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Background: Hiatal hernia (HH) is a common condition. A multidisciplinary expert panel was convened to develop evidence-based recommendations to support clinicians, patients, and others in decisions regarding the treatment of HH., Methods: Systematic reviews were conducted for four key questions regarding the treatment of HH in adults: surgical treatment of asymptomatic HH versus surveillance; use of mesh versus no mesh; performing a fundoplication versus no fundoplication; and Roux-en-Y gastric bypass (RYGB) versus redo fundoplication for recurrent HH. Evidence-based recommendations were formulated using the Grading of Recommendations, Assessment, Development, and Evaluations methodology by subject experts. When the evidence was insufficient to base recommendations on, expert opinion was utilized instead. Recommendations for future research were also proposed., Results: The panel provided one conditional recommendation and two expert opinions for adults with HH. The panel suggested routinely performing a fundoplication in the repair of HH, though this was based on low certainty evidence. There was insufficient evidence to make evidence-based recommendations regarding surgical repair of asymptomatic HH or conversion to RYGB in recurrent HH, and therefore, only expert opinions were offered. The panel suggested that select asymptomatic patients may be offered surgical repair, with criteria outlined. Similarly, it suggested that conversion to RYGB for management of recurrent HH may be appropriate in certain patients and again described criteria. The evidence for the routine use of mesh in HH repair was equivocal and the panel deferred making a recommendation., Conclusions: These recommendations should provide guidance regarding surgical decision-making in the treatment of HH and highlight the importance of shared decision-making and consideration of patient values to optimize outcomes. Pursuing the identified research needs will improve the evidence base and may allow for stronger recommendations in future evidence-based guidelines for the treatment of HH., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Gallbladder cancer (GBC) is associated with a high mortality rate. Asian American (AsA) are among the fastest-growing populations in the United States, yet little is known about the disparity of GBC within this cohort. This study identified trends in treatment and outcomes for GBC in a disaggregated fashion, specifically for this population., Methods: A retrospective analysis of the National Cancer Database (NCDB) between 2010 and 2019 examining all patients treated for gallbladder cancer was performed. Basic demographic factors were identified for patients of Caucasian, African American, and disaggregated Asian subpopulations. Survival curves were used to identify differences in median overall survival, and a multivariate analysis was performed to determine which factors impact overall survival., Results: A total of 1317 (5%) patients were of AsA origin. Median survival for the overall AsA population is 15.1 months compared with Caucasian (11.5 months) and African Americans (11.4 months) (p < 0.0001). Within the AsA groups, the Korean subpopulation had the lowest survival at 12.6 months, whereas Filipinos had the longest survival at 19.1 months (p < 0.0001). Patients of Filipino descent had the highest rate of surgical resection but lower chemotherapy utilization. Conversely, Korean patients had the highest utilization of multimodality therapy. Multivariate analysis demonstrated that belonging to Chinese, Filipino, or Indian ethnicity was associated with decreased risk of mortality., Conclusions: There are disparate differences in survival for patients with GBC between AsA groups. Socioeconomic, genetic, and epigenetic factors may influence these differences. Further research is needed to delineate the causes of this disparity., (© 2024. The Author(s).)

