Late Clinical Outcomes Research Articles

Impact of Care Interventions on the Survival of Patients with Cardiac Chest Pain.

Chest pain is considered the second most frequent complaint among patients seeking emergency services. However, there is limited information in the literature about how the care provided to patients with chest pain, when being attended to in the emergency room, influences their clinical outcomes. To assess the relationship between care interventions performed on patients with cardiac chest pain and their immediate and late clinical outcomes and to identify which care interventions were essential to survival. In this retrospective study. We analyzed 153 medical records of patients presenting with chest pain at an emergency service center, São Paulo, Brazil. Participants were divided into two groups: (G1) remained hospitalized for a maximum of 24 h and (G2) remained hospitalized for between 25 h and 30 days. Most of the participants were male 99 (64.7%), with a mean age of 63.2 years. The interventions central venous catheter, non-invasive blood pressure monitoring, pulse oximetry, and monitoring peripheral perfusion were commonly associated with survival at 24 h and 30 days. Advanced cardiovascular life support and basic support life (p = 0.0145; OR = 8053; 95% CI = 1385-46,833), blood transfusion (p < 0.0077; OR = 34,367; 95% CI = 6489-182,106), central venous catheter (p < 0.0001; OR = 7.69: 95% CI 1853-31,905), and monitoring peripheral perfusion (p < 0.0001; OR = 6835; 95% CI 1349-34,634) were independently associated with survival at 30 days by Cox Regression. Even though there have been many technological advances over the past decades, this study demonstrated that immediate and long-term survival depended on interventions received in an emergency room for many patients.

Long-term durability and clinical outcome of a prospective randomized trial comparing carotid endarterectomy with ACUSEAL polytetrafluoroethylene patching versus pericardial patching: Presented at the Forty-seventh Annual Meeting of Southern Association of Vascular Surgery, Puerto Rico, January 18-21, 2023.

Background: Several studies have shown the superiority of carotid endarterectomy (CEA) with patch closure over primary closure. However, no definite study has shown any significant differences in clinical outcome between various types of patches. Because more vascular surgeons have used pericardial patching recently, this study will analyze the late clinical outcome (≥10 years) of our previously reported prospective randomized trial comparing CEA with ACUSEAL (polytetrafluoroethylene) vs pericardial patching.

Coronary covered stents in the management of late-onset arterial complications post-hepato-pancreato-biliary surgery.

To retrospectively evaluate the safety, efficacy, and late clinical outcome of coronary covered stent placement for the treatment of late-onset arterial complications after hepato-pancreato-biliary surgery. Consecutive patients presenting with post-hepato-pancreato-biliary surgery-related arterial lesions and subsequently treated with a covered coronary stent in the authors institution between January 2012 and November 2021 were included. Primary endpoints were technical and clinical success; secondary endpoints were covered stent patency and end-organ perfusion of the affected artery. The study included 22 patients (13 men and 9 women) with a mean age of 67years ± 9.6years. Initial surgery included pancreaticoduodenectomy (n = 15; 68%), liver transplantation (n = 2; 9%), left hepatectomy (n = 1; 5%), bile duct resection (n = 1; 5%), hepatogastrostomy (n = 1; 5%), and segmental enterectomy (n = 1; 5%). Technically, coronary covered stents were successfully placed in n = 22 patients (100%) without immediate complication. Definitive bleeding control was observed in n = 18 patients (81.1%) with recurrent bleeding within 30days postintervention in n = 5 patients (23%). No ischemic liver or biliary complications occurred during the follow-up period. The 30-day mortality rate was 0%. Coronary covered stents are a safe and efficient treatment option in most of the patients presenting with late-onset postoperative arterial injuries following hepato-pancreato-biliary surgery and are associated with an acceptable recurrent bleeding rate and no late, ischemic, parenchymal complications.

Role of intravenous alteplase on late lesion growth and clinical outcome after stroke treatment

