The impact of low and high dialysate calcium concentrations on cardiovascular disease and death in patients undergoing maintenance hemodialysis: a systematic review and meta-analysis.

BACKGROUND: The optimal dialysate calcium (Ca) concentration for patients undergoing hemodialysis remains inconclusive, particularly concerning cardiovascular protection. METHODS: We conducted a systematic review of 19 randomized controlled trials (RCTs) and a meta-analysis of eight RCTs to determine the optimal dialysate Ca concentration for cardiovascular protection. We compared outcomes in patients receiving maintenance hemodialysis treated with either a low-Ca dialysate (LCD) (1.125 or 1.25 mmol/L) or a high-Ca dialysate (HCD) (1.5 or 1.75 mmol/L). The outcomes were coronary artery calcification score (CACS), all-cause and cardiovascular death, cardiovascular function and structure, and serum biochemical parameters. RESULTS: There was no significant difference between LCD and HCD concerning CACS (standardized mean difference [SMD] = -0.16, 95% confidence interval [CI]: [-0.38, 0.07]), the risk of all-cause death, and cardiovascular death in patients treated with chronic maintenance hemodialysis. Conversely, LCD was associated with a significantly lower intima-media thickness (SMD = -0.49, 95% CI [-0.94, -0.05]) and pulse wave velocity than HCD (SMD = -0.86, 95% CI [-1.21, -0.51]). Furthermore, LCD significantly decreased serum Ca levels (mean difference [MD] = 0.52 mg/dL, 95% CI [0.19, 0.85]) and increased serum parathyroid hormone levels (MD = 44.8 pg/mL, 95% CI [16.2, 73.3]) compared with HCD. Notably, most RCTs examined in our analysis did not include patients receiving calcimimetics. CONCLUSIONS: Our meta-analysis showed no significant differences in cardiovascular calcification and death between LCD and HCD and revealed a paucity of RCTs on dialysate Ca concentrations, including those involving patients on calcimimetics, indicating the urgent need for further studies.

Transportation price, product differentiation, and R&D in an oligopoly.

In this article, we construct an international oligopoly that explicitly incorporates transporter behavior. In each country, there is one firm that produces differentiated goods and invests in product-differentiating R&D and one transporter that transports the differentiated goods. We adopt a three-stage game in which the firms decide their R&D investment level to determine the degree of horizontal differentiation, the transporters determine the transportation prices through Cournot competition, and then the firms determine the quantities of production. We find that an increase in R&D efficiency in the product differentiation of firms leads to a decrease in transportation prices. We also reveal that an increase in the efficiency of product differentiation always reduces the profits of firms. These results explain the empirically plausible long-term trend of declining transportation prices and also provide a counterintuitive implication that efficiency gains reduce the degree of product differentiation.

Posterior Oblique Square Decompression with a Three-Step Wanding Technique in Tubular Minimally Invasive Transforaminal Lumbar Interbody Fusion: Technical Report and Mid-Long-Term Clinical Outcomes.

Although minimally invasive transforaminal lumbar interbody fusion (MIS-TLIF) is the most common procedure in minimally invasive spine stabilization (MISt), details of the technique remain unclear. This technical report shows the mid-long-term clinical outcomes in patients who underwent posterior oblique square decompression (POSDe) with the three-step wanding technique of tubular MIS-TLIF for degenerative lumbar disease. Tubular MIS-TLIF (POSDe) was performed on 50 patients (males, 19; age, 69.2 ± 9.6 years), and traditional open surgery was performed (OS) on 27 (males, 4; age, 67.9 ± 6.6 years). We evaluated the clinical outcomes using the Visual Analog Scale for back pain, Japanese Orthopedic Association (JOA) scores, and JOA Back Pain Evaluation Questionnaire. We also assessed the fusion rate using the Bridwell grading system with computed tomography or plain radiography for at least 2 years postoperatively. Although there was no significant difference in the improvement rate of JOA scores between the two groups, the mean operation time and blood loss were significantly lower with MIS-TLIF than with OS. In the tubular MIS-TLIF group, there were no cases of deep wound infection; four cases had a pseudarthrosis, two had dural injury, and three had cage retropulsion. We revealed good clinical outcomes in patients who underwent POSDe.

Association Between Osteochondritis Dissecans of the Humeral Capitellum and Medial Epicondyle Lesion in Baseball Players.

