Total anomalous origin of the coronary arteries from the pulmonary artery: a systematic review.

BACKGROUND: Although rare, coronary artery anomalies can have significant clinical implications. Total anomalous origin of the coronary arteries from the pulmonary artery (TCAPA) represents a rare subtype of coronary artery anomaly for which little is known. The aim of this review was to characterise the presentation, utilised diagnostic modalities, associated cardiac lesions, and treatment strategies in patients with TCAPA. METHODS: A systematic review was performed for cases of TCAPA using PubMed, Embase, and Web of Science. Keywords searched included "total anomalous origin of the coronary arteries from the pulmonary artery," "single ostium anomalous coronary artery from the pulmonary artery," and "anomalous origin of both coronary arteries from the pulmonary artery." RESULTS: Fifty-seven cases of TCAPA were identified in 50 manuscripts. Fifty-eight per cent of patients were male and the median age at presentation was 10 days (mean 1.71 ± 6.6 years, range 0 days-39 years). Most patients were symptomatic at the time of presentation; cyanosis (n = 22) and respiratory distress (n = 14) were the most common symptoms. Cases were most commonly diagnosed at autopsy (n = 26, 45.6%), but operative intervention was pursued in 22 cases (45.6%); aortic re-implantation (n = 14) and a Takeuchi-type repair (n = 7) were the most common routes of repair. CONCLUSIONS: The clinical presentation of patients with TCAPA was found to be variable, likely related to the presence of associated cardiac lesions. TCAPA should be considered in patients with suspected anomalous origin of the left coronary artery from the pulmonary artery for the serious consequences that can occur if not promptly corrected.

Multimeric disintegrin protein polymer fusions that target tumor vasculature.

Recombinant protein therapeutics have increased in number and frequency since the introduction of human insulin, 25 years ago. Presently, proteins and peptides are commonly used in the clinic. However, the incorporation of peptides into clinically approved nanomedicines has been limited. Reasons for this include the challenges of decorating pharmaceutical-grade nanoparticles with proteins by a process that is robust, scalable, and cost-effective. As an alternative to covalent bioconjugation between a protein and nanoparticle, we report that biologically active proteins may themselves mediate the formation of small multimers through steric stabilization by large protein polymers. Unlike multistep purification and bioconjugation, this approach is completed during biosynthesis. As proof-of-principle, the disintegrin protein called vicrostatin (VCN) was fused to an elastin-like polypeptide (A192). A significant fraction of fusion proteins self-assembled into multimers with a hydrodynamic radius of 15.9 nm. The A192-VCN fusion proteins compete specifically for cell-surface integrins on human umbilical vein endothelial cells (HUVECs) and two breast cancer cell lines, MDA-MB-231 and MDA-MB-435. Confocal microscopy revealed that, unlike linear RGD-containing protein polymers, the disintegrin fusion protein undergoes rapid cellular internalization. To explore their potential clinical applications, fusion proteins were characterized using small animal positron emission tomography (microPET). Passive tumor accumulation was observed for control protein polymers; however, the tumor accumulation of A192-VCN was saturable, which is consistent with integrin-mediated binding. The fusion of a protein polymer and disintegrin results in a higher intratumoral contrast compared to free VCN or A192 alone. Given the diversity of disintegrin proteins with specificity for various cell-surface integrins, disintegrin fusions are a new source of biomaterials with potential diagnostic and therapeutic applications.

Differential protein-protein interactions underlie signaling mediated by the TCR and a 4-1BB domain-containing CAR.

Cells rely on activity-dependent protein-protein interactions to convey biological signals. For chimeric antigen receptor (CAR) T cells containing a 4-1BB costimulatory domain, receptor engagement is thought to stimulate the formation of protein complexes similar to those stimulated by T cell receptor (TCR)-mediated signaling, but the number and type of protein interaction-mediating binding domains differ between CARs and TCRs. Here, we performed coimmunoprecipitation mass spectrometry analysis of a second-generation, CD19-directed 4-1BB:ζ CAR (referred to as bbζCAR) and identified 128 proteins that increased their coassociation after target engagement. We compared activity-induced TCR and CAR signalosomes by quantitative multiplex coimmunoprecipitation and showed that bbζCAR engagement led to the activation of two modules of protein interactions, one similar to TCR signaling that was more weakly engaged by bbζCAR as compared with the TCR and one composed of TRAF signaling complexes that was not engaged by the TCR. Batch-to-batch and interindividual variations in production of the cytokine IL-2 correlated with differences in the magnitude of protein network activation. Future CAR T cell manufacturing protocols could measure, and eventually control, biological variation by monitoring these signalosome activation markers.

