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The current treatment paradigm of abdominal aortic aneurysms (AAA) focuses on observing patients until their disease reaches certain thresholds for intervention, with no preceding treatment available. There is an opportunity to develop novel therapies to prevent further aneurysmal growth and decrease the risk of a highly morbid rupture. We used a porcine model of aortic dilation to assess the ability of human adipose-derived mesenchymal stem cells (MSCs) to attenuate aortic dilation.Twelve Yorkshire pigs received periadventitial injections (collagenase and elastase) into a 4-cm segment of infrarenal aorta. Animals were treated with either 1 × 10All animals survived until POD 21. The mean aortic diameter was reduced in the aortic dilation + MSC treatment group compared to aortic dilation control animals (1.10 ± 0.126 versus 1.48 cm ± 0.151, P 0.001). Aortic media thickness was reduced in the aortic dilation group compared to the aortic dilation + MSC group (609.14 IQR 445.21-692.93 μm versus 643.55 IQR 560.91-733.88 μm, P = 0.0048). There was a significant decrease in the content of collagen and alpha-smooth muscle actin and elastin perturbation in the aortic dilation group as compared to the aortic dilation + MSC group. Immunohistochemistry demonstrated an increased level of vascular endothelial growth factor, tissue inhibitor of matrix metalloproteinase 1, and tissue inhibitor of matrix metalloproteinase 3 expression in the aorta of aortic dilation + MSC animals.Stem cell therapy suppressed the aortic dilation in a porcine model. Animals from the aortic dilation group showed more diseased gross features, histologic changes, and biochemical properties of the aorta compared to that of the aortic dilation + MSC treated animals. This novel finding should prompt further investigation into translatable drug and cell therapies for aneurysmal disease.

During the coronavirus-19 pandemic, experts recommended delaying routine cancer screening and modifying treatment strategies. We sought to understand the sequalae of these recommendations.We performed a retrospective single-center analysis of screening, diagnosis, and treatment of lung, colorectal, and breast cancer. Data was collected from our institutional cancer registry. Prepandemic (2016-2019) was compared with pandemic (2020) data.Three thousand three sixty one screening chest computed tomography scans (CTs), 35,917 colonoscopies, and 48,093 screening mammograms were performed. There was no difference in CTs [81.0 (SEM10.0) vs. 65.6 (SEM3.29), P =0.067] or mammograms [1017.0 (SEM171.8) vs. 809.4 (SEM56.41), P =0.177] in 2020 versus prepandemic. There were fewer colonoscopies in 2020 [651.4 (SEM103.5) vs. 758.91 (SEM11.79), P =0.043]. There was a decrease in cancer diagnoses per month in 2020 of lung [22.70 (SEM1.469) vs. 28.75 (SEM0.8216), P =0.003] and breast [38.56 (SEM6.133) vs. 51.82 (SEM1.257), P =0.001], but not colorectal [13.11 (SEM1.467) vs. 15.88 (SEM0.585), P =0.074] cancer. There was no change in stage at presentation for lung ( P =0.717), breast ( P =0.115), or colorectal cancer ( P =0.180). Lung had a shorter time-to-treatment in 2020 [38.92 days (SEM 2.48) vs. 66 (SEM1.46), P =0.002].In 2020, there was no difference in screening studies for lung and breast cancer but there was a decrease in new diagnoses. Although there were fewer colonoscopies performed in 2020, there was no change in new colorectal cancer diagnoses. Despite changes in guidelines during the pandemic, the time-to-treatment for lung cancer was shorter and was unchanged for colorectal and breast cancer. These findings highlight the importance of continuing care for a vulnerable patient population despite a pandemic.