Several acute ischemic stroke mechanisms that cause lesion growth continue after treatment which is detrimental to long-term clinical outcome. The potential role of intravenous alteplase treatment (IVT), a standard in stroke care, in cessing the physiological processes causing post-treatment lesion development is understudied. We analyzed patients from the MR CLEAN-NO IV trial with good quality 24-hour and 1-week follow-up Non-Contrast CT scans. We delineated hypo- and hyper-dense regions on the scans as lesion. We performed univariable logistic and linear regression to estimate the influence of IVT on the presence (growth > 0 ml) and extent of late lesion growth. The association between late lesion growth and mRS was assessed using ordinal logistic regression. Interaction analysis was performed to evaluate the influence of IVT on this association. Of the 63/116 were randomized to included patients, IVT. Median growth was 8.4(−0.88–26) ml. IVT was not significantly associated with the presence (OR: 1.24 (0.57–2.74, p = 0.59) or extent (β = 5.1(−8.8–19), p = 0.47) of growth. Late lesion growth was associated with worse clinical outcome (aOR: 0.85(0.76–0.95), p < 0.01; per 10 ml). IVT did not influence this association (p = 0.18). We did not find evidence that IVT influences late lesion growth or the relationship between growth and worse clinical outcome. Therapies to reduce lesion development are necessary.

Late Clinical Outcomes of Total Arterial Revascularization or Multiple Arterial Grafting Compared to Conventional Single Arterial with Saphenous Vein Grafting for Coronary Surgery.

Coronary surgery provides better long-term outcomes than percutaneous coronary intervention. Conventional practice is to use a single arterial conduit supplemented by saphenous vein grafts. The use of multiple arterial revascularization (MAG), or exclusive arterial revascularization (TAR), however, is reported as having improved late survival. Survival is a surrogate for graft failure that may lead to premature death, and improved survival reflects fewer graft failures in the non-conventional strategy groups. The reasons for not using MAG or TAR may be due to perceived technical difficulties, a lack of definitive large-scale randomized evidence, a lack of confidence in arterial conduits, or resources or time constraints. Most people consider radial artery (RA) grafting to be new, with use representing approximately 2-5% worldwide, despite select centers reporting routine use in most patients for decades with improved results. In conclusion, the current body of evidence supports more extensive use of total and multiple arterial revascularization procedures in the absence of contraindications.

Extensive aortic root endocarditis with extension into the intervalvular fibrous body: an updated report of a mitral valve sparing approach.

Aortic root abscess can spread to include adjacent cardiac structures, including the central or intervalvular fibrous body and mitral valve. After radical debridement, complex surgical correction is needed. We describe the results of our mitral valve sparing approach. Between January 2004 and December 2020, 60 patients underwent operation for infective endocarditis of the aortic root with extension towards the mitral valve at 2 centres in the Netherlands. Early and late clinical and echocardiographic outcomes were studied. Prosthetic valve endocarditis was present in 42 (70%) patients and emergent or salvage surgery was performed in 8 (13%) patients. After radical debridement of all infected tissue, mitral valve repair was feasible in 48 (80%) patients. Early mortality occurred in 11 (18%) patients while mechanical circulatory support was needed in 8 (13%) patients. At 10 years after surgery, the estimated reintervention-free survival rate was 51.9% (95% confidence interval 37.0-66.8%). Eight patients underwent reintervention; this was more common in patients who underwent aortic valve rather than root replacement and in patients in whom mitral valve repair was performed without ring annuloplasty. For 48 patients who underwent mitral valve repair, the estimated freedom from recurrent mitral regurgitation rate was 64.4% (95% confidence interval 40.1-88.7%) at 10 years after surgery. Surgical intervention for extensive infective endocarditis of the aortic root is related to reasonable perioperative morbidity and mortality. Optimal surgical technique is crucial to lower the risk of late reintervention. Mitral valve repair is feasible in the majority of patients with satisfactory durability.

Long-term durability and clinical outcome of a prospective randomized trial comparing carotid endarterectomy with ACUSEAL polytetrafluoroethylene patching versus pericardial patching

