Publications by authors named "Peter Gordon"

173 Publications

Attitudes and Perceived Barriers to Sexually Transmitted Infection Screening Among Graduate Medical Trainees.

Sex Transm Dis 2021 Feb 11. Epub 2021 Feb 11.

1 Department of Medicine, Division of Infectious Disease, Columbia University Irving Medical Center 2New York-Presbyterian Hospital 3Aaron Diamond AIDS Research Center at Vagelos College of Physicians and Surgeons 4 Department of Internal Medicine, Columbia University Irving Medical Center 5Department of Pediatrics, Columbia University Irving Medical Center 6HIV Center for Clinical and Behavioral Studies at Columbia University and New York State Psychiatric Institute.

Graduate medical training is an opportune time to improve provider delivery of STI screening. A survey of trainees found that the majority feel sexually transmitted infection screening is their job but identified barriers to successful screening. Training that intentionally address service-specific barriers will be valuable in ending the STI epidemic.
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http://dx.doi.org/10.1097/OLQ.0000000000001396DOI Listing
February 2021

Preclinical efficacy of prexasertib in acute lymphoblastic leukemia.

Br J Haematol 2021 Jun 7. Epub 2021 Jun 7.

Department of Pediatrics, Division of Pediatric Hematology and Oncology, University of Minnesota, Minneapolis, MN, USA.

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http://dx.doi.org/10.1111/bjh.17610DOI Listing
June 2021

Attitudes and Perceived Barriers to Routine HIV Screening and Provision and Linkage of Postexposure Prophylaxis and Pre-Exposure Prophylaxis Among Graduate Medical Trainees.

AIDS Patient Care STDS 2021 05 23;35(5):180-187. Epub 2021 Apr 23.

Division of Infectious Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, New York, USA.

New York City is the metropolitan area in the United States with the highest number of new HIV diagnoses nationwide. The End-The-Epidemic (EtE) initiative calls for identifying persons with HIV who remain undiagnosed, linking and retaining persons living with HIV to maximize viral suppression, and facilitate access to pre-exposure prophylaxis (PrEP) for patients at increased risk of HIV. HIV screening represents the first step to both the primary and secondary HIV prevention cascades. We conducted an online, anonymous, cross-sectional survey of residents at all stages of training within four residency programs at one institution in Northern Manhattan between August 2017 and August 2018. All internal medicine, emergency medicine, obstetrics and gynecology trainees, and pediatrics were invited to complete the survey via email. Of 298 eligible trainees, 142 (48%) completed the survey. Most trainees were aware of the HIV testing law and agreed that HIV testing was their responsibility, but few successfully screened most of their patients. Most trainees were not knowledgeable about non-occupational post-exposure prophylaxis (nPEP) or PrEP, but felt that it was important to provide these services across settings. Barriers to HIV, nPEP, and PrEP varied across specialties. Ending the HIV epidemic will require efforts across clinical specialties. In this survey from an EtE jurisdiction, most trainees felt that it is important to provide HIV prevention services in most settings; however, their knowledge and comfort with HIV prevention services other than testing were low. Barriers varied across specialties, and developing specialty-specific materials for trainees may be beneficial.
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http://dx.doi.org/10.1089/apc.2021.0029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106251PMC
May 2021

Parametric transition from deflagration to detonation in stellar medium.

Phys Rev E 2021 Mar;103(3-1):033106

School of Mathematical Sciences, Tel Aviv University, Tel Aviv 69978, Israel.

The nature of thermonuclear explosions of white-dwarf stars is a fundamental astrophysical issue, the first principle interpretation of which is still commonly regarded as an unresolved problem. There is a general consensus that stellar explosions are a manifestation of the deflagration-to-detonation transition of an outward propagating self-accelerating thermonuclear flame subjected to instability-induced corrugations. A similar problem arises in unconfined terrestrial flames where a positive feedback mechanism leading to the pressure runaway has been identified. The present study is an application of this finding to the stellar environment. Notwithstanding a substantial modification of the equation of state the runaway effect endures. Approaching the runaway point the pretransition flame may stay perfectly subsonic, which challenges the view that to ensure the transition the flame should cross the threshold of Chapman-Jouguet deflagration.
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http://dx.doi.org/10.1103/PhysRevE.103.033106DOI Listing
March 2021

Therapeutic Leukapheresis in Pediatric Leukemia: Utilization Trend and Early Outcomes in a US Nationwide Cohort.

J Pediatr Hematol Oncol 2021 May 5. Epub 2021 May 5.

Division of Pediatric Hematology/Oncology Division of Transfusion Medicine, Department of Laboratory Medicine and Pathology Biostatistics Core, Masonic Cancer Center Division of Epidemiology and Clinical Research, Department of Pediatrics, University of Minnesota, Minneapolis, MN.

