Single Cohort Study Research Articles

Safety of Upfront Locoregional Therapy in Conjunction with Atezolizumab and Bevacizumab for Unresectable Hepatocellular Carcinoma

<h3>Purpose/Objective(s)</h3> The use of atezolizumab and bevacizumab for advanced hepatocellular carcinoma (HCC) is a recently established standard of care. Addition of locoregional therapies (LRT) such as external beam radiotherapy (RT), radioembolization (Y90), transarterial chemoembolization (TACE), and/or radiofrequency ablation (RFA) may hold promise for further improving outcomes, but the safety of these approaches with atezolizumab/bevacizumab has not been established. This study assessed the safety of upfront LRT in conjunction with this immunotherapy regimen in HCC. <h3>Materials/Methods</h3> We reviewed all patients initiating atezolizumab with or without bevacizumab (IO) for HCC from July 2020 to January 2022 at a single institution. Patients receiving LRT (RT, Y90, TACE, and/or RFA) within 30 days of IO initiation (LRT+IO) were identified alongside a comparison arm of all patients initiating IO alone. Bevacizumab was typically held until after LRT. Treatment-related toxicities were recorded according to CTCAE definitions from the date of treatment initiation until discontinuation of IO or last follow up. Baseline, 1 month, and 3-month Child-Pugh (CP) score, ALBI score, transaminases, and total bilirubin were additionally recorded and analyzed using a repeated-measure mixed effects model. <h3>Results</h3> 50 HCC patients initiating atezolizumab were identified, 49 (98%) of these in combination with bevacizumab. Median follow up was 6.5 months (range 1.2-20), median age was 64 (34-79). 37 (74%) patients had BCLC stage C disease and 12 (34%) BCLC stage B. The majority of patients (86%) had CP class A liver function. Baseline characteristics were balanced between arms on univariate analysis (p>0.05). Of 27 (54%) patients in the LRT+IO arm, 9 received RT alone, 4 received RT combined with Y90 or TACE, 10 received Y90 alone, 3 received TACE alone, and 1 received RFA. The majority of the LRT+IO arm (63%) received LRT after the first infusion of atezolizumab. Grade 3 toxicities were observed in 2 (7.4%) patients in the LRT+IO arm, compared to 2 (8.6%) patients in the IO-only arm (p=0.87); grade 2 toxicity incidence was 63% in the LRT+IO arm versus 43% in the IO-only arm (p=0.17). The receipt of LRT+IO was associated with transient increase in CP and ALBI scores at 1 month relative to IO alone (median score increase 1 and 0.34, respectively, p<0.01); this association did not persist at 3 months. There was no treatment-related liver failure or grade 4/5 toxicity reported in either arm. LRT+IO was not associated with increased ALT, AST, or total bilirubin at 1 or 3 months. <h3>Conclusion</h3> In this single institution retrospective cohort study, upfront locoregional therapy with atezolizumab and bevacizumab for HCC was not associated with a significantly greater incidence of grade 2/3 toxicity or clinically significant liver dysfunction relative to the initiation of atezolizumab and bevacizumab alone. Further studies are needed to verify the safety of combination therapy and to assess clinical benefit.

Endobronchial Implanted Real-Time Radiofrequency (RF) Transponder Beacon Guided, Respiratory-Gated, Stereotactic Body Radiotherapy for Moving Lung Tumors: Interim Analysis of a Prospective Phase I/II Cohort Study

<h3>Purpose/Objective(s)</h3> Endobronchially implanted real-time tracking system (technology company) radiofrequency (RF) transponder beacons provide real-time, high precision, positional data of moving lung tumors. We report interim results of a Phase I/II prospective single arm prospective cohort study evaluating feasibility and dosimetric impact of real-time tracking system beacons for patients undergoing SBRT for moving lung tumors. <h3>Materials/Methods</h3> Eligible patients were adults, ECOG 0-2, with T1-T2N0 Non-small cell lung cancer (NSCLC) or pulmonary metastasis ≤4cm of the right middle/lower lobe, or lingula. Upper lobe tumors were eligible if they moved ≥5mm. Three real-time tracking system beacons were endobronchially implanted at prespecified peritumoral locations using SuperDimension™ navigational bronchoscopy (Medtronic, USA). Four-dimensional free-breathing CT simulation scans were obtained and end-exhalation phases were selected to define a gating window (GW). A 3mm expansion of the ITV_GW defined the PTV. Real-time tracking system-guided, respiratory phase-gated, SBRT (GW-SBRT) was delivered using 10MV VMAT photon arcs at 2400MU/min to total doses of 54Gy/3# or 48Gy/4#. For each GW-SBRT plan, a corresponding 10-phase plan was generated for comparison to standard image-guided (IG)SBRT. PTV, and OAR metrics were tabulated and differences between GW-SBRT and IG-SBRT plans analyzed using non-parametric Wilcoxon Signed-Rank pair test. Treatment related toxicity was graded using the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0. <h3>Results</h3> From November 2017 to December 2021, 41 patients were screened and 17 patients consented to participate. Two patients did not undergo beacon implant: one had tumor progression; another withdrew consent. Of the 15 patients with beacon implants, median age was 73, with 7 females. 47% were T1 NSCLC, 40% were M1 and remaining 13% were T2 NSCLC. Median tumor dimension was 1.9cm. 73% of targets were located peripherally, and 27% centrally with a median respiratory tumor motion of 1.25 cm (range 0.53 cm to 4.04 cm). No beacon migration was observed between CT simulation scan and the completion of SBRT treatments. Of the N=12 tumor targets were treated with GW-SBRT, 47% of patients received 48Gy/4# and 53% received 54Gy/3#. GW-SBRT yielded an average relative reduction of PTV of 46.9% (p<0.005) compared with IG-SBRT. Lung V5, V10, V20 and D2 had mean relative reductions of 11.3%, 20.3%, 31.1% and 15.5% respectively (p<0.005). Dose to OARs was significantly reduced (p<0.05) except for spinal cord. At 6 months follow-up, mean radiographic tumor volume reduction was 53.5% (p<0.005); No treatment related grade 3 toxicity was observed. <h3>Conclusion</h3> Endobronchial RF beacons are safe and effective at reducing SBRT treatment volumes for patients with moving lung tumors and can be considered for tumors with large motion amplitude or those located in close proximity to organs at risk. This study has the ClinicalTrials.gov identifier NCT03322072.

