A Framework for Outpatient Infusion of Antispike Monoclonal Antibodies to High-Risk Patients with Mild-to-Moderate Coronavirus Disease-19: The Mayo Clinic Model.

The administration of spike monoclonal antibody treatment to patients with mild to moderate COVID-19 is very challenging. This article summarizes essential components and processes in establishing an effective spike monoclonal antibody infusion program. Rapid identification of a dedicated physical infrastructure was essential to circumvent the logistical challenges of caring for infectious patients while maintaining compliance with regulations and ensuring the safety of our personnel and other patients. Our partnerships and collaborations among multiple different specialties and disciplines enabled contributions from personnel with specific expertise in medicine, nursing, pharmacy, infection prevention and control, electronic health record (EHR) informatics, compliance, legal, medical ethics, engineering, administration, and other critical areas. Clear communication and a culture in which all roles are welcomed at the planning and operational tables are critical to the rapid development and refinement needed to adapt and thrive in providing this time-sensitive beneficial therapy. Our partnerships with leaders and providers outside our institutions, including those who care for underserved populations, have promoted equity in the access of monoclonal antibodies in our regions. Strong support from institutional leadership facilitated expedited action when needed, from a physical, personnel, and system infrastructure standpoint. Our ongoing real-time assessment and monitoring of our clinical program allowed us to improve and optimize our processes to ensure that the needs of our patients with COVID-19 in the outpatient setting are met.

Feasibility Study of Vascularized Composite Urinary Bladder Allograft Transplantation in a Cadaver Model.

PURPOSE: The purpose of this study was to establish the feasibility of performing a urinary bladder vascularized composite allograft transplantation for either bladder augmentation or neobladder creation. MATERIALS AND METHODS: Six adult cadavers were studied. Cadavers were excluded for any previous pelvic surgery, radiation, vascular surgery or history of pelvic malignancy. An intravascular colored silicone and barium mixture was injected and both computerized tomography scans and gross dissections were performed. Contrast enhanced computerized tomography imaging was used to delineate urinary bladder vascular anatomy variability. Bladders were explanted en bloc from 2 cadavers with bilateral vascular pedicles based on the external iliac vessels and "transplanted" to replicate a bladder transplant. RESULTS: Contrast enhanced 3-D-computerized tomography reconstructions and cadaver dissections revealed distal vascular variability with proximal blood supply based primarily on the internal iliac artery. Urinary bladder vascularized composite allograft transplantation was successfully performed during 2 mock transplants with the vascular anastomosis done to the recipient external iliac artery and vein. CONCLUSIONS: Urinary bladder vascularized composite allograft transplantation is technically and anatomically feasible. This procedure may obviate the use of intestinal segments for bladder reconstruction in select patients. A phase 1 clinical trial is in progress.

Growth hormone deficiency in a child with branchio-oto-renal spectrum disorder: Clinical evidence of EYA1 in pituitary development and a recommendation for pituitary function surveillance.

Branchio-oto-renal spectrum disorder (BORSD) is a rare autosomal dominant condition characterized by ear abnormalities with hard of hearing/deafness, second branchial arch malformations and renal anomalies. Pathogenic variations in EYA1 gene are found in the majority of clinically diagnosed individuals with BORSD. We describe an infant with BORSD related to a paternally inherited heterozygous pathogenic variation in EYA1 gene presenting with poor growth and hypoglycemia due to growth hormone deficiency. Magnetic resonance imaging revealed a diminutive pituitary gland and morphologically abnormal sella. Upon initiation of growth hormone therapy, the hypoglycemia resolved and catch up growth ensued. Pituitary abnormalities have not been reported previously in patients with BORSD. The zebrafish ortholog of eya1 is important for the development of adenohypophysis, suggesting that this patient's growth hormone deficiency and pituitary abnormality are part of BORSD. Inclusion of screening for pituitary hormone deficiency and pituitary imaging should be considered as a part of surveillance in patients with BORSD.

Using a Modified CPD Blood Bag to Store Blood from either ECMO or RRT Circuit Blood in Pediatric Patients.

