David Zurakowski

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Verified

David verified their affiliation via an institutional email.

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• MS, PhD
• Director of Biostatistics at Boston Children's Hospital

Background Breast cancer (BC) is a complex heterogenous disease that is a leading cause of death in women. For patients with early stage disease following primary BC therapy, approximately 30% will develop metastatic BC (MBC). The median survival of MBC patients is ~ 2–3 yr. While the early detection and monitoring of BC progression have improved p...

Artificial intelligence and machine learning are rapidly transforming medicine, healthcare, and surgery. Machine learning is a valuable tool for surgeons and researchers in pediatric cardiovascular and thoracic surgery, with innovative applications constantly evolving and expanding. Utilizing machine learning in addition to traditional statistical...

Alpha‐1 antitrypsin deficiency (AATD) can manifest at any age, including the perinatal period. Its manifestations include obstructive lung disease, which can be severe and for which current therapies are of limited benefit. We sought to determine whether the transamniotic route could be a viable alternative for administering AAT mRNA to the fetus....

Purpose To evaluate the effect of corneal cross-linking (CXL) on corneal neovascularization (CNV) between eyes that were randomized to receive either CXL or non-CXL donor corneas as the carrier tissue for Boston Keratoprosthesis (BKPro) surgery. Design A retrospective, masked analysis of CNV from slit-lamp photographs taken at post-operative week...

Capillary malformation (CM) is a congenital, non-hereditary lesion composed of enlarged and tortuous blood vessels. CM is associated with a somatic GNAQ p.R183Q activating mutation in endothelial cells (EC). Cutaneous CMs are present in 1/300 infants and in 55-70% of CM cases soft tissue overgrowth is observed. Pharmacotherapy for CM does not exist...

Background Recent studies indicate that up to 36% of pediatric and adult kidney transplant recipients with stable serum creatinine levels will have acute rejection detected on surveillance biopsy. The purpose of this study was to develop and validate a risk algorithm for identifying low- and high-risk patients using a novel automated platform that...

Background Patients with craniosynostosis are at high risk of developing elevated intracranial pressure (ICP) causing papilledema and secondary optic atrophy. Diagnosing and monitoring optic neuropathy is challenging because of multiple causes of vision loss including exposure keratopathy, amblyopia, and cognitive delays that limit examination. Per...

Background The incidence of severe adverse events in children with SARS-CoV-2 undergoing anaesthesia has not been well established. We examined the relationship between SARS-CoV-2 infection and severe perioperative adverse events in children. Methods This multicentre (21 North American institutions), retrospective cohort study included children <...

Introduction/Background: Neurodevelopmental impairment is a challenge for many children with complex congenital heart disease who undergo surgical intervention with cardiopulmonary bypass during the early postnatal period. Research Questions/Hypothesis: We hypothesized that bone marrow-derived mesenchymal stromal cell (BM-MSC) delivery through card...

Background: Heart transplantation remains definitive therapy for children with heart failure, but the burden of acute graft rejection remains. While adult data has shown cardiac magnetic resonance (CMR) offers reliable, non-invasive identification of graft rejection1-3, endo-myocardial biopsy (EMB) continues to be the gold-standard in children. Hyp...

Background Distal femoral diffusion tensor imaging (DTI) is a predictor of height gain but it is uncertain whether DTI can demonstrate differences in growth potential between the tibia and femur. Objective To explore the differences in structure and growth potential of the proximal tibia physeal-metaphyseal complex compared to those of the distal...

Background Surveillance for heart transplant rejection by endomyocardial biopsy is invasive and may yield false negatives. T1 and T2 mapping from cardiac magnetic resonance can demonstrate elevations with rejection. We sought to evaluate longitudinal changes in T1 and T2 mapping in pediatric patients with heart transplant. Methods and Results A co...

