Antibody-mediated rejection in pediatric kidney transplant recipients: A report from the Pediatric Nephrology Research Consortium.

BACKGROUND: Antibody-mediated rejection (AMR) is a major cause of kidney allograft loss. There is a paucity of large-scale pediatric-specific data regarding AMR treatment outcomes. METHODS: Data were obtained from 14 centers within the Pediatric Nephrology Research Consortium. Kidney transplant recipients aged 1-18 years at transplant with biopsy-proven AMR between 2009 and 2019 and at least 12 months of follow-up were included. The primary outcome was graft failure or an eGFR <20 mL/min/1.73 m2 at 12 months following AMR treatment. AMR treatment choice, histopathology, and DSA class were also examined. RESULTS: We reviewed 123 AMR episodes. Median age at diagnosis was 15 years at a median 22 months post-transplant. The primary outcome developed in 27.6%. eGFR <30 m/min/1.73 m2 at AMR diagnosis was associated with a 5.6-fold higher risk of reaching the composite outcome. There were no significant differences in outcome by treatment modality. Histopathology scores and DSA class at time of AMR diagnosis were not significantly associated with the primary outcome. CONCLUSIONS: In this large cohort of pediatric kidney transplant recipients with AMR, nearly one-third of patients experienced graft failure or significant graft dysfunction within 12 months of diagnosis. Poor graft function at time of diagnosis was associated with higher odds of graft failure.

Successful use of eculizumab in immediate ANCA vasculitis recurrence in a pediatric kidney transplant.

BACKGROUND: Kidney transplantation is an acceptable therapy end-stage kidney disease secondary to antineutrophil cytoplasmic antibody-associated vasculitis with risk of disease recurrence ranging from 3% to 17%. Standard posttransplant immunosuppression is the mainstay of therapy after recurrence. Recently, new medications focused on complement regulation and avoidance of steroids have been shown to be effective in treating antineutrophil cytoplasmic antibody (ANCA) vasculitis with no studies in the pediatric population. METHODS: We report a 5-year-old patient with immediate recurrence of positive myeloperoxidase (MPO)-ANCA vasculitis after deceased donor kidney transplant and the novel use of eculizumab to salvage the graft. RESULTS: Eculizumab and transition to ravulizumab has been successful in improving graft function and maintenance of disease remission after immediate MPO-ANCA vasculitis recurrence posttransplant. CONCLUSIONS: Complement inhibitors may be used in addition to standard immunosuppression postkidney transplant in a pediatric patient with MPO-ANCA vasculitis recurrence without higher rates of infections.

Continuous allocation: The problem with EPTS and pediatric kidney candidates.

BACKGROUND: The 2014 Kidney Allocation System (KAS) introduced longevity matching for adult candidates using the Estimated Post-Transplant Survival (EPTS) score, which includes candidate age, time on dialysis, diabetes status, and number of previous solid organ transplants. The proposed continuous distribution framework may expand the use of this attribute to pediatric candidates, but there is no data on its performance among pediatric kidney transplant recipients. METHODS: We performed a retrospective cohort study of 6800 pediatric kidney transplant recipients from 2001 to 2011 using Organ Procurement and Transplantation Network (OPTN) data. EPTS score was calculated for each patient and compared to reported patient survival to estimate the validity of the score in children. RESULTS: The median age of patients was 14.01 years (IQR 9.29-16.37 years), and dialysis vintage was 0.67 years (IQR 0-1.82 years). 18.2% of the cohort had a prior transplant and 1% had diabetes. Median EPTS score was 2 (IQR 1-2). Seven percent of patients died during the study period and 54.7% of the cohort was censored prior to 10 years. The c-statistic was 0.505 (95% CI: 0.49-0.53). CONCLUSION: Overall, EPTS is not a valid predictor of patient survival among pediatric kidney transplant recipients.

COVID-19 in pediatric kidney transplantation: a follow-up report of the Improving Renal Outcomes Collaborative.