BACKGROUND: Osteochondritis dissecans (OCD) of the humeral capitellum occurs in adolescent overhead athletes, and medial epicondyle (ME) lesions are also common in this population. PURPOSE: To evaluate the association between elbow OCD and ME lesions in adolescent baseball players. STUDY DESIGN: Cross-sectional study; Level of evidence, 3. METHODS: This study retrospectively evaluated adolescent baseball players with unstable elbow OCD who underwent surgery between January 2000 and February 2020. Patients were excluded if they had osteoarthritis of the elbow. A total of 139 elbows were included in this study (138 male and 1 female athlete; mean ± SD age, 13.6 ± 1.5 years). The patients were first divided into 2 groups based on OCD location: a central lesion group (72 elbows) and a lateral group (67 elbows). Next, patients were divided according to OCD size into a localized group (56 elbows) and a widespread group (83 elbows). Finally, OCD lesions that were both lateral and widespread were defined as lateral-widespread (60 elbows), resulting in 5 groups. ME apophyseal fragmentation and elongation were evaluated and defined as ME lesions. We then compared the relationship between OCD and ME lesions. RESULTS: Of the 139 elbows, 63 (45.3%) had ME lesions. The prevalence of ME lesion was higher in the lateral group than the central group (56.7% vs 34.7%; P = .009) and higher in the widespread group than the localized group (55.4% vs 30.4%; P = .004). Furthermore, the prevalence ratio of ME lesion was significantly higher in the lateral-widespread group than for other lesions (58.3% vs 35.4%; P = .007). CONCLUSION: In patients undergoing surgery for capitellar OCD, the presence of ME lesions was more commonly associated with lateral and widespread capitellar lesions when compared with central and localized lesions.

Ulnar collateral ligament dysfunction increases stress on the humeral capitellum: a finite element analysis.

BACKGROUND: Repetitive mechanical stress on the elbow joint during throwing is a cause of ulnar collateral ligament dysfunction that may increase the compressive force on the humeral capitellum. This study aimed to examine the effects of ulnar collateral ligament material properties on the humeral capitellum under valgus stress using the finite element method. METHODS: Computed tomography data of the dominant elbow of five healthy adults were used to create finite element models. The elbows were kept at 90° of flexion with the forearm in the neutral position, and the ulnar collateral ligament was reproduced using truss elements. The proximal humeral shaft was restrained, and valgus torque of 40 N·m was applied to the forearm. The ulnar collateral ligament condition was changed to simulate ulnar collateral ligament dysfunction. Ulnar collateral ligament stiffness values were changed to 72.3 N/mm, 63.3 N/mm, 54.2 N/mm, 45.2 N/mm, and 36.1 N/mm to simulate ulnar collateral ligament laxity. The ulnar collateral ligament toe region width was changed in increments of 0.5 mm from 0.0 to 2.5 mm to simulate ulnar collateral ligament loosening. We assessed the maximum equivalent stress and stress distribution on the humeral capitellum under these conditions. RESULTS: As ulnar collateral ligament stiffness decreased, the maximum equivalent stress on the humeral capitellum gradually increased under elbow valgus stress (P < .001). Regarding the change in the ulnar collateral ligament toe region width, as the toe region elongated, the maximum equivalent stress of the humeral capitellum increased significantly under elbow valgus stress (P < .001). On the capitellum, the equivalent stress on the most lateral part was significantly higher than that on other parts (P < .01 for all). CONCLUSION: Under elbow valgus stress with elbow flexion of 90° and the forearm in the neutral position, ulnar collateral ligament dysfunction increased equivalent stress on the humeral capitellum during the finite element analysis. The highest equivalent stress was noted on the lateral part of the capitellum.

Prevalence of cervical canal stenosis in farmers: Epidemiological study based on radiographic parameter of spinal cord injury patients.

