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Background: With an increasing demand for critical care expertise and limitations in intensivist availability, innovative staffing models, such as the utilization of advanced practice providers (APPs), have emerged., Objectives: The purpose of the study was to compare patient outcomes between APP and housestaff teams in the cardiac intensive care unit (CICU)., Methods: This retrospective study, spanning March 2022 to July 2023, compares patient characteristics and outcomes between two CICU teams embedded in the same CICU at a large urban academic hospital: one staffed by housestaff and the other by APPs (80% physician assistants, 20% nurse practitioners) who each had approximately 1 to 2 years of experience in the CICU. The primary outcome was CICU mortality. Multivariable Cox regression analyses and Kaplan-Meier curves were used to assess the primary outcome., Results: A total of 1,620 admissions were analyzed: 1,013 patients on the housestaff service and 607 patients on the APP service. There were no significant differences in patient demographics, admitting diagnoses, use of vasoactive medications, inotropes, or mechanical circulatory support. There was no difference in CICU mortality (8.4% vs 8.2%, adjusted hazard ratio 0.73; 95% CI: 0.51-1.05; P  = 0.10), in-hospital mortality (13.5% vs 13.8%, aHR 0.82; 95% CI: 0.62-1.08; P  = 0.17), or in-hospital length of stay between the housestaff and APP teams. Patients managed by the housestaff team had a lower CICU length of stay (2 days IQR: 1-4 days] vs 3 days [IQR: 1-5 days], P  = 0.047). Fellowship rotation scores (based on surveys completed by the cardiology fellows) of the CICU also improved after the implementation of the APP-based team (3.87 ± 0.14 before vs 4.61 ± 0.06 after, P  < 0.0001)., Conclusions: Our moderately sized study demonstrated no difference in CICU or in-hospital mortality between patients managed by a housestaff team versus those managed by an APP team., Competing Interests: Dr Bangalore serves on the advisory board of Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer, Merck, REATA, Inari, and Truvic. Dr Alviar serves as a consultant at Zoll Inc, Abbott, and Abiomed and receives research grants from Baxter Medical. Dr Katz has received research support (modest) from Abbott Corporation, Speaker Honoraria of Zoll Inc, and the member of the Data Safety & Monitoring Board of Abiomed Inc. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 Published by Elsevier on behalf of the American College of Cardiology Foundation.)

Background and Objective: Few studies have examined pediatric hospital utilization across the spectrum of eating disorder (ED) diagnoses among hospitalized patients. We describe sociodemographic and clinical characteristics, hospital utilization, and enteral tube feeding and examine factors associated with hospital utilization among patients with EDs., Methods: Using data from the Pediatric Health Information System, we included patients aged 4 to 20 years with primary ED diagnoses hospitalized from 2018 to 2022. We examined sociodemographic factors, length of stay, costs, and enteral tube feeding by ED diagnosis. Adjusted regression models compared hospital utilization by diagnosis, adjusting for sociodemographic and clinical factors., Results: Among N = 10 279 hospitalizations from 49 hospitals, anorexia nervosa (AN) was most common (70.9%), followed by avoidant restrictive food intake disorder (ARFID) (15.6%). Mean age was 15.1 years (SD = 2.5), and most were female (86.6%), of white non-Hispanic race (70.9%), with private insurance (70.1%), with 63.9% occurring after the coronavirus disease 2019 pandemic onset. Median (interquartile range) length of stay was 8.0 days (7.0), and hospital costs were $18 099 ($15 592). A total of 18.8% received enteral tube feeding, with significant hospital variation. In adjusted models, compared with AN, ARFID, binge disorders, and unspecified feeding and ED had shorter stays, whereas hospital costs were lower for binge disorders, and enteral feeding was more likely for ARFID., Conclusions: Our findings indicate long and costly hospitalizations, especially for AN, with implications for hospital and treatment capacity, highlighting the need for earlier diagnosis and treatment to prevent the need for hospitalization., Competing Interests: CONFLICT OF INTEREST DISCLOSURES: The authors have indicated they have no potential conflicts of interest relevant to this article to disclose., (Copyright © 2024 by the American Academy of Pediatrics.)

