Faculty Bibliography

BACKGROUND:Although 20 pancreatic cancer susceptibility loci have been identified through genome-wide association studies (GWAS) in individuals of European ancestry, much of its heritability remains unexplained and the genes responsible largely unknown. METHODS:To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study (TWAS) in Europeans using three approaches, FUSION, MetaXcan and SMulTiXcan. We integrated GWAS summary statistics from 9,040 pancreatic cancer cases and 12,496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics, LTG (n = 95) and Genotype-Tissue Expression, GTEx v7 (n = 174) datasets), and data from 48 different tissues (GTEx v7, n = 74-421 samples). RESULTS:We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (FDR < 0.05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12:, PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22: RP11-888D10.3; and 19p13.11: PGPEP1) and 11 at 6 known risk loci (5p15.33: TERT, CLPTM1L, ZDHHC11B; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci, and TERT, CLPTM1L, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1 and BCAR1 at known loci) remained statistically significant after Bonferroni correction. CONCLUSIONS:By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation.

The destruction of the World Trade Center (WTC) towers on 11 September 2001 released many tons of aerosolized dust and smoke with potential for carcinogenic exposures to community members as well as responders. The WTC Environmental Health Center (WTC EHC) is a surveillance and treatment program for a diverse population of community members ("Survivors"), including local residents and workers, present in the NYC disaster area on 9/11 or in the days or weeks following. We report a case series of cancers identified in the WTC EHC as of 31 December 2019. Descriptive characteristics are presented for 2561 cancer patients (excluding non-melanoma skin cancer) and 5377 non-cancer WTC-EHC participants who signed informed consent. We identified a total of 2999 cancer diagnoses in 2561 patients: 2534 solid tumors (84.5%) and 465 lymphoid and hematopoietic tissue cancers (15.5%) with forty-one different cancer types. We describe the distribution, frequency, median age of cancer diagnosis and median latency from 9/11 by cancer site. In addition to common cancer types, rare cancers, including male breast cancers and mesotheliomas have been identified. The current study is the first report on cancer characteristics of enrollees at WTC EHC, a federally designated treatment and surveillance program for local community members affected by the 9/11 terrorist attack on the WTC.

OBJECTIVE:Increasingly, patients are seeking same-day care at urgent care (UC) facilities. Little is known about the health care utilization patterns of patients who visit UC facilities for headache and migraine. We examined the frequency of headache and migraine visits and revisits at UC facilities. METHODS:We conducted a retrospective cohort study of headache not otherwise specified (NOS) and migraine visits from 67 NYC UC facilities over an eight-month period. We report descriptive analyses, the frequency of headache NOS revisits, and the elapsed time to revisits. RESULTS:There were 10,240 patients who visited UC facilities for headache NOS or migraine within the eight-month period. The majority of patients, 6,994 (68.3%), were female, and the mean age (SD) was 35.1 (15.0) years. Most (93.9%) patients (N = 9,613) lived within 60 miles of NYC; 5.5% (N = 564) had at least one revisit, and among re-visitors, there was an average (SD) of 2.2 (0.7) visits to UC facilities during the study period and an average time to revisit (SD) of 61.3 (55.2) days. CONCLUSIONS:In just eight months, there were >10,000 headache NOS and migraine visits to UC facilities in NYC, with half of revisits occurring within 90 days. Future work should examine headache management in UC facilities.

: As coronavirus disease 2019 (Covid-19) restrictions upend the community bonds that have enabled African communities to thrive in the face of numerous challenges, it is vital that the gains made in community-based healthcare are preserved by adapting our approaches. Instead of reversing the many gains made through locally driven development partnerships with international funding agencies for other viral diseases like HIV, we must use this opportunity to adapt the many lessons learned to address the burden of Covid-19. Programs like the Academic Model Providing Access to Healthcare are currently leveraging widely available technologies in Africa to prevent patients from experiencing significant interruptions in care as the healthcare system adjusts to the challenges presented by Covid-19. These approaches are designed to preserve social contact while incorporating physical distancing. The gains and successes made through approaches like group-based medical care must not only continue but can help expand upon the extraordinary success of programs like President's Emergency Plan for AIDS Relief.

OBJECTIVES/OBJECTIVE:To determine impact of a primary care-based child obesity prevention intervention beginning during pregnancy on early childhood weight outcomes in low-income Hispanic families. METHODS:-scores (WFAzs) from clinical anthropometric measures, obesity prevalence (weight for age ≥95th percentile), and excess weight gain (WFAz trajectory) from birth to age 3 years. Secondary outcomes included dose effects. RESULTS:= .02) decreased as attendance increased with low, medium, and high attendance. CONCLUSIONS:Mean WFAz and growth trajectories were lower for the intervention group through age 2 years, but there were no group differences at age 3. Further study is needed to enhance sustainability of effects beyond age 2.

BACKGROUND:Optimizing antithymocyte globulin (ATG) dosage is critical, particularly for high-risk kidney transplant (KT) recipients without cytomegalovirus (CMV) prophylaxis. METHODS:We studied 630 KT recipients with expanded criteria donors or panel reactive antibody ≥50% at Hospital do Rim, Brazil (January 1, 2013 to May 21, 2015) to determine whether a single ATG dose was safe and effective in patients without CMV prophylaxis. Patients received ≥4 doses (1-1.5 mg/kg/per dose) until June 17, 2014, when the induction protocol changed to a single ATG dose (3 mg/kg). We used Cox regression to compare the risk of CMV infection and acute rejection (AR) among KT recipients by ATG dose. RESULTS:Adjusting for clinical and transplant factors, a single ATG dose was associated with a lower risk of CMV infection (adjusted hazard ratio [aHR]: 0.63; 95% confidence interval [CI], 0.42-0.93; P = 0.02) and a similar risk of AR (aHR: 1.16; 95% CI, 0.47-2.83; P = 0.8), compared to multiple doses. We found no differences in death-censored graft loss (5.0% versus 4.8%, aHR: 1.06; 95% CI, 0.51-2.23; P = 0.9) or mortality (4.7% versus 3.4%; aHR: 1.42; 95% CI, 0.62-3.24; P = 0.4) at 1-year post-KT by ATG dose. CONCLUSIONS:In our study of high-risk KT recipients without CMV prophylaxis, a single ATG dose decreased the risk of CMV infection without increasing the risk of AR or compromising graft or patient survival.

