Clinical utility of geriatric assessment tools in older patients with gastrointestinal cancer.

Background: Geriatric 8 (G8) and instrumental activities of daily living (IADL) are recommended to predict overall survival (OS) or risk of serious adverse events (SAEs) in older cancer patients. However, the clinical utility is relatively unknown in older patients suffering malnutrition with gastrointestinal (GI) cancer, including gastric cancer (GC) and pancreatic cancer (PC). Materials and methods: We retrospectively included patients aged ≥65 years with GC, PC, and colorectal cancer (CRC) who received a G8 questionnaire at first visit from April 2018 to March 2020. The associations between G8/IADL and safety or OS were assessed in patients with advanced/unresectable tumors. Results: Of 207 patients (median age: 75 years), the median G8 score was 10.5 and normal G8 score rate was 6.8%. Both the median G8 score and normal G8 (>14) score rate numerically increased in the order of GC < PC < CRC. There was no clear association between the G8 standard cutoff value of 14 and SAEs or OS. However, OS was significantly longer in patients with G8 >11 than in those with G8 ≤11 (19.3 vs. 10.5 months, p = 0.0017). Furthermore, OS was significantly better in patients with normal IADL than in those with abnormal IADL (17.6 vs. 11.4 months, p = 0.049). Conclusion: The G8 cutoff value of 14 would not be clinically useful in patients with GI cancer for predicting OS or SAEs; however, the cutoff value of 11 and IADL may be useful to predict OS for older patients with GI cancers including GC and PC.

Regulation of the high-specificity Rubisco genes by the third CbbR-type regulator in a hydrogen-oxidizing bacterium Hydrogenovibriomarinus.

The obligate chemolithoautotrophic bacterium, Hydrogenovibrio marinus MH-110, has three ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) isoenzymes, CbbM, CbbLS-1, and CbbLS-2, which differ in CO2/O2 specificity factor values. Expressions of CbbM and CbbLS-1 are regulated differently by transcriptional regulators of the LysR family, CbbRm and CbbR1, respectively. CbbLS-2 has the highest specificity and is induced under low CO2 conditions, but the regulator for the cbbL2S2 genes encoding CbbLS-2 remains unidentified. In this study, the cbbR2 gene encoding the third CbbR-type regulator was identified in the downstream region of the cbbL2S2 and carboxysome gene cluster via transposon mutagenesis. CO2 depletion induced the cbbR2 gene. The cbbR2 knockout mutant could not grow under low CO2 conditions and did not produce CbbLS-2. Recombinant CbbR2 protein was bound to the promoter region of the cbbL2S2 genes. These results indicate that CbbR2 is the specific regulator for CbbLS-2 expression.

Prospective assessment of plate-haptic rotationally asymmetric multifocal toric intraocular lens with near addition of + 1.5 diopters.

BACKGROUND: To prospectively evaluate surgical results following implantation of rotationally asymmetric, plate-haptic, refractive segmented multifocal toric intraocular lenses (IOLs) with near addition of + 1.5 diopters (D) (Lentis Comfort LS-313 MF15T, Oculentis GmbH). METHODS: In 59 eyes of 41 patients, ocular examinations were conducted before and 1 day, 1 week, 1, 3, and 6 months after surgery. Uncorrected (UDVA) and corrected (CDVA) distance visual acuity, uncorrected (UIVA) and distance-corrected (DCIVA) intermediate visual acuity at 70 cm, and uncorrected (UNVA) and distance-corrected (DCNVA) near visual acuity at 30 cm were tested. A defocus curve was drawn, and the degree of disturbing photic phenomena were questioned. RESULTS: The IOL showed excellent rotational stability; the average absolute rotation was 1.66 ± 1.17 degrees from 1 day 1 to 6 months postoperatively, and 98.1 and 100% of eyes yielded rotation of less than 5 and 10 degrees, respectively. Postoperative distance and intermediate visual acuity were highly satisfactory; UDVA, CDVA, UIVA, and DCIVA were about 20/20, 20/16, 20/25, 20/25, respectively. Near visual acuity was suboptimal; UNVA and DCNVA were at approximately 20/60. The defocus curve analysis showed that 20/25 and 20/40 uncorrected visual acuity was attained at as close as 60 and 40 cm, respectively. Contrast sensitivity was within a normal range, and subjective photic phenomena were minimum. CONCLUSIONS: The refractive segmented, rotationally asymmetric multifocal toric IOLs with + 1.5 D near addition showed superb rotational stability and highly satisfactory distance and intermediate vision. Contrast sensitivity was high and incidence of photic symptoms was very low. TRIAL REGISTRATION: This study was registered at JAPIC Clinical Trials Information, ID: JapicCTI-183,877, https://www.clinicaltrials.jp/cti-user/trial/Search.jsp (February 5, 2018).

