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Background: Work-related musculoskeletal disorders (WRMSD) among sonographers is a major problem with a high prevalence rate of more than 80% in North America and United Kingdom. In Singapore, this is particularly relevant because statistics have showed WRMSD accounted for 60% of all confirmed occupational diseases cases. The ROBotic UltraSonography sysTem (ROBUST) was developed to overcome the WRMSD challenges sonographers faced in their daily clinical practice and, more importantly, increase their career longevity and productivity. Objectives: To evaluate the effectiveness of ROBUST in producing diagnostic images equivalent to conventional ultrasound (US) scans and to assess its clinical feasibility and receptiveness. Methods: A total of 50 adult patients from two tertiary hospitals underwent conventional abdominal US followed by ROBUST scans. Six sonographers performed the US scans using the standard protocol. Four expert readers, blinded to the scanning methods, graded the image quality of 2,218 images (1,317 conventional, 901 ROBUST). Surveys were distributed immediately after the scan to assess the patient’s and sonographers’ opinions on maneuverability, pain, and comfort. Results: Wilcoxon signed rank test showed no significant difference between conventional US and ROBUST for image quality (p = 0.317). Sixteen (16/50 = 32%) patients responded feeling slight to moderate pain when scanned by ROBUST (p = 0.251). All the sonographers felt that the imaging task using ROBUST was not physically strenuous. One sonographer felt that the ROBUST was easy to manipulate; two were neutral (p = 0.007), and three experienced difficulties manipulating the ROBUST. Conclusion: ROBUST can produce diagnostic images equivalent to conventional scans. It is feasible in clinical settings with good acceptance by sonographers and patients. Adoption of this innovation in clinical practice could potentially increase career longevity and productivity by alleviating pain and discomfort experienced by sonographers.

Rupture of a postirradiated internal carotid artery (ICA) pseudoaneurysm in patients with nasopharyngeal carcinoma (NPC) is a rare yet life-threatening emergency. In contrast to pseudoaneurysms found in patients with other head and neck malignancies, those identified in NPC patients have a propensity to occur in the petrous segment of the ICA, which pose a serious challenge to clinical physicians. Over the past few decades, endovascular treatment with covered stents has widely been adopted as the treatment of choice for patients at risk of brain ischemia after occluding the parent vessel of the pseudoaneurysm. Although recent series have demonstrated that immediate hemostasis can be achieved in most of the patients undergoing covered stent placement, a high incidence of delayed complications has been reported, including delayed cerebral ischemia, in-stent thrombosis, and septic thromboembolism.We present two NPC patients with a postirradiated pseudoaneurysm involving the petrous segment of the internal carotid artery. As direct parent vessel occlusion was infeasible, we established an emergency high-flow extracranial-intracranial (EC-IC) bypass followed by endovascular parent vessel occlusion. Both of the patients were followed-up for more than 24 months without neurological deficit or rebleeding. We suggest that EC-IC bypass with parent vessel occlusion should be considered as a practical and durable treatment option for patients with postirradiated ICA pseudoaneurysms who cannot tolerate direct carotid occlusion. Keywords: Pseudoaneurysm, Nasopharyngeal carcinoma, High-flow bypass

Multidrug resistance (MDR) cancer is one of the major issues in systemic chemotherapy. Development of MDR reversal agents from natural products has been considered as a potential and safe solution. The present study aimed at investigating whether cordycepin, a major constituent in dietary mushrooms, exhibited MDR reversal effect and the mechanisms of kinetic interactions were further explored. Treatment of cordycepin not only modulated the expression of human P-glycoprotein (P-gp), but inhibited P-gp function through stimulating P-gp ATPase activity in cells that stably expressed human P-gp (ABCB1/Flp-InTM-293) and in MDR cancer cells (KB-vin) without influencing cell viability. The molecular docking model demonstrated that cordycepin may interact with P-gp by hydrogen bonds at the nucleotide binding domain. Furthermore, cordycepin significantly re-sensitized MDR cancer cells (KB-vin, HepG2-vin and NCI-H460/MX20) to conventional chemotherapeutic agents, such as paclitaxel and mitoxantrone. These findings suggest a promising combination use of cordycepin with chemotherapeutic agents in cancer treatment.

