A cardiac microRNA governs systemic energy homeostasis by regulation of MED13.

Obesity, type 2 diabetes, and heart failure are associated with aberrant cardiac metabolism. We show that the heart regulates systemic energy homeostasis via MED13, a subunit of the Mediator complex, which controls transcription by thyroid hormone and other nuclear hormone receptors. MED13, in turn, is negatively regulated by a heart-specific microRNA, miR-208a. Cardiac-specific overexpression of MED13 or pharmacologic inhibition of miR-208a in mice confers resistance to high-fat diet-induced obesity and improves systemic insulin sensitivity and glucose tolerance. Conversely, genetic deletion of MED13 specifically in cardiomyocytes enhances obesity in response to high-fat diet and exacerbates metabolic syndrome. The metabolic actions of MED13 result from increased energy expenditure and regulation of numerous genes involved in energy balance in the heart. These findings reveal a role of the heart in systemic metabolic control and point to MED13 and miR-208a as potential therapeutic targets for metabolic disorders.

Percutaneous management of ureteropelvic junction obstruction.

PURPOSE OF REVIEW: The development of endoscopic and minimally invasive techniques has revolutionized the treatment of ureteropelvic junction obstruction (UPJO). Patients can now undergo successful UPJO repair without the morbidity and complications associated with open surgery. Laparoscopic and robotic repair has supplanted open surgery as the gold standard, but percutaneous endoscopic treatment remains a relevant alternative to more invasive surgery. This review will focus on the percutaneous approach for the treatment of UPJO. RECENT FINDINGS: Percutaneous endopyelotomy was popularized during the 1980 s due to advances in the field of endourology, allowing for well tolerated and reliable percutaneous access to the kidney. After percutaneous access to the kidney is achieved, the narrowed ureter at the UPJ is incised in a full thickness fashion in the posterolateral position from the ureteral lumen to the periureteral fat. Success rates for this procedure are nearly 90% at high-volume centres. The ideal patient who has success with percutaneous endopyelotomy has a short segment of narrowing less than 2 cm, no crossing vessel, good ipsilateral renal function and mild hydronephrosis. SUMMARY: Although the development of laparoscopic and robotic approaches to pyeloplasty has produced outcomes that surpass those of percutaneous endopyelotomy, it remains a viable option in the appropriately selected patient, but success rates tend to decrease with longer follow up.

Catabolism of the Lipofuscin Cycloretinal by MsP1.

Age-related macular degeneration (AMD) is a debilitating eye disease that tends to affect people over the age of 55. Lipofuscins are autofluorescent, toxic byproducts of the visual cycle thought to contribute toward the progression of the disease. Targeting the accumulation of lipofuscin through catabolism may serve as a method for the early treatment of AMD. Thus, an enzymatic approach capable of degrading lipofuscin, cycloretinal (all-trans retinal dimer), was examined. A peroxidase from the organism Marasmius scorodonius (MsP1) has shown capability of degrading this toxic metabolite into nontoxic byproducts. A catalytic triad within MsP1 (D228, H365, and R388) was identified through multiple-sequence alignment and homology modeling and confirmed by kinetic analysis. MsP1-associated cleavage products were detected by gas chromatography-mass spectrometry (GC-MS), high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), and liquid chromatography-tandem mass spectrometry (LC-MSMS). MsP1 degradation byproducts of cycloretinal show reduced cytotoxicity within cell culture (ARPE-19), demonstrating its potential as a gene therapeutic to alleviate the buildup of lipofuscin within AMD.

Efficacy of Intramuscular Ketorolac for Preventing Renal Colic Post Stent Removal: Randomized Controlled Trial.