Leukapheresis (LA) in pediatric leukemia is performed for leukostasis, a life-threatening emergency in the setting of extremely increased blast cell counts. The authors aimed to assess the epidemiology of pediatric leukemia who received LA. The authors reviewed US nationally representative admission records of patients aged less than 20 years in the Kids' Inpatient Database for the years 2000, 2003, 2006, 2009, 2012, and 2016. Incidence of new leukemia cases who underwent LA were calculated for the years 2009, 2012, and 2016. Cox and logistic regression analyses were performed to ascertain the risk factors for adverse outcomes. There were 526 admissions for pediatric patients with acute lymphoblastic leukemia (ALL) (n=328), acute myeloid leukemia (AML) (n=124), or chronic myeloid leukemia (CML) (n=74) who underwent LA over the study period. The incidence of leukemia cases that required LA was lower in 2016 than in 2009 or 2012 (1.4%, 2.2%, and 2.7%, respectively; P=0.001). In-hospital mortality was higher in AML than ALL (hzard ratio, 3.2; 95% confidence interval, 1.1-9.1). None with CML died during admission. This first population-based study of LA in pediatric leukemia showed a decreased utilization of LA over recent years. The higher inpatient mortality in AML, as compared with ALL or CML, warrant further investigations.
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http://dx.doi.org/10.1097/MPH.0000000000002140DOI Listing
May 2021

Filtering efficiency measurement of respirators by laser-based particle counting method.

Measurement (Lond) 2021 May 20;176:109173. Epub 2021 Feb 20.

Department of Electronics Technology, Faculty of Electrical Engineering and Informatics, Budapest University of Technology and Economics, Műegyetem rkp. 3-9, H-1111, Budapest, Hungary.

Respirators are one of the most useful personal protective equipment which can effectively limit the spreading of coronavirus (COVID-19). There are a worldwide shortage of respirators, melt-blown non-woven fabrics, and respirator testing possibilities. An easy and fast filtering efficiency measurement method was developed for testing the filtering materials of respirators. It works with a laser-based particle counting method, and it can determine two types of filtering efficiencies: Particle Filtering Efficiency (PFE) at given particle sizes and Concentration Filtering Efficiency (CFE) in the case of different aerosols. The measurement method was validated with different aerosol concentrations and with etalon respirators. Considerable advantages of our measurement method are simplicity, availability, and the relatively low price compared to the flame-photometer based methods. The ability of the measurement method was tested on ten different types of Chinese KN95 respirators. The quality of these respirators differs much, only two from ten reached 95% filtering efficiency.
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http://dx.doi.org/10.1016/j.measurement.2021.109173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7896493PMC
May 2021

HIV-1 Infection Does Not Change Disease Course or Inflammatory Pattern of SARS-CoV-2-Infected Patients Presenting at a Large Urban Medical Center in New York City.

Open Forum Infect Dis 2021 Feb 28;8(2):ofab029. Epub 2021 Jan 28.

Department of Medicine, Division of Infectious Diseases, Columbia University Irving Medical Center, New York, New York, USA.

Background: The clinical impact of coronavirus disease 2019 (COVID-19) among people with HIV (PWH) remains unclear. In this retrospective cohort study of COVID-19, we compared clinical outcomes and laboratory parameters among PWH and controls.

Methods: Sixty-eight PWH diagnosed with COVID-19 were matched 1:4 to patients without known HIV diagnosis, drawn from a study population of all patients who were diagnosed with COVID-19 at an academic urban hospital. The primary outcome was death/discharge to hospice within 30 days of hospital presentation.

Results: PWH were more likely to be admitted from the emergency department than patients without HIV (91% vs 71%;  = .001). We observed no statistically significant difference between admitted PWH and patients without HIV in terms of 30-day mortality rate (19% vs 13%, respectively) or mechanical ventilation rate (18% vs 20%, respectively). PWH had higher erythrocyte sedimentation rates than controls on admission but did not differ in other inflammatory marker levels or nasopharyngeal/oropharyngeal severe acute respiratory syndrome coronavirus 2 viral load estimated by reverse transcriptase polymerase chain reaction cycle thresholds.

Conclusions: HIV infection status was associated with a higher admission rate; however, among hospitalized patients, PWH did not differ from HIV-uninfected controls by rate of mechanical ventilation or death/discharge to hospice.
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http://dx.doi.org/10.1093/ofid/ofab029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7880266PMC
February 2021

Clinical and Demographic Characteristics of HIV Post-Exposure Prophylaxis Users in New York City.

J Health Care Poor Underserved 2020 ;31(2):672-681

Incidence of HIV infection remains high in New York City and, while considerable attention has been paid to the scale-up of pre-exposure prophylaxis (PrEP), post-exposure prophylaxis (PEP) plays an important role in the HIV prevention continuum. We conducted a retrospective analysis of clinical and demographic characteristics of individuals receiving HIV post-exposure prophylaxis at a large academic medical center in northern Manhattan. Post-exposure prophylaxis users were predominantly Latinx (52.8%) and/or African American (33.7%) men who have sex with men (72%), representing the underserved groups at highest risk of HIV infection. Many individuals (20%) requiring PEP presented to their clinician seeking initiation of PrEP. Frequent PEP users may be good candidates for PrEP but psychosocial barriers such as home environment and recreational drug use must be addressed for successful transitions. Patient counseling for at-risk groups should involve both PEP and PrEP screening and must be sensitized to the needs and cultures of the communities they serve.
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http://dx.doi.org/10.1353/hpu.2020.0053DOI Listing
January 2020

Comparative Evaluation of Pellet Cushioning Agents by Various Imaging Techniques and Dissolution Studies.