Background/purpose: We studied the correlation between clinical covariates and blood loss under hypotensive anesthesia, in patients undergoing a bilateral vertical ramus osteotomy (BVRO). Materials and methods: BVROs were performed on 37 patients with mandibular prognathism. The preoperative and postoperative values of blood constituents were examined and analyzed. Correlations among blood loss, sex, age, operative time, and reduced values of blood constituents were statistically assessed. Results: The average operative time was 255.5 ± 42.56 minutes, and blood loss was 105.9 ± 66.83 mL. No patient required a blood transfusion in this study. There were no significant correlations between blood loss and related factors (sex, operative time, and reductions in blood constituents). Comparing sexes, blood loss and reductions in blood constituents exhibited non-significant differences. However, male patients had significantly larger values for presurgical and postsurgical blood constituents than female patients. Conclusion: In our study, blood loss was acceptable in patients who underwent a BVRO, and thus, no preoperative autologous blood donation was necessary.

Background/purpose: Improper assessment of the maxillary buccal vestibular space can contribute to the fabrication of maxillary dentures with inadequate buccal flange extensions. The purpose of this study was to determine whether a significant difference existed between the anatomic dimensions of the buccal vestibules and the corresponding buccal flanges of maxillary complete dentures in an edentulous population. Materials and methods: The anterior, middle, and posterior depth and width of the maxillary buccal vestibules in 100 randomly selected subjects were measured with a periodontal probe. Corresponding measurements of the buccal flanges of the subjects' existing dentures were recorded. The differences between buccal vestibule widths and depths and denture flange widths and lengths were statistically compared according to site. Results: The difference in the mean depth between the vestibules and the flanges in the posterior area (6.4 mm and 10.3 mm, respectively) was approximately 38% (P

Background/purpose: This study evaluated the fracture resistance of different metal substructure designs for implant-supported porcelain-fused-to-metal (PFM) crowns. Materials and methods: Eighteen PFM crowns were fabricated using different metal substructure designs and were conventionally cemented on an implant abutment analog. The crowns were divided according to the metal substructure design for manufacturing the metal framework into three groups of six specimens each: Group A had a minimum required thickness; Group B had a conventional design; and Group C had a wrinkled design. After applying a load of 200 N at a frequency of 2 Hz with 300,000 cycles of dynamic loading, all specimens were tested for fracture resistance using compression loading on the buccal functional cusp. Results: Among these three groups, Groups A and B, respectively, had the minimum and maximum fracture resistance strengths. Respective data for Groups A, B, and C were 111.13 ± 27.15 kg, 236.13 ± 39.21 kg, and 188.63 ± 12.10 kg. Statistically significant differences were observed among the three groups (P

Background/purpose: Although proper training of medical and dental interns is particularly important, there are no studies to date in Taiwan examining the quality of dental services provided to the public by interns. The purpose of study is to investigate the significant factors that influence the patient's satisfaction with the quality of dental treatment provided by Interns. Materials and methods: This study randomly selected patients from a dental department in a medical center located in southern Taiwan and used a structured questionnaire and response scales (Likert) to investigate the level of emphasis and satisfaction of patients with the dental treatment provided by interns in February to April 2004 (52 total valid questionnaires). Results: With regard to technical competence compared to that of dentists, we found statistically significant differences according to the type of treatment received, gender, marital status, educational level attained, and household income (P

Background/purpose: The objective of this study was to assess the relationship between the essential functional qualities of complete dentures and participants' oral health-related well-being among an elderly edentulous population. Materials and methods: Four hundred elderly participants from Taiwan, aged ≥ 65 years, with diverse levels of formal education, received intraoral examinations in accordance with the 10 criteria embedded in the Functional Assessment of Dentures (FAD) and personal interviews in accordance with the Oral Health Impact Profile (OHIP)-14. The mean OHIP-14 scores were compared among categories using a t test or ANOVA. A multiple-regression analysis was used to identify significant FAD criteria related to specific OHIP-14 domains, while adjusting for gender, age, and educational level. Results: Maxillary stability and retention, denture articulation, and occlusion demonstrated significant relationships with the mean OHIP-14 scores and individual mean OHIP-14 domain scores. Maxillary denture stability and denture articulation were the two most significant denture-related variables. Conclusion: A stable and retentive maxillary denture with adequate articulation provided the optimal environment for oral function with the highest level of patient oral health-related well-being in this elderly population.