Drug-regulated CD33-targeted CAR T cells control AML using clinically optimized rapamycin dosing.

Chimeric antigen receptor (CAR) designs that incorporate pharmacologic control are desirable; however, designs suitable for clinical translation are needed. We designed a fully human, rapamycin-regulated drug product for targeting CD33+ tumors called dimerizaing agent-regulated immunoreceptor complex (DARIC33). T cell products demonstrated target-specific and rapamycin-dependent cytokine release, transcriptional responses, cytotoxicity, and in vivo antileukemic activity in the presence of as little as 1 nM rapamycin. Rapamycin withdrawal paused DARIC33-stimulated T cell effector functions, which were restored following reexposure to rapamycin, demonstrating reversible effector function control. While rapamycin-regulated DARIC33 T cells were highly sensitive to target antigen, CD34+ stem cell colony-forming capacity was not impacted. We benchmarked DARIC33 potency relative to CD19 CAR T cells to estimate a T cell dose for clinical testing. In addition, we integrated in vitro and preclinical in vivo drug concentration thresholds for off-on state transitions, as well as murine and human rapamycin pharmacokinetics, to estimate a clinically applicable rapamycin dosing schedule. A phase I DARIC33 trial has been initiated (PLAT-08, NCT05105152), with initial evidence of rapamycin-regulated T cell activation and antitumor impact. Our findings provide evidence that the DARIC platform exhibits sensitive regulation and potency needed for clinical application to other important immunotherapy targets.

Synthesis and characterization of a matrix-metalloproteinase responsive silk-elastinlike protein polymer.

Silk-elastinlike protein polymers (SELPs) are recombinant polymers consisting of tandem repeats of silk (GAGAGS) and elastin (GVGVP) units. By modification of the length and composition of these repeats, the properties of SELP hydrogels can be controlled for specific applications including nucleic acid and virus delivery and tissue engineering. Here, the structure of SELPs is further modified to include a sequence that is sensitive to matrix-metalloproteinases (MMPs). MMPs are a ubiquitous family of extracellular matrix-modifying enzymes that are commonly associated with numerous vital processes. Increased levels of MMPs are found at high levels locally in many types of solid tumors. By modifying the SELP backbone with MMP-sensitive peptide sequences, a hydrogel that is degradable by MMPs was produced. The MMP-sensitivity of the polymer was examined by incubation with MMP-2 and MMP-9, which yielded complete cleavage of all full-length polymers by 36 hours and 48 hours, respectively, with no observable effect on unmodified SELP. Hydrogel sensitivity was tested by exposure to MMP-2 or MMP-9 for 2 weeks, during which samples were taken to analyze protein loss from the hydrogel and release of 100 nm fluorescent beads. Following the incubation period, hydrogels were tested in mechanical compression to examine the loss of hydrogel stiffness due to degradation. It was found that MMP-2 and MMP-9 caused 63% and 44% increased protein loss and 65% and 95% increased release from MMP-sensitive hydrogels, while the compressive modulus decreased by 41% and 29%. These results suggest the potential of MMP-responsive SELPs for localized delivery of bioactive agents where MMPs are overexpressed.

Context-specific synthetic T cell promoters from assembled transcriptional elements.

Genetic engineering of human lymphocytes for therapeutic applications is constrained by a lack of transgene transcriptional control, resulting in a compromised therapeutic index. Incomplete understanding of transcriptional logic limits the rational design of contextually responsive genetic modules1. Here, we juxtaposed rationally curated transcriptional response element (TRE) oligonucleotides by random concatemerization to generate a library from which we selected context-specific inducible synthetic promoters (iSynPros). Through functional selection, we screened an iSynPro library for "IF-THEN" logic-gated transcriptional responses in human CD8+ T cells expressing a 4-1BB second generation chimeric antigen receptor (CAR). iSynPros exhibiting stringent off-states in quiescent T cells and CAR activation-dependent transcriptional responsiveness were cloned and subjected to TRE composition and pattern analysis, as well as performance in regulating candidate antitumor potency enhancement modules. These data reveal synthetic TRE grammar can mediate logic-gated transgene transcription in human T cells that, when applied to CAR T cell engineering, enhance potency and improve therapeutic indices.

