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A key feature distinguishing high-grade glioma (HG) from low-grade glioma (LG) is the extensive neovascularization and endothelial hyperproliferation. Prior work has shown that tumor-associated vasculature from HG is molecularly and functionally distinct from normal brain vasculature and expresses higher levels of protumorigenic factors that promote glioma growth and progression. However, it remains unclear whether vessels from LG also express protumorigenic factors, and to what extent they functionally contribute to glioma growth. Here, we profile the transcriptomes of glioma-associated vascular cells (GVC) from IDH-mutant (mIDH) LG and IDH-wild-type (wIDH) HG and show that they exhibit significant molecular and functional differences. LG-GVC show enrichment of extracellular matrix-related gene sets and sensitivity to antiangiogenic drugs, whereas HG-GVC display an increase in immune response-related gene sets and antiangiogenic resistance. Strikingly, conditioned media from LG-GVC inhibits the growth of wIDH glioblastoma cells, whereas HG-GVC promotes growth. In vivo cotransplantation of LG-GVC with tumor cells reduces growth, whereas HG-GVC enhances tumor growth in orthotopic xenografts. We identify ASPORIN (ASPN), a small leucine-rich repeat proteoglycan, highly enriched in LG-GVC as a growth suppressor of wIDH glioblastoma cells in vitro and in vivo. Together, these findings indicate that GVC from LG and HG are molecularly and functionally distinct and differentially regulate tumor growth. Implications: This study demonstrated that vascular cells from IDH-mutant LG and IDH-wild-type HG exhibit distinct molecular signatures and have differential effects on tumor growth via regulation of ASPN-TGFβ1-GPM6A signaling.

Glioblastoma is a highly aggressive neoplasm and the most common primary malignant brain tumor. Endothelial tissue plays a critical role in glioblastoma growth and progression, facilitating angiogenesis, cellular communication, and tumorigenesis. In this review, we present an up-to-date and comprehensive summary of the role of endothelial cells in glioblastomas, along with an overview of recent developments in glioblastoma therapies and tumor endothelial marker identification.

BACKGROUND: Loss of AZGP1 expression is a biomarker associated with progression to castration resistance, development of metastasis, and poor disease-specific survival in prostate cancer. However, high expression of AZGP1 cells in prostate cancer has been reported to increase proliferation and invasion. The exact role of AZGP1 in prostate cancer progression remains elusive. METHOD: AZGP1 knockout and overexpressing prostate cancer cells were generated using a lentiviral system. The effects of AZGP1 under- or over-expression in prostate cancer cells were evaluated by in vitro cell proliferation, migration, and invasion assays. Heterozygous AZGP1± mice were obtained from European Mouse Mutant Archive (EMMA), and prostate tissues from homozygous knockout male mice were collected at 2, 6 and 10 months for histological analysis. In vivo xenografts generated from AZGP1 under- or over-expressing prostate cancer cells were used to determine the role of AZGP1 in prostate cancer tumor growth, and subsequent proteomics analysis was conducted to elucidate the mechanisms of AZGP1 action in prostate cancer progression. AZGP1 expression and microvessel density were measured in human prostate cancer samples on a tissue microarray of 215 independent patient samples. RESULT: Neither the knockout nor overexpression of AZGP1 exhibited significant effects on prostate cancer cell proliferation, clonal growth, migration, or invasion in vitro. The prostates of AZGP1-/- mice initially appeared to have grossly normal morphology; however, we observed fibrosis in the periglandular stroma and higher blood vessel density in the mouse prostate by 6 months. In PC3 and DU145 mouse xenografts, over-expression of AZGP1 did not affect tumor growth. Instead, these tumors displayed decreased microvessel density compared to xenografts derived from PC3 and DU145 control cells, suggesting that AZGP1 functions to inhibit angiogenesis in prostate cancer. Proteomics profiling further indicated that, compared to control xenografts, AZGP1 overexpressing PC3 xenografts are enriched with angiogenesis pathway proteins, including YWHAZ, EPHA2, SERPINE1, and PDCD6, MMP9, GPX1, HSPB1, COL18A1, RNH1, and ANXA1. In vitro functional studies show that AZGP1 inhibits human umbilical vein endothelial cell proliferation, migration, tubular formation and branching. Additionally, tumor microarray analysis shows that AZGP1 expression is negatively correlated with blood vessel density in human prostate cancer tissues. CONCLUSION: AZGP1 is a negative regulator of angiogenesis, such that loss of AZGP1 promotes angiogenesis in prostate cancer. AZGP1 likely exerts heterotypical effects on cells in the tumor microenvironment, such as stromal and endothelial cells. This study sheds light on the anti-angiogenic characteristics of AZGP1 in the prostate and provides a rationale to target AZGP1 to inhibit prostate cancer progression.

MRI plays an important role in the evaluation of kidney allografts for vascular complications as well as parenchymal insults. Transplant renal artery stenosis, the most common vascular complication of kidney transplant, can be evaluated by MRA using gadolinium and nongadolinium contrast agents as well as by unenhanced MRA techniques. Parenchymal injury occurs through a variety of pathways, including graft rejection, acute tubular injury, BK polyomavirus infection, drug-induced interstitial nephritis, and pyelonephritis. Investigational MRI techniques have sought to differentiate among these causes of dysfunction as well as to assess the degree of interstitial fibrosis or tubular atrophy (IFTA)-the common end pathway for all of these processes-which is currently evaluated by invasively obtained core biopsies. Some of these MRI sequences have shown promise in not only assessing the cause of parenchymal injury but also assessing IFTA noninvasively. This review describes current clinically used MRI techniques and previews promising investigational MRI techniques for assessing complications of kidney grafts.

BACKGROUND: The superiority of balloon angioplasty plus aggressive medical management (AMM) to AMM alone for symptomatic intracranial artery stenosis (sICAS) on efficacy and safety profiles still lacks evidence from randomised controlled trials (RCTs). AIM: To demonstrate the design of an RCT on balloon angioplasty plus AMM for sICAS. DESIGN: Balloon Angioplasty for Symptomatic Intracranial Artery Stenosis (BASIS) trial is a multicentre, prospective, randomised, open-label, blinded end-point trial to investigate whether balloon angioplasty plus AMM could improve clinical outcome compared with AMM alone in patients with sICAS. Patients eligible in BASIS were 35-80 years old, with a recent transient ischaemic attack within the past 90 days or ischaemic stroke between 14 days and 90 days prior to enrolment due to severe atherosclerotic stenosis (70%-99%) of a major intracranial artery. The eligible patients were randomly assigned to receive balloon angioplasty plus AMM or AMM alone at a 1:1 ratio. Both groups will receive identical AMM, including standard dual antiplatelet therapy for 90 days followed by long-term single antiplatelet therapy, intensive risk factor management and life-style modification. All participants will be followed up for 3 years. STUDY OUTCOMES: Stroke or death in the next 30 days after enrolment or after balloon angioplasty procedure of the qualifying lesion during follow-up, or any ischaemic stroke or revascularisation from the qualifying artery after 30 days but before 12 months of enrolment, is the primary outcome. DISCUSSION: BASIS trail is the first RCT to compare the efficacy and safety of balloon angioplasty plus AMM to AMM alone in sICAS patients, which may provide an alternative perspective for treating sICAS. TRIAL REGISTRATION NUMBER: NCT03703635; https://www. CLINICALTRIALS: gov.

BACKGROUND: There are ≈5 million annual dizziness visits to US emergency departments, of which vestibular strokes account for over 250 000. The head impulse, nystagmus, and test of skew eye examination can accurately distinguish vestibular strokes from peripheral dizziness. However, the eye-movement signs are subtle, and lack of familiarity and difficulty with recognition of abnormal eye movements are significant barriers to widespread emergency department use. To break this barrier, we sought to assess the accuracy of EyePhone, our smartphone eye-tracking application, for quantifying nystagmus. METHODS AND RESULTS: We prospectively enrolled healthy volunteers and recorded the velocity of induced nystagmus using a smartphone eye-tracking application (EyePhone) and then compared the results with video oculography (VOG). Following a calibration protocol, the participants viewed optokinetic stimuli with incremental velocities (2-12 degrees/s) in 4 directions. We extracted slow phase velocities from EyePhone data in each direction and compared them with the corresponding slow phase velocities obtained by the VOG. Furthermore, we calculated the area under the receiver operating characteristic curve for nystagmus detection by EyePhone. We enrolled 10 volunteers (90% men) with an average age of 30.2±6 years. EyePhone-recorded slow phase velocities highly correlated with the VOG recordings (r=0.98 for horizontal and r=0.94 for vertical). The calibration significantly increased the slope of linear regression for horizontal and vertical slow phase velocities. Evaluating the EyePhones performance using VOG data with a 2 degrees/s threshold showed an area under the receiver operating characteristic curve of 0.87 for horizontal and vertical nystagmus detection. CONCLUSIONS: We demonstrated that EyePhone could accurately detect and quantify optokinetic nystagmus, similar to the VOG goggles.