PURPOSE: The treatment of stones ureteroscopically is associated with postoperative pain, thought to be due largely to the use of ureteral stents. In some, stent removal precipitates renal colic that can last from minutes to hours. We sought to determine if intramuscular ketorolac could reduce post-stent removal renal colic. MATERIALS AND METHODS: We performed a prospective, randomized, double-blind, placebo-controlled trial assessing the effects of ketorolac administered at time of stent removal. Patients were randomized to receive an intramuscular ketorolac 30 mg or placebo immediately prior to stent removal. Patients were contacted 1 and 7 days after stent removal to assess pain, need for opioids, emergency department or clinic visits and the need for surgical/medical interventions. RESULTS: A total of 124 patients (62 patients each in the control and treatment groups) were included in the study. The groups were comparable in demographic/operative characteristics. No difference in mean pain scores or proportion of patients who experienced severe pain at 1 and 7 days post stent removal was detected between groups. However, use of ketorolac resulted in significantly fewer renal colic-related unplanned emergency department/clinic visits in the treatment group (2%) compared with the control group (13%, p=0.032). CONCLUSIONS: Although administration of ketorolac prior to stent removal does not significantly reduce overall subjective pain experienced post stent removal compared to placebo, it does reduce the likelihood of severe renal colic requiring emergency department or office visits. Eligible patients may benefit from routine use of ketorolac injection at the time of stent removal.

Artificial intelligence in endourology: emerging technology for individualized care.

PURPOSE OF REVIEW: Artificial intelligence in medicine has allowed for efficient processing of large datasets to perform cognitive tasks that facilitate clinical decision-making, and it is an emerging area of research. This review aims to highlight the most pertinent and recent research in artificial intelligence in endourology, where it has been used to optimize stone diagnosis, support decision-making regarding management, predict stone recurrence, and provide new tools for bioinformatics research within endourology. RECENT FINDINGS: Artificial neural networks (ANN) and machine learning approaches have demonstrated high accuracy in predicting stone diagnoses, stone composition, and outcomes of spontaneous stone passage, shockwave lithotripsy (SWL), or percutaneous nephrolithotomy (PCNL); some of these models outperform more traditional predictive models and existing nomograms. In addition, these approaches have been used to predict stone recurrence, quality of life scores, and provide novel methods of mining the electronic medical record for research. SUMMARY: Artificial intelligence can be used to enhance existing approaches to stone diagnosis, management, and prevention to provide a more individualized approach to endourologic care. Moreover, it may support an emerging area of bioinformatics research within endourology. However, despite high accuracy, many of the published algorithms lack external validity and require further study before they are more widely adopted.

Prospective performance of clear cell likelihood scores (ccLS) in renal masses evaluated with multiparametric magnetic resonance imaging.

OBJECTIVES: Solid renal masses have unknown malignant potential with commonly utilized imaging. Biopsy can offer a diagnosis of cancer but has a high non-diagnostic rate and complications. Reported use of multiparametric magnetic resonance imaging (mpMRI) to diagnose aggressive histology (i.e., clear cell renal cell carcinoma (ccRCC)) via a clear cell likelihood score (ccLS) was based on retrospective review of cT1a tumors. We aim to retrospectively assess the diagnostic performance of ccLS prospectively assigned to renal masses of all stages evaluated with mpMRI prior to histopathologic evaluation. METHODS: In this retrospective cohort study from June 2016 to November 2019, 434 patients with 454 renal masses from 2 institutions with heterogenous patient populations underwent mpMRI with prospective ccLS assignment and had pathologic diagnosis. ccLS performance was assessed by contingency table analysis. The association between ccLS and ccRCC was assessed with logistic regression. RESULTS: Mean age and tumor size were 60 ± 13 years and 5.4 ± 3.8 cm. Characteristics were similar between institutions except for patient age and race (both p < 0.001) and lesion laterality and histology (both p = 0.04). The PPV of ccLS increased with each increment in ccLS (ccLS1 5% [3/55], ccLS2 6% [3/47], ccLS3 35% [20/57], ccLS4 78% [85/109], ccLS5 93% [173/186]). Pooled analysis for ccRCC diagnosis revealed sensitivity 91% (258/284), PPV 87% (258/295) for ccLS ≥ 4, and specificity 56% (96/170), NPV 94% (96/102) for ccLS ≤ 2. Diagnostic performance was similar between institutions. CONCLUSIONS: We confirm the optimal diagnostic performance of mpMRI to identify ccRCC in all clinical stages. High PPV and NPV of ccLS can help inform clinical management decision-making. KEY POINTS: • The positive predictive value of the clear cell likelihood score (ccLS) for detecting clear cell renal cell carcinoma was 5% (ccLS1), 6% (ccLS2), 35% (ccLS3), 78% (ccLS4), and 93% (ccLS5). Sensitivity of ccLS ≥ 4 and specificity of ccLS ≤ 2 were 91% and 56%, respectively. • When controlling for confounding variables, ccLS is an independent risk factor for identifying clear cell renal cell carcinoma. • Utilization of the ccLS can help guide clinical care, including the decision for renal mass biopsy, reducing the morbidity and risk to patients.

