ABSTRACT
Topological materials with boundary (surface/edge/hinge) states have attracted tremendous research interest. Additionally, unconventional (obstructed atomic) materials have recently drawn lots of attention owing to their obstructed boundary states. Experimentally, Josephson junctions (JJs) constructed on materials with boundary states produce the peculiar boundary supercurrent, which was utilized as a powerful diagnostic approach. Here, we report the observations of boundary supercurrent in NiTe2-based JJs. Particularly, applying an in-plane magnetic field along the Josephson current can rapidly suppress the bulk supercurrent and retain the nearly pure boundary supercurrent, namely the magnetic field filtering of supercurrent. Further systematic comparative analysis and theoretical calculations demonstrate the existence of unconventional nature and obstructed hinge states in NiTe2, which could produce hinge supercurrent that accounts for the observation. Our results reveal the probable hinge states in unconventional metal NiTe2, and demonstrate in-plane magnetic field as an efficient method to filter out the bulk contributions and thereby to highlight the hinge states hidden in topological/unconventional materials.
ABSTRACT
Background: Osteoarthritis (OA) is the most common age-related musculoskeletal disease. However, there is still a lack of therapy that can modify OA progression due to the complex pathogenic mechanisms. The aim of the study was to explore the role and mechanism of XJB-5-131 inhibiting chondrocytes ferroptosis to alleviate OA progression. Methods: We treated tert-butyl hydroperoxide (TBHP)-induced ferroptosis of mouse primary chondrocytes with XJB-5-131 in vitro. The intracellular ferroptotic hallmarks, cartilage anabolic and catabolic markers, ferroptosis regulatory genes and proteins were detected. Then we established a mouse OA model via destabilization of the medial meniscus (DMM) surgery. The OA mice were treated with intra-articular injection of XJB-5-131 regularly (2 µM, 3 times per week). After 4 and 8 weeks, we performed micro-CT and histological examination to evaluate the protection role of XJB-5-131 in mouse OA subjects. RNA sequencing analysis was performed to unveil the key downstream gene of XJB-5-131 exerting the anti-ferroptotic effect in OA. Results: XJB-5-131 significantly suppressed TBHP-induced increases of ferroptotic hallmarks (ROS, lipid peroxidation, and Fe2+ accumulation), ferroptotic drivers (Ptgs2, Pgd, Tfrc, Atf3, Cdo1), while restored the expression of ferroptotic suppressors (Gpx4, Fth1). XJB-5-131 evidently promoted the expression of cartilage anabolic and decreased the expression of cartilage catabolic markers. Moreover, intra-articular injection of XJB-5-131 significantly inhibited the expression of Cox2 and Mmp13, while promoted the expression of Col2a1, Gpx4 and Fth1 in DMM-induced mouse articular cartilage. Further, we identified Pebp1 as a potential target of XJB-5-131 by RNA sequencing analysis. The anti-ferroptosis and chondroprotective effects of XJB-5-131 were significantly diminished by Locostatin, a specific antagonist of Pebp1. Conclusion: XJB-5-131 significantly protects chondrocytes from ferroptosis in TBHP-induced mouse primary chondrocytes and DMM surgery-induced OA mice model via restoring the expression of Pebp1. XJB-5-131 is a potential therapeutic drug in the management of OA progression.
ABSTRACT
Transient receptor potential vanilloid family member 1 (TRPV1) has been revealed as a therapeutic target of osteoarthritis (OA), the most common deteriorating whole joint disease, by impeding macrophagic inflammation and chondrocytes ferroptosis. However, the clinical application for capsaicin as the TRPV1 agonist is largely limited by its chronic toxicity. To address this issue, we developed a bifunctional controllable magnetothermal switch targeting TRPV1 for the alleviation of OA progression by coupling of magnetic nanoparticles (MNPs) to TRPV1 monoclonal antibodies (MNPs-TRPV1). Under the alternating magnetic field (AMF) stimulation, MNPs-TRPV1 locally dissipated heat, which was sufficient to trigger the opening and activation of TRPV1, and effectively impeded macrophagic inflammation and chondrocyte ferroptosis. This magnetothermal modulation of TRPV1 simultaneously attenuated synovitis and cartilage degeneration in mice incurred by destabilization of medial meniscus surgery, indicating the delayed OA progression. Furthermore, MNPs-TRPV1 with AMF exposure remarkably reduced knee pain sensitivity, alleviated the crippled gait, and improved spontaneous ambulatory activity performance in the mice OA model. Overall, this work provides a potential pathogenesis-based precise OA therapy with temporally and spatially magnetothermal modulation of TRPV1 in a controllable manner.
