Person: Lee, Hang
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Lee, Hang
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Publication Management and Outcome of Patients With Acute Coronary Syndrome Caused by Plaque Rupture Versus Plaque Erosion: An Intravascular Optical Coherence Tomography Study(John Wiley and Sons Inc., 2017) Hu, Sining; Zhu, Yinchun; Zhang, Yingying; Dai, Jiannan; Li, Lulu; Dauerman, Harold; Soeda, Tsunenari; Wang, Zhao; Lee, Hang; Wang, Chao; Zhe, Chunyang; Wang, Yan; Zheng, Gonghui; Zhang, Shaosong; Jia, Haibo; Yu, Bo; Jang, Ik‐KyungBackground: Plaque rupture and erosion are the 2 most common mechanisms for acute coronary syndromes. However, the outcome of these 2 distinct pathologies in patients with acute coronary syndromes has never been studied. Methods and Results: We retrospectively studied 141 patients with acute coronary syndromes who underwent optical coherence tomography (OCT) imaging of the culprit lesion prior to stenting from the Massachusetts General Hospital OCT Registry. Management (stent versus no stent), poststent OCT findings, and outcomes were compared. Among the 141 culprit lesions, rupture was found in 79 (56%) patients and erosion in 62 (44%). Stent implantation was performed in 77 (97.5%) patients with rupture versus 49 (79.0%) in those with erosion (P<0.001). Immediately after percutaneous coronary intervention, OCT showed a higher incidence of malapposition (37.5% versus 7.3%, P<0.001), thrombus (59.4% versus 14.6%, P<0.001), and protrusion (93.8% versus 73.2%, P=0.008) in the rupture group compared with the erosion group. Plaque rupture was associated with a higher incidence of no reflow or slow flow and distal embolization. Although cardiac event rates were comparable between the two groups at the 1‐year follow‐up, none of the erosion patients who were treated conservatively without stenting had adverse cardiac events. Conclusions: Unfavorable poststent OCT findings were more frequent in rupture patients compared with erosion patients. A subset of erosion patients who were treated conservatively without stenting remained free of adverse cardiac events for up to 1 year.Publication The Magnetic Levator Prosthesis for Temporary Management of Severe Blepharoptosis: Initial Safety and Efficacy(The Association for Research in Vision and Ophthalmology, 2017) Houston, Kevin; Tomasi, Matteo; Amaral, Christina; Finch, Nicole; Yoon, Michael; Lee, Hang; Paschalis, Eleftherios I.Purpose We further optimized and evaluated the safety of the magnetic levator prosthesis (MLP) for temporary management of severe blepharoptosis, and compared efficacy and comfort against the ptosis crutch. Methods: The interpalpebral fissure (IPF) of participants (n = 12) with ptosis was measured during attempted eyelid opening, volitional closing, and spontaneous closing with no device, ptosis crutch, or the MLP. A 10-point scale documented comfort. Additionally, a 20 minute and then 1 week trial of the MLP was offered. Safety measures were skin erythema rating, change in visual acuity, and change in corneal staining. Results: The MLP and crutch opened the eye (IPF 11.2 and 9.3 mm), but the MLP allowed better volitional closure (IPF 1.0 vs. 4.9 mm, P = 0.009), but was no better in allowing spontaneous blink (IPF 7.5 vs. 7.7 mm, P = 0.722). Both devices were equally comfortable (both median 8/10 comfort, P = 0.46). With extended use, opening with the MLP showed IPF 9.24 mm at 20 minutes and 9.46 mm at 1 week, and volitional closure was IPF 0.95 and 0.52 mm, respectively. Closure on spontaneous blink improved with extended wear to IPF 5.14 and 5.18 mm, respectively (P = 0.002). Two participants exhibited moderate skin erythema and one had increased corneal staining without change in acuity. Conclusions: The MLP is safe and feasible for temporary correction of severe ptosis. Translational Relevance First group data in patients showing successful reanimation of the eyelid with magnetic force.Publication Incidental Statin Use and the Risk of Stroke or Transient Ischemic Attack after Radiotherapy for Head and Neck Cancer(Korean Stroke Society, 2018) Addison, Daniel; Lawler, Patrick R.; Emami, Hamed; Janjua, Sumbal A.; Staziaki, Pedro V.; Hallett, Travis R.; Hennessy, Orla; Lee, Hang; Szilveszter, Bálint; Lu, Michael; Mousavi, Negar; Nayor, Matthew; Delling, Francesca