Objectives: Endothelial cells (ECs), as the main cell types in the micro- and macro-vascular structure, are crucial to many vital physiological processes occurring in human body among which are both physiologic and pathologic angiogenesis. Due to their great heterogeneity, it is recommended that the ECs of each tissue should be studied separately. Recently, targeting angiogenesis in cancer has become one of the main strategies for cancer management. Accordingly, this study aimed to introduce a simple, costeffective, and practical model for studying tumor angiogenesis, which can contribute to studies focused on antiangiogenic-based treatments for cancer. Materials and Methods: In this original study, the explants of both normal and tumor tissues of mouse lung and 4T1 mouse cancer model were cultured separately in a collagen type 1 bed. Sprouting ECs formed a network of vessel-liked structures that were photographed as a model for investigating cancerous and normal angiogenesis. These ECs were then isolated from the collagen matrix using collagenase to confirm their endothelial nature. Results: The results showed that the cells invading the collagen matrix and forming a vessel-liked network were of endothelial nature. They were also found to have EC-specific characteristics and express EC-specific markers. These embedded cells may have been treated with the desired drug or further isolated from the collagen matrix and investigated in a genome or protein level. Conclusions: In sum, this modeling had the potential to become a suitable model for studying the pathological angiogenesis such as tumors in human and animal tissues. [ABSTRACT FROM AUTHOR]

OBJECTIVES Endoscopic evaluation of anastomosis is effective for the early detection of anastomotic complications after a bronchoplastic procedure. Herein, we aimed to clarify important findings for predicting anastomotic complications. METHODS This single-centre retrospective study included patients who underwent bronchoplastic surgery between April 2013 and September 2023. Only cases in which bronchoscopy was performed both 1 and 2 weeks after surgery were included. Endoscopic findings (classification by Ludwig and Stoelben, mucosa colour, oedema, slough area and colour and depression) were reviewed for all cases. The accuracy of these findings for predicting anastomotic complications was evaluated. RESULTS Of the 190 patients included in this study, 14 (7.4%) experienced anastomotic abnormalities, 11 had fistulas (5.8%) and 7 had stenosis (3.7%). The onsets of fistula and stenosis were 20–28 and 20–44 days after surgery, respectively. In 102 patients (53.7%), the slough worsened from the first to the second week postsurgery. Therefore, it was easier to evaluate slough 2 weeks postsurgery rather than 1-week postsurgery. The positive/negative predicted values of anastomotic complications in endoscopic findings 2 weeks postsurgery were circular slough, 34.2%/99.3%; slough with dark colour, 39.3%/98.1%; and depression, 54.2%/99.4%. The incidence of anastomotic abnormalities was 0% in cases without the 3 findings, 10% in cases with at least 1 finding and 67% in cases with all 3 findings. CONCLUSIONS The endoscopic findings of slough on the anastomosis 2 weeks after bronchoplasty can be easily evaluated and accurately predict complications. Three important endoscopic findings were circular slough, dark colour and depression. [ABSTRACT FROM AUTHOR]

Background Carotid endarterectomy and carotid artery stenting are common procedures for the treatment of carotid artery stenosis. The aim of this study was to identify factors that modify the effect between type of treatment and outcome, and could thus be used to refine the selection of treatment procedure. Methods All patients who underwent either carotid endarterectomy or carotid artery stenting between 2012 and 2018 in German hospitals were included. The analysis of effect modification was focused on baseline patient characteristics. The outcome was a composite of any stroke or death until discharge from hospital. For multivariable analyses, a generalized linear mixed regression model was used. Results Some 221 282 patients were included, of whom 68% were male. In patients who underwent carotid endarterectomy or carotid artery stenting, the risk of any stroke or death was 2.3% and 3.7% respectively. Patient age was statistically significantly associated with a higher risk of a composite outcome of any stroke or death (main effect of age: adjusted OR 1.21 (95% c.i. 1.17 to 1.26), P < 0.001). The age effect was stronger in patients treated with carotid artery stenting (interaction effect: adjusted OR 1.29 (95% c.i. 1.20 to 1.38), P < 0.001). Statistically significant interaction effects were identified for side of treatment, ASA grade, contralateral degree of stenosis, and the time interval between the index event and treatment. Conclusion This analysis shows that carotid artery stenting may be particularly disadvantageous in older patients, in patients with right-sided stenosis, and in symptomatic patients treated within the first 2 days after the index event. In patients with contralateral occlusion, carotid artery stenting appears equivalent to carotid endarterectomy. [ABSTRACT FROM AUTHOR]

Background Even though cytoreductive nephrectomy (CN) was once the standard of care for patients with advanced renal cell carcinoma (RCC), its role in treatment has not been well analyzed or defined in the era of immunotherapy (IO). Materials and Methods This study analyzed pathological outcomes in patients with advanced or metastatic RCC who received IO prior to CN. This was a multi-institutional, retrospective study of patients with advanced or metastatic RCC. Patients were required to receive IO monotherapy or combination therapy prior to radical or partial CN. The primary endpoint assessed surgical pathologic outcomes, including American Joint Committee on Cancer (AJCC) staging and frequency of downstaging, at the time of surgery. Pathologic outcomes were correlated to clinical variables using a Wald-chi squared test from Cox regression in a multi-variable analysis. Secondary outcomes included objective response rate (ORR) defined by response evaluation criteria in solid tumors (RECIST) version 1.1 and progression-free survival (PFS), which were estimated using the Kaplan-Meier method with reported 95% CIs. Results Fifty-two patients from 9 sites were included. Most patients were male (65%), 81% had clear cell histology, 11% had sarcomatoid differentiation. Overall, 44% of patients experienced pathologic downstaging, and 13% had a complete pathologic response. The ORR immediately prior to nephrectomy was stable disease in 29% of patients, partial response in 63%, progressive disease in 4%, and 4% unknown. Median follow-up for the entire cohort was 25.3 months and median PFS was 3.5 years (95% CI, 2.1-4.9). Conclusions IO-based interventions prior to CN in patients with advanced or metastatic RCC demonstrates efficacy, with a small fraction of patients showing a complete response. Additional prospective studies are warranted to investigate the role of CN in the modern IO-era. [ABSTRACT FROM AUTHOR]

Introduction Cervical spondylosis in the warfighter is a common musculoskeletal problem and can be career-ending especially if it requires fusion. Head-mounted equipment and increased biomechanical forces on the cervical spine have resulted in accelerated cervical spine degeneration. Current surgical gold standard is anterior cervical discectomy and fusion (ACDF). Posterior cervical foraminotomy (PCF) is a nonfusion surgical alternative, and this can be effective in alleviating radiculopathy from foraminal stenosis caused by disc-osteophyte complex. Biomechanical studies have not been done to analyze motion associated with military aircrew personnel following PCF. The aim of this study was to compare the biomechanical responses of the effects of ACDF and PCF with different grades of facet resection under simulated military aircrew conditions using range of motion, disc pressure, and facet loads at the index and adjacent levels. Materials and Methods A validated 3D finite element model of the human cervical spinal column was used to simulate various graded PCF and ACDF. All surgical simulations were performed at the most commonly operated level (C5-C6) in warfighters. Pure moment loading under flexion, extension, and lateral bending, and in vivo follower force of 75 N were applied to the intact spine. Hybrid loading protocol was used to achieve 134 degrees of combined flexion-extension and 83 degrees of lateral bending in intact and surgical models to reflect military loading conditions. Segmental motions, disc pressure, and facet load were obtained and normalized with respect to the intact model to quantify the biomechanical effect. Results Anterior cervical discectomy and fusion decreased range of motion at the index and increased motion at the adjacent levels, while all graded PCF responses had an opposite trend: increased motion at the index and decreased motion at adjacent levels. The magnitude of changes depended on the level of resection, spinal level, and loading mode. Disc pressure increased at the index level and decreased at the adjacent levels after PCF. These changes were exaggerated with increasing extent of facet resection. Facet load increased at the index level after PCF especially with extension and right (contralateral) lateral bending. Complete facetectomy led to facet load increases greater than ACDF at the adjacent levels in both flexion and extension. Conclusions Posterior cervical foraminotomy is a motion-preserving implant-free surgical alternative to ACDF for warfighters with cervical radiculopathy after failure of conservative management. The treating surgeon must pay close attention to the extent of facet resection to avoid potential spinal instability and future disc and facet degeneration after PCF. Posterior cervical foraminotomy can be more advantageous than ACDF in terms of adjacent segment degeneration, motion preservation, reoperation rate, surgical cost, and retention of warfighters. [ABSTRACT FROM AUTHOR]