AAPS PharmSciTech 2020 Dec 29;22(1):14. Epub 2020 Dec 29.

Department of Pharmaceutics, Semmelweis University, Hőgyes E. Str. 7, Budapest, 1092, Hungary.

Most of the commercially available pharmaceutical products for oral administration route are marketed in the tablet dosage forms. However, compression of multiparticulate systems is a challenge for the pharmaceutical research and industry, especially if the individual unit is a coated particle, as the release of the active ingredient depends on the integrity of the coating. In the present study, polymer-coated pellets tableted with different types of excipients (powder, granules, pellets) then were investigated by various tablet-destructive (microscopic) and tablet non-destructive (microfocus X-ray; microCT) imaging methods. The information obtained from the independent evaluation of the in vitro drug release profiles model is confirmed by the results obtained by image analysis, regardless of whether X-ray or stereomicroscopic images of the coated, tableted pellets were used for image analysis. The results of this study show that the novel easy-to-use, fast, and non-destructive MFX method is a good alternative to the already used microscopic image analysis methods regarding the characterization of particulates, compressed into tablets.
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http://dx.doi.org/10.1208/s12249-020-01902-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7772162PMC
December 2020

Women Are Less Likely to Be Tested for HIV or Offered Preexposure Prophylaxis at the Time of Sexually Transmitted Infection Diagnosis.

Sex Transm Dis 2021 01;48(1):32-36

Department of Internal Medicine, Division of Infectious Diseases.

Background: Ending the HIV epidemic requires linkage of at-risk individuals from diverse health care settings to comprehensive HIV prevention services. Sexually transmitted infections (STIs) are significant biomarkers of HIV risk and should trigger preexposure prophylaxis (PrEP) discussion. We reviewed STI testing practices outside of sexual health clinics to identify opportunities for improvement in the provision of HIV prevention services.

Methods: An electronic sexual health dashboard was used to identify patient encounters with a positive gonorrhea, chlamydia, and/or rapid plasma reagin test result between January 1, 2019, and August 23, 2019, at a large urban academic medical center. A retrospective chart review was performed to assess HIV testing, completeness of STI screening, and HIV prevention discussion; inadequate screening was defined as no HIV test in 12 months before STI diagnosis.

Results: A total of 815 patients with 856 patient encounters were included. Patients were predominantly female (64.4%); median age was 24 years (range, 18-85 years). The most common test and most common positive test result was the genitourinary gonorrhea/chlamydia nucleic acid amplification test. Multisite testing was rare (7.5% of patient encounters) and performed more frequently in men than in women (20.3% vs. 0.36%). Women were also more likely to be inadequately screened for HIV (15.1% vs. 25.8%).Documentation of PrEP discussion was rare (4.7% of patient encounters) compared with safe sex (44.6%) and condoms (49.8%). Preexposure prophylaxis was discussed almost exclusively with men compared with women (17% vs. 1.1%).

Conclusions: In patients diagnosed with bacterial STI outside of sexual health clinics, gaps in HIV prevention exist. HIV screening, multisite STI screening, and discussion of PrEP were particularly infrequent among women.
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http://dx.doi.org/10.1097/OLQ.0000000000001265DOI Listing
January 2021

The translational repressor 4E-BP1 regulates RRM2 levels and functions as a tumor suppressor in Ewing sarcoma tumors.

Oncogene 2021 Jan 15;40(3):564-577. Epub 2020 Nov 15.

Division of Pediatric Hematology/Oncology, Department of Pediatrics, University of Iowa, Iowa City, IA, 52242, USA.

Ribonucleotide reductase (RNR), which is a heterodimeric tetramer composed of RRM1 and RRM2 subunits, is the rate-limiting enzyme in the synthesis of deoxyribonucleoside triphosphates (dNTPs) and essential for both DNA replication and the repair of DNA damage. The activity of RNR is coordinated with the cell cycle and regulated by fluctuations in the level of the RRM2 subunit. Multiple cancer types, including Ewing sarcoma tumors, are sensitive to inhibitors of RNR or a reduction in the levels of either the RRM1 or RRM2 subunits of RNR. Here, we show that the expression of the RRM2 protein is dependent on active protein synthesis and that 4E-BP1, a repressor of cap-dependent protein translation, specifically regulates the level of the RRM2 protein. Furthermore, inhibition of mTORC1/2, but not mTORC1, activates 4E-BP1, inhibits protein synthesis, and reduces the level of the RRM2 protein in multiple sarcoma cell lines. This effect of mTORC1/2 inhibitors on protein synthesis and RRM2 levels was rescued in cell lines with the CRISPR/Cas9-mediated knockout of 4E-BP1. In addition, the inducible expression of a mutant 4E-BP1 protein that cannot be phosphorylated by mTOR blocked protein synthesis and inhibited the growth of Ewing sarcoma cells in vitro and in vivo in a xenograft. Overall, these results provide insight into the multifaceted regulation of RRM2 protein levels and identify a regulatory link between protein translation and DNA replication.
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http://dx.doi.org/10.1038/s41388-020-01552-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7856031PMC
January 2021

Immediate Antiretroviral Therapy: The Need for a Health Equity Approach.