Background/purpose: In this study, we investigated outcomes for conventional deltopectoral (DP) flaps and L-extension deltopectoral (L-DP) flaps in head-and-neck reconstructions. Materials and methods: Twenty-three conventional DP flaps and 10 L-DP flaps were created in 33 patients. The latter flaps were applied with no delay. The flaps were folded only in the L-DP-flap group. Seven of 10 L-DP flaps were folded to become bilayered flaps in order to repair full-thickness defects. Flap success rates and complication rates were compared between the conventional DP-flap and L-DP-flap groups. Results: Success rates were 91.3% in the DP-flap group and 90% in the L-DP-flap group. Overall complication rates of the transferred flaps were 30.4% and 40% for DP and L-DP flaps, respectively. Complications in the two groups were analyzed by a Chi-square test, and no significant differences were found. Conclusions: Although the DP flap is considered to be the “aged workhorse” in contemporary head-and-neck reconstructions, it was shown to be a beneficial regional flap with a dependable pedicle and easy technique. The L-DP flap is of value particularly when used to treat full-thickness defects of the head-and-neck.

Background/purpose: Different denture cleaning methods have different effects. The purpose of this study was to evaluate the efficiency of six different denture cleaning methods to remove Candida albicans that had accumulated on denture-based materials. Materials and methods: We generated 140 identical acrylic resin specimens and soaked them in a suspension of C albicans. The reduction in microorganism counts after application of the different denture cleaning methods was calculated. Six cleaning methods were evaluated: a mechanical method of brushing with a toothbrush, a chemical method of soaking in a commercial cleansing tablet solution, a combined method of brushing and soaking in a commercial cleansing tablet solution, a chemical method of soaking in a commercial mouthwash solution, irradiation in an ultraviolet (UV)-light e-box, and soaking in distilled water. The effectiveness of the denture-cleaning methods in reducing C albicans was evaluated following a single cleaning event. Results: The denture cleaning techniques had considerably different efficacies in reducing C albicans. There was no significant difference among the effectiveness levels of cleaning by brushing, soaking in a commercial cleansing tablet solution, or a combination of both in removing C albicans. Similarly, the effectiveness levels of soaking in a commercial mouthwash solution or irradiation in a UV-light e-box were statistically similar. Conclusion: Compared to other methods, brushing, soaking in a commercial cleansing tablet solution, or a combination of both methods can significantly reduce the adherence of C albicans to denture samples. Compared to soaking in distilled water, soaking in a commercial mouthwash solution or irradiation with UV-light had more significant cleaning effects, but these methods were not as effective as the aforementioned three methods.

Background/purpose: The concept of miniscrews-miniplates has been used in orthodontic practice to reinforce skeletal anchorage. The aim of this study was to evaluate the mechanical strength of miniplates in vertical and horizontal pull-out tests. Materials and methods: The insertion torques and pull-out strengths of 10 miniscrew–miniplate orthopedic sets (five for the vertical and five for the horizontal pull-out tests) within synthetic bone were determined. Each miniscrew–miniplate orthopedic set was composed of one miniplate and two 7-mm miniscrews, which were manually driven into the artificial bone. Insertion torque values and the vertical and horizontal pull-out strengths were measured. The Kruskal-Wallis test was used to test for significant differences. Results: The horizontal pull-out strength (mean, 233.1 N cm) was significantly greater than the vertical pull-out strength (mean, 106.8 N cm). The mean peak level of breaking force of the power chain was only 21.9 N cm. There was no significant relationship between the insertion torque and pull-out strength. Conclusions: Successful outcomes were confirmed for the skeletal anchorage concept for orthodontic treatment using miniscrews and miniplates. The mechanical strength of the miniscrews and miniplates was studied to prove the stability of fixation to resist orthodontic forces in the vertical and horizontal directions.

Oral appliances are a range of devices that are designed to alter upper airway patency. The efficiency of these appliances for treatment of obstructive sleep apnea (OSA) has been rarely discussed. This case report describes two designs of mandibular repositioning appliances used to treat OSA. A 36-year-old man was diagnosed with mild OSA by his physician. A single-piece, soft oral appliance and a two-piece, acrylic appliance were used in this patient. Polysomnography was performed three times (baseline, and with the single-piece, and two-piece appliances). The apnea/hypopnea index was improved significantly with both appliances, but to a greater degree with the single-piece soft appliance. Our study concluded that oral appliances may assist in the management of OSA.