Gallstone ileus is a relatively rare complication of cholelithiasis, and an uncommon cause of small bowel obstruction most commonly seen in elderly and debilitated people with associated comorbidities. Symptoms of gallstone ileus are insidious and may be vague while the delay in diagnosis results in a high mortality rate. Herein we report two cases of gallstone ileus in elderly patients with complex medical history who presented at the emergency department with abdominal pain and distension, vomiting and fluid/electrolyte disorders due to cholecysto-enteric fistula and bowel obstruction. [ABSTRACT FROM AUTHOR]

Surgical resection of the stenotic segment with end-to-end anastomosis is considered the gold standard in postintubation tracheal stenosis. However, outcomes of this concrete aetiology are not well described. With the aim to examine the extent, range and characteristics of the existing evidence, a scoping review was performed. Data sources included MEDLINE, Scopus, Ovid and the Cochrane databases. Inclusion criteria consisted of studies in adult patients with postintubation tracheal stenosis that reported characteristics, surgical management and outcomes. A total of 125 articles were identified, of which 10 were included in the final analysis. All studies were case reports or case series (level 4 evidence) grouping 110 patients, 75 males and 35 females. The age ranged from 15 to 71 years. Cotton–Myer stenosis grade was 1 [1 (0.9%)], 2 [25 (22.7%)], 3 [70 (63.6%)] and 4 [14 (12.7%)]. Stenosis location was in the tracheal upper-third in 108 (98.2%), in the middle-third in 1 (0.9%) and in the lower-third in 1 (0.9%). Stenosis length ranged from 1 to 5.6 cm. Follow-up ranged from 1 to 60 months (2 years for the most). Most frequent complications were transitory dysphagia in 13 (11.3%), granuloma formation in 8 (7.3%), dehiscence or air leak in 5 (4.5%) and wound infection in 4 (3.6%). Restenosis rate ranged from 2% to 25%. There was no perioperative mortality. Tracheal resection and primary anastomosis in postintubation tracheal stenosis appear to be safe and effective in the short and mid-terms; however, the very low level of evidence found prevents definitive conclusions. [ABSTRACT FROM AUTHOR]

Intracranial atherosclerotic disease (ICAD) is a common cause of ischaemic stroke and transient ischaemic attack (TIA) with a high recurrence rate. It is often referred to as intracranial atherosclerotic stenosis (ICAS), when the plaque has caused significant narrowing of the vessel lumen. The lesion is usually considered symptomatic ICAD/ICAS (sICAD/sICAS) when it has caused an ischaemic stroke or TIA. The severity of luminal stenosis has long been established as a prognostic factor for stroke relapse in sICAS. Yet, accumulating studies have also reported the important roles of plaque vulnerability, cerebral haemodynamics, collateral circulation, cerebral autoregulation and other factors in altering the stroke risks across patients with sICAS. In this review article, we focus on cerebral haemodynamics in sICAS. We reviewed imaging modalities/methods in assessing cerebral haemodynamics, the haemodynamic metrics provided by these methods and application of these methods in research and clinical practice. More importantly, we reviewed the significance of these haemodynamic features in governing the risk of stroke recurrence in sICAS. We also discussed other clinical implications of these haemodynamic features in sICAS, such as the associations with collateral recruitment and evolution of the lesion under medical treatment, and indications for more individualised blood pressure management for secondary stroke prevention. We then put forward some knowledge gaps and future directions on these topics.

ObjectiveTo describe the characteristics, management, and functional outcomes of patients with synchronous urethral stricture disease (SUSD) utilizing a multi-institutional cohort.MethodsData were collected and assessed from a prospectively maintained, multi-institutional database. Patients who underwent anterior urethroplasty for urethral stricture disease (USD) were included and stratified by the presence or absence of SUSD. USD location and etiology were classified according to the Trauma and Urologic Reconstruction Network of Surgeons Length, Segment and Etiology Anterior Urethral Stricture Classification System. Anterior urethroplasty techniques were recorded for both strictures. Functional failure was compared between groups.ResultsOne thousand nine hundred eighty-three patients were identified, of whom, 137/1983 (6.9%) had SUSD. The mean primary stricture length for patients with SUSD was 3.5 and 2.6 cm for the secondary stricture. Twelve anterior urethroplasty technique combinations were utilized in treating the 27 different combinations of SUSD. Functional failure was noted in 18/137 (13.1%) patients with SUSD vs 192/1846 (10.4%) patients with solitary USD, P = .3. SUSD was not associated with increased odds of functional failure. S classifications: S1b, P = .003, S2a, P = .001, S2b, P = .01 and S2c, P = .02 and E classifications: E3a, P = .004 and E6, P = .03, were associated with increased odds of functional failure.ConclusionRepair of SUSD in a single setting does not increase the risk of functional failure compared to patients with solitary USD. Increasing S classification, S1b through S2c and E classifications E3a and E6 were associated with increased functional failure. This reinforces the importance of the Trauma and Urologic Reconstruction Network of Surgeons Length, Segment and Etiology Anterior Urethral Stricture Classification System as a necessary tool in large-scale multi-institutional analysis when assessing highly heterogenous patient populations.

BACKGROUND: The contemporary burden and characteristics of coronary atherosclerosis, assessed using coronary computed tomography angiography (CCTA), is unknown among asymptomatic adults with diabetes and prediabetes in the United States. The pooled cohort equations and coronary artery calcium (CAC) score stratify atherosclerotic cardiovascular disease risk, but their association with CCTA findings across glycemic categories is not well established. METHODS: Asymptomatic adults without atherosclerotic cardiovascular disease enrolled in the Miami Heart Study were included. Participants underwent CAC and CCTA testing and were classified into glycemic categories. Prevalence of coronary atherosclerosis (any plaque, noncalcified plaque, plaque with ≥1 high-risk feature, maximal stenosis ≥50%) assessed by CCTA was described across glycemic categories and further stratified by pooled cohort equations-estimated atherosclerotic cardiovascular disease risk and CAC score. Adjusted logistic regression was used to evaluate the associations between glycemic categories and coronary outcomes. RESULTS: Among 2352 participants (49.5% women), the prevalence of euglycemia, prediabetes, and diabetes was 63%, 30%, and 7%, respectively. Coronary plaque was more commonly present across worsening glycemic categories (euglycemia, 43%; prediabetes, 58%; diabetes, 69%), and similar pattern was observed for other coronary outcomes. In adjusted analyses, compared with euglycemia, prediabetes and diabetes were each associated with higher odds of any coronary plaque (OR, 1.30 [95% CI, 1.05-1.60] and 1.75 [1.17-2.61], respectively), noncalcified plaque (OR, 1.47 [1.19-1.81] and 1.99 [1.38-2.87], respectively), and plaque with ≥1 high-risk feature (OR, 1.65 [1.14-2.39] and 2.53 [1.48-4.33], respectively). Diabetes was associated with stenosis ≥50% (OR, 3.01 [1.79-5.08]; reference=euglycemia). Among participants with diabetes and estimated atherosclerotic cardiovascular disease risk

BackgroundTo report objective long-term complications and health related quality of life (HRQOL) outcomes after radical prostatectomy (RP) with and without radiation therapy (RT) for prostate cancer (CaP).MethodsWe analyzed patients diagnosed with CaP who underwent RP from the UCSF Cancer of the Prostate Strategic Urologic Research Endeavor (CaPSURE) registry between 1995 and 2020. Cox proportional hazards were used to assess risk of postoperative complications which included cystitis, gastrointestinal (GI) toxicity, incontinence requiring a surgical procedure, ureteral injury and urinary stricture. Repeated measures mixed models were used to assess the effects of radiation and complications on patient-reported urinary, bowel, and sexual function after surgery.ResultsOf 6,258 men who underwent RP, cumulative incidence of EBRT was 9.1% at 5 years after surgery. Patients who received postoperative radiation were at increased risk for onset of cystitis (HR 5.60, 95% CI 3.40-9.22, P < 0.01). Receipt of RT was not associated with other complications. In repeated measures analysis, postoperative RT was associated with worsening general health scores, adjusting for complications of incontinence, urinary stricture, GI toxicity or ureteral injury, independent of whether patients had those complications.ConclusionsRT after RP was associated with an increase in the risk of cystitis and worse general health in the long term. Other complications and HRQOL outcomes did not demonstrate differences by whether patients had RT or not. While post-operative RT is the only curative option for CaP after RP, patients and providers should be aware of the increased risks when making treatment decisions.