Locoregional CAR T cells for children with CNS tumors: Clinical procedure and catheter safety.

Central nervous system (CNS) tumors are the most common solid malignancy in the pediatric population. Based on adoptive cellular therapy's clinical success against childhood leukemia and the preclinical efficacy against pediatric CNS tumors, chimeric antigen receptor (CAR) T cells offer hope of improving outcomes for recurrent tumors and universally fatal diseases such as diffuse intrinsic pontine glioma (DIPG). However, a major obstacle for tumors of the brain and spine is ineffective T cell chemotaxis to disease sites. Locoregional CAR T cell delivery via infusion through an intracranial catheter is currently under study in multiple early phase clinical trials. Here, we describe the Seattle Children's single-institution experience including the multidisciplinary process for the preparation of successful, repetitive intracranial T cell infusion for children and the catheter-related safety of our 307 intracranial CAR T cell doses.

Intraventricular B7-H3 CAR T Cells for Diffuse Intrinsic Pontine Glioma: Preliminary First-in-Human Bioactivity and Safety.

Diffuse intrinsic pontine glioma (DIPG) remains a fatal brainstem tumor demanding innovative therapies. As B7-H3 (CD276) is expressed on central nervous system (CNS) tumors, we designed B7-H3-specific chimeric antigen receptor (CAR) T cells, confirmed their preclinical efficacy, and opened BrainChild-03 (NCT04185038), a first-in-human phase I trial administering repeated locoregional B7-H3 CAR T cells to children with recurrent/refractory CNS tumors and DIPG. Here, we report the results of the first three evaluable patients with DIPG (including two who enrolled after progression), who received 40 infusions with no dose-limiting toxicities. One patient had sustained clinical and radiographic improvement through 12 months on study. Patients exhibited correlative evidence of local immune activation and persistent cerebrospinal fluid (CSF) B7-H3 CAR T cells. Targeted mass spectrometry of CSF biospecimens revealed modulation of B7-H3 and critical immune analytes (CD14, CD163, CSF-1, CXCL13, and VCAM-1). Our data suggest the feasibility of repeated intracranial B7-H3 CAR T-cell dosing and that intracranial delivery may induce local immune activation. SIGNIFICANCE: This is the first report of repeatedly dosed intracranial B7-H3 CAR T cells for patients with DIPG and includes preliminary tolerability, the detection of CAR T cells in the CSF, CSF cytokine elevations supporting locoregional immune activation, and the feasibility of serial mass spectrometry from both serum and CSF. This article is highlighted in the In This Issue feature, p. 1.

Short-term outcomes of ablation therapy for hepatic tumors: evidence from the 2006-2009 nationwide inpatient sample.

BACKGROUND: Radiofrequency ablation (RFA) for the treatment of hepatic tumors has been increasingly used across the United States. Whether treatment-related morbidity has remained low with broader adoption is unclear. We conducted this study to describe in-hospital morbidity associated with RFA for hepatic tumors and to identify predictors of adverse events in a nationally representative database. METHODS: Using the 2006-2009 Nationwide Inpatient Sample, we evaluated all patients aged ≥40 years who underwent an elective RFA for primary or metastatic liver tumors (N = 1298). Outcomes included in-hospital procedure-specific and postoperative complications. Multivariable logistic regression analyses were performed to identify patient and facility predictors of complications. RESULTS: Most patients underwent a percutaneous (39.9 %) or laparoscopic (22.0 %) procedure for metastatic liver tumors (57.5 %). Procedure-specific complications were frequent (18.2 %), with transfusion requirements (10.7 %), intraoperative bleeding (4.3 %), and hepatic failure (2.8 %) being the most common. Arrhythmias [adjusted odds ratio (AOR) = 1.93 (1.23-3.04)], coagulopathy [AOR = 4.65 (2.95-7.34)], and an open surgical approach [AOR = 2.77 (1.75-4.36)] were associated with an increased likelihood of procedure-specific complications, whereas hospital RFA volume ≥16/year was associated with a reduced likelihood [AOR = 0.59 (0.38-0.91)]. Postoperative complications were also common (12.0 %), with arrhythmias, heart failure, coagulopathy, and open surgical approach acting as significant predictors. CONCLUSIONS: In-hospital morbidity is common after RFA for hepatic tumors. While several patient factors are associated with more frequent procedure-specific complications, treatment at hospitals with an annual volume ≥16 cases/year was associated with a 41 % reduction in the odds of procedure-specific complications.

