Yuk M. Law
University of Washington
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Featured researches published by Yuk M. Law.
Journal of the American College of Cardiology | 2008
D. Dunbar Ivy; Aimee Doran; Kelly J. Smith; G.B. Mallory; Maurice Beghetti; Robyn J. Barst; Daniela Brady; Yuk M. Law; Donna K. Parker; Lori Claussen; Steven H. Abman
OBJECTIVESnThis study investigated the short- and long-term outcome of children with pulmonary arterial hypertension (PAH) treated with inhaled iloprost.nnnBACKGROUNDnInhaled iloprost has been approved for the treatment of adults with PAH, but little is known about the effects in children with PAH.nnnMETHODSnWe evaluated the acute effects of inhaled iloprost on hemodynamic status and lung function and the response to long-term therapy in 22 children (range 4.5 to 17.7 years) with PAH (idiopathic, n = 12; congenital heart disease, n = 10). Cardiac catheterization, standard lung function testing before and after iloprost inhalation, 6-min walk test, World Health Organization functional class, and hemodynamic parameters were monitored.nnnRESULTSnAcute administration of inhaled iloprost lowered mean pulmonary artery pressure equivalent to the response to inhaled nitric oxide with oxygen. Acute iloprost inhalation reduced forced expiratory volume in 1 s and mid-volume forced expiratory flow by 5% and 10%, respectively, consistent with acute bronchoconstriction. At 6 months, functional class improved in 35%, decreased in 15%, and remained unchanged in 50% of children. Sixty-four percent of patients continued receiving long-term iloprost therapy, 36% stopped iloprost, due to lower airway reactivity, clinical deterioration, or death. In 9 patients on chronic intravenous prostanoids, 8 transitioned from intravenous prostanoids to inhaled iloprost, which continued during follow-up.nnnCONCLUSIONSnInhaled iloprost caused sustained functional improvement in some children with PAH, although inhaled iloprost occasionally induced bronchoconstriction. Most patients tolerated the transition from intravenous to inhaled prostanoid therapy. Clinical deterioration, side effects, and poor compliance, owing to the frequency of treatments, could limit chronic treatment in children.
Journal of the American College of Cardiology | 2009
Yuk M. Law; Andrew W Hoyer; Mark D. Reller; Michael Silberbach
OBJECTIVESnThe purpose of this study was to assess the ability of plasma B-type natriuretic peptide (BNP) to diagnose significant cardiovascular disease (CVD) in the pediatric population.nnnBACKGROUNDnBNP has been shown to be reliable in detecting ventricular dysfunction and heart failure in adults. Timely and accurate identification of significant pediatric heart disease is important but challenging. A simple blood test could aid the front-line physician in this task.nnnMETHODSnSubjects without a history of heart disease with findings possibly attributable to significant CVD in the acute care setting requiring a cardiology consult were enrolled. Clinicians were blinded to the BNP result, and confirmation of disease was made by cardiology consultation.nnnRESULTSnSubjects were divided into a neonatal (n = 42, 0 to 7 days) and older age group (n = 58, >7 days to 19 years). CVD was present in 74% of neonates and 53% of the older age group. In neonates with disease, median BNP was 526 pg/ml versus 96 pg/ml (p < 0.001) for those without disease. In older children with disease, median BNP was 122 pg/ml versus 22 pg/ml in those without disease (p < 0.001). Subjects with disease from an anatomic defect, a longer hospital stay, or who died had higher BNP. A BNP of 170 pg/ml yielded a sensitivity of 94% and specificity of 73% in the neonatal group and 87% and 70% in the older age group, respectively, using a BNP of 41 pg/ml.nnnCONCLUSIONSnBNP is a reliable test to diagnose significant structural or functional CVD in children. Optimal cutoff values are different from adult values.
