Faculty Bibliography

AIMS:The purpose of this study was to report on outcomes of a cohort of patients who were treated with reirradiation with stereotactic body radiation therapy (SBRT) for locally recurrent pancreatic adenocarcinoma. MATERIALS AND METHODS:Patients treated with SBRT reirradiation for locally recurrent pancreatic adenocarcinoma from December 2009 to April 2020 were included in the study. Descriptive statistics were used to record patient demographics, tumour and treatment characteristics. Kaplan-Meier analysis was used to evaluate overall survival, local progression-free survival (LPFS), distant metastasis-free survival and progression-free survival (PFS). RESULTS:In total, 27 patients were included in the study. The median follow-up time from local recurrence was 19.7 months (range 4.2-43.1 months). Most patients received five-fraction SBRT (26/27, 96%). The median overall survival after local recurrence treatment was 18.3 months (range 3.0-42.6 months), with 6-month, 1-year and 2-year overall survival rates of 88.5%, 73.1% and 33.6%. The median LPFS after local recurrence treatment was 16.2 months (range 2.3-33.6 months), with 6-month, 1-year and 2-year LPFS rates of 95.8%, 62.9% and 27.2%. Peri-SBRT chemotherapy improved LPFS (median 17.5 versus 8.5 months; P = 0.010) and overall survival (median 19.3 versus 5.5 months; P = 0.049). Tumours ≤ 3 cm in the greatest dimension showed better local control (median LPFS 19.2 versus 10.2 months; P = 0.130). There was one case (4%) of acute grade 3 pain and one case (4%) of late grade 3 gastrointestinal toxicity. CONCLUSIONS:Reirradiation with five-fraction SBRT is safe, but local control remains suboptimal. Patients with smaller tumours experienced improved outcomes, as did patients whose treatment plan included the administration of peri-SBRT chemotherapy.

Purpose : Deep learning of optical coherence tomography (OCT) may help discriminate glaucomatous eyes from healthy controls. However, the underlying decision making processes remain unclear. Recently, through computing class activation maps, our feature agnostic artificial intelligence of OCT images using a 3D convolutional neural network identified the optic nerve head (ONH) and its surrounding regions as structures significantly associated with glaucoma classification (PMID: 31260494). To pursue their contributions further, here we analyzed the optic nerve morphology from OCT and magnetic resonance imaging (MRI) in a subset of glaucoma and healthy subjects. Methods : Nine early glaucoma, 12 advanced glaucoma, and 4 healthy control subjects underwent spectral-domain OCT at 30x30x2 mum³ and 3-Tesla anatomical MRI at 1x1x1mm³ . Maximum intensity projection was applied to en-face OCT scans at the ONH (Fig. 1). The areas of the ONH [inner regions of interest, (ROI)] and surrounding regions (outer ROIs) visible in OCT were measured using global thresholding in ImageJ. One-way ANOVAs with post-hoc Tukey's tests were performed on the inner and outer ROIs between the 3 groups. Also, a Pearson correlation analysis was performed between the ROI areas in OCT and optic nerve volume extracted from MRI between the eye and optic chiasm. Results : For OCT of the ONH, significant group effect was observed for the areas in the inner ROIs (ANOVA: F= 7.823, p=0.00133). Post-hoc analyses revealed a significant difference between healthy controls and advanced glaucoma (p=0.0082) and between early and advanced glaucoma (p=0.0057) but no significance between healthy controls and early glaucoma (p=0.80) (Fig. 2A). No significant group effect was observed in the outer ROIs (ANOVA: F=0.004, p=0.996) (Fig. 2B). There was a negative correlation between the inner ROI area in OCT and optic nerve volume in MRI (R=-0.47, p=0.0011) (Fig. 2C). Conclusions : The ONH tissues visible on OCT appeared to contribute more than their surrounding regions to distinguishing between glaucomatous eyes and healthy eyes. The negative correlation between ONH area in OCT and optic nerve volume in MRI suggested the need to further understand the interactions between ONH and deeper brain structures in glaucoma. (Figure Presented)