Clinical and radiographic outcomes following salvage intervention for ureteropelvic junction obstruction.

PURPOSE: We aimed to assess failure rates of salvage interventions and changes in split kidney function (SKF) following failed primary repair of ureteropelvic junction obstruction (UPJO). MATERIALS AND METHODS: A retrospective review of adult patients at an academic medical center who underwent salvage intervention following primary treatment for UPJO was performed. Symptomatic failure was defined as significant flank pain. Radiographic failure was defined as no improvement in drainage or a decrease in SKF by ≥7%. Overall failure, the primary outcome, was defined as symptomatic failure, radiographic failure, or both. RESULTS: Between 2008-2017, 34 patients (median age 38 years, 50% men) met study criteria. UPJO management was primary pyeloplasty/secondary endopyelotomy for 21/34 (62%), primary pyeloplasty/secondary pyeloplasty for 6/34 (18%), and primary endopyelotomy/secondary pyeloplasty for 7/34 (21%). Median follow-up was 3.3 years following secondary intervention. Patients undergoing primary pyeloplasty/secondary endopyelotomy had significantly higher overall failure than those undergoing primary pyeloplasty/secondary pyeloplasty (16/21 [76%] vs. 1/6 [17%], p=0.015). Among patients undergoing secondary endopyelotomy, presence of a stricture on retrograde pyelogram, stricture length, and SKF were not associated with symptomatic, radiographic, or overall failure. Serial renography was performed for 28/34 (82%) patients and 2/28 (7%) had a significant decline in SKF. CONCLUSIONS: Following failed primary pyeloplasty, secondary endopyelotomy had a greater overall failure rate than secondary pyeloplasty. No radiographic features assessed were associated with secondary endopyelotomy failure. Secondary intervention overall failure rates were higher than reported in the literature. Unique to this study, serial renography demonstrated that significant functional loss was overall infrequent.

Ten-Year Outcomes of Renal Tumor Radio Frequency Ablation.

PURPOSE: We reviewed long-term oncologic outcomes in patients with renal tumors treated with radio frequency ablation more than 10 years ago. MATERIALS AND METHODS: We retrospectively reviewed the records of patients with renal tumors who underwent radio frequency ablation from November 2000 to August 2007. Demographic, clinical and radiological data were assessed to determine evidence of disease recurrence. Patients with familial renal cell carcinoma syndromes were excluded from study. We calculated disease-free, metastasis-free, cancer specific and overall survival with the Kaplan-Meier method. Subgroup analysis of patients who had at least 10 years followup was performed to determine actual 10-year survival. Analysis was also performed based on tumor size. RESULTS: A total of 112 tumors in 106 patients were treated with radio frequency ablation. Median followup was 79 months (IQR 28.9-121.1) and mean ± SD tumor size was 2.5 ± 0.8 cm. Initial technical success was achieved in 97% of cases. There were 10 recurrences. Kaplan-Meier 6-year disease-free and cancer specific survival rates were 89% and 96%, respectively. Disease-free survival decreased to 68% for tumors greater than 3 cm. In the subgroup with at least 10-year followup the actual disease-free, cancer specific and overall survival rates were 82%, 94% and 49%, respectively. No patient experienced recurrence after 5 years. CONCLUSIONS: Radio frequency ablation is a safe and effective treatment option for small renal masses less than 3 cm in diameter. We report good oncologic outcomes with actual 10-year survival data. No recurrence developed after 5 years. Tumors greater than 3 cm have significantly poorer outcomes.

Current opinion in urology 2017: focal therapy of small renal lesions.