Transplantation | 2015
Michael Green; S. Covington; S. Taranto; Cameron R. Wolfe; Walter C. Bell; Scott W. Biggins; David Conti; G. David DeStefano; Edward A. Dominguez; Donna Ennis; Thomas G. Gross; Mary Klassen-Fischer; Camille N. Kotton; Dianne Lapointe-Rudow; Yuk M. Law; Kristen Ludrosky; Marilyn A. Menegus; Michele I. Morris; Michael A. Nalesnik; Martha Pavlakis; Timothy L. Pruett; Costi D. Sifri; Daniel R. Kaul
Background The Organ Procurement Transplant Network Disease Transmission Advisory Committee (DTAC), a multidisciplinary committee, evaluates potential donor-derived transmission events (PDDTE), including infections and malignancies, to assess for donor transmitted events. Methods Reports of unexpected PDDTE to Organ Procurement Transplant Network in 2013 were fully reviewed by DTAC. A standardized algorithm was used to assess each PDDTE from a given donor and to classify each individual recipient from that donor. Results Of 443 total PDDTE submitted, 159 were triaged and not sent out to the full DTAC. Of 284 fully evaluated reports, 32 (11.3%) resulted in a proven/probable (P/P) transmission of infection, malignancy or other conditions to 42 recipients. Of 204 infection events, 24 were classified as P/P affecting 30 recipients, with four deaths. Bacteria were the most frequently reported type of infection, accounting for 99 reports but only 12 recipients from 11 donors experienced P/P transmission. There were 65 donors reported with potential malignancy events and 5 were classified as P/P transmissions with 8 affected recipients and 2 deaths. Additionally, there were 16 noninfection, nonmalignancy reports resulting in 3 P/P transmissions to 4 recipients and 1 death. Conclusions There was a 43% increase in the number of PDDTE reported and reviewed in 2013 over 2012. However, the percent with P/P transmission remains low, affecting recipients from 32 donors especially when compared with the more than 14,000 donors recovered annually in the United States. The continued use of the new standard algorithm and triaging process will enhance the reproducibility of DTAC assessments and allow more robust analysis of our aggregate DTAC experience.
Heart Failure Reviews | 2014
Massimiliano Cantinotti; Yuk M. Law; Simona Vittorini; Maura Crocetti; Marotta Marco; Bruno Murzi; A. Clerico
The aim of this article is to review the diagnostic and prognostic relevance of measurement of brain natriuretic peptide (BNP) and N-terminal pro-brain natriuretic peptide (NT-proBNP) in pediatric patients with heart failure caused by various acquired and congenital heart diseases (CHD). In January 2013, we performed a computerized literature search in the National Library of Medicine (PubMed access to MEDLINE citations; http://www.ncbi.nlm.nih.gov/PubMed/). The search strategy included a mix of Medical Subject Headings and free-text terms for the key concepts, starting from BNP assay and ‘NT-proBNP assay’, children, CHD. The search was further refined by adding the keywords neonate/s, newborn/s, heart failure, cardiomyopathy, screening, prognosis, follow-up, and management. BNP values are age and method dependent, even in pediatric populations. Regardless of age, there is great variability in BNP/NT-proBNP values within CHD characterized by different hemodynamic and clinical conditions. There is enough evidence to support the use of BNP/NT-proBNP as an adjunctive marker in the integrated evaluation of patients with congenital and acquired heart disease to help define severity and progression of heart failure as well in the monitoring of response to treatment. BNP/NT-proBNP can also be used for the screening of heart failure and as a prognostic marker in children undergoing cardiac surgery; however, to date, there are studies with heterogeneous patient groups, and diverse outcome measures selected are still few. BNP/NT-proBNP can be used as adjunctive markers in the integrated screening, diagnosis, management, and follow-up of children with heart failure caused by various acquired and congenital heart disease.
Pediatric Transplantation | 2011
Brian Feingold; Jie Zheng; Yuk M. Law; W. Robert Morrow; Timothy M. Hoffman; Kenneth B. Schechtman; Anne I. Dipchand; Charles E. Canter
Feingold B, Zheng J, Law YM, Morrow WR, Hoffman TM, Schechtman KB, Dipchand AI, Canter CE and the Pediatric Heart Transplant Study Investigators. Risk factors for late renal dysfunction after pediatric heart transplantation: A multi‐institutional study.u2028Pediatr Transplantation 2011: 15: 699–705.