ABSTRACT
In this study, we used alkaloids from Sophora flavescens to inhibit the SASP, leading to fibroblast-into-myofibroblast transition (FMT) to maintain intestinal mucosal homeostasis in vitro and in vivo. We used western blotting (WB) and immunofluorescence staining (IF) to assess whether five kinds of alkaloids inhibit the major inflammatory pathways and chose the most effective compound (sophocarpine; SPC) to ameliorate colorectal inflammation in a dextran sulfate sodium (DSS)-induced UC mouse model. IF, Immunohistochemistry staining (IHC), WB, disease activity index (DAI), and enzyme-linked immunosorbent assay (ELISA) were conducted to investigate the mechanism of action of this compound. Next, we detected the pharmacological activity of SPC on the senescence-associated secretory phenotypes (SASP) and FMT in interleukin 6 (IL-6)-induced senescence-like fibroblasts and discussed the mucosal protection ability of SPC on a fibroblast-epithelium/organoid coculture system and organ-on-chip system. Taken together, our results provide evidence that SPC alleviates the inflammatory response, improves intestinal fibrosis and maintains intestinal mucosal homeostasis in vivo. Meanwhile, SPC was able to prevent IL-6-induced SASP and FMT in fibroblasts, maintain the expression of TJ proteins, and inhibit inflammation and genomic stability of colonic mucosal epithelial cells by activating SIRT1 in vitro. In conclusion, SPC treatment attenuates intestinal fibrosis by regulating SIRT1/NF-κB p65 signaling, and it might be a promising therapeutic agent for inflammatory bowel disease.
Subject(s)
Alkaloids , Colitis, Ulcerative , Colitis , Matrines , Animals , Mice , Alkaloids/pharmacology , Alkaloids/therapeutic use , Colitis/chemically induced , Colitis/drug therapy , Colitis/pathology , Colitis, Ulcerative/chemically induced , Colon , Dextran Sulfate/adverse effects , Disease Models, Animal , Fibroblasts/metabolism , Fibrosis , Inflammation/drug therapy , Inflammation/pathology , Interleukin-6/adverse effects , Mice, Inbred C57BL , Myofibroblasts/metabolism , NF-kappa B/metabolism , Sirtuin 1ABSTRACT
Osteoarthritis (OA) is the most common degenerative joint disease worldwide, with the main pathological manifestation of articular cartilage degeneration. It have been investigated that pharmacological activation of transient receptor potential vanilloid 1 (TRPV1) significantly alleviated cartilage degeneration by abolishing chondrocyte ferroptosis. In this work, in view of the thermal activated feature of TRPV1, Citrate-stabilized gold nanorods (Cit-AuNRs) is conjugated to TRPV1 monoclonal antibody (Cit-AuNRs@Anti-TRPV1) as a photothermal switch for TRPV1 activation in chondrocytes under near infrared (NIR) irradiation. The conjugation of TRPV1 monoclonal antibody barely affect the morphology and physicochemical properties of Cit-AuNRs. Under NIR irradiation, Cit-AuNRs@Anti-TRPV1 exhibited good biocompatibility and flexible photothermal responsiveness. Intra-articular injection of Cit-AuNRs@Anti-TRPV1 followed by NIR irradiation significantly activated TRPV1 and attenuated cartilage degradation by suppressing chondrocytes ferroptosis. The osteophyte formation and subchondral bone sclerosis are remarkably alleviated by NIR-inspired Cit-AuNRs@Anti-TRPV1. Furthermore, the activation of TRPV1 by Cit-AuNRs@Anti-TRPV1 evidently improved physical activities and alleviated pain of destabilization of the medial meniscus (DMM)-induced OA mice. The study reveals Cit-AuNRs@Anti-TRPV1 under NIR irradiation protects chondrocytes from ferroptosis and attenuates OA progression, providing a potential therapeutic strategy for the treatment of OA.