ObjectiveSignificant regional variation is known with multiple surgical procedures. This study describes regional variation in carotid revascularization within the Vascular Quality Initiative (VQI).MethodsData from the VQI carotid endarterectomy (CEA) and carotid artery stenting (CAS) databases from 2016 to 2021 were used. Nineteen geographic VQI regions were divided into three tertiles based on the average annual volume of carotid procedures performed per region (low-volume: 956 cases [range, 144-1382]; medium-volume: 1533 cases [range, 1432-1589]; and high-volume: 1845 cases [range, 1642-2059]). Patients' characteristics, indications for carotid revascularization, practice patterns, and outcomes (perioperative and 1-year stroke/death) of different revascularization techniques were compared between these regional groups. Regression models that adjust for known risk factors and allow for random effects at the center level were used.ResultsCEA was the most common revascularization procedure (>60%) across all regional groups. Significant regional variation was observed in the practice of CEA such as variability in the use of shunting, drain placement, stump pressure and electroencephalogram monitoring, intraoperative protamine, and patch angioplasty. For transfemoral CAS, high-volume regions had a higher proportion of asymptomatic patients with

OBJECTIVES Our objective was to explore the safety and efficacy of a graphene oxide-loaded rapamycin-coated self-expandable metallic airway stent (GO@RAPA-SEMS) in a rabbit model. METHODS The dip coating method was used to develop a GO@RAPA-SEMS and a poly(lactic-co-glycolic)-acid loaded rapamycin-coated self-expandable metallic airway stent (PLGA@RAPA-SEMS). The surface structure was evaluated using a scanning electronic microscope. The in vitro drug-release profiles of the 2 stents were explored and compared. In the animal study, a total of 45 rabbits were randomly divided into 3 groups and underwent 3 kinds of stent placements. Computed tomography was performed to evaluate the degree of stenosis at 1, 2 and 3 months after the stent operation. Five rabbits in each group were sacrificed after the computed tomography scan. The stented trachea and blood were collected for further pathological analysis and laboratory testing. RESULTS The in vitro drug-release study revealed that GO@RAPA-SEMS exhibited a sudden release on the first day and maintained a certain release rate on the 14th day. The PLGA@RAPA-SEMS exhibited a longer sustained release time. All 45 rabbits underwent successful stent placement. Pathological results indicated that the granulation tissue thickness in the GO@RAPA-SEMS group was less than that in the PLGA@RAPA-SEMS group. The TUNEL and hypoxia-inducible factor-1α staining results support the fact that the granulation inhibition effect in the GO@RAPA-SEMS group was greater than that in the PLGA@RAPA-SEMS group. CONCLUSIONS GO@RAPA-SEMS effectively inhibited stent-related granulation tissue hyperplasia. [ABSTRACT FROM AUTHOR]

BackgroundWhile Transfemoral Carotid Artery Stenting (TFCAS) is a valid minimally invasive option for patients who also might be suitable for carotid endarterectomy (CEA) or transcarotid artery revascularization (TCAR), alternative access sites such as transbrachial (TB) or transradial (TR) are only utilized when anatomic factors preclude direct carotid or transfemoral access. In this study, we aimed to evaluate the outcomes of TR/TB access in comparison to TF for percutaneous carotid artery revascularization.MethodsAll patients undergoing non-TCAR carotid artery stenting (CAS) from January 2012 to June 2021 in the Vascular Quality Initiative (VQI) Database were included. Patients were divided into 2 groups based on the access site for CAS: TF or TR/TB. Primary outcomes included stroke/death, technical failure and access site complications (hematoma, stenosis, infection, pseudoaneurysm and AV fistula). Secondary outcomes included stroke, TIA, MI, death, non-home discharge, extended length of postoperative stay (LOS) (>1 day), and composite endpoints of stroke/MI and stroke/death/MI. Univariable and multivariable logistic regression models were used to assess postoperative outcomes, and results were adjusted for relevant potential confounders including age, gender, race, degree of stenosis, symptomatic status, anesthesia, comorbidities, and preoperative medications.ResultsOut of the 23,965 patients, TR/TB approach was employed in 819 (3.4%) while TF was used in 23,146 (96.6%). Baseline characteristics found men were more likely to undergo revascularization using TR/TB approach (69.4% vs. 64.9%, P = 0.009). Patients undergoing TR/TB approach were also more likely to be symptomatic (49.9% vs. 28.6%, P

BackgroundPeripheral vascular disease remains a leading cause of vascular morbidity and mortality worldwide despite advances in medical and surgical therapy. Besides traditional approaches, which can only restore blood flow to native arteries, an alternative approach is to enhance the growth of new vessels, thereby facilitating the physiological response to ischemia.MethodsThe ActinCreER/R26VT2/GK3 Rainbow reporter mouse was used for unbiased in vivo survey of injury-responsive vasculogenic clonal formation. Prospective isolation and transplantation were used to determine vessel-forming capacity of different populations. Single-cell RNA-sequencing was used to characterize distinct vessel-forming populations and their interactions.ResultsTwo populations of distinct vascular stem/progenitor cells (VSPCs) were identified from adipose-derived mesenchymal stromal cells: VSPC1 is CD45-Ter119-Tie2+PDGFRa-CD31+CD105highSca1low, which gives rise to stunted vessels (incomplete tubular structures) in a transplant setting, and VSPC2 which is CD45-Ter119-Tie2+PDGFRa+CD31-CD105lowSca1high and forms stunted vessels and fat. Interestingly, cotransplantation of VSPC1 and VSPC2 is required to form functional vessels that improve perfusion in the mouse hindlimb ischemia model. Similarly, VSPC1 and VSPC2 populations isolated from human adipose tissue could rescue the ischemic condition in mice.ConclusionsThese findings suggest that autologous cotransplantation of synergistic VSPCs from nonessential adipose tissue can promote neovascularization and represents a promising treatment for ischemic disease.

Cancer is one of the leading causes of mortality worldwide. Numerous strategies have been developed for cancer treatment. Metastasis, heterogeneity, chemotherapy resistance, recurrence, and evasion of immune surveillance are the primary reasons for the failure of cancer treatment. Cancer stem cells (CSCs) can give rise to tumors via self-renewal and differentiation into various cell types. They show resistance to chemotherapy and radiotherapy and have a strong capability of invasion and metastasis. Extracellular vesicles (EVs) are bilayered vesicles that carry biological molecules and are released under both healthy and unhealthy conditions. It has been shown that one of the leading causes of cancer treatment failure is cancer stem cell-derived EVs (CSC-EVs). CSC-EVs have essential roles in tumor progression, metastasis, tumor angiogenesis, chemoresistance, and immunosuppressants. In the future, controlling EV production in CSCs may be one of the most promising strategies to stop cancer treatment failures.

Angiogenesis is an essential process in normal development and in adult physiology, but can be disrupted in numerous diseases. The concept of targeting angiogenesis for treating diseases was proposed more than 50 years ago, and the first two drugs targeting vascular endothelial growth factor (VEGF), bevacizumab and pegaptanib, were approved in 2004 for the treatment of cancer and neovascular ophthalmic diseases, respectively. Since then, nearly 20 years of clinical experience with anti-angiogenic drugs (AADs) have demonstrated the importance of this therapeutic modality for these disorders. However, there is a need to improve clinical outcomes by enhancing therapeutic efficacy, overcoming drug resistance, defining surrogate markers, combining with other drugs and developing the next generation of therapeutics. In this Review, we examine emerging new targets, the development of new drugs and challenging issues such as the mode of action of AADs and elucidating mechanisms underlying clinical benefits; we also discuss possible future directions of the field.