Purpose Treatment of invasive rectal adenocarcinoma is stratified into upfront surgery versus neoadjuvant chemoradiotherapy, in part, based on tumor distance from the anal verge (AV). This study examines the correlation between tumor distance measurements (endoscopic and MRI) and relationship to the anterior peritoneal reflection (APR) on MRI. Methods A single-center retrospective study was performed at a tertiary center accredited by the National Accreditation Program for Rectal Cancer (NAPRC). 162 patients with invasive rectal cancer were seen between October of 2018 and April of 2022. Sensitivity and specificity were determined for MRI and endoscopic measurements in their ability to predict tumor location relative to the APR. Results 119 patients had tumors endoscopically and radiographically measured from the AV. Pelvic MRI characterized tumors as above (intraperitoneal) or at/straddles/below the APR (extraperitoneal). True positives were defined as extraperitoneal tumors 10cm. Endoscopy was 81.9% sensitive and 64.3% specific in predicting tumor location with respect to the APR. MRI was 86.7% sensitive and 92.9% specific. Utilizing a 12cm cutoff, sensitivity of both modalities increased (94.3%, 91.4%) but specificity decreased (50%, 64.3%). Conclusion For locally invasive rectal cancers, tumor position relative to the APR is an important factor in determining the role of neoadjuvant therapy. These results suggest endoscopic tumor measurements do not accurately predict tumor location relative to the APR, and may lead to incorrect treatment stratification. When the APR is not identified, MRI-reported tumor distance may be a better predictor of this relationship.

Surgical education has evolved over time to incorporate supplemental modalities of training beyond the operating room. Even with the utility of simulation software and didactic education, there is still a need to provide surgical residents with experience in live tissue dissection and tissue handling while maintaining patient safety. In our program, after two clinical years, residents participate in a year of translational research which uses porcine models for complex open abdominal procedures. During the porcine surgeries, our residents are guided by the supervising attending to perform key portions of the procedure typically reserved for those more senior trainees. We found in a survey that research residents after two clinical years found this experience with large animal surgeries helped them better navigate anatomic structures and would recommend this to future trainees. We believe this dual-purpose research-training model provides a valuable resource that can be adapted to other programs.

Adoptive cell therapies include multiple cell-based therapies to harness the immune system's power to mount a robust anticancer effect. Early successes in solid tumors with checkpoint inhibition have increased the research and development of immunotherapy. The utilization of cell-based therapy for gastrointestinal malignancies is still in its infancy because of challenges of antigen specificity and access to the tumor microenvironment. In this review, we discuss the current state of adoptive cell therapies in terms of challenges and early successes in preclinical and clinical studies.

Computed tomography (CT) imaging is routinely obtained for diagnostics, especially in trauma and emergency rooms, often identifying incidental findings. We utilized a natural language processing (NLP) algorithm to quantify the incidence of clinically relevant pancreatic lesions in CT imaging.We utilized the electronic medical record to perform a retrospective chart review of adult patients admitted for trauma to a level 1 tertiary care center between 2010 and 2020 who underwent abdominal CT imaging. An open-source NLP software was used to identify patients with intrapapillary mucinous neoplasms (IPMN), pancreatic cysts, pancreatic ductal dilation, or pancreatic masses after optimizing the algorithm using a test group of patients who underwent pancreatic surgery.The algorithm identified pancreatic lesions in 27 of 28 patients who underwent pancreatic surgery and excluded 1 patient who had a pure ampullary mass. The study cohort consisted of 18,769 patients who met our inclusion criteria admitted to the hospital. Of this population, 232 were found to have pancreatic lesions of interest. There were 48 (20.7%) patients with concern for IPMN, pancreatic cysts in 36 (15.5%), concerning masses in 30 (12.9%), traumatic findings in 44 (19.0%), pancreatitis in 41 (17.7%), and ductal abnormalities in 19 (18.2%) patients. Prior pancreatic surgery and other findings were identified in 14 (6.0%) patients.In this study, we propose a novel use of NLP software to identify potentially malignant pancreatic lesions annotated in CT imaging performed for other purposes. This methodology can significantly increase the screening and automated referral for the management of precancerous lesions.