Open versus laparoscopic liver resection: looking beyond the immediate postoperative period.

BACKGROUND: Laparoscopic liver resection for malignant disease has shown short-term benefit. This study aimed to compare in-house, 30-day, and 1-year morbidity between laparoscopic and open liver resections. METHODS: The charts for all patients who underwent liver resection for malignant disease between April 2006 and October 2009 were reviewed. Patient, operative, and outcomes data at 30 days and 1 year were collected. RESULTS: For 76 patients, 49 open and 27 laparoscopic resections were performed. The two groups were similar in terms of age, gender, body mass index (BMI), extent of liver resection, use of ablation therapy, and tumor pathology (P > 0.05). The laparoscopic group had less blood loss (P = 0.004) and shorter hospital stays (P = 0.002). During their hospital stay, patients treated laparoscopically had fewer complications, but the difference was not significant. Home disposition was similar in the laparoscopic (96%) and open (90%) groups. More patients were readmitted at 30 days (2 vs. 9; P = 0.31) and 1 year (4 vs. 19; P = 0.04) in the open group. The all-cause 1-year mortality rates were similar between the laparoscopic and open groups (14.8% vs. 10.2%). CONCLUSION: The benefits of laparoscopic liver resection may extend beyond the initial postoperative period, with fewer readmissions despite shorter hospital stays. This also may suggest lower long-term hospital costs.

A model for a medical school surgery interest group.

The purpose of this report is to record some of the recent accomplishments of the Surgery Interest Group (SIG) at the Uniformed Services University of the Health Sciences, and to provide a framework for others to follow, with the goal of encouraging students to become interested in the exciting field of surgery. We will outline some of the events that our SIG planned and carried out in order to provide a quality experience to its members.

Thymic adenocarcinoma presenting as an incidental mediastinal mass.

BACKGROUND: Primary thymic adenocarcinoma represents an exceptionally rare malignancy, for which the cornerstone of therapy is margin-negative resection, with radiation and systemic therapy reserved for invasive and advanced disease. Thymic adenocarcinoma has not been previously reported in the setting of a concomitant malignancy, as reported herein. CASE PRESENTATION: We present a case of a 55-year-old previously healthy male diagnosed with acute myeloid leukemia, also found to have a mediastinal mass. Evaluation of the mediastinal mass with tumor markers, biopsies, and next-generation sequencing proved non-diagnostic, while he was simultaneously treated with induction chemotherapy to prevent leukemia-related blast crisis. After completing and recovering from induction chemotherapy, he underwent successful thymectomy during a chemotherapy holiday, with a margin-negative resection of thymic adenocarcinoma. He has subsequently recovered and undergone successful allogeneic hematopoietic stem cell transplant. CONCLUSIONS: We present a case of synchronous adult acute myeloid leukemia and primary thymic adenocarcinoma requiring a tailored approach for management of simultaneous malignancies.

Midterm Durability and Structural Valve Degeneration of Transcatheter Aortic Valve Replacement in a Federal Facility.

OBJECTIVE: Transcatheter aortic valve replacement (TAVR), previously reserved for patients of intermediate to prohibitive surgical risk, has now been expanded to patients of any surgical risk with severe aortic stenosis. Bioprostheses are prone to structural valve degeneration (SVD), a progressive and multifactorial process that limits valve durability. As the population undergoing TAVR shifts toward a lower-risk and younger profile, long-term durability is a crucial determinant for patient outcomes. Our objective was to determine the incidence and risk factors of SVD at midterm follow-up in a veteran TAVR population. METHODS: Patients undergoing TAVR at our federal facility were retrospectively evaluated for SVD and other endpoints with standardized consensus criteria. Multivariable Cox proportional hazards analysis was performed to evaluate risk factors for mortality and SVD. RESULTS: From 2013 to 2020, 344 patients (median age, 78 years) underwent TAVR. Survival from all-cause mortality was 91.3% at 1 year, 75.1% at 3 years, and 61.7% at 5 years. Cumulative freedom from SVD was 98.2% at 1 year, 96.5% at 3 years, and 93.7% at 5 years. All 13 patients with SVD met hemodynamic criteria, and 1 required intervention. Median time to hemodynamic SVD was 1.04 years. Independent risk factors for SVD included age (hazard ratio [HR] = 0.92, 95% confidence interval [CI]: 0.86 to 0.99) and valve size (HR = 0.19, 95% CI: 0.04 to 0.89). CONCLUSIONS: SVD was evident at a low but detectable rate at 5-year follow-up. Further understanding of TAVR biomechanics as well as continued longer-term follow-up will be essential for informing patient-specific risk of SVD.

