York University Langone Medical Center Research Articles

Recurrence prediction of lung adenocarcinoma using an immune gene expression and clinical data trained and validated support vector machine classifier.

Immune microenvironment plays a critical role in cancer from onset to relapse. Machine learning (ML) algorithm can facilitate the analysis of lab and clinical data to predict lung cancer recurrence. Prompt detection and intervention are crucial for long-term survival in lung cancer relapse. Our study aimed to evaluate the clinical and genomic prognosticators for lung cancer recurrence by comparing the predictive accuracy of four ML models. A total of 41 early-stage lung cancer patients who underwent surgery between June 2007 and October 2014 at New York University Langone Medical Center were included (with recurrence, n=16; without recurrence, n=25). All patients had tumor tissue and buffy coat collected at the time of resection. The CIBERSORT algorithm quantified tumor-infiltrating immune cells (TIICs). Protein-protein interaction (PPI) network and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were conducted to unearth potential molecular drivers of tumor progression. The data was split into training (75%) and validation sets (25%). Ensemble linear kernel support vector machine (SVM) ML models were developed using optimized clinical and genomic features to predict tumor recurrence. Activated natural killer (NK) cells, M0 macrophages, and M1 macrophages showed a positive correlation with progression. Conversely, T CD4+ memory resting cells were negatively correlated. In the PPI network, TNF and IL6 emerged as prominent hub genes. Prediction models integrating clinicopathological prognostic factors, tumor gene expression (45 genes), and buffy coat gene expression (47 genes) yielded varying receiver operating characteristic (ROC)-area under the curves (AUCs): 62.7%, 65.4%, and 59.7% in the training set, 58.3%, 83.3%, and 75.0% in the validation set, respectively. Notably, merging gene expression with clinical data in a linear SVM model led to a significant accuracy boost, with an AUC of 92.0% in training and 91.7% in validation. Using ML algorithm, immune gene expression data from tumor tissue and buffy coat may enhance the precision of lung cancer recurrence prediction.

Reducing the burden of surveillance in pregnant women with no history of fetal atrioventricular block using the negative predictive value of anti-Ro/SSA antibody titers

The risk of fetal atrioventricular block in anti-Ro/SSA antibody-exposed pregnancies with no previous affected offspring is approximately 2%. A high antibody titer is necessary but not sufficient for atrioventricular block, and specific antibody titers do not predict risk. However, there are no data on the negative predictive value of antibody titer to identify pregnancies at low risk of fetal atrioventricular block, and may not require surveillance. This study aimed to define anti-Ro52 and anti-Ro60 antibody thresholds for the identification of fetuses unlikely to develop atrioventricular block using clinically validated and research laboratory tests. This study performed a multicenter review of pregnant subjects who tested positive in their local commercial laboratories for anti-Ro/SSA antibodies at the University of Colorado Children's Hospital (2014-2021) and Phoenix Children's Hospital (2014-2021) and enrolled in the Research Registry for Neonatal Lupus (RRNL) at New York University Langone Medical Center (2002-2021). The subjects were referred on the basis of rheumatologic symptoms or history of atrioventricular block in a previous pregnancy and were retrospectively grouped on the basis of pregnancy outcome. Group 1 indicated no fetal atrioventricular block in current or past pregnancies; group 2 indicated fetal atrioventricular block in the current pregnancy; and group 3 indicated normal current pregnancy but with fetal atrioventricular block in a previous pregnancy. Maternal sera were analyzed for anti-Ro52 and anti-Ro60 antibodies using a clinically validated multiplex bead assay (Associated Regional and University Pathologists Laboratories, Salt Lake City, UT) and a research enzyme-linked immunosorbent immunoassay (New York University). This study calculated the negative predictive value separately for anti-Ro52 and anti-Ro60 antibodies and for the 2 combined using a logistic regression model and a parallel testing strategy. This study recruited 270 subjects (141 in group 1, 66 in group 2, and 63 in group 3). Of note, 89 subjects in group 1 had data on hydroxychloroquine treatment: anti-Ro/SSA antibody titers were no different between those treated (n=46) and untreated (n=43). Mean anti-Ro52 and anti-Ro60 titers were the lowest in group 1 and not different between groups 2 and 3. No case of fetal atrioventricular block developed among subjects with anti-Ro52 and anti-Ro60 titers of <110 arbitrary units per milliliter using the multiplex bead assay of the Associated Regional and University Pathologists Laboratories (n=141). No case of fetal atrioventricular block developed among subjects with research laboratory anti-Ro52 titers of <650 and anti-Ro60 of <4060 enzyme-linked immunosorbent immunoassay units (n=94). Using these 100% negative predictive value thresholds, more than 50% of the anti-Ro/SSA antibody pregnancies that ultimately had no fetal atrioventricular block could be excluded from surveillance based on clinical and research titers, respectively. Study data suggested that there is a clinical immunoassay level of maternal anti-Ro/SSA antibodies below which the pregnancy is at low risk of fetal atrioventricular block. This study speculated that prospectively applying these data may avert the costly serial echocardiograms currently recommended for all anti-Ro/SSA-antibody positive pregnancies and guide future management.