Patients with glomerular disease are at high risk of cardiovascular disease but the contribution of immunosuppression to this risk is unclear. In this retrospective cohort study of 1912 patients (comprised of 759 with IgA nephropathy, 540 with focal segmental glomerulosclerosis, 387 with membranous nephropathy and 226 with minimal change disease) from British Columbia, Canada, we evaluated the association between exposure to specific immunosuppressive medications and a composite outcome including coronary artery, cerebrovascular and peripheral arterial events. Survival models were adjusted for baseline cardiovascular risk factors, type of glomerular disease, estimated glomerular filtration rate (eGFR) and proteinuria over time. During a median follow-up of 6.8 years, 212 patients (11.1%) experienced the primary outcome. Corticosteroid exposure was not significantly associated with the primary outcome after adjusting for cardiovascular risk factors. In fully adjusted models, cumulative calcineurin inhibitor exposure at modest (150-300 defined daily doses [DDD]) and higher (300 or more DDD) doses were associated with a 2-fold higher risk of cardiovascular events (hazard ratio 2.98, 95% confidence interval 1.27-6.95) and (2.78, 1.32-5.84), respectively. A peak daily dose of antimetabolite (azathioprine, mycophenolate mofetil and mycophenolate sodium) of 0.5 or more DDD was associated with higher risk of cardiovascular events after adjustment for baseline risk factors and type of glomerular disease, but not after adjusting for time-varying eGFR and proteinuria (1.70, 0.91-3.20). Each 10 grams of cumulative cyclophosphamide exposure was associated with a 1.5-fold higher risk of cardiovascular events in a fully adjusted model (1.46, 1.22-1.75) Thus, our findings suggest that immunosuppressive therapies used in the treatment of glomerular disease may have different cardiovascular risk profiles, which should be considered when deciding on immunosuppression for individual patients and as a safety endpoint in future clinical trials., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

The pediatric International IgA Nephropathy (IgAN) Prediction Tool comprises two models with and without ethnicity and is the first method to predict the risk of a 30% decline in estimated glomerular filtration rate (eGFR) or kidney failure in children at the time of biopsy using clinical risk factors and Oxford MEST histology scores. However, it is unknown if the Prediction Tool can be applied after a period of observation post-biopsy. Using an international multi-ethnic cohort of 947 children with IgAN, 38% of whom were followed into adulthood, the Prediction Tool was updated for use one year after biopsy. Compared to the original pediatric Prediction Tool, the updated post-biopsy Prediction Tool had a better model fit with higher R 2 D (51%/50% vs 20%), significant increase in 4-year C-statistics (0.83 vs 0.73/0.69, ΔC 0.09 [95% confidence interval 0.07-0.10] and ΔC 0.14 [0.12-0.15]) and better 4-year calibration with lower integrated calibration indices (0.74/0.54 vs 2.45/1.01). Results were similar after internal validation and when the models were applied two years after biopsy. Trajectories of eGFR after a baseline one year post-biopsy were non-linear and those at higher predicted risk started with a lower eGFR and experienced a more rapid decline over time. In children, eGFR had a variable rate of increase until 15-18 years old and then decreased linearly with a more rapid decline in higher risk groups that was similar to young adults of comparable risk. Thus, the original pediatric Prediction Tool should be used in children at the time of biopsy, and the updated pediatric Prediction Tool should be used to re-evaluate risk one or two years after biopsy., (Copyright © 2024 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: We investigated the implications of implementing race-free Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) 2021 equation among real-world patients with chronic kidney disease (CKD) from British Columbia (BC), Canada., Methods: This study included nondialysis-dependent patients with CKD aged ≥19 years who were registered in the Patient Records and Outcome Management Information System (PROMIS) as of March 31, 2016 (index date) with ≥1 serum creatinine measurement within 1 year before the index date. Patients with a history of kidney transplantation before the index date were excluded. CKD-EPI 2021 versus 2009 equation was the exposure variable. Difference in mean estimated glomerular filtration rate (eGFR) and number (%) of patients reclassified to a different eGFR category were estimated. We used Fine and Gray subdistribution hazard model to investigate the association between change in eGFR category and progression to kidney failure (incident maintenance dialysis or kidney transplantation) within 2 years., Results: A total of 11,604 patients (median age 73 years, 52% male) were included. Compared to the 2009 equation, eGFR from 2021 equation was on average 2.7 ml/min per 1.73 m 2 higher. Variation was higher among males. Overall, ∼17% of the study sample were reclassified to a category with higher eGFR by 2021 equation (switchers). The highest proportion (28%) of patients were reclassified from G5 to G4. The risk of progressing to kidney failure was 22% less among switchers compared to nonswitchers; adjusted subdistribution hazard ratio (HR) (95% confidence interval [CI]) is 0.78 (0.65, 0.94)., Conclusion: CKD-EPI 2021 equation appeared to provide higher eGFR compared to 2009 equation. This higher eGFR values appeared to be concordant with subsequent real-world CKD progression outcomes. Higher eGFR from the 2021 equation may have substantial clinical implications in both diagnosis as well as long-term care of patients with CKD., (© 2024 International Society of Nephrology. Published by Elsevier Inc.)

