The impact of geriatric nutritional risk index on one-year outcomes in hospitalized elderly patients with heart failure.

Background: Strategies that accurately predict outcomes in elderly heart failure (HF) patients have not been sufficiently established. In previous reports, nutritional status, ability to perform activities of daily living (ADL), and lower limb muscle strength are known prognostic factors associated with cardiac rehabilitation (CR). In the present study, we investigated which CR factors can accurately predict one-year outcomes in elderly patients with HF among the above factors. Methods: Hospitalized patients with HF over 65 years of age from January 2016 to January 2022 were retrospectively enrolled in the Yamaguchi Prefectural Grand Medical (YPGM) Center. They were consequently recruited to this single-center retrospective cohort study. Nutritional status, ADL, and lower limb muscle strength were assessed by geriatric nutritional risk index (GNRI), Barthel index (BI), and short physical performance battery (SPPB) at discharge, respectively. One year after discharge, the primary and secondary outcomes were evaluated by all-cause death or HF readmission and major adverse cardiac and cerebrovascular events (MACCE), respectively. Results: Overall, 1,078 HF patients were admitted to YPGM Center. Of those, 839 (median age 84.0, 52% female) met the study criteria. During the follow-up of 228.0 days, 72 patients reached all-cause death (8%), 215 experienced HF readmission (23%), and 267 reached MACCE (30%: 25 HF death, six cardiac death, and 13 strokes). A multivariate Cox proportional hazard regression analysis revealed that the GNRI predicted the primary outcome (Hazard ratio [HR]: 0.957; 95% confidence interval [CI]: 0.934-0.980; p < 0.001) and the secondary outcome (HR: 0.963; 95%CI: 0.940-0.986; p = 0.002). Furthermore, a multiple logistic regression model using the GNRI most accurately predicted the primary and secondary outcomes compared to those with the SPPB or BI models. Conclusion: A nutrition status model using GNRI provided a better predictive value than ADL ability or lower limb muscle strength. It should be recognized that HF patients with a low GNRI at discharge may have a poor prognosis at one year.

Practical Considerations for the Clinical Application of Bone Turnover Markers in Osteoporosis.

Bone turnover markers (BTMs) are released during the bone remodelling cycle and are measurable in blood or urine, reflecting bone remodelling rate. They have been useful in elucidating the pharmacodynamics and effectiveness of osteoporosis medication in clinical trials and are increasingly used in routine clinical management of osteoporosis, especially for monitoring therapy, in addition to their use in other metabolic bone disease such as Paget's disease of bone and osteomalacia. Serum ß isomerised C-terminal telopeptide of type I collagen and pro-collagen I N-terminal propeptide have been designated as reference BTMs for use in osteoporosis. In addition, bone-specific isoenzyme of alkaline phosphatase (B-ALP) secreted by osteoblasts and tartrate-resistant acid phosphatase 5b (TRACP-5b) secreted by osteoclasts are also found to be specific markers of bone formation and resorption, respectively. The concentrations of the latter enzymes in blood measured by immunoassay provide reliable measures of bone turnover even in the presence of renal failure. B-ALP is recommended for use in the assessment of renal bone disease of chronic kidney disease, and TRACP-5b shows promise as a marker of bone resorption in that condition. BTMs in blood do not suffer from biological variation to the same extent as the older BTMs that were measured in urine. Appropriate patient preparation and sample handling are important in obtaining accurate measures of BTMs for clinical use. Reference change values and treatment targets have been determined for the reference BTMs for their use in monitoring osteoporosis treatment. Further ongoing studies will enhance their clinical applications.

Corrigendum: Malnutrition and Frailty Are Critical Determinants of 6-Month Outcome in Hospitalized Elderly Patients With Heart Failure Harboring Surgically Untreated Functional Mitral Regurgitation.

[This corrects the article DOI: 10.3389/fcvm.2021.764528.].

Campylobacter lari Vertebral Osteomyelitis.

We report a case of Campylobacter lari vertebral osteomyelitis with iliopsoas abscess. This is the first case report of vertebral osteomyelitis due to C. lari, which was identified from a vertebral biopsy sample collected using CT-guided percutaneous needle biopsy in a patient without obvious episodes of immunodeficiency. Cultureing using the HK semisolid medium aided in pathogen ideutification. It is important to make every possible effort to identify the causative pathogen in vertebral osteomyelitis.

