Browsing by Subject "pediatrics"
Now showing 1 - 10 of 10
Results Per Page
Sort Options
Item Open Access An age-independent gene signature for monitoring acute rejection in kidney transplantation.(Theranostics, 2020-01) Shaw, Brian I; Cheng, Daniel K; Acharya, Chaitanya R; Ettenger, Robert B; Lyerly, Herbert Kim; Cheng, Qing; Kirk, Allan D; Chambers, Eileen TAcute rejection (AR) remains a significant problem that negatively impacts long-term renal allograft survival. Numerous therapies are used to prevent AR that differ by center and recipient age. This variability confounds diagnostic methods. Methods: To develop an age-independent gene signature for AR effective across a broad array of immunosuppressive regimens, we compiled kidney transplant biopsy (n=1091) and peripheral blood (n=392) gene expression profiles from 12 independent public datasets. After removing genes differentially expressed in pediatric and adult patients, we compared gene expression profiles from biopsy and peripheral blood samples of patients with AR to those who were stable (STA), using Mann-Whitney U Tests with validation in independent testing datasets. We confirmed this signature in pediatric and adult patients (42 AR and 47 STA) from our institutional biorepository. Results: We identified a novel age-independent gene network that identified AR from both kidney and blood samples. We developed a 90-probe set signature targeting 76 genes that differentiated AR from STA and found an 8 gene subset (DIP2C, ENOSF1, FBXO21, KCTD6, PDXDC1, REXO2, HLA-E, and RAB31) that was associated with AR. Conclusion: We used publicly available datasets to create a gene signature of AR that identified AR irrespective of immunosuppression regimen or recipient age. This study highlights a novel model to screen and validate biomarkers across multiple treatment regimens.Item Open Access Association of Wolff-Parkinson-White With Left Ventricular Noncompaction Cardiomyopathy in Children.(Journal of cardiac failure, 2019-12) Howard, Taylor S; Valdes, Santiago O; Hope, Kyle D; Morris, Shaine A; Landstrom, Andrew P; Schneider, Andrew E; Miyake, Christina Y; Denfield, Susan W; Pignatelli, Ricardo H; Wang, Yunfei; Kim, Jeffrey JBACKGROUND:Wolff-Parkinson-White (WPW) has been associated with left ventricular noncompaction (LVNC) in children. Little is known about the prevalence of this association, clinical outcomes, and treatment options. METHODS:Retrospective review of subjects with LVNC. LVNC was defined by established criteria; those with congenital heart disease were excluded. Electrocardiograms (ECGs) were reviewed for presence of pre-excitation. Outcomes were compared between those with isolated LVNC and those with WPW and LVNC. RESULTS:A total of 348 patients with LVNC were identified. Thirty-eight (11%) were found to have WPW pattern on ECG, and 84% of those with WPW and LVNC had cardiac dysfunction. In Kaplan-Meier analysis, there was significantly lower freedom from significant dysfunction (ejection fraction ≤ 40%) among those with WPW and LVNC (P < .001). Further analysis showed a higher risk of developing significant dysfunction in patients with WPW and LVNC versus LVNC alone (hazard ratio 4.64 [2.79, 9.90]). Twelve patients underwent an ablation procedure with an acute success rate of 83%. Four patients with cardiac dysfunction were successfully ablated, 3 having improvement in function. CONCLUSION:WPW is common among children with LVNC and is associated with cardiac dysfunction. Ablation therapy can be safely and effectively performed and may result in improvement in function.Item Open Access Borrowing from Adult Cardiac Surgeons-Bringing Congenital Heart Surgery Up to Speed in the Minimally Invasive Era.(Innovations (Philadelphia, Pa.), 2020-03) Alsarraj, Mohammed K; Nellis, Joseph R; Vekstein, Andrew M; Andersen, Nicholas D; Turek, Joseph WThe majority of congenital and adult cardiac surgery is performed through a median sternotomy. For surgeons, this incision provides excellent exposure; however, for patients, a median sternotomy confers a poorer cosmetic outcome and the possibility of postoperative respiratory dysfunction, chronic pain, and deep sternal wound infections. Despite the advances in adult cardiac surgery, the use of minimally invasive techniques in pediatric patients is largely limited to small case series and less complex repairs. In this article, we review the risks, benefits, and limitations of the minimally invasive congenital cardiac approaches being performed today. The interest in these approaches continues to grow as more data supporting reduced morbidity, decreased length of stay, and faster recovery are published. In the future, as the technology and surgical familiarity improve, these alternative approaches will become more common, and may someday become the standard of care.Item Open Access Household Food Insufficiency and Chronic Pain among Children in the US: A National Study.