BACKGROUND: Farming is one of the effective community activities for preventing the need for new long-term care insurance services. This study was conducted to compare spinal canal diameters between patients injured during orchard work (i.e., cultivating apples) and other situations that lead to cervical spinal cord injury without major fracture or dislocation and to investigate the frequency of cervical spinal canal stenosis among farmers in a Japanese community. METHODS: Subjects were 23 patients with cervical spinal cord injury without major fracture and dislocation. Charts and radiographs of these patients were retrospectively reviewed to evaluate the characteristics of the spinal cord injury. The spinal canal diameter at the injury level in the mid-sagittal plane of magnetic resonance imaging (MRI) and mechanism of injury were compared between patients injured by orchard work and other situations. Moreover, 358 Japanese general residents were evaluated for the prevalence of cervical canal stenosis using MRI and comparisons were made between farmers group and non-farmers group. RESULTS: Spinal canal diameters at the injury level were 5.8 ± 1.4 mm in patients injured during orchard work and 5.6 ± 1.0 mm in those injured in other situations; there were no differences between the two groups. Head contusion as mechanism of injury was more frequent in the orchard work group than in other situations group. Among farmers, the rate of spinal canal stenosis increased with age, and it was 62.3% in men and 66.2% in women. CONCLUSIONS: The frequency of cervical spinal canal stenosis was high with age regardless of farming work. In addition, head contusion might be a characteristic mechanism that causes spinal cord injury during orchard work. Therefore, screening of cervical degenerative conditions among farmers and education for prevention of cervical spinal cord injury during farming work are necessary.

A study of the factors associated with cervical spinal disc degeneration, with a focus on bone metabolism and amino acids, in the Japanese population: a cross sectional study.

BACKGROUND: The physical and biochemical factors responsible for cervical disc degeneration, and resulting in various spinal disorders, remain unclear. This study aimed to evaluate the correlation between cervical spinal canal stenosis and degeneration of intervertebral discs, and to analyze the factors related to disc degeneration in the Japanese population. METHODS: Three hundred and forty-four Japanese general residents underwent investigations, including magnetic resonance imaging of the cervical spine, in our health check project. We measured anteroposterior diameters at the levels of the cervical spinal disc in mid sagittal plane magnetic resonance imaging and evaluated disc degeneration. Spearman correlation coefficient was used to evaluate whether the diameters were correlated with disc degenerative scores. Stepwise multiple linear regression analysis was conducted with the score of disc degeneration as the dependent variable; and age, physical measurement values, bone mineral density of the forearm, and the value of serum bone metabolic markers and amino acids as the independent variables for each sex. RESULTS: As the age increased, the anteroposterior diameters decreased in both sexes. The minimum anteroposterior diameters were correlated with the disc degenerative scores (Spearman r = - 0.59, p < 0.001 in men, Spearman r = - 0.53, p < 0.001 in women). In multiple linear regression analysis, age, cross-linked N-telopeptide of type 1 collagen and isoleucine were significantly correlated with the cervical disc degenerative score in men (R2 = 0.47), and age and lysine were significantly correlated with the degenerative score in women (R2 = 0.50). CONCLUSION: The factors responsible for cervical disc degeneration differed between men and women. Whether modifying these significant factors is possible, or whether this intervention would contribute to prevention of disc degeneration requires future studies.

The Association between Glomerular Filtration Rate Estimated Using Different Equations and Mortality in the Japanese Community-Based Population: The Yamagata (Takahata) Study.

BACKGROUND: To evaluate renal function, the indices of estimated glomerular filtration rate (eGFR) obtained using several equations, including the Japanese versions of the serum creatinine-based MDRD equation (eGFRcreat), Chronic Kidney Disease Epidemiology Collaboration equation (eGFR-EPI), and serum cystatin C-based equation (eGFRcys), are utilized. This study prospectively examined the association between these eGFR values and all-cause mortality during a 12-year observational period in a community-based population. METHODS AND RESULTS: The subjects of this study were 1312 participants undergoing a health checkup, aged ≥40 years. In the total population, the mean eGFR values (mL·min-1·1.73 m-2) were 81.5 for eGFRcreat, 78.1 for eGFR-EPI, and 76.6 for eGFRcys. There were 141 deaths during the observation period, and the area under the receiver operating characteristic curve for predicting mortality was 0.59 for eGFRcreat, 0.67 for eGFR-EPI, and 0.70 for eGFRcys (all P < 0.01). In the Cox proportional analysis adjusted for age and sex, eGFRcys, but not eGFRcreat and eGFR-EPI, showed a significant association with all-cause mortality (per 15 mL·min-1·1.73 m-2 decrease: hazard ratio 1.40, 95% confidence interval 1.18-1.67). CONCLUSIONS: This study revealed that eGFRcys showed lower values than eGFRcreat and eGFR-EPI and was significantly associated with all-cause mortality in the Japanese community-based population.

The Association between Serum Uric Acid and Renal Damage: The Takahata Study - New Insights.

