Paul J Christos

Weill Cornell Medical College, New York, New York, United States

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Publications (237)993.86 Total impact

  • Neurosurgery 08/2015; DOI:10.1227/NEU.0000000000000986 · 3.62 Impact Factor
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    ABSTRACT: The purpose of this study was to investigate and compare the cause-specific survival (CSS) of stage I (tumor [T]1 node [N]0 metastasis [M]0) versus stage II (T2N0M0) glottic cancer in a large population cohort. We analyzed data from the Surveillance, Epidemiology, and End Results 18 database from 1973 to 2009, comprising patients diagnosed with T1N0M0 or T2N0M0 squamous cell glottic cancer. Kaplan-Meier survival analysis, multivariable Cox proportional hazards regression analysis, and competing-risks survival regression were used for statistical analysis. There were 4,422 patients who met all inclusion criteria. The 36-month CSS was 93.9% for stage I verus 86.5% for stage II, with P < 0.0001. Stage II status conferred a 2.494 hazard ratio for increased risk of cause-specific death compared to stage I. Stage II glottic cancers have a significantly worse prognosis and may need a different approach to management than stage I tumors. 4. Laryngoscope, 2015. © 2015 The American Laryngological, Rhinological and Otological Society, Inc.
    The Laryngoscope 06/2015; 90(1). DOI:10.1002/lary.25338 · 2.14 Impact Factor
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    ABSTRACT: The purpose of the study was to evaluate the outcomes for wedge resection (WR), WR plus brachytherapy (WRB), or stereotactic body radiation therapy (SBRT) for early-stage non-small lung cancer. Retrospectively collected data of patients treated with WR, WRB, or SBRT (1993-2012). Cesium-131 (Cs131) used in WRB group in patients with close or positive margins based on surgical assessment. Kaplan-Meier survival analysis, log-rank test used to compare disease-free survival/overall survival between different groups. Multivariable analysis, using Cox proportional hazards regression analysis, was performed to evaluate the independent effect of age, gender, and treatment procedure on disease-free survival. A total of 272 patients were included in the study (123 WR, 52 WR+Cs-131, 97 SBRT). Cs-131 was used with WRs that the surgeons deemed high risk. Local control (LC) was similar in the three groups and was achieved in 92.2% for WR group vs. 96.2% for WR+Cs-131 and 95.5% for SBRT (p = 0.60). On multivariate analysis, although females showed a higher LC, neither LC nor distant metastasis were associated with age or gender (p = 0.65 and p = 0.41, respectively). Five-year overall survival was 100% in the WR+B group, 97.7% in the WR group, and 89.6% in the SBRT group (p = 0.02). Toxicity was similar in the three groups. WR, WR+ Cs-131, or SBRT are all excellent treatment options for patients with early-stage non-small cell lung cancer that are not candidates for lobectomy. For high risk WRs, we favor use of Cesim-131 brachytherapy. Until a prospective randomized comparative study is done to evaluate the best treatment approach for early-stage NSCLC, treatment selection should be based on a multidisciplinary team approach. Copyright © 2015 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.
