Rituximab or Cyclosporine in the Treatment of Membranous Nephropathy.

BACKGROUND: B-cell anomalies play a role in the pathogenesis of membranous nephropathy. B-cell depletion with rituximab may therefore be noninferior to treatment with cyclosporine for inducing and maintaining a complete or partial remission of proteinuria in patients with this condition. METHODS: We randomly assigned patients who had membranous nephropathy, proteinuria of at least 5 g per 24 hours, and a quantified creatinine clearance of at least 40 ml per minute per 1.73 m2 of body-surface area and had been receiving angiotensin-system blockade for at least 3 months to receive intravenous rituximab (two infusions, 1000 mg each, administered 14 days apart; repeated at 6 months in case of partial response) or oral cyclosporine (starting at a dose of 3.5 mg per kilogram of body weight per day for 12 months). Patients were followed for 24 months. The primary outcome was a composite of complete or partial remission of proteinuria at 24 months. Laboratory variables and safety were also assessed. RESULTS: A total of 130 patients underwent randomization. At 12 months, 39 of 65 patients (60%) in the rituximab group and 34 of 65 (52%) in the cyclosporine group had a complete or partial remission (risk difference, 8 percentage points; 95% confidence interval [CI], -9 to 25; P = 0.004 for noninferiority). At 24 months, 39 patients (60%) in the rituximab group and 13 (20%) in the cyclosporine group had a complete or partial remission (risk difference, 40 percentage points; 95% CI, 25 to 55; P<0.001 for both noninferiority and superiority). Among patients in remission who tested positive for anti-phospholipase A2 receptor (PLA2R) antibodies, the decline in autoantibodies to anti-PLA2R was faster and of greater magnitude and duration in the rituximab group than in the cyclosporine group. Serious adverse events occurred in 11 patients (17%) in the rituximab group and in 20 (31%) in the cyclosporine group (P = 0.06). CONCLUSIONS: Rituximab was noninferior to cyclosporine in inducing complete or partial remission of proteinuria at 12 months and was superior in maintaining proteinuria remission up to 24 months. (Funded by Genentech and the Fulk Family Foundation; MENTOR ClinicalTrials.gov number, NCT01180036.).

Clinical trial recommendations for potential Alport syndrome therapies.

Alport syndrome is experiencing a remarkable increase in preclinical investigations. To proactively address the needs of the Alport syndrome community, as well as offer clarity for future clinical research sponsors, the Alport Syndrome Foundation hosted a workshop to generate consensus recommendations for prospective trials for conventional drugs. Opinions of key stakeholders were carefully considered, including those of the biopharmaceutical industry representatives, academic researchers, clinicians, regulatory agency representatives, and-most critically-patients with Alport syndrome. Recommendations were established for preclinical researchers, the use and selection of biomarkers, standards of care, clinical trial designs, trial eligibility criteria and outcomes, pediatric trial considerations, and considerations for patient engagement, recruitment, and treatment. This paper outlines their recommendations.

Primary Care Physicians' Perceived Barriers to Nephrology Referral and Co-management of Patients with CKD: a Qualitative Study.

BACKGROUND: Effective co-management of patients with chronic kidney disease (CKD) between primary care physicians (PCPs) and nephrologists is increasingly recognized as a key strategy to ensure the delivery of efficient and high-quality CKD care. However, the co-management of patients with CKD remains suboptimal. OBJECTIVE: We aimed to identify PCPs' perceptions of key barriers and facilitators to effective co-management of patients with CKD at the PCP-nephrology interface. STUDY DESIGN: Qualitative study SETTING AND PARTICIPANTS: Community-based PCPs in four US cities: Baltimore, MD; St. Louis, MO; Raleigh, NC; and San Francisco, CA APPROACH: We conducted four focus groups of PCPs. Two members of the research team coded transcribed audio-recorded interviews and identified major themes. KEY RESULTS: Most of the 32 PCPs (59% internists and 41% family physicians) had been in practice for > 10 years (97%), spent ≥ 80% of their time in clinical care (94%), and practiced in private (69%) or multispecialty group practice (16%) settings. PCPs most commonly identified barriers to effective co-management of patients with CKD focused on difficulty developing working partnerships with nephrologists, including (1) lack of timely adequate information exchange (e.g., consult note not received or CKD care plan unclear); (2) unclear roles and responsibilities between PCPs and nephrologists; and (3) limited access to nephrologists (e.g., unable to obtain timely consultations or easily contact nephrologists with concerns). PCPs expressed a desire for "better communication tools" (e.g., shared electronic medical record) and clear CKD care plans to facilitate improved PCP-nephrology collaboration. CONCLUSIONS: Interventions facilitating timely adequate information exchange, clear delineation of roles and responsibilities between PCPs and nephrologists, and greater access to specialist advice may improve the co-management of patients with CKD.