Introduction: Despite recognized geographic and sex-based differences in hemoglobin in the general population, these factors are typically ignored in patients with chronic kidney disease (CKD) in whom a single therapeutic range for hemoglobin is recommended. We sought to compare the distribution of hemoglobin across international nondialysis CKD populations and evaluate predictors of hemoglobin., Methods: In this cross-sectional study, hemoglobin distribution was evaluated in each cohort overall and stratified by sex and estimated glomerular filtration rate (eGFR). Relationships between candidate predictors and hemoglobin were assessed from linear regression models in each cohort. Estimates were subsequently pooled in a random effects model., Results: A total of 58,613 participants from 21 adult cohorts (median eGFR range of 17-49 ml/min) and 3 pediatric cohorts (median eGFR range of 26-45 ml/min) were included with broad geographic representation. Hemoglobin values varied substantially among the cohorts, overall and within eGFR categories, with particularly low mean hemoglobin observed in women from Asian and African cohorts. Across the eGFR range, women had a lower hemoglobin compared to men, even at an eGFR of 15 ml/min (mean difference 5.3 g/l, 95% confidence interval [CI] 3.7-6.9). Lower eGFR, female sex, older age, lower body mass index, and diabetic kidney disease were all independent predictors of a lower hemoglobin value; however, this only explained a minority of variance (R 2 7%-44% across cohorts)., Conclusion: There are substantial regional differences in hemoglobin distribution among individuals with CKD, and the majority of variance is unexplained by demographics, eGFR, or comorbidities. These findings call for a renewed interest in improving our understanding of hemoglobin determinants in specific CKD populations., (© 2023 Published by Elsevier, Inc., on behalf of the International Society of Nephrology.)

The International IgA Nephropathy (IgAN) Prediction Tool is the preferred method in the 2021 KDIGO guidelines to predict, at the time of kidney biopsy, the risk of a 50% drop in estimated glomerular filtration rate or kidney failure. However, it is not known if the Prediction Tool can be accurately applied after a period of observation post-biopsy. Using an international multi-ethnic derivation cohort of 2,507 adults with IgAN, we updated the Prediction Tool for use one year after biopsy, and externally validated this in a cohort of 722 adults. The original Prediction Tool applied at one-year without modification had a coefficient of variation (R 2 ) of 55% and 54% and four-year concordance (C statistic) of 0.82 but poor calibration with under-prediction of risk (integrated calibration index (ICI) 1.54 and 2.11, with and without race, respectively). Our updated Prediction Tool had a better model fit with higher R 2 (61% and 60%), significant increase in four-year C-statistic (0.87 and 0.86) and better four-year calibration with lower ICI (0.75 and 0.35). On external validation, the updated Prediction Tool had similar R 2 (60% and 58%) and four-year C-statistics (both 0.85) compared to the derivation analysis, with excellent four-year calibration (ICI 0.62 and 0.56). This updated Prediction Tool had similar prediction performance when used two years after biopsy. Thus, the original Prediction Tool should be used only at the time of biopsy whereas our updated Prediction Tool can be used for risk stratification one or two years post-biopsy., (Copyright © 2022 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: Immunoglobulin (Ig)A nephropathy (IgAN) is the most frequently diagnosed primary glomerulonephritis worldwide. Despite the common diagnostic feature of mesangial IgA-containing immune complex deposition, the clinical course of the disease is extremely variable, with 30% of patients developing end-stage kidney disease within 20 years of diagnosis. Therefore, identifying which patients are likely to progress is paramount., Results: In this pilot study, we found that urinary exosomal miR-204 expression was significantly reduced in IgAN compared with healthy subjects. However, there was no difference in miR-204 expression between IgAN and non-IgAN chronic kidney disease controls. Analysis of miR-204 expression in kidney biopsy cores by next-generation sequencing followed by quantitative polymerase chain reaction validation in independent cohorts demonstrated that expression of miR-204 was significantly lower in IgAN compared with thin-membrane nephropathy but not compared with membranous nephropathy. Patients with IgAN at high risk of future progression had significantly lower expression of miR-204 than those at low risk of progression. Cortical localization indicated that miR-204 was preferentially expressed in the interstitium compared with glomeruli in IgAN nonprogressors and that this distribution was lost in IgAN progressors. Receiver operating characteristic curve analysis between the 2 IgAN cohorts revealed an area under the curve of 0.82. In addition, miR-204 expression correlated with known clinicopathological prognostic risk factors. Importantly, incorporating miR-204 into the International IgAN risk prediction tool improved the diagnostic power of the algorithm to predict risk of progression., Conclusion: Additional large-scale studies are now needed to validate the additive value of miR-204 in improving risk prediction in IgAN and more broadly in chronic kidney disease., (© 2021 International Society of Nephrology. Published by Elsevier Inc.)