Future development of artificial organs related with cutting edge emerging technology and their regulatory assessment: PMDA's perspective.

Future development of innovative artificial organs is closely related with cutting edge emerging technology. These technologies include brain machine or computer interface, organs made by three dimensional bioprinting, organs designed from induced-pluripotent stem cell for personalized tissue or organ, and xenotransplantation. To bridge the gap between scientific innovation and regulatory product review, Pharmaceuticals and Medical Devices Agency of Japan (PMDA) started the science board to discuss about the new scientific topics regarding medical products including medical device and regenerative products with external experts since 2012. Topics which PMDA raised for science board included cellular and tissue-based products from iPS cells, artificial intelligence and genome editing technology. In addition, PMDA started the horizon scanning to identify a new cutting edge technology which could potentially lead to innovative health technology or product, which has a strong impact on clinical medicine. Although the effectiveness and safety of the medical products must be reasonably assured before clinical use, PMDA introduced Sakigake review assignment (a review partner of device development) and conditional approval system to balance between pre-market and post-market evaluation.

Assessment of Gait Symmetry in Elderly Women with Low Bone Mineral Density Using a Portable Trunk Accelerometer: A Pilot Study.

BACKGROUND Convincing evidence regarding gait and balance function in elderly women with low bone mineral density (BMD) and/or osteoporosis is limited. In the present study, we aimed to compare the gait characteristics in elderly women with and without low BMD and to analyze plausible parameter(s) for predicting low BMD. MATERIAL AND METHODS We retrospectively analyzed prospectively collected data of 26 consecutive postmenopausal women aged >65 years who were admitted to our geriatric outpatient service. They were assigned to 2 groups, with (n=14) and without (n=12) low BMD based on T-score (0.05). Receiver operating characteristic curve analysis demonstrated that LI can predict low BMD in the femur neck with moderate accuracy (area under the curve=0.75, 95% confidence interval 0.55-0.95; P=0.031). The optimal cut-off value was 17%, with 67% specificity and 86% sensitivity. CONCLUSIONS These results suggest that elderly women with low BMD may walk with asymmetrical trunk movement, but they are able to generate gait patterns similar to healthy peers. The LI may provide valuable quantitative information for preventing fractures in subjects with osteoporosis.

Development of the Dementia Assessment Sheet for Community-based Integrated Care System 8-items, a short version of the Dementia Assessment Sheet for Community-based Integrated Care System 21-items, for the assessment of cognitive and daily functions.

AIM: The present study aimed to: (i) examine the reliability and validity of the Dementia Assessment Sheet for Community-based Integrated Care System 21-items for classifying patients to the appropriate categories for glycemic targets in older patients; and (ii) develop a short version of the tool and examine its reliability and validity. METHODS: A total of 410 older individuals were recruited for this multicenter cross-sectional study. We classified them into three categories used for determining the glycemic target in older patients in Japan based on cognitive functions and activities of daily living. Exploratory factor analyses were used to select the eight items of the shorter version. The reliability and validity of the assessment tools were assessed using Cronbach's alpha coefficients and receiver operating characteristic analyses, respectively. RESULTS: The Dementia Assessment Sheet for Community-based Integrated Care System 21-items had three latent factors: cognitive function, instrumental activities of daily living and basic activities of daily living. The Dementia Assessment Sheet for Community-based Integrated Care System 8-items was developed based on each factor load quantity and was confirmed to have a strong correlation with the original version (r = 0.965, P < 0.001). Both tools significantly discriminated older adults belonging to category I from those belonging to category II or III, and category III from category I or II. CONCLUSIONS: Both tools had sufficient internal consistency and validity to classify older patients into the categories for determining the glycemic target in this population based on cognitive and daily functions. Geriatr Gerontol Int 2018; 18: 1458-1462.

