Circulating tumor HPV DNA assessments after surgery for human papilloma virus-associated oropharynx carcinoma.

PURPOSE: To understand the utility of circulating tumor human papillomavirus DNA (ctHPVDNA) blood testing for HPV-associated oropharynx squamous cell carcinoma (HPV + OPSCC) after definitive surgery. MATERIALS AND METHODS: Prospective cohort study of HPV(+)OPSCC patients with ctHPVDNA test data to assess its accuracy in detecting biopsy-confirmed disease at various post-treatment time points. Eligible patients had p16(+)/HPV(+) OPSCC and ctHPVDNA testing performed at any time pre-operatively and/or postoperatively. In cases of recurrence, patients were excluded from analysis if ctHPVDNA testing was not performed within 6 months of biopsy. RESULTS: 196 all-treatment-type patients had at least one PT ctHPVDNA test. The initial post-treatment (PT) ctHPVDNA sensitivity, specificity, PPV, and NPV were 69.2 % (9/13), 96.7 % (177/183), 60.0 % (9/15), and 97.8 % (177/181). 61 surgery alone (SA) patients underwent 128 PT tests. The initial PT SA ctHPVDNA sensitivity, specificity, PPV, and NPV were 100 % (2/2), 96.0 % (48/50), 50 % (2/4), and 100 % (48/48). 35 of 61 (57.4 %) SA patients had NCCN-based histopathologic indications for adjuvant (chemo)radiation but declined. 3 of 35 (8.57 %) had a positive PT ctHPVDNA test of which 1 of 3 (33 %) had biopsy-proven recurrence. Prospectively, ten patients had a PreT positive ctHPVDNA, underwent SA, refused adjuvant treatment, had an undetectable ctHPVDNA within 2 weeks of SA, and remained free of disease (mean 10.3 months). CONCLUSION: The high specificity and NPV of ctHPVDNA after SA suggest ctHPVDNA may have a role in determining the omission of PT adjuvant (chemo)radiation in select patients.

Long-term laryngological sequelae and patient-reported outcomes after COVID-19 infection.

PURPOSE: We examine prevalence, characteristics, quality of life (QOL) assessments, and long-term effects of interventions for laryngeal dysfunction after recovery from COVID-19 infection. MATERIALS AND METHODS: 653 patients presenting to Yale's COVID clinic from April 2020 to August 2021 were identified retrospectively. Patients with PCR-positive COVID-19 who underwent evaluation by fellowship-trained laryngologists were included. Patient demographics, comorbidities, intubation/tracheostomy, strobolaryngoscopy, voice metrics, and management data were collected. Patient-reported QOL indices were Dyspnea Index (DI), Cough Severity Index (CSI), Voice Handicap Index-10 (VHI-10), Eating Assessment Tool-10 (EAT-10), and Reflux Symptom Index (RSI). RESULTS: 57 patients met inclusion criteria: 37 (64.9 %) were hospitalized for COVID-19 infection and 24 (42.1 %) required intubation. Mean duration between COVID-19 diagnosis and presentation to laryngology was significantly shorter for patients who were intubated compared to non-intubated (175 ± 98 days versus 256 ± 150 days, respectively, p = 0.025). Dysphonia was diagnosed in 40 (70.2 %) patients, dysphagia in 14 (25.0 %) patients, COVID-related laryngeal hypersensitivity in 13 (22.8 %), and laryngotracheal stenosis (LTS) in 10 (17.5 %) patients. Of the 17 patients who underwent voice therapy, 11 (64.7 %) reported improvement in their symptoms and 2 (11.8 %) patients reported resolution. VHI scores decreased for patients who reported symptom improvement. 7 (70 %) patients with LTS required >1 procedural intervention before symptom improvement. Improvement across QOL indices was seen in patients with LTS. CONCLUSIONS: Laryngeal dysfunction commonly presents and is persistent for months after recovery from COVID-19 in non-hospitalized and non-intubated patients. Voice therapy and procedural interventions have the potential to address post-COVID laryngeal dysfunction.

Integration of Reinforcement Learning in a Virtual Robotic Surgical Simulation.