Malnutrition and Frailty Are Critical Determinants of 6-Month Outcome in Hospitalized Elderly Patients With Heart Failure Harboring Surgically Untreated Functional Mitral Regurgitation.

Background: Hospitalized patients with acute decompensated heart failure (ADHF) frequently exhibit aggravating mitral regurgitation (MR). Those patients do not always undergo surgical mitral valve repair, but particularly in the elderly, they are often treated by conservative medical therapy. This study was aimed to investigate factors affecting 6-month outcomes in hospitalized patients with heart failure (HF) harboring surgically untreated MR. Methods: We screened the presence of MR in hospitalized patients with HF between September 2017 and May 2020 in the Yamaguchi Prefectural Grand Medical (YPGM) center. At the time of discharge of these patients, individuals with surgically unoperated MR, including primary and secondary origin, were consequently recruited to this single-center prospective cohort study. The patients with severe MR who undergo surgical mitral valve treatment were not included in this study. The primary endpoint was all-cause readmission or all-cause death and the secondary endpoint was HF-related endpoint at 6 months after discharge. The Cox proportional hazard regression analyses were employed to assess the predictors for the composite endpoint. Results: Overall, 489 patients with ADHF were admitted to the YPGM center. Of those, 146 patients (30% of total patients with HF) (median age 83.5 years, 69 men) were identified as harboring grade II MR or greater. Consequently, all the recruited patients were diagnosed as functional MR. During a median follow-up of 186.0 days, a total of 55 patients (38%) reached the primary or secondary endpoints (HF death and readmission in 31 patients, other in 24 patients). As a result of multivariate analysis, geriatric nutritional risk index [hazard ratio (HR) = 0.932; 95% CI = 0.887-0.979, p = 0.005], age (HR = 1.058; 95% CI = 1.006-1.112, p = 0.027), and left ventricular ejection fraction (HR = 0.971; 95% CI = 0.945-0.997, p = 0.030) were independent predictors of all-cause death or all-cause admission. Body mass index (HR = 0.793; 95% CI = 0.614-0.890, p = 0.001) and ischemic heart disease etiology (HR = 2.732; 95% CI = 1.056-7.067, p = 0.038) were also independent predictors of the HF-related endpoints. Conclusion: Malnutrition and underweight were substantial predictors of adverse outcomes in elderly patients with HF harboring surgically untreated moderate-to-severe functional MR.

Executive summary of the Japan Osteoporosis Society Guide for the Use of Bone Turnover Markers in the Diagnosis and Treatment of Osteoporosis (2018 Edition).

With the aging of society, the number of osteoporosis-related fractures is increasing. Prevention of osteoporosis and maintenance of the quality of life of osteoporosis patients require early diagnosis, effective treatment, and highly precise treatment monitoring. Although bone biopsy is clinically one of the essential techniques for diagnosis of osteoporosis, it is invasive and difficult to perform in general clinical practice. Bone mineral density measurement is another essential technique available in clinical practice that provides good precision. However, it is not effective for determining the appropriate treatment options or evaluating short-term treatment efficacy. On the other hand, bone turnover markers (BTMs) have gained attention because they provide information that is valuable for both the selection of treatment and short-term monitoring. BTMs are now positioned to become a tool for clinically assessing bone turnover outcomes. Since the Japan Osteoporosis Society issued its Guidelines for the Use of Bone Turnover Markers in the Diagnosis and Treatment of Osteoporosis in 2012, new drugs, drug formulations, and combination drug therapies have been approved; therefore, we updated the 2012 guidelines in the Guide for the Use of Bone Turnover Markers in the Diagnosis and Treatment of Osteoporosis (2018 Edition).

[Significance of Bone Turnover Marker Measurement in the Treatment of Osteoporosis].

