The storage and access of genetic testing results have unique considerations for medical records. Initially, genetic testing was limited to patients with single gene diseases. Genetic medicine and ...testing have expanded, as have concerns about appropriately handling genetic information. In this study, we surveyed the management of genetic information in general hospitals in Japan using a questionnaire on access restrictions. Our questions included whether any other medical information was managed in a unique way. We identified 1037 hospitals designated for clinical training located throughout Japan and received responses from 258 hospitals, and 191 reported that they handle genetic information and results of genetic tests. Of the 191 hospitals that handle genetic information, 112 hospitals implement access restrictions to genetic information. Seventy-one hospitals, one of which uses paper medical records rather than electrical medical records, do not enforce access restrictions. For eight hospitals, it was not known whether access restrictions were enforced or not. The responses from these hospitals indicated that access restrictions and storage methods varied across institution type (e.g., general vs. university hospitals), institution size, and the presence of a clinical genetics department. Other information, such as infectious disease diagnosis, psychological counseling records, abuse, and criminal history, was also subject to access restriction in 42 hospitals. The disparity in how medical facilities handle sensitive genetic information demonstrates a need for discussion between medical professionals and the general public on the storage of sensitive records, including genetic information.
Cancers are genetically categorized into common diseases showing a so‐called multifactorial inheritance except for rare familial cancers. And as a measure to estimate the strength of genetic factors ...in the multifactorial diseases, heritability (h2) is generally used. However, there have been few reports on the estimation of heritability for cancers. We calculated the heritability from the incidence in subject population and the familial recurrence rate in first‐degree relatives of the affected for cancers quoting the data from a large‐scale prospective cohort study by Hidaka et al. published in 2020. This is the first report for heritability of any cancers in Japanese population. The results showed that heritability of overall cancers in Japanese population is 0.064, which is much lower than Nordic population reported by Mucci et al. that was 0.33. For individual cancers, stomach cancer (h2 = 0.14), colorectum cancer (0.006), lung cancer (0.08) and uterine cancer (0.16) accounted for half of the total patients, and each heritability tends to be lower than previously reported for the European descent. The results of this study suggest that heritability of cancers varies greatly by ethnicity. And these results should be important in terms of cancer genetics and in the genetic counseling for cancers.
Incidence of cancer in Japan has been increasing rapidly in recent years. Cancers are genetically categorized into the multifactorial diseases, and as a measure to estimate the strength of genetic factors in multifactorial diseases, heritability is used. We calculated heritability of various cancers in Japan using the liability threshold model.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
In this study, three fluoroquinolones, pazufloxacin, ciprofloxacin and levofloxacin, were simultaneously determined in spiked human serum by high-performance liquid chromatography (HPLC) method with ...fluorescence detection. Chromatography was performed using a C
8 column with an isocratic mobile phase consisting of 1% triethylamine (pH 3.0)/acetonitrile (86/14, v/v). Protein precipitation was conducted using perchloric acid and methanol. The calibration curves for the three fluoroquinolones were linear over concentrations ranging from 0.1 to 20.0
μg/mL. The within-day and between-day coefficients of variation obtained from three fluoroquinolones were less than 7%, and relative errors ranged from −1.6% to 9.3%. Mean recoveries of pazufloxacin, ciprofloxacin, and levofloxacin from spiked human serum were 97%, 88%, and 90%, respectively. The proposed method proved to be simple and reliable for the determination of three fluoroquinolones.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Hospital ethics committees (HECs) are expected to play extremely broad and pivotal roles such as case consultation, education of staffs on healthcare ethics, and institutional policy formation. ...Despite the growing importance of HECs, there are no standards for setup and operation of HECs, and composition and activities of HECs at each institution are rarely disclosed in Japan. In addition, there is also a lack of information sharing and collaboration among HECs. Therefore, the authors established the Consortium of Hospital Ethics Committees (CHEC) in October 2020, which has been regularly hosting a couple of core activities. One is the Healthcare Ethics Forum, held monthly online for CHEC members to freely discuss HECs and healthcare ethics consultation. The other is the Collaboration Conference of Hospital Ethics Committees, intended to provide a place for HEC members and administrative officers from across Japan to exchange information of their HECs, learn from each other, and cooperate to operate HECs appropriately. In this paper, the authors introduced CHEC as well as reported the results of a questionnaire survey conducted at the first conference among participating facilities, suggesting the diverse structures and activities of HECs in Japan.