Subject(s)
Chondrocytes , Gold , Nanotubes , Osteoarthritis , Animals , Male , Mice , Chondrocytes/metabolism , Chondrocytes/drug effects , Disease Models, Animal , Disease Progression , Gold/chemistry , Infrared Rays , Mice, Inbred C57BL , Nanotubes/chemistry , Osteoarthritis/metabolism , Osteoarthritis/drug therapy , TRPV Cation Channels/metabolismABSTRACT
Background and Purpose. Breast cancer ranks first in the incidence of female tumors. Triple-negative breast cancer (TNBC), one type of breast cancer, is more aggressive and has a worse prognosis. Demethylzeylasteral (T-96) is isolated from Tripterygium wilfordii Hook F. Our previous study found that T96 could inhibit TNBC invasion via suppressing the canonical and noncanonical TGF-ß signaling pathways. However, the antitumor effects and mechanisms of T-96 on TNBC have not been studied. This study is aimed at investigating the antitumor effect and mechanism of T-96 on breast cancer. Experimental approach. MTT assay, Live and Dead cell assay, and TUNEL were used to observe the antitumor effect of breast cancer cells treated with T-96. siRNA of LSD1, Co-IP, and molecular docking were used to explore the direct target and mechanism of T-96. Subcutaneous murine xenograft models were used to detect the efficacy of T-96 antitumor activity in vivo. Key Results. T-96 was more susceptible to inducing the apoptosis of highly metastatic TNBC cell lines (SUM-1315). An abnormal level of histone methylation is a crucial characteristic of metastatic cancer cells. LSD1 is a histone demethylase. We found that T-96 could significantly decrease the protein expression of LSD1, increase its target protein PTEN expression and enhance histone methylation. T-96 could also down-regulate the PI3K/AKT signaling pathway, which could be blocked by PTEN. Knockdown of LSD1 by siRNA blocked the pharmacological activity of T-96. And the molecular docking predicted T-96 processed affinity toward LSD1 through hydrogen bonding. Finally, T-96 was evaluated in a murine xenograft model of SUM-1315 cells. And T-96 could significantly inhibit tumor growth without showing marked toxicity. Conclusions & Implications. The results illustrated that T-96 exerted antitumor activity in highly metastatic TNBC by inactivating the LSD1 function.
Subject(s)
Triple Negative Breast Neoplasms , Humans , Female , Mice , Animals , Triple Negative Breast Neoplasms/drug therapy , Triple Negative Breast Neoplasms/genetics , Triple Negative Breast Neoplasms/metabolism , RNA, Small Interfering/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Histones/genetics , Histones/metabolism , Histones/pharmacology , Cell Line, Tumor , Molecular Docking Simulation , Histone Demethylases/genetics , Histone Demethylases/metabolism , Apoptosis , Epigenesis, Genetic , Transforming Growth Factor beta/pharmacology , Xenograft Model Antitumor Assays , Cell ProliferationABSTRACT
Extraperitoneal bladder ruptures account for 70-90% of all bladder injuries. Management of uncomplicated extraperitoneal bladder ruptures may be treated conservatively with catheter drainage via foley or suprapubic tube. The extend of contrast extravasation at the time of cystogram does not typically affect therapy. We presented a case of a 59 -year-old- male who sustained a traumatic extraperitoneal bladder rupture after falling off a horse. The patient had severe contrast extravasation into the extraperitoneal space. Conservative management was the treatment of choice. The patient's bladder injury successfully healed after prolonged management with foley catheter decompression.
ABSTRACT
Mammalian hindlimb development involves a variety of cells and the regulation of spatiotemporal molecular events, but regulatory networks of transcription factors contributing to hindlimb morphogenesis are not well understood. Here, we identified transcription factor networks during mouse hindlimb morphology establishment through transcriptome analysis. We used four stages of embryonic hindlimb transcription profiles acquired from the Gene Expression Omnibus database (GSE30138), including E10.5, E11.5, E12.5 and E13.5, to construct a gene network using Weighted Gene Co-expression Network Analysis (WGCNA), and defined seven stage-associated modules. After filtering 7625 hub genes, we further prioritized 555 transcription factors with AnimalTFDB3.0. Gene ontology enrichment showed that transcription factors of different modules were enriched in muscle tissue development, connective tissue development, embryonic organ development, skeletal system morphogenesis, pattern specification process and urogenital system development separately. Six regulatory networks were constructed with key transcription factors, which contribute to the development of different tissues. Knockdown of four transcription factors from regulatory networks, including Sox9, Twist1, Snai2 and Klf4, showed that the expression of limb-development-related genes was also inhibited, which indicated the crucial role of transcription factor networks in hindlimb development.
