders to transdermal patches alleviates extrapyramidal symptoms in patients with schizophrenia: A 52-week open-label study

Abstract: Blonanserin is a second-generation antipsychotic for the treatment of schizophrenia. Blonanserin has two different routes of administration: oral tablets/powder and transdermal patches. The aim of this study was to investigate as a post-hoc analysis of an original study whether switching from blonanserin tablets/powders to transdermal patches would reduce extrapyramidal symptoms (EPS) and/or the dose of antiparkinsonian drugs for the stabilization of blood pharmacokinetics in patients with schizophrenia. Patients with schizophrenia (n = 155) were enrolled in either cohort 1 or 2. In cohort 1 (n = 97), patients received 40-80 mg/day blonanserin transdermal patches for one year after taking 8-16 mg/day blonanserin tablets for 6 weeks, and the dose of patches was determined based on the dose of the tablets. In cohort 2 (n = 58), all patients started with 40 mg/day blonanserin patches and then received 40-80 mg/day for a year after taking blonanserin tablets/powders. Changes from the start of transdermal patch treatment in EPS and the dose of antiparkinsonian drugs at 3, 6, and 12 months were assessed using the Drug-Induced EPS Scale (DIEPSS) and biperiden equivalents of total antiparkinsonian drugs (BPD-eq), respectively. Among 155 patients, only four patients in cohort 1 discontinued owing to EPS during a patch period. Significant improvements from the start of patch treatment in the DIEPSS total score at any point were observed (mean change±SD): -0.44 ± 1.50 (p = 0.013), -0.07 ± 1.78 (p = 0.73), and - 0.14 ± 1.37 (p = 0.44) in cohort 1 and - 0.16 ± 1.32 (p = 0.40), -0.74 ± 1.92 (p = 0.020), and - 0.81 ± 2.22 (p = 0.047) in cohort 2 at 3, 6, and 12 months, respectively. In contrast, there were no significant changes from the start of patch treatment in BPD-eq at any month (p > 0.05). Transdermal patches of blonanserin are a more effective route of administration to diminish EPS than oral tablets/powder.

Benzalkonium Chloride-Induced Corneal Epithelial Injury in Rabbit Reduced by Rebamipide

Abstract: Purpose: We assessed the effect of rebamipide ophthalmic solution on corneal epithelial injury due to benzalkonium chloride (BAK) by fluorescein (FL) staining and corneal resistance (CR). Methods: After determining the absence of corneal epithelial damage by FL and CR, rebamipide ophthalmic solution (50 μL) was instilled five times, each interspaced by 5 min, into one eye of mature New Zealand white rabbits, and likewise physiological saline was instilled into the contralateral eye as the control. After 30 min, eyes were similarly treated with one of the following solutions: BAK solution 0.02%, latanoprost ophthalmic solution (0.02% BAK), or latanoprost ophthalmic solution without BAK. The presence of corneal epithelial damage was quantitated at 10, 30, and 60 min by CR after the last instillation. FL staining was also performed at 60 min after the last instillation. Results: CR ratios (%) at 60 min after the last instillation in rebamipide/BAK and rebamipide/latanoprost (0.02% BAK) groups were significantly increased by 18.3% and 25.6% compared with saline/BAK and saline/latanoprost (0.02% BAK) groups, respectively (P < 0.05). Findings by FL staining were consistent with those by CR; BAK and latanoprost with BAK groups were positive, and eyes with the most severe area and density of corneal epithelial damage (A2D2) were in the saline/BAK group. Conclusion: The rebamipide ophthalmic solution reduces the severity of corneal epithelial injury caused by BAK, an ophthalmic solution preservative.

Switching from blonanserin oral tablets/powders to transdermal patches alleviates extrapyramidal symptoms in patients with schizophrenia: A 52-week open-label study

Abstract: Blonanserin is a second-generation antipsychotic for the treatment of schizophrenia. Blonanserin has two different routes of administration: oral tablets/powder and transdermal patches. The aim of this study was to investigate as a post-hoc analysis of an original study whether switching from blonanserin tablets/powders to transdermal patches would reduce extrapyramidal symptoms (EPS) and/or the dose of antiparkinsonian drugs for the stabilization of blood pharmacokinetics in patients with schizophrenia. Patients with schizophrenia (n = 155) were enrolled in either cohort 1 or 2. In cohort 1 (n = 97), patients received 40-80 mg/day blonanserin transdermal patches for one year after taking 8-16 mg/day blonanserin tablets for 6 weeks, and the dose of patches was determined based on the dose of the tablets. In cohort 2 (n = 58), all patients started with 40 mg/day blonanserin patches and then received 40-80 mg/day for a year after taking blonanserin tablets/powders. Changes from the start of transdermal patch treatment in EPS and the dose of antiparkinsonian drugs at 3, 6, and 12 months were assessed using the Drug-Induced EPS Scale (DIEPSS) and biperiden equivalents of total antiparkinsonian drugs (BPD-eq), respectively. Among 155 patients, only four patients in cohort 1 discontinued owing to EPS during a patch period. Significant improvements from the start of patch treatment in the DIEPSS total score at any point were observed (mean change±SD): -0.44 ± 1.50 (p = 0.013), -0.07 ± 1.78 (p = 0.73), and - 0.14 ± 1.37 (p = 0.44) in cohort 1 and - 0.16 ± 1.32 (p = 0.40), -0.74 ± 1.92 (p = 0.020), and - 0.81 ± 2.22 (p = 0.047) in cohort 2 at 3, 6, and 12 months, respectively. In contrast, there were no significant changes from the start of patch treatment in BPD-eq at any month (p > 0.05). Transdermal patches of blonanserin are a more effective route of administration to diminish EPS than oral tablets/powder.