By adapting a citrate phosphate dextrose (CPD) whole blood storage bag, residual blood from a renal replacement therapy (RRT) circuit can be saved in pediatric patients, decreasing in donor exposure later. The techniques used for autologous preoperative blood storage are the basis of storing the RRT circuit blood. The CPD anticoagulant has a benefit of having a commonly used reversal agent for its anticoagulant properties, i.e., calcium. Also, unlike the traditional anticoagulants used in extracorporeal membrane oxygenation (ECMO), i.e., heparin, and direct thrombin inhibitors, i.e., bivalirudin, there is no increase in anticoagulation laboratory parameters after administration. The CPD volume in the bag is reduced but keeps the original ratio the same between CPD and blood. This is accomplished by removing all CPD from the bag, adding back only the exact amount of CPD needed for the smaller amount of blood being transferred from the circuit. The RRT circuit managed at our institution uses 23 mL of CPD for 165 mL of circuit blood when stored with this technique. This calculation assumes a normal patient calcium level. This technique has been used successfully multiple times in more than 30 pediatric patients without incident for 7 years at our center. The CPD bag can also be used to store the residual blood from ECMO circuits after removal of ECMO to allow the blood to be given back to the patient at a later time by keeping the same citrate-to-blood ratio.

Kidney transplant practice patterns and outcome benchmarks over 30 years: The 2018 report of the NAPRTCS.

The NAPRTCS has collected clinical information on children undergoing renal transplantation since 1987 and now includes information on 12 920 renal transplants in 11 870 patients. Since the first data analysis in 1989, NAPRTCS reports have documented marked improvements in patient and allograft outcomes after pediatric renal transplantation in addition to identifying factors associated with both favorable and poor outcomes. The registry has served to document and influence practice patterns, clinical outcomes, and changing trends in renal transplantation and also provides historical perspective. This report highlights current practices in an era of major changes in DD kidney allocation and continuing steroid minimization. This report presents outcomes of the patients in the NAPRTCS transplant registry up to end of 2017. In particular, an increase in the cumulative incidence of late first AR has occurred in the most recent cohort, while all prior cohorts had a lower cumulative incidence of late first AR.

Negative Staining for COL4A5 Correlates With Worse Prognosis and More Severe Ultrastructural Alterations in Males With Alport Syndrome.

INTRODUCTION: Alport syndrome (AS) is a genetic disorder characterized by progressive hematuric nephropathy with or without sensorineural hearing loss and ocular lesions. Previous studies on AS included mostly children. METHODS: To determine the prognostic value of loss of staining for collagen type IV alpha 5 (COL4A5) and its relationship with the ultrastructural glomerular basement membrane alterations, we performed direct immunofluorescence using a mixture of fluorescein isothiocyanate-conjugated and Texas-red conjugated antibodies against COL4A5 and COL4A2, respectively, on renal biopsies of 25 males with AS (including 16 who were diagnosed in adulthood). RESULTS: All patients showed normal positive staining of glomerular basement membranes and tubular basement membranes for COL4A2. Of the 25 patients, 10 (40%) patients showed loss of staining for COL4A5 (including 89% of children and 13% of adults) and the remaining 15 (60%) had intact staining for COL4A5. Compared with patients with intact staining for COL4A5, those with loss of staining had more prominent ultrastructural glomerular basement membrane alterations and were younger at the time of biopsy. By Kaplan-Meier survival analysis and Cox regression analysis, loss of staining for COL4A5 predicted earlier progression to overt proteinuria and stage 2 chronic kidney disease or worse. By multivariate Cox regression analysis, loss of staining for COL4A5 was an independent predictor of the development of overt proteinuria and stage 2 chronic kidney disease or worse. DISCUSSION: Thus, the COL4A5 expression pattern has an important prognostic value and it correlates with the severity of ultrastructural glomerular basement membrane alterations in males with AS. Loss of COL4A5 staining is uncommon in patients with AS diagnosed in their adulthood.

Charcoal hemoperfusion in the treatment of medically refractory pruritus in cholestatic liver disease.