Background. The revolutions in AI hold tremendous capacity to augment human achievements in surgery, but robust integration of deep learning algorithms with high-fidelity surgical simulation remains a challenge. We present a novel application of reinforcement learning (RL) for automating surgical maneuvers in a graphical simulation.Methods. In the Unity3D game engine, the Machine Learning-Agents package was integrated with the NVIDIA FleX particle simulator for developing autonomously behaving RL-trained scissors. Proximal Policy Optimization (PPO) was used to reward movements and desired behavior such as movement along desired trajectory and optimized cutting maneuvers along the deformable tissue-like object. Constant and proportional reward functions were tested, and TensorFlow analytics was used to informed hyperparameter tuning and evaluate performance.Results. RL-trained scissors reliably manipulated the rendered tissue that was simulated with soft-tissue properties. A desirable trajectory of the autonomously behaving scissors was achieved along 1 axis. Proportional rewards performed better compared to constant rewards. Cumulative reward and PPO metrics did not consistently improve across RL-trained scissors in the setting for movement across 2 axes (horizontal and depth).Conclusion. Game engines hold promising potential for the design and implementation of RL-based solutions to simulated surgical subtasks. Task completion was sufficiently achieved in one-dimensional movement in simulations with and without tissue-rendering. Further work is needed to optimize network architecture and parameter tuning for increasing complexity.

Review of probiotic use in otolaryngology.

OBJECTIVE: Probiotics have garnered considerable attention as an intervention for various conditions common to otolaryngology. The purpose of this review is to evaluate the current literature to offer recommendations about the safety and efficacy of probiotic management in otolaryngologic conditions. STUDY DESIGN: Narrative review. METHODS: PubMed and Google Scholar were queried using pertinent keywords to retrieve relevant studies with particular focus in the recent 5 years. All abstracts were assessed and studies, reviews and meta-analyses achieving evaluation of probiotic therapies or characterization of microbiome changes were included for further review. Studies were categorized by condition or anatomic region across various subspecialties. Key data parameters were extracted and evaluated across studies and treatment types. RESULTS: Strong evidence exists for the use probiotic agents to improve symptoms for allergic rhinitis, chronic rhinosinusitis and certain dental conditions. Despite promising results, further investigation is needed to evaluate and optimize probiotic delivery for mitigating otitis media, oropharyngeal inflammation and upper respiratory tract infections. Preclinical studies suggest that probiotics may potentially offer benefit for voice prosthesis maintenance, wound healing and mitigation of oral dysplasia. CONCLUSION: Probiotic therapies may offer clinical benefit in a variety of contexts within the field of otolaryngology, especially for short-term relief of certain inflammatory conditions of the oral cavity, auditory and nasal cavities. Further investigation is warranted for evaluation of long-term outcomes and pathogenic deterrence.

Safety considerations for esophageal dilation by anesthetic type: A systematic review.

OBJECTIVES: Esophageal dilation (ED) may be performed in the office under local anesthesia or in a procedure/operating room under general anesthesia or intravenous (IV) sedation. However, indications for type of anesthesia during these procedures have not been established. The purpose of this review is to assess outcomes of esophageal dilation performed using different types of anesthesia to assess the safety of office-based techniques. METHODS: We conducted a systematic review and meta-analysis comparing the outcomes of anesthesia techniques for ED in adults. Exclusion criteria included reviews, small case series, use of stents, diagnoses with high morbidity, and rare diseases. A comprehensive literature search of the PubMed, CINAHL, and EMBASE databases was performed for articles relating to esophageal dilation. RESULTS: 876 papers were identified of which 164 full text studies were assessed and 25 were included in the analysis using the PRISMA guidelines. Data regarding demographics, dilation technique, and adverse events were extracted. The DerSimonian-Laird random-effect models with inverse-variance weighting were fit to estimate the combined effects. There were no statistically significant differences among mortality, perforation, or bleeding based on anesthetic. CONCLUSIONS: With office-based procedures gaining popularity in laryngology, there is a need to profile their safety. Office-based ED appears to have equivalent safety to general and IV sedation, although further research is necessary to define indications favoring office-based techniques.

Anesthesia screen use may impact operating room communication practices in otolaryngology.