Background Colostomy reversal is a common procedure. Patients often have baseline comorbidities associated with postoperative morbidity. We utilized a modified frailty index (mFI-5) to predict postoperative complications. Methods Patients who underwent elective, open Hartmann’s reversal were queried from the National Surgical Quality Improvement Program (NSQIP) database. Patients were stratified to low, medium, or high frailty groups. Statistical analysis was performed using chi-squared, ANOVA, and logistic regression. Results There were 9272 patients with Hartmann’s reversal. 48.78%, 30.31%, and 12.89% had low, moderate, or high frailty, respectively. High frailty was associated with cardiac arrest, myocardial infarction, reintubation, prolonged intubation, early reoperation, and mortality. After multivariate analysis, high frailty was associated with prolonged intubation (OR 3.147, P = .001), reintubation (OR 2.548, P = .002), and reoperation (OR 1.67, P < .001). Conclusions Frailty was associated with greater risk of postoperative complications in patients undergoing Hartmann’s reversal. Frailty may be a useful adjunct to stratify for patients who are at risk for postoperative complications.

Summary: Aging-associated functional decline is accompanied by alterations in the epigenome. To explore DNA modifications that could influence visual function with age, we perform whole-genome bisulfite sequencing of purified mouse rod photoreceptors at four ages and identify 2,054 differentially methylated regions (DMRs). We detect many DMRs during early stages of aging and in rod regulatory regions, and some of these cluster at chromosomal hotspots, especially on chromosome 10, which includes a longevity interactome. Integration of methylome to age-related transcriptome changes, chromatin signatures, and first-order protein-protein interactions uncover an enrichment of DMRs in altered pathways that are associated with rod function, aging, and energy metabolism. In concordance, we detect reduced basal mitochondrial respiration and increased fatty acid dependency with retinal age in ex vivo assays. Our study reveals age-dependent genomic and chromatin features susceptible to DNA methylation changes in rod photoreceptors and identifies a link between DNA methylation and energy metabolism in aging. : The crosstalk between chromatin modifications and aging hallmarks is poorly understood, especially in neurons. Using purified rod photoreceptors, Corso-Díaz et al. identify aging-associated differentially DNA methylated regions that greatly overlap regulatory elements and are linked to lower mitochondrial basal respiration and higher fatty acid dependency. Keywords: retinal aging, epigenome, DNA methylome, gene regulation, rod photoreceptor, mitochondria, differential methylation clusters, beta oxidation

Purpose To describe surgical outcomes and structural characteristics of intraocular lenses (IOLs) implanted with transconjunctival sutureless intrascleral (SIS) fixation in human eyes. Design Retrospective interventional surgical case series involving live and cadaveric human eyes. Methods In this study, we investigated the surgical outcomes and structural anatomy of secondary IOLs implanted with the SIS technique in human eyes. All cases involving SIS IOL fixation performed at a single academic center from January 1, 2012, through July 30, 2016, were reviewed to describe the surgical technique, common indications, clinical outcomes, and the rate of common operative complications. To investigate the structure of SIS-fixated IOLs in vivo, slit-lamp biomicroscopy, ultrasound biomicroscopy, and intraoperative endoscopy were analyzed to describe anatomical outcomes. The primary anatomical outcomes were the optic pupillary centration and location of haptic externalization. Results were correlated with cadaveric human eyes that underwent the SIS-IOL technique. Cadaveric eyes were imaged and analyzed using high-resolution photography for centration, stress measurements at the haptic-optic junction, and qualitative descriptors of IOL optic and haptic position. Results A total of 122 consecutive patients who underwent IOL placement using SIS technique were included in the study with mean follow-up of 1.52 years (range, 0.4-4.5 years). The majority (75%) of patients received a new 3-piece IOL for primary aphakia or after IOL exchange. The other patients (25%) had a dislocated 3-piece IOL that was rescued using the SIS technique. Preoperative mean Snellen visual acuity was 20/633 (logarithm of the minimum angle of resolution = 1.501). At the final visit, the mean best-corrected visual acuity was 20/83 (logarithm of the minimum angle of resolution = 0.6243) and final mean spherical equivalent was -0.57 diopters. The most common complications were vitreous hemorrhage (22% of eyes), which resolved spontaneously in most cases, and cystoid macular edema. The rates of IOL dislocation, IOL decentration, haptic erosion, IOL tilting, iris capture, and endophthalmitis were low. Intraoperative endoscopy and ultrasound biomicroscopy demonstrated a securely fixated IOL and well-centered optic without iris or ciliary body touch. Structural study of cadaveric eyes confirmed IOL optic and haptic anatomy observed during live human surgery. The ab interno haptic insertion was the anterior pars plana, away from the iris, ciliary processes and ora serrata. The degree of haptic externalization was correlated with the degree of strain on the haptic-optic junction. The angle of the haptic-optic junction in SIS-fixated IOLs (33.97°) was not significantly different compared with overlaid native nonfixated IOL (32.93°) but increased slightly with degree of haptic tip externalization (36.26 and 39.16 for 2 and 3 mm haptic externalizations, respectively). Conclusion In this comprehensive study, we demonstrate the surgical outcomes achieved with SIS fixation of IOLs. Surgical and postoperative complications do occur, albeit at a low rate, and can effectively be managed with excellent anatomical and visual outcomes. The structural and anatomical data in this study may help guide SIS placement and optimize long-term surgical results.