Background: Advanced care planning (ACP) is the process of establishing goals for end-of-life care. We aimed to examine ACP's prevalence, associated factors, and impact in a cohort of patients undergoing gastrostomy tube procedures., Methods: Adult patients who underwent gastrostomy tube placement from 2016 to 2021 ​at a tertiary center were identified. Variables evaluated included age, sex, race, comorbidities, and median income of patient home zip code. Primary outcomes included the presence of ACP, length of stay (LOS), and 90-day mortality. Analysis was performed using independent T tests, Mann Whitney U-tests, and Chi Square analysis. ACP, LOS, and 90-day mortality were analyzed with multivariate analysis., Results: 877 patients underwent gastrostomy tube placement and 10.6 ​% had ACP. Black race was an isolated factor negatively associated with ACP (OR 0.423, p ​= ​0.013). There was no difference in the proportion of patients with or without ACP who died within 90 days of the procedure (17 ​% vs. 15 ​%, p ​= ​0.836). Average LOS was 6 days shorter for patients with ACP (p ​< ​0.001)., Conclusion: This study highlights the significant underutilization and racial disparity in ACP, and found that ACP does not negatively impact outcomes or perioperative mortality for patients undergoing gastrostomy tube placement., Competing Interests: Declaration of competing interest Each of the authors have no conflicts of interest to disclose., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Collaboration between the health care industry and surgeons is critical in modern medicine. Conflict of interest (COI) has the risk of introducing bias into research studies. We investigated the accuracy of self-disclosed COI for studies that researched the use of microwave ablation for liver metastasis., Methods: A literature search identified studies that investigated the use of microwave ablation for liver cancer between 2016 and 2022. We utilized the Open Payments Database to query individual authors' financial contributions from the industry. The accuracy of the disclosure statement and financial contribution for each study and author was calculated. We compared the amount of financial contribution authors received based on the accuracy of their COI statement., Results: Twenty-five studies of interest were identified. The mean number of authors was 8.24. A disclosure statement was present in 52% of studies. Of those, 28% had an incongruent disclosure statement. 9/25 (36%) of studies had a conflict of interest based on financial payments provided by industry. Overall, authors received an average of $440,483.41 (SD $1,889,375.34). We did not find a difference in the financial contribution's value based on the disclosure statement's accuracy ( P = .55)., Conclusions: Over a quarter of studies in our review of microwave ablation literature had discrepancies in the reporting of conflicts of interest, highlighting the need for improved reporting of potential conflicts of interest to protect the integrity of clinical research. Compared to other fields of surgery, we found a lower rate of undisclosed COI, suggesting that the scope of cancer-directed surgery may be more resistant to industry influence., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The surgical management of hiatal hernia remains controversial. We aimed to compare outcomes of mesh versus no mesh and fundoplication versus no fundoplication in symptomatic patients; surgery versus observation in asymptomatic patients; and redo hernia repair versus conversion to Roux-en-Y reconstruction in recurrent hiatal hernia., Methods: We searched PubMed, Embase, CINAHL, Cochrane Library and the ClinicalTrials.gov databases between 2000 and 2022 for randomized controlled trials (RCTs), observational studies, and case series (asymptomatic and recurrent hernias). Screening was performed by two trained independent reviewers. Pooled analyses were performed on comparative data. Risk of bias was assessed using the Cochrane Risk of Bias tool and Newcastle Ottawa Scale for randomized and non-randomized studies, respectively., Results: We included 45 studies from 5152 retrieved records. Only six RCTs had low risk of bias. Mesh was associated with a lower recurrence risk (RR = 0.50, 95%CI 0.28, 0.88; I 2  = 57%) in observational studies but not RCTs (RR = 0.98, 95%CI 0.47, 2.02; I 2  = 34%), and higher total early dysphagia based on five observational studies (RR = 1.44, 95%CI 1.10, 1.89; I 2  = 40%) but was not statistically significant in RCTs (RR = 3.00, 95%CI 0.64, 14.16). There was no difference in