Xenotransplantion: Defeating the "Shumway Curse" An Interview With Drs. Bartley Griffith, Jayme Locke, Robert Montgomery, and Bruno Reichart.

An interview with Drs. Bartley Griffith (BG), Jayme Locke (JL), Robert Montgomery (RM), Bruno Reichart (BR). Dr Robert Montgomery, is a Professor and Chair of Surgery, and Director of the Transplant Institute at New York University (NYU) Langone Medical Center, USA On Sep. 25, 2021, Dr Montgomery transplanted a kidney from a genetically modified pig into a deceased human body donor, an experiment he successfully reproduced a few weeks later. Urine production could be observed for up to 3 days. Dr Jayme Locke, is a Professor of Surgery and Director of the Comprehensive Transplant Institute and Division of Transplantation at the University of Alabama at Birmingham (UAB), USA On Sep. 30, 2021, Dr Locke transplanted two genetically modified pig kidneys inside the abdomen of a brain-dead human after removing the recipient’s native kidneys. Urine production for over 72 hours was also observed (1). Dr. Bartley Griffith, is a Professor of Surgery and Director of the Cardiac and Lung Transplant Programs at the University of Maryland School of Medicine, Baltimore, USA On Jan 7, 2022, Dr Griffith performed the first successful xenogeneic heart transplant from a genetically modified pig to a human. Dr. Bruno Reichart, is an Emeritus Professor of Surgery and project leader at the Walter Brendel Center for Experimental Medicine, Ludwig-Maximilian University (LMU), Munich, Germany Dr. Reichart performed Germany's first successful heart transplant in 1981, and has been a leading scientist and a spokesman for experimental xenotransplantation since over 20 years.

Stakeholder Perspectives on Advancing Understanding of Prenatal Opioid Exposure and Brain Development From the iOPEN Consortium of the Healthy Brain and Child Development Study.

Introduction: There is a dire need for research regarding the implications of opioid use during pregnancy on fetal and childhood development to better inform both medical practice and policy. The Healthy Brain and Child Development Study will examine brain and behavioral development from birth through the first decade of life. Due to large scope and anticipated complexity of this initiative, an 18-month planning phase was implemented across 28 sites across the nation. A core element of the Phase I initiative involved the development of Stakeholder Advisory Committees to inform the next phase of the initiative.Methods: Phase I stakeholder meetings were conducted at Oregon Health and Science University, New York University Langone Medical Center, the University of Pittsburgh, and the University of Vermont to better understand perspectives and inform upcoming research. Despite differences in the structure of the stakeholder meetings by site, the overarching goals for the meetings included establishing relationships, gathering input, and learning about research engagement. Documents from each meeting were reviewed for location, duration, attendees, common research themes, and pertinent suggestions for improving research approaches.Results: All stakeholders had high levels of interest in research for pregnant people with substance use disorders and agreed on research priorities including collaboration, connection, communication, and support. Different stakeholders offered unique perspectives on various aspects of study design and themes that emerged through meetings.Discussion: Overall, there was excitement about the research, especially the opportunity to include the voices of people with lived experience; collaboration between providers, peer support specialists, patients, and others; and excitement around contributing to research that could elucidate new and pertinent findings in the realm of addiction medicine and child development. Sites also found that there is mistrust between people with substance use disorder and the medical system, and this could be addressed by including people with lived experience on the research team, forming connections, communicating clearly, training the research team in implicit bias, and practicing trauma-informed care. In conclusion, these stakeholder meetings provided valuable information for structuring upcoming studies; however, researchers would have benefitted from more time and more opportunities for in-person connection.