Although IgA nephropathy (IgAN) is a common cause of glomerulonephritis in children, the absence of a method to predict disease progression limits personalized risk-based treatment decisions. The adult International IgAN Prediction Tool comprises two validated Cox survival models that predict a 50% decline in estimated glomerular filtration rate (eGFR) or end stage kidney disease (ESKD) using clinical risk factors and Oxford MEST histology scores. Here, we updated the Prediction Tool for use in children using a multiethnic international cohort of 1,060 children with IgAN followed into adulthood. The updated pediatric Prediction Tool had better model fit than the original adult tool with lower Akaike Information Criterion, higher R 2 D and similar C-statistics. However, calibration showed very poor agreement between predicted and observed risks likely due to the observed disease trajectory in children. Therefore, the Tool was updated using a secondary outcome of a 30% reduction in eGFR or ESKD, resulting in better R 2 D (30.3%/22.2%) and similar C-statistics (0.74/0.68) compared to the adult tool but with good calibration. The trajectory of eGFR over time in children differed from adults being highly non-linear with an increase until 18 years old followed by a linear decline similar to that of adults. A higher predicted risk was associated with a smaller increase in eGFR followed by a more rapid decline, suggesting that children at risk of a 30% decrease in eGFR will eventually experience a larger 50% decrease in eGFR when followed into adulthood. As such, these two outcomes are analogous between pediatric and adult Prediction Tools. Thus, our pediatric Prediction Tool can accurately predict the risk of a 30% decline in eGFR or ESKD in children with IgAN., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Understanding why certain patients with IgA nephropathy progress to kidney failure while others maintain normal kidney function remains a major unanswered question. To help answer this, we performed miRNome profiling by next generation sequencing of kidney biopsies in order to identify microRNAs specifically associated with the risk of IgA nephropathy progression. Following sequencing and validation in independent cohorts, four microRNAs (-150-5p, -155-5p, -146b-5p, -135a-5p) were found to be differentially expressed in IgA nephropathy progressors compared to non-progressors, and patients with thin membrane nephropathy, lupus nephritis and membranous nephropathy, and correlated with estimated glomerular filtration rate, proteinuria, and the Oxford MEST-C scores (five histological features that are independent predictors of clinical outcome). Each individual microRNA increased the discrimination score of the International IgAN Prediction Tool, although due to the small number of samples the results did not reach statistical significance. miR-150-5p exhibited the largest amplitude of expression between cohorts and displayed the best discrimination between IgA nephropathy progressors and non-progressors by receiver operating curve analysis (AUC: 0.8). However, expression was similarly upregulated in kidneys with established fibrosis and low estimated glomerular filtration rates at the time of biopsy. Consistent with a more generic role in kidney fibrosis, in situ hybridization revealed that miR-150-5p was found in lymphoid infiltrates, and areas of proliferation and fibrosis consistent with the known drivers of progression. Thus, miR-150-5p may be a potential functional mediator of kidney fibrosis that may add value in predicting risk of progression in IgA nephropathy and other kidney diseases., (Copyright © 2021 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Immunosuppression in IgA nephropathy (IgAN) should be reserved for patients at high-risk of disease progression, which KDIGO guidelines determine based solely on proteinuria 1g or more/day. To investigate if treatment decisions can be more accurately accomplished using individualized risk from the International IgAN Prediction Tool, we simulated allocation of a hypothetical immunosuppression therapy in an international cohort of adults with IgAN. Two decision rules for treatment were applied based on proteinuria of 1g or more/day or predicted risk from the Prediction Tool above a threshold probability. An appropriate decision was defined as immunosuppression allocated to patients experiencing the primary outcome (50% decline in eGFR or ESKD) and withheld otherwise. The net benefit and net reduction in treatment are the proportion of patients appropriately allocated to receive or withhold immunosuppression, adjusted for the harm from inappropriate decisions, calculated for all threshold probabilities from 0-100%. Of 3299 patients followed for 5.1 years, 522 (15.8%) experienced the primary outcome. Treatment allocation based solely on proteinuria of 1g or more/day had a negative net benefit (was harmful) because immunosuppression was increasingly allocated to patients without progressive disease. Compared to using proteinuria, treatment allocation using the Prediction Tool had a larger net benefit up to 23.4% (95% confidence interval 21.5-25.2%) and a larger net reduction in treatment up to 35.1% (32.3-37.8%). Thus, allocation of immunosuppression to high-risk patients with IgAN can be substantially improved using the Prediction Tool compared to using proteinuria., (Copyright © 2020 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.)