complications, reintervention, heartburn, reflux, or quality of life. There were no appropriate studies comparing surgery to observation in asymptomatic patients. Fundoplication resulted in higher early dysphagia in both observational studies and RCTs ([RR = 2.08, 95%CI 1.16, 3.76] and [RR = 20.58, 95%CI 1.34, 316.69]) but lower reflux in RCTs (RR = 0.31, 95%CI 0.17, 0.56, I 2  = 0%). Conversion to Roux-en-Y was associated with a lower reintervention risk after 30 days compared to redo surgery., Conclusions: The evidence for optimal management of symptomatic and recurrent hiatal hernia remains controversial, underpinned by studies with a high risk of bias. Shared decision making between surgeon and patient is essential for optimal outcomes., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Computed tomography imaging routinely detects incidental findings; most research focuses on malignant findings. However, benign diseases such as hiatal hernia also require identification and follow-up. Natural language algorithms can help identify these non-malignant findings., Methods: Imaging of adult trauma patients from 2010 to 2020 who underwent CT chest/abdomen/pelvis was evaluated using an open-source natural language processor to query for hiatal hernias. Patients who underwent subsequent imaging, endoscopy, fluoroscopy, or operation were retrospectively reviewed., Results: 1087(10.6%) of 10 299 patients had incidental hiatal hernias: 812 small (74.7%) and 275 moderate/large (25.3%). 224 (20.7%) had subsequent imaging or endoscopic evaluation. Compared to those with small hernias, patients with moderate/large hernias were older (66.3 ± 19.4 vs 79.6 ± 12.6 years, P < .001) and predominantly female (403[49.6%] vs 199[72.4%], P < .001). Moderate/large hernias were not more likely to grow (small vs moderate/large: 13[7.6%] vs 8[15.1%], P = .102). Patients with moderate/large hernias were more likely to have an intervention or referral (small vs moderate/large: 6[3.5%] vs 7[13.2%], P = .008). No patients underwent elective or emergent hernia repair. Three patients had surgical referral; however, only one was seen by a surgeon. One patient death was associated with a large hiatal hernia., Conclusions: We demonstrate a novel utilization of natural language processing to identify patients with incidental hiatal hernia in a large population, and found a 10.6% incidence with only 1.2%. (13/1087) of these receiving a referral for follow-up. While most incidental hiatal hernias are small, moderate/large and symptomatic hernias have high risk of loss-to-follow-up and need referral pipelines to improve patient outcomes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The Asian American, Native Hawaiian, and Pacific Islander (AANHPI) population is among the fastest-growing population in the USA. However, this is not reflected in scientific research, in which ethnic groups are often combined. We identified trends in treatment and outcomes for pancreatic cancer in a disaggregated AANHPI population. We hypothesize that patients from different AANHPI groups have differences in survival., Patients and Methods: A retrospective analysis of the National Cancer Database between 2010 and 2019 identified patients treated for pancreatic cancer. We identified demographic factors for patients of Caucasian, African American, and disaggregated Asian subpopulations. Survival curves were generated and multivariate analysis was performed to help determine which factors impacted overall survival., Results: A total of 296,448 patients met the inclusion criteria. Of those, 8568 (3%) patients were Asian. Median survival of AANHPI patients was 11.3 months, as compared with Caucasians (8.9 months) and African Americans (8.1 months) (p < 0.0001). Asian Indians had the highest median survival (14.3 months), whereas the Japanese subpopulation had the lowest (7.6 months) (p < 0.0001). There were significant differences in median survival between the different AANHPI subpopulations irrespective of stage. Multivariate analysis demonstrated that belonging to an AANHPI racial/ethnic group, excluding Japanese and Filipino, was associated with decreased risk of overall mortality., Discussion: Significant differences were identified in the overall median survival for patients with pancreatic cancer between AANHPI subpopulations. Disparities in socioeconomic factors may have played a role in overall survival. This study highlights the need to include disaggregated data in future studies to subdue disparities in cancer care for patients., (© 2023. Society of Surgical Oncology.)