BackgroundSeveral studies have shown the superiority of carotid endarterectomy (CEA) with patch closure over primary closure. However, no definite study has shown any significant differences in clinical outcome between various types of patches. Because more vascular surgeons have used pericardial patching recently, this study will analyze the late clinical outcome (≥10 years) of our previously reported prospective randomized trial comparing CEA with ACUSEAL (polytetrafluoroethylene) vs pericardial patching. MethodsA total of 200 CEAs were randomized (1:1) to either Vascu-Guard pericardial patching or ACUSEAL patching. All patients had immediate duplex ultrasound imaging, which was repeated at 6 months and annually thereafter. Kaplan-Meier analysis was used to estimate rates of freedom from stroke, stroke-free survival, and rates of freedom from ≥50% and ≥80% restenosis. ResultsOverall demographic and clinical characteristics were somewhat similar with a mean follow-up of 80 months (range: 0-149 months). The rates of freedom from stroke were 97, 97, 97, 96, 93 for ACUSEAL vs 99, 98, 97, 97, 92 for pericardial patching (P = .1112) at 1, 2, 3, 5, and 10 years, respectively. Similarly, the rates of freedom from stroke/death were 94, 93, 90, 76, 50 for ACUSEAL vs 99, 96, 91, 78, 47 for pericardial patching (P = .8591). The rates of freedom from ≥50% restenosis were 98, 98, 96, 89, 79 for ACUSEAL vs 87, 83, 83, 81, 71 for pericardial patching (P = .0489). The rates of freedom from ≥80% restenosis were 99, 99, 99, 96, 85 for ACUSEAL vs 96, 96, 96, 93, 93 for pericardial patching (P = .9407). The overall survival rates were 95, 94, 91, 77, 51 for ACUSEAL vs 100, 98, 93, 79, 50 for pericardial patching (P = .9123). Other patch complications (eg, rupture, aneurysmal dilation, infection, etc) were similar. ConclusionsBoth CEA with ACUSEAL (polytetrafluoroethylene) and pericardial patching are durable and have similar clinical outcomes at 10 years except that ACUSEAL patching has significantly better rates of freedom from ≥50% restenosis.

Aortic Valve Replacement and Concomitant Multi-Vessel Coronary Artery Bypass: The Impact of Using the Bilateral Internal Thoracic Arteries on Early and Late Clinical Outcomes.

The survival benefit of coronary artery bypass grafting (CABG) using the bilateral internal thoracic arteries (BITA) is well known; however, the role of BITA in concomitant aortic valve replacement (AVR) and CABG has not been studied. We retrospectively reviewed patients who underwent concomitant AVR and CABG. Cases not using an internal thoracic artery and less than 2 bypass grafts were excluded. We enrolled 114 patients in this study. The mean follow-up duration was 61.5±43.5 months. Forty patients (35.1%) underwent CABG with a single internal thoracic artery (SITA) and 74 patients (64.9%) underwent CABG with BITA. The preoperative clinical characteristics were not significantly different between the 2 groups, with the exception of a higher prevalence of atrial fibrillation in the SITA group. Postoperative mortality and morbidity were not significantly higher in the BITA group than in the SITA group. In the univariable analysis, the survival of the BITA group was similar to that of the SITA group (p=0.157). Multivariable analysis showed that only mean age was a predictor of death (p=0.042), but using BITA was not an independent predictor (p=0.094). In low-risk patients whose preoperative ejection fraction was >45%, the survival of the BITA group was significantly better than that of the SITA group (p=0.043). BITA use in concomitant AVR and CABG showed no difference in mortality compared to using SITA. Although its impact on long-term survival was inconclusive, BITA use can be considered for low-risk patients.

Long-Term (&gt;10 Years) Durability and Clinical Outcome Comparing Carotid Endarterectomy With ACUSEAL (PTFE) Patching Versus Pericardial Patching: Results From a Prospective Randomized Trail

Several studies have shown the superiority of carotid endarterectomy (CEA) with patch closure over primary closure. However, no definite study has shown any significant differences in clinical outcome between various types of patches. Because more vascular surgeons have used pericardial patching recently, this study will analyze the late clinical outcome (≥10 years) of our previously reported prospective randomized trial comparing CEA with ACUSEAL (PTFE) vs pericardial patching.

Tissue Stents (Bio Stents): Search For Non- Metallic Stent And Can It Be A Game Changer In Cardiovascular Interventions?