Pediatric Transplantation | 2013
David Villeneuve; Eric Harvey; M. Kemna; Yuk M. Law; Thomas Nemeth; Soren Gantt
Pediatric valganciclovir dosing recommendations have not been extensively validated for prevention or treatment for CMV infection. As such, we performed a pharmacokinetic study to compare different valganciclovir dosing regimens and the potential benefits of individualized dose adjustments in children following organ transplantation. Ganciclovir AUCs were calculated from four plasma drug levels in pediatric SOT recipients aged six months through three yr receiving valganciclovir suspension by mouth. Of the 28 ganciclovir AUC calculations performed, 11 (39%) were outside the therapeutic target range of 40–60 mcg h/L leading to a valganciclovir dose adjustment. Current manufacturer‐recommended dosing based on BSA and CrCl was estimated to result in therapeutic AUCs in fewer patients than the simple weight‐based formula used in our institution (4 vs. 13; p = 0.017). An AUC calculation using only the two‐ and five‐h measurements was strongly correlated with the AUC using all four time measurements (R2 = 0.846; p < 0.001). A simple weight‐based dosing approach gives a higher probability for therapeutic AUCs compared to the manufacturer‐recommended dosing in pediatric transplant patients aged six months through three yr with normal renal function. An AUC calculated using two sample times might allow for fewer blood draws in the future.
Journal of the American College of Cardiology | 2015
Steven J. Kindel; Yuk M. Law; Clifford Chin; Michael Burch; James K. Kirklin; David C. Naftel; Elizabeth Pruitt; Michael P. Carboni; Anna Arens; Andrew M. Atz; William J. Dreyer; William T. Mahle; Elfriede Pahl
BACKGROUNDnRecent guidelines recommend assessment of systolic function and filling pressures to augment angiographic grading of cardiac allograft vasculopathy (CAV); however, no data exist on the utility of these guidelines.nnnOBJECTIVESnThe aims of this study were to evaluate whether the assessment of systolic and diastolic graft function, in addition to angiography, improves recognition of patients at high risk of graft loss and to assess the ability of adult filling-pressure thresholds to discriminate graft dysfunction in pediatric patients.nnnMETHODSnThis study reviewed Pediatric Heart Transplant Study data from 1993 to 2009. Graft dysfunction was defined as significant systolic dysfunction (ejection fraction [EF]xa0<45%) or the presence of restrictive hemodynamic features. Additional pediatric hemodynamic cutpoints of right atrial pressure (RAP) >12 mmxa0Hg or pulmonary capillary wedge pressure (PCWP) >15 mmxa0Hg were analyzed.nnnRESULTSnIn the study, 8,122 angiograms were performed in 3,120 patients, and 70% of patients had at least 1 angiogram. Angiographic incidence of CAV was 5%, 15%, and 28% at 2, 5, and 10 years, respectively, and most disease was mild. The presence of graft dysfunction identified patients at greater risk for graft loss even in children with mild angiographic vasculopathy (pxa0< 0.0001). An RAP >12 mmxa0Hg or a PCWP >15 mmxa0Hg was sufficient to detect patients at high risk of graft loss even with mild angiographic disease.nnnCONCLUSIONSnPatients with only mild angiographic CAV have significantly better outcomes than do patients with moderate or severe disease. The presence of an EFxa0<45%, an RAP >12 mmxa0Hg, or a PCWP >15 mmxa0Hg identifies children at increased risk of graft loss even in the presence of only mild angiographic vasculopathy.