COVID-19 outcomes in hospitalized patients with active cancer: Experiences from a major New York City health care system.

BackgroundThe authors sought to study the risk factors associated with severe outcomes in hospitalized coronavirus disease 2019 (COVID‐19) patients with cancer.MethodsThe authors queried the New York University Langone Medical Center's records for hospitalized patients who were polymerase chain reaction–positive for severe acute respiratory syndrome coronavirus 2 (SARS CoV‐2) and performed chart reviews on patients with cancer diagnoses to identify patients with active cancer and patients with a history of cancer. Descriptive statistics were calculated and multivariable logistic regression was used to determine associations between clinical, demographic, and laboratory characteristics with outcomes, including death and admission to the intensive care unit.ResultsA total of 4184 hospitalized SARS CoV‐2+ patients, including 233 with active cancer, were identified. Patients with active cancer were more likely to die than those with a history of cancer and those without any cancer history (34.3% vs 27.6% vs 20%, respectively; P < .01). In multivariable regression among all patients, active cancer (odds ratio [OR], 1.89; CI, 1.34‐2.67; P < .01), older age (OR, 1.06; CI, 1.05‐1.06; P < .01), male sex (OR for female vs male, 0.70; CI, 0.58‐0.84; P < .01), diabetes (OR, 1.26; CI, 1.04‐1.53; P = .02), morbidly obese body mass index (OR, 1.87; CI, 1.24‐2.81; P < .01), and elevated D‐dimer (OR, 6.41 for value >2300; CI, 4.75‐8.66; P < .01) were associated with increased mortality. Recent cancer‐directed medical therapy was not associated with death in multivariable analysis. Among patients with active cancer, those with a hematologic malignancy had the highest mortality rate in comparison with other cancer types (47.83% vs 28.66%; P < .01).ConclusionsThe authors found that patients with an active cancer diagnosis were more likely to die from COVID‐19. Those with hematologic malignancies were at the highest risk of death. Patients receiving cancer‐directed therapy within 3 months before hospitalization had no overall increased risk of death.Lay Summary Our investigators found that hospitalized patients with active cancer were more likely to die from coronavirus disease 2019 (COVID‐19) than those with a history of cancer and those without any cancer history.Patients with hematologic cancers were the most likely among patients with cancer to die from COVID‐19.Patients who received cancer therapy within 3 months before hospitalization did not have an increased risk of death.

Editorial introductions

Editorial introductions

Use, Yield, and Risk of Device-assisted Enteroscopy in the United States: Results From a Large Retrospective Multicenter Cohort.