    Brachytherapy 05/2015; 14(5). DOI:10.1016/j.brachy.2015.04.001 · 2.76 Impact Factor
  • Cancer Research 05/2015; 75(9 Supplement):S6-03-S6-03. DOI:10.1158/1538-7445.SABCS14-S6-03 · 9.33 Impact Factor
  • European Urology Supplements 04/2015; 14(2). DOI:10.1016/S1569-9056(15)60024-0 · 3.37 Impact Factor
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    ABSTRACT: Background Variations in single nucleotide polymorphisms (SNPs) have been associated with enhanced drug efficacy and toxicity in cancer therapy. SNP variations in the ErbB2 gene have been identified that alter the protein sequence of the HER2-neu protein, but how these polymorphisms affect prognosis and response to HER2 targeted therapy is unknown. We examined eleven ErbB2 SNPs that alter the HER2-neu amino acid sequence to determine whether any of these particular polymorphisms were associated with increased trastuzumab cardiotoxicity in a case–control study. Methods 140 subjects were enrolled from a single institution under Weill Cornell Medical College IRB protocol #0804009734. Patients were eligible if they had histologically or cytologically proven HER2-neu positive breast cancer and more than 3 months of trastuzumab therapy. Cases had either symptomatic CHF or a decline in LVEF of 15% (or if the LVEF <55%, a decline in LVEF of 10%) that resulted in at least temporary discontinuation of trastuzumab, whereas controls had no decline in their LVEF. Eleven ErbB2 single gene SNPs that resulted in an alteration in the HER2-neu protein amino acid sequence were studied. Single gene SNP analysis was carried out using SNP genotyping assays from genomic DNA obtained from peripheral blood or buccal swab. Results Only two of the ErbB2 SNPs (Ile 655 Val and Pro 1170 Ala) were found to have variation. There was no association between codon 665 and cardiotoxicity; however the proline variant of amino acid 1170 was more likely than the alanine variant to be found in cases with trastuzumab cardiotoxicity (35% of case patients as compared to 17% of controls, p = 0.04). This association remained significant in multivariable analysis taking into account age, race, and history of hypertension (adjusted OR = 2.60, 95% CI = 1.02, 6.62, p = 0.046). Conclusions The Her2/neu Pro 1170 Ala polymorphism can be used to identify a subset of patients who are at increased risk of cardiotoxicity from trastuzumab therapy. Her2/neu single nucleotide polymorphisms may be useful in conjunction with other biomarkers to risk stratify patients in order to optimize clinical management.
    BMC Cancer 04/2015; 15(1). DOI:10.1186/s12885-015-1298-6 · 3.36 Impact Factor
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    European Urology Supplements 04/2015; 193(4):e807-e808. DOI:10.1016/j.juro.2015.02.2293 · 3.37 Impact Factor
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    European Urology Supplements 04/2015; 14(2):e744. DOI:10.1016/S1569-9056(15)60736-9 · 3.37 Impact Factor
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    ABSTRACT: Concerns remain whether robot-assisted radical cystectomy (RARC) compromises survival because of inadequate oncologic resection or alteration of recurrence patterns. To describe recurrence patterns following open radical cystectomy (ORC) and RARC. Retrospective review of 383 consecutive patients who underwent ORC (n=120) or RARC (n=263) at an academic institution from July 2001 to February 2014. ORC and RARC. Recurrence-free survival estimates were illustrated using the Kaplan-Meier method. Recurrence patterns (local vs distant and anatomic locations) within 2 yr of surgery were tabulated. Cox regression models were built to evaluate the effect of surgical technique on the risk of recurrence. The median follow-up time for patients without recurrence was 30 mo (interquartile range [IQR] 5-72) for ORC and 23 mo (IQR 9-48) for RARC (p=0.6). Within 2 yr of surgery, there was no large difference in the number of local recurrences between ORC and RARC patients (15/65 [23%] vs 24/136 [18%]), and the distribution of local recurrences was similar between the two groups. Similarly, the number of distant recurrences did not differ between the groups (26/73 [36%] vs 43/147 [29%]). However, there were distinct patterns of distant recurrence. Extrapelvic lymph node locations were more frequent for RARC than ORC (10/43 [23%] vs 4/26 [15%]). Furthermore, peritoneal carcinomatosis was found in 9/43 (21%) RARC patients compared to 2/26 (8%) ORC patients. In multivariable analyses, RARC was not a predictor of recurrence. Limitations of the study include selection bias and a limited sample size. Within limitations, we found that RARC is not an independent predictor of recurrence after surgery. Interestingly, extrapelvic lymph node locations and peritoneal carcinomatosis were more frequent in RARC than in ORC patients. Further validation is warranted to better understand the oncologic implications of RARC. In this study, the locations of bladder cancer recurrences following conventional and robotic techniques for removal of the bladder are described. Although the numbers are small, the results show that the distribution of distant recurrences differs between the two techniques. Copyright © 2015 European Association of Urology. Published by Elsevier B.V. All rights reserved.