The bone turnover marker (BTM) measurement in osteoporosis treatment includes evaluation of bone metabolism status or evaluation of bone loss risk level, determination of fracture risk, and evaluation of drug treatment. Currently, by using the BTM, it has become possible to evaluate and select an effective treatment for osteoporosis. The BTM has become widely used as a clinical test item in actual clinical practice. Patients' low adherence to osteoporosis medication regimens increases the risk of vulnerable fractures and affects the cost effectiveness of therapeutics. A joint working group has been established, with International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) and International Osteoporosis Foundation (IOF) in a central role. The joint policy document of the joint working group is intended to increase the international application of BTM in clinical medicine, and to eliminate blood type I procollagen-N-propeptide (P1NP) and type I collagen cross-linked C-telopeptide (CTX) in observational research and intervention studies, in order to eliminate the inherent uncertainty of these measurements in clinical use. Current osteoporotic drug treatment has been proven to prevent bone fractures, but poor adherence to dosage regimens is an ongoing problem in clinical practice; various attempts have been made to improve adherence. Low adherence to an osteoporosis medication regimen increases the risk of fracture, and affects cost effectiveness. The BTM is an effective indicator in monitoring reactivity to osteoporosis drug therapy, and can be used to individually evaluate guidelines for treatment continuity and medication. In addition, providing BTM information to patients has reportedly improved their adherence to therapeutics, thereby potentially improving both the outcome and cost-effectiveness of osteoporosis drug therapy.

Surveillance evaluation of the standardization of assay values for serum total 25-hydroxyvitamin D concentration in Japan.

Background To assess the vitamin D nutritional status, serum total 25-hydroxyvitamin D (25(OH)D) concentration is measured. We used six automated 25(OH)D immunoassays (AIAs) available in Japan and certified by the Vitamin D Standardization Program (VDSP) at the U.S. Center for Disease Control and Prevention to assess the concordance of the assay results. Methods Serum total 25(OH)D concentrations in SRM 972a and 20 serum samples from patients were determined using three liquid chromatography-tandem mass spectrometry (LC-MS/MS) and six AIAs (pilot study), and an additional 110 serum samples were assessed by the six AIAs (surveillance study). The assay bias from the results of LC-MS/MS by Chiba University or consensus values (i.e. average of six AIAs) was estimated using the procedure described in CLSI document EP09-A3. Results LC-MS/MS at Chiba University could completely separate 25(OH)D2, 25(OH)D3 and 3-epi-25(OH)D3, and the observed values including total 25(OH)D in SRM 972a were all within ±1·SD of the assigned values. All AIAs produced results greater than ±3·SD. In the pilot study, four of the six AIAs had an average percentage bias, as estimated by confidence interval (CI), larger than ±5% (acceptance criterion in CLSI); the bias converged from -6.5% to 3.2% after adjustment by LC-MS/MS. In the surveillance study, 25(OH)D concentrations in AIAs all adjusted to LC-MS/MS converged within ±5% from consensus values. However, some AIAs showed negative or positive bias from the consensus values. Conclusions Current AIAs in Japan continue to lack standardization. Manufacturers should implement quality assurance strategies so that their values more closely align to those of standard reference material 972a.

Ratio of Endogenous Secretory Receptor for Advanced Glycation End Products to Pentosidine Predicts Fractures in Men.

Context: Although the endogenous secretory receptor for advanced glycation end products (esRAGE) has been associated with reduced activity of pentosidine (PEN), the association between PEN, esRAGE, and fracture is poorly understood. Objectives: To evaluate the ability of serum PEN and esRAGE levels to predict fragility fractures. Methods: A cohort of 1285 Japanese men aged ≥65 years old participated in a 2007 to 2008 Fujiwara-kyo Osteoporosis Risk in Men study baseline survey, as part of the Fujiwara-kyo prospective cohort study. Those participants provided information regarding any fractures they experienced during 5 years. The baseline bone mineral density (BMD) was measured. Hazard ratios (HRs) per one standard deviation increase of log-transformed serum levels of PEN, esRAGE, and esRAGE-to-PEN ratio were estimated at baseline. Results: Twenty-five participating men suffered incident clinical fragility fractures. The crude HRs (95% confidence interval) for PEN, esRAGE, and esRAGE-to-PEN ratio were 1.56 (1.05 to 2.31), 0.79 (0.54 to 1.15), and 0.65 (0.44 to 0.95), respectively. HRs for PEN adjusted for age, esRAGE, and T score of BMD at femoral neck (FN) and lumbar spine (LS) were 1.48 (1.00 to 2.18) and 1.51 (1.03 to 2.21), respectively. The marginal significance adjusted for BMD at FN and the statistical significance adjusted for BMD at LS were attenuated after additional adjustment for glycated hemoglobin A1c level (P = 0.111 and 0.072, respectively). The HRs for esRAGE-to-PEN ratio adjusted for age, glycated hemoglobin A1c, and T-score of BMD at FN and LS were 0.67 (0.45 to 0.98) and 0.64 (0.43 to 0.95). Conclusions: Higher esRAGE-to-PEN ratios were associated with decreased risk of fragility fractures independent of BMD among elderly Japanese men.