Since 2001, device-assisted enteroscopy (DAE) has revolutionized the diagnostic and therapeutic capabilities for managing small bowel pathology. Though commonly performed, there have been no recent large studies to assess the use, yield, and risks of DAE and none that include all 3 DAE modalities. We hypothesized that DAE is safe with high diagnostic and therapeutic yields achieved within reasonable procedure duration and here we present a large retrospective multicenter US study evaluating the use, yield, and complications of DAE. After obtaining institutional review board approval, electronic records were used to identify all DAE's performed for luminal small bowel evaluation in adult patients at 4 US referral centers (Duke University Medical Center, New York University Langone Medical Center, Louisiana State University Health Sciences Center, and University of Massachusetts Medical Center) from January 1, 2014 to January 1, 2019. Electronic medical records were reviewed to collect and analyze a variety of procedure-related outcomes. Using the data pooled across centers, descriptive statistics were generated for the patient and procedure-related characteristics and outcomes; relationships between characteristics and outcomes were explored. A total of 1787 DAE's were performed over this 5-year period (392 at Duke University Medical Center, 887 at Louisiana State University Health Sciences Center, 312 at New York University Langone Medical Center, and 195 at University of Massachusetts Medical Center). Of these, there were 1017 (57%) double-balloon, 391 (29%) single-balloon, and 378 (21%) spiral enteroscopies. The mean age of patients undergoing DAE was 66 years and 53% of examinations were performed on women; 18% of patients in the cohort underwent >1 DAE over this time span. A total of 53% of examinations were performed for suspected small bowel bleeding, 31% were directly guided by video capsule endoscopy findings and 8% were performed for abnormal imaging. A total of 85% of examinations used an antegrade approach and DAE took a mean of 45 minutes to complete; 76% of examinations revealed abnormal findings, with vascular, inflammatory, and neoplastic findings seen in 49%, 17%, and 15% of the cohort, respectively. Older age was significantly associated with any abnormal finding, including arteriovenous malformations (P<0.0001); 50% of examinations included a therapeutic maneuver, most commonly argon plasma coagulation/cautery (43%). There were complications in 16 examinations (0.9%) including 2 perforations (0.1%), 6 cases with bleeding (0.3%) and 1 episode of pancreatitis (0.1%). DAE is most commonly performed to evaluate suspected small bowel bleeding and is commonly directed by video capsule findings. DAE is safe, has a high diagnostic yield, with 76% of examinations showing abnormal findings, and frequently features therapeutic maneuvers. Advancing age is associated with abnormal findings on DAE.

Sociodemographic Predictors of Treatment Success and Difficulty in Nasoalveolar Molding

To assess social and demographic influences on caregiver success and difficulty with nasoalveolar molding (NAM). Retrospective review identified patients who began NAM between April 22, 2013, and April 18, 2017, at the New York University Langone Medical Center. Records were reviewed, and the following sociodemographic data retrieved: parental marital status, parental ages, number of siblings, distance traveled to clinic, insurance coverage, concurrent medical conditions, and need for an interpreter. Patients were included if complete charting was available; 106 patients met the inclusion criteria; 79 patients with unilateral and 27 with bilateral clefts. Chart entries indicating incorrect appliance usage, emergency visits, phone calls, and noncompliance were recorded. Alveolar cleft gap closure was measured on pre- and posttreatment models in unilateral cases. Multiple regression analyses were performed to assess the influence of social variables on these outcomes. Alveolar cleft gap closure was 7.2 ± 3.0 mm, or 78.5% ± 19.1%. Cleft closure increased with paternal age by 0.33 mm (P = .007) or 2.0% (P = .017) per year, decreased with maternal age by 0.29 mm (P = .041) per year, and increased in married and partnered parents by 39% (P = .018). Incorrect appliance usage averaged 0.62 fewer instances for married and partnered parents (P = .018) and 0.43 fewer for those with private insurance (P = .019). Alveolar cleft gap closure was more successful for older fathers, younger mothers, and married couples. Married couples were also less likely to experience treatment difficulties such as incorrect appliance usage or inadequate duration of wear, as were those with private insurance coverage.

Brain Imaging Use and Findings in COVID-19: A Single Academic Center Experience in the Epicenter of Disease in the United States.

Coronavirus disease 2019 (COVID-19) is a serious public health crisis and can have neurologic manifestations. This is a retrospective observational case series performed March 1-31, 2020, at New York University Langone Medical Center campuses. Clinical and imaging data were extracted, reviewed, and analyzed. Two hundred forty-two patients with COVID-19 underwent CT or MRI of the brain within 2 weeks after the positive result of viral testing (mean age, 68.7 ± 16.5 years; 150 men/92 women [62.0%/38.0%]). The 3 most common indications for imaging were altered mental status (42.1%), syncope/fall (32.6%), and focal neurologic deficit (12.4%). The most common imaging findings were nonspecific white matter microangiopathy (134/55.4%), chronic infarct (47/19.4%), acute or subacute ischemic infarct (13/5.4%), and acute hemorrhage (11/4.5%). No patients imaged for altered mental status demonstrated acute ischemic infarct or acute hemorrhage. White matter microangiopathy was associated with higher 2-week mortality (P < .001). Our data suggest that in the absence of a focal neurologic deficit, brain imaging in patients with early COVID-19 with altered mental status may not be revealing.