    European Urology 02/2015; 68(3). DOI:10.1016/j.eururo.2015.02.003 · 13.94 Impact Factor
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    ABSTRACT: Background Matrix metalloproteinase-23 (MMP-23) can block the voltage-gated potassium channel Kv1.3, whose function is important for sustained Ca2+ signaling during T cell activation. MMP-23 may also alter T cell activity and phenotype through cleavage of proteins affecting cytokine and chemokine signaling. We therefore tested the hypothesis that MMP-23 can negatively regulate the anti-tumor T cell response in human melanoma.Methods We characterized MMP-23 expression in primary melanoma patients who received adjuvant immunotherapy. We examined the association of MMP-23 with the anti-tumor immune response - as assessed by the prevalence of tumor-infiltrating lymphocytes and Foxp3+ regulatory T cells. Further, we examined the association between MMP-23 expression and response to immunotherapy. Considering also an in trans mechanism, we examined the association of melanoma MMP-23 and melanoma Kv1.3 expression.ResultsOur data revealed an inverse association between primary melanoma MMP-23 expression and the anti-tumor T cell response, as demonstrated by decreased tumor-infiltrating lymphocytes (TIL) (P¿=¿0.05), in particular brisk TILs (P¿=¿0.04), and a trend towards an increased proportion of immunosuppressive Foxp3+ regulatory T cells (P¿=¿0.07). High melanoma MMP-23 expression is also associated with recurrence in patients treated with immune biologics (P¿=¿0.037) but not in those treated with vaccines (P¿=¿0.64). Further, high melanoma MMP-23 expression is associated with shorter periods of progression-free survival for patients receiving immune biologics (P¿=¿0.025). On the other hand, there is no relationship between melanoma MMP-23 and melanoma Kv1.3 expression (P¿=¿0.27).Conclusions Our data support a role for MMP-23 as a potential immunosuppressive target in melanoma, as well as a possible biomarker for informing melanoma immunotherapies.
    Journal of Translational Medicine 12/2014; 12(1):342. DOI:10.1186/s12967-014-0342-7 · 3.93 Impact Factor
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    ABSTRACT: Background Single nucleotide polymorphisms (SNPs) in platelet-associated genes partly explain inherent variability in platelet counts. Patients with monoallelic Bernard Soulier syndrome due to the Bolzano mutation (GPIBA A156V) have variable platelet counts despite a common mutation for unknown reasons.Objectives We investigated the effect of the most common SNP (R307H) in the hematopoietic-specific tubulin isotype β-1 in these Bernard Soulier patients and potential microtubule-based mechanisms of worsened thrombocytopenia.Patients/Methods Ninety-four monoallelic Bolzano mutation patients were evaluated for the R307H β-1 SNP and had platelet counts measured by three methods; the Q43P SNP was also evaluated. To investigate possible mechanisms underlying this association, we used molecular modeling of β-1 tubulin with and without the R307H SNP. We transfected SNP or non-SNP β-1 tubulin into MCF-7 and CMK cell lines and measured microtubule regrowth after nocodazole-induced depolymerization.ResultsWe found that patients with at least one R307H SNP allele had significantly worse thrombocytopenia; manual platelet counting revealed a median platelet count of 124 in non-SNP and 76 in SNP patients (both x 109/L; p<0.01). The Q43P SNP had no significant association with platelet count. Molecular modeling suggested a structural relationship between the R307H SNP and microtubule stability via alterations in the M-loop of β tubulin; in vitro microtubule recovery assays revealed cells transfected with R307H SNP β-1 had significantly impaired microtubule recovery.Conclusions Our data show that the R307H SNP is significantly associated with the degree of thrombocytopenia in congenital and acquired platelet disorders, and may affect platelets by altering microtubule behavior.This article is protected by copyright. All rights reserved.