OBJECTIVES: Failures in communication are a leading contributor to medical error. There is increasing attention on cultivating robust communication practices in the Operating Room (OR) to mitigate against patient injury and optimize efficient patient care. Few studies have evaluated how surgical equipment may introduce barriers to team dynamics. DESIGN: We conducted a pilot observational study to examine the relationship between anesthesia screen drapes (which are used inconsistently) and the frequency of verbal exchanges between surgical and anesthesia members. 25 procedures spanning various procedures in Otolaryngology were covertly observed, 12 of which employed a screen. Verbal exchanges were recorded across three stages of the surgery: pre-procedure (before the draping), procedure (drapes placed throughout) and post-procedure (after the removal of the draping). Speaker and content of the exchange was noted as well as various features about the procedure. RESULTS: Decreases in rates of exchanges were most pronounced during the procedure stage, although they did not reach significance on T-testing (p = 0.0719). After controlling for attending, table orientation and number of professionals, regression analysis did reveal a statistically significant decrease in rates of verbal exchanges during the procedure in the presence of the anesthesia screen (7.17 (± 6.33) versus 2.23 (± 1.00), p = 0.0318). Differences were also significant among surgeon-initiated and patient-care-related exchanges (p = 0.0168 and p = 0.0432, respectively). Decreases in anesthesiologist-initiated and non-clinical exchanges did not reach significance (p = 0.1530 and p = 0.5120, respectively). CONCLUSION: This pilot study suggests that anesthesia screens may negatively impact communication practices in the OR.

Acellular therapeutic approach for heart failure: in vitro production of extracellular vesicles from human cardiovascular progenitors.

Aims: We have shown that extracellular vesicles (EVs) secreted by embryonic stem cell-derived cardiovascular progenitor cells (Pg) recapitulate the therapeutic effects of their parent cells in a mouse model of chronic heart failure (CHF). Our objectives are to investigate whether EV released by more readily available cell sources are therapeutic, whether their effectiveness is influenced by the differentiation state of the secreting cell, and through which mechanisms they act. Methods and results: The total EV secreted by human induced pluripotent stem cell-derived cardiovascular progenitors (iPSC-Pg) and human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) were isolated by ultracentrifugation and characterized by Nanoparticle Tracking Analysis, western blot, and cryo-electron microscopy. In vitro bioactivity assays were used to evaluate their cellular effects. Cell and EV microRNA (miRNA) content were assessed by miRNA array. Myocardial infarction was induced in 199 nude mice. Three weeks later, mice with left ventricular ejection fraction (LVEF) ≤ 45% received transcutaneous echo-guided injections of iPSC-CM (1.4 × 106, n = 19), iPSC-Pg (1.4 × 106, n = 17), total EV secreted by 1.4 × 106 iPSC-Pg (n = 19), or phosphate-buffered saline (control, n = 17) into the peri-infarct myocardium. Seven weeks later, hearts were evaluated by echocardiography, histology, and gene expression profiling, blinded to treatment group. In vitro, EV were internalized by target cells, increased cell survival, cell proliferation, and endothelial cell migration in a dose-dependent manner and stimulated tube formation. Extracellular vesicles were rich in miRNAs and most of the 16 highly abundant, evolutionarily conserved miRNAs are associated with tissue-repair pathways. In vivo, EV outperformed cell injections, significantly improving cardiac function through decreased left ventricular volumes (left ventricular end systolic volume: -11%, P < 0.001; left ventricular end diastolic volume: -4%, P = 0.002), and increased LVEF (+14%, P < 0.0001) relative to baseline values. Gene profiling revealed that EV-treated hearts were enriched for tissue reparative pathways. Conclusion: Extracellular vesicles secreted by iPSC-Pg are effective in the treatment of CHF, possibly, in part, through their specific miRNA signature and the associated stimulation of distinct cardioprotective pathways. The processing and regulatory advantages of EV could make them effective substitutes for cell transplantation.

Computer Vision-Radiomics & Pathognomics.

The role of computer vision in extracting radiographic (radiomics) and histopathologic (pathognomics) features is an extension of molecular biomarkers that have been foundational to our understanding across the spectrum of head and neck disorders. Especially within head and neck cancers, machine learning and deep learning applications have yielded advances in the characterization of tumor features, nodal features, and various outcomes. This review aims to overview the landscape of radiomic and pathognomic applications, informing future work to address gaps. Novel methodologies will be needed to potentially engineer ways of integrating multidimensional data inputs to examine disease features to guide prognosis comprehensively and ultimately clinical management.

An Ear Mystery: Conductive Hearing Loss with Normal Acoustic Reflexes and VEMPs.

The cause of sudden conductive loss in the absences of other vestibulo-audiologic abnormalities can be isolated to specific subsites of the ossicular chain using audiometric testing. In the absence of such abnormalities, a rare etiology may be the cause after an inciting trauma. Laryngoscope, 2024.

Identifying Opportunities to Deliver High-Quality Cancer Care Across a Health System: A Clinical Responsibility.