BACKGROUND: We report follow-up data from an ongoing prospective cohort study of COVID-19 in pediatric kidney transplantation through the Improving Renal Outcomes Collaborative (IROC). METHODS: Patient-level data from the IROC registry were combined with testing, indication, and outcomes data collected to describe the epidemiology of COVID testing, treatment, and clinical outcomes; determine the incidence of a positive COVID-19 test; describe rates of COVID-19 testing; and assess for clinical predictors of a positive COVID-19 test. RESULTS: From September 2020 to February 2021, 21 centers that care for 2690 patients submitted data from 648 COVID-19 tests on 465 patients. Most patients required supportive care only and were treated as outpatients, 16% experienced inpatient care, and 5% experienced intensive care. Allograft complications were rare, with acute kidney injury most common (7%). There was 1 case of respiratory failure and 1 death attributed to COVID-19. Twelve centers that care for 1730 patients submitted complete testing data on 351 patients. The incidence of COVID-19 among patients at these centers was 4%, whereas the incidence among tested patients was 19%. Risk factors to predict a positive COVID-19 test included age > 12 years, symptoms consistent with COVID-19, and close contact with a confirmed case of COVID-19. CONCLUSIONS: Despite the increase in testing and positive tests over this study period, the incidence of allograft loss or death related to COVID-19 remained extremely low, with allograft loss or death each occurring in < 1% of COVID-19-positive patients and in less than < 0.1% of all transplant patients within the IROC cohort. A higher resolution version of the Graphical abstract is available as Supplementary information.

Acceptability of an mHealth Family Self-management Intervention (myFAMI) for Pediatric Transplantation Families: Qualitative Focus.

BACKGROUND: Around 1800 pediatric transplantations were performed in 2021, which is approximately 5% of the annual rate of solid organ transplantations carried out in the United States. Effective family self-management in the transition from hospital to home-based recovery promotes successful outcomes of transplantation. The use of mHealth to deliver self-management interventions is a strategy that can be used to support family self-management for transplantation recipients and their families. OBJECTIVE: The study aims to evaluate the acceptability of an mHealth intervention (myFAMI) that combined use of a smartphone app with triggered nurse communication with family members of pediatric transplantation recipients. METHODS: This is a secondary analysis of qualitative data from family members who received the myFAMI intervention within a larger randomized controlled trial. Eligible participants used the app in the 30-day time frame after discharge and participated in a 30-day postdischarge telephone interview. Content analysis was used to generate themes. RESULTS: A total of 4 key themes were identified: (1) general acceptance, (2) positive interactions, (3) home management after hospital discharge, and (4) opportunities for improvement. CONCLUSIONS: Acceptability of the intervention was high. Family members rated the smartphone application as easy to use. myFAMI allowed the opportunity for families to feel connected to and engage with the medical team while in their home environment. Family members valued and appreciated ongoing support and education specifically in this first 30 days after their child's hospital discharge and many felt it contributed positively to the management of their child's medical needs at home. Family members provided recommendations for future refinement of the app and some suggested that a longer follow-up period would be beneficial. The development and refinement of mHealth care delivery strategies hold potential for improving outcomes for solid organ transplantation patients and their families and as a model to consider in other chronic illness populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT03533049; https://clinicaltrials.gov/ct2/show/NCT03533049.

Lack of renoprotective effects of targeting the endothelin A receptor and (or) sodium glucose transporter 2 in a mouse model of Type 2 diabetic kidney disease.

Two recent clinical trials, using sodium glucose cotransporter (SGLT2) or endothelin-A receptor (ET-A) blocker, reported the first efficacious treatments in 18 years to slow progression of diabetic kidney disease (DKD). We hypothesized that combined inhibition of SGLT2 and ET-A receptor may confer greater protection against renal injury than either agent alone. Uninephrectomized male db/db mice were randomized to four groups: vehicle, SGLT2 inhibitor (dapagliflozin (dapa), 1 mg/kg/day), ET-A blocker (atrasentan (atra), 5 mg/kg/day), or dual treatment from 10 weeks until 22 weeks of age. At 10 weeks of age, no differences were observed in body weight, blood glucose or urinary albumin excretion among the four groups. At 16 and 22 weeks of age, body weight was lower and blood glucose levels higher in the vehicle and atra groups compared with dapa- and dual-treated groups. No notable differences were observed among the four groups in urinary albumin excretion at weeks 16 and 22. Histological analysis showed mild glomerulosclerosis and tubular injury (<5%) in all four groups with reduced glomerulosclerosis in the dual treatment group compared with vehicle. Individual or combined treatment with an SGLT2 inhibitor and (or) an ET-A antagonist did not confer renoprotective effects in this model.

Feasibility and Acceptability of a mHealth Self-Management Intervention for Pediatric Transplant Families.