Coronary and Vascular stenosis poses great challenge in terms of cardiovascular disease burden. Evolution of metallic stents has been key in treating Coronary Artery Disease both acute and chronic and has met challenges successfully. The last 2 decades have seen substantial reform in technology, bringing second and third generations of coronary and vascular stents mainly metallic drug-eluting stents (DES). Though stent related stenosis is big challenge, DES has met relatively much success especially during initial years. DES are found to be associated with good first-year outcomes but subsequent risk of stentrelated adverse events like thrombosis, myocardial infarction, restenosis usually appear after 1 year following implantation. The pathogenesis of these late events is related to the permanent presence of the metal stent frame or polymer within coronaries. Besides intimal hyperplasia, late stent thrombosis, and noncompliance with DAPT are still major issues leading to stent failure and often the need for reintervention. As an effective alternative to metallic stents, Bioresorbable scaffolds were developed to provide drug delivery and mechanical support functions similar to metallic drug-eluting stents (DES), followed by complete resorption with recovery of vascular structure and function, potentially improving very late clinical outcomes. A first-generation bioresorbable scaffold demonstrated to be no inferior to a contemporary metallic drug-eluting stents for overall 1-year patient-oriented and deviceoriented outcomes. However, increased rates of scaffold thrombosis and target vessel-related myocardial infarction were noted subsequently at 5 year follow up. Tissue/Bio Stents can present as a path breaking alternative approach to avoid intimal hyperplasia. They are characterised by presence of biodegradable struts with tissue mesh and complete absence of metal preventing ingrowth of the neointimal tissue into the lumen. Currently used stent materials include mainly metals and synthetic polymers. Their main limitation is lack of hemocompatibility, which can induce thrombosis and ultimately reocclusion, thus impairing the long-term performance of these devices. We are proposing use of biologically derived material to overcome this issue with the aim of enhancing the biocompatibility and the capability of this type of stents to support endothelialilzation. The aim of this article is to give a comprehensive overview of the manufacturing and applications of Tissue or Bio Stents as well as the different strategies followed for their development from the perspective of the material selection, fabrication approaches, and logical validation of the different concepts into animal and clinical trials.

2300. Neonates born to mothers with SARS-CoV-2 infection in pregnancy: a follow-up and serological study

Abstract Background To evaluate the early and late clinical outcomes of neonates born to mothers with SARS-CoV-2 infection in pregnancy, the dynamics of maternal IgG trans placental transfer and its persistence during the first month of life. Methods Prospective study enrolling neonates born to mothers with SARS-CoV-2 infection in pregnancy at IRCCS Azienda Ospedaliero Universitaria di Bologna, Italy, between April 2020 and September 2021. Neonates born to women with infection onset before 2 weeks prior to delivery were enrolled in a 12-month follow-up, including clinical and laboratory evaluations, cranial ultrasound, fundoscopy evaluation. Quantitative IgG to S1/S2 subunits of spike protein were assessed in mother-neonate dyads within 48 hours post-delivery and during follow-up until negative. Transplacental IgG transfer ratio was assessed in relation to the type and trimester of maternal infection. Results One hundred and forty-five neonates were included. the rate of preterm delivery was similar between women with and without SARS-CoV-2 infection (6.2% versus 8.7%, P=0.53). No clinical, laboratory, cerebral and fundoscopy abnormalities were detected at birth or during follow-up, through 11 months (range 8–12). MedianIgG level at birth was not different between neonates born to asymptomatic or symptomatic mothers (18.5 AU/mL, IQR 12–49, versus 31.5 AU/mL, IQR 15–71, P=0.07) nor in relation to the trimester of maternal infection (Table 1), even though mothers with third trimester infections had higher IgG level at birth. Transplacental transfer ratio was higher following second trimester maternal infections and was the lowest following third trimester infections (Table 1). Maternally derived IgG were rapidly weaned, with most infants (115/140, 82%) seronegative by 4 months of age. Conclusion Early and later outcomes of infants born to SARS-CoV-2 infected mothers were favorable. IgG trans placental transfer was higher following second trimester maternal infections, which could be relevant to inform studies on appropriate vaccination strategies aimed at neonatal protection. Maternally derived IgG are rapidly weaned in the first months of life. Disclosures All Authors: No reported disclosures.

Robotic and endoscopic mitral valve repair for degenerative disease.

Minimally invasive mitral valve repair has been proven to be a safe alternative to open sternotomy and may be accomplished through classic endoscopic and robotic endoscopic approaches. Outcomes across different minimally invasive techniques have been insufficiently described. We compare early and late clinical outcomes across matched patients undergoing robotic endoscopic and classic endoscopic repair. From 2011 to 2020, 786 patients underwent minimally invasive mitral surgery, from which we were able to generate 124 matched patients (62 patients in each cohort). Clinical results were then compared between the two matched populations. Survival analysis was used to compare freedom from mortality to 10 years among matched classic endoscopic and robotic endoscopic mitral valve repair cohorts and to calculate freedom from moderate or severe mitral insufficiency at latest follow-up. Histograms of cardiopulmonary bypass (CPB) and aortic cross-clamp times were constructed, and mean bypass and cross-clamp times were compared between classic endoscopic and robotic endoscopic cohorts. There was no difference in early or late mortality at 10 years in either cohort. Freedom from moderate or severe mitral regurgitation or mitral valve replacement at last echocardiogram was 86.4% vs. 73.5% at 10 years, P=0.97. Patients undergoing robotic endoscopic mitral repair had a significantly longer CPB run when compared to the classic endoscopic cohort, with 148 min of CPB in the robotic endoscopic cohort compared to 133 min in the classic endoscopic group, P=0.03. Overall post-operative length of stay was not statistically significant between the robotic endoscopic and classic endoscopic groups, 6.3±0.5 and 6.0±0.3 days, respectively. No patients in either cohort developed renal failure or wound infection. The classic endoscopic group had a slightly higher risk of prolonged ventilation when compared to the robotic endoscopic group, with three classic endoscopic patients remaining intubated >8 hours post-operatively, compared to a single patient in the robotic endoscopic group. There were no unplanned reoperations in either group. Rates of postoperative stroke were comparable between groups (three in the classic endoscopic cohort, and two in the robotic endoscopic cohort). Index mitral valve surgery via a classic endoscopic approach yields similar clinical outcomes when compared to robotic endoscopic surgery. We demonstrate that both classic endoscopic and robotic endoscopic approaches allow repair of degenerative mitral valves with excellent short- and medium-term outcomes in a tertiary referral center.