Introduction We describe an abnormality in fetal and neonatal vertebral bodies whose most conspicuous characteristic is an increase in cartilaginous matrix within cancellous osseous trabeculae. We have termed this finding fetal chondrostasis (FC). Methods We initiated a retrospective review of autopsy reports in which this condition had been prosp...

Introduction: We sought to determine whether exogenous surfactant protein B (SPB) mRNA could be incorporated and translated by the fetal lung after simple transamniotic administration. Methods: Fetuses (n=149) of twelve time-dated dams underwent intra-amniotic injections of either human SPB (hSPB) mRNA encapsulated into lipopolyplex (mRNA, n=99)...

Introduction: Secretory immunoglobulin-A (SIgA), which is not produced perinatally, binds bacteria enhancing mucosal immunity. Higher levels of intestinal bacteria bound by SIgA are protective against necrotizing enterocolitis. Transamniotic fetal immunotherapy (TRAFIT) has previously been used to deliver SIgA to the fetal digestive tract, however...

Background: The use of machine learning (ML) in cardiovascular and thoracic surgery is evolving rapidly. Maximizing the capabilities of ML can help improve patient risk stratification and clinical decision making, improve accuracy of predictions, and improve resource utilization in cardiac surgery. The many nuances and intricacies of ML modeling ne...

Image analysis of subcellular structures and biological processes relies on specific, context-dependent pipelines, which are labor-intensive, constrained by the intricacies of the specific biological system, and inaccessible to broader applications. Here we introduce the application of dispersion indices, a statistical tool traditionally employed b...

Background Congenital mitral valve disease (CMVD) presents major challenges in its medical and surgical management. Objectives The purpose of this study was to investigate the value of 3-dimensional echocardiography (3DE) and identify associations with MV reoperation in this setting. Methods All children <18 years of age who underwent MV reconstr...

Background Despite widespread acceptance of the importance of diversity in leadership, systemic challenges in leadership attainment in orthopaedic surgery still exist for several groups. We hypothesize that women, underrepresented in medicine groups, and Asians have decreased odds of achieving program director and chairperson positions compared wit...

Phase 1 trials are primarily conducted to evaluate the safety and feasibility of new interventions, usually without recruiting control patients. This retrospective study aims to characterize clinical and biological outcomes in historical and contemporary cases of neonates and infants undergoing two-ventricle repair to facilitate future secondary en...

Intrauterine Growth Restriction (IUGR) pathophysiology is driven by abnormal uterine natural killer cell (uNK) activity leading to placental dysfunction. Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) can improve experimental IUGR by mechanisms not fully understood. We sought to examine TRASCET's effects in downstream...

Objective To evaluate the short- and long-term outcomes of cardiac repair versus nonoperative management in patients with trisomy 13 and trisomy 18 with congenital heart disease. Methods An institutional review board-approved, retrospective review was undertaken to identify all patients admitted with trisomy 13/18 and congenital heart disease. Pat...

Objectives To evaluate management changes and outcomes in critically ill children after formal echocardiography. Design Retrospective cohort study between January 1, 2011, and December 31, 2020. Setting Tertiary care children’s hospital. Patients Patients from 1 to 18 years who had formal echocardiography within 72 hours of ICU admission and who...

Background Phthalate chemicals are used to manufacture plastic medical products, including many components of cardiopulmonary bypass (CPB) circuits. We aimed to quantify iatrogenic phthalate exposure in pediatric patients undergoing cardiac surgery and examine the link between phthalate exposure and postoperative outcomes. Study Design and Methods...

Background Despite the heavy demand for and knowledge of the benefits of diversity, there is a persistent lack of racial, ethnic, and gender diversity in orthopaedic surgery. Since the implementation of diversity initiatives, data have shown that general surgery has been one of the top competitive surgical fields and has demonstrated growth in raci...

Background Commonly used pediatric lower extremity growth standards are based on small, dated data sets. Artificial intelligence (AI) enables creation of updated growth standards. Purpose To train an AI model using standing slot-scanning radiographs in a racially diverse data set of pediatric patients to measure lower extremity length and to compar...