N.; Romero, Javier; Wirth, Lori; Chan, Wai Fong; Hoffmann, Udo; Neilan, TomasBackground and Purpose Interventions to reduce the risk for cerebrovascular events (CVE; stroke and transient ischemic attack [TIA]) after radiotherapy (RT) for head and neck cancer (HNCA) are needed. Among broad populations, statins reduce CVEs; however, whether statins reduce CVEs after RT for HNCA is unclear. Therefore, we aimed to test whether incidental statin use at the time of RT is associated with a lower rate of CVEs after RT for HNCA. Methods: From an institutional database we identified all consecutive subjects treated with neck RT from 2002 to 2012 for HNCA. Data collection and event adjudication was performed by blinded teams. The primary outcome was a composite of ischemic stroke and TIA. The secondary outcome was ischemic stroke. The association between statin use and events was determined using Cox proportional hazard models after adjustment for traditional and RT-specific risk factors. Results: The final cohort consisted of 1,011 patients (59±13 years, 30% female, 44% hypertension) with 288 (28%) on statins. Over a median follow-up of 3.4 years (interquartile range, 0.1 to 14) there were 102 CVEs (89 ischemic strokes and 13 TIAs) with 17 in statin users versus 85 in nonstatins users. In a multivariable model containing known predictors of CVE, statins were associated with a reduction in the combination of stroke and TIA (hazard ratio [HR], 0.4; 95% confidence interval [CI], 0.2 to 0.8; P=0.01) and ischemic stroke alone (HR, 0.4; 95% CI, 0.2 to 0.8; P=0.01). Conclusions: Incidental statin use at the time of RT for HNCA is associated with a lower risk of stroke or TIA.Publication 313Value of Discontinuation of Contact Precautions (CP) for Methicillin-Resistant Staphylococcus aureus (MRSA)(Oxford University Press, 2014) Seiguer Shenoy, Erica; Lee, Hang; Cotter, Jessica; Ware, Winston; Kelbaugh, Douglas; Weil, Eric; Walensky, Rochelle; Hooper, DavidPublication Irisin Levels Are Lower in Young Amenorrheic Athletes Compared with Eumenorrheic Athletes and Non-Athletes and Are Associated with Bone Density and Strength Estimates(Public Library of Science, 2014) Singhal, Vibha; Lawson, Elizabeth; Ackerman, Kathryn; Fazeli, Pouneh; Clarke, Hannah; Lee, Hang; Eddy, Kamryn; Marengi, Dean A.; Derrico, Nicholas P.; Bouxsein, Mary; Misra, MadhusmitaIrisin and FGF21 are novel hormones implicated in the “browning” of white fat, thermogenesis, and energy homeostasis. However, there are no data regarding these hormones in amenorrheic athletes (AA) (a chronic energy deficit state) compared with eumenorrheic athletes (EA) and non-athletes. We hypothesized that irisin and FGF21 would be low in AA, an adaptive response to low energy stores. Furthermore, because (i) brown fat has positive effects on bone, and (ii) irisin and FGF21 may directly impact bone, we hypothesized that bone density, structure and strength would be positively associated with these hormones in athletes and non-athletes. To test our hypotheses, we studied 85 females, 14–21 years [38 AA, 24 EA and 23 non-athletes (NA)]. Fasting serum irisin and FGF21 were measured. Body composition and bone density were assessed using dual energy X-ray absorptiometry, bone microarchitecture using high resolution peripheral quantitative CT, strength estimates using finite element analysis, resting energy expenditure (REE) using indirect calorimetry and time spent exercising/week by history. Subjects did not differ for pubertal stage. Fat mass was lowest in AA. AA had lower irisin and FGF21 than EA and NA, even after controlling for fat and lean mass. Across subjects, irisin was positively associated with REE and bone density Z-scores, volumetric bone mineral density (total and trabecular), stiffness and failure load. FGF21 was negatively associated with hours/week of exercise and cortical porosity, and positively with fat mass and cortical volumetric bone density. Associations of irisin (but not FGF21) with bone parameters persisted after controlling for potential confounders. In conclusion, irisin and FGF21 are low in AA, and irisin (but not FGF21) is independently associated with bone density and strength in athletes.Publication Blocking the formation