Clinical Efficacy of Temocillin Standard Dosing in Patients Treated with Outpatient Antimicrobial Therapy.

In 2020, EUCAST introduced breakpoints for temocillin. Based on these guidelines, reporting of temocillin susceptibility of Enterobacterales in the context of complicated urinary tract infections (cUTI) implicates the use of a high dose of temocillin (2 g q8h) constantly. We aimed to evaluate the clinical outcome of patients treated with the standard dose (4 g/day) of temocillin in outpatient parenteral antimicrobial therapy (tOPAT). Demographics, clinical and treatment parameters, and late clinical cure (at day 30 after tOPAT completion) were recorded. Univariate generalised estimating equation analyses, with clinical cure as outcome variable, were performed to evaluate covariate associations. Fifty-seven tOPAT episodes in 50 patients were included with a median antimicrobial treatment duration of 21 (range 10-228) days, and cUTI was the main indication (87.7%). Late clinical cure was achieved in 85.7% of the tOPAT episodes. Non-disseminated infections and minimal inhibitory concentrations (MIC) values ≤ 8 mg/L were associated with good late clinical outcome. In conclusion, a standard temocillin dose (4 g/day) results in good clinical outcomes in the treatment of cUTIs in tOPAT patients. Therefore, our centre concluded that the use of standard temocillin dosing should be continued instead of the high dose for cUTI in non-critically ill patients infected with Enterobacterales with an MIC ≤ 4 mg/L.

Reperfusion strategy and late clinical outcomes of patients with ST-elevation myocardial infarction (STEMI) in the absence of standard modifiable risk factors (SMuRFs)

Abstract Introduction There is growing evidence that patients presenting with STEMI in the absence of standard modifiable cardiovascular risk factors (SMuRFs; smoking, hypertension, hypercholesterolemia, diabetes) have poorer outcomes compared to those with atleast one SMuRF. It has been hypothesised that this may be in part due to decreased administration of pharmacotherapies in the post-infarct period due to perceived low risk. Long term outcomes of patients without SMuRFs based on reperfusion strategy received during the index admission have not been investigated. Purpose We sought to analyse late clinical outcomes of STEMI patients with and without SMuRFs based on reperfusion strategy received during the index admission. Methods All patients who underwent PCI between 2003 and 2014 were identified from a PCI centre STEMI database. Late clinical outcomes of patients with and without SMuRFs were analysed overall and based on reperfusion strategy [primary PCI (pPCI) vs pharmaco-invasive PCI (PI-PCI)]. Propensity matching was used to account for differences in baseline characteristics between the groups. Results Amongst 2,091 STEMI patients, 531 (25%) had no SMuRFs (51% pPCI, 49% PI-PCI) and 1560 (75%) had ≥1 SMuRF (52% pPCI, 48% PI-PCI). Unadjusted late mortality in SMuRF-less patients was 13.4% (18.8% pPCI, 7.7% PI-PCI) and for those with ≥1 SMuRF was 9.7% (11.0% pPCI, 8.4% PI-PCI). After propensity-matching clinical and angiographic characteristics, 5 year mortality rates were significantly higher for patients without SMuRFs compared to those with SMuRFs [HR 1.36, CI: 1.03–1.81, p=0.031]. This difference was attenuated for patients who underwent pPCI [HR 1.72, CI: 1.22–2.43, p=0.002]. Interestingly, this discrepancy was not observed amongst individuals who underwent pharmaco-invasive PCI [HR 1.13, CI: 0.53–1.48, p=0.638], as SMuRF-less patients had similar mortality rates to their counterparts. Long term rates of reinfarction, stent thrombosis and target vessel revascularisation were similar between the groups. Additionally, there was no significant difference in rates of stroke and major bleeding amongst all 4 subgroups. Conclusion Patients presenting with STEMI in the absence of SMuRFs have increased overall late mortality compared to those with at least one SMuRF. However, this difference was not observed in patients who underwent a pharmaco-invasive strategy, whereby patients without SMuRFs had similar outcomes to those with SMuRFs after adjusting for confounders. Our findings suggest the use of a pharmaco-invasive strategy in appropriate SMuRF-less patients presenting with STEMI. Funding Acknowledgement Type of funding sources: None.