Subject(s)
Gene Expression Regulation , Transcription Factors , Mice , Animals , Transcription Factors/genetics , Gene Regulatory Networks , Gene Expression Profiling , Hindlimb , Mammals/geneticsABSTRACT
Many proposals for exploring topological quantum computation are based on superconducting quantum devices constructed on materials with strong spin-orbit coupling (SOC). For these devices, full control of both the magnitude and the spatial distribution of the supercurrent is highly demanded, but has been elusive up to now. We constructed a proximity-type Josephson junction on nanoplates of Bi2O2Se, a new emerging semiconductor with strong SOC. Through electrical gating, we show that the supercurrent can be fully turned ON and OFF, and its real-space pathways can be configured either through the bulk or along the edges. Our work demonstrates Bi2O2Se as a promising platform for constructing multifunctional hybrid superconducting devices as well as for searching for topological superconductivity.
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Introduction/Objectives: Despite minimal evidence that evaluates the effect of age on percutaneous nephrolithotomy (PCNL) morbidity, pediatric and elderly patients are considered high-risk groups. Our objective was to assess the effect of the extremes of ages on PCNL readmission and postoperative complication rates. Methods: We identified all PCNL encounters in the 2013 and 2014 Nationwide Readmission Database. Encounters were divided into five age groups: pediatric (<18 years old), young adult (18-25 years old), adult (26-64 years old), geriatric (65-74 years old), and elderly (≥75 years old). Weighted descriptive statistics were used to describe population demographics. We fit an adjusted weighted logistic regression model for 30-day readmission and complication rates. Results: We identified 23,357 encounters. Testing average effect of pediatric and elderly encounters to all other age groups did not reveal a difference in odds for 30-day readmissions, but did result in increased odds for 30-day GU readmissions (odds ratio: 17.7 [95% confidence interval (CI): 2.65-118.9]; p = 0.003). Compared to all other age groups, elderly encounters had 7.5 (95% CI: 2.5-22.7; p = 0.0004) times the odds of a 30-day readmission and 68.3 (95% CI: 29.1-160.4; p < 0.0001) times the odds of a postoperative complication. Conclusions: When comparing the average effect of the extremes of ages to all other age groups, we did not find evidence to suggest a difference in odds for 30-day GU readmissions, but did find increased odds for complications. Further examination revealed that PCNL encounters of elderly patients had significantly increased odds for both readmission and complications, whereas PCNL encounters of pediatric patients did not.
Subject(s)
Kidney Calculi/surgery , Nephrolithotomy, Percutaneous/statistics & numerical data , Nephrostomy, Percutaneous/statistics & numerical data , Patient Readmission/statistics & numerical data , Postoperative Complications/epidemiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Child , Databases, Factual , Female , Humans , Kidney Calculi/mortality , Male , Middle Aged , Regression Analysis , Retrospective Studies , Young AdultABSTRACT
Our objective was to use community-based, national databases to evaluate diagnostic imaging and antibiotic prophylaxis practice patterns before and after the release of the 2011 American Academy of Pediatrics guidelines for acute febrile urinary tract infection. Using the National Ambulatory and Hospital Ambulatory Medical Care Surveys, urinary tract infection encounters were identified for patients aged 2 months to 18 years. Primary outcomes were utilization of antibiotics (as proxy for prophylaxis) and diagnostic imaging during encounters. Weighted multivariate logistic regression models were used to examine the association between time period (before and after 2011) and each of the primary outcomes. Among 8 588 035 weighted encounters, adjusting for covariates, there was insufficient evidence to suggest a difference between time periods for antibiotic utilization (odds ratio = 0.66, P = .12) or diagnostic imaging (odds ratio = 1.16, P = .56). Thus, we did not find evidence of changes in antibiotic utilization or diagnostic imaging practice patterns after the release of the 2011 American Academy of Pediatrics guidelines.