Mature Local Control and Radiation Necroses Outcomes Specific to Brain Metastases Treated with Salvage Stereotactic Radiosurgery for Radiosurgical Failures

<h3>Purpose/Objective(s)</h3> The management of locally recurrent brain metastases is a clinical challenge. A second course of radiosurgery may be delivered as the primary salvage treatment or as postoperative radiosurgery to the surgical cavity if the recurrence resected. We report our institutional experience of repeat radiosurgery for locally recurrent brain metastases, with a focus on local control and radionecrosis (RN) outcomes. <h3>Materials/Methods</h3> We report a single institution retrospective cohort study specific to patients with recurrent brain metastases treated with repeat radiosurgery. Clinical and dosimetric details were collected. Overall survival was estimated using the Kaplan Meier method. Local recurrence and RN rates were estimated using the Aalen-Johnson method, with death from any cause as the competing risk for both endpoints. Univariable competing risk regression using Fine and Gray's methods were performed, and subsequent multivariable (MVA) regression based on a priori variable selection generated final adjusted models. <h3>Results</h3> We identified 96 patients and 130 brain metastases re-treated with radiosurgery (either single fraction or hypofractionation between July 2010 to April 2020. The most common primary sites were lung (N = 44, 33.8%), breast, (N = 38, 29.2%), and melanoma (N = 26, 20%). More than half of the retreated lesions were postoperative cavities (N = 68, 52.3%). Re-treatment was most commonly delivered with 25 Gy in 5 fractions (N = 77, 59.2%) followed by 27.5 Gy in 5 fractions (N = 23, 17.7%). The mean BED₁₀ was 39.71 Gy (standard deviation [SD] 6.16) with a mean treatment volume of 14.94 cm³ (SD, 20.15). Nearly half (N = 64, 49.2%) of lesions were treated in the absence of systemic therapy, while 43.8% (N = 57) and 6.9% (N = 9) were treated while receiving targeted therapy/immunotherapy and chemotherapy, respectively. The median time between treatment courses was 13.7 months (IQR 10.88). With a median follow up of 34.9 months (interquartile range [IQR] 25-41.9), the 1 and 2-year overall survival rates were 59.8% (95% confidence interval [95% CI] 50.4-70.9) and 36.2% (95% CI, 27.2-48.2), respectively. The risk of local failure at 1 and 2 years was 26.2% (95%CI, 18.5-34) and 28% (95%CI, 20.1-35.9), respectively. MVA identified increasing target volume (hazard ratio [HR] 1.03; 95% CI, 1.02-1.04), and a shorter time-interval between radiosurgery courses (HR 0.29; 95% CI, 0.19-0.45) to be associated with worse local control. The crude incidence of RN was 18.5% (N = 24), of which 8 events (6.15%) were symptomatic. The 1 and 2-year rates of RN were 17.6% (95% CI, 10.9-34) and 19.3% (95%CI, 12.3-35.9), respectively. <h3>Conclusion</h3> Repeat radiosurgery for locally recurrent brain metastases results in good local control with a moderate risk of RN. Larger target volume and a shorter timeframe between radiosurgery treatments are associated with worse control.

Definitive Proton Re-Irradiation for Locally Advanced Lung Cancer in the Immunotherapy Era