(Children (Basel, Switzerland), 2023-01) Tham, See Wan; Law, Emily F; Palermo, Tonya M; Kapos, Flavia P; Mendoza, Jason A; Groenewald, Cornelius BThis study aimed to determine the prevalence of pediatric chronic pain by household food sufficiency status and examine whether food insufficiency would be associated with greater risk for chronic pain. We analyzed data from the 2019-2020 National Survey of Children's Health of 48,410 children (6-17 years) in the United States. Across the sample, 26.1% (95% CI: 25.2-27.0) experienced mild food insufficiency and 5.1% (95% CI: 4.6-5.7) moderate/severe food insufficiency. The prevalence of chronic pain was higher among children with mild (13.7%) and moderate/severe food insufficiency (20.6%) relative to children in food-sufficient households (6.7%, p < 0.001). After adjusting for a priori covariates (individual: age, sex, race/ethnicity, anxiety, depression, other health conditions, adverse childhood events; household: poverty, parent education, physical and mental health; community: region of residence), multivariable logistic regression revealed that children with mild food insufficiency had 1.6 times greater odds of having chronic pain (95% CI: 1.4-1.9, p < 0.0001) and those with moderate/severe food insufficiency, 1.9 higher odds (95% CI: 1.4-2.7, p < 0.0001) relative to food-sufficient children. The dose-response relationship between food insufficiency and childhood chronic pain highlights the importance of further research to identify underlying mechanisms and evaluate the impact of food insufficiency on the onset and persistence of chronic pain across the lifespan.Item Open Access Management of Severe Traumatic Brain Injury in Pediatric Patients.(Frontiers in toxicology, 2022-01) Lui, Austin; Kumar, Kevin K; Grant, Gerald AThe optimal management of severe traumatic brain injury (TBI) in the pediatric population has not been well studied. There are a limited number of research articles studying the management of TBI in children. Given the prevalence of severe TBI in the pediatric population, it is crucial to develop a reference TBI management plan for this vulnerable population. In this review, we seek to delineate the differences between severe TBI management in adults and children. Additionally, we also discuss the known molecular pathogenesis of TBI. A better understanding of the pathophysiology of TBI will inform clinical management and development of therapeutics. Finally, we propose a clinical algorithm for the management and treatment of severe TBI in children using published data.Item Open Access Parental Preferences for Vesicoureteral Reflux Treatment: a Crowd-sourced, Best-worst Scaling Study.(Urology, 2019-03-13) Dionise, Zachary R; Gonzalez, Juan Marcos; Garcia-Roig, Michael L; Kirsch, Andrew J; Scales, Charles D; Wiener, John S; Purves, J Todd; Routh, Jonathan COBJECTIVE:To quantitatively evaluate parental preferences for the various treatments for vesicoureteral reflux using crowd-sourced best-worst scaling, a novel technique in urologic preference estimation. METHODS:Preference data were collected from a community sample of parents via two best-worst scaling survey instruments published to Amazon's Mechanical Turk online community. Attributes and attribute levels were selected following extensive review of the reflux literature. Respondents completed an object case best-worst scaling exercise to prioritize general aspects of reflux treatments and multi-profile case best-worst scaling to elicit their preferences for the specific differences in reflux treatments. Data were analyzed using multinomial logistic regression. Results from the object-case provided probability scaled values (PSV) that reflected the order of importance of attributes. RESULTS:We analyzed data for 248 and 228 respondents for object and multi-profile case BWS, respectively. When prioritizing general aspects of reflux treatment, effectiveness (PSV=20.37), risk of future urinary tract infection (PSV=14.85) and complication rate (PSV=14.55) were most important to parents. Societal cost (PSV=1.41), length of