Cognitive performances across individuals at high genetic risk for schizophrenia, high genetic risk for bipolar disorder, and low genetic risks: a combined polygenic risk score approach

Abstract: Abstract Background Individuals with schizophrenia (SCZ) and bipolar disorder (BD) display cognitive impairments, but the impairments in those with SCZ are more prominent, supported by genetic overlap between SCZ and cognitive impairments. However, it remains unclear whether cognitive performances differ between individuals at high and low genetic risks for SCZ or BD. Methods Using the latest Psychiatric Genomics Consortium (PGC) data, we calculated PGC3 SCZ-, PGC3 BD-, and SCZ v. BD polygenic risk scores (PRSs) in 173 SCZ patients, 70 unaffected first-degree relatives (FRs) and 196 healthy controls (HCs). Based on combinations of three PRS deciles, individuals in the genetic SCZ, genetic BD and low genetic risk groups were extracted. Cognitive performance was assessed by the Brief Assessment of Cognition in Schizophrenia. Results SCZ-, BD-, SCZ v. BD-PRSs were associated with case–control status ( R 2 = 0.020–0.061), and SCZ-PRS was associated with relative–control status ( R 2 = 0.023). Furthermore, individuals in the highest decile for SCZ PRSs had elevated BD-PRSs [odds ratio (OR) = 6.33] and SCZ v. BD-PRSs (OR = 1.86) compared with those in the lowest decile. Of the three genetic risk groups, the low genetic risk group contained more HCs, whereas the genetic BD and SCZ groups contained more SCZ patients ( p < 0.05). SCZ patients had widespread cognitive impairments, and FRs had cognitive impairments that were between those of SCZ patients and HCs ( p < 0.05). Cognitive differences between HCs in the low genetic risk group and SCZ patients in the genetic BD or genetic SCZ groups were more prominent (Cohen's d > −0.20) than those between HCs and SCZ patients in the no genetic risk group. Furthermore, SCZ patients in the genetic SCZ group displayed lower scores in verbal fluency and attention than those in the genetic BD group ( d > −0.20). Conclusions Our findings suggest that cognitive impairments in SCZ are partially mediated through genetic loadings for SCZ but not BD.

Challenging the Transition of Civilization: Theory and Practice of “Energy Democracy”

Abstract: Abstract Today, wind powers and solar powers have become the main stream of energies. Everyone, from major electric power utilities to mega capital investors, has entered the renewable energy sector, increasingly and rapidly expanding the mass capital investment projects in the world. It is not rare to find cases of such mega projects developing confrontations with local communities. Since 1990s, the privatization of energy sector has been significant, with Nordic countries and Germany seeing the advancement of privatizations among community-operated energy utilities. Recently, however, there has been the movement to re-review such trend “to revive public utilities”. The recent reversal of privatization trend means that the conventional way of decision-making participated by local governments and handful corporations is no longer appropriate, and there is a rise of common understanding that the decision-making and governance method of local communities must be open and distributed horizontally. The rapid progress of ICT in recent years has raised awareness of risks in the governance system dominated by private companies, while raising technical capabilities to realize new and open decision-making and governance in local communities.

[Cancer Professional Training Program in Hokushin Region].

Abstract: The Hokushin-Gan-pro, consists of Kanazawa University, Shinshu University, Toyama University, Fukui University, Kanazawa Medical University, Ishikawa Prefectural Nursing University, located in Nagano, Toyama, Ishikawa and Fukui prefectures( Hokushin region), conducts educational program to train professionals for management of cancer patients. We have launched 10 graduate student courses and 11 medical staff courses, and are accepting students who exceed our expectation. We give lectures using e-learning system and hold multidisciplinary seminars that utilize the Web conference system. As an overseas staff training, participants learned cancer genomic medicine and cancer palliative care at medical facilities in 3 countries. The regional cancer database project that utilizes cancer registration data from 22 principal hospitals to clarify the characteristics of cancer patients with disabilities, pleural mesothelioma, pleural adenocarcinoma, and pediatric/ adolescents and young adults(AYA)generation cancer patients in Hokushin region. In addition, public lectures were held to provide cancer information to the citizens in Hokushin region.