<h3>Purpose/Objective(s)</h3> Despite advances in the treatment of NSCLC and SCLC, locoregional recurrences or second primary tumors after irradiation (RT) remain a therapeutic challenge due to the toxicity of re-RT and limited efficacy of systemic therapy alone. We evaluated safety and efficacy of definitive intent re-RT with intensity-modulated proton therapy (IMPT). <h3>Materials/Methods</h3> In this single institution retrospective cohort study, consecutive patients with biopsy-confirmed recurrent or second primary NSCLC or SCLC received IMPT re-RT (dose in GyE) after initial definitive intent photon RT (dose in Gy). Univariate associations between variables of interest were examined with ANOVA for categorical variables and Pearson correlation coefficient for continuous variables. Time-to-event variables were estimated using the Kaplan-Meier method and associations modeled by Cox proportional hazards model and log-rank test. <h3>Results</h3> We identified 22 patients with recurrent or second primary NSCLC (n=20) or SCLC (n=2) treated from April 2019 to May 2021. Median initial RT dose was 60 Gy (range 45-70 Gy) with 10 patients (45%) receiving immunotherapy after initial RT. Re-RT started median 28.2 mo (range 8.8-172.9 mo) after initial RT. The median age at re-RT was 71 (range 54-85) with median ECOG performance status 1 (range 0-2). One patient had an actionable mutation and 5 patients had PD-L1 >1%. Most patients had locally advanced recurrences with 50% rT3-4 (n=11) and 59% rN1-3 (n=13). Median re-RT dose was 60 GyE (range 44-60 GyE) frequently in 30 fractions (n=9) or 15 fractions (n=7). With re-RT, 8 patients (36%) received concurrent chemotherapy. Four patients (18%) had immunotherapy after re-RT. Re-RT median lung V20 GyE was 8% (range 2%-26%), lung mean dose was 5.3 GyE (range 0.9-13.9 GyE), heart mean dose was 2.5 GyE (range 0-24.4 GyE), and esophagus mean dose was 6.6 GyE (range 0.2-24.2 GyE). With median follow-up 7.4 months after completion of re-RT, 1-yr OS was 68%, 1-yr PFS was 45%, 1-yr DMFS was 60%, and 1-yr LC was 80%. Higher re-RT and initial RT mean lung doses were significantly associated with worse OS, and there was trend for worse OS among patients with re-RT doses below 50 GyE (Table). Two patients (9%) developed grade 3 toxicities, 1 patient had grade 2 toxicity (5%), and 5 patients (23%) had Grade 1 toxicities. No grade 4 or 5 toxicities were observed. No significant dosimetric correlates were identified with toxicity. <h3>Conclusion</h3> Definitive IMPT re-RT for NSCLC and SCLC can prolong disease control with limited toxicity, particularly in the modern era with routine use of PD-L1 inhibitors. However, careful patient selection and planning are needed for optimal outcomes.

Evaluation of Pneumonitis in EGFR-Mutated Non-Small Cell Lung Cancer Patients Receiving Osimertinib and Thoracic Radiotherapy

<h3>Purpose/Objective(s)</h3> In epidermal growth factor receptor mutated (EGFR+) metastatic non-small cell lung cancer (mNSCLC), pneumonitis is a known side effect independently associated with both Osimertinib and thoracic radiotherapy (TRT). The objective of this study was to examine the relationship between concurrent Osimertinib and TRT with regards to pneumonitis, and to observe patterns of practice regarding the cessation of Osimertinib during TRT. <h3>Materials/Methods</h3> In this single institution retrospective cohort study between 2016 and 2020, patients with EGFR+ mNSCLC who received both Osimertinib and TRT were included. TRT was defined as any course of radiotherapy that involved lung parenchyma within the treated field. The primary endpoint was the incidence of symptomatic (CTCAE grade ≥ 2) pneumonitis. Comparisons were made with multivariable Cox proportional hazards regression for both grade ≥ 2 and any grade pneumonitis. <h3>Results</h3> Of the 151 patients receiving Osimertinib during the study period, 41 underwent 147 courses of radiation either during or within 6 months of Osimertinib initiation, with 68 (46.3%) lesions treated with TRT. In total, 5 patients developed RT-related symptomatic pneumonitis (12.2%), of which 1 was grade 4 and another grade 5. Mean (±SD) age at TRT was 65.5 (±12.0) years. Most patients had de novo metastatic disease (n=31; 75.6%), adenocarcinoma histology (n=38; 92.7%), and 16 (39%) were on Osimertinib as first line systemic therapy. The mean (±SD) number of cycles of Osimertinib was 9.6 (±4.3). Median total dose and fractionations were 20 Gy (interquartile range [IQR]: 20-30 Gy) and 5 (IQR: 1-5), respectively. During TRT, Osimertinib was knowingly held in 12 patients (29.3%), most commonly for 1-2 days before and after (n=7; 17.1%) the course of treatment. Osimertinib was knowingly continued during TRT for 5 patients (12.2%), and in 8 patients (19.5%) it was not documented whether the medication was held. Multivariable analysis identified that each additional cycle of Osimertinib was associated with an increased incidence of grade ≥ 2 pneumonitis (hazard ratio [HR]: 1.54, 95% confidence interval [CI]: 1.15-2.07, p=0.004). Total radiation dose was also associated with increased incidence of any grade of pneumonitis (HR per 5 Gy: 1.38, 95% CI: 1.03-1.86, p=0.031). There was no association with incidence of pneumonitis (any grade) if Osimertinib was continued during TRT (HR: 3.36, 95% CI: 0.13-86.56, p=0.47) or if TRT was given within 6 months of Osimertinib initiation (HR: 0.20, 95% CI: 0.02-2.21, p=0.19). <h3>Conclusion</h3> In patients with EGFR+ mNSCLC treated with Osimertinib and TRT, the risk of symptomatic pneumonitis was moderate, and in 2 instances serious. Patterns on whether to hold Osimertinib during TRT, and for how long, were variable. Symptomatic pneumonitis with TRT was associated with prolonged Osimertinib use. Further research is required to further clarify the safety of the combination of these two treatment modalities.

Building Palliative Care Capacity for Generalist Providers in the Community: Results From the Capaciti Pilot Education Program.