Introduction: Two prediction models for IgA nephropathy (IgAN) using clinical variables and the Oxford MEST scores were developed and validated in 2 multiethnic cohorts. Additional external validation is required., Methods: Biopsy-proven Chinese and Argentinian patients with IgAN were included. The primary outcome was defined as a 50% decline in estimated glomerular filtration rate (eGFR) or end-stage renal disease. C-statistics and stratified analyses were used for model discrimination, coefficient of determination (R 2 D ) for model fit, and calibration plots for model calibration. Baseline survival function was also evaluated., Results: A total of 1275 patients were enrolled, with a mean age of 34 (interquartile range: 27-42) years, 50% of whom (638 of 1275) were men. Use of renin-angiotensin system blockers was higher than in previously reported cohorts, whereas other variables were comparable. The C-statistic of the models was 0.81, and R 2 D was higher than reported. Survival curves in the subgroups (<16th, ∼16th to <50th, ∼50th to <84th, and ≥84th percentiles of linear predictor) were well separated. Most of the predictor variables, including hazard ratio, predicted 5-year risk, and eGFR decline slope, were worse with risk increasing. The baseline survival function was comparable in our cohort and the reported cohorts. The calibration was acceptable for the full model without race. However, the risk probability over 3 years was overestimated in the full model with race included., Conclusion: The prediction models showed good performance on personalized risk assessment, which may be used as drug-specific, precision-medicine approaches to treatment decisionmaking., (© 2020 International Society of Nephrology. Published by Elsevier Inc.)