Subject(s)
Anti-Bacterial Agents/therapeutic use , Community Health Services/methods , Guideline Adherence/statistics & numerical data , Health Care Surveys/statistics & numerical data , Practice Patterns, Physicians'/statistics & numerical data , Urinary Tract Infections/drug therapy , Child , Cohort Studies , Female , Humans , Male , Pediatrics , Retrospective Studies , Societies, Medical , United StatesABSTRACT
OBJECTIVES: To compare and contrast the use of partial nephrectomy (PN) and radical nephrectomy (RN) in pediatric malignant renal tumors using a nationally representative database. METHODS: The 2010-2014 Nationwide Readmissions Database (NRD) was used to obtain PN and RN select postoperative data. ICD-9-CM codes were used to identify children (<10 years), adolescents (10-19 years) and young adults (20-30 years) diagnosed with malignant renal tumors who were treated with a PN or RN. The presence of a 30-day readmission, occurrence of postoperative complications, cost, and length of stay (LOS) were studied and weighted logistic regression models were fit to test for associations. RESULTS: There were 4330 weighted encounters (1289 PNs, 3041 RNs) that met inclusion criteria: 50.8% were children, 7.2% were adolescents, and 42% were young adults. Young adults had the highest rates of PN, whereas children had the highest rates of RN (pâ¯<â¯0.0001). Overall, no evidence was found to suggest a difference in odds between surgical modality and the presence of a 30-day readmission or postoperative complication. While PN was on average $9000 cheaper compared to RN overall, its cost was similar to that of RN for children. Similarly, PN patients had a shorter overall LOS compared to RN patients, but their LOS was similar to that of children who underwent RN. CONCLUSION: There was no evidence of a difference in odds between RN and PN in terms of postoperative readmissions or in-hospital complication rates. Additionally, we observed descriptive differences in both cost and LOS between the surgical modalities across age groups. TYPE OF STUDY: Retrospective comparative study (administrative database analysis). LEVEL OF EVIDENCE: Level III.
Subject(s)
Nephrectomy/statistics & numerical data , Postoperative Complications/epidemiology , Adolescent , Child , Databases, Factual , Female , Humans , Kidney Neoplasms/epidemiology , Kidney Neoplasms/surgery , Length of Stay/statistics & numerical data , Male , Nephrectomy/economics , Nephrectomy/methods , Patient Readmission/statistics & numerical data , Retrospective Studies , United States/epidemiology , Young AdultABSTRACT
BACKGROUND: More children with spina bifida (SB) are surviving into adulthood. Unfortunately, little data exist regarding the economic implications of modern SB care. OBJECTIVE: We examined economic data from two national databases to estimate the annual nationwide hospital and emergency charges of SB from 2006-14. METHODS: We analyzed the 2006-2014 Nationwide Inpatient Sample (NIS) and Nationwide Emergency Department Sample (NEDS). SB patients were defined using ICD-9-CM codes. Demographic and charge data were obtained from each database. Multiple imputation was used to estimate missing data (1.6% for NIS and 22% in NEDS). The principal outcomes were mean, median, and total charges for encounters each year. RESULTS: There were 725,646 encounters for individuals with SB between 2006 and 2014. The average age of captured SB patients who were admitted to a hospital or seen in an ER was 29 years. In 2014, the median charge for inpatient encounters was $31,071 (IQR: $15,947, $63,063) and for ER encounters was $2407.02 (IQR: $1321.91, $4211.35). In total, the sum of charges from all SB-related admissions in 2014 was $1,862,016,217 (95% CI: $1.69 billion, $2.03 billion), while the sum of charges of all SB-related ER encounters in 2014 was $176,843,522 (95% CI: $158 million, $196 million). There was a steady increase in charges over the study period. CONCLUSION: Charges for SB-related inpatient and emergency care in the US in 2014 was in excess of $2 billion in contrast to $1.2 billion in 2006, after adjusting for inflation; this is an impressively high figure for a relatively small number of patients.
Subject(s)
Disabled Persons/statistics & numerical data , Emergency Service, Hospital/economics , Emergency Service, Hospital/trends , Hospitalization/economics , Hospitalization/trends , Pediatrics/economics , Pediatrics/trends , Spinal Dysraphism/economics , Spinal Dysraphism/therapy , Adolescent , Adult , Child , Child, Preschool , Emergency Service, Hospital/statistics & numerical data , Female , Forecasting , Hospitalization/statistics & numerical data , Humans , Infant , Male , Pediatrics/statistics & numerical data , United StatesABSTRACT
The impact of the Patient Protection and Affordable Care Act (PPACA) on children's access to surgical care is not well-defined. Our objective was to describe the early impact of PPACA on children's surgical care before and after Medicaid expansion in 2014. We compared pediatric and young adult surgical outcomes in 2013 and 2014 in Medicaid expansion and nonexpansion states; young adults were included as a control group. From 4 states, 1 597 708 encounters met all inclusion criteria. Comparing expansion to nonexpansion states, modest increases were noted in elective instead of urgent/emergent admissions; in ambulatory instead of inpatient surgeries; in inpatient length of stays; in discharges to home instead of other inpatient care facilities; and in charges for inpatient admissions. A modest decrease of -1.1% was noted in ambulatory admission charges. Overall, we conclude that Medicaid expansion likely increased children's access to surgical care, resulting in improved delivery and slightly reduced charges.