ObjectivesRapid diameter growth is a criterion for ascending thoracic aortic aneurysm repair; however, there are sparse data on aneurysm elongation rate. The purpose of this study was to assess aortic elongation rates in nonsyndromic, nonsurgical aneurysms to understand length dynamics and correlate with aortic diameter over time.MethodsPatients with

An ongoing debate exists regarding the feasibility of placing self-expanding metallic stents (SEMS) within 5 cm of the anal verge. Traditionally, SEMS have been considered contraindicated for patients with a malignant rectal obstruction within this region due to potential impact on the anorectal ring or anal canal, which can cause incontinence, proctalgia, and tenesmus. However, in the case of a 63-year-old female who presented with distention, abdominal pain, and diminishing stool output, the rectal exam identified a bulky fixed mass. Imaging studies revealed large bowel obstruction and high-grade stricture, with a minuscule residual lumen. Endoscopy identified a bulky mass obscuring the lumen at 5 cm from the anal verge, and biopsy confirmed adenocarcinoma. Despite the traditionally held contraindication, a 2.5 cm × 9.0 cm colonic stent was successfully deployed, leading to brisk colonic decompression. This allowed the patient to promptly undergo chemoradiotherapy. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To evaluate a deep learning model for automated and interpretable classification of central canal stenosis, neural foraminal stenosis, and facet arthropathy from lumbar spine MRI. METHODS: T2-weighted axial MRI studies of the lumbar spine acquired between 2008 and 2019 were retrospectively selected (n = 200) and graded for central canal stenosis, neural foraminal stenosis, and facet arthropathy. Studies were partitioned into patient-level train (n = 150), validation (n = 20), and test (n = 30) splits. V-Net models were first trained to segment the dural sac and the intervertebral disk, and localize facet and foramen using geometric rules. Subsequently, Big Transfer (BiT) models were trained for downstream classification tasks. An interpretable model for central canal stenosis was also trained using a decision tree classifier. Evaluation metrics included linearly weighted Cohens kappa score for multi-grade classification and area under the receiver operator characteristic curve (AUROC) for binarized classification. RESULTS: Segmentation of the dural sac and intervertebral disk achieved Dice scores of 0.93 and 0.94. Localization of foramen and facet achieved intersection over union of 0.72 and 0.83. Multi-class grading of central canal stenosis achieved a kappa score of 0.54. The interpretable decision tree classifier had a kappa score of 0.80. Pairwise agreement between readers (R1, R2), (R1, R3), and (R2, R3) was 0.86, 0.80, and 0.74. Binary classification of neural foraminal stenosis and facet arthropathy achieved AUROCs of 0.92 and 0.93. CONCLUSION: Deep learning systems can be performant as well as interpretable for automated evaluation of lumbar spine MRI including classification of central canal stenosis, neural foraminal stenosis, and facet arthropathy. KEY POINTS: • Interpretable deep-learning systems can be developed for the evaluation of clinical lumbar spine MRI. Multi-grade classification of central canal stenosis with a kappa of 0.80 was comparable to inter-reader agreement scores (0.74, 0.80, 0.86). Binary classification of neural foraminal stenosis and facet arthropathy achieved favorable and accurate AUROCs of 0.92 and 0.93, respectively. • While existing deep-learning systems are opaque, leading to clinical deployment challenges, the proposed system is accurate as well as interpretable, providing valuable information to a radiologist in clinical practice.

BackgroundHuman endothelial progenitor cells (hEPCs), originating from hemangioblasts in bone marrow (BM), migrate into the blood circulation, differentiate into endothelial cells, and could act as an alternative tool for tissue regeneration. In addition, trimethylamine-N-oxide (TMAO), one of the gut microbiota metabolites, has been identified as an atherosclerosis risk factor. However, the deleterious effects of TMAO on the neovascularization of hEPCs have not been studied yet.ResultsOur results demonstrated that TMAO dose-dependently impaired human stem cell factor (SCF)-mediated neovascularization in hEPCs. The action of TMAO was through the inactivation of Akt/endothelial nitric oxide synthase (eNOS), MAPK/ERK signaling pathways, and an upregulation of microRNA (miR)-221. Docosahexaenoic acid (DHA) could effectively inhibit the cellular miR-221 level and induce the phosphorylation level of Akt/eNOS, MAPK/ERK signaling molecules, and neovascularization in hEPCs. DHA enhanced cellular amounts of reduced form glutathione (GSH) through an increased expression of the gamma-glutamylcysteine synthetase (γ-GCS) protein.ConclusionsTMAO could significantly inhibit SCF-mediated neovascularization, in part in association with an upregulation of miR-221 level, inactivation of Akt/eNOS and MAPK/ERK cascades, suppression of γ-GCS protein, and decreased levels of GSH and GSH/GSSG ratio. Furthermore, the DHA could alleviate the detrimental effects of TMAO and induce neovasculogenesis through suppression of miR-221 level, activation of Akt/eNOS and MAPK/ERK signaling cascades, increased expression of γ-GCS protein, and increment of cellular GSH level and GSH/GSSG ratio in hEPCs.

CDC42 GTPases (RHOJ, CDC42, and RHOQ) are overexpressed in multiple tumor types and activate pathways critical for tumor growth, angiogenesis, and metastasis. Recently, we reported the discovery of a novel lead compound, ARN22089, which blocks the interaction of CDC42 GTPases with specific downstream effectors. ARN22089 blocks tumor growth in BRAF mutant mouse melanoma models and patient-derived xenografts (PDXs) in vivo. ARN22089 also inhibits tumor angiogenesis in three-dimensional vascularized microtumor models in vitro. Notably, ARN22089 belongs to a novel class of trisubstituted pyrimidines. Based on these results, we describe an extensive structure-activity relationship of ∼30 compounds centered on ARN22089. We discovered and optimized two novel inhibitors (27, ARN25062, and 28, ARN24928), which are optimal back-up/follow-up leads with favorable drug-like properties and in vivo efficacy in PDX tumors. These findings further demonstrate the potential of this class of CDC42/RHOJ inhibitors for cancer treatment, with lead candidates ready for advanced preclinical studies.

BACKGROUND: Accurate detection and grading of atheromatous stenotic lesions within the cardiac, renal, and intracranial vasculature is imperative for early recognition of disease and guiding treatment strategies. PURPOSE: In this work, a stenotic lesion phantom was used to compare high resolution and normal resolution modes on the same CT scanner in terms of detection and size discrimination performance. MATERIALS AND METHODS: The phantom is comprised of three acrylic cylinders (each 15.0 cm in diameter and 1.3 cm thick) with a matching array of holes in each module. The outer two modules contain holes that are slightly larger than the corresponding hole in the central module to simulate stenotic narrowing in vasculature. The stack of modules was submerged in an iodine solution simulating contrast-enhanced stenotic lesions with a range of lumen diameters (1.32-10.08 mm) and stenosis severity (0%, 50%, 60%, 70%, and 80%). The phantom was imaged on the Canon Aquilion Precision high-resolution CT scanner in high-resolution (HR) mode (0.25 mm × 0.50 mm detector element size) and normal-resolution (NR) mode (0.50 mm × 0.50 mm) using 120 kV and two dose levels (14 and 21 mGy SSDE) with 30 repeat scans acquired for each combination. Filtered back-projection (FBP) and a hybrid-iterative reconstruction (AIDR) were used with the FC18 kernel, as well as a deep learning algorithm (AiCE) which is only available for HR. A non-prewhitening model observer with an eye filter was implemented to quantify performance for detection and size discrimination tasks in the axial plane. RESULTS: Detection performance improved with increasing diameter, dose, and for AIDR in comparison to FBP for a fixed resolution mode. Performance in the HR mode was generally higher than NR for the smaller lumen diameters (1-5 mm) with decreasing differences as the diameter increased. Performance in NR mode surpassed HR mode for lumen diameters greater than ∼4 mm and ∼5 mm for 14 mGy and 21 mGy, respectively. AiCE provided consistently higher detection performance compared with AIDR-FC18 (48% higher for a 6 mm lumen diameter). Discrimination performance increased with increasing nominal diameter, dose, and for larger differences in stenosis severity. When comparing discrimination performance in HR to NR modes, the largest relative differences occur at the smallest nominal diameters and smallest differences in stenosis severity. The AiCE reconstruction algorithm produced the highest overall discrimination performance values, and these were significantly higher than AIDR-FC18 for nominal diameters of 7.14 and 10.08 mm. CONCLUSIONS: HR mode outperforms NR for detection up to a specific diameter and the results improve with AiCE and for higher dose levels. For the task of size discrimination, HR mode consistently outperforms NR if AIDR-FC18 is used for dose levels of at least 21 mGy, and the results improve with AiCE and for the smallest differences in stenosis severity investigated (50% vs. 60%). High-resolution CT appears to be beneficial for detecting smaller simulated lumen diameters (

BackgroundImaging factors, specifically baseline plaque features on high-resolution magnetic resonance vessel wall imaging (HR-VWI) that could be associated with in-stent restenosis (ISR), are still unknown. We aimed to investigate the presenting clinical and plaque features on HR-VWI associated with ISR.MethodsSixty-four patients with intracranial stent placement for intracranial atherosclerotic stenosis who had pre- and post-contrast T1-weighted HR-VWI on 3.0T prior to stenting were included in this analysis. Student's t-test, Mann-Whitney U test, χ2 test, or the Cochran-Mantel-Haenszel (CMH) test were used to compare clinical and baseline HR-VWI characteristics of the patients between the ISR and non-ISR groups. Univariable and multivariable logistic analysis were used to test the clinical and imaging factors associated with ISR.ResultsAmong the 64 patients, 9 patients (14.06%) developed ISR during the 2-year follow-up period. Plaque burden (median 0.89 vs 0.92, P=0.04), minimum lumen area (0.009 cm2 vs 0.006 cm2, P=0.04), plaque eccentricity (55.6% vs 89.1%, P＜0.01), enhancement ratio (1.36 vs 0.84, P＜0.01), and enhancement involvement (type 2 represents ≥50% cross-sectional wall involvement; 100% vs 63.6%, P=0.03) all significantly differed between patients with and without ISR. Multivariable analysis revealed that lower frequency of plaque eccentricity (OR 0.18, 95% CI 0.04 to 0.96, P=0.04) and higher enhancement ratio (OR 3.57, 95% CI 1.02 to 12.48, P=0.04) were independently associated with ISR.ConclusionsPreliminary findings showed that ISR was independently associated with plaque concentricity and higher enhancement ratios on pre-stenting HR-VWI for patients with symptomatic intracranial atherosclerotic stenosis.