Background: Using standard cutoffs derived from healthy adults, high-sensitivity cardiac troponin T (hs-cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) are frequently elevated in patients with reduced glomerular filtration rate (GFR), with unclear implications. We sought to compare GFR-specific cutoffs of each biomarker with standard cutoffs for discrimination of cardiovascular risk in asymptomatic patients with chronic kidney disease., Methods: We investigated a prospective cohort of 1956 participants with median GFR of 27 mL/min/1.73 m 2 . Cox proportional hazards models were used to examine the association between each biomarker and first adjudicated cardiovascular event (unstable angina, myocardial infarction, heart failure, stroke, cardiovascular death). We used an outcome-based approach to identify optimal risk-based cutoffs for each biomarker within GFR strata (< 20, 20-29, 30-44 mL/min/1.73 m 2 ). We evaluated the added prognostic value of each biomarker to a multivariable base model, comparing GFR-specific with standard cutoffs., Results: Hs-cTnT and NT-proBNP were elevated in 76% and 82% of participants, respectively. A total of 401 events were recorded during 6772 person-years at risk. Both biomarkers were independent predictors of cardiovascular events. Optimal cutoffs for each biomarker were higher than standard thresholds, being highest at GFR values < 20 mL/min/1.73 m 2 . Addition of hs-cTnT to the base model using GFR-specific cutoffs significantly improved reclassification for events (52%) and nonevents (21%). Similar findings were observed for NT-proBNP. In contrast, use of standard cutoffs failed to reclassify patients who had no event as lower risk., Conclusions: Among asymptomatic patients with advanced chronic kidney disease, optimal cutoffs for hs-cTnT and NT-proBNP differed according to GFR level and outperformed standard cutoffs for discrimination of cardiovascular risk., (Copyright © 2019 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Non-vitamin K antagonist oral anticoagulants (NOACs) require renal dose adjustment. The most common estimates of renal function in clinical practice are derived from estimated glomerular filtration rate (eGFR; Modified Diet in Renal Disease [MDRD] or the Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI]). However, the landmark stroke prevention trials and product monographs recommend the use of the Cockcroft-Gault creatinine clearance equation (eCrCl) for drug eligibility and dose adjustment. We sought to evaluate the agreement in NOAC dosing between these 3 equations in a large population of patients with atrial fibrillation and moderate chronic kidney disease., Methods: We identified 831 patients with non-dialysis-dependent chronic kidney disease and atrial fibrillation (CHA 2 DS 2 -VASc 3.9). For each patient, eCrCl, MDRD eGFR, and CKD-EPI eGFR were prospectively calculated. Eligibility criteria for NOAC medications were evaluated by comparing the eGFR as estimated by MDRD or CKD-EPI equation with the eCrCl as estimated by Cockcroft-Gault, with the latter regarded as the "gold standard.", Results: The use of eGFR resulted in significant misclassification with respect to NOAC dosing. Compared with eCrCl, the MDRD eGFR and CKD-EPI eGFR misclassified 36.2% and 35.8% of patients, respectively. The misclassification resulted in undertreatment (eg, inappropriate dose reduction; 26.9% MDRD, 28.8% CKD-EPI), and to a lesser extent overtreatment (eg, inappropriate use of standard dose; 9.3% MDRD, 7.0% CKD-EPI)., Conclusions: MDRD and CKD-EPI eGFR fail to correctly identify a significant proportion of patients who require NOAC dose adjustment, limiting their clinical utility. Cockcroft-Gault eCrCl should be calculated for all patients in whom a NOAC is being prescribed., (Copyright © 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Objective: Stroke is commonly caused by thromboembolic events originating from ruptured carotid plaque with vulnerable composition. This study assessed the performance of acoustic radiation force impulse (ARFI) imaging, a noninvasive ultrasound elasticity imaging method, for delineating the composition of human carotid plaque in vivo with histologic validation., Methods: Carotid ARFI images were captured before surgery in 25 patients undergoing clinically indicated carotid endarterectomy. The surgical specimens were histologically processed with sectioning matched to the ultrasound imaging plane. Three radiologists, blinded to histology, evaluated parametric images of ARFI-induced peak displacement to identify plaque features such as necrotic core (NC), intraplaque hemorrhage (IPH), collagen (COL), calcium (CAL), and fibrous cap (FC) thickness. Reader performance was measured against the histologic standard using receiver operating characteristic curve analysis, linear regression, Spearman correlation (ρ), and Bland-Altman analysis., Results: ARFI peak displacement was two-to-four-times larger in regions of NC and IPH relative to regions of COL or CAL. Readers detected soft plaque features (NC/IPH) with a median area under the curve of 0.887 (range, 0.867-0.924) and stiff plaque features (COL/CAL) with median area under the curve of 0.859 (range, 0.771-0.929). FC thickness measurements of two of the three readers correlated with histology (reader 1: R 2  = 0.64, ρ = 0.81; reader 2: R 2  = 0.89, ρ = 0.75)., Conclusions: This study suggests that ARFI is capable of distinguishing soft from stiff atherosclerotic plaque components and delineating FC thickness., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

PRELP is a member of the small leucine-rich repeat proteoglycan family that is abundantly expressed in many cartilages compared to other connective tissues. To study the consequence of PRELP overexpression in tissues where it is normally expressed at low abundance, transgenic mice were generated in which the human PRELP transgene was placed under control of the CMV promoter. A connective tissue phenotype was observed in the skin, where the organization of collagen fibrils in the dermis was perturbed and the thickness of the hypodermal fat layer was diminished.

XaiF, a novel 32kDa protein encoded by the ORF located in the immediate downstream of the xynA gene of Bacillus stearothermophilus No. 236, was identified to be the xylanase-specific trans-activator. In this study, the positive effect of XaiF was confirmed to be xylanase-specific, and the results from Northern blot and in vitro transcription assays showed that the XaiF increased the xynA transcripts at post-transcriptional step. Moreover, analysis of the mRNA decay rate led to the assertion that the XaiF functions to stabilize the xynA mRNA. Intriguingly, in vitro RNA-protein binding assay and analysis using gst-xynA 3'-UTR chimeric gene constructs demonstrated that the XaiF stabilizes xynA mRNA by direct binding onto the 3'-UTR of the mRNA.