The usefulness of comprehensive genomic profiling (CGP) in the Japanese healthcare insurance system remains underexplored. Therefore, this large-scale study aimed to determine the usefulness of CGP ...in diagnosing digestive cancers. Patients with various cancer types recruited between March 2020 and October 2022 underwent the FoundationOne
CDx assay at the Keio PleSSision Group (19 hospitals in Japan). A scoring system was developed to identify potentially actionable genomic alterations of biological significance and actionable genomic alterations. The detection rates for potentially actionable genomic alterations, actionable genomic alterations, and alterations equivalent to companion diagnosis (CDx), as well as the signaling pathways associated with these alterations in each digestive cancer, were analyzed. Among the 1587 patients, 547 had digestive cancer. The detection rates of potentially actionable genomic alterations, actionable genomic alterations, and alterations equivalent to CDx were 99.5%, 62.5%, and 11.5%, respectively.
,
, and
alterations were frequently observed in colorectal, pancreatic, and biliary cancers, respectively. Most digestive cancers, except esophageal cancer, were adenocarcinomas. Thus, the classification flowchart for digestive adenocarcinomas proposed in this study may facilitate precise diagnosis. CGP has clinical and diagnostic utility in digestive cancers.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Accumulating evidence has demonstrated that both SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP1Ra) have protective effects in patients with diabetic kidney disease. Combination therapy ...with SGLT2i and GLP1Ra is commonly used in patients with type 2 diabetes (T2D). We previously reported that in combination therapy of SGLT2i and GLP1Ra, the effect on the renal composite outcome did not differ according to the preceding drug. However, it remains unclear how the initiation of combination therapy is associated with the renal function depending on the preceding drug. In this
analysis, we analyzed a total of 643 T2D patients (GLP1Ra-preceding group,
= 331; SGLT2i-preceding group,
= 312) and investigated the differences in annual eGFR decline. Multiple imputation and propensity score matching were performed to compare the annual eGFR decline. The reduction in annual eGFR decline in the SGLT2i-preceding group (pre: -3.5 ± 9.4 mL/min/1.73 m
/year, post: -0.4 ± 6.3 mL/min/1.73 m
/year,
< 0.001), was significantly smaller after the initiation of GLP1Ra, whereas the GLP1Ra-preceding group tended to slow the eGFR decline but not to a statistically significant extent (pre: -2.0 ± 10.9 mL/min/1.73 m
/year, post: -1.8 ± 5.4 mL/min/1.73 m
/year,
= 0.83) after the initiation of SGLT2i. After the addition of GLP1Ra to SGLT2i-treated patients, slower annual eGFR decline was observed. Our data raise the possibility that the renal benefits-especially annual eGFR decline-of combination therapy with SGLT2i and GLP1Ra may be affected by the preceding drug.
Three-dimensional cultured clumps of a mesenchymal stem cell (MSC)/extracellular matrix (ECM) complex (C-MSC) consists of cells and self-produced ECM. C-MSC can regulate the cellular function in ...vitro and induce successful bone regeneration using ECM as a cell scaffold. Potentiating the immunomodulatory capacity of C-MSCs, which can ameliorate the allo-specific immune response, may be helpful in developing beneficial "off-the-shelf" cell therapy for tissue regeneration. It is well reported that interferon (IFN)-γ stimulates the immunosuppressive properties of MSC via upregulation of the immunomodulatory enzyme IDO. Therefore, the aim of this study was to investigate the effect of IFN-γ on the immunomodulatory capacity of C-MSC in vitro and to test the bone regenerative activity of C-MSC or IFN-γ-pretreated C-MSC (C-MSCγ) xenografts in a mice calvarial defect model.
Human bone marrow-derived MSCs were seeded at a density of 2.0 × 10
cells/well into 24-well plates and cultured with growth medium supplemented with 50 μg/mL L-ascorbic acid for 4 days. To obtain C-MSC, confluent cells that had formed on the cellular sheet were scratched using a micropipette tip and were then torn off. The cellular sheet was rolled to make a round clump of cells. C-MSC was stimulated with IFN-γ and IDO expression, immunosuppressive capacity, and immunophenotype were evaluated in vitro. Moreover, C-MSC or C-MSCγ was xenotransplanted into immunocompetent or immunodeficient mice calvarial defect models without artificial scaffold, respectively.