BACKGROUND: Apolipoprotein E gene (APOE) ε4 allele is associated with a higher risk of carotid atherosclerosis, but less is known about the association of APOE with intracranial atherosclerotic disease (IAD). We aimed to investigate the association of APOE alleles with IAD in a cross-sectional autopsy study. METHODS: We measured the stenosis in the 12 arteries of the Circle of Willis using postmortem morphometric measurements. The APOE polymorphism was determined by real-time polymerase chain reaction. We assessed the association between APOE polymorphism and IAD using regression models adjusted for sociodemographic and clinical variables. We also verified the modifier effect of age, sex, and race on this association. We stratified the analysis by age group to investigate the possibility of attrition bias. RESULTS: In 400 participants (mean age=73.2±12.3 years old, 51% female, and 64% White), IAD was evaluated in 4,504 artery segments. APOE-ε4 was not associated with IAD nor with the number of artery stenosis compared to non-APOE-ε4 carriers. Sociodemographic variables did not modify this relationship. Among participants older than 70 years, there was a trend towards an association between APOE allele ε4 and a lower stenosis index in the middle cerebral artery, suggesting attrition bias related to the APOE-ε4 effect on mortality. CONCLUSIONS: APOE alleles were not associated with IAD in this population-based autopsy study. Lower stenosis in older participants suggests the possibility of attrition bias.

BackgroundGiant cell arteritis (GCA) is a systemic vasculitis that may cause ischemic stroke. Rarely, GCA can present with aggressive intracranial stenoses, which are refractory to medical therapy. Endovascular treatment (EVT) is a possible rescue strategy to prevent ischemic complications in intracranial GCA but the safety and efficacy of EVT in this setting are not well-described.MethodsA systematic literature review was performed to identify case reports and series with individual patient-level data describing EVT for intracranial GCA. The clinical course, therapeutic considerations, and technique of seven endovascular treatments in a single patient from the authors' experience are presented.ResultsThe literature review identified 9 reports of 19 treatments, including percutaneous transluminal angioplasty (PTA) with or without stenting, in 14 patients (mean age 69.6 ± 6.3 years). Out of 12 patients 8 (66.7%) with sufficient data had > 1 pre-existing cardiovascular risk factor. All patients had infarction on MRI while on glucocorticoids and 7/14 (50%) progressed despite adjuvant immunosuppressive agents. Treatment was PTA alone in 15/19 (78.9%) cases and PTA + stent in 4/19 (21.1%). Repeat treatments were performed in 4/14 (28.6%) of patients (PTA-only). Non-flow limiting dissection was reported in 2/19 (10.5%) of treatments. The indications, technical details, and results of PTA are discussed in a single illustrative case. We report the novel use of intra-arterial calcium channel blocker infusion (verapamil) as adjuvant to PTA and as monotherapy, resulting in immediate improvement in cerebral blood flow.ConclusionEndovascular treatment, including PTA with or without stenting or calcium channel blocker infusion, may be effective therapies in medically refractory GCA with intracranial stenosis.

OBJECTIVES Surgical treatment for airway stenosis necessitates personalized techniques based on the stenosis location and length, leading to favourable surgical outcomes. However, there is limited literature on functional outcomes following laryngotracheal surgery with an adequate number of patients. Methods We conducted a retrospective analysis of patients who underwent laryngotracheal surgery at the Department of Thoracic Surgery, Medical University of Vienna, from January 2017 to June 2021. The study included standardized functional assessments before and after surgery, encompassing spirometry, voice measurements, swallowing evaluation and subjective patient perception. RESULTS The study comprised 45 patients with an average age of 51.9 ± 15.9 years, of whom 89% were female, with idiopathic being the most common aetiology (67%). Procedures included standard cricotracheal resection in 11%, cricotracheal resection with dorsal mucosal flap in 49%, cricotracheal resection with dorsal mucosal flap and lateral cricoplasty in 24% and single-stage laryngotracheal reconstruction in 16%. There were no in-hospital mortalities or restenosis cases during the mean follow-up period of 20.8 ± 13.2 months. Swallowing function remained intact in all patients. Voice evaluations showed a decrease in fundamental vocal pitch [203 (81–290) Hz vs 150 (73–364) Hz, P  < 0.001] and dynamic voice range (23.5 ± 5.8 semitones vs 17.8 ± 6.7 semitones, P  < 0.001). However, no differences in voice volume were observed (60.0 ± 4.1 dB vs 60.2 ± 4.8 dB, P  = 0.788). The overall predicted voice profile changed from R0B0H0 to R1B0H1. CONCLUSIONS Laryngotracheal surgery proves effective in fully restoring breathing capacity while preserving vocal function. Even in cases of high-grade and complex airway stenosis necessitating laryngotracheal reconstruction, favourable functional outcomes can be achieved. [ABSTRACT FROM AUTHOR]

Subclavian steal syndrome (SSS) is a rare vascular condition characterized by retrograde blood flow in the vertebral artery, often discovered incidentally in asymptomatic patients. We present a 65-year-old male with recurrent transient ischemic attacks (TIAs) attributed to 99% stenosis at the origin of the left subclavian artery, leading to SSS. Diagnostic modalities included duplex ultrasound, confirming inverted left vertebral artery flow, and multi-slice computed tomography angiography, confirming the diagnosis. Despite an unsuccessful attempt at balloon angioplasty, successful vascular surgery was performed, establishing a left carotid-vertebral artery bypass. The patient recovered well without complications. This case underscores the importance of considering SSS in TIA cases, utilizing non-invasive diagnostic tools, and highlighting the successful management of symptomatic SSS through surgical intervention. [ABSTRACT FROM AUTHOR]

Background Increasing mortality and morbidity of coronary artery disease (CAD) highlight the emerging need for novel noninvasive markers such as circulating microRNAs (miRNAs). Objective To evaluate the circulating levels of miR-126-3p, miR-210-3p, let-7g-5p, and miR-326, and their associations with known contributors to CAD, in CAD subgroups. Methods We divided the cohort into 4 groups: non-CAD controls (≤30% stenosis; n = 55), and patients with stable angina pectoris (SAP; n = 48), unstable AP (UAP; n = 46), and myocardial infarction (MI; n = 36). The circulating levels of miR-126-3p, miR-210-3p, let-7g-5p, and miR-326 were determined using TaqMan Advanced miRNA Assays in serum specimens. Results Circulating miR-126-3p levels were lower in the MI and UAP groups, compared with the non-CAD group, whereas miR-210-3p circulating levels were lower in the MI group than others. The levels of circulating let-7g-5p were shown to be useful for distinguishing UAP from MI, and there were substantial differences in circulating let-7g-5p levels between the UAP and MI groups. Moreover, lipid levels and ratios were lower in individuals with high circulating miR-126-3p and miR-210-3p levels. Conclusions The study results suggest that circulating miR-126-3p, miR-210-3p, and let-7g-5p are differentiated between different clinical presentations of CAD and associated with lipid levels, which are important risk factors and determinants of CAD. [ABSTRACT FROM AUTHOR]

Cowper's syringocele is a cystic dilation of the bulbourethral duct or gland. This rare pathology has historically been diagnosed in the pediatric population, with recent literature reporting an increased incidence in adults. Attempts have been made to classify Cowper's syringoceles by their appearance on imaging and endoscopy, however a simpler classification of unobstructed versus obstructed may be of more utility in directing management. Herein, we present a novel case of a Cowper's syringocele developed in adulthood that supports the suspicion for underdiagnosis, as well as one proposed mechanism of acquired etiology of Cowper's syringoceles involving incomplete or intermittent obstruction secondary to the application of external force of the leading to asymptomatic cystic dilation. [ABSTRACT FROM AUTHOR]