Background Restoration of osteochondral defects is critical, because osteoarthritis (OA) can arise. Hypothesis Overexpression of insulin-like growth factor 1 (IGF-1) via recombinant adeno-associated viral (rAAV) vectors (rAAV-IGF-1) would improve osteochondral repair and reduce parameters of early perifocal OA in sheep after 6 months in vivo. Stu...

High-density lipoprotein (HDL) nanoparticles promote endothelial cell (EC) function and suppress inflammation, but their utility in treating EC dysfunction has not been fully explored. Here, we describe a fusion protein named ApoA1-ApoM (A1M) consisting of apolipoprotein A1 (ApoA1), the principal structural protein of HDL that forms lipid nanoparti...

Background We investigated how syndromic versus nonsyndromic forms of micrognathia impacted difficult intubation outcomes in children. Primary outcome was the first‐attempt success rate of tracheal intubation, secondary outcomes were number of intubation attempts and complications. We hypothesized that syndromic micrognathia would be associated wit...

Intracranial vascular malformations manifest on a continuum ranging from predominantly arterial to predominantly venous in pathology. Cerebral cavernous malformations (CCMs) are capillary malformations that exist at the midpoint of this continuum. The axon guidance factor Ephrin B2 and its receptor EphB4 are critical regulators of vasculogenesis in...

Objectives Brain injury is commonly seen on magnetic resonance imaging in infants with complex congenital heart disease. The impact of perioperative brain injury on neurodevelopmental outcomes is not well understood. We evaluate the association of brain injury and other markers on neurodevelopmental outcomes in patients undergoing surgery for conge...

Urinary biomarkers can diagnose and monitor pathophysiologic conditions in the central nervous system (CNS). However, focus is often on single diseases, with limited data on discriminatory capability of this approach in a general setting. Here, we demonstrate that different classes of CNS disease exhibit distinct biomarker patterns, evidence of dis...

Background: There is limited knowledge regarding the impact of perioperative critical care on frequency of neurological imaging findings following esophageal atresia (EA) repair. Methods: This is a retrospective study of infants (n = 70) following EA repair at a single institution (2009-2020). Sex, gestational age at birth, type of surgical repa...

Introduction: Endomyocardial biopsy (EMB) drives rejection diagnosis in pediatric heart transplant patients but is subject to false negatives and carries risk. Cardiac MRI can detect and quantify myocardial fibrosis and edema with T1 and T2 mapping. Hypothesis: Cardiac MRI may improve discernment of acute rejection in pediatric transplant patients....

Vascular rings may cause respiratory or gastrointestinal symptoms due to compression of the trachea and/or esophagus. Advances in imaging have enabled early detection in asymptomatic patients posing new management dilemmas. Surgery is expected to relieve symptoms, although this has not been well studied. We sought to evaluate the presence and patte...

Introduction This international survey explored the ongoing impact of COVID‐19 on pediatric anesthesiology. It assessed COVID‐19's impact on the practice of pediatric anesthesiology, staffing, job satisfaction, and retention at the beginning of 2022 and addressed what should be done to ameliorate COVID‐19's impact and what initiatives hospitals had...

Introduction Quantitative sensory testing (QST) is often used to understand the perceptual basis of acute and chronic conditions, including pain. As the need grows for developing a mechanistic understanding of neurological pathways underlying perception in the basic and clinical sciences, there is a greater need to adapt techniques such as QST to t...

Objectives: To develop, evaluate, and explore the use of a pediatric ordinal score as a potential clinical trial outcome metric in children hospitalized with acute hypoxic respiratory failure caused by viral respiratory infections. Design: We modified the World Health Organization Clinical Progression Scale for pediatric patients (CPS-Ped) and a...

Background: Anastomotic strictures (AS) after esophageal atresia (EA) repair are common. While most respond to endoscopic therapy, some become refractory and require surgical intervention, for which the outcomes are not well established. Methods: All EA children with AS who were treated surgically at two institutions (2011-2022) were retrospecti...

Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) can attenuate placental inflammation and minimize intrauterine growth restriction (IUGR). We sought to determine whether MSC-based TRASCET could mitigate fetal cardiopulmonary effects of IUGR. Pregnant Sprague-Dawley dams were exposed to alternating 12-hour hypoxia (10.5%...

Significance: Quantitative measurement of perisurgical brain function may provide insights into the processes contributing to acute and chronic postsurgical pain. Aim: We evaluate the hemodynamic changes in the prefrontal cortex (medial frontopolar cortex/mFPC and lateral prefrontal cortex) and the primary somatosensory cortex/S1 using functiona...

Purpose The aim of this study was to evaluate the effect of corneal cross-linking on central endothelial cell density (ECD) by comparing masked measurements before and immediately after preparation of cross-linked (CXL) and non–cross-linked (non-CXL) donor corneas. Methods Thirty donor corneas were randomized 1:1 to either CXL or non-CXL using a m...

BACKGROUND Congenital mitral valve disease (CMVD) presents major challenges in medical and surgical management. Data on predictors of mitral valve (MV) reoperation and value of 3D-echocardiography (3DE) in this context are currently limited. Aim of our study was to identify predictors of MV reoperation and to investigate the value of 3DE in risk st...

Importance Phthalate chemicals are used to manufacture disposable plastic medical products, including blood storage bags and components of cardiopulmonary bypass (CPB) circuits. During cardiac surgery, patients can be inadvertently exposed to phthalate chemicals that are released from these plastic products. Objective To quantify iatrogenic phthal...

Introduction: Therapies based on exogenous messenger RNA (mRNA) administration have emerged as a powerful novel strategy for the actual or potential treatment of an assortment of diseases, including congenital surgical pathologies. We sought to determine whether the minimally invasive transamniotic route could be an alternative for prenatal mRNA d...

Objective To study in a masked fashion whether an objective histological feature associated with keratoconus (KCN) occurs in donor corneas in eyes originally receiving a corneal graft for KCN. Methods Two ocular pathologists performed a retrospective masked histological analysis of slides from donor buttons recovered from 21 eyes with a history of...

Objectives To analyze outcomes of pediatric patients with heterotaxy syndrome undergoing cardiovascular surgery and to determine predictors of mortality. Methods Retrospective analysis of 82 patients diagnosed with heterotaxy syndrome who underwent cardiovascular surgery between January 2008 and December 2017. Univariate and multivariable Cox regr...

Introduction: Neuroblastoma is the most common extracranial pediatric tumor, accounting for 5-8% of all childhood cancers. Neuroblastomas arise from catecholamine-secreting neural crest cells and their metabolites, vanillylmandelic acid and homovanillic acid, that are readily detected in urine. Although rarely seen in clinical practice, case repor...

Background: COVID-19 forced healthcare systems to make unprecedented changes in clinical care processes. We hypothesized that the COVID-19 pandemic adversely impacted timely access to care, perioperative processes, and clinical outcomes for pediatric patients undergoing primary appendectomy. Methods: We conducted a retrospective, international,...

Introduction: Breast cancer (BC) is a complex heterogenous disease and is a leading cause of death in women. Following primary BC therapy ~40% of patients will develop metastatic BC (MBC) and 60-70% of the recurrent disease will occur at distant sites. Median survival of MBC patients with distant recurrence is ~2-3 yr. While the early detection and...

Objectives: The aim of the study was to evaluate the course of aortic valve regurgitation in patients with preoperative aortic valve regurgitation and ventricular septal defect who underwent repair of the ventricular septal defect without aortic valve repair. Methods: A total of 37 consecutive patients with a ventricular septal defect and aortic...