Subject(s)
Child Health/legislation & jurisprudence , Delivery of Health Care/legislation & jurisprudence , Health Services Accessibility/legislation & jurisprudence , Patient Protection and Affordable Care Act , Surgical Procedures, Operative , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Infant, Newborn , Male , Medicaid/legislation & jurisprudence , United States , Young AdultABSTRACT
To examine different locations and laser settings' effects on the efficiency of the "popcorn" method of laser lithotripsy, which consists of placing the laser in a group of small stones and firing continuously to break them into smaller particles. Pre-fragmented BegoStones were created between 2 and 4 mm to mimic typical popcorning conditions. A 0.5 g collection of fragments was placed into 3D-printed models (a spherical calyx and ellipsoid pelvis model) and a 200-µm laser fiber was positioned above the stones. The laser was fired for 2 min with irrigation, with 5 trials at each setting: 0.2 J/50 Hz, 0.5 J/20 Hz, 0.5 J/40 Hz, 1 J/20 Hz, 0.2 J/80 Hz, 0.5 J/80 Hz. After drying, fragmentation efficiency was determined by calculating the mass of stones reduced to sub-2 mm particles. Statistical analysis was performed with ANOVA and Student's t test. The trials within the calyx model were significantly more efficient compared to the pelvis (0.19 vs 0.15 g, p = 0.01). When comparing laser settings, there was a difference between groups by one-way ANOVA [F(5,54) = 8.503, p = 5.47 × 10-6]. Post hoc tests showed a power setting of 0.5 J/80 Hz was significantly more efficient than low-power settings 0.2 J/50 Hz and 0.5 J/20 Hz (p < 0.05). Additionally, 0.2 J/50 Hz was significantly less efficient than 0.5 J/40 Hz, 1 J/20 Hz, and 0.2 J/80 Hz. Popcorning is most efficient in smaller spaces; we recommend displacement of stones into a calyx before popcorning. No difference was seen between high-power settings, although 0.5 J/40 Hz and 0.5 J/80 Hz performed best, suggesting that moderate energy popcorning methods with at least 0.5 J per pulse are most efficient.
Subject(s)
Kidney Calculi/therapy , Lasers, Solid-State/therapeutic use , Lithotripsy, Laser/methods , Models, Biological , Humans , Kidney Calculi/pathology , Kidney Calices/pathology , Kidney Calices/radiation effects , Models, Anatomic , Printing, Three-Dimensional , Treatment OutcomeABSTRACT
PURPOSE: The LithoClast Trilogy is a novel single probe, dual-energy lithotripter with ultrasonic (US) vibration and electromagnetic impact forces. ShockPulse and LithoClast Select are existing lithotripters that also use a combination of US and mechanical impact energies. We compared the efficacy and tip motion of these devices in an in vitro setting. MATERIALS AND METHODS: Begostones, in the ratio 15:3, were used in all trials. Test groups were Trilogy, ShockPulse, Select ultrasound (US) only, and Select ultrasound with pneumatic (USP). For clearance testing, a single investigator facile with each lithotripter fragmented 10 stones per device. For drill testing, a hands-free apparatus with a submerged balance was used to apply 1 or 2 lbs of pressure on a stone in contact with the device tip. High-speed photography was used to assess Trilogy and ShockPulse's probe tip motion. RESULTS: Select-USP was slowest and Trilogy fastest on clearance testing (p < 0.01). On 1 lbs drill testing, Select-US was slowest (p = 0.001). At 2 lbs, ShockPulse was faster than Select US (p = 0.027), but did not significantly outpace Trilogy nor Select-USP. At either weight, there was no significant difference between Trilogy and ShockPulse. During its US function, Trilogy's maximum downward tip displacement was 0.041 mm relative to 0.0025 mm with ShockPulse. Trilogy had 0.25 mm of maximum downward displacement during its impactor function while ShockPulse had 0.01 mm. CONCLUSIONS: Single probe dual-energy devices, such as Trilogy and ShockPulse, represent the next generation of lithotripters. Trilogy more efficiently cleared stone than currently available devices, which could be explained by its larger probe diameter and greater downward tip displacement during both US and impactor functions.