OBJECTIVE: We examined process-related quality metrics for oral squamous cell carcinoma (OSCC) depending on treating facility type across a health system and region. STUDY DESIGN: Retrospective in accordance with Strengthening the Reporting of Observational Studies in Epidemiology guidelines. SETTING: Single health system and region. METHODS: Patients with OSCC diagnosed between 2012 and 2018 were identified from tumor registries of 6 hospitals (1 academic and 5 community) within a single health system. Patients were categorized into 3 care groups: (1) solely at the academic center, (2) solely at community facilities, and (3) combined care at academic and community facilities. Primary outcome measures were process-related quality metrics: positive surgical margin rate, lymph node yield (LNY), adjuvant treatment initiation ≤6 weeks, National Comprehensive Cancer Network (NCCN)-guideline adherence. RESULTS: A total of 499 patients were included: 307 (61.5%) patients in the academic-only group, 101 (20.2%) in the community-only group, and 91 (18.2%) in the combined group. Surgery at community hospitals was associated with increased odds of positive surgical margins (11.9% vs 2.5%, odds ratio [OR]: 47.73, 95% confidence interval [CI]: 11.2-275.86, P < .001) and lower odds of LNY ≥ 18 (52.8% vs 85.9%, OR: 0.15, 95% CI: 0.07-0.33, P < .001) relative to the academic center. Compared with the academic-only group, odds of adjuvant treatment initiation ≤6 weeks were lower for the combined group (OR: 0.30, 95% CI: 0.13-0.64, P = .002) and odds of NCCN guideline-adherent treatment were lower in the community only group (OR: 0.35, 95% CI: 0.18-0.70, P = .003). CONCLUSION: Quality of oral cancer care across the health system and region is comparable to or better-than national standards, indicating good baseline quality of care. Differences by facility type and fragmentation of care present an opportunity for bringing best in-class cancer care across an entire region.

Novel Machine Learning Model to Predict Interval of Oral Cancer Recurrence for Surveillance Stratification.

OBJECTIVE(S): We aimed to develop a machine learning (ML) model to accurately predict the timing of oral squamous cell carcinoma (OSCC) recurrence across four 1-year intervals. METHODS: Patients with surgically treated OSCC between 2012-2018 were retrospectively identified from the Yale-New Haven Health system tumor registry. Patients with known recurrence or minimum follow-up of 24 months from surgery were included. Patients were classified into one of five levels: four 1-year intervals and one level for no recurrence (within 4 years of surgery). Three sets of data inputs (comprehensive, feature selection, nomogram) were combined with 4 ML architectures (logistic regression, decision tree (DT), support vector machine (SVM), artificial neural network classifiers) yielding 12 models in total. Models were primarily evaluated using mean absolute error (MAE), lower values indicating better prediction of 1-year interval recurrence. Secondary outcomes included accuracy, weighted precision, and weighted recall. RESULTS: 389 patients met inclusion criteria: 102 (26.2%) recurred within 48 months of surgery. Median follow-up time was 25 months (IQR: 15-37.5) for patients with recurrence and 44 months (IQR: 32-57) for patients without recurrence. MAE of 0.654% and 80.8% accuracy were achieved on a 15-variable feature selection input by 2 ML models: DT and SVM classifiers. CONCLUSIONS: To our knowledge, this is the first study to leverage multiclass ML models to predict time to OSCC recurrence. We developed a model using feature selection data input that reliably predicted recurrence within 1-year intervals. Precise modeling of recurrence timing has the potential to personalize surveillance protocols in the future to enhance early detection and reduce extraneous healthcare costs. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:1652-1659, 2023.

Trends in Private Equity Acquisitions of US Otolaryngology Practices.

With the increasing consolidation of physician practices, private equity (PE) firms have been playing a growing role in healthcare delivery and recently began entering the otolaryngology-head and neck surgery space. To date, no studies have examined the extent of PE investment in otolaryngology. We assessed trends and geographic distribution of US otolaryngology practices acquired by PE using Pitchbook (Seattle, WA), a comprehensive market database. From 2015 to 2021, 23 otolaryngology practices were acquired by PE. The number of PE acquisitions increased over time: 1 practice was acquired in 2015 versus 4 practices in 2019 versus 8 practices in 2021. Nearly half (43.5%, n = 10) of acquired practices were in the South Atlantic region. The median number of otolaryngologists at these practices was 5 (interquartile range: 3-7). As PE investment in otolaryngology continues to grow, further research is needed to assess its impact on clinical decision-making, healthcare costs, physician job satisfaction, clinical efficiency, and patient outcomes.