Late Outcomes of Patients With Prehospital ST‐Segment Elevation and Appropriate Cardiac Catheterization Laboratory Nonactivation

BackgroundPatients with suspected ST‐segment–elevation myocardial infarction (STEMI) and cardiac catheterization laboratory nonactivation (CCL‐NA) or cancellation have reportedly similar crude and higher adjusted risks of death compared with those with CCL activation, though reasons for these poor outcomes are not clear. We determined late clinical outcomes among patients with prehospital ECG STEMI criteria who had CCL‐NA compared with those who had CCL activation.Methods and ResultsWe identified consecutive prehospital ECG transmissions between June 2, 2010 to October 6, 2016. Diagnoses according to the Fourth Universal Definition of myocardial infarction (MI), particularly rates of myocardial injury, were adjudicated. The primary outcome was all‐cause death. Secondary outcomes included cardiovascular death/MI/stroke and noncardiovascular death. To explore competing risks, cause‐specific hazard ratios (HRs) were obtained. Among 1033 included ECG transmissions, there were 569 (55%) CCL activations and 464 (45%) CCL‐NAs (1.8% were inappropriate CCL‐NAs). In the CCL activation group, adjudicated index diagnoses included MI (n=534, 94%, of which 99.6% were STEMI and 0.4% non‐STEMI), acute myocardial injury (n=15, 2.6%), and chronic myocardial injury (n=6, 1.1%). In the CCL‐NA group, diagnoses included MI (n=173, 37%, of which 61% were non‐STEMI and 39% STEMI), chronic myocardial injury (n=107, 23%), and acute myocardial injury (n=47, 10%). At 2 years, the risk of all‐cause death was higher in patients who had CCL‐NA compared with CCL activation (23% versus 7.9%, adjusted risk ratio, 1.58, 95% CI, 1.24–2.00), primarily because of an excess in noncardiovascular deaths (adjusted HR, 3.56, 95% CI, 2.07–6.13). There was no significant difference in the adjusted risk for cardiovascular death/MI/stroke between the 2 groups (HR, 1.23, 95% CI, 0.87–1.73).ConclusionsCCL‐NA was not primarily attributable to missed STEMI, but attributable to “masquerading” with high rates of non‐STEMI and myocardial injury. These patients had worse late outcomes than patients who had CCL activation, mainly because of higher rates of noncardiovascular deaths.

Abstract 4232: TLR2 agonist as a novel therapeutic approach to treat pancreatic adenocarcinoma

Abstract Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with an overall 5-year survival rate of &amp;lt;10% due to late stage diagnosis and poor clinical outcome with existing therapies. PDAC displays a high degree of tumor heterogeneity and immunosuppressive tumor microenvironment with lower tumor infiltrating lymphocytes (TIL). These factors contribute to resistance against chemotherapies and immunotherapies. Immunotherapies have shown activities across different tumor types including chemotherapy or targeted therapy resistant cancers however these options have little efficacy in the PDAC tumor. Here, in this study we tested the efficacy of gemcitabine in combination with Cadi-05 (TLR2 agonist) against established murine PDAC tumor models (Pan02 in C57/BL6 and 688M in B6129SF1/J). Animals were randomized to receive gemcitabine, Cadi-05, their combination or no treatment when they had tumor size ≈ 50 mm3, 65mm3 and 100 mm3. The weekly treatment of gemcitabine, Cadi-05 and their combination inhibited the tumor progression across all tumor sizes. At the end of study, PBMC and tumors were collected and analyzed for different immune parameters. Results revealed that Cadi-05 treatment alone was associated with increase in CD4+ and CD8+ T cells in PBMC as well as amongst TIL with significant decrease in their expression of immunosuppressive markers like FOXP3 and PD-1. Its combination with gemcitabine synergized the effect of each other. There was further increase in absolute TIL as well as TIL expressing CD4+ and CD8+ markers with decrease in FOXP3 and PD-1 expressing CD4+ and CD8+ TIL. Inhibition of tumor progression was associated with improved effector function of PBMC. Synergy between Cadi-05 and gemcitabine was also evident in effector function. In presence of established tumor, TLR2 agonist Cadi-05 improves effector function, increases CD4+ and CD8+ expressing TIL, decreases immune suppressive TIL and retards tumor growth. Our study suggests that combination of gemcitabine and Cadi-05 inhibits the tumor growth irrespective of its size and it is coupled with increased anti-tumor response and decreased immunosuppressive function Citation Format: Arpit Dheeraj, Chandreshwar Shukla, Dhanir Tailor, Nayan K. Jain, Kirsten Stefan, Chintan D. Patel, Rajiv Modi, Bakulesh M. Khamar, Sanjay V. Malhotra. TLR2 agonist as a novel therapeutic approach to treat pancreatic adenocarcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 4232.