BACKGROUND: Hyperuricemia is a risk factor for causing end-stage kidney disease and cardiovascular disease in the general population; however, several aspects, such as the site of kidney damaged by hyperuricemia and the threshold levels of serum uric acid for the development of renal damage, have not been fully clarified. SUMMARY: To examine these aspects, we analyzed data from the Takahata study, a community-based cohort study involving participants of an annual health check-up, and used urinary albumin creatinine ratio (UACR) and urinary ß2-microglobulin creatinine ratio (UBCR) in spot urine as indices of glomerular and tubular damage respectively. In cross-sectional analysis, increased serum uric acid levels were accompanied by higher UACR values and lower UBCR values. Multivariate analysis revealed that albuminuria (UACR ≥30 mg/g), but not elevated UBCR, was independently associated with increased uric acid (≥7 mg/dL for males, ≥6 mg/dL for females). In longitudinal analysis, uric acid at baseline was an independent factor for a 1-year increase in the UACR. Cox-proportional hazard model analysis with adjustment for possible confounders including age, renal function, and comorbidities revealed that hyperuricemia was an independent risk factor for all-cause and cardiovascular mortality in females. Key Messages: Our results revealed that elevated uric acid is an independent risk factor for glomerular damage, but not tubular damage, and that the risk for renal damage and mortality might be increased at the high-normal range of uric acid in the community-based population.

Associations between serum uric acid levels and the incidence of nonfatal stroke: a nationwide community-based cohort study.

BACKGROUND: Hyperuricemia is an established risk factor for cardiovascular events and mortality. This study investigated the association between serum uric acid and the incidence of nonfatal stroke in a Japanese community-based population. METHODS: We used a nationwide database of 155,322 subjects (aged 40-73, male 39 %) who participated in the annual "Specific Health Check and Guidance in Japan" checkup from 2008 to 2010. We examined the relationship between the quintiles of serum uric acid levels at baseline and the incidence of nonfatal stroke during a 2-year study period using self-reported data. RESULTS: The crude incidence of nonfatal stroke was significantly associated with serum uric acid levels at baseline, showing the lowest values in subjects with the 3rd quintile (Q3: men, 5.0-5.6; women, 3.8-4.3) of uric acid levels (mg/dL) and the highest values in subjects with the highest quintile (Q5: men ≥7.1, women ≥5.5) both in men and women (P < 0.05). In multivariate-adjusted logistic regression analysis, the odds ratio (OR) of the Q5 group was significantly higher than for the Q3 group in both men and women [men: OR 1.26, 95 % confidence interval (CI) 1.04-1.54, women: OR 1.24, 95 % CI 1.00-1.48]. In the subgroup analysis, the OR of the Q5 group of uric acid levels for incident stroke was high, irrespective of characteristics such as age, sex, and renal function. CONCLUSIONS: This study has shown that serum uric acid is independently associated with the incidence of nonfatal stroke in the general Japanese population.

Serum uric acid levels and mortality in the Japanese population: the Yamagata (Takahata) study.

BACKGROUND: Serum uric acid level is regulated by gender, dietary habit, genetic predisposition, and renal function, and is associated with the development of renal and cardiovascular diseases. This study prospectively investigated the association between serum uric acid levels and mortality in a community-based population. METHODS: Three thousand four hundred and eighty-seven subjects regardless of the antihyperuricemic medication (45 % male; mean age 62 years old) from the Takahata town in Japan participated in this study and were followed up for 8 years (median 7.5 years). We examined the association between serum uric acid levels at baseline and the all-cause and cardiovascular mortality, respectively, in this population. RESULTS: One hundred seventy-nine subjects died during the follow-up period, with 49 deaths attributed to cardiovascular causes. Kaplan-Meier analysis revealed that the all-cause mortality was significantly higher along with the increase in serum uric acid levels at baseline among female (Log-rank P < 0.01), but not male subjects (P = 0.97). Cox-proportional hazard model analysis with adjustment for possible confounders including age, renal function, and comorbidities revealed that hyperuricemia (uric acid ≥7.0 mg/dL) was an independent risk factor for all-cause and cardiovascular mortality, respectively, in female [hazard ratio (HR) 5.92, 95 % confidence interval (CI) 2.10-14.6 for all-cause mortality, and HR 10.7, 95 % CI 1.76-50.2 for cardiovascular mortality], but not male subjects. CONCLUSION: Hyperuricemia was an independent risk for all-cause and cardiovascular mortality in female, but not among the male subjects in a community-based population.