Right ventricular-pulmonary arterial coupling describes the relation between right ventricular contractility and its afterload and is estimated as the ratio of the tricuspid annular plane systolic excursion (TAPSE) to pulmonary arterial systolic pressure (PASP) by way of echocardiography. Whether TAPSE/PASP is reflective of invasive hemodynamics or occult shock in acute pulmonary embolism (PE) is unknown. This was a single-center retrospective study over a 3-year period of consecutive patients with PE who underwent mechanical thrombectomy and simultaneous pulmonary artery catheterization with echocardiograms performed within 24 hours before the procedure. A total of 70 patients (81% intermediate risk) had complete invasive hemodynamic profiles and echocardiograms, with TAPSE/PASP calculated. The optimal cutoff for TAPSE/PASP as a predictor of a reduced cardiac index (CI) (CI ≤2.2 L/min/m 2 ) was 0.34 mm/mm Hg, with an area under the curve of 0.97 and sensitivity, specificity, positive predictive value, and negative predictive value of 97.3%, 90.9%, 92.3%, and 96.8%, respectively. Every 0.1 mm/mm Hg decrease in TAPSE/PASP was associated with a 0.24-L/min/m 2 decrease in the CI. This relation was similar when restricted to intermediate-risk PE. The TAPSE/PASP ratio was predictive of normotensive shock with an odds ratio of 2.63 (95% confidence interval 1.42 to 4.76, p = 0.002) per unit decrease in the ratio. In conclusion, in patients with acute PE who underwent mechanical thrombectomy, TAPSE/PASP was a strong predictor of a reduced CI and normotensive shock. This means that noninvasive point-of-care assessment of hemodynamics may have added value in PE risk stratification., Competing Interests: Declaration of competing interest Dr. Bangalore reports being part of the advisory board for Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer (New York, New York), Merck, REATA, Inari, Truvic, and Argon. Dr. Horowitz receives funding from Inari Medical. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Colchicine has an expanding role in cardiovascular disease treatment. Colchicine overdose is a toxicologic emergency. Direct cellular toxicity interferes with myocardial contractility, leading to cardiovascular collapse. We present a case of a patient with a colchicine overdose supported with venoarterial extracorporeal membrane oxygenation, highlighting the challenges and limitations., Competing Interests: The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Objective: To assess efficacy of Chinese medicine (CM) on insomnia considering characteristics of treatment based on syndrome differentiation., Methods: A total of 116 participants aged 18 to 65 years with moderate and severe primary insomnia were randomized to the placebo (n=20) or the CM group (n=96) for a 4-week treatment and a 4-week follow-up. Three CM clinicians independently prescribed treatments for each patient based on syndromes differentiation. The primary outcome was change in total sleep time (TST) from baseline. Secondary endpoints included sleep onset latency (SOL), wake time after sleep onset (WASO), sleep efficiency, Pittsburgh Sleep Quality Index (PSQI) and CM symptoms., Results: The CM group had an average 0.6 h more (95% confidence interval (CI): 0.3-0.9, P<0.001) TST and 34.1% (10.3%-58.0%, P=0.005) more patients beyond 0.5 h TST increment than that of the placebo group. PSQI was changed -3.3 (-3.8 to -2.7) in the CM group, a -2.0 (-3.2 to -0.8, P<0.001) difference from the placebo group. The CM symptom score in the CM group decreased -2.0 (-3.3 to -0.7, P=0.003) more than the placebo group. SOL and WASO changes were not significantly different between groups. The analysis of prescriptions by these clinicians revealed blood deficiency and Liver stagnation as the most common syndromes. Prescriptions for these clinicians displayed relative stability, while the herbs varied. All adverse events were mild and were not related to study treatment., Conclusion: CM treatment based on syndrome differentiation can increase TST and improve sleep quality of primary insomnia. It is effective and safe for primary insomnia. In future studies, the long-term efficacy validation and the exploratory of eutherapeutic clinicians' fixed herb formulas should be addressed (Registration No. NCT01613183)., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: This study explores the implementation and outcomes of catheter-based thrombectomy (CBT) for acute pulmonary embolism (PE) within a safety-net hospital (SNH), addressing a critical gap in the literature concerning CBT in underserved and vulnerable populations., Methods: This is a retrospective study of patients undergoing CBT between October 2020 and January 2024 at a SNH. The primary outcome was 30-day all-cause mortality., Results: A total of 107 patients (47.6 % female, mean age 58.4 years) underwent CBT for acute PE, with 23 (21.5 %) high-risk and 84 (78.5 %) intermediate-risk PE. Demographically, 64 % identified as Black, 10 % White, 19 % Hispanic or Latino, and 5 % Asian. In terms of insurance coverage, 50 % had private insurance or Medicare, 36 % had Medicaid, and 14 % were uninsured. Notably, 67 % of the patients resided in high poverty rate zip codes and 11 % were non-citizen non-residents. Over a median follow up period of 30 days, 6 (5.6 %) patients expired (all high-risk PE), 3 of whom presented with cardiac arrest. No patients who presented with intermediate-risk PE died at 30 days. There was no difference in 30-day mortality based on race, insurance type, poverty level or citizenship status., Conclusion: Our study findings reveal no disparities in access or outcomes to CBT at our SNH, emphasizing the feasibility and success of implementing PERT and CBT at a SNH, offering a potential model to address healthcare disparities in acute PE on a broader scale., Competing Interests: Declaration of competing interest Dr. Bangalore- Advisory board- Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer, Merck, REATA, Inari, Truvic., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Clot-in-transit (CIT) is associated with high mortality, and optimal treatment strategies remain uncertain. This study compares the efficacy of catheter-based thrombectomy (CBT) with other treatments for CIT, including anticoagulation, systemic thrombolytic (ST) therapy, and surgical thrombectomy. We conducted a retrospective analysis of patients with CIT documented on echocardiography between January 2020 and May 2024, managed with urgent upfront CBT. We compared the all-cause mortality rates of the CBT cohort to performance goal rates for anticoagulation, systemic thrombolysis (ST), and surgical thrombectomy from a published meta-analysis. Our cohort included 26 patients who underwent CBT (mean age 59.3 ± 17.9 years, 42.3% women, 57.7% Black). Compared to 463 patients from the meta-analysis receiving alternative treatments, the CBT group's short-term mortality was significantly lower (7.7% vs 32.4% for anticoagulation, 13.8% for ST, and 23.2% for surgical thrombectomy). CBT demonstrated noninferiority to anticoagulation (P < .001), ST (P = .031) and surgical thrombectomy (P < .001), and was superior to anticoagulation (P = .0056) and surgical thrombectomy (P = .036). This study suggests CBT is a promising treatment for CIT. Further prospective studies are warranted to validate these findings.

