IMPROvE-CED Trial: Intracoronary Autologous CD34+ Cell Therapy for Treatment of Coronary Endothelial Dysfunction in Patients With Angina and Non-Obstructive Coronary Arteries

Background: Coronary endothelial dysfunction (CED) causes angina/ischemia in patients with no-obstructive CAD (NOCAD). Patients with CED have decreased number and function of CD34+ cells involved in normal vascular repair with microcirculatory regenerative potential and paracrine anti-inflammatory effects. We evaluated safety and potential efficacy of intracoronary (IC) autologous CD34+ cell therapy for CED. Methods: Twenty NOCAD patients with invasively-diagnosed CED and persistent angina despite maximally-tolerated medical therapy (MTMT) underwent baseline exercise stress test (EST), GCSF-mediated CD34+ cell-mobilization, leukapheresis, and selective 1x105 CD34+ cells/kg infusion into LAD. Invasive CED evaluation and EST were repeated 6-months after cell infusion. Primary endpoints were safety and effect of IC autologous CD34+ cell therapy on CED at 6-months follow-up. Secondary endpoints were change in CCS angina class, as-needed sublingual nitroglycerin use/day, Seattle Angina Questionnaire (SAQ) scores, and exercise time at 6-months. Change in CED was compared to that of 51 historic-control NOCAD patients treated with MTMT alone. Results: Mean age was 52{plus minus}13 years, 75% women. No death, myocardial infarction, or stroke occurred. IC CD34+ cell infusion improved microvascular CED [% acetylcholine-mediated coronary blood flow increased from 7.2 (-18.0-32.4) to 57.6 (16.3-98.3) %, p=0.014], decreased CCS angina class (3.7{plus minus}0.5 to 1.7{plus minus}0.9, Wilcoxon signed-rank test p=0.00018) and sublingual nitroglycerin use/day [1 (0.4-3.5) to 0 (0-1), Wilcoxon signed-rank test p=0.00047], and improved all SAQ scores with no significant change in exercise time at 6-months follow-up. Historic-control patients had no significant change in CED. Conclusion: A single IC autologous CD34+ cell infusion was safe and may potentially be an effective disease-modifying therapy for microvascular CED in humans. Clinical Trial Registration: NCT03471611

Virtual inverted classroom to replace in-person radiology lectures at the time of the COVID-19 pandemic - a prospective evaluation and historic comparison

Background In the time of the coronavirus disease 2019 (COVID-19) pandemic, in-person lectures had to be shifted to online learning. This study aimed to evaluate students’ and lecturers’ perception and effectiveness of a virtual inverted classroom (VIC) concept on clinical radiology in comparison to a historic control. Methods In the winter semester 2020/21, 136 fourth year medical students who completed the clinical radiology VIC during the pandemic, were included in the single centre, prospective study. Results were compared with a historic control that had finished the physical inverted classroom (PIC) in the immediately preceding year. The VIC consisted of an initial phase of self-determined preparation with learning videos and a second interactive phase of clinical case studies alternating between the virtual lecture hall and virtual buzz groups. At the end of the lecture series, students rated the lecture on a scale of 1 (most positive assessment) to 6 (most negative assessment) through an online survey platform. Additionally, they reported their impressions in free-form text. Lecturers were invited to comment on the VIC in a group interview. Main outcomes were final grades and student perception of the VIC. Results Students’ general impression of VIC was lower than that of PIC (median value of 3 [IQR 4, 2] and 1 [IQR 0, 0], p < 0.001), respectively, p < 0.001). The highest rating was achieved concerning use of the audience response system (median 1 [IQR 1, 0]), and the lowest concerning the buzz groups (median 4 [IQR 5, 3]). Students stated that they would have appreciated more details on reading images, greater focus on plenary case studies, and provision of exam related scripts. Lecturers would have liked better preparation by students, more activity of students, and stronger assistance for group support. Exam grades after VIC were better than after PIC (median 1 [IQR 2, 1] and 2 [IQR 2,1], respectively, p < 0.001). Conclusions Students’ overall perception of VIC was satisfactory, although worse than PIC. Final grades improved compared to PIC. Provided an adapted buzz group size and support, VIC may serve as complement in medical education once the pandemic is over.