Subject(s)
Kidney Calculi/surgery , Lithotripsy/instrumentation , Nephrostomy, Percutaneous/instrumentation , Surgical Instruments/standards , Analysis of Variance , Humans , KineticsABSTRACT
INTRODUCTION: The surgical comorbidity assessment is important for patient risk stratification, counseling, and research. In adults, risk assessment indices, such as the Charlson Co-morbidity Score (CCS) or Van Walraven Index (VWI), are well established. In pediatrics, however, risk assessment indices are scarce. Recently, a pediatric-specific risk assessment index, the Rhee index, was developed to discriminate mortality for pediatric general surgery patients. Currently, there is no validated risk assessment tool in pediatric urology. OBJECTIVE: We compared the performance of the CCS, VWI, and Rhee Index in discriminating postoperative complications and readmissions to the emergency room/inpatient unit after pediatric urological procedures. METHODS: We analyzed the Nationwide Readmissions Database (NRD), State Inpatient Databases (SID), and State Emergency Department Databases (SEDD). We included patients (<18 years) who underwent the following urological procedures: ureteroneocystostomy, ureteroureterostomy, radical/partial nephrectomy, pyeloplasty, appendicovesicostomy, enterocystoplasty, vesicostomy, and bladder neck sling. Complications were identified based on definitions in the National Surgical Quality Improvement Program (NSQIP). Thirty-day emergency room admission and inpatient readmissions were extracted. Comorbidity scores were calculated using each of the three indices. We compared the performance of each index in discriminate primarily postoperative complications in the NRD and both admission types in the SID/SEDD by constructing a receiver operating characteristics (ROC). AUCs were compared using the Delong method. This protocol was reviewed by our Institutional Review Board and deemed to be exempt. RESULTS: We identified a total of 8006 patients in NRD and 6236 patients in SID/SEDD. The Rhee index had the best performance for discriminating postoperative complications (AUC = 0.67, 95% CI 0.64-0.70) compared to CCS (AUC = 0.62, 95% CI 0.60-0.65) and VWI (AUC = 0.62, 95% CI 0.59-0.65); p < 0.01. The CCS had the best performance for discriminating 30-day inpatient readmissions (AUC = 0.63, 95% CI 0.61-0.66) than VWI (AUC = 0.54, 95% CI 0.52-0.57), and Rhee Index (AUC = 0.56, 95% CI 0.54-0.59); p < 0.0001. All three indices had similarly poor discrimination for 30-day ER admissions: CCS (AUC = 0.52), VWI (AUC = 0.51), and Rhee Index (AUC = 0.50); p = 0.5 (see Table). DISCUSSION: The Rhee Index had the best performance for discriminating postoperative complications, while the CCS was superior for discriminating inpatient readmissions among the three indices. Limitations to our study include inpatient-only procedures, inability to identify complications managed in clinics, omission of secondary operations, accounting for parental anxiety, and the generalizability of SID. CONCLUSIONS: The three comorbidity indices evaluated are poor discriminators for postoperative complications, 30-day inpatient readmissions or 30-day ER admissions. A new index is needed for pediatric urology patients.
Subject(s)
Patient Readmission/trends , Plastic Surgery Procedures/adverse effects , Postoperative Complications/epidemiology , Risk Assessment/methods , Urologic Diseases/surgery , Urologic Surgical Procedures/adverse effects , Child, Preschool , Comorbidity/trends , Female , Humans , Incidence , Male , ROC Curve , Retrospective Studies , Risk Factors , United States/epidemiologyABSTRACT
This study aimed to describe the demographic characteristics, hospital utilizations, patterns of inpatient surgical management, and the overall state/regional variation in surgery rate among patients with disorders of sex development (DSD). We analyzed the Nationwide Inpatient Sample from 2001 to 2012 for patients younger than 21 years. DSD-related diagnoses and procedures were identified via International Classification of Diseases, Ninth Revision (ICD-9) codes. We identified a total of 43,968 DSD-related admissions. Of these, 73.4% of the admissions were designated as female and 642 (1.9%) were inpatient surgical admissions. Among neonates, less than 1% underwent any type of genital surgery. Nonsurgical admissions were associated with longer length of stay and higher cost. There was no significant regional variation in the rate of DSD surgeries, but we observed higher concentrations of DSD surgeries in states associated with tertiary referral centers.