Background and Aim: The presence of blood in the stomach has been thought to affect the performance of diagnostic tests used in detecting Helicobacter pylori (H. pylori) in the stomach. This study evaluates the effect of upper gastrointestinal bleeding on the efficacy of a rapid urease test (RUT) and compares the results with the pathologic method. Methods: In this descriptive study, 100 patients presented with upper gastrointestinal bleeding, confirmed from endoscopy, referred to Shahid Rahimi Hospital in Khorramabad were enrolled. Antral biopsy was performed in all the patients and the samples were extracted for histopathology and RUT. A questionnaire was used to collect rapid urease test outcomes and associated parameters (antibiotic, bismuth, and proton pump inhibitors), histology and demographic data. Histopathology was used as the gold standard for diagnosis of H. pylori. Results: Of the 52 patients who were reported positive for H. pylori in pathology, 36 had RUT‐positive H. pylori, sensitivity 69.2%, and of 48 patients whose pathology was negative, 25 had negative RUT, specificity 52.1%. Of 59 RUT, 36 had positive pathology, positive predictive value was 61% and from 41 with negative RUT, 25 had negative pathology, negative predictive value was 61%. The prevalence of H. pylori infection was significantly associated with the age of 50 years and above, p = 0.042, and previous history of bleeding, p = 0.019. Conclusion: Gastrointestinal bleeding can reduce the sensitivity of RUT. The negative results of these tests in acute upper gastrointestinal bleeding should therefore be interpreted carefully. [ABSTRACT FROM AUTHOR]

Eosinophilic gastroenteritis is a rare disease with an unknown cause, which can manifest independently or as part of a hyper-eosinophilic syndrome. The severity of the condition depends on the extent of eosinophilic infiltration and damage to the digestive tract. Diagnosis relies on histological examination, which reveals a significant presence of eosinophilic polymorphonuclear leukocytes in the digestive wall. The authors present a new case of eosinophilic gastroenteritis in a 28-year-old patient who exhibited obstructive symptoms but lacked peripheral eosinophilia. Esophagogastroduodenoscopy showed no abnormalities, but barium transit imaging revealed gastro-duodeno-jejunal dilation upstream of a tight jejunal stenosis. Surgical examination of the affected area confirmed a diffuse and transparietal eosinophilic infiltrate, with no evidence of parasitic or granulomatous lesions. Fortunately, the patient had a swift recovery following surgery. Biopsies conducted at other locations, including the gastric, hepatic, and medullary levels, produced negative results, indicating the localized nature of the condition. [ABSTRACT FROM AUTHOR]

This case study presents a female patient with progressive dysphagia for solids, heartburn, and obesity that proved refractory to clinical management. Imagenological diagnosis revealed esophageal stenosis and achalasia. Furthermore, metabolic syndrome was established. We proposed intervention through esophagogastric reconstruction due to stenosis, revision of cardiomyotomy and robotic gastric bypass revealing scar tissue and fibrosis on the anterior aspect of the stomach resulting from prior fundoplication surgery. The patient underwent esophagogastric reconstruction due to adhesion bands which conditioned partial angulation of the gastroesophageal junction, cardiomyotomy revision, anterior and posterior hiatal plasty, and Roux Y Gastric Bypass assisted by a robot without complications. The intervention resulted in significant improvement in postoperative symptoms. This case highlights the importance of considering the probability of mechanical obstruction due to postsurgical adhesions in the initial evaluation of recurrent and persistent dysphagia, with surgical reintervention being the ideal option for resolution. [ABSTRACT FROM AUTHOR]

Objective: To outline the clinical picture of bilateral posterior canal benign paroxysmal positional vertigo. Methods: A total of 573 patients with posterior canal benign paroxysmal positional vertigo were classified as having unilateral, or true or pseudo bilateral, posterior canal benign paroxysmal positional vertigo, and were treated with the Epley manoeuvre. Statistical significance was set at p < 0.05. Results: Of the patients, 483 had unilateral and 90 (15.7 per cent) had bilateral presentation. Of the latter, 72 patients had pseudo bilateral posterior canal benign paroxysmal positional vertigo. Comparisons of site of involvement, male to female ratio and the incidence of associated problems in unilateral, and true and pseudo bilateral posterior canal benign paroxysmal positional vertigo did not reveal any statistically significant differences (p = 0.828, p = 0.200, p = 0.142). Comparisons of the number of manoeuvres required to provide symptom relief and the rate of recurrence were significant (p < 0.05). Conclusion: Identification of true and pseudo bilateral posterior canal benign paroxysmal positional vertigo is important given the differences in aetiology and treatment outcome. Treatment of patients with true bilateral posterior canal benign paroxysmal positional vertigo requires several therapeutic manoeuvre attempts, and patients should be warned about recurrence. [ABSTRACT FROM AUTHOR]

AimsWe determined the feasibility and diagnostic performance of segmental 18F-flurpiridaz myocardial blood flow (MBF) measurement by positron emission tomography (PET) compared with the standard territory method, and assessed whether flow metrics provide incremental diagnostic value beyond relative perfusion quantitation (PQ).Methods and resultsAll evaluable pharmacological stress patients from the Phase III trial of 18F-flurpiridaz were included (n = 245) and blinded flow metrics obtained. For each coronary territory, the segmental flow metric was defined as the lowest 17-segment stress MBF (SMBF), myocardial flow reserve (MFR), or relative flow reserve (RFR) value. Diagnostic performances of segmental and territory MBF metrics were compared by receiver operating characteristic (ROC) areas under the curve (AUC). A multiple logistic model was used to evaluate whether flow metrics provided incremental diagnostic value beyond PQ alone. The diagnostic performances of segmental flow metrics were higher than their territory counterparts; SMBF AUC = 0.761 vs. 0.737; MFR AUC = 0.699 vs. 0.676; and RFR AUC = 0.716 vs. 0.635, respectively (P < 0.001 for all). Similar results were obtained for per-vessel coronary artery disease (CAD) ≥70% stenosis categorization and per-patient analyses. Combinatorial analyses revealed that only SMBF significantly improved the diagnostic performance of PQ in CAD ≥50% stenoses, with PQ AUC = 0.730, PQ + segmental SMBF AUC = 0.782 (P < 0.01), and PQ + territory SMBF AUC = 0.771 (P < 0.05). No flow metric improved diagnostic performance when combined with PQ in CAD ≥70% stenoses.ConclusionAssessment of segmental MBF metrics with 18F-flurpiridaz is feasible and improves flow-based epicardial CAD detection. When combined with PQ, only SMBF provides additive diagnostic performance in moderate CAD.

PurposeWe aimed to provide a thorough comparative review of the available guidelines on the diagnosis, management, and follow-up for patients with posterior urethral stenosis by the American Urologic Association (2016), Société Internationale d'Urologie (2010), and European Urologic Association (2022).MethodsThe AUA, SIU, and EAU guidelines were evaluated for recommendations on the diagnosis, evaluation, and treatment of posterior urethral stenosis. We also included the EAU and AUA urologic trauma guidelines for the trauma-related stenosis. The level or strength of recommendations is included in case of disparity between the guidelines.ResultsThe three guidelines align considerably in recommendations provided for the diagnosis, management, and follow-up of patients with posterior urethral stenosis. SIU and EAU emphasize the role of repeat endoscopic treatment in guidelines compared to AUA.ConclusionThe preferred method to repair bulbo-membranous stricture/stenosis following radiation therapy remains an area of active interest, focusing on continence preservation. Additionally, there may be a role for advanced endoscopic treatments with or without adjunct therapies to manage even obliterated stenoses.

BACKGROUND AND PURPOSE: Quantitative metrics of the dural sac such as the cross-sectional area are commonly used to evaluate central canal stenosis. The aim of this study was to analyze 2 new metrics to measure spinal stenosis on the basis of the ratio between the dural sac and disc cross-sectional areas (DDRCA) and the dural sac and disc anterior-posterior diameters (DDRDIA) and compare them with established quantitative metrics of the dural sac. MATERIALS AND METHODS: T2-weighted axial MR images (n = 260 patients) were retrospectively evaluated, graded for central canal stenosis as normal (no stenosis), mild, moderate, or severe from L1/L2 through L5/S1 with 1 grade per spinal level and annotated to measure the DDRCA and DDRDIA. Thresholds were obtained using a decision tree classifier on a subset of patients (n = 130) and evaluated on the remaining patients (n = 130) for accuracy and consistency across demographics, anatomic variation, and clinical outcomes. RESULTS: DDRCA and DDRDIA had areas under the receiver operating characteristic curve of 98.6 (97.4-99.3) and 98.0 (96.7-98.9) compared with dural sac cross-sectional area at 96.5 (95.0-97.7) for binary classification. DDRDIA and DDRCA had κ scores of 0.75 (0.71-0.79) and 0.80 (0.75-0.83) compared with dural sac cross-sectional area at 0.62 (0.57-0.66) for multigrade classification. No significant differences (P > .1) in the area under the receiver operating characteristic curve were observed for the DDRDIA across variations in the body mass index. The DDRDIA also had the highest area under the receiver operating characteristic curve among symptomatic patients (visual analog scale ≥ 7) or patients who underwent surgery. CONCLUSIONS: Ratio-based metrics (DDRDIA and DDRCA) are accurate and robust to anatomic and demographic variability compared with quantitative metrics of the dural sac and better correlated with symptomatology and surgical outcomes.