of radiation–induced breast cancer stem cells(Impact Journals LLC, 2014) Wang, YangYang; Li, Wende; Patel, Shalin; Cong, Juan; Zhang, Nan; Sabbatino, Francesco; Liu, Xiaoyan; Qi, Yuan; Huang, Peigen; Lee, Hang; Taghian, Alphonse; Li, Jian-Jian; DeLeo, Albert B.; Ferrone, Soldano; Epperly, Michael W.; Ferrone, Cristina; Ly, Amy; Brachtel, Elena; Wang, XinhuiThe goal of adjuvant (post-surgery) radiation therapy (RT) for breast cancer (BC) is to eliminate residual cancer cells, leading to better local tumor control and thus improving patient survival. However, radioresistance increases the risk of tumor recurrence and negatively affects survival. Recent evidence shows that breast cancer stem cells (BCSCs) are radiation-resistant and that relatively differentiated BC cells can be reprogrammed into induced BCSCs (iBCSCs) via radiation-induced re-expression of the stemness genes. Here we show that in irradiation (IR)-treated mice bearing syngeneic mammary tumors, IR-induced stemness correlated with increased spontaneous lung metastasis (51.7%). However, IR-induced stemness was blocked by targeting the NF-κB- stemness gene pathway with disulfiram (DSF)and Copper (Cu2+). DSF is an inhibitor of aldehyde dehydrogenase (ALDH) and an FDA-approved drug for treating alcoholism. DSF binds to Cu2+ to form DSF-Cu complexes (DSF/Cu), which act as a potent apoptosis inducer and an effective proteasome inhibitor, which, in turn, inhibits NF-κB activation. Treatment of mice with RT and DSF significantly inhibited mammary primary tumor growth (79.4%) and spontaneous lung metastasis (89.6%) compared to vehicle treated mice. This anti-tumor efficacy was associated with decreased stem cell properties (or stemness) in tumors. We expect that these results will spark clinical investigation of RT and DSF as a novel combinatorial treatment for breast cancer.Publication Effect of Chronic Athletic Activity on Brown Fat in Young Women(Public Library of Science, 2016) Singhal, Vibha; Maffazioli, Giovana D.; Ackerman, Kate E.; Lee, Hang; Elia, Elisa F.; Woolley, Ryan; Kolodny, Gerald; Cypess, Aaron M.; Misra, MadhusmitaBackground: The effect of chronic exercise activity on brown adipose tissue (BAT) is not clear, with some studies showing positive and others showing negative associations. Chronic exercise is associated with increased resting energy expenditure (REE) secondary to increased lean mass and a probable increase in BAT. Many athletes are in a state of relative energy deficit suggested by lower fat mass and hypothalamic amenorrhea. States of severe energy deficit such as anorexia nervosa are associated with reduced BAT. There are no data regarding the impact of chronic exercise activity on BAT volume or activity in young women and it is unclear whether relative energy deficiency modifies the effects of exercise on BAT. Purpose We assessed cold induced BAT volume and activity in young female athletes compared with non-athletes, and further evaluated associations of BAT with measures of REE, body composition and menstrual status. Methods: The protocol was approved by our Institutional Review Board. Written informed consent was obtained from all participants prior to study initiation. This was a cross-sectional study of 24 women (16 athletes and8 non-athletes) between 18–25 years of age. Athletes were either oligo-amenorrheic (n = 8) or eumenorrheic (n = 8).We used PET/CT scans to determine cold induced BAT activity, VMAX Encore 29 metabolic cart to obtain measures of REE, and DXA for body composition. Results: Athletes and non-athletes did not differ for age or BMI. Compared with non-athletes, athletes had lower percent body fat (p = 0.002), higher percent lean mass (p = 0.01) and trended higher in REE (p = 0.09). BAT volume and activity in athletes trended lower than in non-athletes (p = 0.06; p = 0.07, respectively). We found negative associations of BAT activity with duration of amenorrhea (r = -0.46, p = 0.02).BAT volume correlated inversely with lean mass (r = -0.46, p = 0.02), and positively with percent body fat, irisin and thyroid hormones. Conclusions: Our study shows a trend for lower BAT in young female athletes compared with non-athletes, and shows associations of brown fat with menstrual status and body composition. Brown fat may undergo adaptive