Int J Environ Res Public Health 2020 10 8;17(19). Epub 2020 Oct 8.

HIV Center for Clinical and Behavioral Studies, NY State Psychiatric Institute and Columbia University, New York, NY 10032, USA.

Immediate antiretroviral therapy (iART), defined as same-day initiation of ART or as soon as possible after diagnosis, has recently been recommended by global and national clinical care guidelines for patients newly diagnosed with human immunodeficiency virus (HIV). Based on San Francisco's Rapid ART Program Initiative for HIV Diagnoses (RAPID) model, most iART programs in the US condense ART initiation, insurance acquisition, housing assessment, and mental health and substance use evaluation into an initial visit. However, the RAPID model does not explicitly address structural racism and homophobia, HIV-related stigma, medical mistrust, and other important factors at the time of diagnosis experienced more poignantly by African American, Latinx, men who have sex with men (MSM), and transgender patient populations. These factors negatively impact initial and subsequent HIV care engagement and exacerbate significant health disparities along the HIV care continuum. While iART has improved time to viral suppression and linkage to care rates, its association with retention in care and viral suppression, particularly in vulnerable populations, remains controversial. Considering that in the US the HIV epidemic is sharply defined by healthcare disparities, we argue that incorporating an explicit health equity approach into the RAPID model is vital to ensure those who disproportionately bear the burden of HIV are not left behind.
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http://dx.doi.org/10.3390/ijerph17197345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7579579PMC
October 2020

At-Home Testing for Sexually Transmitted Infections During the COVID-19 Pandemic.

Sex Transm Dis 2021 01;48(1):e11-e14

Division of Infectious Diseases, Department of Internal Medicine, Columbia University Irving Medical Center, New York, NY.

During the COVID-19 pandemic in New York City, NewYork-Presbyterian Hospital provided HIV prevention patients with gonorrhea/chlamydia testing kits at home. This report describes the program implementation to provide other sexual health clinics with a roadmap in adapting to a "new normal" in providing comprehensive sexual health care virtually to patients.
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http://dx.doi.org/10.1097/OLQ.0000000000001313DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130547PMC
January 2021

Creep attenuation in glassy polymer nanocomposites with variable polymer-nanoparticle interactions.

Soft Matter 2020 Oct;16(38):8912-8924

Department of Materials Science & Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA. and Department of Chemical & Biomolecular Engineering, University of Pennsylvania, Philadelphia, PA 19104, USA.

The use of nanoparticle reinforced polymer matrices in continuous fiber composites for infrastructure applications requires a comprehensive understanding of viscoelastic creep. Critical parameters affecting the mechanical reinforcement offered by nanoparticles include nanoparticle size and concentration, as well as the interaction between the nanoparticle surface and polymer matrix. Here, we study the viscoelastic creep of nanocomposite systems comprised of glassy thermoplastic polymers and spherical silica nanoparticles of varying sizes and surface functionalization using a dynamic mechanical analysis (DMA) accelerated testing methodology. Significant differences in the nanoparticle dispersions in these nanocomposites were observed via transmission electron microscopy (TEM) and small-angle X-ray scattering (SAXS) and are attributed to differences in the polymer-polymer and polymer-particle interaction strengths. The DMA measurements indicate a decrease in compliance at short times with increased nanoparticle loading that is largely independent of nanoparticle dispersion morphology and polymer-particle interaction strength. Conversely, long term creep behavior shows a much stronger dependence on these parameters with the creep onset time increasing by up to three orders of magnitude. For similar nanoparticle loadings, the time to critical deformation in systems with well-distributed, networked nanoparticle morphologies was larger by an order of magnitude compared to systems exhibiting strong nanoparticle aggregation. The networked systems delayed the time to critical deformation by three orders of magnitude over that of neat polymer. The increase in time to critical deformation is also greater in composites with smaller nanoparticles at similar loadings, which we attribute to the development of percolated nanoparticle networks. These results demonstrate the significant effects polymer-particle interactions and dispersion morphologies can have on the long-term creep compliance of thermoplastic nanocomposites.
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http://dx.doi.org/10.1039/d0sm01247eDOI Listing
October 2020

Psychosocial Factors and the Care Cascade for Hepatitis C Treatment Colocated at a Syringe Service Program.

J Infect Dis 2020 09;222(Suppl 5):S392-S400

Comprehensive Health Program, New York Presbyterian Hospital, New York, USA.

Background: Direct-acting antiviral (DAA) therapy for hepatitis C virus (HCV) is highly effective. However, people who inject drugs face significant barriers to DAA access.

Methods: We describe a program that colocates HCV management within a syringe service program in New York City. We performed a retrospective chart review of all patients with confirmed HCV viremia.