Defects in mitochondrial respiration and oxidative phosphorylation are associated with pleiotropic phenotypes, which, at least in part, can be attributed to aberrant generation of reactive oxygen (O2) and nitrogen species.1–4 Mitochondrial dysfunction has been correlated with the accumulation of cellular damage in aging and in late-onset neurodegenerative diseases.5–8 Tissues with a high metabolic requirement, such as the retina, are especially vulnerable to mitochondrial damage, which is implicated as a causal factor in neuronal cell death in retinal and macular degeneration.9,10 Within the retina, rod and cone photoreceptors exhibit high energy metabolism and associated O2 consumption, primarily driven by ion transport and synaptic transmission in the dark and by cGMP turnover in the light.11–14 Quantification of O2 consumption rate (OCR) is generally adopted as a readout of overall mitochondrial function.15 Measurements of respiration have traditionally been conducted with the O2-consuming Clark-type electrode on mitochondria preparations,16 which require sample volumes in the milliliter range and continuous stirring of samples in suspension, with loss of cellular/tissue context. The Clark-type electrode has also been used to measure O2 consumption in the intact rat retina, detecting higher O2 consumption in the outer retina compared to inner retina, with downward or upward changes, respectively, during light adaptation.17 Microelectrodes that are O2-sensitive and intraretinal measurements taken at differential tissue depths18 confirmed that photoreceptors have the highest O2 consumption.18 Finally, fresh mouse retina slices in a flow culture system have been used to determine the metabolic dependence of photoreceptors on glucose as a fuel.19 A limitation of all of the above experimental conditions is that they only permit evaluation of one retina/sample at a time and are not readily amenable for simultaneous and high throughput evaluation of multiple experimental conditions. Microplate-based assays using an extracellular flux (XF) analyzer (Seahorse XF Analyzer; Seahorse Bioscience, Billerica, MA, USA) allow parallel comparison of different samples in small microliter volumes without the need for sample suspension, continuous stirring, or large measuring volumes in the order of ∼2 mL, as is the case with typical Clark-type electrode systems. The XF analyzer (Seahorse Bioscience) has been used to determine the effects of Ca++ and oxidative stress on mitochondrial function in the photoreceptor-like cell line 661W.20 Using the same technology, mitochondrial function has been examined and compared in acutely derived sections from several brain areas of a rat model of migraine.21 Direct comparative OCR determination has not yet been accomplished in the freshly isolated mouse retina. Here, we introduce an improved protocol for microplate-based measurement of O2 consumption in acute retina samples. Photoreceptors account for the majority of O2 consumption in the retina,22 with the entire inner retina consuming at most 17% of the amount used by photoreceptors.13 Thus, the measurement of O2 consumption in the intact retina largely reflects photoreceptor respiration. Our newly optimized method directly evaluates retinal mitochondrial function and should be valuable for assessing alterations associated with retinal dysfunction and/or disease.