Objective: Primary care providers play an important role in providing early palliative care, however they often lack practical supports to operationalize this approach in practice. CAPACITI is a virtual training program aimed at providing practical tips, strategies, and action plans to help primary care providers offer an early palliative approach to care. The CAPACITI pilot program consisted of 10 facilitated, monthly training sessions, covering identification and assessment, communication, and engaging caregivers and specialists. We present the findings of an evaluation of the pilot program. Method: We conducted a single cohort study of primary care providers who participated in CAPACITI. Study outcomes were the change in the percentage of caseload reported as requiring palliative care and improved confidence in competencies measured on a 20-item, study-created survey. Pre and post survey data were analyzed using paired t-tests. Results: Twenty-two teams representing 127 care providers (including 36 physicians and 28 Nurse Practitioners) completed CAPACITI. Paired comparisons showed a moderate improvement in confidence across the competencies covered (.6 to 1.3 mean improvement across items using seven-point scales, all P < .05). Pre-CAPACITI, clinician prescribers (N = 32) identified a mean of 1.2% of their caseload requiring a palliative approach to care, which increased to 1.6% post-program (P = .02). Said differently, the total group of paired clinician prescribers identified 338 patients as requiring palliative care in their caseloads at baseline vs 482 patients following the intervention, for an overall increase of 144 patients in their collective caseloads. Conclusion: CAPACITI improved self-assessed palliative care identification and provider confidence in core competencies. The program demonstrated potential for building palliative care capacity in primary care teams.

DD-01 THE INVITE STUDY: INCISIONAL HERNIA PREVENTION: RISK-BENEFIT FROM A PATIENT'S PERSPECTIVE

Abstract Introduction Incisional Hernia (IH) is a common complication of abdominal surgery. IH is associated with significant morbidity to patients, and costs to the NHS. With no singular intervention demonstrated to bring the rate of IH below 12%, focus is now on pre-operative risk-prediction. High-risk patients may benefit from prophylactic mesh placement during their index operation, however with controversy surrounding the use of mesh, there is no understanding of whether this intervention is acceptable to patients. Methods This is a retrospective, single centre mixed-methods cohort study. Patients with and without IH who have undergone colorectal surgery will be approached, along with a smaller cohort of patients about to undergo surgery. Participants will be asked to complete a questionnaire and a sub-set of participants will be invited to semi-structured interviews. The primary objective is to assess the acceptability of prophylactic mesh to patients. Secondary outcomes include understanding patient's views on risk-predictive modelling, and factors that may influence or alter the acceptability of mesh. Analysis Questionnaires have been developed using a 5-point Likert scale to allow quantitative analysis. Qualitative analysis of interviews will be conducted using Clarke and Braun's framework of thematic analysis. Data will be presented using the Journal Article Reporting Standards (JARS) for mixed-methods research. Outcomes Ethical approval has been granted, and the trial is currently in set-up. Results from this study will be used to inform both in the design and recruitement of patients to future interventional trials using prophylactic mesh in the UK.

Multidisciplinary Postoperative Care Pathway to Reduce Readmissions following Endoscopic Transsphenoidal Pituitary Surgery: Improving Quality of Patient Care.

Background Thirty-day unplanned readmission following endoscopic transsphenoidal pituitary surgery (ETPS) occurs in up to 14% of patients. Delayed hyponatremia is one of the most common causes, accounting for 30% of readmissions and often occurs within 1 week of surgery. The authors' prior retrospective review identified endocrinology follow-up as protective factor. Objectives Implementation of a multidisciplinary postoperative care (POC) pathway: (1) to reduce 30-day hospital readmissions following ETPS and (2) improve inpatient and outpatient coordination of care with endocrinologist. Methods This study is a single institution temporal cohort study of patients prior to (control cohort) and after implementation of the POC pathway (intervention cohort). The POC pathway utilized postdischarge 1 to 1.5 L/d fluid restriction, postoperative days 5 to 7 serum sodium, and endocrinology follow-up within 1 week of discharge to stratify patients into tiered hyponatremia regimens. Results A total of 542 patients were included in the study, 409 (75%) in the control cohort and 133 (25%) in the intervention cohort. All-cause readmission was significantly reduced following implementation of the POC pathway (14 vs. 6%, p = 0.015). Coordination with endocrinologist significantly increased in the inpatient (96 vs. 83%, p < 0.001) and outpatient (77 vs. 68%, p = 0.042) settings. Patients who were not in the POC pathway had the highest risk of readmission (odds ratio: 2.5; 95% confidence interval: 1.1-5.5). Conclusion A multidisciplinary POC pathway incorporating endocrinologist in conjunction with postdischarge weight-based fluid restriction and postoperative serum sodium levels can safely be used to reduce 30-day readmissions following ETPS.

Association of coagulation markers and antiphospholipid antibodies with ischemic and bleeding risk in patients with atrial fibrillation undergoing percutaneous coronary intervention