Results: From 2015 to 2018, 102 patients with viremia completed intake. Fifty-eight patients started DAAs. Nine patients discontinued treatment or were lost to follow-up before completion; 1 is continuing DAA treatment. Of 48 patients who completed therapy, sustained virologic response (SVR) was achieved in 43 (89.6%). Age and established mental health treatment at intake were associated with SVR. Regular cocaine use was negatively associated with SVR in univariate analysis, but this association was not significant after adjustment for age. Of 30 patients completing DAA therapy with active illicit opioid use at intake, 14 (46.4%) engaged in opioid use disorder (OUD) treatment during therapy, and 9 remained in OUD treatment after completion of DAA treatment.

Conclusions: Loss to follow-up is a challenge for people who inject drugs, but among those who completed treatment, SVR was achieved at a high rate. Mental health treatment may facilitate HCV cure. Conversely, HCV therapy may facilitate engagement in OUD treatment and other services.
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http://dx.doi.org/10.1093/infdis/jiaa142DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7566642PMC
September 2020

Rapid automatized naming (RAN): effects of aging on a predictor of reading skill.

Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 2021 07 17;28(4):632-644. Epub 2020 Aug 17.

Department of Communication Sciences and Disorders, East Carolina University , Greenville, USA.

Rapid Automatized Naming (RAN), a task in which participants must name a series of items as rapidly as possible, has been very useful as a measure of cognitive abilities that predict reading skill both in children and in young adults (YAs). This study examined RAN performance of 100 YAs and 80 cognitively healthy older adults (OAs). RAN performance was highly reliable but showed only a few weak correlations to other measures of individual differences used to study cognitive aging. RAN performance did not differ significantly by age group for symbolic RANs but was significantly slower for OAs than YAs for non-symbolic RANs. This pattern suggests that healthy aging is associated with little to no decline in the ability to sustain overlapping encoding and production of a sequence of items when it involves the form-to-form mapping required by symbolic RANs but with measurable decline in that ability when it involves the concept-to-form mapping required by non-symbolic RANs.
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http://dx.doi.org/10.1080/13825585.2020.1806987DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7887125PMC
July 2021

Body mass index associated with childhood and adolescent high-risk B-cell acute lymphoblastic leukemia risk: A Children's Oncology Group report.

Cancer Med 2020 09 24;9(18):6825-6835. Epub 2020 Jul 24.

Division of Hematology/Oncology, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.

Background: Obesity is a risk factor for many adulthood cancers, but its role in childhood, adolescent, and young adult (AYA) cancer is unknown. Childhood and AYA acute lymphoblastic leukemia (ALL) incidence and obesity prevalence have shown concurrent increases. We sought to identify whether obesity may be a risk factor for childhood and AYA ALL.

Methods: Characteristics from individuals with ALL, aged 2-30 years, diagnosed 2004-2017 and treated on Children's Oncology Group (COG) protocols with available pre-treatment anthropometric data (N = 4726) were compared to National Health and Nutrition Examination Survey controls (COG AALL17D2). Body mass index (BMI) was defined using standard CDC definitions. Multivariate conditional logistic regression assessed associations between BMI and ALL with additional analyses stratified by sex and race/ethnicity.

Results: Among cases (72% high-risk (HR) B-ALL, 28% T-ALL), 5% had underweight, 58% normal weight, 17% overweight, and 20% obesity. Underweight (OR 2.11, 95% CI 1.56-2.85) and obesity (OR 1.32, 95% CI 1.15-1.53) were associated with B-ALL diagnosis. Specifically, obesity was associated with B-ALL among males (OR 1.57, 95% CI 1.30-1.91) and Hispanic children (OR 1.78, 95% CI 1.39-2.29). Obesity was also associated with central nervous system (CNS) involvement.

Conclusion: Pre-treatment obesity is associated with HR B-ALL among males and Hispanics, as well as with CNS involvement, suggesting common physiology between obesity and leukemogenesis. An association between underweight and ALL was confirmed, likely due to cancer-associated wasting. These results have important public health implications for obesity prevention and treatment in children and adolescents to reduce cancer risk.
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http://dx.doi.org/10.1002/cam4.3334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7520304PMC
September 2020

Successful Rituximab Monotherapy in Advanced-stage, Epstein-Barr Virus-positive Diffuse Large B-Cell Lymphoma in an Adolescent With Systemic Juvenile Idiopathic Arthritis.

J Pediatr Hematol Oncol 2021 05;43(4):e498-e500

Department of Pediatrics, Division of Pediatric Hematology/Oncology.

Epstein-Barr virus-positive diffuse large B-cell lymphoma (EBV+ DLBCL) in pediatrics most commonly occurs as an iatrogenic immunodeficiency-associated lymphoproliferative disease. We report an 18-year-old female individual with refractory systemic juvenile idiopathic arthritis, treated with multiple immunosuppressive agents, who was diagnosed with stage III, EBV+ DLBCL. The patient achieved sustained complete remission after 4 weekly doses of rituximab monotherapy and reduction of immunosuppression. This case suggests that a post-transplant lymphoproliferative disease-like treatment approach can be a safe and effective therapy in a nontransplant, yet severely immunosuppressed, patient with EBV+ DLBCL.
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http://dx.doi.org/10.1097/MPH.0000000000001869DOI Listing
May 2021

COVID-19, Telemedicine, and Patient Empowerment in HIV Care and Research.