[New methods for the evaluation of bone quality. Bone Quality Marker.]

In recent years, undercarboxylated osteocalcin(ucOC), advanced glycation endproducts(AGEs)and homocysteine are attracting attention as factors defining bone strength. However, there are still many problems in its measurement, and it has not yet been routinely used in clinical practice. If solving the problem in the future, it is expected that the utility on bone quality will also increase.

[Bone turnover marker].

Recently the clinical application of bone turnover markers (BTMs) have been achieved significant progress and the measurements of these indices give us better understanding of pathogenesis of osteoporosis. BTMs are known the bone formation marker, the bone resorption marker and the bone matrix-related marker, respectively. In the Guidelines for the Use of Bone Metabolic Markers in the Diagnosis and Treatment of Osteoporosis (2012 Edition) from publishing Japan Osteoporosis Society Committee, the newly and commonly BTMs were considered to give the normal reference value in Japanese people, the influence of renal function on BTMs. The flow chart of the measurement of bone resorption markers and bone formation markers when selecting drug treatment for osteoporosis, the evaluation of therapeutic effects of bone antiresorption drugs and/or bone formation promoting drug using bone resorption markers and/or bone formation marker were corrected newly in the guideline 2012 edition. Moreover, BTMs were suggested to contribute to adhere with osteoporosis treatment. BTMs are adapted to selection of the drug for osteoporosis and to evaluate the drug efficacy. Therefore, it is very important to guide the proper application and assessment of BTMs in clinical practice.

[Clinical usefulness of bone turnover markers with the treatment of osteoporosis].

Bone turnover markers (BTMs) are known the bone formation marker, the bone resorption marker and the bone matrix related marker participating in bone quality, respectively. In the Guidelines for the Use of Bone Metabolic Markers in the Diagnosis and Treatment of Osteoporosis (2012 Edition) from publishing Japan Osteoporosis Society Committee, the newly and commonly BTMs were considered to give the normal reference value in Japanese people, the reevaluation of MSC, and the influence of renal function on BTMs, respectively. The flow chart of the measurement of bone resorption markers and bone formation markers when selecting drug treatment for osteoporosis, the measurement of ucOC and bone resorption markers when selecting drug treatment in osteoporosis, and the evaluation of therapeutic effects of bone antiresorption drugs using bone resorption markers were corrected newly in the guideline 2012 edition. It is thought that the BTMs have been continued more developing as essential biomarker with the treatment of osteoporosis in the future.

[Evaluation of bone for using of bone metabolic markers in the diagnosis and treatment of osteoporosis].

Quantification of BMD is being used as the main method to diagnose osteoporosis and measurement accuracy has dramatically improved. However, essential clinical parameters of osteoporosis include more dynamic markers such as bone metabolic markers. Bone metabolism undergoes daily dynamic changes, and even with the same BMD, the metabolic state differs and the pathologic significance also differs. Therefore, to use BMD measurement as a dynamic marker, one must wait for an observation period of 6 months to 1 year before remeasurement, whereas bone metabolic markers accurately reflect the state of bone metabolism at the point in time of the measurement. Bone metabolic markers can also be used as a guide to selecting pharmacotherapy. When there is doubt about choosing a drug, the use of bone metabolic markers can enable more appropriate selection. Furthermore, to evaluate the effects of drug therapy on disease improvement, assessing the state of bone metabolism at the time of diagnosis is recommended whenever possible. However, if a decision is made to select treatment with little influence on bone metabolism, then measuring bone metabolic markers to monitor drug treatment effects has little clinical significance. Recently the clinical application of bone metabolic markers have been achieved significant progress and the measurements of these indices give us better understanding of pathological of osteoporosis. Therefore, it is very important to guide the proper application and assessment of bone metabolic markers in clinical practice.