Silk-elastinlike protein polymers improve the efficacy of adenovirus thymidine kinase enzyme prodrug therapy of head and neck tumors.

BACKGROUND: Adenoviral-directed enzyme prodrug therapy is a promising approach for head and neck cancer gene therapy. The challenges faced by this approach, however, comprise transient gene expression and dissemination of viruses to distant organs. METHODS: We used recombinant silk-elastinlike protein polymer (SELP) matrices for intratumoral delivery of adenoviruses containing both thymidine kinase-1 and luciferase genes in a nude mouse model of JHU-022 head and neck tumor. Hydrogels made from two SELP analogues (47K and 815K), with similar silk to elastinlike block ratios but different block lengths, were studied for intratumoral viral delivery. Tumor-bearing mice were followed up for tumor progression and luciferase gene expression concomitantly for 5 weeks. Polymer safety was evaluated through body weight change, blood count, and liver and kidney functions, in addition to gross and microscopic histological examination. RESULTS: SELP-815K analogues efficiently controlled the duration and extent of transfection in tumors for up to 5 weeks with no detectable spread to the liver. An approximately five-fold greater reduction in tumor volume was obtained with matrix-mediated delivery compared to intra-tumoral injection of adenoviruses in saline. SELP matrix proved safe in all injected mice compared to the control group. CONCLUSIONS: The SELP-controlled gene delivery approach could potentially improve the anticancer activity of virus-mediated gene therapy at the same time as limiting viral spread to normal organs.

Silk-elastin-like hydrogel improves the safety of adenovirus-mediated gene-directed enzyme-prodrug therapy.

Recombinant silk-elastin-like protein polymers (SELPs) are well-known for their highly tunable properties on both the molecular and macroscopic hydrogel levels. One specific structure of these polymers, SELP-815K, has been investigated as an injectable controlled delivery system for the treatment of head and neck cancer via a gene-directed enzyme prodrug therapy (GDEPT) approach. Due to its pore size and gelation properties in vivo, SELP restricts the distribution and controls the release of therapeutic viruses for up to one month. It has been shown that SELP-mediated delivery significantly improves therapeutic outcome of the herpes simplex virus thymidine kinase (HSVtk)/ganciclovir (GCV) system in xenograft models of human head and neck cancer. However little is known about potential benefits of this approach with regard to toxicity in the presence of a fully intact immune system. The studies presented here were designed to assess the change in toxicity of the SELP-mediated viral delivery compared to free viral injection in a non-tumor-bearing immune competent mouse model. Toxicity was assessed at 1, 2, 4, and 12 weeks via body weight monitoring, complete blood count (CBC), and blood chemistry. It was found that in the acute and subacute phases (weeks 1-4) there is significant toxicity in groups combining the virus and the prodrug, and matrix-mediated gene delivery with SELP demonstrates a reduction in toxicity from the 2 week time point through the 4 week time point. At the end of the subchronic phase (12 weeks), signs of toxicity had subsided in both groups. Based on these results, recombinant SELPs offer a significant reduction in toxicity of virus-mediated GDEPT treatment compared to free virus injection in the acute and subacute phases.

Recurrent Spontaneous Pneumothorax in a 47-Year-Old Woman.

Pneumothorax is a condition where air exists in the chest cavity, outside the lung. The causes of pneumothorax are numerous and determining the etiology can aid in treatment and prevent recurrence. We describe a 47-year-old female patient with past medical history of endometriosis who presented to the emergency room with recurrent right sided pneumothorax, its onset correlating with onset of menses. She underwent video assisted thorascopic surgery for a suspected catamenial pneumothorax whereby nodular "chocolate" appearing areas were noted on the middle lobe and multiple similar appearing lesions and fenestrations were noted on the diaphragm. A biologic mesh was affixed to the diaphragm after which mechanical and chemical pleurodesis were performed. She tolerated the procedure well and has been symptom free since. Herein, we review the pathophysiology, diagnosis, and treatment strategies for catamenial pneumothorax in the hopes of increasing awareness and understanding of this rare cause of spontaneous pneumothorax.

