Sequential emergence and contraction of epithelial subtypes in the prenatal human choroid plexus revealed by a stem cell model.

Despite the major roles of choroid plexus epithelial cells (CPECs) in brain homeostasis and repair, their developmental lineage and diversity remain undefined. In simplified differentiations from human pluripotent stem cells, derived CPECs (dCPECs) displayed canonical properties and dynamic multiciliated phenotypes that interacted with Aß uptake. Single dCPEC transcriptomes over time correlated well with human organoid and fetal CPECs, while pseudotemporal and cell cycle analyses highlighted the direct CPEC origin from neuroepithelial cells. In addition, time series analyses defined metabolic (type 1) and ciliogenic dCPECs (type 2) at early timepoints, followed by type 1 diversification into anabolic-secretory (type 1a) and catabolic-absorptive subtypes (type 1b) as type 2 cells contracted. These temporal patterns were then confirmed in independent derivations and mapped to prenatal stages using human tissues. In addition to defining the prenatal lineage of human CPECs, these findings suggest new dynamic models of ChP support for the developing human brain.

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.

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.

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.

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.

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.

An augmented reality and high-speed optical tracking system for laparoscopic surgery.

While minimally invasive laparoscopic surgery can help reduce blood loss, reduce hospital time, and shorten recovery time compared to open surgery, it has the disadvantages of limited field of view and difficulty in locating subsurface targets. Our proposed solution applies an augmented reality (AR) system to overlay pre-operative images, such as those from magnetic resonance imaging (MRI), onto the target organ in the user's real-world environment. Our system can provide critical information regarding the location of subsurface lesions to guide surgical procedures in real time. An infrared motion tracking camera system was employed to obtain real-time position data of the patient and surgical instruments. To perform hologram registration, fiducial markers were used to track and map virtual coordinates to the real world. In this study, phantom models of each organ were constructed to test the reliability and accuracy of the AR-guided laparoscopic system. Root mean square error (RMSE) was used to evaluate the targeting accuracy of the laparoscopic interventional procedure. Our results demonstrated a registration error of 2.42 ± 0.79 mm and a procedural targeting error of 4.17 ± 1.63 mm using our AR-guided laparoscopic system that will be further refined for potential clinical procedures.

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.

Prospective Randomized Trial of Single-Use vs Reusable Cystoscope for Ureteral Stent Removal.

Background: Reusable cystoscopes are associated with risks of cross-contamination, need for chemical reprocessing, mechanical breakdown, maintenance costs, and labor for cleaning. A sterile, single-use cystoscope may reduce or eliminate the source of these infections while also decreasing exposure to reprocessing chemical agents. In this multicenter, randomized trial, we sought to compare single use with reusable endoscopes for ureteral stent removal. Methods: A three-center, randomized, dual-arm postmarket clinical trial was performed to compare the single-use cystoscope (Ambu A/S) with standard-of-care flexible reusable cystoscopes for outpatient ureteral stent removal. A total of 102 patients were randomized and evaluated from baseline through day 10 postprocedure. Primary endpoint was successful stent removal. Secondary endpoints were time from preparation to disposal/reprocessing, adverse events (AEs), and clinician satisfaction. Results: A total of 102 subjects were randomized in a 1:1 manner. The successful stent removal rate was 51/51 (reusable) and 50/51 (single use). One patient required the conversion to reusable cystoscope owing to grasper passage issue. Median time from prep for the procedure to disposal/prep for reprocessing was 10.2 minutes for the single use and 18.4 minutes for the reusable (p < 0.001). There was no difference in clinician satisfaction between both arms. There was no difference in AEs between arms and no device causal attribution for any AE reports. There was one serious AE necessitating hospitalization for infection in the reusable arm. Conclusion: The randomized-controlled trial of single-use cystoscopes vs reusables showed comparable device success with significant time savings for single use and equivalent clinician satisfaction. The study was registered on clinicaltrials.gov database (NCT04829461) on April 2, 2021.

Toll-Like Receptor 4 Induction During Renal Ischemia Correlates with Serum Creatinine in a Pig Model.

Objectives: To determine whether toll-like receptor 4 (TLR4), a mediator of organ ischemia-reperfusion injury, is overexpressed during warm ischemia in a porcine solitary kidney model, and whether its expression correlates with creatinine, a surrogate for kidney function. Materials and Methods: Eight adult Yorkshire pigs underwent initial laparoscopic nephrectomy. After 1 week, animals were randomized into two groups: group 1 underwent laparoscopic renal hilar dissection, renal ischemia by cross-clamping, and reperfusion (ischemia group); group 2 underwent laparoscopic renal hilar dissection alone (sham group). Animals were survived to day 7 postrandomization. Peripheral blood was sampled for serum creatinine (sCr) and TLR4 expression at the following time points or corresponding intervals: prenephrectomy, 1-week postnephrectomy (preischemia), after 90 minutes of ischemia, 30 minutes postreperfusion, and at sacrifice. Intragroup TLR4 expression changes were analyzed using repeated measures ANOVA. Intergroup TLR4 expression was compared using Mann-Whitney's test. Correlation between sCr and TLR4 was assessed using Spearman's test. Results: Seven animals completed the experiment (four ischemia and three sham). Relative TLR4 expression significantly increased from baseline levels during ischemia, reperfusion, and sacrifice time points only in the ischemia group, and was significantly higher for the ischemia group after 90 minutes of ischemia (p = 0.034). sCr was significantly higher for the ischemia group during the reperfusion phase (p = 0.048). Relative TLR4 expression level significantly correlated with sCr in the overall cohort (Spearman's rho = 0.69) and in the ischemia group (Spearman's rho = 0.82; p < 0.0001 for each). Conclusions: Warm ischemia in a porcine solitary kidney induces acute overexpression of TLR4 in peripheral blood leukocytes, which is detectable. Relative TLR4 expression level strongly correlated with sCr but had an observable change sooner than change in sCr. Pending further investigation, TLR4 overexpression during renal ischemia may represent a sensitive quantitative marker of unilateral renal injury sustained during nephron-sparing surgery.