hospitalization (PSV=1.09), and cosmesis (PSV=0.91) were least important. Parents perceived no difference in preference for the cosmetic outcome of open versus minimally invasive surgery (p=0.791). Bundling attribute preference weights, parents in our study would choose open surgery 74.9% of the time. CONCLUSIONS:High treatment effectiveness was the most important and preferred attribute to parents. Alternatively, cost and cosmesis were among the least important. Our findings serve to inform shared parent-physician decision-making for vesicoureteral reflux.Item Open Access Pharmacokinetics Alterations in Critically Ill Pediatric Patients on Extracorporeal Membrane Oxygenation: A Systematic Review.(Frontiers in pediatrics, 2020-01) Sutiman, Natalia; Koh, Janine Cynthia; Watt, Kevin; Hornik, Christoph; Murphy, Beverly; Chan, Yoke Hwee; Lee, Jan HauObjectives: This study aimed to identify alterations in pharmacokinetics in children on extracorporeal membrane oxygenation (ECMO), identify knowledge gaps, and inform future pharmacology studies. Data Sources: We systematically searched the databases MEDLINE, CINAHL, and Embase from earliest publication until November 2018 using a controlled vocabulary and keywords related to "ECMO" and "pharmacokinetics," "pharmacology," "drug disposition," "dosing," and "pediatrics." Study Selection: Inclusion criteria were as follows: study population aged <18 years, supported on ECMO for any indications, received any medications while on ECMO, and reported pharmacokinetic data. Data Extraction: Clearance and/or volume of distribution values were extracted from included studies. Data Synthesis: Forty-one studies (total patients = 574) evaluating 23 drugs met the inclusion criteria. The most common drugs studied were antimicrobials (n = 13) and anticonvulsants (n = 3). Twenty-eight studies (68%) were conducted in children <1 year of age. Thirty-three studies (80%) were conducted without intra-study comparisons to non-ECMO controls. Increase in volume of distribution attributable to ECMO was demonstrated for nine (56%) drugs: cefotaxime, gentamicin, piperacillin/tazobactam, fluconazole, micafungin, levetiracetam, clonidine, midazolam, and sildenafil (range: 23-345% increase relative to non-ECMO controls), which may suggest the need for higher initial dosing. Decreased volume of distribution was reported for two drugs: acyclovir and ribavirin (50 and 69%, respectively). Decreased clearance was reported for gentamicin, ticarcillin/clavulanate, bumetanide, and ranitidine (range: 26-95% decrease relative to non-ECMO controls). Increased clearance was reported for caspofungin, micafungin, clonidine, midazolam, morphine, and sildenafil (range: 25-455% increase relative to non-ECMO controls). Conclusions: There were substantial pharmacokinetic alterations in 70% of drugs studied in children on ECMO. However, studies evaluating pharmacokinetic changes of many drug classes and those that allow direct comparisons between ECMO and non-ECMO patients are still lacking. Systematic evaluations of pharmacokinetic alterations of drugs on ECMO that incorporate multidrug opportunistic trials, physiologically based pharmacokinetic modeling, and other methods are necessary for definitive dose recommendations. Trial Registration Prospero Identifier: CRD42019114881.Item Open Access Psychosocial Assessment of Candidates for Transplantation (PACT) Score Identifies High Risk Patients in Pediatric Renal Transplantation.(Frontiers in pediatrics, 2019-01) Freischlag, Kyle W; Chen, Vivian; Nagaraj, Shashi K; Chua, Annabelle N; Chen, Dongfeng; Wigfall, Delbert R; Foreman, John W; Gbadegesin, Rasheed; Vikraman, Deepak; Chambers, Eileen TBackground: Currently, there is no standardized approach for determining psychosocial readiness in pediatric transplantation. We examined the utility of the Psychosocial Assessment of Candidates for Transplantation (PACT) to identify pediatric kidney transplant recipients at risk for adverse clinical outcomes. Methods: Kidney transplant patients <21-years-old transplanted at Duke University Medical Center between 2005 and 2015 underwent psychosocial assessment by a social worker with either PACT or unstructured interview, which were used to determine transplant candidacy. PACT assessed candidates on a scale of 0 (poor candidate) to 4 (excellent candidate) in areas of social support, psychological health, lifestyle factors, and understanding. Demographics and clinical outcomes were analyzed by presence or absence of PACT and further