AIDS Behav 2020 07;24(7):1990-1993

Division of Infectious Disease, Department of Internal Medicine, Columbia University Irving Medical Center, New York, NY, USA.

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http://dx.doi.org/10.1007/s10461-020-02926-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7241062PMC
July 2020

Longitudinal analysis of social and behavioral determinants of health in the EHR: exploring the impact of patient trajectories and documentation practices.

AMIA Annu Symp Proc 2019 4;2019:399-407. Epub 2020 Mar 4.

Department of Biomedical Informatics, Columbia University, New York, NY, USA.

Social and behavioral determinants of health (SBDH) are environmental and behavioral factors that impede disease self-management and can exacerbate clinical conditions. While recent research in the informatics community has focused on building systems that can automatically infer SBDH from the patient record, it is unclear how such determinants change overtime. This study analyzes the longitudinal characteristics of 4 common SBDH as expressed in the patient record and compares the rates of change among distinct SBDH. In addition, manual review of patient notes was undertaken to establish whether changes in patient SBDH status reflected legitimate changes in patient status or rather potential data quality issues. Our findings suggest that a patient's SBDH status is liable to change over time and that some changes reflect poor social history taking by clinicians.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153098PMC
August 2020

Acceptability of electronic healthcare predictive analytics for HIV prevention: a qualitative study with men who have sex with men in New York City.

Mhealth 2020 5;6:11. Epub 2020 Apr 5.

Division of Infectious Diseases, Department of Internal Medicine, Columbia University Irving Medical Center, New York, NY, USA.

Background: Large data sets, also known as "big data", shared in health information exchanges (HIEs), can be used in novel ways to advance health, including among communities at risk for HIV infection. We examined values and opinions about the acceptability of using electronic healthcare predictive analytics (eHPA) to promote HIV prevention in men who have sex with men (MSM). Our aims were twofold: (I) to evaluate the perspectives of MSM with diverse race/ethnicity and age on the acceptability of predictive analytics to determine individual HIV risk and (II) to determine acceptability of having targeted prevention messaging based upon those risk estimates sent directly to the consumer. Two of the authors facilitated 12 focus groups (n=57) with adult MSM without HIV, living in NYC. Groups were divided by ethnicity (Black, Latino, and White) and age (under 35 and 35 and over). Participants were recruited through HIV prevention sites, community-based organizations, social media, and Internet sites that serve these communities. Grounded theory methods were used to analyze the data with Dedoose.

Results: We identified six main themes related to acceptability: (I) reach, relevance, and potential uptake of using predictive analytics to establish HIV risk and deliver targeted prevention messaging; (II) patient-provider communication; (III) public health and individual rights; (IV) perceptions of intervention effectiveness; (V) electronic health data security; and (VI) stigma. Within each thematic domain, MSM discussed concerns, benefits, and provided recommendations for implementation.

Conclusions: MSM in this study were supportive of the use of "big data" and technology to reach marginalized populations and improve public health, yet expressed concerns about the relevance, effectiveness, and security eHPA. Efforts to advance eHPA for HIV prevention should address these concerns, especially among the most-at-risk communities of color. Development of eHPA for HIV prevention should involve targeted messaging that addresses specific concerns regarding eHPA security, accuracy, and relevance.
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http://dx.doi.org/10.21037/mhealth.2019.10.03DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7136656PMC
April 2020

Detecting Social and Behavioral Determinants of Health with Structured and Free-Text Clinical Data.

Appl Clin Inform 2020 01 4;11(1):172-181. Epub 2020 Mar 4.

Department of Biomedical Informatics, Columbia University, New York, New York, United States.

Background: Social and behavioral determinants of health (SBDH) are environmental and behavioral factors that often impede disease management and result in sexually transmitted infections. Despite their importance, SBDH are inconsistently documented in electronic health records (EHRs) and typically collected only in an unstructured format. Evidence suggests that structured data elements present in EHRs can contribute further to identify SBDH in the patient record.

Objective: Explore the automated inference of both the presence of SBDH documentation and individual SBDH risk factors in patient records. Compare the relative ability of clinical notes and structured EHR data, such as laboratory measurements and diagnoses, to support inference.

Methods: We attempt to infer the presence of SBDH documentation in patient records, as well as patient status of 11 SBDH, including alcohol abuse, homelessness, and sexual orientation. We compare classification performance when considering clinical notes only, structured data only, and notes and structured data together. We perform an error analysis across several SBDH risk factors.

Results: Classification models inferring the presence of SBDH documentation achieved good performance (F1 score: 92.7-78.7; F1 considered as the primary evaluation metric). Performance was variable for models inferring patient SBDH risk status; results ranged from F1 = 82.7 for LGBT (lesbian, gay, bisexual, and transgender) status to F1 = 28.5 for intravenous drug use. Error analysis demonstrated that lexical diversity and documentation of historical SBDH status challenge inference of patient SBDH status. Three of five classifiers inferring topic-specific SBDH documentation and 10 of 11 patient SBDH status classifiers achieved highest performance when trained using both clinical notes and structured data.