Sharing innovations to enhance renal fellow education in dialysis.

Dialysis care is an integral part of the practice of nephrology. Despite this, education of fellows in providing dialysis often remains rudimentary, relying on a combination of didactics and learning through experience. This runs the risk of training nephrologists who can provide dialysis care without truly being experts on the subject. In this article, a collection of novel or innovative teaching methods is presented that are meant to provide training programs with additional tools with which to improve the training of their fellows in dialysis.

The importance of the cement spacer for proper crown seating Erratum.

Marginal integrity is important for the longevity of a restoration. An increase in the marginal discrepancy after cementation contributes adversely to the longevity of a restoration. In the past, the preferred method to overcome this discrepancy was to create internal space for the cement by using a number of coats of a die-spacing material. In the digital age, however, this method is no longer the only option. Currently, an amount of die spacer is engineered into the computer program and forms part of the milling process. The present study attempted to identify the optimal setting of the Spacer parameter that a) is necessary for the complete cementation of a Cerec milled all-ceramic crown, and b) does not compromise the strength of the crown postcementation.

Fibrillary glomerulonephritis associated with limited scleroderma: a case report.

Fibrillary glomerulonephritis (GN) is a rare glomerular disorder that has been associated with monoclonal gammopathies, malignancies, chronic infections, and autoimmune disorders. We present the case of a 56-year-old woman with limited-type scleroderma and remote discoid lupus, evaluated for dipstick positive hematuria and preserved kidney function. Serologies were negative. Kidney biopsy revealed fibrillary GN. Her renal function and proteinuria remain stable 4 years after her initial diagnosis. This case is unusual both in its presentation and evolution, but mostly because it is the first reported case of fibrillary GN in association with limited type scleroderma.

Technological Innovations in the Restorative Department at the University of Tennessee College of Dentistry.

The UT College of Dentistry has been one of the leaders in the introduction of the CAD/CAM delivery of dentistry to the dental students. The integration of technology into a dental school curriculum requires a change in thinking and a modification of the curriculum in order to introduce it to the present day students This article updates the integration of the CEREC system into the UT Dental School curriculum, discussing the changes in equipment and teaching techniques since the last article in 2012.

Chronic kidney disease in an electronic health record problem list: quality of care, ESRD, and mortality.

BACKGROUND: Whether chronic kidney disease (CKD) recognition in an electronic health record (EHR) problem list improves processes of care or clinical outcomes of end-stage renal disease (ESRD) and death is unclear. METHODS: We identified patients who had at least 1 year of follow-up (2005-2009) in our EHR-based CKD registry (n = 25,742). CKD recognition was defined by having ICD-9 codes for CKD, diabetic kidney disease, or hypertensive kidney disease in the problem list. We calculated proportions of patients with and without CKD recognition and examined differences by demographics, clinical factors, and development of ESRD or mortality. We evaluated differences in the proportion of patients with CKD-specific laboratory results checked before and after recognition among cases and propensity-matched controls. RESULTS: Only 11% (n = 2,735) had CKD recognition in the problem list and they were younger (68 vs. 71 years), a higher proportion were male (61 vs. 37%) and African-American (21 vs. 10%) compared to those unrecognized. CKD-specific laboratory results for patients with estimated glomerular filtration rate (eGFR) 30-59 including intact parathyroid hormone (23 vs. 6%), vitamin D (22 vs. 18%), phosphorus (29 vs. 7%), and a urine check for proteinuria (55 vs. 36%) were significantly more likely to be done among those with CKD recognition (all p < 0.05). Similar results were found for eGFR <30 except for proteinuria and in our propensity score-matched control analysis. There was no independent association of CKD recognition with ESRD or mortality. CONCLUSIONS: CKD recognition in the EHR problem list was low, but translated into more CKD-specific processes of care; however ESRD or mortality were not affected.

Placebo-controlled clinical trial evaluating 9.5% hydrogen peroxide high-adhesion whitening strips.