Purpose: We sought to determine the feasibility and routing kinetics of transamniotic fetal delivery of secretory immunoglobulin-A (SIgA), in a rodent model. Methods: Fetuses (n = 94) from seven time-dated pregnant dams received intra-amniotic injections on gestational day 17 (E17, term = E21-22) of either saline (n = 15) or a solution of 1 mg/m...

Recent findings implicate brain vulnerability following long-gap esophageal atresia (LGEA) repair. We explored the relationship between easily quantifiable clinical measures and previously reported brain findings in a pilot cohort of infants following LGEA repair. MRI measures (number of qualitative brain findings; normalized brain and corpus callo...

Purpose: Fetal alloimmune hemolytic anemia (AHA) resulting from maternal antibodies against fetal erythrocytes may require fetal administration of immunoglobulin-G (IgG) via invasive methods. IgG can reach the fetal circulation after transamniotic fetal immunotherapy (TRAFIT). We sought to both develop a model of AHA and to test TRAFIT as a potent...

Background Prolonged morphine treatment in infancy is associated with a high incidence of opioid tolerance and dependence, but our knowledge of the long-term consequences of this treatment is sparse. Using a rodent model, we examined the (1) short- and (2) long-term effects of prolonged morphine administration in infancy on body weight and brain vo...

Hematopoietic stem cell (HSC)-based gene therapy has already reached clinical reality in a few applications. Fetal administration of genetically modified HSCs has only been feasible to date via invasive and morbid methods. It has been recently shown that native donor HSCs can reach the fetal circulation and bone marrow after simple delivery into th...

Background: The optimal timing of surgical repair for infants with congenital diaphragmatic hernia (CDH) treated with extracorporeal membrane oxygenation (ECMO) support remains controversial. The risk of surgical bleeding is considered by many centers as a primary factor in determining the preferred timing of CDH repair for infants requiring ECMO...

Physical insult from a mild Traumatic Brain Injury (mTBI) leads to changes in blood flow in the brain and measurable changes in white matter, suggesting a physiological basis for chronic symptom presentation. Post-traumatic headache (PTH) is frequently reported by persons after an mTBI that may persist beyond the acute period (>3 months). It remain...

Objective Osteoarthritis (OA) is a serious consequence of focal osteochondral defects. Gene transfer of human transforming growth factor beta (hTGF-β) with recombinant adeno-associated virus (rAAV) vectors offers a strategy to improve osteochondral repair. However, the long-term in vivo effects of such rAAV-mediated TGF-β overexpression including i...

Purpose: Assess whether cross-linking the carrier donor cornea of the Boston Keratoprosthesis (BKPro) improves retention of the device in participants at high risk of keratolysis. Design: Prospective, double-masked randomized clinical trial. Methods: In this multicenter study, sixty-eight adult participants who were scheduled for BKPro implant...

Introduction: Endomyocardial biopsy (EMB) drives rejection diagnosis in pediatric heart transplant patients but is subject to false negatives. Cardiac magnetic resonance imaging (CMR) can detect and quantify fibrosis and edema with T1 and T2 mapping. Overlaying CMR data onto X-ray images may be used for EMB procedural guidance. Hypothesis: Overlayi...

Introduction: Endocardial fibroelastosis (EFE) can be the cause of diastolic dysfunction in congenital heart defects. It is derived through endothelial-to-mesenchymal transformation (EndMT), and flow disturbances have been associated with its development. Surgical resection is the only available treatment, but recurrence is often observed. We sough...

Background: The Pediatric Anesthesia COVID-19 Collaborative (PEACOC) is a research network to advance the care of children during the pandemic. Here we calculate the prevalence of coronavirus disease 2019 (COVID-19) among children undergoing anesthesia, look at prevalence in the population data from the Centers for Disease Control and Prevention (...

Substantial advances in biotherapeutics are distinctly lacking for musculoskeletal diseases. Musculoskeletal diseases are biomechanically complex and localized, highlighting the need for novel therapies capable of addressing these issues. All frontline treatment options for arthrofibrosis, a debilitating musculoskeletal disease, fail to treat the d...