BACKGROUND: Pruritus is a distressing symptom in a considerable proportion of cholestatic patients and a few of them do not respond to conventional treatment. Charcoal hemoperfusion (CH) is an extracorporeal technique that is effective in eliminating protein-bound substances which may have accumulated during cholestasis. Several case reports have shown significant reduction of bilirubin in mechanical jaundice and neonatal hemolytic jaundice. However, the published data of CH for the treatment of refractory pruritus in cholestatic patients are scarce. METHODS: Procedure code "Charcoal hemoperfusion" (90997) was used to identify patients who received CH at Mayo Clinic, Rochester, from 1 January 2000 to 5 January 2015. Patients who received CH for refractory cholestatic pruritus were retrospectively reviewed. RESULTS: Thirteen patients were identified. A median of 5 (range 1-18) sessions for a total of 20 (1-72) h were performed. CH resulted in a significant decrease of pruritus in nine patients (69%). Two patients did not have significant relief and two patients did not pursue further treatments after having adverse reactions during the first session. Median pruritus numerical rating scale significantly decreased from 9/10 (9-10) to 4/10 (0-9) post-treatment (p = 0.004). Duration of symptom-free periods ranged from 8 to 90 days (median 18 days) in six patients who returned for follow-up. Most common adverse reactions were pain, bleeding from the catheter site and fever. CONCLUSION: CH temporarily improves the severity of medically refractory cholestatic pruritus in some patients. However, the improvement is not sustained and the short duration of benefit should be balanced with the invasive nature of the therapy and the relatively common adverse reactions.

Thrombotic Microangiopathy Care Pathway: A Consensus Statement for the Mayo Clinic Complement Alternative Pathway-Thrombotic Microangiopathy (CAP-TMA) Disease-Oriented Group.

Thrombotic microangiopathies (TMAs) comprise a heterogeneous set of conditions linked by a common histopathologic finding of endothelial damage resulting in microvascular thromboses and potentially serious complications. The typical clinical presentation is microangiopathic hemolytic anemia accompanied by thrombocytopenia with varying degrees of organ ischemia. The differential diagnoses are generally broad, while the workup is frequently complex and can be confusing. This statement represents the joint recommendations from a multidisciplinary team of Mayo Clinic physicians specializing in the management of TMA. It comprises a series of evidence- and consensus-based clinical pathways developed to allow a uniform approach to the spectrum of care including when to suspect TMA, what differential diagnoses to consider, which diagnostic tests to order, and how to provide initial empiric therapy, as well as some guidance on subsequent management.

Discontinuation of dialysis with eculizumab therapy in a pediatric patient with dense deposit disease.

BACKGROUND: Dense deposit disease (DDD) is a rare glomerular disease caused by an uncontrolled activation of the alternative complement pathway leading to end-stage renal disease in 50 % of patients. As such, DDD has been classified within the spectrum of complement component 3 (C3) glomerulopathies due to its pathogenesis from alternative pathway dysregulation. Conventional immunosuppressive therapies have no proven effectiveness. Eculizumab, a terminal complement inhibitor, has been reported to mitigate disease in some cases. CASE-DIAGNOSIS/TREATMENT: We report on the efficacy of eculizumab in a pediatric patient who failed to respond to cyclophosphamide, corticosteroids, and plasma exchange. Complement biomarker profiling was remarkable for low serum C3, low properdin, and elevated soluble C5b-9. Consistent with these findings, the alternative pathway functional assay was abnormally low, indicative of alternative pathway activity, although neither C3-nephritic factors nor Factor H autoantibodies were detected. Eculizumab therapy was associated with significant improvement in proteinuria and renal function allowing discontinuation of hemodialysis (HD). Repeat C3 and soluble C5b-9 levels normalized, showing that terminal complement pathway activity was successfully blocked while the patient was receiving eculizumab therapy. Repeat testing for alternative pathway activation allowed for a successful decrease in eculizumab dosing. CONCLUSIONS: The case reported here demonstrates the successful recovery of renal function in a pediatric patient on HD following the use of eculizumab.

Defining and diagnosing burning mouth syndrome: Perceptions of directors of North American postgraduate oral medicine and orofacial pain programs.