OBJECTIVE: To evaluate the effectiveness and tolerability of an experimental 9.5% hydrogen peroxide whitening strip relative to a placebo control over a three-week period. METHODS: In this parallel-design, double-blind clinical trial, 54 adult volunteers were randomized to an experimental 9.5% hydrogen peroxide whitening strip or placebo strip balancing for age and baseline tooth color, and received treatment. Strips were worn on the maxillary arch 30 minutes daily for 20 days. Efficacy was measured objectively as L*a*b* color change from digital images at Days 4, 7, 15, and 21. RESULTS: As early as Day 4 and at all subsequent visits, the 9.5% strip group experienced significant (p < 0.004) color improvement relative to placebo for b* and L* color parameters. The amount of color improvement increased with continuing peroxide strip use. Mean ± SE between-group differences in Ab* were -0.6 ± 0.16, -0.8 ± 0.15, -1.6 ± 0.19, and -1.9 ± 0.20 at Days 4, 7, 15, and 21, respectively. Similar results were noted for AL*. Minor tooth sensitivity was the most common adverse event, as reported by 12% of subjects in the 9.5% strip group and 11% of subjects in the placebo group. No subjects discontinued treatment due to an adverse event. CONCLUSION: This placebo-controlled clinical trial demonstrated that an experimental 9.5% hydrogen peroxide strip yielded significant tooth whitening relative to a placebo strip as early as after three days of product use.

Prognostic importance of serum alkaline phosphatase in CKD stages 3-4 in a clinical population.

BACKGROUND: Elevated total serum alkaline phosphatase (ALP) levels have been associated with mortality in the general population and in dialysis patients. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: 28,678 patients with chronic kidney disease (CKD) stages 3 and 4 (estimated glomerular filtration rate, 15-59 mL/min/1.73 m(2)) were identified using the Cleveland Clinic CKD Registry. CKD was defined as 2 estimated glomerular filtration rate values <60 mL/min/1.73 m(2) drawn more than 90 days apart using the CKD-EPI (CKD Epidemiology Collaboration) creatinine equation. PREDICTOR: ALP levels measured using the calorimetric assay were examined as quartiles (quartile [Q]1, <66 U/L; Q2, 66-81 U/L; Q3, 82-101 U/L; and Q4, ≥102 U/L) and as a continuous measure. OUTCOMES & MEASUREMENTS: All-cause mortality and end-stage renal disease (ESRD) were ascertained using the Social Security Death Index and US Renal Data System. RESULTS: After a median follow-up of 2.2 years, 588 patients progressed to ESRD and 4,755 died. There was a graded increase in risk of mortality with higher ALP quartiles (Q2, Q3, and Q4) compared to the reference quartile (Q1) after adjusting for demographics, comorbid conditions, use of relevant medications, and liver function test results. The highest ALP quartile was associated with an HR for ESRD of 1.38 (95% CI, 1.09-1.76). Each 1-SD (42.7 U/L) higher ALP level was associated with 15% (95% CI, 1.09-1.22) and 16% (95% CI, 1.14-1.18) increased risk of ESRD and mortality, respectively. LIMITATIONS: Single-center observational study; lack of complete data, including parathyroid hormone level, for all study participants, and attrition bias. CONCLUSIONS: Higher serum ALP levels in patients with CKD stages 3-4 were associated independently with all-cause mortality and ESRD.

Cementation of indirect restorations: an overview of resin cements.

The process of ensuring proper retention, marginal seal, and durability of indirect restorations depends heavily on effective cementation. Careful consideration must be made when selecting an adhesive cement for a given application. This article provides information on resin cements that can guide clinicians in determining which type of cement is best suited to their clinical needs regarding cementation of indirect restorations. Emphasis is placed on successful cementation of all-ceramic restorations.

Black Patients Equally Benefit From Renal Genetics Evaluation but Substantial Barriers in Access Exist.

Introduction: Genetic testing is increasingly accessible to patients with kidney diseases. Racial disparities in renal genetics evaluations have not been investigated. Methods: A cohort of patients evaluated by the Cleveland Clinic Renal Genetics Clinic (RGC) from January 2019 to March 2022 was analyzed. Results: Forty-eight Black patients, including 27 (56.3%) males, median age 34 (22-49) years and 232 White patients, including 76 (32.8%) males, median age 35 (21-53) years, were evaluated. Black patients were more likely to have end-stage kidney disease (ESKD) at the time of referral compared with White patients (23% vs. 7.3%, P = 0.004), more likely to be covered by Medicaid (46% vs. 15%, P < 0.001), and less likely to be covered by private insurance (35% vs. 66%, P < 0.001). Black patients were more likely to "no show" to scheduled appointment(s) or not submit specimens for genetic testing compared with White patients (24.1% vs. 6.7%, P = 0.0005). Genetic testing was completed in 35 Black patients. Of these, 37% had a positive result with 9 unique monogenic disorders and 1 chromosomal disorder diagnosed. Sixty-nine percent of Black patients with positive results received a new diagnosis or a change in diagnosis. Of these, 44% received a significant change in disease management. No differences in diagnostic yield and implications of management were noted between Black and White patients. Conclusion: Black patients equally benefit from renal genetics evaluation, but barriers to access exist. Steps must be taken to ensure equitable and early access for all patients. Further studies investigating specific interventions to improve access are needed.