Some chronic pain conditions and comorbidities suppress the hypothalamic-pituitary-adrenal (HPA) axis and response to dynamic testing. We measured HPA axis responses to corticotropin-releasing hormone (CRH) administration in relation to chronic pelvic pain and endometriosis. In a cross-sectional study of women (n = 54) with endometriosis-associated chronic pelvic pain (n = 22), chronic pelvic pain alone (n = 12), or healthy volunteers (n = 20), adrenocorticotropic-releasing hormone (ACTH) and cortisol levels were measured at 0, 15, 30, and 45 min after intravenous ovine CRH administration. ACTH and cortisol delta (peak-baseline) and area under the curve (AUC) were compared by study group and assessed for association with race and menstrual and non-menstrual pain severity. HPA axis responses did not differ among the racially diverse groups or in those with pain compared with healthy volunteers. However, when stratified by race, ACTH delta (129.9 ± 130.7 vs. 52.5 ± 66.0 pg/mL; p = 0.003), ACTH AUC (4813 ± 4707 vs. 2290 ± 2900 min*pg/mL; p = 0.013), and cortisol delta (26.3 ± 21.5 vs. 13.2 ± 9.7 μg/mL; p = 0.005) were significantly higher in black (n = 10) than predominately white (non-black) subjects (n = 44; 39/44 white). In analyses among primarily white (non-black) women, greater menstrual pain severity was associated with blunted ACTH delta (p = 0.015) and cortisol delta (p = 0.023), and greater non-menstrual pain severity with blunted cortisol delta (p = 0.017). Neuroendocrine abnormalities in women with chronic pelvic pain may differ by pain manifestations and may vary by race. The higher HPA axis response in black women merits investigation in pelvic pain studies stratified by race. In white (non-black) women experiencing pain, a blunted response was related to pain severity suggesting pain affects women independently of endometriosis lesions.

BACKGROUND:The coronavirus disease (COVID)-19 pandemic quickly challenged New York City health care systems. Telemedicine has been suggested to manage acute complaints and divert patients from in-person care. OBJECTIVES/OBJECTIVE:The objective of this study was to describe and assess the impact of a rapidly scaled virtual urgent care platform during the COVID-19 pandemic. METHODS:This was a retrospective cohort study of all patients who presented to a virtual urgent care platform over 1 month during the COVID-19 pandemic surge. We described scaling our telemedicine urgent care capacity, described patient clinical characteristics, assessed for emergency department (ED) referrals, and analyzed postvisit surveys. RESULTS:During the study period, a total of 17,730 patients were seen via virtual urgent care; 454 (2.56%) were referred to an ED. The most frequent diagnoses were COVID-19 related or upper respiratory symptoms. Geospatial analysis indicated a wide catchment area. There were 251 providers onboarded to the platform; at peak, 62 providers supplied 364 h of coverage in 1 day. The average patient satisfaction score was 4.4/5. There were 2668 patients (15.05%) who responded to the postvisit survey; 1236 (49.35%) would have sought care in an ED (11.86%) or in-person urgent care (37.49%). CONCLUSIONS:A virtual urgent care platform was scaled to manage a volume of more than 800 patients a day across a large catchment area during the pandemic surge. About half of the patients would otherwise have presented to an ED or urgent care in person. Virtual urgent care is an option for appropriate patients while minimizing in-person visits during the COVID-19 pandemic.

Cardiovascular diseases (CVD) are the world's leading cause of death. High blood pressure (BP) is the leading global risk factor for all-cause preventable morbidity and mortality. Globally, only about 14% of patients achieve BP control to systolic BP <140 mm Hg and diastolic BP <90 mm Hg. Most patients (>60%) require two or more drugs to achieve BP control, yet poor adherence to therapy is a major barrier to achieving this control. Fixed-dose combinations (FDCs) of BP-lowering drugs are one means to improve BP control through greater adherence and efficacy, with favorable safety and cost profiles. The authors present a review of the supporting data from a successful application to the World Health Organization (WHO) for the inclusion of FDCs of two BP-lowering drugs on the 21st WHO Essential Medicines List. The authors discuss the efficacy and safety of FDCs of two BP-lowering drugs for the management of hypertension in adults, relevant hypertension guideline recommendations, and the estimated cost of such therapies.

We performed a retrospective cohort study to analyze all 87 CAD patients with MGUS and 178 CAD patients without MGUS admitted in Zhongshan Hospital Fudan University from 2015 to 2017. Patients were followed up via regular patient visits or telephone, and the median follow-up period was 2.9 years. The end point of follow-up was the occurrence of major adverse cardiac events (MACE). CAD patients with MGUS had a higher risk of MACE than those without MGUS (log-rank P = 0.0015). After adjustment for other markers in the stepwise Cox regression model, MGUS was still related to the increasing risk of MACE incident (P = 0.002, HR = 2.308). Then, we constructed the nomogram based on the Cox regression model, and the concordance index (C-index) was 0.667. Hence, MGUS might be added into the risk model of CAD.