Function of three RuBisCO enzymes under different CO2 conditions in Hydrogenovibrio marinus.

The obligate chemolithoautotrophic bacterium, Hydrogenovibrio marinus MH-110 has three ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) isoenzymes, designated CbbLS-1, CbbLS-2, and CbbM, which are encoded by the cbbL1S1, cbbL2S2, and cbbM genes, respectively. Functions of these isoenzymes at different CO2 concentrations were investigated using deletion mutants of their genes. Deletion of cbbL1 had no effect on cell growth under any of the test growth conditions. The cbbL2 mutant was unable to grow under lower (≤0.15%) CO2 conditions, though it grew normally under higher (≥2%) CO2 conditions. Growth of the cbbM mutant was retarded under higher CO2 conditions but was not affected by lower CO2 conditions. These results indicate that CbbLS-2 and CbbM specifically function under lower and higher CO2 conditions, respectively. The growth retardation of the cbbL2 and cbbM mutants was not restored by complementation with plasmids carrying the cbbL2S2 and cbbM genes, respectively. The cbbL2S2 and cbbM genes are followed by the carboxysome genes and the cbbQmOm genes, respectively. Co-expression of these downstream genes was probably necessary for the in vivo function of CbbLS-2 and CbbM. CbbLS-1 was upregulated in the cbbL2 and cbbM mutants under the lower and higher CO2 conditions, respectively, indicating that the expression of cbbL1S1 was controlled to compensate the deficiency of the other RuBisCO isoenzymes.

Longitudinal Assessment of Tau Pathology in Patients with Alzheimer's Disease Using [18F]THK-5117 Positron Emission Tomography.

The formation of neurofibrillary tangles is believed to contribute to the neurodegeneration observed in Alzheimer's disease (AD). Postmortem studies have shown strong associations between the neurofibrillary pathology and both neuronal loss and the severity of cognitive impairment. However, the temporal changes in the neurofibrillary pathology and its association with the progression of the disease are not well understood. Tau positron emission tomography (PET) imaging is expected to be useful for the longitudinal assessment of neurofibrillary pathology in the living brain. Here, we performed a longitudinal PET study using the tau-selective PET tracer [18F]THK-5117 in patients with AD and in healthy control subjects. Annual changes in [18F]THK-5117 binding were significantly elevated in the middle and inferior temporal gyri and in the fusiform gyrus of patients with AD. Compared to patients with mild AD, patients with moderate AD showed greater changes in the tau load that were more widely distributed across the cortical regions. Furthermore, a significant correlation was observed between the annual changes in cognitive decline and regional [18F]THK-5117 binding. These results suggest that the cognitive decline observed in patients with AD is attributable to the progression of neurofibrillary pathology. Longitudinal assessment of tau pathology will contribute to the assessment of disease progression and treatment efficacy.

Impact of blunted perception of dyspnea on medical care use and expenditure, and mortality in elderly people.

