Correlation of Volume of Macular Edema with Retinal Tomography Features in Diabetic Retinopathy Eyes

Optical coherence tomography (OCT) enables the detection of macular edema, a significant pathological outcome of diabetic retinopathy (DR). The aim of the study was to correlate edema volume with the severity of diabetic retinopathy and response to treatment with intravitreal injections (compared to baseline). Diabetic retinopathy (DR; n = 181) eyes were imaged with OCT (Heidelberg Engineering, Germany). They were grouped as responders (a decrease in thickness after intravitreal injection of Bevacizumab), non-responders (persistent edema or reduced decrease in thickness), recurrent (recurrence of edema after injection), and treatment naïve (no change in edema at follow-up without any injection). The post-treatment imaging of eyes was included for all groups, except for the treatment naïve group. All eyes underwent a 9 × 6 mm raster scan to measure the edema volume (EV). Central foveal thickness (CFT), central foveal volume (CFV), and total retinal volume (TRV) were obtained from the early treatment diabetic retinopathy study (ETDRS) map. The median EV increased with DR severity, with PDR having the greatest EV (4.01 mm3). This correlated positively with TRV (p < 0.001). Median CFV and CFT were the greatest in severe NPDR. Median EV was the greatest in the recurrent eyes (4.675 mm3) and lowest (1.6 mm3) in the treatment naïve group. Responders and non-responders groups had median values of 3.65 and 3.93 mm3, respectively. This trend was not observed with CFV, CFT, and TRV. A linear regression yielded threshold values of CFV (~0.3 mm3), CFT (~386 µm), and TRV (~9.06 mm3), above which EV may be detected by the current scanner. In this study, EV provided a better distinction between the response groups when compared to retinal tomography parameters. The EV increased with disease severity. Thus, EV can be a more precise parameter to identify subclinical edema and aid in better treatment planning.

Is Sunflower Cooking Oil Desirable for Colorectal Cancer? In Vivo Studies on Azoxymethane-Induced Colon Cancer in Rats

Background: The incorporation of oils in the diet may have promoting or inhibitory effects on Colorectal Cancer (CRC). In this study, azoxymethane (AOM) was used to mimic CRC in rats and the effect of sunflower oil on cancer progression in the colon of the rats was tested. Objective: This study was conducted to investigate the effect of sunflower oil on preneoplastic cancer properties on the colonic mucosal surface for tumors and the aberrant crypt foci (ACF). Methods: Six weeks old Sprague-Dawley male rats were randomized into 4 groups of 6 rats each, namely naïve, positive control, negative control and sunflower oil-fed. CRC was induced by AOM by subcutaneous injection of 20 mg/kg. After CRC induction, the rats were given respective treatment of either basal diet (naïve group), 10 mg/kg indomethacin (positive control), 0.9% saline (negative control), and 7% sunflower oil (experimental group) daily by oral gavage for 42 days. Rats were sacrificed by cervical dislocation; colon samples were visually observed for any tumors on the colonic mucosal surface and evaluated for ACF; histopathological examinations were also performed. Results: The mean body weights of the rats were similar in all groups as per one-way ANOVA. A total of 3 ACF were found in the negative group while none were observed in others. The crypts appeared regular with circular luminal openings and were arranged closely packed together in the naïve group. Crypts in the positive and treated group had a similar appearance like naïve group. Conclusion: Sunflower oil inhibition of the preneoplastic cancer ACF properties were tested but were found to be insignificant when administered during CRC treatment or management. However long-term experiment with a greater number of days will yield better development of tumor and ACF development and will be useful identifying the molecular mechanism.