    Journal of Thrombosis and Haemostasis 12/2014; 13(4). DOI:10.1111/jth.12824 · 5.72 Impact Factor
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    ABSTRACT: Type II diabetes mellitus (DM) is one of the leading chronic diseases in Qatar as well as worldwide. However, the risk factors for DM in Qatar and their prevalence are not well understood. We conducted a case-control study with the specific aim of estimating, based on data from outpatients with DM in Qatar (cases) and outpatient/inpatient controls, the association between demographic/lifestyle factors and DM. A total of 459 patients with DM from Hamad General Hospital (HGH) outpatient adult diabetes clinics, and 342 control patients from various outpatient clinics and inpatient departments within Hamad Medical Corporation (HMC) (years 2006-2008), were recruited. The association between risk factors and DM was evaluated using bivariate and multivariable logistic regression analyses. In addition to odds ratios (OR) and 95% confidence intervals (95% CI), we estimated the population attributable risk fractions for the DM demographic/lifestyle risk factors. Qatari nationality was the strongest risk factor for DM (adjusted OR = 5.5; 95% CI = 3.5-8.6; p < 0.0001), followed by higher monthly income (defined as ≥ 3000 Qatari Riyals, adjusted OR = 5.1; 95% CI = 3.0-8.7; p < 0.0001), age >65 years (adjusted OR = 3.3; 95% CI = 0.9-11.4; p = 0.06), male gender (adjusted OR = 2.9; 95% CI = 1.8-4.8; p < 0.0001), obesity (BMI ≥ 30, adjusted OR = 2.2; 95% CI = 1.5-3.2; p < 0.0001), no college education (adjusted OR = 1.7; 95% CI = 1.2-2.6; p = 0.009), and no daily vigorous/moderate activity (adjusted OR = 1.5; 95% CI = 0.9-2.3; p = 0.12). Among Qatari nationals, obesity was found to be the main risk factor for DM (unadjusted OR = 3.0; 95% CI = 1.6-5.6; p < 0.0001), followed by no college education (unadjusted OR = 2.7; 95% CI = 1.5-5.1; p = 0.001), while consanguinity did not appear to play a major role in predicting DM (unadjusted OR = 1.5; 95% CI = 0.8-2.8; p = 0.21). Our findings further suggested that eliminating obesity and improving access to education may reduce DM cases by up to one third for the population at large (31.7% and 26.8%, respectively) and up to half (46.9% and 49.3%, respectively) for Qatari nationals. Promoting physical activity may reduce the burden of DM by up to 9.4% for the population at large and up to 17.3% for Qatari nationals. Demographic/lifestyle factors appear to be the main risk factors for the high DM levels observed in Qatar, with a contribution that outweighs that of genetic risk factors. While further evaluation of DM risk factors among the Qatari population (as opposed to the resident population) is important and of interest, these findings highlight the need to focus short-term DM interventions on addressing demographic/lifestyle risk factors to achieve substantial and timely declines in DM levels.
    12/2014; 2014(2):13. DOI:10.5339/qmj.2014.13
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    ABSTRACT: Background: Transcatheter arterial chemoembolization (TACE) has been used to curtail tumor vasculature and delay tumor progression in hepatocellular carcinoma (HCC). We conducted a phase I trial to evaluate the efficacy and toxicity of thalidomide when combined with TACE in patients with advanced HCC. Methods: Between June 2000 and November 2003, 56 patients with unresectable HCC and amenable to TACE were enrolled. The starting dose of thalidomide was 200 mg/day and was escalated every 2 weeks as tolerated to a maximum dose of 1,000 mg/day. Dose reductions and discontinuation were determined by toxicity. TACE was performed 4 weeks after initiation of thalidomide therapy and repeated as necessary. Results: Overall, 47 and 55 patients were evaluable for response and toxicity, respectively; the median dose of thalidomide given was 200 mg/day. Three patients (6.38%) patients achieved complete responses, whereas 10 (21.3%) had partial responses, for an overall response rate of 27.7%, and 27 (57.5%) had stable disease. Median progression-free survival was 7 months (95% confidence interval [CI]: 5-10 months), and median OS was 21 months (95% CI: 16-28 months) (Fig. 1). Fatigue and lethargy (49.1%), constipation (47.3%), and nausea (43.6%) were common. Grade 3-4 toxicities consisted mostly of increased aspartate aminotransferase (43.6%) and elevated alanine aminotransferase (38.2%) (Table 1). Conclusion: Thalidomide and TACE were commonly associated with nonhematologic side effects, with fatigue and constipation being prominent. With a lack of clear therapeutic benefit, this combination is unlikely to be pursued for HCC.