PURPOSE OF REVIEW: With the increasing incidence of small renal masses (SRMs), ablative technologies are becoming more commonly utilized. With any nascent treatment modality, outcomes literature needs to be constantly re-evaluated. The purpose of this review is to revisit the most updated literature regarding the safety and efficacy of ablative treatments of renal lesions. RECENT FINDINGS: Recent literature demonstrates that small renal tumor ablation is safe and effective. Although it does not have the same oncological efficacy of surgical extirpation, local recurrence-free survival has consistently shown to be around 90%. Cryoablation and radiofrequency ablation have longer-term data demonstrating durable responses. Microwave ablation and irreversible electroporation are promising modalities with longer-term data coming. Complication rates and procedural morbidity of ablation are consistently lower than for partial nephrectomy. SUMMARY: Image-guided focal ablation is a valuable tool in the management of SRMs. Although it does not have the same efficacy of surgical extirpation, with the ability to perform repeat procedures and salvage surgery if necessary, oncologic outcomes are comparable to those of upfront surgery. Ultimately, longer-term studies and prospective trials are needed to further elucidate these modalities.

Drivers of redistribution of fishing and non-fishing effort after the implementation of a marine protected area network.

Marine spatial planning (MSP) is increasingly utilized to sustainably manage ocean uses. Marine protected areas (MPAs), a form of spatial management in which parts of the ocean are regulated to fishing, are now a common tool in MSP for conserving marine biodiversity and managing fisheries. However, the use of MPAs in MSP often neglects, or simplifies, the redistribution of fishing and non-fishing activities inside and outside of MPAs following their implementation. This redistribution of effort can have important implications for effective MSP. Using long-term (14 yr) aerial surveys of boats at the California Channel Islands, we examined the spatial redistribution of fishing and non-fishing activities and their drivers following MPA establishment. Our data represent 6 yr of information before the implementation of an MPA network and 8 yr after implementation. Different types of boats responded in different ways to the closures, ranging from behaviors by commercial dive boats that support the hypothesis of fishing-the-line, to behaviors by urchin, sport fishing, and recreational boats that support the theory of ideal free distribution. Additionally, we found that boats engaged in recreational activities targeted areas that are sheltered from large waves and located near their home ports, while boats engaged in fishing activities also avoided high wave areas but were not constrained by the distance to their home ports. We did not observe the expected pattern of effort concentration near MPA borders for some boat types; this can be explained by the habitat preference of certain activities (for some activities, the desired habitat attributes are not inside the MPAs), species' biology (species such as urchins where the MPA benefit would likely come from larval export rather than adult spillover), or policy-infraction avoidance. The diversity of boat responses reveals variance from the usual simplified assumption that all extractive boats respond similarly to MPA establishment. Our work is the first empirical study to analyze the response of both commercial and recreational boats to closure. Our results will inform MSP in better accounting for effort redistribution by ocean users in response to the implementation of MPAs and other closures.

Regulation of neonatal and adult mammalian heart regeneration by the miR-15 family.

We recently identified a brief time period during postnatal development when the mammalian heart retains significant regenerative potential after amputation of the ventricular apex. However, one major unresolved question is whether the neonatal mouse heart can also regenerate in response to myocardial ischemia, the most common antecedent of heart failure in humans. Here, we induced ischemic myocardial infarction (MI) in 1-d-old mice and found that this results in extensive myocardial necrosis and systolic dysfunction. Remarkably, the neonatal heart mounted a robust regenerative response, through proliferation of preexisting cardiomyocytes, resulting in full functional recovery within 21 d. Moreover, we show that the miR-15 family of microRNAs modulates neonatal heart regeneration through inhibition of postnatal cardiomyocyte proliferation. Finally, we demonstrate that inhibition of the miR-15 family from an early postnatal age until adulthood increases myocyte proliferation in the adult heart and improves left ventricular systolic function after adult MI. We conclude that the neonatal mammalian heart can regenerate after myocardial infarction through proliferation of preexisting cardiomyocytes and that the miR-15 family contributes to postnatal loss of cardiac regenerative capacity.

A dual-camera hyperspectral laparoscopic imaging system.