Combination antiretroviral therapy is associated with reduction in liver fibrosis scores in patients with HIV and HBV co-infection

Background Liver fibrosis is common in individuals with HIV/HBV co-infection, but whether cART could reverses liver fibrosis is unclear. Methods This was a retrospective observational study. Binary logistic regression was used to assess predictors of liver fibrosis in individuals with HIV/HBV co-infection. Comparison of FIB-4 scores before and after cART were compared using X2 test and t test. Results Four hundred and fifty-eight individuals with HIV/HBV co-infection were included in this study. It was found that cART (HR 0.016, 95% CI: 0.009–0.136; P < 0.001) was one of protection factors to against liver fibrosis. Forty individuals who had normal levels of ALT, AST and PLT during the whole course of diseases were stratified into FIB-4 < 1.45 (n = 14), 1.45 ≤ FIB-4 ≤ 3.25 (n = 19) and FIB-4 > 3.25 (n = 7) groups by their FIB-4 scores before cART. In 1.45 ≤ FIB-4 ≤ 3.25 group, 57.9%(11/19) of the individuals dropped to FIB-4 < 1.45 group by cART; in FIB-4 > 3.25 group, 85.7%(6/79) dropped to 1.45 ≤ FIB-4 ≤ 3.25 group, while 14.3%(1/7) dropped to FIB-4 < 1.45 group. In cART-naive group, 1 year, 2–5 years and 5–10 years post-cART groups, FIB-4 scores were 4.29 ± 0.43, 3.63 ± 0.38, 2.90 ± 0.36 and 2.52 ± 0.38, respectively (P = 0.034); and the incidence of liver fibrosis were 7.38%(104/141), 63.6%(98/154), 60.8%(62/102) and 47.5%(29/61), respectively (P = 0.004). Conclusion cART was associated with decreased FIB-4 scores and the benefit of cART in reversing liver fibrosis can sustain for a decade in patients with HIV/HBV co-infection.

Effect of Steroid Treatment on the Diagnostic Yield of Baseline PET CT in Aggressive B Cell Lymphoma

Aggressive B cell lymphomas often require prompt steroid treatment prior to baseline 18f-fluorodeoxyglucose positron-emission tomography (PET CT) scan and definitive treatment in order to alleviate symptoms and/or prevent organ damage. Since lymphomas are a steroid sensitive malignancy, there is a concern that steroid prophase might affect PET CT results and diagnostic yield. We conducted a retrospective cohort study to evaluate the effect of steroid treatment prior to baseline PET CT scan on the standardized uptake value (SUV) max and additional PET CT parameters by examining two groups of patients: steroid-naïve and steroid-treated patients. The effect of steroid administration on SUV max was examined across different daily and weekly steroid doses and durations of treatment. Between January of 2017 and May 2020, 187 newly diagnosed patients with aggressive B cell lymphoma who had a pre-treatment PET CT scan were evaluated. 160 patients (85.5%) had Diffuse large B-cell lymphoma (DLBCL)/ High-grade B-cell lymphoma, 13 patients (7%) had primary mediastinal (thymic) large B-cell lymphoma, 9 patients (4.8%) had primary DLBCL of the central nervous system and 5 patients (2.7%) had Burkitt lymphoma. 132 patients (70.6%) were included in the steroid-naïve group and 55 patients (29.4%) in the steroid-treated group. In the steroid-treated group, the mean duration of steroid treatment was 10.49 (±9.28) days. Average daily dose of steroid treatment was equivalent to 72.27 (±36) mg of prednisone and the mean cumulative prednisone dose during the week prior to PET CT scan was equivalent to 367.95 (±239.9) mg of prednisone. There was no statistical significant difference between the groups in age, gender or KI67. However, patients in the steroid treated group had a significantly higher stage of disease compared to the steroid-naïve group (mean 3.44 compared to 2.99, respectively, p=0.01). The steroid-treated group also had a trend towards a higher IPI score (mean 2.45 versus 2.08, p=0.08) and a trend towards a higher LDH level (mean 2309.89 U/L, range 250-81374 versus mean 877.65 U/L, range 272-22036, p= 0.07), as depicted in table 1. There was no statistical difference in SUV max between the steroid-naïve and steroid-treated groups (p=0.97). This was consistent across various steroid treatment durations and dosage regimes. Patients in the steroid-treated group had a trend towards a higher tumor burden and a larger tumor volume compared to the steroid-naïve group, however it did not reach statistical significance. Mean tumor volume was 179.04 cm 3 in the steroid naïve group and 337.06 cm 3 in the steroid treated group (p=0.17). Mean tumor burden was 1944.84 in the steroid-naïve group and 3016.94 in the steroid-treated group (p=0.09). There was no difference in additional PET CT parameters including SUV mean, SUV max and SUV mean of liver and mediastinum between the groups as depicted in table 2. In conclusion, in aggressive B cell lymphoma, pre-treatment with steroids prior to initial PET CT scan does not affect SUV max or other PET CT parameters and does not reduce PET CT diagnostic yield. Figure 1 Figure 1. Disclosures Gurion: Medison: Consultancy; Gilead Sciences: Consultancy; Takeda Pharmaceuticals: Consultancy; JC Health Care: Honoraria; Roche: Honoraria.