    The Oncologist 10/2014; 19(12). DOI:10.1634/theoncologist.2014-0283 · 4.87 Impact Factor
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    ABSTRACT: To determine the relationship between sacroiliac joint (SIJ) contrast dispersal patterns during SIJ corticosteroid injection and pain relief at 2 and 8 weeks after the procedure. The association between the number of positive provocative SIJ physical examination maneuvers (minimum of one in all patients undergoing SIJ injection) and the patient's response to the intervention was also assessed. Retrospective chart review. Academic outpatient musculoskeletal practice. Fifty-four subjects who underwent therapeutic SIJ corticosteroid injection were screened for inclusion; 49 subjects were included in the final analysis. A retrospective review of electronic medical records identified patients who underwent SIJ corticosteroid injection. Fluoroscopic contrast flow patterns were categorized as type I (intra-articular injection with cephalad extension within the SIJ) or type II (intra-articular injection with poor cephalad extension). Self-reported numeric pain rating scale (NPRS) values at the time of injection and 2 and 8 weeks after the procedure were recorded. The number of positive provocative SIJ physical examination maneuvers at the time of the initial evaluation was also recorded. The primary outcome measure was the effect of contrast patterns (type I or type II) on change in NPRS values at 2 weeks and 8 weeks after the injection. The secondary outcome measure was the association between the number of positive provocative SIJ physical examination maneuvers and decrease in the level of pain after the procedure. At 2 weeks after the procedure, type I subjects demonstrated a significantly lower mean NPRS value compared with type II subjects (2.8 ± 1.4 versus 3.8 ± 1.6, respectively, P = .02). No statistically significant difference was observed at 8 weeks after the procedure. NPRS values were significantly reduced both at 2 weeks and 8 weeks, compared with baseline, in both subjects identified as having type I flow and those with type II flow (P < .0001 for all within-group comparisons). Fluoroscopically guided corticosteroid injections into the SIJ joint are effective in decreasing NPRS values in patients with SIJ-mediated pain. Delivery of corticosteroid to the superior portion of the SIJ leads to a greater reduction in pain at 2 weeks, but not at 8 weeks. Patients with at least one positive provocative maneuver should benefit from an intra-articular corticosteroid injection. Copyright © 2014 American Academy of Physical Medicine and Rehabilitation. Published by Elsevier Inc. All rights reserved.
    PM&R 10/2014; 7(4). DOI:10.1016/j.pmrj.2014.10.007 · 1.53 Impact Factor
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    ABSTRACT: Purpose:: Studies have shown that older women are undertreated for breast cancer. Few data are available on cancer-related death in elderly women aged 70 years and older with pathologic stage T1a-b N0 breast cancer and the impact of prognostic factors on cancer-related death. Methods:: The Surveillance, Epidemiology, and End Results (SEER) database was queried for women aged 70 years or above diagnosed with pT1a or pT1b, N0 breast cancer who underwent breast conservation surgery from 1999 to 2003. The Kaplan-Meier survival analysis was performed to evaluate breast cause-specific survival (CSS) and overall survival (OS), and the log-rank test was employed to compare CSS/OS between different groups of interest. Multivariable analysis (MVA), using Cox proportional hazards regression analysis, was performed to evaluate the independent effect of age, race, stage, grade, ER status, and radiation treatment on CSS. Adjusted hazard ratios were calculated from the MVA and reflect the increased risk of breast cancer death. Competing-risks survival regression was also performed to adjust the univariate and multivariable CSS hazard ratios for the competing event of death due to causes other than breast cancer. Results:: Patients aged 85 and above had a greater risk of breast cancer death compared with patients aged 70 to 74 years (referent category) (adjusted hazard ratio [HRs]=1.98). Race had no effect on CSS. Patients with stage T1bN0 breast cancer had a greater risk of breast cancer death compared with stage T1aN0 patients (adjusted HR=1.35; P=0.09). ER negative patients had a greater risk of breast cancer death compared with ER positive patients (adjusted HR=1.59; P<0.017). Patients with higher grade tumors had a greater risk of breast cancer death compared with patients with grade 1 tumors (referent category) (adjusted HRs=1.69 and 2.96 for grade 2 and 3, respectively). Patients who underwent radiation therapy had a lower risk of breast cancer death compared with patients who did not (adjusted HR=0.55; P<0.0001). Conclusions:: Older patients with higher grade, pT1b, ER-negative breast cancer had increased risk of breast cancer-related death. Adjuvant radiation therapy may provide a CSS benefit in this elderly patient population.