Guidelines for the use of bone metabolic markers in the diagnosis and treatment of osteoporosis (2012 edition).

Recently the clinical application of bone metabolic markers has achieved significant progress and the measurements of these indices give us a better understanding of the pathogenesis of osteoporosis. Bone metabolic markers were adapted to select drug treatment for osteoporosis and to evaluate drug efficacy. Therefore, the proper application and assessment of bone metabolic markers in clinical practice is very important. To achieve these aims, the committee on the guidelines for the use of biochemical markers of bone turnover in osteoporosis authorized by the Japan Osteoporosis Society has summarized recent progress in bone markers and proposed the proper utilization of bone markers. Although the use of bone metabolic markers now has an important role in the daily management of osteoporosis, their use in Japan is still insufficient because of insurance coverage limitations. Since the Japan Osteoporosis Society first created the 2001 guidelines, new bone metabolic markers have been introduced into clinical practice. The availability of new osteoporosis treatments that promote bone formation has changed the clinical application of bone metabolic markers in current practice. Therefore, revisions to the current clinical practice are needed which led to the proposal to create these new 2012 guidelines.

Commutability of National Institute of Standards and Technology standard reference material 1955 homocysteine and folate in frozen human serum for total folate with automated assays.

BACKGROUND: The aim of the present study was to evaluate standard reference material (SRM) 1955 commutability as a reference material for serum folate using automated methods. We also designed so as to reduce the intermethod variability present in different automated methods. METHODS: Using a microbiological assay related to the 'information value' of SRM 1955 as a comparison method, we investigated the possibility of standardization for the assay values of serum folate as measured by the automated methods (Access, Centaur and Elecsys). In the assay of 50 patient sera by these automated methods, we corrected observed values by the SRM 1955 and compared with comparison values. RESULTS: The observed values of SRM 1955 Levels I, II and III were within or outside (but near) a 95% prediction interval obtained from patient sera by the automated methods. The normalized residuals obtained from SRM 1955 were within ±3.0 (in SD units), which enabled us to conclude that the SRM 1955 had a physicochemical characterization similar to native serum. Twelve patients were assessed as hypofolataemia (<6.0 ng/mL) and 38 patients as normal (≥6.0 ng/mL). Before correction, folate levels in six of 12 patients were lower than 6.0 ng/mL, and those in seven of 38 patients were higher than 6.0 ng/mL with the automated methods. After correction, low levels were found in four of 12 patients, and normal levels were found in 33 of 38 patients. CONCLUSIONS: The use of SRM 1955 would help to reduce the intermethod variability present in different automated methods for serum folate measurement.

The performance of Cochlin-tomoprotein detection test in the diagnosis of perilymphatic fistula.

BACKGROUND: Perilymphatic fistula (PLF), defined as an abnormal communication between the inner and middle ear, presents with a symptomatology of hearing loss and vestibular disorder that is indistinguishable from a number of other inner ear diseases. Methods of diagnosis remain controversial. We have previously shown that Cochlin-tomoprotein (CTP) is selectively detected in the perilymph. To establish a definite diagnostic test for PLF using CTP as a biochemical marker, we examined the diagnostic performance of the CTP detection test. METHODS: CTP detection test was performed by Western blot using recombinant human CTP (rhCTP) as a spiked standard. We evaluated the specificity of the CTP detection test by testing non-PLF cases. To describe the limitations of the test, we tested samples from patients with middle ear infection. We also studied the stability of CTP protein by storing the samples at room temperature (25 degrees C) or 4 degrees C for 55 days. The effects of repeated freezing and thawing were also evaluated. Serially diluted perilymph was tested to find out the detection limit of CTP. FINDINGS: We have established a standardized CTP detection test using high (0.27 ng) and low (0.13 ng) spiked standards of rhCTP in Western blotting. Middle ear lavages (MEL) from 54 of 55 non-PLF cases were negative in the CTP detection test, i.e. the specificity of the test is 98.2%. MEL from 43 out of 46 cases with chronic suppurative otitis media or middle ear cholesteatoma were negative for CTP. CTP is a stable protein and detection was not affected by the storage, or freezing and thawing. The detection limit of perilymph was 0.161 microl/lane in an average of 5 samples. INTERPRETATION: CTP is a stable perilymph-specific protein, and this CTP detection could be the first clinically established diagnostic tool to detect PLF with a high specificity. PLF is surgically correctable by sealing the fistula. Appropriate recognition and treatment of PLF can improve hearing and balance in afflicted patients.