Minimally invasive surgery (MIS) has expanded broadly in the field of abdominal and pelvic surgery. However, there are still prevalent issues surrounding intracorporeal surgery, such as iatrogenic injury, anastomotic leakage, or the presence of positive tumor margins after resection. Current approaches to address these issues and advance laparoscopic imaging techniques often involve fluorescence imaging agents, such as indocyanine green (ICG), to improve visualization, but these have drawbacks. Hyperspectral imaging (HSI) is an emerging optical imaging modality that takes advantage of spectral characteristics of different tissues. Various applications include tissue classification and digital pathology. In this study, we developed a dual-camera system for high-speed hyperspectral imaging. This includes the development of a custom application interface and corresponding hardware setup. Characterization of the system was performed, including spectral accuracy and spatial resolution, showing little sacrifice in speed for the approximate doubling of the covered spectral range, with our system acquiring 29 spectral images from 460-850 nm. Reference color tiles with various reflectance profiles were imaged and a RMSE of 3.56 ± 1.36% was achieved. Sub-millimeter resolution was shown at 7 cm working distance for both hyperspectral cameras. Finally, we image ex vivo tissues, including porcine stomach, liver, intestine, and kidney with our system and use a high-resolution, radiometrically calibrated spectrometer for comparison and evaluation of spectral fidelity. The dual-camera hyperspectral laparoscopic imaging system can have immediate applications in various surgeries.

Feature Extraction of Ultrasound Radiofrequency Data for the Classification of the Peripheral Zone of Human Prostate.

Prostate cancer ranks among the most prevalent types of cancer in males, prompting a demand for early detection and noninvasive diagnostic techniques. This paper explores the potential of ultrasound radiofrequency (RF) data to study different anatomic zones of the prostate. The study leverages RF data's capacity to capture nuanced acoustic information from clinical transducers. The research focuses on the peripheral zone due to its high susceptibility to cancer. The feasibility of utilizing RF data for classification is evaluated using ex-vivo whole prostate specimens from human patients. Ultrasound data, acquired using a phased array transducer, is processed, and correlated with B-mode images. A range filter is applied to highlight the peripheral zone's distinct features, observed in both RF data and 3D plots. Radiomic features were extracted from RF data to enhance tissue characterization and segmentation. The study demonstrated RF data's ability to differentiate tissue structures and emphasizes its potential for prostate tissue classification, addressing the current limitations of ultrasound imaging for prostate management. These findings advocate for the integration of RF data into ultrasound diagnostics, potentially transforming prostate cancer diagnosis and management in the future.

Dense surface reconstruction using a learning-based monocular vSLAM model for laparoscopic surgery.

Augmented reality (AR) has seen increased interest and attention for its application in surgical procedures. AR-guided surgical systems can overlay segmented anatomy from pre-operative imaging onto the user's environment to delineate hard-to-see structures and subsurface lesions intraoperatively. While previous works have utilized pre-operative imaging such as computed tomography or magnetic resonance images, registration methods still lack the ability to accurately register deformable anatomical structures without fiducial markers across modalities and dimensionalities. This is especially true of minimally invasive abdominal surgical techniques, which often employ a monocular laparoscope, due to inherent limitations. Surgical scene reconstruction is a critical component towards accurate registrations needed for AR-guided surgery and other downstream AR applications such as remote assistance or surgical simulation. In this work, we utilize a state-of-the-art (SOTA) deep-learning-based visual simultaneous localization and mapping (vSLAM) algorithm to generate a dense 3D reconstruction with camera pose estimations and depth maps from video obtained with a monocular laparoscope. The proposed method can robustly reconstruct surgical scenes using real-time data and provide camera pose estimations without stereo or additional sensors, which increases its usability and is less intrusive. We also demonstrate a framework to evaluate current vSLAM algorithms on non-Lambertian, low-texture surfaces and explore using its outputs on downstream tasks. We expect these evaluation methods can be utilized for the continual refinement of newer algorithms for AR-guided surgery.

Study protocol of a systematic review and metaanalysis of stress and burnout among general surgery residents.