Conclusion: Our findings suggest that combining clinical free-text notes and structured data provide the best approach in classifying patient SBDH status. Inferring patient SBDH status is most challenging among SBDH with low prevalence and high lexical diversity.
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http://dx.doi.org/10.1055/s-0040-1702214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7056402PMC
January 2020

Oral and Gut Microbial Diversity and Immune Regulation in Patients with HIV on Antiretroviral Therapy.

mSphere 2020 02 5;5(1). Epub 2020 Feb 5.

Department of Medicine, Division of Infectious Diseases, Columbia University Medical Center, New York, New York, USA

Despite evidence of a chronic inflammatory phenotype in people living with HIV (PLWH) on antiretroviral therapy (ART), the role of oral microbiota in chronic immune activation has not been fully explored. We aimed to determine the relationship between oral and gut microbiome diversity and chronic systemic inflammation in ART-treated PLWH with prevalent severe periodontitis, an inflammatory condition commonly associated with HIV infection. We assessed bacterial and fungal communities at oral and gastrointestinal sites in a cohort ( = 52) of primarily postmenopausal women on ART using 16S rRNA and internal transcribed spacer (ITS) sequencing and measured cellular and soluble markers of inflammation and immune dysfunction. Linear mixed-effect regression and differential abundance analyses were used to associate clinical characteristics and immunological markers with bacterial and fungal diversity and community composition. Bacterial α-diversity in plaque, saliva, and gut was associated with different immunological markers, while mycobial diversity was not associated with soluble or cellular biomarkers of immune stimulation or T cell dysfunction. Furthermore, lipopolysaccharide-positive (LPS) bacteria previously linked to inflammatory outcomes were enriched at oral sites in patients with severe periodontitis. Fungal α-diversity was reduced in plaque from teeth with higher clinical attachment loss, a marker of periodontitis, and in saliva and plaque from patients with a history of AIDS. Our results show that both bacterial and fungal oral microbiome communities likely play a role in chronic systemic immune activation in PLWH. Thus, interventions targeting both inflammation and the microbiome, particularly in the oral cavity, may be necessary to reduce chronic immune dysregulation in patients with HIV. A feedback loop between dysbiotic gut microbiota, increased translocation of microbial products such as lipopolysaccharide, and inflammation has been hypothesized to cause immune system dysfunction in early HIV infection. However, despite evidence of a chronic inflammatory phenotype in patients on antiretroviral therapy (ART), the role of oral microbiota in systemic immune activation and the relationship between oral and gut bacterial and fungal diversity have not been explored. Our study suggests a crucial role for oral bacterial and fungal communities in long-term systemic immune activation in patients on ART, expanding the current paradigm focused on gut bacteria. Our results indicate that interventions targeting both inflammation and microbial diversity are needed to mitigate oral inflammation-related comorbidities, particularly in HIV-positive patients. More broadly, these findings can bolster general models of microbiome-mediated chronic systemic immune activation and aid the development of precise microbiota-targeted interventions to reverse chronic inflammation.
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http://dx.doi.org/10.1128/mSphere.00798-19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7002309PMC
February 2020

The meninges enhance leukaemia survival in cerebral spinal fluid.

Br J Haematol 2020 05 12;189(3):513-517. Epub 2020 Jan 12.

Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USA.

Central nervous system (CNS) relapse is a common cause of treatment failure in patients with acute lymphoblastic leukaemia (ALL) despite current CNS-directed therapies that are also associated with significant short- and long-term toxicities. Herein, we showed that leukaemia cells exhibit decreased proliferation, elevated reactive oxygen species (ROS) and increased cell death in cerebral spinal fluid (CSF) both in vitro and in vivo. However, interactions between leukaemia and meningeal cells mitigated these adverse effects. This work expands our understanding of the pathophysiology of CNS leukaemia and suggests novel therapeutic approaches for more effectively targeting leukaemia cells in the CNS.
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http://dx.doi.org/10.1111/bjh.16270DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7192757PMC
May 2020

Individual differences in reading: Separable effects of reading experience and processing skill.

Mem Cognit 2020 05;48(4):553-565

Department of Psychology, University of Richmond, Richmond, VA, USA.

A large-scale eye-tracking study examined individual variability in measures of word recognition during reading among 546 college students, focusing on two established individual-differences measures: the Author Recognition Test (ART) and Rapid Automatized Naming (RAN). ART and RAN were only slightly correlated, suggesting that the two tasks reflect independent cognitive abilities in this large sample of participants. Further, individual variability in ART and RAN scores were related to distinct facets of word-recognition processes. Higher ART scores were associated with increased skipping rates, shorter gaze duration, and reduced effects of word frequency on gaze duration, suggesting that this measure reflects efficiency of basic processes of word recognition during reading. In contrast, faster times on RAN were associated with enhanced foveal-on-parafoveal effects, fewer first-pass regressions, and shorter second-pass reading times, suggesting that this measure reflects efficient coordination of perceptual-motor and attentional processing during reading. These results demonstrate that ART and RAN tasks make independent contributions to predicting variability in word-recognition processes during reading.
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http://dx.doi.org/10.3758/s13421-019-00989-3DOI Listing
May 2020

Disrupting the leukemia niche in the central nervous system attenuates leukemia chemoresistance.