TAMI-19. IMMUNOHISTOLOGICAL ANALYSIS OF ANGIOGENIC FACTORS OTHER THAN VEGF IN GLIOBLASTOMAS IN RELATION TO THE USE OF BEVACIZUMAB

Although bevacizumab was shown to improve progression-free survival and performance status of the patients with high-grade gliomas, clinical trials consistently showed lack of benefit in terms of patients’ overall survival. The recurrent tumors are inevitably more aggressive and invasive as compared with the original tumors, and the in-situ observation in actual human specimens is essential to elucidate the mechanism of resistance. In Japan, bevacizumab was approved not only for recurrent but also for newly diagnosed cases. The safety as well as efficacy of resection following neoadjuvant bevacizumab has been reported, and a phase II study is currently ongoing (UMIN-000025579). In the present study, the expression of angiogenic factors other than VEGF (basic fibroblast growth factor (bFGF), placenral growth factor (PlGF), angiopoietin1/2 and ephrinA2) was investigated by immunohistochemistry to be compared among tumors with no previous bevacizumab treatment, those resected following bevacizumab, and those refractory to bevacizumab. Fifty-nine samples from 42 patients were included; 24 of newly diagnosed glioblastomas with no previous bevacizumab (naïve group), 16 resected following neoadjuvant bevacizumab (effective group), and 6 resected after recurrence or autopsied (refractory/autopsied group). 12 were paired samples (8 naïve and refractory, 4 effective and refractory). The expression of PlGF significantly increased in the effective group as compared with the naïve group (p=0.003). In the paired specimens, there was a trend towards increased expression of PlGF in the second specimens (refractory/autopsied group) as compared with the specimens of initial surgery (p=0.083). Angiopoietin1, angiopoietin2 and ephrinA2 were characteristically expressed in the microvessels less than 15μm. The increased expression of PlGF might be associated with the recurrence after bevacizumab.

Clinical Features and Resistance to Entecavir Monotherapy of Patients with Hepatitis B

Aim. Hepatitis B virus (HBV) infection is a major public health concern worldwide. Entecavir (ETV), a first-line nucleos(t)ide analogue (NA) for HBV, has a low risk of resistance. We evaluated the efficacy of ETV monotherapy, ratio of ETV-resistant, and the clinical features of patients with ETV resistance. Methods. A total of 130 patients (72 males, 58 females; mean age, 61 ± 15 years) were divided into a NA-naïve group (n = 108) and NA-experienced group (n = 22). We examined the clinical outcomes of ETV monotherapy and associated factors. We also assessed the clinical features of 15 patients with resistance to ETV (mean, 51.0 ± 27.4 weeks). Results. Among the 130 patients, 94.1% achieved ALT normalization and 63.6% achieved serum HBV DNA negativity after ETV monotherapy for 96 weeks. Of the patients in the NA-naïve group, 93.1% and 60.4% achieved ALT normalization and HBV DNA negativity, respectively. Of the patients in the NA-experienced group, 100% and 74.9% achieved ALT normalization and HBV DNA negativity, respectively. Compared to patients on ETV continuously, 15 ETV-resistant patients had a higher baseline HBV viral load. There was a significant difference in the time to HBV DNA negativity, but not ALT normalization after ETV monotherapy in these groups. Rescue treatment with other NAs led to ALT normalization in all of these patients, but not HBV DNA negativity. Conclusions. ETV monotherapy has a long-term clinical efficacy. While some patients especially with HBV DNA high viral load developed ETV resistance, rescue treatment led to ALT normalization in these patients.