Dyspnea is an alarming symptom responsible for millions of patient visits each year. Poor perception of dyspnea might be reasonably attributed to an inappropriately low level of fear and inadequate earlier medical treatment for both patients and physicians, resulting in subsequent intensive care. This study was conducted to evaluate medical care use and cost, and mortality according to the perception of dyspnea in community-dwelling elderly people. We analyzed baseline data from a community-based Comprehensive Geriatric Assessment in 2002. The perception of dyspnea in 479 Japanese community-dwelling elderly people with normal lung function was measured in August 2002. The sensation of dyspnea during breathing with a linear inspiratory resistance of 10, 20, and 30 cmH(2)O/L/s was rated using the Borg scale. According to the perception of dyspnea, we divided the elderly into tertiles and compared all hospitalizations, out-patient visits, costs, and death through computerized linkage with National Health Insurance beneficiaries claims history files between August 2002 and March 2008. In-patient hospitalization days and medical care costs significantly increased with the blunted perception of dyspnea, resulting in an increase in total medical-costs with blunted perception of dyspnea. With low perception group as reference, the hazard ratios of all-cause mortality were 0.65 (95% CI 0.23-1.89) for intermediate perception group and 0.31 (0.10-0.97) for high perception group, indicating the mortality rate also significantly increased with the blunted perception of dyspnea after multivariates adjustment (p = 0.04). The blunted perception of dyspnea is related to hospitalization, large medical costs, and all-cause mortality in community-dwelling elderly people. These findings provide a rational for preventing serious illness with careful monitoring of objective conditions in the elderly.

C-reactive protein (CRP) is a predictor of high medical-care expenditures in a community-based elderly population aged 70 years and over: the Tsurugaya project.

Because CRP is a strong independent predictor of various diseases, it was hypothesized that CRP may be a useful predictor or treatment target for medical-care expenditures. The aim of this study was to investigate the relationship between CRP and medical-care expenditures in a community-dwelling elderly population. This prospective cohort study was conducted including 925 Japanese subjects aged ≥70 years. A high-sensitivity CRP assay was used by applying the nephelometric method. Hospitalizations, outpatient visits, and expenditures were ascertained through computerized linkage with claims lodged between August 2002 and March 2008 with the Miyagi National Health Insurance (NHI) Association. Since medical-care expenditures were not normally distributed, the category of high medical-care expenditures (>75th percentile of medical-care expenditures: inpatient expenditures >$494/month; outpatient expenditure >$522/month; total expenditures >$1103/month) was used to examine the relation of CRP levels with medical-care expenditures. Multiple logistic regression analysis was used to examine the relationship between CRP cutoff points (low concentrations: <1.0mg/L; intermediate concentrations: 1.0-3.0mg/L; or high concentrations: ≥3.0 mg/L) and medical-care expenditures during 6 year-follow up period. After adjustment for potential confounding factors, a positive association of CRP with hospitalization, and total expenditures (p for trend=0.03 and 0.02, respectively) was found. An elevated baseline CRP level is an independent predictor of increases in prospective medical-care expenditures among community-dwelling elderly. Further study is required to clarify whether reducing CRP by intervention is a cost-effective measure.

Impact of physical activity and performance on medical care costs among the Japanese elderly.

AIM: Physical activity (PA) is known to be inversely associated with medical care costs. The amount of PA is strongly associated with the level of physical performance among the elderly population. Therefore, it is possible that known relation between PA and medical care merely shows the relation between physical performance and medical care. To know whether PA itself relates to medical care, considering physical performance is necessary. The aim of this study was to ascertain the impact of PA on medical care expenditure by considering the physical performance in an elderly community-dwelling population. METHODS: We investigated 483 subjects who did not have any history of diseases relating to limited PA and who completed both a self-administered questionnaire including questions on PA and underwent a physical performance measurement. We ascertained the total medical care costs through a computerized linkage with claims lodged between August 2002 and March 2008 with the Miyagi National Health Insurance Association. RESULTS: The physical performance was positively associated with their level of PA. After multivariate adjustment for covariables including the levels of physical performance, the per capita medical care costs were found to be $US 827.3 (598.0-1056.7) (mean, 95% confidence interval), $US 711.1 (476.4-945.8) and $US 702.0 (461.6-942.4) (P for linear trend = 0.02) per month for those who had the lowest, average and the highest level of PA, respectively. CONCLUSION: This prospective study indicates that a higher level of PA is associated with lower medical care costs among the Japanese elderly irrespective of physical performance.

Serum lysophospholipase D/autotaxin may be a new nutritional assessment marker: study on prostate cancer patients.