BACKGROUND: The authors conducted a study to ascertain participants' perceptions of and confidence in their responses regarding the definition and diagnosis of burning mouth syndrome (BMS). METHODS: The authors developed an eight-question questionaire with input from several experienced clinicians in the fields of oral medicine (OM) and orofacial pain (OFP) and sent it to directors (n = 20; OM = 10; OFP = 10) of accredited postgraduate training programs in North America. They used descriptive statistics to analyze the results. RESULTS: The response rate was 65 percent (n = 13; OM = 6; OFP = 7). Participants reported a mean of 7.3 cases of BMS in any given three-month period, with 89 percent of these cases managed within the programs. They identified, with a high degree of confidence, overall criteria for establishing a definition and definitive diagnosis of BMS. CONCLUSIONS: There were multiple similarities among participants' responses regarding the elements to be included in the definition and diagnosis of BMS. PRACTICAL IMPLICATIONS: These data provide information on current status of definitions and diagnostic guidelines and may assist in development of future consensus statements on BMS that incorporate additional geographical representation and appropriate methodology.

Empiric switch from calcineurin inhibitor to sirolimus-based immunosuppression in pediatric heart transplantation recipients.

Sirolimus is used in heart transplant patients with CAV and CNI-induced nephropathy. However, little is known regarding the tolerability, rejection rate, and effect on renal function when used empirically in children. We describe our experience with the empiric use of a sirolimus-based immunosuppressive regimen in pediatric heart transplantation recipients. We reviewed records of patients in whom conversion was attempted to a CNI-free sirolimus-based regimen. Rejection episodes and measures of renal function were recorded. We attempted to convert 20 patients, of which 16 were successful. In total, six of 20 patients (30%) experienced adverse effects. Of the 16 converted, four patients converted to sirolimus due to CNI-induced disease (three nephropathy, one CAV), while 12 patients (mean age 5.5 yr, range 0.1-21 yr; 33% female; 33% with a history of congenital heart disease) were empirically switched to sirolimus at a mean of 2.3 yr after transplant. Follow-up was available for a mean of 2.5 yr after conversion (range 0.5-8.3 yr). The rate of rejection while taking CNIs was 0.18 rejection episodes per patient-year (total of five episodes), compared with 0.03 rejection episodes per patient-year (total of one episode) while on sirolimus. Renal function, in terms of GFR, significantly improved after sirolimus conversion at latest follow-up (from 86 ± 37 mL/min to 130 ± 49 mL/min, p = 0.02). Here, we demonstrate the potential benefit of empiric use of sirolimus in pediatric heart transplant patients in a CNI-free regimen. Larger and longer studies are needed to further clarify risks of rejection and adverse effect profiles.

Pseudohypoaldosteronism presenting with thrombocytosis and bilateral pneumothoraces in an infant.

Pseudohypoaldosteronism type 1 (PHA-1) is a rare salt-wasting syndrome caused by a peripheral resistance to aldosterone. Here, we describe an unusual presentation of the autosomal dominant PHA-1 featuring bilateral pneumothoraces at birth, thrombocytosis in infancy, and hypercalcemia in addition to the well-described findings of hyponatremia, hyperkalemia, and failure to thrive. These findings contribute to the limited case descriptions of PHA-1 and may suggest additional diagnostic considerations in a neonate presenting with hyperkalemia, hyponatremia, and failure to thrive.

Correlation of blood pressure readings from 6-hour intervals with the daytime period of 24-hour ambulatory blood pressure monitoring in pediatric patients.