Characterization of Trapezial Pommel in Relation to Radiographic and Wear Patterns in Carpometacarpal Osteoarthritis.

BACKGROUND: Trapezial pommel, or ulnar osteophyte positioned at the vertex of the saddle-shaped facet, is a consistent structural appearance in osteoarthritis (OA) of the first carpometacarpal. This study investigates its relation to radiographic measures (modified Eaton staging and thumb OA [ThOA] index) and wear patterns (trapezial surface morphology and cartilaginous eburnation). METHODS: In all, 137 whole trapezia were explanted from 116 patients and evaluated for Eaton staging, morphology (saddle, cirque, or dish), and eburnation (degree of cartilaginous effacement) of the articular surface of the trapezium. In total, 131 Robert's views and 126 stress views were reviewed by 2 blinded senior surgeons for ThOA index and pommel size. Statistical analyses included Spearman correlation and linear regression. RESULTS: Standardized pommel size achieved good intrarater reliability (correlation coefficient: 0.80-0.98) and moderate interrater reliability (correlation coefficient: 0.60-0.67). The ThOA index and pommel size were significantly correlated across Robert's (rs = 0.51) and stress views (rs = 0.64). The ThOA index better distinguished between stages compared with pommel size. All the radiographic measures inversely correlated with preserved cartilage and varied across morphologies. Pommel size differed significantly between dish and saddle, and the ThOA index was significantly different between all morphologies when using stress views. CONCLUSIONS: We reliably quantified the pommel feature and demonstrated significant correlations with other radiographic and topologic measures of arthritic disease. If future studies can demonstrate that the pommel is a pathogenic process in ThOA and its correction can curb disease progression, the identification of the pommel feature may help guide targeted intervention.

Trends in Residency Applicant Volume in Otolaryngology-Head and Neck Surgery and Peer Specialties.

OBJECTIVE: To evaluate the 2020 to 2021 Otolaryngology residency application cycle in the context of recent trends. STUDY DESIGN: Retrospective data analysis. SETTING: Disruptions caused by the COVID-19 pandemic may significantly alter trends among residency applicants, especially in highly competitive and/or smaller specialties. METHODS: Applicant and residency statistics from Electronic Residency Application Service (ERAS) and National Residency Matching Program (NRMP) were extracted from the 2016 to 2021 and 2011 to 2021, respectively. Trends in Otolaryngology-Head and Neck Surgery (OHNS) were compared to peer specialties (PS) including Dermatology, Neurological Surgery, Orthopedic Surgery, and Integrated Pathway for Plastic and Reconstructive Surgery (PRS). The ratio of the number of applicants per positions (APP) was used to reflect the degree of competition. RESULTS: Between 2011 and 2021, the number of OHNS programs and positions expanded less than those of PS and General Surgery. The increase in the APP ratio was significantly greater for OHNS compared to those Dermatology, Orthopedic Surgery, General Surgery and all PGY1 residency positions for both US MD and all applicants (P < .01 for each). OHNS expansion of US MD (P = .046), but not all applicants (P = .169), outgrew that of Neurosurgery. CONCLUSION: The 2020 to 2021 cycle affected by the COVID-19 pandemic saw a continuation of the recent trend in the expanding OHNS applicant pool. OHNS remains one of the specialties with the highest APP ratio and has observed a significant growth compared to PS since 2018. Understanding and anticipating trends in residency application cycles is critical for designing processes to optimize the best fit between applicants and programs.

Correlations of Radiographic and Endoscopic Observations in Subglottic Stenosis.

OBJECTIVE(S): Subglottic stenosis (SGS) represents a constellation of diverse pathologic processes that ultimately lead to narrowing of the subglottic region and can produce significant morbidity. Existing endoscopic and radiographic assessments may not be consistent in practice. METHODS: Severity of stenosis was evaluated and reported using the Cotton-Myer classification system from 33 endoscopic procedures from 32 unique subjects. Radiographic imaging within the preceding 3 month period was subsequently reviewed and narrowing was measured by a blinded radiologist. Degree of stenosis was reported as a percentage in 30 out of 33 endoscopic evaluations and subsequently compared to radiographically determined percentage of stenosis. Statistical analyzes were conducted to evaluate concordance between endoscopic and radiographic assessments. RESULTS: About 45.5% (15/33) of the evaluations were in agreement using Cotton-Myer scoring, while 27.3% (9/33) were discrepant by 1 grade and 27.3% (9/33) by 2 grades. Correlation of degree of stenosis as a percentage using Spearman (coefficient: 0.233, P-value: .214) and Pearson (coefficient: 0.138, P-value: .466) methods demonstrated very weak relationships. Radiographic scoring did not predict endoscopic classification to a significant degree using mixed effects regression. CONCLUSIONS: Radiographic and endoscopic grading of subglottic stenosis may not be reliably concordant in practice.