Abstract Background Antiphospholipid antibodies and other coagulation markers are associated with ischemic risk in patients with coronary artery disease without oral anticoagulation (OAC). Aim To assess the association of antiphospholipid antibodies (aPL) and conventional markers of coagulation with ischemic and bleeding risk in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). Patients and methods In this prospective single center observational cohort study, patients with AF and an indication for OAC were enrolled after PCI. Dilute Russell's viper venom time (DRVVT) was used to determine lupus anticoagulants (LA) in direct OAC-free plasma. Anti-cardiolipin IgG (aCL), IgM and anti-beta2GP-1-IgG (aβ2GP1) were analyzed by enzyme linked immunosorbent assay (ELISA). Fibrinogen C (FIBC), d-dimers and prothrombin fragments 1 and 2 (PF1+2) were measured in citrated plasma. Immature platelet fraction (IPF [%]) and absolute (IPF abs. [103/μl]) were measured in EDTA-blood. The primary ischemic outcome was defined as time to major adverse cardiovascular events (MACE: all-cause death, myocardial infarction, or stroke) assessed at 6 months. Bleeding was defined according to the International Society of Thrombosis and Haemostasis (ISTH) and the Bleeding Academic Research Consortium (BARC). Results 158 patients were enrolled between May 2020 and May 2021. The median age was 78 years (interquartile range, IQR 72–82), 111 (70%) were male, and 39 (25%) presented with acute coronary syndrome. All Patients were treated with clopidogrel and OAC, 145 (92%) in addition with acetylsalicylic acid (ASA). 32 patients (20%) had ≥1 antiphospholipid antibody (aPL; LA: 19 [12%], aCL: 14 [9%], aβ2GP1: 2 [1%]). D-dimers were elevated in 74 patients (47%), FIBC was increased in 40 (25%) and PF1+2 in 68 patients (43%). IPF [%] was elevated in 28 (18%) and IPF abs. [103/μl] in 11 (7%). The presence of aPL was neither significantly associated with MACE, nor with bleeding risk. Elevated d-dimers were significantly associated with higher risk for MACE (HR=5.1, 95% CI [1.1; 23.4], p=0.04), major ISTH bleeding events (HR= 6.9, 95% CI [1.5; 30.8], p=0.01) and BARC bleeding type 3 or 5 (HR=6.4, 95% CI [1.4; 28.7], p=0.02). Increased levels of FIBC were associated with risk of MACE (HR= 3.6, 95% CI [1.1; 12.0], p=0.03 (Table 1). Conclusion In patients with AF undergoing PCI, high levels of d-dimers and fibrinogen C indicate an increased ischemic risk. Elevated d-dimers are associated with higher risk for bleeding. aPL positivity was not significantly associated with outcome possibly due to low sample size. A combined panel of biomarkers might be suitable to assess ischemic and bleeding risk in patients with AF following PCI. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Faculty of Medicine, Freiburg

Manganese-enhanced magnetic resonance imaging in Takotsubo syndrome

Abstract Background Takotsubo syndrome is an increasingly common acute cardiac emergency characterised by profound transient left ventricular systolic dysfunction following a stressful event. Its pathophysiology remains poorly understood and a third of patients will have a major adverse cardiac or cerebrovascular event by 5 years [1]. Defective myocardial calcium homeostasis is central to contractile dysfunction and may be implicated in its pathophysiology. Manganese-enhanced magnetic resonance imaging is a novel non-invasive imaging technique that assesses myocardial manganese uptake as a measure of myocardial calcium handling [2]. Our aim was to investigate myocardial calcium handling using manganese-enhanced magnetic resonance imaging during the acute and recovery phase of takotsubo syndrome. Methods This single centre case-controlled observational longitudinal cohort study was conducted in accordance with the Declaration of Helsinki and ethical committee approval with written informed consent. Twenty patients with takotsubo syndrome and 20 age, sex and cardiovascular risk factor matched volunteers were recruited between March 2020 and September 2021. Patients underwent gadolinium and manganese-enhanced magnetic resonance imaging during the index event with repeat manganese-enhanced magnetic resonance imaging after 3 months. Myocardial manganese uptake was characterised by Patlak modelling. Results During the acute presentation, most patients had an “apical” pattern of takotsubo syndrome with reduced left ventricular ejection fraction (51±11 versus 67±8%, P&amp;lt;0.001, Figure 1), elevated left ventricular mass (89±11 versus 57±14 g/m2, P&amp;lt;0.01) and native T1 (1358±49 versus 1211±28 ms, P&amp;lt;0.001) and T2 (60±7 versus 38±3 ms, P&amp;lt;0.001) values compared to matched volunteers. Patlak modelling demonstrated reduced myocardial manganese uptake (5.1±0.5 versus 8.0±1.0 mL/100g of tissue/min, P&amp;lt;0.0001) consistent with a major abnormality of myocardial calcium handling. Reduced myocardial manganese uptake attributable to apical takotsubo syndrome could be seen in one patient, scanned 18 days after symptom onset despite apparent resolution of cardiac function. Beyond 3 months of convalescence, left ventricular mass, ejection fraction, native T1 and T2 values were comparable to matched volunteers. Despite this, myocardial calcium handling remained abnormal compared to matched volunteers (6.7±0.7 versus 8.0±1.0 mL/100 g of tissue/min, P&amp;lt;0.001, Figure 2). Conclusions In patients with takotsubo syndrome, there is a profound perturbation of myocardial calcium handling which is most marked acutely but persists after apparent recovery of left ventricular ejection fraction and resolution of myocardial oedema. Abnormal myocardial calcium handling is implicated in the pathophysiology of takotsubo syndrome and manganese-enhanced magnetic resonance imaging could play a major role in the diagnosis and risk stratification of patients with takotsubo syndrome. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): Medical Research CouncilBritish Heart Foundation

Impact of wallet cards compared to conventional chemotherapy education in patients with newly-diagnosed cancer.