Shorter-interval (6-hour) ambulatory blood pressure monitoring (ABPM) has been shown to correlate well with 24-hour ABPM in adults, but this has not been studied in children. The authors selected 131 patients aged 9 to 18 who underwent 24-ABPM from 2000-2008. Six-hour intervals beginning at different start times were compared with the daytime and 24-hour period, with subset analysis for normotensive and hypertensive patients. Concordance correlation coefficients (CCCs) were used to assess for agreement. Among normotensive patients, the mean difference between daytime and 6-hour intervals ranged from -0.1 mm Hg to 0.0 mm Hg for diastolic blood pressure (DBP) and -1.1 mm Hg to 0.6 mm Hg for systolic blood pressure (SBP) with CCCs of 0.88 to 0.93 for DBP and 0.93 to 0.96 for SBP. For hypertensive patients, mean difference ranged from -0.6 to 1.3 mm Hg for DBP and -0.8 to 1.1 mm Hg for SBP with CCCs of 0.89 to 0.98 for DBP and 0.86 to 0.95 for SBP. Shorter-interval monitoring correlates significantly with full daytime monitoring in children, allowing for assessment of blood pressure with improved convenience.

Proliferative glomerulonephritis secondary to dysfunction of the alternative pathway of complement.

BACKGROUND AND OBJECTIVES: dense deposit disease (DDD) is the prototypical membranoproliferative glomerulonephritis (MPGN), in which fluid-phase dysregulation of the alternative pathway (AP) of complement results in the accumulation of complement debris in the glomeruli, often producing an MPGN pattern of injury in the absence of immune complexes. A recently described entity referred to as GN with C3 deposition (GN-C3) bears many similarities to DDD. The purpose of this study was to evaluate AP function in cases of GN-C3. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Five recent cases of MPGN with extensive C3 deposition were studied. Renal biopsy in one case exhibited the classic findings of DDD. Three cases showed GN-C3 in the absence of significant Ig deposition; however, the classic hallmark of DDD-dense deposits along the glomerular basement membranes and mesangium-was absent. The remaining case exhibited features of both DDD and GN-C3. RESULTS: Evidence of AP activation was demonstrable in all cases and included increased levels of soluble membrane attack complex (all cases), positive AP functional assays (four cases), and a positive hemolytic assay (one case). Autoantibodies were found to C3 convertase (two cases) and to factor H (one case). Factor H mutation screening identified the H402 allele (all cases) and a c.C2867T p.T956M missence mutation (one case). Laser microdissection and mass spectrometry of glomeruli of GN-C3 (two cases) showed a proteomic profile very similar to DDD. CONCLUSIONS: These studies implicate AP dysregulation in a spectrum of rare renal diseases that includes GN-C3 and DDD.

Nurturing social responsibility through community service-learning: Lessons learned from a pilot project.

BACKGROUND: Community service-learning (CSL) has been proposed as one way to enrich medical and dental students' sense of social responsibility toward people who are marginalized in society. AIM: We developed and implemented a new CSL option in the integrated medical/dental curriculum and assessed its educational impact. METHODS: Focus groups, individual open-ended interviews, and a survey were used to assess dental students', faculty tutors' and community partners' experiences with CSL. RESULTS: CSL enabled a deeper appreciation for the vulnerabilities that people who are marginalized experience; students gained a greater insight into the social determinants of health and the related importance of community engagement; and they developed useful skills in health promotion project planning, implementation and evaluation. Community partners and faculty tutors indicated that equal partnership, greater collaboration, and a participatory approach to course development are essential to sustainability in CSL. CONCLUSIONS: CSL can play an important role in nurturing a purposeful sense of social responsibility among future practitioners. Our study enabled the implementation of an innovative longitudinal course (professionalism and community service) in all 4 years of the dental curriculum.

The Delphi process in dental research.

OBJECTIVE: To explore how Delphi formal consensus procedures may augment decision making in oral health care in the absence of high-quality clinical and epidemiological data. METHODS: A review and appraisal of the literature regarding the Delphi method was conducted using Medline databases and Google. RESULTS: The Delphi method has a long history that highlights both its strengths and limitations. Delphi uses a series of anonymous questionnaires designed to develop a consensus of opinion and can provide guidance on topics that have not or cannot be studied in randomized controlled trials. The Delphi technique has been used to achieve consensus of opinion on a variety of issues including those related to oral health. Guidelines for the use of Delphi are presented. CONCLUSION: Like any other research methodology, the process guidelines need to be systematic and comprehensive. Delphi expert opinion consensus may improve decision making in a wide variety of oral health circumstances.