Pediatric Transplantation | 2013
David M. Peng; Yuk M. Law; Mariska S. Kemna; Paul Warner; Karen Nelson; Robert J. Boucek
There is limited evidence regarding the utility of circulating DSA in surveillance for AMR of pediatric heart recipients. Our hypothesis is that quantitation of DSA improves their power for predicting a C4d+, an integral component in the current diagnostic criteria of AMR. All pediatric recipients transplanted between 10/2005 and 1/2011 were retrospectively reviewed for DSA determined within 48 h of EMB. C4d+ was defined as >25% endothelial cell staining by immunohistochemical methods. A total of 183 paired DSA–EMB determinations were identified in 60 patients, a median of three paired studies per patient (range: 1–9). DSA were detected in 60 of these determinations. A receiver‐operating characteristic plot identified a threshold single‐antibody MFI of >6000 that strongly correlated with C4d+ (p < 0.0001) with a high negative predictive value (0.97) and specificity (0.95). The sensitivity and positive predictive values were 0.71 and 0.60, respectively. The predictive power of single‐antigen DSA for C4d deposition was improved in pediatric heart recipients using an institution‐specific MFI threshold value. In post‐transplant care, quantitative DSA should be an essential component in the surveillance for AMR.
Journal of Heart and Lung Transplantation | 2015
Patrick M. Sullivan; Paul Warner; M. Kemna; Erin L. Albers; Sabrina P. Law; Noel S. Weiss; Yuk M. Law
BACKGROUNDnAlthough evidence links HLA allele mismatching to worse outcomes in pediatric heart transplantation, no studies to our knowledge have applied the quantification of structural HLA differences between donor and recipient to risk evaluation. We examine the association between molecular-level HLA mismatching and long-term graft loss in pediatric recipients of heart transplants.nnnMETHODSnHLA Matchmaker was used to quantify the number of mismatched class-specific HLA eplets among 4,851 heart transplant recipients ≤18 years of age in the Scientific Registry of Transplant Recipients (1987-2012). Survival analysis was used to compare long-term probabilities of graft loss by number of eplet mismatches and allele mismatches stratified by eplet mismatches.nnnRESULTSnRecipients with 10 to 20 or >20 class I (HLA-A and HLA-B) eplet mismatches experienced increased long-term graft loss compared with recipients with <10 class I eplet mismatches (adjusted hazard ratio = 1.23 [95% confidence interval = 1.06-1.42], adjusted hazard ratio = 1.27 [95% confidence interval = 1.08-1.50], respectively). Recipients with 2 to 4 class I allele mismatches had increased long-term graft loss compared with recipients with 0 to 1 class I allele mismatches. Neither class II (HLA-DR) eplet mismatching nor class II allele mismatching was associated with graft loss. On stratification by allele and structural eplet mismatching, only recipients with 2 to 4 class I allele mismatches and ≥10 class I eplet mismatches had an increased probability of graft loss compared with recipients with 0 to 1 class I allele mismatches (adjusted hazard ratio = 1.42 [95% confidence interval = 1.09-1.57]).nnnCONCLUSIONSnMolecular-level HLA mismatching may aid in identifying recipients at increased risk of long-term graft loss who could benefit from intensified post-transplant surveillance and management.
Pediatric Transplantation | 2015
Jane A. Dickerson; Marian Sinkey; Kathleen Jacot; Jennifer Stack; Katerina Sadilkova; Yuk M. Law; Rhona M. Jack
Therapeutic drug monitoring of tacrolimus and sirolimus plays a significant role in the clinical follow‐up of transplant patients receiving IMS therapy. Success of transplant and favorable patient outcome relies on maintaining adequate therapeutic drug levels. The purpose of this research is to assess the clinical utility of remote collection of DBS for immunosuppressant monitoring and compare the IMS level in paired collections of venous whole blood and DBS. Sirolimus and tacrolimus levels were clinically correlated in capillary blood collected from a finger poke with venous whole blood from pediatric, post‐transplant patients. The participants took the dried blood spot card home with them with a pre‐addressed, postage‐paid envelope and mailed it back to the laboratory. Overall, a small but statistically significant negative bias was observed (−0.6 ng/mL, p = 0.0011). A chart review was performed to assess whether clinical management would have changed, and none of the cases revealed a clinically significant change. Sirolimus in DBS also correlated with venous levels. Overall, a small but statistically negative bias was observed (−0.8 ng/mL, p = 0.029). In summary, analysis of IMS levels in DBS is possible, and the difference noted between capillary and venous blood is within the clinically acceptable limits.