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.

A Novel Technique of Robotic-Assisted Simple Cystectomy During Urinary Diversion for Benign Indications.

BACKGROUND: When urinary diversion is necessary for benign indications, the defunctionalized bladder is at risk of a number of severe complications such as bleeding, pain, pyocystis and secondary urothelial carcinoma. These complications occur in 54%-80% of patients left with native bladder after diversion, and these patients go on to require completion cystectomy 20%-25% of the time. Rowley et al. at the University of Michigan reported their experience in open simple cystectomy in 2011 in a series of 23 patients. This operation, to our knowledge, has not been previously adapted to the robotic platform despite the growing prevalence of robotic surgery including for complex reconstruction and urinary diversion. Here we report our novel adapted technique of performing robotic simple cystectomy in 2 index patients. OBJECTIVE: To visually demonstrate and report our technique of simple cystectomy, utilizing the robotic platform, including outcomes in 2 index patients. METHODS: Two index patients are presented, including outcomes: One female with spinal cord injury, smoking and chronic infections in the setting of suprapubic catheter diversion, and one male with multiply failed local treatments including radiation and cryotherapy for prostate cancer that have resulted in chronic fistula, prior Fournier's gangrene, and sympheseal osteomyelitis. RESULTS: he operations were completed without difficulty, in an expedient fashion (35-48 minutes) and without significant blood loss (10cc or less). The technique is illustrated in the accompanying video. CONCLUSION: This novel adapted robotically-assisted operation appears to be a rapid and reproducible operation that recapitulates the principles of open surgery with little time or blood loss, thus avoiding the morbidity of radical cystectomy or of delayed secondary operations, while at the same time providing all the benefits inherent to a robotic operation. Outcomes appear excellent. Further study is needed.

Alkali Citrate Content of Common Over-the-Counter and Medical Food Supplements.

Objective: Potassium citrate effectively decreases kidney stone recurrence, but it is costly and associated with side effects. While several over-the-counter supplements and medical foods purport to provide sufficient citrate to prevent recurrent stones, corroborating data on their actual citrate content is limited. Materials and Methods: Nine common nonprescription products were purchased online. Reported citrate content was obtained from packaging, promotional materials, or ingredient labels. Using a single serving of each product, actual citrate, sodium, potassium, calcium, magnesium, and oxalate content was measured using spectrophotometry and chromatography. Total alkali citrate, cost, and amounts of each component per 10 mEq of alkali citrate were also calculated. Results: Nearly all products contained more citrate than advertised, except for Litholyte® powder, Litholyte® Coffee, and Horbäach® potassium citrate. Per serving, Moonstone® powder, LithoBalance™, and KSP tabs™ contained the most citrate (means of 63.9, 33.5, and 26.9 mEq, respectively). Moonstone and LithoBalance had the greatest discrepancy between total citrate and alkali citrate (15.7 and 11.8 mEq per serving, respectively). NOW® potassium citrate was least expensive ($0.04/10 mEq alkali citrate). KSP tabs delivered the most daily sodium (mean 158 mg/10 mEq alkali citrate, Litholyte Coffee provided the most potassium (mean of 13 mEq/10 mEq alkali citrate), and Kidney COP® provided the most calcium (mean 147 mg/10 mEq alkali citrate). Conclusion: Some common over-the-counter products contain sufficient alkali to potentially promote a citraturic response; Moonstone provides the most alkali citrate, but at a higher cost than other products. Sodium, potassium, and calcium from these products must also be considered in daily consumption.

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.

Single-port robotic-assisted simple prostatectomy is associated with decreased post-operative narcotic use in a propensity score matched analysis.

Robotic-assisted simple prostatectomy (RASP) has proven to be an effective minimally invasive option for benign prostatic enlargement (BPE) in recent years. Single-site surgery is theorized to reduce post-operative pain beyond traditional minimally invasive approaches. We sought to assess whether use of a single-port robotic platform decreases post-operative opioid use in patients undergoing robotic-assisted simple prostatectomy (RASP). A retrospective review was performed of all patients undergoing RASP our institution from November 2017 to July 2019. Demographic, intraoperative, and post-operative data, including morphine equivalent (ME) use, were collected. Patients were stratified by robotic platform utilized. Propensity score matching using nearest neighbor method was performed using prostate volume, Charlson comorbidity index (CCI), and post-op ketorolac use in 4:1 fashion. Chi-squared analysis and Kruskal-Wallis analyses were utilized. Two-hundred-and-seven men underwent RASP. After matching, 80 patients (64 multi-port, 16 single-port) were included in the analysis. Groups were comparable for age, body mass index, CCI, prostate volume, prior opioid use, and use of scheduled ketorolac post op. The single-port approach was associated with a reduction in MEs once admitted to the floor (5 vs. 11 mg, p = 0.025) and an increase in the proportion of patients who did not require any narcotics post-operatively (44 vs. 19%, p = 0.036). In a propensity matched cohort of patients undergoing RASP at a single institution, use of the single-port robotic system conferred a significant decrease in post-operative narcotic use by approximately 50%.