P14.76 Bevacizumab (BEV) alone or in combination with chemotherapy in recurrent Glioblastoma Multiforme (GBM): A real world experience

BACKGROUND Patients with glioblastoma multiforme (GBM) have a median survival of about 14 months. In recurrent GBM no active intervention has shown improvement in survival. Clinical trials has shown that bevacizumab (BEV) alone or in combination with chemotherapy is associated with better progression free survival (PFS). The current study aims to assess efficacy of BEV in real-world setting. MATERIAL AND METHODS Population-based retrospective cohort study patients with recurrent GBM diagnosed in the province of Saskatchewan during 2008–2018 and received BEV alone or in combination with chemotherapy were evaluated. Survival was compared with historic control. RESULTS 43 eligible patients with GBM treated with BEV with or without chemotherapy. 25 patients were treated with Bev alone and 18 patients treated with chemotherapy+ BEV. Median age of the patients were noted to be 53 years. 28 male, and 15 female. 80% of patients treated with single agent BEV had a performance status of either 2 or 3 compared to 33% of patient treated with BEV+ chemotherapy. Median PFS was 4.6 months with 95% CI 2.9–6.9. Median Overall survival (OS) from the time of diagnosis was 17.5 month. Median OS from the time of start of BEV was 5.4 months with 95% CI 3.4–6.8. Partial response (PR) was noted in 3 patients (7%) with stable disease (SD) in 6 patients (14%). 33 (77%) had progressive disease (PD). We were unable to confirm response status in one patient (2%). No statistically significant difference in response rate for patients treated with BEV and BEV+ Chemotherapy. From the start of Bev to the best response, 11 patients (30.56%) noted decrease in the dose of steroids, 14 patients (38.89%) dose remained unchanged. 7 patients (19.44%) required increase in the dose of steroids. 4 patients (11.11%) were not on steroids. For 7 patients we did not have the information on use of steroids. PFS was better for patients treated with chemotherapy + BEV with median PFS of 6.9 months, 95% CI 3.2- 22.3 verses BEV alone with median PFS 3.53 months 95% CI 1.4–5.3, P-value 0.0449. The Cox regression model for PFS to test comparing Bev with chemotherapy vs. Bev alone with the co-variables of sex, age, and ECOG performance status (PS). The model showed that patient with higher ECOG PS were noted to have inferior PFS with a Hazard ratio of 1.92 95% CI 1.09–3.37. P value of 0.2. Patient treated with BEV+ chemo had better PFS with a HR of 6.44 95% CI 1.86–22.28. P value of 0.003. CONCLUSION Retrospective real world study confirms that, patients with recurrent GBM, treatment with BEV is associated with similar PFS as reported in literature. Our study showed similar overall survival from the diagnosis compared to historic control. However the Median OS from Start of BEV was noted to be inferior to what is reported in EORTC EH1.3. Better ECOG performance status is associated with better PFS. Higher number of patients with ECOG 2 and 3 received BEV alone.

Using an online CBT-based intervention to improve academic performance in students with low mood: A pre-post study with historical control

Background Online CBT-based interventions have shown potential to improve mental health in university students. However, their impacts in West Asian cultures and on educational achievement have yet to be fully investigated. This study aims to explore the feasibility, acceptability and potential effectiveness of a self-directed, internet-delivered, cognitive-behavioural skills training program (MoodGYM) in reducing depression and improving academic performance in university students in the United Arab Emirates (UAE). Methods This exploratory pre-post intervention study with an historic control group recruited 50 students from one UAE university, with GPA < 2 and self-reporting at least one of two key depressive symptoms. Pre-intervention, participants completed an online survey including most recent grade point average (GPA), number of attendance warnings and the Hospital Anxiety and Depression Scale (HADS). Participants were then sent a link to MoodGYM. After eight weeks, 44 participants repeated the survey and provided feedback on MoodGYM (88% follow-up). A subgroup of 19 students with GPA scores < 2 at baseline formed an historical control group for change in GPA and attendance warnings. Results Total HADS-Depression scores fell at post intervention (P = 0.004) and the proportion of participants scoring above the cut-off for depression (HADS-D ≥ 8) fell from 77.2–27.3% (p < 0.001). There was also a substantial fall in HADS-Anxiety scores (p < 0.001) and the proportion of participants above the cut-off for anxiety (HADS-A ≥ 8) fell from 50% to 11.4 % (p = 0.001). GPA scores improved substantially over time (p < 0.001, d = 1.3) and attendance warnings reduced (p = 0.008, d = 0.6). Compared to historic control, the intervention group had higher GPA at follow-up (p < 0.030 d = 0.6) fewer attendance warnings (p = 0.036 d = 0.7). Most students (79.6%) evaluated MoodGYM as useful and all students completed at least 2 MoodGYM modules. More modules completed (p = 0.005) and greater reduction in attendance warnings (p = 0.007) were independently associated with greater improvement in GPA scores at follow-up. Conclusions This study provides support for a web based mental health promotion intervention (MoodGYM) to improve academic achievement in university students with depressive symptoms. Further research is needed to explore how MoodGYM can be best implemented within University settings.