Transcatheter Pulmonary Valve Replacement from Autologous Pericardium with a Self-Expandable Nitinol Stent in an Adult Sheep Model.

Transcatheter pulmonary valve replacement has been established as a viable alternative approach for patients suffering from right ventricular outflow tract or bioprosthetic valve dysfunction, with excellent early and late clinical outcomes. However, clinical challenges such as stented heart valve deterioration, coronary occlusion, endocarditis, and other complications must be addressed for lifetime application, particularly in pediatric patients. To facilitate the development of a lifelong solution for patients, transcatheter autologous pulmonary valve replacement was performed in an adult sheep model. The autologous pericardium was harvested from the sheep via left anterolateral minithoracotomy under general anesthesia with ventilation. The pericardium was placed on a 3D shaping heart valve model for non-toxic cross-linking for 2 days and 21 h. Intracardiac echocardiography (ICE) and angiography were performed to assess the position, morphology, function, and dimensions of the native pulmonary valve (NPV). After trimming, the crosslinked pericardium was sewn onto a self-expandable Nitinol stent and crimped into a self-designed delivery system. The autologous pulmonary valve (APV) was implanted at the NPV position via left jugular vein catheterization. ICE and angiography were repeated to evaluate the position, morphology, function, and dimensions of the APV. An APV was successfully implanted insheep J. In this paper, sheep J was selected to obtain representative results. A 30 mm APV with a Nitinol stent was accurately implanted at the NPV position without any significant hemodynamic change. There was no paravalvular leak, no new pulmonary valve insufficiency, or stented pulmonary valve migration. This study demonstrated the feasibility and safety, in a long-time follow-up, of developing an APV for implantation at the NPV position with a self-expandable Nitinol stent via jugular vein catheterization in an adult sheep model.

Outcomes and toxicity following post-operative hypofractionated radiotherapy to the regional nodes and the breast or the chest wall in locally advanced breast cancer.

We aimed to analyze the impact of a 3-week schedule of HypoFractionated (HF) radiotherapy (RT) after axillary dissection and breast surgery, in terms of safety and efficacy in patients with locally advanced breast cancer (BC). Eligible patients were females with Stage IIA - IIIC BC who underwent axillary dissection and breast surgery, either quadrantectomy or mastectomy. HF RT was delivered in 15 or 16 fractions for a total dose of 40.05 Gy or 42.56 Gy, respectively, to the clavicular nodal region along with the whole breast (HF WBRT) or the chest wall (HF PMRT), according to the type of surgery. Locoregional recurrence (LRR), distant metastases-free survival (DMFS), overall survival (OS) and acute and late treatment-related toxicities were estimated. 57 patients with a median age of 60 years (32-85) were retrospectively analyzed. 34 (60%) of patients underwent breast conservative surgery in the form of quadrantectomy and 23 (40%) were offered radical mastectomy. All patients underwent hypofractionated regional nodal irradiation (HF RNI). 34 (60%) of them underwent HF WBRT, while 23 (40%) received HF PMRT.At a median follow-up of 80 months (30-113), the 7-year LRR-free survival was 93% (95% CI, 74%-95%). The same features for DMFS and OS were 76% (95% CI, 52%-78%) and 67% (95% CI, 50%-80%), respectively. Only one (2%) patient experienced G3 acute skin toxicity. No grade ≥2 late toxicity was observed. Our study shows that HF RNI with HF RT to the whole breast or the chest wall after breast surgery is safe and effective in patients with locally advanced BC. Longer follow-up is needed to strengthen further analyses on late toxicity and clinical outcomes. This paper adds to the evidence that post-operative RNI with WBRT or PMRT can be safely and effectively delivered with 3-week HF regimen. Locally advanced BC patients can be offered HF RT to the regional nodes and the breast or the chest wall regardless the type of surgery.