Nephrotoxicity Risk of Cyclophosphamide in Lupus Model

Cyclophosphamide is one of the standard therapies for lupus, especially lupus nephritis based on its immunosuppressive effect. However, cyclophosphamide is also known as a nephrotoxic agent. Therefore, this research was aimed to measure the effect of cyclophosphamide at the dose that comparable to the human dose of 1 mg/kg BW on the kidney of lupus mice induced by means of 2,6,10,14-tetramethylpentadecane (TMPD). In this research, the IL-6 as a pro-inflammatory cytokine was tested by using flow cytometry method. In addition, the structural damage of the kidney tissues was assessed by means of Moroni’s kidney organ scoring method for lupus. The result showed that cyclophosphamide reduced the IL-6 significantly with the value of 36.72±22.79% for the TMPD-treated group; 32.59±9.97% for the cyclophosphamide group; and 30.25±4.48% for the naïve group. Moreover, the damages of the kidney tissues on the cyclophosphamide group were more severe than the TMPD-treated group. In conclusion, despite its anti-inflammatory effect which is useful for lupus, cyclophosphamide has a severe nephrotoxic effect which harms the patient. The effects may be a cause of the long interval use of cyclophosphamide. It can be a consideration for the further research and the next revision of the guideline for lupus nephritis treatment.

People Living with HIV Easily lose their Immune Response to SARS-CoV-2: Result From A Cohort of COVID-19 Cases in Wuhan, China

Background To date, whether the immune response for SARS-CoV-2 infection among people living with HIV(PLWH) is different from HIV-naïve individuals is still not clear. Methods In this cohort study, COVID-19 patients admitted to hospital in Wuhan between January 15 and April 1, 2020, were enrolled. Patients were categorized into PLWH and HIV-naïve group. All patients were followed up regularly (every fifteen days) until November 30, 2020, and the immune response towards SARS-CoV-2 was observed. Results Totally, 18 PLWH and 185 HIV-naïve individuals with COVID-19 were enrolled. The positive conversion rates of IgG were 56% in PLWH and 88% in HIV-naïve patients respectively, and the peak was on the 45th day after COVID-19 onset. However, the positive rate of IgG dropped to 12% in PLWH and 33% among HIV-naïve individuals by the end of the study. The positive conversion rate of IgG among asymptomatic carriers is significantly lower than that among moderate patients (AOR = 0.18, 95% CI: 0.05–0.65) and PLWH had a lower IgG seroconversion rate compared to the HIV-naive group (AOR = 0.22, 95% CI: 0.05–0.90). Patients with lower lymphocyte counts at onset had a higher positive conversion rate (AOR = 0.29, 95% CI: 0.09–0.90) and longer duration for IgG (AHR = 4.01, 95% CI: 1.78–9.02). Conclusions The positive conversion rate of IgG for SARS-CoV-2 was relatively lower and quickly lost in PLWH, which meant PLWH was in a disadvantaged situation when affected with COVID-19.