Families of pediatric solid organ transplant recipients need ongoing education and support in the first 30 days following hospital discharge for the transplantation. The purpose of this report is to describe the feasibility, acceptability, and preliminary efficacy of a mHealth family-self management intervention, (myFAMI), designed to improve post-discharge outcomes of coping, family quality of life, self-efficacy, family self-management, and utilization of health care resources. We enrolled 46 primary family members. myFAMI was feasible and acceptable; 81% (n=17/21) of family members completed the app at least 24/30 days (goal 80% completion rate). Family members generated 134 trigger alerts and received a nurse response within the goal timeframe of < 2 h 99% of the time. Although there were no significant differences between groups, primary outcomes were in the expected direction. The intervention was well received and is feasible for future post-discharge interventions for families of children who receive an organ transplant.

Winter Wheat (Triticum aestivum L.) Tolerance to Mulch.

Mulch from cover crops can effectively suppress weeds in organic corn (Zea mays L.) and soybean (Glycine max L.) as part of cover crop-based rotational no-till systems, but little is known about the feasibility of using mulch to suppress weeds in organic winter small grain crops. A field experiment was conducted in central NY, USA, to quantify winter wheat (Triticum aestivum L.) seedling emergence, weed and crop biomass production, and wheat grain yield across a gradient of mulch biomass. Winter wheat seedling density showed an asymptotic relationship with mulch biomass, with no effect at low rates and a gradual decrease from moderate to high rates of mulch. Selective suppression of weed biomass but not wheat biomass was observed, and wheat grain yield was not reduced at the highest level of mulch (9000 kg ha-1). Results indicate that organic winter wheat can be no-till planted in systems that use mulch for weed suppression. Future research should explore wheat tolerance to mulch under different conditions, and the potential of no-till planting wheat directly into rolled-crimped cover crops.

Loss of Soluble (Pro)renin Receptor Attenuates Angiotensin-II Induced Hypertension and Renal Injury.

[Figure: see text].

Commercial integrated crop-livestock systems achieve comparable crop yields to specialized production systems: A meta-analysis.

Production systems that feature temporal and spatial integration of crop and livestock enterprises, also known as integrated crop-livestock systems (ICLS), have the potential to intensify production on cultivated lands and foster resilience to the effects of climate change without proportional increases in environmental impacts. Yet, crop production outcomes following livestock grazing across environments and management scenarios remain uncertain and a potential barrier to adoption, as producers worry about the effects of livestock activity on the agronomic quality of their land. To determine likely production outcomes across ICLS and to identify the most important moderating variables governing those outcomes, we performed a meta-analysis of 66 studies comparing crop yields in ICLS to yields in unintegrated controls across 3 continents, 12 crops, and 4 livestock species. We found that annual cash crops in ICLS averaged similar yields (-7% to +2%) to crops in comparable unintegrated systems. The exception was dual-purpose crops (crops managed simultaneously for grazing and grain production), which yielded 20% less on average than single-purpose crops in the studies examined. When dual-purpose cropping systems were excluded from the analysis, crops in ICLS yielded more than in unintegrated systems in loamy soils and achieved equal yields in most other settings, suggesting that areas of intermediate soil texture may represent a "sweet-spot" for ICLS implementation. This meta-analysis represents the first quantitative synthesis of the crop production outcomes of ICLS and demonstrates the need for further investigation into the conditions and management scenarios under which ICLS can be successfully implemented.

Yields and resilience outcomes of organic, cover crop, and conventional practices in a Mediterranean climate.

Adaptive management practices that maximize yields while improving yield resilience are required in the face of resource variability and climate change. Ecological intensification such as organic farming and cover cropping are lauded in some studies for fostering yield resilience, but subject to criticism in others for their low productivity. We implemented a quantitative framework to assess yield resilience, emphasizing four aspects of yield dynamics: yield, yield stability, yield resistance (i.e., the ability of systems to avoid crop failure under stressful growing conditions), and maximum yield potential. We compared the resilience of maize-tomato rotation systems after 24 years of irrigated organic, cover cropped, and conventional management in a Mediterranean climate, and identified crop-specific resilience responses of tomato and maize to three management systems. Organic management maintained tomato yields comparable to those under conventional management, while increasing yield stability and resistance. However, organic and cover cropped system resulted in 36.1% and 35.8% lower maize yields and reduced yield stability and resistance than the conventional system. Our analyses suggest that investments in ecological intensification approaches could potentially contribute to long-term yield resilience, however, these approaches need to be tailored for individual crops and systems to maximize their benefits, rather than employing one-size-fits-all approaches.