BACKGROUND: It is now established that the bioactive lipid lysophosphatidic acid (LPA) contributes to cancer initiation, progression and metastasis, including those of prostate cancer. LPA is produced in the serum and plasma mainly by conversion from lysophospholipids through the action of lysophospholipase D (lysoPLD), which is identical to the soluble form of autotaxin (ATX) originally isolated as a tumour cell motility-stimulating factor. In this study, we evaluated the usefulness of lysoPLD/ATX activity as a diagnostic marker. METHODS: The serum lysoPLD activity, assessed by measuring choline liberation from the substrate lysophosphatidylcholine, was measured in patients with prostate cancer and compared with the concentrations of prostate-specific antigen (PSA) and conventional nutritional assessment markers. RESULTS: The serum lysoPLD activity in prostate cancer patients was not statistically different from that in the controls. Consistent with this, there was no correlation between the serum lysoPLD activity and the serum PSA concentrations. However, the lysoPLD/ATX activity did decrease after operation in the prostate cancer patients and seemed to reflect the postoperative damage or the nutritional status. CONCLUSIONS: We postulate that while the serum lysoPLD/ATX may not be a marker of prostate cancer, it promises to instead be a new marker of nutritional status.

The role of two CbbRs in the transcriptional regulation of three ribulose-1,5-bisphosphate carboxylase/oxygenase genes in Hydrogenovibrio marinus strain MH-110.

Hydrogenovibrio marinus MH-110 possesses three different sets of genes for ribulose 1,5-bisphosphate carboxylase/oxygenase (RubisCO): two form I (cbbLS-1 and cbbLS-2) and one form II (cbbM). We have previously shown that the expression of these RubisCO genes is dependent on the ambient CO2 concentration. LysR-type transcriptional regulators, designated CbbR1 and CbbRm, are encoded upstream of the cbbLS-1 and cbbM genes, respectively. In this study, we revealed by gel shift assay that CbbR1 and CbbRm bind with higher affinity to the promoter regions of cbbLS-1 and cbbM, respectively, and with lower affinity to the other RubisCO gene promoters. The expression patterns of the three RubisCOs in the cbbR1 and the cbbRm gene mutants showed that CbbR1 and CbbRm were required to activate the expression of cbbLS-1 and cbbM, respectively, and that neither CbbR1 nor CbbRm was required for the expression of cbbLS-2. The expression of cbbLS-1 was significantly enhanced under high-CO2 conditions in the cbbRm mutant, in which the expression of cbbM was decreased. Although cbbLS-2 was not expressed under high-CO2 conditions in the wild-type strain or the single cbbR mutants, the expression of cbbLS-2 was observed in the cbbR1 cbbRm double mutant, in which the expression of both cbbLS-1 and cbbM was decreased. These results indicate that there is an interactive regulation among the three RubisCO genes.

Factors associated with suicidal ideation in an elderly urban Japanese population: a community-based, cross-sectional study.

The objective of the present study was to evaluate the association between suicidal ideation and potentially related factors in an elderly urban Japanese population. This was a community-based, cross-sectional study. Urban community residents aged 70 years or more were interviewed regarding suicidal ideation and sociodemographic and health-related variables. Subjects with depressive symptoms underwent further evaluation by psychiatrists using criteria of the Diagnostic and Statistical Manual of Mental Disorders, 4th edition. Associations were evaluated using univariate and multivariate logistic regression analyses. Of the 1145 eligible participants, 52 (4.5%) reported thoughts of suicide. Of 143 subjects with depressive symptoms (Geriatric Depression Scale, 14+), 22 (15.4%) reported suicidal ideation over a 2-week period. After controlling for depressive symptoms, lack of social support and impaired instrumental activities of daily living were significantly associated with thoughts of suicide. After controlling for the potentially associated factors detected in the univariate analysis, depressive symptoms were strongly associated with thoughts of suicide. In the elderly with depressive symptoms, mental disorders, including depressive and alcohol-related disorders, were significantly associated with suicidal ideation over a 2-week period. In the urban community setting, screening for lack of social support, impaired instrumental activities of daily living, and depressive symptoms, followed by diagnostic evaluation for mental disorders, particularly for depressive syndromes and alcohol-related disorders, may provide a practical and effective means of identifying elders at high risk of suicide.