IFN-γ stimulated IDO expression in C-MSC. C-MSCγ, but not C-MSC, attenuated CD3/CD28-induced T cell proliferation and its suppressive effect was reversed by an IDO inhibitor. C-MSCγ showed upregulation of HLA-DR expression, but its co-stimulatory molecule, CD86, was not detected. Xenotransplantation of C-MSCγ into immunocompetent mice calvarial defect induced bone regeneration, whereas C-MSC xenograft failed and induced T cell infiltration in the grafted area. On the other hand, both C-MSC and C-MSCγ xenotransplantation into immunodeficient mice caused bone regeneration.
Xenotransplantation of C-MSCγ, which exerts immunomodulatory properties via the upregulation of IDO activity in vitro, may attenuate xenoreactive host immune response, and thereby induce bone regeneration in mice. Accordingly, C-MSCγ may constitute a promising novel allograft cell therapy for bone regeneration.
Full text
Available for:
IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
1,5-Anhydro-d-glucitol (1,5-AG) is fairly widespread in food products. It is also one of the major polyols in the human body, and its concentration is homeostatically regulated. We report here on the ...beneficial effects of 1,5-AG in preventing hyperglycemia and its role in improving metabolic syndrome. The findings revealed that it does not affect blood glucose levels itself under normal conditions but clearly has a suppressive effect on the levels of dietary sugars, such as glucose, maltose, and sucrose. A long-term administration study revealed that feeding db/db diabetic mice 3% 1,5-AG for 8 weeks significantly decreased blood glucose levels compared to untreated mice (339 ± 30 versus 438 ± 34 mg/dL; p < 0.05). Furthermore, this treatment also significantly suppressed serum cholesterol levels (110.2 ± 18.0 versus 168.4 ± 9.8 mg/dL; p < 0.01). 1,5-AG did not inhibit intestinal α-glucosidase activities but regulated liver glucose levels via affecting both the glycogenolysis and gluconeogenesis pathways. Furthermore, the oral administration of 1,5-AG significantly increased urinary glucose excretion in hyperglycemic conditions. These results clearly suggest that dietary 1,5-AG acts as a modulator of glucose levels in hyperglycemia. 1,5-AG therefore represents a new class of promising functional sweeteners, where the daily consumption of 1,5-AG with meals could inhibit the progress of hyperglycemia and metabolic syndrome.
Full text
Available for:
IJS, KILJ, NUK, PNG, UL, UM, UPUK
Highlights • Increase in GMCs of serotype-specific IgG levels in PCV7 group. • Increase in GMTs of OIs of serotype-specific IgG levels in PCV7 group. • Our study confirmed the safety of both PCV7 and ...PPV23 vaccines in elderly people. • PCV7 displayed superior immunogenicity than PPV23 in 4/7 serotypes included in PCV7.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background: The objective of this study was to find an optimal initial combination chemotherapy that includes clarithromycin (CAM) for
treatment-naive patients with Mycobacterium avium complex (MAC) ...pulmonary disease, as assessed by microbiological conversion using a Mycobacterium growth indicator tube (MGIT).
Methods: Thirty-four patients with treatment-naive MAC pulmonary disease (determined using 1997 American Thoracic Society criteria)
were evaluated retrospectively. They demonstrated a nodular and bronchiectatic pattern without cavity on high-resolution CT
(HRCT) scans. The following three regimens were administered: regimen A (n = 9) consisted of CAM (400 mg/d), ethambutol (EB)
750 mg/d, and rifampicin (RFP) 450 mg/d; regimen B (n = 12) consisted of CAM (800 mg/d), EB (750 mg/d), and RFP (450 mg/d);
and regimen C (n = 13) consisted of CAM (800 mg/d), EB (1,000 mg/d), and RFP (600 mg/d) during the first 2 months followed
by a reduction of the dosage of EB from 1,000 to 750 mg/d. Gender, age, BMI, and HRCT scan finding scores were not significantly
different among the three groups. Chemotherapy was continued for 18 months. Sputum culture was periodically assessed by MGIT.
Results: Culture conversion at 18 months in regimen A (55.6%), which included a daily dosage of 400 mg of CAM (9.5 mg/kg), was significantly
inferior to that in regimen B (91.7%), which included daily 800 mg of CAM (17.6 mg/kg; p < 0.05), but regimen B and C (92.3%)
showed no between-group difference after > 18 months of chemotherapy.
Conclusions: The higher dose of CAM allowed for better culture conversion. Daily combination chemotherapy that includes CAM (800 mg) seems
appropriate as an initial treatment against treatment-naive patients with nodular and bronchiectatic MAC pulmonary disease.
PDF