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: [details omitted for double-anonymized peer review].

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: One hundred nineteen 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 [Formula: see text] 10 cm. True negatives were defined as intraperitoneal tumors > 10 cm. 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 12 cm 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 recommendation. When the aPR is not identified, MRI-reported tumor distance may be a better predictor of this relationship., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: Abdominal Aortic Aneurysm (AAA) is a highly morbid condition and is the 11th leading cause of death in the United States. Treatment options are limited to operative interventions, with minimal non-operative options. Prior literature has demonstrated a benefit to the use of mesenchymal stem cells (MSCs) in attenuating AAA formation. We demonstrate the utility of MSCs in treating AAA in swine, focusing on the mechanical and structural characteristics of aortic tissue after treatment., Methods: 16 Yorkshire pigs underwent retroperitoneal exposure of the infrarenal aorta, with subsequent induction of AAA with peri-adventitial elastase and collagenase. A 1 × 4 cm piece of Gelfoam, an absorbable gelatin-based hemostatic agent, was soaked in media or human MSCs and placed directly on the vessel for control and experimental animals. At postoperative day 21, animals were sacrificed and the infrarenal aorta at this location was harvested for analysis. Tensile strength was measured using a tensiometer, from which Young's modulus and maximum strain were calculated., Results: All animals survived the surgery and post-operative course. Young's elastic modulus for the aneurysm control group was 15.83 ± 1.61 compared to 22.13 ± 2.34 for the stem cell treated segment, p  = 0.0316. There was no significant difference in the peak stress between groups., Conclusions: This is the first study to demonstrate the mechanical effects of stem cell therapy on a model of AAA in swine. Young's modulus, which characterizes the intrinsic capacity of a tissue to withstand stress, was greater in the animals treated with MSCs compared to control animals with aneurysms. This methodology can be utilized in future large animal models to develop cell and drug-based therapies for AAA., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Adoptive cell therapy (ACT) using tumor-infiltrating lymphocytes (TILs) has been gaining promise as a therapeutic option for metastatic melanoma. By harnessing the power of patients' tumor-resident lymphocytes, TIL therapy has shown promise in delivering durable, complete responses for patients who have progressed with other treatments, including checkpoint inhibition. This form of personalized medicine has traditionally been limited to select academic facilities with the infrastructure and resources to generate TIL cells and care for patients during the treatment phase. In this review, the authors discuss the role of TIL therapy for patients with metastatic melanoma, including the current state of therapeutic options, logistics of TIL harvest and infusion, management of infusion-specific toxicities, and foundational steps for surgeons and oncologists to establish cell-based therapies in individual hospitals and cancer centers., (© 2022. Society of Surgical Oncology.)

Background: 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., Patients and Methods: 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., Results: 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., Conclusions: 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., (© 2022. Society of Surgical Oncology.)

Introduction: 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., Materials and Methods: Twelve Yorkshire pigs received periadventitial injections (collagenase and elastase) into a 4-cm segment of infrarenal aorta. Animals were treated with either 1 × 10 6 MSCs placed onto Gelfoam or treated with media as a control. Aortic diameters were measured at the time of surgery and monitored at postoperative day (POD) 7 and 14 with ultrasound. Animals were sacrificed on POD 21. Aortic tissue was harvested for histopathological analyses and immunohistochemistry. Groups were compared with paired t-tests or Mann-Whitney U-tests., Results: All 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., Conclusions: 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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objectives: During the coronavirus-19 pandemic, experts recommended delaying routine cancer screening and modifying treatment strategies. We sought to understand the sequalae of these recommendations., Materials and Methods: 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., Results: 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]., Conclusions: 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., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: 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., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

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., Competing Interests: Declaration of Interests The authors declare no competing interests., (Published by Elsevier Inc.)

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.

Purpose: Cell death in neurodegeneration occurs at the convergence of diverse metabolic pathways. In the retina, a common underlying mechanism involves mitochondrial dysfunction since photoreceptor homeostasis and survival are highly susceptible to altered aerobic energy metabolism. We sought to develop an assay to directly measure oxygen consumption in intact retina with the goal of identifying alterations in respiration during photoreceptor dysfunction and degeneration., Methods: Circular punches of freshly isolated mouse retina, adjacent to the optic nerve head, were used in the microplate-based Seahorse Extracellular Flux Analyzer to measure oxygen consumption. Tissue integrity was evaluated by propidium iodide staining and live imaging. Different substrates were tested for mitochondrial respiration. Basal and maximal respiration were expressed as oxygen consumption rate (OCR) and respectively measured in Ames' medium before and after the addition of mitochondrial uncoupler, BAM15., Results: We show that glucose is an essential substrate for retinal mitochondria. At baseline, mitochondria respiration in the intact wild-type retina was close to maximal, with limited reserve capacity. Similar OCR and limited mitochondrial reserve capacity was also observed in cone-only Nrl-/- retina. However, the retina of Pde6brd1/rd1, Cep290rd16/rd16 and Rpgrip1-/- mice, all with dysfunctional or no photoreceptors, had reduced OCR and higher mitochondrial reserve capacity., Conclusions: We have optimized a method to directly measure oxygen consumption in acutely isolated, ex vivo mouse retina and demonstrate that photoreceptors have low mitochondrial reserve capacity. Our data provide a plausible explanation for the high vulnerability of photoreceptors to altered energy homeostasis caused by mutations or metabolic challenges.