Cost-Utility of Antimicrobial Prophylaxis for Treatment of Children With Vesicoureteral Reflux.

Objective: Antimicrobial prophylaxis for children with vesicoureteral reflux (VUR) reduces recurrences of urinary tract infection (UTI) but requires daily antimicrobials for extended periods. We used a cost-utility model to evaluate whether the benefits of antimicrobial prophylaxis outweigh its risks and, if so, to investigate whether the benefits and risks vary according to grade of VUR. Methods: We compared the cost per quality-adjusted life-year (QALY) gained in four treatment strategies in children aged <6 years diagnosed with VUR after a first UTI, considering these treatment strategies: (1) prophylaxis for all children with VUR, (2) prophylaxis for children with Grade III or Grade IV VUR, (3) prophylaxis for children with Grade IV VUR, and (4) no prophylaxis. Costs and effectiveness were estimated over the patient's lifetime. We used $100,000/QALY gained as the threshold for considering a treatment strategy cost effective. Results: Based on current data and plausible ranges to account for data uncertainty, prophylaxis of children with Grades IV VUR costs $37,903 per QALY gained. Treating children with Grade III and IV VUR costs an additional $302,024 per QALY gained. Treating children with all grades of VUR costs an additional $339,740 per QALY gained. Conclusions: Treating children with Grades I, II, and III VUR with long-term antimicrobial prophylaxis costs substantially more than interventions typically considered economically reasonable. Prophylaxis in children with Grade IV VUR is cost effective.

Animal production and soil characteristics from integrated crop-livestock systems: toward sustainable intensification.

Sustainable intensification of land-use practices has never been more important to ensure food security for a growing world population. When combined under thoughtful management, cover cropping and crop-livestock integration under no-till systems can benefit from unexpected synergies due to their unique features of plant-animal diversification and complex agroecosystem functions. Mimicking the nutrient coupling/decoupling processes of natural ecosystems by diversifying plant and animal components of no-till integrated crop-livestock operations is an essential feature of the design of agroecological systems that support self-regulating feedbacks and lend resilience while increasing productivity and ecosystem service provision. Focusing on grazing animals as drivers of agroecosystem change, we highlight the benefits of grazed cover crops in rotation with cash crops for primary and secondary production and for soil physical, chemical, and biological parameters. However, careful management of grazing intensity is imperative; overgrazing drives soil deterioration, while light to moderate grazing enhances overall system functioning and allows for the generation of emergent properties.

Academic-Related Factors and Emotional Eating in Adolescents.

BACKGROUND: Existing literature indicates a relationship between stress and emotional eating in adults, yet limited research has examined the impact of school-related stress on emotional eating in adolescents. This study investigated the influence of academic factors on emotional eating among minority adolescents. METHODS: A survey was implemented among a sample of minority adolescents (N = 666) to investigate the relationship between emotional eating and 3 academic factors: academic self-esteem, grade point average (GPA), and academic worries. Forced-entry multiple linear regressions were used to test for relationships. RESULTS: Findings indicate that GPA, academic self-esteem, and academic worries were related to emotional eating scores in adolescents. There were no significant differences in academic factors between emotional eaters and nonemotional eaters. CONCLUSIONS: Additional research is needed to further elucidate the complex interaction between emotional eating behavior and academics.

Experiences of recovery in binge-eating disorder: a qualitative approach using online message boards.

PURPOSE: In this study, qualitative methods were employed to analyze secondary data from the anonymous postings of a pro-recovery website in an effort to investigate the changes in thinking of binge-eating disorder (BED) sufferers who were able to recover from the disorder, understand more fully how guilt and self-blame affect recovery, and explore the perceived motivators and challenges to recovery. METHOD: 681 messages from 65 participants pertaining to BED were analyzed from January 1, 2014-January 1, 2015 through thematic analysis. Coding strategies were employed to reveal patterns within the experiences of the participants. RESULTS: The researchers identified three themes surrounding "changes in thinking" from analysis of the message board postings: admitting the disorder, recognizing unhealthy coping behaviors, and seeing recovery. Further analysis of postings suggested that guilt and self-blame hinder recovery by promoting a feedback cycle of binging, which leads to further guilt and self-blame. The data ultimately identified experiences that resulted in or hindered recovery. The experience of validation appeared to result in recovery; those who experienced validation were less inclined to engage in disordered eating behaviors. Conversely, weight loss or attempts at weight loss hindered recovery by ultimately promoting more disordered eating behaviors. CONCLUSION: This qualitative analysis of message board postings offers authentic, credible data with a unique perspective. Practitioners working in the field of eating disorders such as registered dietitian nutritionists or therapists might use evidence from the data to guide their practice.