Metabolic Syndrome Prevalence and Cardiovascular Risk Assessment in HIV-Positive Men with and without Antiretroviral Therapy

Treatment of HIV infection is a lifelong process and associated with chronic diseases. We evaluated the prevalence and predictors of metabolic syndrome (MetS) and cardiovascular diseases (CVDs) with individual antiretroviral drugs exposure among HIV-infected men in Taiwan. A total of 200 patients’ data were collected with a mean age of 32.9. Among them, those who had CD4 positive cell number less than 350/mL were eligible to have highly active antiretroviral therapy (HAART). Patients were divided into group-1 that contains 45 treatment-naïve participants, and group-2 that includes 155 HAART treatment-experienced participants. MetS prevalence between group-1 and group-2 was 18% and 31%, respectively. The Framingham Risk Score (FRS) for the naïve and experienced groups were 4.7 ± 4.2 and 3.87 ± 5.92, respectively. High triglyceride (TG > 150 mg/dL) in group-1 and group-2 were 15.6% and 36.6% (p < 0.05), whereas, lower high-density lipoprotein (HDL < 39 mg/dL) in group-1 and group-2 presented as 76.7% versus 51% (p < 0.05), respectively. In group-2, treatment with protease inhibitors (PIs) resulted in higher TG levels when compared with non-nucleotide reverse transcriptase inhibitors (NNRTIs) and integrase inhibitors (InSTIs). The prevalence of MetS in the treatment-naïve group was lower than that of the treatment-experienced group; high TG level resulted in higher MetS prevalence in the treatment-experienced group. In contrast, the cardiovascular risk of FRS in the treatment-naïve group was higher than that of the treatment-experienced group, which may result from the low HDL level. Although group-1 participants have a higher risk of developing CVDs, in group-2, an increasing TG level in PIs user indicated higher CVDs risk. TG and HDL are two significant biofactors that required regular evaluation in HIV-positive individuals.

Stereotactic body radiation therapy and in situ oncolytic virus therapy followed by immunotherapy in metastatic non-small cell lung cancer.

9115 Background: The introduction of immunotherapy has altered the treatment paradigm for metastatic non-small cell cancer (mNSCLC). Unfortunately, many patients with mNSCLC have limited or no benefit from immune checkpoint inhibitors (ICIs). A variety of approaches have been explored to augment the efficacy of ICIs. Our study’s aim was to determine whether the addition of stereotactic body radiation therapy (SBRT) and intratumoral injection of the oncolytic virus ADV/HSV-tk (adenovirus-mediated expression of herpes simplex virus thymidine kinase) to a monoclonal antibody targeting programmed cell death-1 (PD-1) would improve the ICI’s efficacy in the treatment of mNSCLC. Methods: In this single-arm, open-label phase II study, patients with mNSCLC (squamous or non-squamous) who were ICI-naive or who were previously treated with a maximum of one line of therapy that included an ICI received an intratumoral injection of ADV/HSV-tk (5 x 1011 vp) followed by SBRT (30 Gy in 5 fractions) to the same tumor. An anti-PD-1 agent (pembrolizumab 200 mg IV every 3 weeks or nivolumab 240 mg IV every 2 weeks) was then given for up to 24 months (pembrolizumab) or 12 months (nivolumab), or until disease progression or intolerable toxicity. The primary endpoint was objective response rate (ORR) as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. A secondary endpoint was clinical benefit rate (CBR). Results: A total of 35 patients were enrolled, with 28 (80%) receiving pembrolizumab and 7 (20%) receiving nivolumab; 14 (40%) had previous ICI therapy while 21 (60%) were ICI-naive. The ORR and CBR were 28.5% and 61.9% in the ICI-naive group, and 14.2% and 64.2% in the group that previously received an ICI, respectively. Grade 3 or higher toxicity was seen in five patients (26.3%) in the ICI-naive group and in one patient (7.1%) in the previously ICI-treated group. No treatment-related deaths were observed. Conclusions: The addition of SBRT and intratumor injection of ADV/HSV-tk to anti-PD-1 therapy in mNSCLC resulted in a CBR of over 60% for both ICI-naive and previously ICI-treated patients without the use of chemotherapy. The combination was able to reinstitute sensitivity to ICIs in patients previously treated with an ICI, and also benefited some patients whose tumors did not express PD-L1. These findings should be further explored in a larger study population. Clinical trial information: NCT03004183. [Table: see text]