Background & Aims Intermittent enteral nutrition (EN) may have physiologic benefits over continuous feeding in critical illness. We aimed to compare nutrition and infection outcomes in critically ill children receiving intermittent or continuous EN. Methods International, multi-center prospective observational study of mechanically ventilated chil...

Purpose Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) has been shown experimentally to reverse some of the effects of intrauterine growth restriction (IUGR), apparently by attenuating placental inflammation. Neurodevelopmental deficits driven by neuroinflammation are major complications of IUGR. We sought to determine...

Aim of the Study Small bowel obstruction (SBO) is a known complication after congenital diaphragmatic hernia (CDH) repair, which can require surgery and even extensive bowel resection causing short bowel syndrome (SBS). We investigate whether specific bowel rotation and fixation can be used as a predictor for SBO including volvulus. Methods A retr...

Purpose Transamniotic stem cell therapy (TRASCET) with donor mesenchymal stem cells (MSCs) has been shown experimentally to reverse central effects of intrauterine growth restriction (IUGR). We sought to compare amniotic-fluid and placenta-derived MSCs (afMSCs and pMSCs, respectively) as TRASCET donor cells in a murine IUGR model. Methods Pregnant...

The Gram-negative pathogen Pseudomonas aeruginosa is a common cause of pneumonia in hospitalized patients. Its increasing antibiotic resistance and widespread occurrence present a pressing need for vaccines. We previously showed that a P. aeruginosa type III secretion system protein, PopB, elicits a strong Th17 response in mice after intranasal (IN...

The Gram-negative pathogen Pseudomonas aeruginosa is a common cause of pneumonia in hospitalized patients. Its increasing antibiotic resistance and widespread occurrence present a pressing need for vaccines. We previously showed that a P. aeruginosa type III secretion system protein, PopB, elicits a strong Th17 response in mice after intra-nasal (I...

Objectives The purpose of this article is to provide thoracic and cardiovascular surgeons with the necessary tools for performing sample size and power calculations for studies with time-to-event outcomes. Power and sample size calculations enhance the overall quality of research studies by providing readers with assurance and insight into the numb...

Purpose : Transamniotic stem cell therapy (TRASCET) with mesenchymal stem cells (MSCs) has been shown to impact pulmonary vascular development and remodeling in experimental congenital diaphragmatic hernia (CDH), with secondary structural cardiac effects. We sought to determine whether TRASCET has any functional impact on term fetal pulmonary hemod...

Background: Autologous fractional full-thickness skin grafting is a method of harvesting full-thickness skin with reduced donor site morbidity compared with conventional skin grafting. Objective: To demonstrate that full-thickness skin microbiopsies can be harvested with minimal scarring or complications. Materials and methods: In a nonrandomi...

Background Subchondral drilling is an established marrow stimulation technique for small cartilage defects, but whether drilling is required at all and if the drill hole density affects repair remains unclear. Hypotheses Osteochondral repair is improved when the subchondral bone is perforated by a higher number of drill holes per unit area, and dr...

Importance Extracellular matrix proteins and enzymes involved in degradation have been found to be associated with tissue fibrosis and ureteropelvic junction obstruction (UPJO). In this study we developed a promising urinary biomarker model which can identify reduced renal function in UPJ obstruction patients. This can potentially serve as a non-in...

Background : Indocyanine green (ICG) is commonly used to assess perfusion, but quality defining features are lacking. We sought to establish qualitative features of esophageal ICG perfusion assessments, and develop an esophageal anastomotic scorecard to risk-stratify anastomotic outcomes. Methods : Single institution, retrospective analysis of chi...

Objectives: The mechanism of many neuropsychiatric disorders remains unknown, but the ineffectiveness of the sodium channel blocker lidocaine has been suggested to be a biomarker for Attention Deficit Hyperactivity Disorder (ADHD) and a severe form of Premenstrual Syndrome (PMS) that is considered psychiatric. We conducted single-arm double-blind...