    American Journal of Clinical Oncology 10/2014; DOI:10.1097/COC.0000000000000144 · 3.06 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):CT304-CT304. DOI:10.1158/1538-7445.AM2014-CT304 · 9.33 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):CT310-CT310. DOI:10.1158/1538-7445.AM2014-CT310 · 9.33 Impact Factor
  • Cancer Research 10/2014; 74(19 Supplement):CT413-CT413. DOI:10.1158/1538-7445.AM2014-CT413 · 9.33 Impact Factor
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    ABSTRACT: Background Adult respiratory distress syndrome (ARDS) has a high mortality rate and consumes considerable health care resources. It is not clear whether specimens obtained from open lung biopsy (OLB) in ARDS provide a specific diagnosis, alter therapy, or affect outcome. This meta-analysis attempts to determine whether OLB is safe, provides a specific diagnosis, changes therapy, or affects survival. Methods A computerized search was performed of Medline and PubMed from January 1988 to December 2012 of English language studies of acute respiratory failure and diffuse pulmonary infiltrates that evaluated OLB in primarily adult mechanically ventilated patients. Of 194 abstracts retrieved, 64 articles were reviewed; 130 articles were excluded because they did not evaluate OLB. After applying the selection criteria, 24 articles were included. Results OLB in ARDS provided a specific diagnosis in 84% of patients and altered management in 73%. Hospital mortality was 43%. The complication rate for OLB in ARDS was 22%, but death from OLB was rare. Conclusions OLB in ARDS is a potentially productive procedure that provides a specific diagnosis and leads to a change in management in high proportions of patients. ARDS has a high mortality rate, which OLB does not appear to increase. Owing to a lack of randomized controlled trials, a survival advantage of OLB in ARDS could not be demonstrated.
    The Annals of Thoracic Surgery 10/2014; 98(4). DOI:10.1016/j.athoracsur.2014.05.029 · 3.85 Impact Factor
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    ABSTRACT: To evaluate whether non-gated CT can assess left ventricular (LV) function, 101 patients with both CT and echocardiography were selected, with EF < 50% on echocardiography used as a reference standard. CTs were blindly reevaluated, and qualitative assessment of LV dysfunction on CT correlated with echocardiographic dysfunction, odds ratio of 21.0 (95%CI = 6.55-71.0), specificity of 86% (56/65). Systolic and diastolic images were identified on CT, and the ratio of systolic to diastolic LV internal diameters, and ratio of LV to RV internal diameter, were performed, both showing correlation with LV dysfunction on echocardiography (p < 0.0001). Non-gated CT can be used to predict LV dysfunction.
    Clinical imaging 09/2014; 38(5). DOI:10.1016/j.clinimag.2014.03.015 · 0.81 Impact Factor

Publication Stats

5k Citations
993.86 Total Impact Points


  • 1999–2015
    • Weill Cornell Medical College
      • • Division of Biostatistics and Epidemiology
      • • Department of Neurological Surgery
      • • Department of Public Health
      New York, New York, United States
  • 2014
    • Albert Einstein College of Medicine
      • Department of Radiology
      New York, New York, United States
  • 2003–2014
    • Cornell University
      • Department of Public Health
      Итак, New York, United States
    • Temple University
      • Department of Medicine
      Filadelfia, Pennsylvania, United States
  • 2000–2014
    • New York Presbyterian Hospital
      • Department of Public Health
      New York City, New York, United States
  • 2012
    • CUNY Graduate Center
      New York City, New York, United States
  • 2011
    • Cornell College
      New York, New York, United States
  • 2000–2004
    • Memorial Sloan-Kettering Cancer Center
      • • Department of Medicine
      • • Hematology Service
      New York City, NY, United States