Introduction: Chronic workplace stress and burnout are impediments to physicians' professional fulfillment, healthcare organizations' efficiency, and patient care quality/safety. General surgery residents are especially at risk due to the complexity of their training. We report the protocol of a metaanalysis of chronic stress and burnout among Accreditation Council for Graduate Medical Education (ACGME)-affiliated general surgery residents in the era after duty-hour reforms, plus downstream effects on their health and clinical performance. Methods: The proposed systematic review and metaanalysis (PROSPERO registration CRD42021277626) will synthesize/pool data from studies of chronic stress and burnout among general surgery residents at ACGME-affiliated programs. The timeframe under review is subdivided into three intervals: (a) after the 2003 duty-hour restrictions but before 2011 reforms, (b) after the 2011 reforms but before the coronavirus pandemic, and (c) the first 3 years after the pandemic's outbreak. Only studies reporting outcomes based on validated instruments will be included. Qualitative studies, commentaries/editorials, narrative reviews, and studies not published in English will be excluded. Multivariable analyses will adjust for sample characteristics and the methodological quality of included studies. Conclusions: The metaanalysis will yield evidence reflecting experiences of North American-based general surgery residents in the years after ACGME-mandated duty-hour restructuring.

Visualization of Optic Nerve Structural Patterns in Papilledema Using Deep Learning Variational Autoencoders.

Purpose: To visualize and quantify structural patterns of optic nerve edema encountered in papilledema during treatment. Methods: A novel bi-channel deep-learning variational autoencoder (biVAE) model was trained using 1498 optical coherence tomography (OCT) scans of 125 subjects over time from the Idiopathic Intracranial Hypertension Treatment Trial (IIHTT) and 791 OCT scans of 96 control subjects from the University of Iowa. An independent test dataset of 70 eyes from 70 papilledema subjects was used to evaluate the ability of the biVAE model to quantify and reconstruct the papilledema spatial patterns from input OCT scans using only two variables. Results: The montage color maps of the retinal nerve fiber layer (RNFL) and total retinal thickness (TRT) produced by the biVAE model provided an organized visualization of the variety of morphological patterns of optic disc edema (including differing patterns at similar thickness levels). Treatment effects of acetazolamide versus placebo in the IIHTT were also demonstrated in the latent space. In image reconstruction, the mean signed peripapillary retinal nerve fiber layer thickness (pRNFLT) difference ± SD was -0.12 ± 17.34 µm, the absolute pRNFLT difference was 13.68 ± 10.65 µm, and the RNFL structural similarity index reached 0.91 ± 0.05. Conclusions: A wide array of structural patterns of papilledema, integrating the magnitude of disc edema with underlying disc and retinal morphology, can be quantified by just two latent variables. Translational Relevance: A biVAE model encodes structural patterns, as well as the correlation between channels, and may be applied to visualize individuals or populations with papilledema throughout treatment.

Hybrid deep learning and optimal graph search method for optical coherence tomography layer segmentation in diseases affecting the optic nerve.

Accurate segmentation of retinal layers in optical coherence tomography (OCT) images is critical for assessing diseases that affect the optic nerve, but existing automated algorithms often fail when pathology causes irregular layer topology, such as extreme thinning of the ganglion cell-inner plexiform layer (GCIPL). Deep LOGISMOS, a hybrid approach that combines the strengths of deep learning and 3D graph search to overcome their limitations, was developed to improve the accuracy, robustness and generalizability of retinal layer segmentation. The method was trained on 124 OCT volumes from both eyes of 31 non-arteritic anterior ischemic optic neuropathy (NAION) patients and tested on three cross-sectional datasets with available reference tracings: Test-NAION (40 volumes from both eyes of 20 NAION subjects), Test-G (29 volumes from 29 glaucoma subjects/eyes), and Test-JHU (35 volumes from 21 multiple sclerosis and 14 control subjects/eyes) and one longitudinal dataset without reference tracings: Test-G-L (155 volumes from 15 glaucoma patients/eyes). In the three test datasets with reference tracings (Test-NAION, Test-G, and Test-JHU), Deep LOGISMOS achieved very high Dice similarity coefficients (%) on GCIPL: 89.97±3.59, 90.63±2.56, and 94.06±1.76, respectively. In the same context, Deep LOGISMOS outperformed the Iowa reference algorithms by improving the Dice score by 17.5, 5.4, and 7.5, and also surpassed the deep learning framework nnU-Net with improvements of 4.4, 3.7, and 1.0. For the 15 severe glaucoma eyes with marked GCIPL thinning (Test-G-L), it demonstrated reliable regional GCIPL thickness measurement over five years. The proposed Deep LOGISMOS approach has potential to enhance precise quantification of retinal structures, aiding diagnosis and treatment management of optic nerve diseases.