Development of a porcine model of emergency resternotomy at a low-volume cardiac surgery centre.

Emergency resternotomy in the intensive care unit (ICU) is a rarely performed, yet potentially life-saving intervention. Success relies on recognition of a deteriorating clinical condition, timely deployment of equipment/personnel and rapid execution. Given how infrequently it is performed, we sought to develop a large animal model of resternotomy to prepare ICU nurses and technicians at our low-volume cardiac surgery military centre. A porcine model of resternotomy was developed at the end of an already-scheduled trauma lab. Participants worked their way through a pre-planned simulation scenario, culminating in the need for resternotomy. Pre-simulation surveys assessing knowledge and comfort level with aspects of resternotomy were compared to post-simulation surveys. Participants improved their knowledge of resternotomy by 20.4% (P < 0.0001; 14.7% for nurses and 26.9% for technicians). Improvements were seen in all aspects assessed relating to subjective comfort/preparedness of resternotomy. The model was an effective and realistic method to augment training of ICU staff about resternotomy. Costs associated with this model can be reduced when used in conjunction with large animal labs. This model should be used together with mannequin-based methods of resternotomy training to provide a realistic training environment and assessment of skills at capable institutions.

Anomalous Origin of the Circumflex or Left Anterior Descending Artery From the Pulmonary Artery.

Anomalous origin of the circumflex or left anterior descending artery from the pulmonary artery (ACxAPA and ALADAPA, respectively) are rare congenital coronary anomalies with clinical presentation varying from an asymptomatic murmur to sudden cardiac arrest. A systematic review was performed, and 46 cases of ACxAPA and 51 cases of ALADAPA were identified in 87 articles. Data were collected and analyzed from each case. A better understanding of ACxAPA/ALADAPA can provide information to providers who encounter this lesion as well as provide insight into coronary artery development which may help in the understanding of coronary artery anomalies.

Penetrating thoracic injury from a bean bag round complicated by development of post-operative empyema.

Bean bag guns were developed as a nonlethal means for law enforcement personnel to subdue individuals. The large surface area and lower velocities of the bean bag round theoretically result in transfer of most of the energy to the skin/subcutaneous tissue and minimize the likelihood of dermal penetration, thereby 'stunning' intended victims without causing injury to deeper structures. However, this technology has been associated with significant intra-abdominal and intrathoracic injuries, skin penetration and death. We present a 59-year-old man who sustained a penetrating thoracic injury from a bean bag gun. Although the bean bag was successfully removed, the patient developed a postoperative empyema requiring operative management. We discuss the unique aspects of thoracic trauma from bean bag ballistics as well as considerations in management of patients with this uncommon mechanism of injury.

Anomalous Origin of the Right Coronary Artery From the Pulmonary Artery: A Systematic Review.

BACKGROUND: Anomalous origin of the right coronary artery from the pulmonary artery (ARCAPA) is a rare congenital cardiac lesion that has been diagnosed in both children and adults with symptoms ranging from an asymptomatic murmur to sudden cardiac death. The aim of this review was to characterize published cases of ARCAPA to better understand this rare congenital coronary anomaly. METHODS: A systematic review was performed using PubMed, Embase, and Google Scholar for cases of ARCAPA. Keywords searched included: "anomalous origin of the right coronary artery from the pulmonary artery" and "ARCAPA." RESULTS: A total of 223 cases of ARCAPA were identified in 193 case reports. There was a slight male predominance (54.5%) and the median age at presentation was 14.0 years. Thirty-eight percent of patients were asymptomatic and most commonly identified during evaluation of a murmur. Angina and dyspnea were the most common presenting symptoms (22.4% and 17.0%, respectively). In symptomatic patients, a bimodal distribution of age at presentation was observed with a peak near birth and another between ages 40 and 60 years. The condition was most commonly diagnosed with coronary angiography (40.4%). Most cases were repaired surgically (72.6%) and reimplantation of the right coronary artery onto the aorta was the most common method of repair (62.3%). CONCLUSIONS: ARCAPA represents a rare coronary anomaly with great variability in clinical presentation. An understanding of the pathophysiology associated with the lesion is critical when determining treatment strategies.