reductions with increasing energy deficit.Publication Differential relationships of hepatic and epicardial fat to body composition in HIV(John Wiley and Sons Inc., 2017) Fourman, Lindsay; Lu, Michael; Lee, Hang; Fitch, Kathleen; Hallett, Travis R.; Park, Jakob; Czerwonka, Natalia; Weiss, Julian; Stanley, Takara; Lo, Janet; Grinspoon, StevenAbstract HIV‐infected patients commonly experience changes in central and peripheral fat content as well as ectopic fat accumulation. However, whether hepatic and epicardial fat stores relate differentially to body composition or how these associations are modified by HIV status has not been well explored. A previously recruited sample of 124 HIV‐infected patients and 58 healthy controls had undergone dual energy X‐ray absorptiometry (DEXA) and computed tomography (CT) from which body composition measures, liver–spleen ratio, and epicardial fat volume were obtained. Unique to the HIV‐infected group, there was a parabolic association between abdominal subcutaneous adipose tissue (SAT) area and liver–spleen ratio (P = 0.03, inflection point 324 cm2) such that hepatic fat content was greatest at the extremes of low and high SAT. A quadratic model also closely described the relationship between mean leg fat and liver–spleen ratio among patients with HIV (P = 0.02, inflection point 4.7 kg), again suggesting greater liver fat content with both low and high leg fat. Notably, an analogous relationship of epicardial fat with SAT was not evident among HIV‐infected individuals or healthy controls. In contrast, visceral adipose tissue (VAT) linearly related to both liver–spleen ratio in HIV and epicardial fat volume irrespective of HIV status in multivariable models. In conclusion, our analyses implicate both low and high SAT as risk factors for hepatic fat accumulation in HIV. These findings add to growing evidence of SAT dysfunction in the setting of HIV infection, and highlight key physiologic differences between hepatic and epicardial fat depots.Publication Clinical Predictors for Lack of Favorable Vascular Response to Statin Therapy in Patients With Coronary Artery Disease: A Serial Optical Coherence Tomography Study(John Wiley and Sons Inc., 2017) Minami, Yoshiyasu; Wang, Zhao; Aguirre, Aaron; Ong, Daniel S.; Kim, Chong‐Jin; Uemura, Shiro; Soeda, Tsunenari; Lee, Hang; Fujimoto, James; Jang, Ik‐KyungBackground: Previous studies have demonstrated that statin therapy improves cardiac outcomes, probably by stabilizing thin‐cap fibroatheroma in patients with coronary artery disease. However, major adverse cardiac events still occur in some patients, despite statin therapy. The aim of this study is to identify clinical predictors for the lack of a favorable vascular response to statin therapy in patients with coronary artery disease. Methods and Results: A total of 140 nonculprit plaques from 84 patients with coronary artery disease who were treated with a statin and had serial optical coherence tomography imaging (median interval, 6.3 months) were included. Thin‐cap area (fibrous cap thickness, <200 μm) was measured using a novel 3‐dimensional computer‐aided algorithm. Overall, the thin‐cap area significantly decreased from baseline (median, 2.852 mm2; 25th–75th percentile, 1.023–6.157 mm2) to follow‐up (median, 1.210 mm2; 25th–75th percentile, 0.250–3.192 mm2; P<0.001), and low‐density lipoprotein cholesterol significantly decreased from baseline (mean±SD, 92.9±30.1 mg/dL) to follow‐up (mean±SD, 76.3±23.3 mg/dL; P<0.001). The general linear model with multiple predictor variables revealed that the thin‐cap area was significantly higher in patients with chronic kidney disease than in those without it (regression coefficient b, 1.691 mm2; 95% confidence interval, 0.350–3.033 mm2; P=0.013) and lower in patients with acute coronary syndrome (regression coefficient b, −1.535 mm2; 95% confidence interval, −2.561 to −0.509 mm2; P=0.003). Conclusions: Chronic kidney disease is an independent predictor for the lack of a favorable vascular response to statin therapy, whereas acute coronary syndrome is an independent predictor for favorable vascular response to statin therapy. These findings should be further warranted in future prospective studies. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT01110538.