Blood Pressure, Proteinuria, and Renal Function Decline: Associations in a Large Community-Based Population.

BACKGROUND: Hypertension and proteinuria are risk factors for adverse renal outcomes in patients with chronic kidney disease. This study investigated the associations of blood pressure and proteinuria on renal function in a community-based population. METHODS: We analyzed data from a nationwide database of 141,514 subjects who participated in the annual "Specific Health Check and Guidance in Japan" checkup in 2008 and 2010. The study subjects were aged between 29 and 74 years, and the cohort comprised 40% men. We examined relationships between blood pressure levels, proteinuria at baseline, and the 2-year change in the estimated glomerular filtration rate (eGFR), which was determined using the Japanese equation. RESULTS: After adjusting for possible confounders, the change in the eGFR was inversely correlated with systolic blood pressure (SBP), but not diastolic blood pressure (DBP), at baseline, irrespective of the presence of proteinuria. Compared with the lowest SBP sixtile (≤118mm Hg), eGFRs declined significantly at SBPs ≥ 134mm Hg in subjects with proteinuria, while eGFRs declined significantly at SBPs ≥ 141mm Hg in those without proteinuria. At the same SBPs, renal function decline was faster and the risk for incident renal insufficiency was higher in subjects with proteinuria compared with those without proteinuria. CONCLUSIONS: This study showed that a difference in SBP, but not DBP, is independently associated with a rapid eGFR decline in the general Japanese population, and that the association of SBP on the decline of renal function was greater in subjects with proteinuria compared with those without proteinuria.

A slight increase within the normal range of serum uric acid and the decline in renal function: associations in a community-based population.

BACKGROUND: Hyperuricemia is a risk factor for adverse renal outcomes in patients with chronic kidney disease. This study investigated the effect of uric acid on renal function in a community-based population. METHODS: We used a nationwide database of 165 847 subjects (aged 29-74, male 40%) who participated in the annual 'Specific Health Check and Guidance in Japan' checkup between 2008 and 2010; we examined the relationship between serum uric acid levels at baseline and 2-year change in the estimated glomerular filtration rate (eGFR) obtained by using the Japanese equation. RESULTS: After adjusting for possible confounders, the eGFR change was inversely correlated with uric acid at baseline. In the multivariable analysis, the decline in eGFR was significantly more rapid in subjects with the slight increase in uric acid (males ≥5.7 mg/dL, females ≥4.4 mg/dL), and the risk for incidental renal insufficiency (eGFR <60 mL/min/1.73 m(2)) was increased at uric acid of ≥6.3 mg/dL in males and ≥5.5 mg/dL in females, compared with the lowest quintile. The multiple linear regression analysis revealed that the effect of uric acid on eGFR changes was significant, especially in females, those with proteinuria and diabetes and those without alcohol consumption. CONCLUSION: This study showed that serum uric acid is independently associated with a more rapid decline of eGFR and incident renal insufficiency, and that a slight increase within the normal range of serum uric acid might be a risk for renal damage in the general population.

A microarray analysis of urinary microRNAs in renal diseases.

BACKGROUND: MicroRNAs (miRNAs), a family of endogenous small non-coding RNAs, are associated with the development of renal diseases. To clarify whether urinary miRNAs (UmiRNAs) can be used for the evaluation of renal disease, we examined the profiles of UmiRNAs in various renal diseases. METHODS: We extracted miRNAs from urine specimens of 5 healthy controls and 71 patients with renal diseases, and we examined the correlation between clinical and histological parameters and the profile of UmiRNAs by microarray analysis. RESULTS: The urinary concentration of miRNAs increased in patients with renal disease compared with healthy controls, and the levels correlated with urinary protein and the degree of glomerular sclerosis. The microarray analysis detected 83-137 distinct UmiRNAs. We observed 80-99 % of the miRNAs in both the healthy controls and the renal disease patients. The majority of UmiRNAs displayed higher signal intensity in renal disease patients than in healthy controls, including 39 miRNAs exhibiting signal intensities 100 times greater than in healthy controls. A different pattern of UmiRNAs was observed in each type of renal disease. A comparison of renal tissue and UmiRNAs revealed that the sample profiles were similar and that their signal intensity was significantly correlated. CONCLUSION: This study demonstrated that UmiRNAs are correlated with renal pathological changes and that the profile of UmiRNAs presented different patterns corresponding to the type of renal disease. These results suggest that UmiRNAs can potentially be used as novel biomarkers for renal diseases.