Childcare Center Evacuation to Vertical Shelters in a Nankai Trough Tsunami: Models to Predict and Mitigate Risk

Abstract: Following the Great East Japan Earthquake, vertical evacuation shelters (VES) were constructed to reduce tsunami risk. Childcare centers (CCs) in the inundation area are required to evacuate to the nearest VES in the event of a tsunami. The study aim was to identify CCs and VES predicted to be inundated by a Nankai Trough earthquake-generated tsunami, and to clarify CC inundation risk. We identified 52 (45.6%) CCs in the tsunami inundation area and found that 14 (25.9%) would evacuate toward the tsunami. If the walking speed was 2.24 km/h and a 0.3 m tsunami arrived in 10 min, nine (17.3%) CCs would be late to safe evacuation. If the tsunami arrival time was 20 min, four (7.7%) CCs would have late evacuation. At a walking speed of 1.00 km/h, 38 (73.1%) and 20 (38.5%) CCs would have late evacuation, with tsunami arrival times of 10 min and 20 min, respectively. Evacuation direction is important in avoiding tsunami damage. An evacuation strategy is needed that evacuates people away from the tsunami, and takes into account children’s age, walking speed, and evacuation method. The evaluation of tsunami risk in this study may support the development of tsunami countermeasures in other coastal areas with latent tsunami risks.

Families

Abstract: The distinct style of human communication develops gradually during a child’s life course. Researchers have reported that caregivers often try to involve young children in culturally and historically developed interaction patterns. Together with colleagues, I conducted a longitudinal study of Japanese caregiver (mainly parents and siblings) – child (0 to 5 years old) interactions naturally occurring at home, focusing on the developmental transition whereby children’s responses become behavioural patterns that meet caregivers’ expectations. The topics of study included managing attention in child pointing and the caregiver’s response, generating morality while caregivers issue directives (i.e. making their children do something), and caregivers’ strategies for eliciting storytelling from toddlers. Based on these findings, I argue that family interactions provide the foundation for children’s language socialization. Moreover, I explore possible ways that caregivers and nursery or preschool teachers can establish a link between family life and educational settings for children in their care. The recommended practices are summarized as (1) caregivers should communicate to teachers about their child’s recent behavioural accomplishments (e.g. pointing); (2) caregivers and teachers should share a list of directives they have used and the child’s responses to them, and so on.

Genomics of Tumor Origin and Characteristics for Adenocarcinoma and Malignant Pleural Mesothelioma: A Case Report

Abstract: A female underwent a right middle lobectomy for a pulmonary adenocarcinoma (AD). She eventually died of a right malignant pleural mesothelioma (MPM; sarcomatoid type) 4 years and 7 months after the removal of the AD even though she did not have any history of asbestos exposure, smoking, or radiation exposure. Her chest CT revealed multiple pulmonary nodules and bilateral pleural effusion with a right pleural tumor directly invading into the abdominal cavity. The genomics of tumor origin and characteristics were examined for the AD and the MPM. As a result, 50 somatic variants were detected in the AD, and 29 somatic variants were detected in the MPM. The variants which were common in both the AD and the MPM were not present, which suggested that the AD and the MPM had occurred independently in different origins. The MPM had two driver oncogenes of TP53 and EP300, but the AD did not. Two driver oncogenes of TP53 and EP300 were hypothesized to make the MPM aggressive. The speed at which the MPM progressed without the patient having a history of asbestos exposure, smoking, or radiation exposure was alarming.

Evaluation of a Japanese brief CBT-I administered by a nurse: a pilot study

Abstract: Abstract Aim: The aim of this pilot study is to evaluate a Japanese version of brief Cognitive Behavioral Therapy for Insomnia (CBT-I) and contribute to primary care which leads to prevention of a lifestyle-related disease or a psychiatric disorder. Method: A single-arm study in nine patients with chronic insomnia who were under the pharmacotherapy was executed. The Insomnia Severity Index (ISI), the Athens Insomnia Scale (AIS), and the European Quality of Life 5 Items (EQ-5D) were assessed at the beginning of intervention, at the end of intervention, and after 12 weeks. Findings: There were no patient dropouts nor adverse events. The average change in ISI score was −7.33 (95% CI: −10.31 to −4.36) at post-treatment and −6.11 (95% CI: −8.20 to −4.03) at the 12-week follow-up point (Cohen’s d = 2.25). The AIS score improved as well, and the EQ-5D score improved after 12 weeks. The safety and efficacy of the brief CBT-I were suggested.