The Use of Ambulatory Blood Pressure Monitoring As Standard of Care in Pediatrics.

Hypertension (HTN) is a significant global health problem, responsible for 7.5 million deaths each year worldwide. The prevalence of HTN is increasing in the pediatric population likely attributed to the increase in childhood obesity. Recent work has also shown that blood pressure (BP) tends to track from childhood to adulthood including BP-related target organ damage. In the last 25-30 years, pediatric use of ambulatory blood pressure monitoring (ABPM) has been expanding mainly in the setting of initial elevated BP measurement evaluation, HTN therapy efficacy follow-up, and renal disease. However, there are many clinical areas where ABPM could potentially be used but is currently underutilized. This review summarizes the current knowledge and the uses of pediatric ABPM and explores clinical areas where it can be very useful both to detect HTN and its longitudinal follow-up. And thus, ABPM could serve as a critical tool to potentially prevent early cardiovascular mortality and morbidity in wide variety of populations. With solid data to support ABPM's superiority over clinic BP measurements and these clinical areas for its expansion, ABPM should now be part of standard of care in BP evaluation and management in pediatrics.

Tethering the Extensor Apparatus Limits PIP Flexion Following K-wire Placement for Pinning Extra-articular Fractures at the Base of the Proximal Phalanx.

Background: Closed reduction with percutaneous Kirschner wires (K-wires) is the most minimally invasive surgical option for stabilizing phalanx fractures. This study examines the effect of K-wire placement on proximal interphalangeal (PIP) joint motion. Methods: PIP joint flexion was measured in the digits of 4 fresh-frozen cadaver hands after placing a suture loop through the flexor tendons and placing tension on the flexors via a mechanical scale. The load necessary to flex the PIP joint to 90° or to maximum flexion was recorded. The load was removed and K-wires were inserted in 3 locations about the metacarpophalangeal joint (MPJ): through the extensor tendon and across the MPJ, adjacent to the extensor tendon insertion site and across the MPJ, and through the sagittal band and into the base of the proximal phalanx (P1). The load on the tendons was reapplied, and angles of PIP joint flexion were recorded for each of the 3 conditions. Results: The mean angle of PIP joint flexion prior to K-wire insertion was 87°, and the mean load applied was 241 g. The angles of flexion were 53° when the K-wire was placed through the extensor tendon, 70° when the K-wire was placed adjacent to the tendon, and 75° when the K-wire was placed into the base of P1 by going through the sagittal band, midway between the volar plate and the extensor tendon. Conclusions: K-wires placed remote from the extensor tendon create less of an immediate tether to PIP joint flexion than those placed through or adjacent to the extensor tendon.

Clinal variation in stomatal characteristics of an Arctic sedge, Eriophorum vaginatum (Cyperaceae).

PREMISE OF THE STUDY: In a large reciprocal transplant experiment, Eriophorum vaginatum tussocks transplanted along a latitudinal gradient in Alaska's interior exhibited genetic differentiation and phenotypic plasticity for vegetative traits. Using the same tussocks 30 yr later, we used estimates of growing season temperature at each site to ask whether there was a climatic cline for stomatal density, size, and conductance. METHODS: We created impressions of the abaxial leaf surfaces of the transplanted individuals for viewing under a microscope and measured stomatal density (SD) and length (SL) for 224 individuals. We used SD and SL to estimate stomatal conductance (C). Separate one-way analyses of variance were performed to quantify the effect of population genetic differences and latitudinal environmental variation on stomatal characteristics. KEY RESULTS: Our data suggest that stomatal size was influenced by both genetics and environment and that plasticity for stomatal density produced highest densities at the coolest sites. Stomatal conductance increased with decreasing temperature of site from which the populations originated. CONCLUSIONS: Our results demonstrate a cline in stomatal conductance in E. vaginatum, with some ability of populations to plastically produce an appropriate phenotypic response in a new environment. Because the species is a dominant species in many arctic plant communities, its ability to produce an appropriate stomatal phenotype and to optimize water use efficiency by decreasing stomatal conductance in warmer environments could affect both community composition and total primary productivity in future, warmer climates.