Subject(s)
Demography/methods , Disorders of Sex Development/classification , Disorders of Sex Development/surgery , Hospitalization/statistics & numerical data , Sex Reassignment Surgery/methods , Age Factors , Child, Preschool , Cohort Studies , Databases, Factual , Disorders of Sex Development/epidemiology , Female , Hospital Mortality , Humans , Infant , Infant, Newborn , International Classification of Diseases , Length of Stay/economics , Male , Postoperative Complications/epidemiology , Postoperative Complications/physiopathology , Retrospective Studies , Risk Assessment , Sex Factors , Sex Reassignment Surgery/mortality , Survival Rate , Tertiary Care Centers , Treatment Outcome , United StatesABSTRACT
INTRODUCTION: Cost-utility analyses (CUA) are useful when the treatment conditions depend on patient preferences that are in turn dependent on health state utility value. Spina bifida (SB) is an example of such a preference-sensitive condition. Historically, the SB utility value for CUA has been gathered via a traditional face-to-face interview. However, due to funding and time constrains, utility estimation via online crowdsourcing has recently gained popularity. Our aim was to estimate the utility value for a generic SB health state using a validated online tool. METHODS: A cross-sectional survey of American adults was conducted using the time-trade-off (TTO) method. Participants were recruited from an online crowdsourcing interface, Amazon's Mechanical Turk (mTurk). Demographic information and prior knowledge of SB were assessed. Respondents were provided a written passage and an online video explaining SB and its potential associated comorbidities. Participants were queried on hypothetical ascending time-trades from a child-parent dyad perspective to determine the utility of a SB health state in an affected 6-year-old child. Respondents were also asked to indicate the percentage of time traded from their life in relation to their child's. Utility estimates were then calculated and compared using bivariate and multivariate analyses. RESULTS: We obtained 503 responses (85% response rate). Mean respondent age was 34 (± 11); 247 (49%) were female; 386 (77%) were white; 189 (38%) were married, and 234 (46%) had children. Mean proportion of longevity traded by participants in the dyadic interaction was 66% (± 27) from the parent's life. Only 51 respondents (9%) reported having "ample" prior knowledge of SB; 8 respondents (0.02%) had SB themselves. Few others had previous experience with SB or myelomeningocele either in a child (4, 1%), or friend/relative (28, 5%). Compared with a perfect health state of 1.0, we found mean utilities of 0.85 (± 0.20) for SB. CONCLUSIONS: Utility estimation for SB is feasible through crowdsourcing, and the resultant values are similar to previous estimates using traditional techniques. Subjects view the SB health state to be inferior to perfect health.
Subject(s)
Attitude to Health , Cost-Benefit Analysis , Crowdsourcing , Spinal Dysraphism , Adult , Child , Cross-Sectional Studies , Feasibility Studies , Female , Humans , Internet , Male , Parent-Child Relations , Spinal Dysraphism/economics , Spinal Dysraphism/psychology , Spinal Dysraphism/therapy , United StatesABSTRACT
INTRODUCTION: Single-use ureteroscopes have been gaining popularity in recent years. We compare the optics, deflection, and irrigation flow of two novel single-use flexible ureteroscopes-the YC-FR-A and the NeoFlex-with contemporary reusable and single-use flexible ureteroscopes. METHODS: Five flexible ureteroscopes, YC-FR-A (YouCare Tech, China), NeoFlex (Neoscope, Inc., USA), LithoVue (Boston Scientific, USA), Flex-Xc (Karl Storz, Germany), and Cobra (Richard Wolf, Germany), were assessed in vitro for image resolution, distortion, field of view, depth of field, color representation, and grayscale imaging. Ureteroscope deflection and irrigation were also compared. RESULTS: The YC-FR-A showed a resolution of 5.04 lines/mm and 4.3% image distortion. NeoFlex showed a resolution of 17.9 lines/mm and 14.0% image distortion. No substantial difference was demonstrated regarding the other optic characteristics between the two. Across all tested ureteroscopes, single-use or reusable, the digital scopes performed best with regard to optics. The YC-FR-A had the greatest deflection at baseline, but lacks two-way deflection. The NeoFlex had comparable deflection at baseline to reusable devices. Both ureteroscopes had substantial loss of deflection with instruments in the working channel. The YC-FR-A had the greatest irrigation rate. The NeoFlex has comparable irrigation to contemporary ureteroscopes. CONCLUSIONS: The YouCare single-use fiberoptic flexible ureteroscope and NeoFlex single-use digital flexible ureteroscope perform comparably to current reusable ureteroscopes, possibly making each a viable alternative in the future. Newer YouCare single-use flexible ureteroscopes with a digital platform and two-way deflection may be more competitive, while the NeoFlex devices are undergoing rapid improvement as well. Further testing is necessary to validate the clinical performance and utility of these ureteroscopes, given the wide variety of single-use devices under development.