Use of Anesthesia Machines in a Critical Care Setting During the Coronavirus Disease 2019 Pandemic.

The coronavirus disease 2019 (COVID-19) pandemic created an unprecedented need for mechanical ventilation in critically ill patients. To meet this increased demand, some facilities were forced to use anesthesia gas machines (AGMs) as intensive care unit (ICU) ventilators. While an off-label use, AGM manufacturers, the Anesthesia Patient Safety Foundation, and the American Society of Anesthesiologists have guidelines for AGM use in the ICU, however, there is scant literature describing their use. This article describes our experiences at New York University Langone Medical Center using AGMs in the ICU for ventilating critically ill COVID-19 patients.

Spotlight in Plastic Surgery: April 2020

Spotlight in Plastic Surgery: April 2020

Safety Checklist Implementation Did Not Reduce Central Venous Catheter Duration in Pediatric Cardiac ICU Patients.

Introduction:The Center for Disease Control recommends prompt removal of nonessential central venous catheters (CVCs) to reduce the risk for central line–associated bloodstream infections. Safety checklists have been trialed to reduce nonessential CVC days, but pediatric studies are lacking. Our specific aim was to detect >10% reduction in mean CVC duration after implementation of a safety checklist addressing CVCs in our unit.Methods:All patients admitted to the Congenital Cardiovascular Care Unit at New York University Langone Medical Center who had a CVC placed between January 1, 2012, and December 31, 2017, were included. We implemented a checklist addressing CVC use in our unit on June 7, 2013, and modified it on March 10, 2016. We analyzed quarterly mean CVC duration and postsurgical CVC duration over the study period using statistical process control charts.Results:We placed 778 CVCs for 7,947 CVC days during the study period. We noted special cause variation from Q4 2013 to Q2 2014 and a centerline shift in mean CVC duration from 8.91 to 11.10 days in Q1 2015. In a subgroup analysis of the 657 lines placed in surgical patients, there was a centerline shift in mean CVC duration from 6.48 to 8.86 days in Q4 2013.Conclusions:Our study demonstrated an unexpected increase in mean CVC duration after the implementation of a safety checklist designed to decrease nonessential CVC days. Additional studies are needed to identify the ideal method to detect and remove nonessential CVCs and reduce the risk of preventable harm.

Editorial introductions

Editorial introductions

Spotlight in Plastic Surgery: January 2020

Spotlight in Plastic Surgery: January 2020

Editorial introductions

Editorial introductions

Journal Digest

Journal Digest

Evaluating the effects of HIPK2 Inhibition on Castration‐Resistant Prostate Cancer Cells

Prostate cancer is the second leading cause of death in men in the United States. It depends on the signaling by the androgen receptor (AR), which is activated by testosterone. AR signaling promotes normal prostate development as well as cancer. Current treatments for prostate cancer include prostatectomy and androgen deprivation therapy. Although androgen deprivation is effective in halting prostate cancer growth, a group of men are often diagnosed with castration resistant prostate cancer (CRPC), which is refractory to hormone deprivation. Therefore, new targets are needed to stop prostate cancer growth. In this study, we investigated whether Homeodomain‐interacting protein kinase 2 (HIPK2) affects AR signaling and prostate cancer cell growth. To do this, we utilized doxycycline‐induced shRNA‐mediated silencing of HIPK2 expression in 22Rv1 and LNCaP‐95, two cell lines that are refractory to androgen deprivation, and demonstrated substantial knockdown of both HIPK2 mRNA and protein. In addition, we observed significant changes in AR target gene expression. To determine the effects of HIPK2 knockdown on AR subcellular localization, we fractionated control and doxycycline‐treated 22Rv1 and LNCaP‐95 cells. We observed modest changes in chromatin‐bound AR upon HIPK2 depletion, suggesting that HIPK2 influences AR chromatin occupancy and in turn AR‐dependent transcription. We also tested HIPK2 catalytic inhibitors by examining their effects on 22Rv1 and LNCaP‐95 cellular proliferation, and phosphorylation a HIPK2 substrate, SIAH2. We found that HIPK2 inhibitors modestly affected the proliferation and substrate phosphorylation. Thus, HIPK2 can modulate AR activity, highlighting the role of HIPK2 as a new drug target for prostate cancer.Support or Funding InformationNew York University Langone Medical CenterThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

The Diagnosis and Management of Agitationedited by Scott L. Zeller, Kimberly D. Nordstrom, and Michael P. Wilson. New York, Cambridge University Press, 2017, 292 pp., $110.00 (hardcover).