Haematologica 2020 08 17;105(8):2130-2140. Epub 2019 Oct 17.

Division of Pediatric Hematology and Oncology, Department of Pediatrics, University of Minnesota

Protection from acute lymphoblastic leukemia relapse in the central nervous system (CNS) is crucial to survival and quality of life for leukemia patients. Current CNS-directed therapies cause significant toxicities and are only partially effective. Moreover, the impact of the CNS microenvironment on leukemia biology is poorly understood. In this study we showed that leukemia cells associated with the meninges of xenotransplanted mice, or co-cultured with meningeal cells, exhibit enhanced chemoresistance due to effects on both apoptosis balance and quiescence. From a mechanistic standpoint, we found that leukemia chemoresistance is primarily mediated by direct leukemia-meningeal cell interactions and overcome by detaching the leukemia cells from the meninges. Next, we used a co-culture adhesion assay to identify drugs that disrupted leukemia-meningeal adhesion. In addition to identifying several drugs that inhibit canonical cell adhesion targets we found that Me6TREN (Tris[2-(dimethylamino)ethyl]amine), a novel hematopoietic stem cell-mobilizing compound, also disrupted leukemia-meningeal adhesion and enhanced the efficacy of cytarabine in treating CNS leukemia in xenotransplanted mice. This work demonstrates that the meninges exert a critical influence on leukemia chemoresistance, elucidates mechanisms of relapse beyond the well-described role of the blood-brain barrier, and identifies novel therapeutic approaches for overcoming chemoresistance.
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http://dx.doi.org/10.3324/haematol.2019.230334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7395284PMC
August 2020

Engaging a Predominantly Latino Community in HIV Prevention: Laying the Groundwork for Pre-exposure Prophylaxis and HIV Sexual Health Programs.

J Assoc Nurses AIDS Care 2020 Jan-Feb;31(1):92-97

Caroline Carnevale, DNP, MPH, is a Principal Investigator, HIV Prevention Program, New York Presbyterian Hospital Comprehensive Health Center, New York City, New York, USA. Jason Zucker, MD, MS, is a Postdoctoral Clinical Fellow, Divisions of Infectious Diseases, Departments of Internal Medicine and Pediatrics, Columbia University Medical Center, New York City, New York, USA. Alexander Borsa, HIV Prevention Program, New York Presbyterian Hospital Comprehensive Health Center, New York City, New York, USA. Bianka Northland, is a Research Assistant, Division of Infectious Diseases, Department of Internal Medicine, Columbia University Medical Center, New York City, New York, USA. Jonathan Castro, MSW, HIV, Prevention Program, New York Presbyterian Hospital Comprehensive Health Center, New York City, New York, USA. Emma Molina, HIV Prevention Program, New York Presbyterian Hospital Comprehensive Health Center, New York City, New York, USA. Paul Richards, MPH, HIV Prevention Program, New York Presbyterian Hospital Comprehensive Health Center, New York City, New York, USA. Jose Dominguez, HIV Prevention Program, New York Presbyterian Hospital Comprehensive Health Center, New York City, New York, USA. William George, HIV Prevention Program, New York Presbyterian Hospital Comprehensive Health Center, New York City, New York, USA. Alwyn Cohall, MD, is a Professor, Divisions of Sociomedical Sciences, Population and Family Health, and Pediatrics at the Columbia University Medical Center. Susan Olender, MD, is an Assistant Professor, Division of Infectious Diseases, Department of Internal Medicine, Columbia University Medical Center, New York City, New York, USA. Peter Gordon, MD, is an Assistant Professor, Division of Infectious Diseases, Department of Internal Medicine, Columbia University Medical Center, New York City, New York, USA. Magdalena E. Sobieszczyk, MD, MPH, is an Associate Professor, Division of Infectious Diseases, Department of Internal Medicine, Columbia University Medical Center, New York City, New York, USA.

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http://dx.doi.org/10.1097/JNC.0000000000000121DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8117719PMC
September 2020

Mixed epithelial and stromal tumor after pediatric kidney transplant.

Pediatr Transplant 2019 12 8;23(8):e13575. Epub 2019 Sep 8.

Division of Pediatric Nephrology, University of Minnesota, Minneapolis, Minnesota.

MEST of the kidney are a benign group of tumors with very rare incidence of malignant transformation. First described in 1998, this tumor has never been reported in a transplanted organ before. We present a unique case of de novo MEST in a donor kidney 4 years after transplant into a pediatric patient. Although removal of the lesions is curative without risking malignant transformation, in this case, surgical removal was not attempted to prevent reduction in transplant longevity. In this unique report of MEST in a transplanted kidney, we describe the patient/transplant outcomes without MEST resection.
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http://dx.doi.org/10.1111/petr.13575DOI Listing
December 2019

Ruxolitinib combined with chemotherapy can eradicate chemorefractory central nervous system acute lymphoblastic leukaemia.

Br J Haematol 2019 10 5;187(1):e24-e27. Epub 2019 Aug 5.

Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.

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http://dx.doi.org/10.1111/bjh.16142DOI Listing
October 2019