Effectiveness of the Coronavirus Disease 2019 Bivalent Vaccine.

Background: The purpose of this study was to evaluate whether a bivalent coronavirus disease 2019 (COVID-19) vaccine protects against COVID-19. Methods: The study included employees of Cleveland Clinic in employment when the bivalent COVID-19 vaccine first became available. Cumulative incidence of COVID-19 over the following 26 weeks was examined. Protection provided by vaccination (analyzed as a time-dependent covariate) was evaluated using Cox proportional hazards regression, with change in dominant circulating lineages over time accounted for by time-dependent coefficients. The analysis was adjusted for the pandemic phase when the last prior COVID-19 episode occurred and the number of prior vaccine doses. Results: Among 51 017 employees, COVID-19 occurred in 4424 (8.7%) during the study. In multivariable analysis, the bivalent-vaccinated state was associated with lower risk of COVID-19 during the BA.4/5-dominant (hazard ratio, 0.71 [95% confidence interval, .63-79]) and the BQ-dominant (0.80 [.69-.94]) phases, but decreased risk was not found during the XBB-dominant phase (0.96 [.82-.1.12]). The estimated vaccine effectiveness was 29% (95% confidence interval, 21%-37%), 20% (6%-31%), and 4% (-12% to 18%), during the BA.4/5-, BQ-, and XBB-dominant phases, respectively. The risk of COVID-19 also increased with time since the most recent prior COVID-19 episode and with the number of vaccine doses previously received. Conclusions: The bivalent COVID-19 vaccine given to working-aged adults afforded modest protection overall against COVID-19 while the BA.4/5 lineages were the dominant circulating strains, afforded less protection when the BQ lineages were dominant, and effectiveness was not demonstrated when the XBB lineages were dominant.

Considerations for proper selection of dental cements.

Selecting the proper cement for sufficient bond strength has become progressively complicated as the number of different materials for indirect restorations has increased. The success of any restoration is highly dependent on the proper cement being chosen and used. The function of the cement is not only to seal the restoration on the tooth but also, in some cases, to support the retention of the restoration. This ability to strengthen retention varies by the cement chosen by the clinician; therefore, careful consideration must precede cement selection.

Integrating the CEREC technology at UT College of Dentistry.

The computer-aided design/computer-aided manufacturing (CAD/CAM) has evolved during the past 25 years, and this evolution has improved the speed and precision in which dentists can deliver high quality esthetic restorations. CEREC is an acronym for "ceramic reconstruction" and is one of the CAD/CAM systems available to dentists in private practice. The University of Tennessee College of Dentistry was one of the first dental schools in the United States to embrace this technology and integrate it into the four-year curriculum. In a dental school setting, this technology can prove to be an educational tool for the dental students, cost effective for the University and provide exceptional service for the patients.

Anemia of chronic kidney disease: Will new agents deliver on their promise?

Anemia is a well-known complication of chronic kidney disease, and its treatment remains a challenge. Although erythropoiesis-stimulating agents (ESAs) raise hemoglobin levels, their benefits appear to be limited to decreasing the number of blood transfusions needed and perhaps improving quality of life. The newly developed prolyl hydroxylase inhibitors (PHIs)-agents that increase endogenous erythropoietin production-promise to improve outcomes for patients with anemia of chronic kidney disease. Randomized controlled trials have found these drugs to be at least as effective as ESAs, and the drugs are used in other countries. However, PHIs have yet to be approved in the United States.

Low 25-hydroxyvitamin D levels and mortality in non-dialysis-dependent CKD.