[Biochemical markers of bone turnover. New aspect. An automated assay for measuring bone turnover markers].

Recently, the measurement of biochemical bone turnover markers by automated immunoassay analyzer system was performed for the routine clinical laboratory tests in patients with osteoporosis and other metabolic bone diseases. Measurement of serum and/or urine bone turnover markers has been reported to be easy assay, rapid measurement and highly precision for routine tests using the automated immunoassay analyzer system. These measurements may be enabled as cheap routine tests in the future for all medical institution if automated measurement of the bone turnover marker spreading for medical examination and treatment. In conclusion, it indicates that the measurement of automated immunoassay analyzer system may be applicable for routine measurement and provide a useful tool to bone turnover markers.

Cochlin-tomoprotein: a novel perilymph-specific protein and a potential marker for the diagnosis of perilymphatic fistula.

BACKGROUND: Perilymphatic fistula (PLF) is an abnormal connection between the inner and middle ear. A procedure for obtaining definite proof of a PLF remains elusive, and methods of diagnosis remain controversial. To date, there is no clinically relevant biochemical marker for perilymph leakage. Using proteomic analysis of inner ear proteins, we have previously found unique properties of cochlin, encoded by the COCH gene. We detected 3 cochlin isoforms (p63s, p44s and p40s) in the inner ear tissue and a short 16-kDa isoform of cochlin-tomoprotein (CTP) in the perilymph. Since cochlin was found to be highly specific to the inner ear, we speculated that CTP might also be specific to the perilymph. The aim of this study was to determine whether CTP, a novel perilymph-specific protein, could be used as a marker for the diagnosis of PLF. METHODS: By Western blotting, we investigated the specificity of CTP expression in a range of body fluids that included perilymph, serum, saliva and cerebrospinal fluid. To elucidate the detection limit of CTP, serially diluted recombinant human (rh)CTP as well as human perilymph was tested. RESULTS: CTP was selectively expressed in all 20 perilymph samples tested, but not in 77 samples of the other body fluids. The detection limit of rhCTP was 0.27 ng or 0.022 microl of perilymph per well on Western blot analysis. CONCLUSION: The results strongly suggest that CTP can be a specific marker of perilymph leakage. Moreover, CTP has the potential to be a biochemical marker that allows a definitive diagnosis of the etiology of PLF-related hearing loss and vestibular disorders.

Change in serum undercarboxylated osteocalcin concentration in bilaterally oophorectomized women.

OBJECTIVE: We investigated changes in serum undercarboxylated osteocalcin (ucOC) concentrations, bone turnover markers and spine bone mineral density (BMD) in women who had undergone bilateral oophorectomy during the premenopausal period. METHODS: The study population comprised 141 bilaterally oophorectomized and 32 premenopausal women for a cross-sectional study. The longitudinal study consisted of 21 bilaterally oophorectomized women. Serum ucOC concentration, serum concentrations of intact osteocalcin (OC) and bone-specific alkaline phosphatase (BAP) as bone formation markers, urine N-telopeptide (NTx) concentration as a bone resorption marker and serum parathyroid hormone (PTH) concentration were measured. RESULTS: Serum concentration of ucOC in women at 1 month after bilateral oophorectomy was significantly (p<0.05) higher than that in premenopausal women and the high level was sustained after surgical menopause. On the other hand, serum OC concentration at 1 month after surgical menopause was not different from that in premenopausal women. In the longitudinal study, serum ucOC concentration at 1 month after surgical menopause was significantly (p<0.05) increased compared to that before bilateral oophorectomy, while serum OC concentrations before and at 1 month after surgical menopause were not significantly different. CONCLUSION: The results of this study showed that serum ucOC concentration rapidly increases in women after bilateral oophorectomy and that change in serum ucOC concentration after surgical menopause is different from change in serum OC concentration.