363 Background: According to American Cancer Society, 1.9 million new cases of cancer were diagnosed in year 2021, majority of who will undergo chemotherapy (1). With these treatments, there is often an overwhelming amount of information given to patients. We will first assess the percentage of new cancer patients that can recall their cancer treatments with the current patient education format. We then aim to improve patient understanding of their treatment with the introduction of a chemotherapy wallet card. Methods: This is a single center prospective cohort study at the University of Louisville, Brown Cancer Center. In phase one 50 new patients will be recruited from various oncology clinics who will receive conventional verbal chemotherapy education. On cycle two of their treatment, we will administer a survey (figure 1) to assess their understanding of their regimen. In phase two we will recruit 50 new patients and introduce a chemotherapy wallet card filled by the pharmacist to be given during their chemotherapy education and administer the survey on cycle two. We will then compare these two populations to evaluate the impact of the chemotherapy wallet cards. Results: Preliminary results from the first phase have been obtained of 15 newly diagnosed cancer patients. Surveys obtained on cycle two revealed 100% patients correctly identified their cancer diagnosis and 60% were able to correctly name their chemotherapy regimen. 53% of patients were able to identify three correct treatment side effects. Conclusions: Preliminary results show 60% of patients have suboptimal identification of their chemotherapy regimens. Previous studies have shown many patients will visit the emergency department in their first year of treatment. This is of concern as patients may not be able to provide accurate information of their current treatment to these providers resulting in suboptimal care. Our goal will be to see if chemotherapy wallet cards will help to increase patient knowledge and improve patient quality of care.[Table: see text]

S977 Ectopic Pregnancy in Women With IBD: Experience at a Tertiary Care IBD Center

Introduction: Women with IBD often have risk factors for ectopic pregnancy (EP) including previous abdominal or pelvic surgery, pelvic sepsis or intra-abdominal adhesions. The prevalence of an ectopic pregnancy among healthy women who present to an emergency department with first trimester bleeding, pain, or both ranges from 6% to 16%. To date, the single large population-based cohort study for EP in IBD was not able to account for medication use, disease activity or severity, and was published prior to wide-spread use of anti-TNF agents in the preconception and pregnancy states. We were interested in assessing EP in our population from a tertiary care IBD center, in particular taking into account disease activity and use of biologics prior to conception. Methods: The electronic medical record was queried for legal sex females with a diagnosis of ulcerative colitis (UC), Crohn's disease (CD) or inflammatory bowel disease (IBD) and a history of a pregnancy event receiving all of their care at our tertiary care center. From this cohort the term “ectopic pregnancy” using ICD-10 code and SNOMED concepts between 1/1/13 and 2/28/2022 were used to identify our population of interest. Chart review including diagnosis, surgical history, current and previous medications, and disease activity at the time of conception was then performed. Pregnancy specific variables include age at time of conception, parity, history of previous pregnancy loss, history of Caesarean section, or endometriosis. Results: 20,624 legal sex females with CD, UC or IBD were identified and 335 patients were diagnosed with a pregnancy event with all of their care at our center. 6 patients were diagnosed with an EP. Of interest, only 4 had their EP after an established diagnosis of UC or CD. Of these 4 patients, 3 had UC and 1 had CD. Duration of disease prior to EP ranged from 6 months to 4 years. Of the 3 patients with UC, all were in remission on either aminosalicylate or anti TNF therapy. The patient with CD had mild activity, was status post one resection and on no medication at the time of the EP. None had other common risk factors for EP. Conclusion: EP in our practice was uncommon, with an incidence of only 2%. Whether this is because of improved control of disease activity or preconception counseling has yet to be determined. Larger population-based studies are needed to assess the impact of newer medical therapies and disease management on the risk of this pregnancy outcome.

O118 / #926 REAL WORLD EVIDENCE FOR RESTORATIVE NEUROSTIMULATION IN CHRONIC LOW BACK PAIN – A CONSECUTIVE COHORT STUDY: TRACK 3: NEUROSTIMULATION FOR BACK AND LEG PAIN

Functional instability of the lumbar spine resulting from impaired motor control and degeneration of the multifidus muscle is a known root cause of refractory chronic low back pain (CLBP). An implantable neurostimulation system that aims to restore multifidus motor control by stimulating the L2 medial branch of the dorsal ramus (ReActiv8, Mainstay Medical) and thereby relieving pain and reducing disability has demonstrated clinically significant benefits. The 1-year results of a single site real-world cohort study are presented here.

A retrospective cohort study of new-onset refractory status epilepticus (NORSE): clinical features, timing of immunotherapy and outcomes

To describe clinical characteristics associated with immunotherapy in patients with new-onset refractory status epilepticus (NORSE) and assess its timing and effect on outcomes at hospital discharge after six and 12 months of follow-up. Our secondary aim was to apply the cryptogenic NORSE (C-NORSE) score to subjects in order to evaluate its utility in identifying C-NORSE in our cohort. This was a retrospective single university hospital cohort study (2004-2021) of adults and children with NORSE. First-line immunotherapy was defined as corticosteroids, intravenous immunoglobulin (IVIg), and plasmapheresis (PLEX). Early immunotherapy was defined as administration of a first-line agent within seven days of presentation. Twenty-one subjects with NORSE were identified between 2004 and 2021, which was cryptogenic in 18 and immune-mediated in three. All patients received immunotherapy. Seventeen patients received early immunotherapy (81%). There was no significant difference between early versus late immunotherapy regarding “good or favorable” outcomes (mRS 0-2) at hospital discharge or during follow-up. For cryptogenic NORSE patients, 7/11 (64%) achieved good outcomes at six months, 9/11 (82%) at 12 months, and 8/10 (80%) at the last follow-up visit at >13 months. For immune-mediated NORSE patients, 3/3 (100%) achieved good outcomes at six months and 2/2 (100%) at the last follow-up visit at >13 months. In our cohort, a C-NORSE score of ≥5 was obtained in 12/18 (67%) of cryptogenic cases and a score <5 in all three immunemediated cases. There is a paucity of published data on the timing of immunotherapy for NORSE. Although at our institution early administration of immunotherapy is feasible, more research is needed to determine which patients may benefit from immunotherapy and if the timing of immunotherapy affects short and long-term outcomes. Among the patients who survived hospitalization, long-term follow-up of our NORSE cohort demonstrated that a subset achieved good mRS (0-2) scores.