Intracorporeal anastomosis in right hemicolectomy for colon cancer: short-term outcomes with the DaVinci Xi robot

Intracorporeal anastomosis (IA) may improve outcomes compared with extracorporeal anastomosis (EA) in minimally invasive right colectomy. This is a prospective series of robotic right hemicolectomies (RRC) with IA from one institution. 35 consecutive patients with verified or suspected right colon cancer undergoing RRC with IA, and historic control groups of 22 RRC and 40 laparoscopic right colectomies (LRC), both with EA. Primary outcome measure was length of stay (LOS). Secondary outcome measures were 30-day complication rates, readmissions, pain scores, analgesic consumption, and specimen quality. Median LOS did not differ significantly between the groups (RRC-IA, 4 days; LRC-EA, 4 days; RRC-EA, 5 days). In-hospital surgical complications Clavien–Dindo 3 + were seen in 1, 2, and 0 patients, respectively, and 3, 5, and 3 patients were readmitted to hospital within 30 days. Median pain score was 2 in all groups on postoperative day (POD) 2. Relatively more patients in the RRC-IA group received gabapentin on POD 2 (p = 0.006), but use of other analgetics did not differ between groups. Mean specimen lengths were 31, 25 and 27 cm, respectively (RRC-IA vs. LRC-EA, p = 0.003), but mesentery width, proportion of mesocolic excisions and number of lymph nodes did not differ between the groups. RRC-IA was not associated with shorter LOS, fewer complications or better specimen quality than recent controls undergoing either RRC-EA or LRC-EA.

Intracavernous injection of stem cell-derived bioactive molecules for erectile dysfunction—a pilot phase non-randomized controlled trial

Background and objective: Experimental and few clinical studies have indicated great potential of stem cell treatments as both a causal and symptomatic approach for the treatment of male erectile dysfunction (ED). We investigated the effect of a one-time injection of stem-cell derived bioactive molecules in patients with self-reported ED. Materials and methods: Twenty self-referred male patients with at least one-year history of ED received a one-time intra-penile injection of acellular stem cell-derived bioactive molecules. ED was evaluated by the International Index of Erectile Function questionnaire (IIEF-5), and quality of life was assessed by the Short-Form-36 questionnaire, (SF-36) at baseline and at 6 months. Six male patients with ED, who received a similar injection using saline served as a historic control. Primary outcome was erectile function as measured by IIEF-5 scores. Secondary outcomes were quality of life, assessed by SF-36 questionnaire. Results: IIEF-5 scores improved from 12.9 ± 4.47 at baseline to 18 ± 3.37 at follow-up (p < 0.05). No significant difference of IIEF-5 scores were observed in the historic controls during the observation period (11 ± 2.53 at baseline vs 10.67 ± 3.5 at follow-up; p > 0.05). Patients, who received stem cell injections, demonstrated significantly enhanced IIEF-5 scores compared to the historic control (p < 0.05). Quality of life scores were significantly improved (role limitations due to physical health issues 56.25 ± 42.82 at baseline vs 68.75 ± 40.45 at follow-up, p < 0.05, energy 51.57 ± 19.33 at baseline vs 57.75 ± 12.3 at follow-up, p < 0.05, emotional wellbeing 56.32 ± 16.28 at baseline vs 68.1 ± 11.73 at follow-up, p < 0.05, and social functioning 67.5 ± 23.79 at baseline vs 76.25 ± 18.98 at follow-up, p < 0.05). Conclusions: A one-time intracavernous acellular stem cell-derived bioactive molecule injection improves IIEF-5 scores and quality of life in men with ED in this small pilot phase study (ClinicalTrials.gov Identifier: NCT04684602).