BACKGROUND: Low 25-hydroxyvitamin D (25[OH]D) levels are common in patients with non-dialysis-dependent chronic kidney disease (CKD). The associations between low 25(OH)D levels and mortality in non-dialysis-dependent patients with CKD are unclear. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Patients with stages 3-4 CKD (estimated glomerular filtration rate, 15-59 mL/min/1.73 m(2); n = 12,673) who had 25(OH)D levels measured after the diagnosis of CKD in the Cleveland Clinic Health System. PREDICTOR: 25(OH)D levels categorized into 3 groups: <15, 15-29, and ≥30 ng/mL. OUTCOMES: We examined factors associated with low 25(OH)D levels and associations between low 25(OH)D levels and all-cause mortality (ascertained using the Social Security Death Index and our electronic medical record) using logistic regression, Cox proportional hazard models, and Kaplan-Meier survival curves. MEASUREMENTS: 25(OH)D was measured using chemiluminescence immunoassay. RESULTS: Of 12,763 patients with CKD, 15% (n = 1,970) had 25(OH)D levels <15 ng/mL, whereas 45% (n = 5,749) had 25(OH)D levels of 15-29 ng/mL. Male sex, African American race, diabetes, coronary artery disease, and lower estimated glomerular filtration rate were associated significantly with 25(OH)D level <30 ng/mL. A graded increase in risk of 25(OH)D level <30 ng/mL was evident across increasing body mass index levels. Patients who had 25(OH)D levels measured in fall through spring had higher odds for 25(OH)D levels <30 ng/mL. After covariate adjustment, patients with CKD with 25(OH)D levels <15 ng/mL had a 33% increased risk of mortality (95% CI, 1.07-1.65). The group with 25(OH)D levels of 15-29 ng/mL did not show a significantly increased risk of mortality (HR, 1.03; 95% CI, 0.86-1.22) compared with patients with 25(OH)D levels ≥30 ng/mL. LIMITATIONS: Single-center observational study, lack of data for albuminuria and other markers of bone and mineral disorders, and attrition bias. CONCLUSIONS: 25(OH)D level <15 ng/mL was associated independently with all-cause mortality in non-dialysis-dependent patients with CKD.

Tensile bond strength of ceramic crowns to dentin using resin cements.

PURPOSE: This study measured the bond strength of the self-adhesive resin cements and a bonded resin cement for crowns bonded to extracted teeth with preparations having a total taper greater than 30 degrees. A crown pull-off test was used with direction of pull along the path of insertion. The CAD/CAM system Cerec was used to create crowns with the pull-off loop as an integral part of the crown structure. MATERIALS AND METHODS: One hundred extracted human molars were prepared for all-ceramic crowns with a 1.5-mm shoulder, greater than 30-degree axial wall convergence, a flat occlusal surface and 3 to 5 mm occlusal/ gingival height. All-ceramic crowns were cemented with five different self-adhesive cements (Rely X Unicem, Maxcem Elite, BisCem, SmartCem 2, and G-Cem) and one bonded resin cement (Multilink). Forfour cements (excluding GCem and Multilink) there were 2 groups, one with HF etching and one without ceramic surface treatment. The crowns were then subject to tensile stress until either the crown fractured or the crown was lifted off from the tooth. RESULTS: For several cements, the bond strength exceeded the tensile strength of the all-ceramic crown; thus, the crown fractured, leaving the cemented part of the crown on the tooth. The effect of ceramic surface etching was not statistically significant at p = 0.05; however, for each cement, the treated crowns showed a lower coefficient of variance (COV). For this study, the COV ranged from 24.9 % to 97.9 %. Loads ranged from 41.3 to 190.3 N. CONCLUSION: Some of the new self-etching resin cements can create bonds to non-retentive crown preparations that are stronger than the strength of a ceramic crown; however, these high bond strengths may not be able to be achieved consistently.

Operationalizing COVID-19 testing: Who, what, when, where, why, and how.

The authors review the rationale behind and approaches to testing for COVID-19, the quality of currently available tests, the role of data analytics in strategizing testing, and using the electronic medical record and other programs designed to steward COVID-19 testing and follow-up of patients.

An In Vitro Comparison of Indirect Versus Direct Restorations of Incisal Edge Fractures.

Purpose: To compare fracture strength, failure mode, and chairside time of Class IV fractures restored with CEREC (Chairside Economic Restorations of Esthetic Ceramics) technology or direct composite. Methods: Forty-eight fractured anterior bovine teeth were randomly assigned to three experimental groups (indirect restoration) with margin designs including: A) butt joint, B) short chamfer (one mm), and C) long chamfer (two mm) and a control group (direct composite). Preparations were scanned; restorations were milled from zirconia-reinforced lithium-silicate blocks and cemented. Fracture load (N) and failure mode were analyzed. Techniques were timed from start of margin preparation through finishing. Results were analyzed using one-way analysis of variance or the Kruskal-Wallis test (significance level: P=0.05). Results: Fracture loads (mean±standard deviation) for groups A, B, and C and control group were 2,177±644 N, 2,183±507 N, 2,666±609 N, and 2,358±886 N, respectively (not significantly different; P=0.26). The direct composite was significantly different from all indirect groups (P<0.01) for failure mode. Chairside time was longer for direct restoration. Conclusions: Fracture strength is similar for directly and indirectly fabricated Class IV restorations, with margin design not affecting strength or failure mode. Practitioner's chairside time, but not total time, is reduced when using indirect methods.