characterized by high (≥3) and low (≤2) scores. Results: Of 54 pediatric patients, 25 (46.3%) patients underwent pre-transplant evaluation utilizing PACT, while 29 (53.7%) were not evaluated with PACT. Patients assessed with PACT had a significantly lower percentage of acute rejection (16.0 vs. 55.2%, p = 0.007). After adjusting for HLA mismatch, a pre-transplant PACT score was persistently associated with lower odds of acute rejection (Odds Ratio 0.119, 95% Confidence Interval 0.027-0.52, p = 0.005). In PACT subsection analysis, the lack of family availability (OR 0.08, 95% CI 0.01-0.97, p = 0.047) and risk for psychopathology (OR 0.34, 95% CI 0.13-0.87, p = 0.025) were associated with a low PACT score and post-transplant non-adherence. Conclusions: Our study highlights the importance of standardized psychosocial assessments and the potential use of PACT in risk stratifying pre-transplant candidates.Item Open Access RECENT IMPROVEMENTS IN UPPER LIMB PEDIATRICS(2005) Mandacina, StephenNot only are children fit with myoelectric arms at a much earlier age than years before, but also they are now much more functional and successful with these devices. Advancements such as microprocessor-based controls, longer lasting batteries, improved socket design, and flexible socket materials have improved the functionality of children, especially those under the age of 5, with their prosthesis. Because the pediatric population is so small in our field, it is infrequent that the practitioner knows these advancements. Understanding these improvements and changes to fitting protocols not only helps the child with the device, but also strengthens the rehab team, including the O&P practitioner and OT, as well as strengthens the relationship with referrals and payors. Yet, most importantly, the entire rehab team becomes aware of these advances and can provide optimum care not seen even just a few years ago. Having a child born without a limb is an emotional trying time for parents. Although many children develop a one-handed independence, parents do not want their child to struggle physically or psychologically. Our organization has found an increasing acceptance of myoelectric control for this young population, primarily from the results received in improved socket design and components. However, the three most important criteria for functionality at this age comes from 1) a team approach, 2) continual follow up, and 3) discussions by the parents, Certified Prosthetists, Occupational Therapists, manufacturers, and other referrals such as Case Managers.Item Open Access Variant R94C in TNNT2-Encoded Troponin T Predisposes to Pediatric Restrictive Cardiomyopathy and Sudden Death Through Impaired Thin Filament Relaxation Resulting in Myocardial Diastolic Dysfunction.(Journal of the American Heart Association, 2020-03) Ezekian, Jordan E; Clippinger, Sarah R; Garcia, Jaquelin M; Yang, Qixin; Denfield, Susan; Jeewa, Aamir; Dreyer, William J; Zou, Wenxin; Fan, Yuxin; Allen, Hugh D; Kim, Jeffrey J; Greenberg, Michael J; Landstrom, Andrew PBackground Pediatric-onset restrictive cardiomyopathy (RCM) is associated with high mortality, but underlying mechanisms of disease are under investigated. RCM-associated diastolic dysfunction secondary to variants in TNNT2-encoded cardiac troponin T (TNNT2) is poorly described. Methods and Results Genetic analysis of a proband and kindred with RCM identified TNNT2-R94C, which cosegregated in a family with 2 generations of RCM, ventricular arrhythmias, and sudden death. TNNT2-R94C was absent among large, population-based cohorts Genome Aggregation Database (gnomAD) and predicted to be pathologic by in silico modeling. Biophysical experiments using recombinant human TNNT2-R94C demonstrated impaired cardiac regulation at the molecular level attributed to reduced calcium-dependent blocking of myosin's interaction with the thin filament. Computational modeling predicted a shift in the force-calcium curve for the R94C mutant toward submaximal calcium activation compared within the wild type, suggesting low levels of muscle activation even at resting calcium concentrations and hypercontractility following activation by calcium. Conclusions The pathogenic TNNT2-R94C variant activates thin-filament-mediated sarcomeric contraction at submaximal calcium concentrations, likely resulting in increased muscle tension during diastole and hypercontractility during systole. This describes the proximal biophysical mechanism for development of RCM in this family.