Interactions between angiogenesis and neurogenesis regulate embryonic brain development. However, a comprehensive understanding of the stages of vascular cell maturation is lacking, especially in the prenatal human brain. Using fluorescence-activated cell sorting, single-cell transcriptomics, and histological and ultrastructural analyses, we show that an ensemble of endothelial and mural cell subtypes tile the brain vasculature during the second trimester. These vascular cells follow distinct developmental trajectories and utilize diverse signaling mechanisms, including collagen, laminin, and midkine, to facilitate cell-cell communication and maturation. Interestingly, our results reveal that tip cells, a subtype of endothelial cells, are highly enriched near the ventricular zone, the site of active neurogenesis. Consistent with these observations, prenatal vascular cells transplanted into cortical organoids exhibit restricted lineage potential that favors tip cells, promotes neurogenesis, and reduces cellular stress. Together, our results uncover important mechanisms into vascular maturation during this critical period of human brain development.

A 73-year-old male presented with angina symptoms and was diagnosed with three-vessel coronary artery disease by use of computed tomography angiography and coronary angiography. This diagnosis necessitated coronary artery bypass grafting (CABG) surgery. A custom made AI-driven algorithm was used to generate a patient-specific three-dimensional coronary artery model from computed tomography angiography imaging data. This framework enabled precise segmentation and reconstruction of the coronary vasculature, yielding an accurate anatomical and pathological representation. Subsequently, this generated model was integrated into a novel extended reality tool for preoperative planning and intraoperative guidance in CABG surgery. Both preoperatively and intraoperatively, the tool augmented spatial orientation and facilitated precise stenosis localization, thereby enhancing the surgeon's operative proficiency. This case report underscores the utility of advanced extended reality tools in cardiovascular surgery, emphasizing their pivotal role in refining surgical planning and execution. [ABSTRACT FROM AUTHOR]

ObjectiveTo raise awareness that patients with proximal ureteral stricture who elect for nephrectomy can consider donating the kidney. We present a series of patients undergoing therapeutic living donor nephrectomy (TLDN), a scenario in which a patient undergoing nephrectomy for an underlying medical problem donates the kidney to a person with end-stage renal disease. This practice is underutilized, and only a single TLDN with proximal ureteral stricture has been previously described. We aim to help define the indications, risks, and benefits for patients.MethodsThis is a retrospective case series of seven therapeutic donors with proximal ureteral pathology and stone disease. Patient characteristics, donor work up, operative details, and donor and recipient outcome were collected.ResultsAll seven donors had proximal ureteral pathology, and six of the seven had nephrolithiasis or ureterolithiasis. After electing for nephrectomy, the mean time to TLDN was 57.9 days. No recipients experienced delayed graft function . Mean follow up was 40.1 months (range 8-131), and the most recent follow-up mean creatinine was 1.08 (mg/dL). Graft and recipient survival is 100%. No recipients developed recurrence of ureteral stricture or stones.ConclusionThis is the first series demonstrating patients with proximal ureteral stricture, even with concomitant stone disease, may donate kidneys for transplantation. Recipient outcomes suggest this practice is safe, and appropriately selected patients that have already elected for nephrectomy should receive counseling about this opportunity. Importantly, patients who donate a kidney receive waiting list priority if they ever need a kidney transplant in the future.

BackgroundThere is limited "real-world" evidence examining treatment modalities and outcomes in patients with symptomatic peripheral arterial disease undergoing endovascular treatment of femoropopliteal (FP) in-stent restenosis (ISR).Materials and methodsWe compared outcomes in 2,895 patients from the XLPAD registry (NCT01904851) between 2006 and 2019 treated for FP ISR (n = 347) and non-ISR (n = 2,548) lesions. Primary endpoint included major adverse limb events (MALE) at 1 year, a composite of all-cause death, target limb repeat revascularization, or major amputation.ResultsISR patients were more frequently on antiplatelet (94.5% vs 89.4%, p=0.007) and statin (68.9% vs 60.3%, p=0.003) therapies. Lesion length was similar (ISR: 145 ± 99 mm vs. non-ISR: 142 ± 99 mm, p=0.55). Fewer treated ISR lesions were chronic total occlusions (47.3% vs. 53.7%, p=0.02) and severely calcified (22.4% vs. 44.7%, p < 0.001). Atherectomy (63.5% vs. 45.0%, p < 0.001) and drug-coated balloons (DCB; 4.7% vs. 1.7%, p < 0.001) were more frequently used in ISR lesions. The distal embolization rate was higher in ISR lesions (2.4% vs. 0.9%, p=0.02). Repeat revascularization (21.5% vs. 16.7%, p=0.04; Figure) was higher and freedom from MALE at 1 year was significantly lower (87% vs. 92.5%, p < 0.001) in the ISR group.ConclusionAtherectomy and DCB are more frequently used to treat FP ISR lesions. Patients with FP ISR have more intraprocedural distal embolization, higher repeat revascularization procedures, and lower freedom from MALE at 1 year.

Collateral circulation in the circle of Willis (CoW), closely associated with disease mechanisms and treatment outcomes, can be effectively investigated using one-dimensional-zero-dimensional hemodynamic simulations. As the entire cardiovascular system is considered in the simulation, it captures the systemic effects of local arterial changes, thus reproducing collateral circulation that reflects biological phenomena. The simulation facilitates rapid assessment of clinically relevant hemodynamic quantities under patient-specific conditions by incorporating clinical data. During patient-specific simulations, the impact of clinical data uncertainty on the simulated quantities should be quantified to obtain reliable results. However, as uncertainty quantification (UQ) is time-consuming and computationally expensive, its implementation in time-sensitive clinical applications is considered impractical. Therefore, we constructed a surrogate model based on machine learning using simulation data. The model accurately predicts the flow rate and pressure in the CoW in a few milliseconds. This reduced computation time enables the UQ execution with 100 000 predictions in a few minutes on a single CPU core and in less than a minute on a GPU. We performed UQ to predict the risk of cerebral hyperperfusion (CH), a life-threatening condition that can occur after carotid artery stenosis surgery if collateral circulation fails to function appropriately. We predicted the statistics of the postoperative flow rate increase in the CoW, which is a measure of CH, considering the uncertainties of arterial diameters, stenosis parameters, and flow rates measured using the patients' clinical data. A sensitivity analysis was performed to clarify the impact of each uncertain parameter on the flow rate increase. Results indicated that CH occurred when two conditions were satisfied simultaneously: severe stenosis and when arteries of small diameter serve as the collateral pathway to the cerebral artery on the stenosis side. These findings elucidate the biological aspects of cerebral circulation in terms of the relationship between collateral flow and CH.

Background and aimsPeople living with HIV (HIV+) are surviving longer due to effective antiretroviral therapy. Cardiovascular disease is a leading cause of non-AIDS related clinical events. We determined HIV-related factors associated with coronary artery stenosis progression.MethodsWe performed serial coronary CT angiography among HIV+ and HIV-uninfected (HIV-) men in the Multicenter AIDS Cohort Study. The median inter-scan interval was 4.5 years. Stenosis was graded as 0, 1-29, 30-49, 50-69 or ≥70%. Progression was defined as an increase ≥2 categories. Suppressed HIV infection was consistent viral loads 1 viral load >500 copies/ml demonstrated greatest stenosis progression (RR 3.01; 95% CI, 1.53-4.92, p = 0.001 compared with HIV- men). Suppressed HIV+ men with suboptimal antiretroviral adherence had greater stenosis progression (RR 1.91; 95% CI 1.12-3.24, p = 0.02) than HIV + suppressed men with optimal adherence.ConclusionsCoronary artery stenosis progression was associated with suboptimal HIV RNA suppression and antiretroviral therapy adherence. Effective ongoing HIV virologic suppression and antiretroviral therapy adherence may mitigate risk for coronary disease events among people living with HIV.

PurposeA successful urethroplasty has been defined in different ways across studies. This variety in the literature makes it difficult to compare success rates and techniques across studies. We aim to evaluate the success of anterior urethroplasty based on different definitions of success in a single cohort.Materials and methodsData were collected from a multi-institutional, prospectively maintained database. We included men undergoing first-time, single-stage, anterior urethroplasty between 2006 and 2020. Exclusion criteria included lack of followup, hypospadias, extended meatotomy, perineal urethrostomy, posterior urethroplasty and staged repairs. We compared 5 different ways to define a "failed" urethroplasty: 1) stricture retreatment, 2) anatomical recurrence on cystoscopy, 3) peak flow rate