Sequential Observation of Antibody Response Pattern at 3 and 6 Months Following ChAdOx1 nCoV-19 Vaccination Among Health Care Workers-A Prospective Single Cohort Study

Background: The duration of the immune response induced by ChAdOx1 nCoV-19 vaccination in a real-world setting is unknown. Objectives: This study is aimed to estimate the 6-month trend of SARS-CoV-2 antibody titer after Covishield vaccination among Health Care workers (HCW) and their associated factors. Materials &amp; Methods: A prospective single cohort study of health care workers was done in a tertiary care-teaching institute of central Kerala from January 2021 to October 2021. HCWs who have given pre-vaccination serum sample for SARS-CoV-2 antibody estimation and negative for SARS-CoV-2 antibody were included. They were followed up and their blood samples to check for antibody levels were taken 28 days after first dose, 2 weeks after second dose, and 3 and 6 months after first dose of ChAdOx1 nCoV-19 vaccine. Samples taken from 102 HCW were sent for SARS-CoV-2 IgG antibody testing. Results: Mean age of the study participants was 39.3 (age range:19 - 71) yrs. and 71.6% were females. Antibody levels of participants at 3rd month ranged from 0.28 S/C to 21.2 S/C with a mean of 8.01. Only 34 (33.3%) HCW had IgG antibody levels &gt;9.5 S/C. Mean antibody level further declined to 6.09 S/C at 6th month. Only 19 (28.4%) had antibody levels more than 9.5 S/C at 6th month. HCW with aged less than 50 years and those who had COVID disease during the study period had a significantly higher level of IgG antibody titres. Quantitative results were reported as signal to cut-off (S/C) value. Conclusion: The study found that after vaccination with Covishield vaccine IgG levels peaked at 14 days following second dose of vaccine, then getting decreased in the third month and further in sixth month confirming the need for a booster dose. COVID antibody levels were significantly higher in COVID infected HCW and in young age participants

Air pollution exposure induces a decrease in type II interferon response: A paired cohort study.

SummaryBackgroundWhile air pollution is a major issue due to its harmful effects on human health, few studies focus on its impact on the immune system and vulnerability to viral infections. The lockdown declared following the COVID-19 pandemic represents a unique opportunity to study the large-scale impact of variations in air pollutants in real life. We hypothesized that variations in air pollutants modify Th1 response represented by interferon (IFN) γ production.MethodsWe conducted a single center paired pilot cohort study of 58 participants, and a confirmation cohort of 320 participants in Nice (France), with for each cohort two samplings at six months intervals. We correlated the variations in the production of IFNγ after non-specific stimulation of participants’ immune cells with variations in key regulated pollutants: NO2, O3, PM2.5, and PM10 and climate variables. Using linear regression, we studied the effects of variations of each pollutant on the immune response.FindingsIn the pilot cohort, IFNγ production significantly decreased by 25.7% post-lockdown compared to during lockdown, while NO2 increased significantly by 46.0%. After the adjustment for climate variations during the study period (sunshine and temperature), we observed a significant effect of NO2 variation on IFNγ production (P=0.03). In the confirmation cohort IFNγ decreased significantly by 47.8% and after adjustment for environmental factors and intrinsic characteristics we observed a significant effect of environmental factors: NO2, PM10, O3, climatic conditions (sunshine exposure, relative humidity) on variation in IFNγ production (P=0.005, P<0.001, P=0.001, P=0.002 and P<0.001 respectively) but not independently from the BMI at inclusion and the workplace P=0.007 and P<0.001 respectively).InterpretationWe show a weakening of the antiviral cellular response in correlation with an increase of pollutants exposition.FundingAgence Nationale de la Recherche, Conseil Départemental des Alpes-Maritimes and Region Sud.

The Impact of Neurogenic Lower Urinary Tract Symptoms and Erectile Dysfunctions on Marital Relationship in Men with Multiple Sclerosis: A Single Cohort Study.

Aims: Multiple sclerosis (MS) is an autoimmune and neurodegenerative disease that is characterized by a great variety symptoms. Most MS patients suffer from neurogenic lower urinary tract symptoms (nLUTS) and erectile dysfunctions (ED). The aim this study is to assess the impact of nLUTS and ED on marital relationships in MS patients. Materials and Methods: MS male patients that arrived for our attention were prospectively enrolled in the study. All of the patients were evaluated on an Expanded Disability Status Scale (EDSS), an IIEF-5 for sexual function, an ICIQ-MLUTS for urinary function, and a Dyadic Adjustment Scale (DAS) for marital relationships. The data were analyzed using descriptive and inferential statistical tests in STATA/MP14. Results: The data of 57 male MS patients were eligible. The mean age was 45 (13.7) years, the mean disease duration was 15.49 (7.86) years, and the mean EDSS score was 3.5 (1.89). In total, 33 (57.89%) MS patients reported urine incontinence, of those, 24 (42.11%) reported UUI. The mean DAS score was 74.40 (34.58). The mean IIEF-5 score was 12.40 (8.05). The mean ICIQ-MLUTS score was 71.94 (41.06). The DAS and ICIQ-MLUTS scores were negatively correlated (r = −0.30, p < 0.001). The DAS and IIEF-5 were moderately correlated (r = 0.47, p < 0.001). The DAS and EDSS were strongly correlated (r = −0.72, p < 0.001). A univariate analysis showed that increasing age (p < 0.001), a longer disease duration (p = 0.029), a higher EDSS score (p < 0.001), and a higher ICIQ-MLUTS score (p < 0.001) were all significantly associated with lower DAS scores. Conclusions: This study demonstrated the large negative impact that nLUTS and ED due to MS have on patients’ marital relationships, highlighting the importance of a multidisciplinary approach in MS patients.