Treatment outcomes in patients with drug-resistant TB-HIV co-infection treated with bedaquiline and linezolid

BACKGROUND: Bedaquiline (BDQ) has not been extensively studied among patients co-infected with HIV drug-resistant tuberculosis (DR-TB). We compared treatment outcomes in DR-TB patients treated with BDQ- and linezolid (LZD) containing regimens to historic controls treated with second-line injectable-containing regimens.METHODS: Retrospective cohort study of consecutive DR-TB patients initiated on BDQ- and LZD-containing regimens at a TB referral hospital in KwaZulu-Natal, South Africa. Participants were prospectively followed through 24 months for treatment outcome and adverse events. Outcomes were compared to a historic control cohort of DR-TB HIV patients enrolled at the same facility prior to BDQ introduction.RESULTS: Adult DR-TB patients initiating BDQ between January 2014 and November 2015 were enrolled (n = 151). The majority of patients were female (52%), HIV co-infected (77%) and on antiretroviral therapy (100%). End of treatment outcomes included cure (63%), TB culture conversion (83%), completion (0.7%), loss to follow-up (15%), treatment failure (5%), and death (17%). Compared to historic controls (n = 105), patients treated with BDQ experienced significantly higher TB culture conversion and cure, with significantly lower mortality. Adverse effects were common (92%), and most frequently attributed to LZD (24.1%). QT segment prolongation was common but without clinical sequelae.CONCLUSION: Treatment with BDQ- and LZD-containing regimens was associated with improved treatment outcomes and survival in DR-TB HIV patients.

75. Less is More: A Physician-Driven Quality Improvement Stewardship Initiative to Reduce Excessive Duration of Antibiotic Therapy in Veterans Hospitalized with Community-Acquired Pneumonia

Background The IDSA and American Thoracic Society (IDSA/ATS) Community Acquired Pneumonia (CAP) guidelines recommend 5 days of therapy for clinically stable patients that defervesce, however, duration of therapy (DOT) is often longer. Pharmacists curb this via antimicrobial stewardship (AMS), but budgetary constraints are barriers to robust AMS programs in some hospitals. Physicians are increasingly encouraged to participate in quality improvement (QI) and are a potential resource to improve AMS. We sought to determine the impact of a prospective, physician-driven stewardship intervention on DOT and clinical outcomes in hospitalized veterans with CAP, with the goal to reduce the median DOT by at least 1 day within 5 months. Methods This single center, quasi-experimental QI study evaluated two concurrent physician-driven interventions over a 5-month period in an inner-city Veterans Affairs Hospital. Using DMAIC (Define, measure, analyze, improve, and control) methodology, the Chief Resident in Quality and Safety (CRQS) provided monthly education and daily audit and feedback with patient-specific DOT recommendations. Clinical outcomes were followed until 30 days post discharge. Results A total of 123 patients with CAP were included (57 in the historic control group and 66 in the AMS intervention group). The AMS intervention significantly increased the proportion of CAP patients treated with a 5-day treatment course (56% versus 5.3%, p&lt; 0.0001), and reduced the proportion of patients treated beyond 7 days (12.1% versus 70.2%, p&lt; 0.0001). Median DOT per patient was reduced significantly (5 versus 8 days, p&lt; 0.0001). Median excess antibiotic days were significantly reduced (0 versus 3, p&lt; 0.0001) and 118 days of unnecessary antibiotics were avoided (62 versus 180). 30-day all-cause mortality, all-cause readmission, and Clostridium difficile infection were similar between groups. Median LOS was similar between groups (p=0.246). DOT in the Historic Control Group Versus Stewardship Intervention Group Conclusion A physician driven QI stewardship intervention in hospitalized CAP patients significantly reduced the total antibiotic DOT and excess antibiotic days without adversely affecting patient outcomes. Providers can be educated through physician driven interventions resulting in substantial improvements in appropriate antibiotic use. Disclosures All Authors: No reported disclosures