Comparing short-term/long-term outcomes of heart transplants that occur inside and outside of normal working hours.

AimsHeart transplantation involves many factors such as donor selection, recipient management, multidisciplinary assessment, coordination with other organ teams, and transportation. Because of some unpredictable factors, heart transplantation can be conducted at any time of day. The purpose of this study is to investigate if outcomes differ between heart transplants taking place inside or outside of normal working hours.Methods and resultsWe reviewed patients who underwent heart transplantation at our institution from January 2010 to July 2020 (n = 329). Based on the documented start time of the recipient surgeries, the cohort was divided into two groups: working hours (Group A: 7:30 to 17:00; n = 92) and after hours (Group B: 17:00 to 7:30; n = 237). We compared these groups using propensity score matching analysis. After propensity score matching, 78 pairs of patients were successfully matched. We reviewed early and late clinical outcomes including survival. Long‐term survival was compared using the Kaplan–Meier method. In the propensity‐score matched patients, there were no significant differences in the baseline characteristics between two groups. In‐hospital mortality was not significantly different between the two groups (Group A: 6.4% vs. Group B: 2.6%, P = 0.44). Ischaemic time and cross‐clamp time did not differ between the groups. In terms of postoperative complications, there were no significant differences between two groups in stroke (6.4% vs. 3.9%, P = 0.72), primary graft dysfunction requiring extracorporeal membrane oxygenation (5.1% vs. 7.7%, P = 0.75), re‐exploration for bleeding (9.0% vs. 12.8%, P = 0.44), and newly required haemodialysis (7.7% vs. 6.4%, P = 0.75). The survival rate in Group A (88.1% at 1 year, 81.3% at 3 years) was not significantly different from Group B (90.5% at 1 year, 82.3% at 3 years, log rank = 0.96).ConclusionThere was no significant difference in clinical outcomes between heart transplants taking place inside or outside of working hours. A high quality of care can be provided for heart transplant patients even during after hours.

Can Malnutrition at the Time of Heart Transplantation Affect Early and Late Mortality?

<h3>Purpose</h3> To analyze early and late clinical outcomes of malnourished patients undergoing heart transplantation. <h3>Methods</h3> We retrospectively evaluated all patients ≥18 years of age, who received a heart transplant between January 2015 and July 2020 at our center. For each patient, we calculated the semi-quantitative Malnutrition Universal Screening Tool (MUST) score at the time of transplantation to assess the patient nutritional status. A Cox regression analysis was performed to assess follow-up mortality and postoperative complications risk. <h3>Results</h3> Data from 177 patients (median age 58, IQR 49-65; M 134, 76%) were collected. Median preoperative BMI was 24kg/mq (IQR 21-28). Preoperative MUST score was 0, 1, 2 or >2 in 100 (57%), 24 (14%), 40 (23%) and 12 (6%) patients, respectively. Median preoperative eGFR was 64 ml/min (IQR 49-83). An increase in MUST score (from 0 to 2) was not associated with higher in-hospital mortality (hazard ratio 0.99, 95% CI 2.06-0.45, p=0.99), and was only related to increased risk of postoperative acute kidney injury requiring renal replacement therapy (hazard ratio 2.04, 95% CI 1.06-3.95, p=0.033) or septicemia (hazard ratio 3.37, 95% CI 1.08-10.54, p=0.036) within 24 hours after transplantation. Postoperative data and associated hazard ratios are summarized in Table 1. Survival rates at 3 and 5 years were respectively 77% (95% CI 71-84, patients at risk n=83) and 73% (95 CI 66-82, patients at risk 28). An analogous increase in MUST score was associated with increased follow-up mortality risk (hazard ratio 1.67, 95% CI 1.07-2.61, p=0.025). <h3>Conclusion</h3> Severe malnutrition (evaluated with a multi-variable semi-quantitative parameter as MUST score) in patients receiving heart transplantation is a risk factor for late death. However, it is not associated with increased in-hospital mortality or major postoperative complications except for early septicemia or renal function.