YESS: A feasibility study of a supported employment program for youths with mental health disorders.

ObjectiveIn Canada, employment/education support is rarely embedded as a component of mental health service delivery. This study describes a supported education/employment program (SEP) that integrates both clinical and community mental health services. The main objectives were to estimate the feasibility of a 5-week SEP among youths aged 17–24 with mental illness and to estimate the extent to which participation in this program improved employment and mental health outcomes.MethodsThis was a single cohort study. Feasibility outcomes assessed were demand, acceptability, practicality, integration, adaptation, and effectiveness. These were assessed through recruitment and retention rates, recording patterns of missing data, and examining differences between completers and non-completers. Appropriateness of the outcome measures was assessed through the strength of the association between the outcome measures at baseline. Effectiveness of the program was assessed through employment and as measured using MyLifetracker (MLT), Satisfaction with Life Scale (SWLS), and the Canadian Personal Recovery Outcome Measure (CPROM).ResultsA total of 110 youths with a mean age of 20.6 (SD: 2.2) were recruited. At 5 weeks, 82 (74.5%) of participants remained in the program. Of the people who completed the program, 56.1% were women, 76.6% were in stable housing and 64.1% had depression. Approximately 60% of non-completers used two or more services and were in at-risk housing. More than 25% of participants improved on the patient-reported outcomes. Scores on these measures were moderately to highly correlated with each other. Employment rates varied and corresponded to the waves of the COVID-19 pandemic in Canada.ConclusionResults showed that this program was feasible and there was high demand for SEP during the COVID-19 pandemic but gaining employment remained difficult. Educational or employment outcomes, measured over a short period, may not be adequate. Instead, individualized and patient-reported outcome measures may be more appropriate for SEP programs.

Analysis of the Influence of Pre-Pregnancy BMI and Weight Gain during Pregnancy on the Weight of Healthy Children during the First 2 Years of Life: A Prospective Study.

Background: Increased pre-pregnancy maternal BMI (pBMI) and gestational weight gain (GWG) have been found to increase infants’ birthweight and result in the programming of child weight and impact its later weight gain. Aim: To assess the impact of pBMI and GWG on the weight of children from birth to 2 years of age and over the duration of breastfeeding. Methods: Single Centre observational prospective longitudinal cohort study. Data were collected from medical records, and medical history. The analysis of multiple linear and mixed models was involved. Findings: 20% of females were overweight, while 13% were obese before the pregnancy. An overall model, including gender and smoking, indicated a significant impact of pBMI category on a child’s birth mass (p = 0.01). The GWG category affected a child’s birth weight (p = 0.018, Effect size 0.41). pBMI did not affect the breastfeeding duration. Conclusion: pBMI and GWG correlate with birth weight and weight in neonatal period, however they become insignificant in later childhood. Weight assessment methods among children aged up to two years of age require standardization. Maternal weight before the pregnancy nor the weight gain during the pregnancy do not influence the length of breastfeeding. The biggest limitation was the small sample size and the failure to account for weight gain per trimester of pregnancy. Further research on a larger population should be continued.

High Inferior Vena Cava Diameter with High Left Ventricular End Systolic Diameter as a Risk Factor for Major Adverse Cardiovascular Events, Cardiovascular and Overall Mortality among Chronic Hemodialysis Patients.

Background: Little is known about the association of inferior vena cava diameter (IVCD) and left ventricular end-systolic diameter (LVESD) with mortality in patients undergoing hemodialysis (HD). Methods: The single medical center observational cohort study enrolled 241 adult chronic HD patients from 1 October 2018 to 31 December 2018. Echocardiography results of IVCD and LVESD prior to dialysis were retrieved and patients were divided into high IVCD and low IVCD groups. Patients who received HD via a tunneled cuffed catheter were excluded. Study outcomes included all-cause mortality, cardiovascular mortality, and major adverse cardiovascular events (MACE). Subgroup analyses of HD patients with high and low LVESD were also performed. Results: The incidence of all-cause mortality, cardiovascular mortality, and MACE were higher in chronic HD patients with high IVCD (p < 0.01). High IVCD patients had significantly greater all-cause mortality, cardiovascular mortality, and MACE (log-rank test; p < 0.05). High IVCD patients are also associated with an increased risk of all-cause mortality and MACE relative to low IVCD patients (aHRs, 2.88 and 3.42; 95% CIs, 1.06–7.86 and 1.73–6.77, respectively; all p < 0.05). In the subgroup analysis of patients with high or low LVESD, the high IVCD remained a significant risk factor for all-cause mortality and MACE, and the HR is especially high in the high LVESD group. Conclusions: Dilated IVCD is a risk factor for all-cause mortality and MACE in chronic HD patients. In addition, these patients with high LVESD also have a significantly higher HR of all-cause mortality and MACE.