The minimal information for studies of extracellular vesicles (EVs, MISEV) is a field-consensus rigour initiative of the International Society for Extracellular Vesicles (ISEV). The last update to MISEV, MISEV2018, was informed by input from more than 400 scientists and made recommendations in the six broad topics of EV nomenclature, sample collection and pre-processing, EV separation and concentration, characterization, functional studies, and reporting requirements/exceptions. To gather opinions on MISEV and ideas for new updates, the ISEV Board of Directors canvassed previous MISEV authors and society members. Here, we share conclusions that are relevant to the ongoing evolution of the MISEV initiative and other ISEV rigour and standardization efforts.
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Background: HA is a major component of the tumor microenvironment (TME) in PDA. PEGPH20 degrades tumor HA, remodeling the TME. In PDA models, PEGPH20 has shown antitumor activity and increased TME delivery of anticancer agents to improve efficacy. A randomized phase 2 study showed promising results for PEGPH20+AG (PAG) in mPDA and identified HA accumulation as a biomarker. We present results from a phase 3 study (NCT02715804) of PAG for pts with HA-high mPDA.
Method(s): Pts >=18 years with untreated HAhigh mPDA were randomized (stratified by geographic region) 2:1 to PAG or placebo+AG (AG). HA status was prospectively determined with VENTANA HA RxDx Assay, with HA-high defined as >=50% staining of a tumor sample. Treatment was administered IV in 4-wk cycles (3 wks on, 1 wk off) until progression or intolerable adverse events (AEs): PEGPH20 3.0 mug/kg twice wkly for Cycle 1 and once wkly (QW) thereafter, A 125 mg/m QW and G 1000 mg/m² QW. Prophylactic enoxaparin 1 mg/kg was given daily for thromboembolism (TE) risk. The primary endpoint was overall survival (OS); secondary endpoints included progression-free survival (PFS), objective response rate (ORR) and safety. Response was independently assessed per RECIST v1.1. The estimated sample size was ~500 pts to detect a hazard ratio (HR) for OS of 0.67 (93% power, 2-sided alpha = 0.05) after 330 deaths.
Result(s):As of 20 May 2019, 494 pts were randomized with 492 (327 for PAG and 165 for AG) included in ITT analyses (2 pts excluded due to site violations). Baseline characteristics were balanced for PAG vs AG. After 330 deaths, median OS for PAG vs AG was 11.2 vs 11.5 mo (HR 1.00, 95% CI 0.80-1.27; P = 0.97); median PFS was 7.1 vs 7.1 mo (HR 0.97, 95% CI 0.75-1.26); confirmed ORR was 34% vs 27%. Grade (G) 3+ AEs (PAG vs AG) included neutropenia (44% vs 47%), thrombocytopenia (21% vs 16%) and fatigue (16% vs 10%); G3+ rates were 6% vs 7% for TE events, 5% vs 2% for bleeding events and 13% vs 5% for musculoskeletal events.
Conclusion(s): PAG did not improve clinical outcomes vs AG. The PAG safety profile was consistent with that of previous studies

BACKGROUND/AIMS/OBJECTIVE:Glomerular endothelial cell injury plays a crucial role in the development of diabetic nephropathy (DN). CD146, an endothelial marker, was shown to increase in chronic kidney disease (CKD), but its role in DN remains unknown. We aim to assess whether CD146 could be used to evaluate disease severity and predict renal outcomes in DN at early stages. METHODS:159 non-dialysis type 2-DN patients from 2008 to 2015 were enrolled to measure the plasma concentration of soluble CD146 (sCD146). 94 type 2 diabetes mellitus patients without DN and 100 healthy subjects were used as controls. The patients with CKD stage 1-3 were referred as early stage patients. Another independent cohort of 48 patients with biopsy-proved DN was used for the immunohistochemistry study of CD146. Renal outcomes were defined as doubling of serum creatinine, initiation of renal replacement therapy or death. RESULTS:We found that plasma level of sCD146 was upregulated and associated with renal function in DN patients. sCD146 was proved to be a more optimal marker than urine albumin creatinine ratio to evaluate disease severity in these DN patients. The kidney expression of CD146 was co-localized with endothelial marker CD31 and increased in DN. CD146 staining in kidney was correlated with the severity of pathological changes in DN patients. Survival analysis suggested that both plasma and biopsy expression of CD146 were correlated with renal outcomes. CONCLUSIONS:CD146 is associated with kidney injury and could be a good marker to predict renal outcomes in patients with early stages of DN.

BACKGROUND:Oral health has been found to be associated with cognitive function in basic research and epidemiology studies. Most of these studies had no comprehensive clinical diagnosis on cognitive function. This study firstly reported the association between tooth loss and cognitive function among Chinese older population. METHODS:The study included 3,063 community dwelling older adults aged 60 or above from the Shanghai Aging Study. Number of teeth missing was obtained from self-reporting questionnaire and confirmed by trained interviewers. Participants were diagnosed as "dementia", "mild cognitive impairment (MCI)", or "cognitive normal" by neurologists using DSM-IV and Petersen criteria. Multivariate logistic regression model was applied to examine the association between number of teeth missing and cognitive function. RESULTS:The study participants had an average of 10.2 teeth lost. Individuals with dementia lost 18.7 teeth on average, much higher than those with MCI (11.8) and cognitive normal (9.3) (p<0.001). After adjusted for sex, age, education year, living alone, body mass index, cigarette smoking, alcohol drinking, anxiety, depression, heart disease, hypertension, diabetes, and APOE-ε4, tooth loss of >16 were significantly associated with dementia with an OR of 1.56 (95%CI 1.12-2.18). CONCLUSION/CONCLUSIONS:Having over 16 missing teeth was associated with severe cognitive impairment among Chinese older adults. Poor oral health might be considered as a related factor of neurodegenerative symptom among older Chinese population.

BACKGROUND:High school students are an important target audience for organ donation education. A novel educational intervention focused on Hispanic American (HA) high school students might improve organ donation rates. METHODS:A prospective observational study was conducted in five Los Angeles High Schools with a high percentage of HA students. A "culturally sensitive" educational program was administered to students in grades 9 to 12. Preintervention surveys that assessed awareness, knowledge, perception, and beliefs regarding donation as well as the intent to become an organ donor were compared to postintervention surveys. RESULTS:A total of 10,146 high school students participated in the study. After exclusions, 4876 preintervention and 3182 postintervention surveys were analyzed. A significant increase in the overall knowledge, awareness, and beliefs regarding donation was observed after the intervention, as evidenced by a significant increase in the percentage of correct answers on the survey (41% pre- versus 44% postintervention, P < .0001). When specifically examining HA students, there was a significant increase in the intent to donate organs (adjusted odds ratio 1.21, 95% confidence interval: 1.09, 1.34, P = .0003). CONCLUSION/CONCLUSIONS:This is the first study to demonstrate a significant increase in the intent to donate among HA high school students following an educational intervention.