The Diagnosis and Management of Agitationedited by Scott L. Zeller, Kimberly D. Nordstrom, and Michael P. Wilson. New York, Cambridge University Press, 2017, 292 pp., $110.00 (hardcover).

Building and Crossing the Translational Bridge: 2016Alopecia Areata Research Summit Highlights.

Alopecia areata (AA) is a common autoimmune skin disease that results in the loss of hair on the scalp and elsewhere on the body and affects over 146 million people worldwide at some point in their lives. Founded in 1981, the National Alopecia Areata Foundation is a nonprofit organization that supports research to find a cure or acceptable treatment for AA, supports those with the disease, and educates the public about AA. The National Alopecia Areata Foundation conducts research summits every 2 years to review progress and create new directions in its funded and promoted research. The Foundation brings together scientists from all disciplines to get a broad and varied perspective. These AA research summits are part of the Foundation's main strategic initiative, the AA Treatment Development Program, to enhance the understanding of AA and accelerate progress toward a viable treatment.

Association of White Matter Structure With Autism Spectrum Disorder and Attention-Deficit/Hyperactivity Disorder

Clinical overlap between autism spectrum disorder (ASD) and attention-deficit/hyperactivity disorder (ADHD) is increasingly appreciated, but the underlying brain mechanisms remain unknown to date. To examine associations between white matter organization and 2 commonly co-occurring neurodevelopmental conditions, ASD and ADHD, through both categorical and dimensional approaches. This investigation was a cross-sectional diffusion tensor imaging (DTI) study at an outpatient academic clinical and research center, the Department of Child and Adolescent Psychiatry at New York University Langone Medical Center. Participants were children with ASD, children with ADHD, or typically developing children. Data collection was ongoing from December 2008 to October 2015. The primary measure was voxelwise fractional anisotropy (FA) analyzed via tract-based spatial statistics. Additional voxelwise DTI metrics included radial diffusivity (RD), mean diffusivity (MD), axial diffusivity (AD), and mode of anisotropy (MA). This cross-sectional DTI study analyzed data from 174 children (age range, 6.0-12.9 years), selected from a larger sample after quality assurance to be group matched on age and sex. After quality control, the study analyzed data from 69 children with ASD (mean [SD] age, 8.9 [1.7] years; 62 male), 55 children with ADHD (mean [SD] age, 9.5 [1.5] years; 41 male), and 50 typically developing children (mean [SD] age, 9.4 [1.5] years; 38 male). Categorical analyses revealed a significant influence of ASD diagnosis on several DTI metrics (FA, MD, RD, and AD), primarily in the corpus callosum. For example, FA analyses identified a cluster of 4179 voxels (TFCE FEW corrected P < .05) in posterior portions of the corpus callosum. Dimensional analyses revealed associations between ASD severity and FA, RD, and MD in more extended portions of the corpus callosum and beyond (eg, corona radiata and inferior longitudinal fasciculus) across all individuals, regardless of diagnosis. For example, FA analyses revealed clusters overall encompassing 12121 voxels (TFCE FWE corrected P < .05) with a significant association with parent ratings in the social responsiveness scale. Similar results were evident using an independent measure of ASD traits (ie, children communication checklist, second edition). Total severity of ADHD-traits was not significantly related to DTI metrics but inattention scores were related to AD in corpus callosum in a cluster sized 716 voxels. All these findings were robust to algorithmic correction of motion artifacts with the DTIPrep software. Dimensional analyses provided a more complete picture of associations between ASD traits and inattention and indexes of white matter organization, particularly in the corpus callosum. This transdiagnostic approach can reveal dimensional relationships linking white matter structure to neurodevelopmental symptoms.