Characterization of Laryngotracheal Fractures and Repairs: A TQIP Study.

OBJECTIVES: Laryngotracheal trauma is poorly studied and associated with serious morbidity and mortality. This study reports features associated with laryngotracheal fractures, and factors associated with laryngeal fracture repair. STUDY DESIGN: Retrospective database study SETTING: American College of Surgeons Trauma Quality Improvement Program (ACS-TQIP®) METHODS: ACS-TQIP® 2014-2015 participant user data files were queried for laryngotracheal fractures using the International Classification of Diseases (ICD) 9th edition encodings. Demographic, diagnostic and procedure characteristics were analyzed with univariate chi-squared analysis and multivariate logistic regression. RESULTS: We extracted 635 cases of laryngotracheal injury, with a median Injury Severity Score of 16 (IQR: 10 - 25). Most were caused unintentionally (65.7%), followed by assault (28.8%). Blunt trauma (79.5%) was more common than penetrating trauma (20.0%). These trends were upheld in the subgroup of repaired fractures, which made up 12.6% (80/635) of cases. The median length of hospital stay was 6 days (IQR: 3 - 13) in all fractures and 10 days (IQR: 6 - 14) in the subgroup of repaired fractures, while the median length of ICU stay was 4 days (IQR: 2 - 9) in all fractures and 4.5 (IQR: 6 - 14.3) in the subgroup of repaired fractures. Cut/pierce injuries (OR: 4.7, P < 0.001) and ISS (OR: 0.97, pP = 0.026) significantly affected rate of laryngeal fracture repair. CONCLUSION: Laryngotracheal fractures are uncommon but serious injuries. Our results show that penetrating causes of injuries have the shortest time to repair, and that a higher ISS score is negatively associated with repair.

Biomimetic six-axis robots replicate human cardiac papillary muscle motion: pioneering the next generation of biomechanical heart simulator technology.

Papillary muscles serve as attachment points for chordae tendineae which anchor and position mitral valve leaflets for proper coaptation. As the ventricle contracts, the papillary muscles translate and rotate, impacting chordae and leaflet kinematics; this motion can be significantly affected in a diseased heart. In ex vivo heart simulation, an explanted valve is subjected to physiologic conditions and can be adapted to mimic a disease state, thus providing a valuable tool to quantitatively analyse biomechanics and optimize surgical valve repair. However, without the inclusion of papillary muscle motion, current simulators are limited in their ability to accurately replicate cardiac biomechanics. We developed and implemented image-guided papillary muscle (IPM) robots to mimic the precise motion of papillary muscles. The IPM robotic system was designed with six degrees of freedom to fully capture the native motion. Mathematical analysis was used to avoid singularity conditions, and a supercomputing cluster enabled the calculation of the system's reachable workspace. The IPM robots were implemented in our heart simulator with motion prescribed by high-resolution human computed tomography images, revealing that papillary muscle motion significantly impacts the chordae force profile. Our IPM robotic system represents a significant advancement for ex vivo simulation, enabling more reliable cardiac simulations and repair optimizations.

An innovative biologic system for photon-powered myocardium in the ischemic heart.

Coronary artery disease is one of the most common causes of death and disability, afflicting more than 15 million Americans. Although pharmacological advances and revascularization techniques have decreased mortality, many survivors will eventually succumb to heart failure secondary to the residual microvascular perfusion deficit that remains after revascularization. We present a novel system that rescues the myocardium from acute ischemia, using photosynthesis through intramyocardial delivery of the cyanobacterium Synechococcus elongatus. By using light rather than blood flow as a source of energy, photosynthetic therapy increases tissue oxygenation, maintains myocardial metabolism, and yields durable improvements in cardiac function during and after induction of ischemia. By circumventing blood flow entirely to provide tissue with oxygen and nutrients, this system has the potential to create a paradigm shift in the way ischemic heart disease is treated.