Targeted protein degradation technology has gained substantial momentum over the past two decades as a revolutionary strategy for eliminating pathogenic proteins that are otherwise refractory to treatment. Among the various approaches developed to harness the body's innate protein homeostasis mechanisms for this purpose, lysosome targeting chimeras (LYTACs) that exploit the lysosomal degradation pathway by coupling the target proteins with lysosome-trafficking receptors represent the latest innovation. These chimeras are uniquely tailored to degrade proteins that are membrane-bound and extracellular, encompassing approximately 40% of all proteome. Several novel LYTAC formulas have been developed recently, providing valuable insights for the design and development of therapeutic degraders. This review delineates the recent progresses of LYTAC technology, its practical applications, and the factors that dictate target degradation efficiency. The potential and emerging trends of this technology are discussed as well. LYTAC technology offers a promising avenue for targeted protein degradation, potentially revolutionizing the therapeutic landscape for numerous diseases., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Seeking high-performance photoresists is an important item for semiconductor industry due to the continuous miniaturization and intelligentization of integrated circuits. Polymer resin containing carbonate group has many desirable properties, such as high transmittance, acid sensitivity and chemical formulation, thus serving as promising photoresist material. In this work, a series of aqueous developable CO 2 -sourced polycarbonates (CO 2 -PCs) were produced via alternating copolymerization of CO 2 and epoxides bearing acid-cleavable cyclic acetal groups in the presence of tetranuclear organoborane catalyst. The produced CO 2 -PCs were investigated as chemical amplification resists in deep ultraviolet (DUV) lithography. Under the catalysis of photogenerated acid, the acetal (ketal) groups in CO 2 -PC were hydrolysed into two equivalents of hydroxyl groups, which change the exposed area from hydrophobicity to hydrophilicity, thus enabling the exposed area to be developed with water. Through normalized remaining thickness analysis, the optimal CO 2 -derived resist achieved a remarkable sensitivity of 1.9 mJ/cm 2 , a contrast of 7.9, a favorable resolution (750 nm, half pitch), and a good etch resistance (38 % higher than poly(tert-butyl acrylate)). Such performances outperform commercial KrF and ArF chemical amplification resists (i.e., polyhydroxystyrene-derived and polymethacrylate-based resists), which endows broad application prospects in the field of DUV (KrF and ArF) and extreme ultraviolet (EUV) lithography for nanomanufacturing., (© 2024 Wiley-VCH GmbH.)

Background: Clot-in-transit is associated with high mortality, but optimal management strategies remain uncertain. The aim of this study was to compare the outcomes of different treatment strategies in patients with clot-in-transit., Methods: This is a retrospective study of patients with documented clot-in-transit in the right heart on echocardiography across 2 institutions between January 2020 and October 2023. The primary outcome was a composite of in-hospital mortality, resuscitated cardiac arrest, or hemodynamic decompensation., Results: Among 35 patients included in the study, 10 patients (28.6%) received anticoagulation alone and 2 patients (5.7%) received systemic thrombolysis, while 23 patients (65.7%) underwent catheter-based therapy (CBT; 22 mechanical thrombectomy and 1 catheter-directed thrombolysis). Over a median follow-up of 30 days, 9 patients (25.7%) experienced the primary composite outcome. Compared with anticoagulation alone, patients who received CBT or systemic thrombolysis had significantly lower rates of the primary composite outcome (12% versus 60%; log-rank P <0.001; hazard ratio, 0.13 [95% CI, 0.03-0.54]; P =0.005) including a lower rate of death (8% versus 50%; hazard ratio, 0.10 [95% CI, 0.02-0.55]; P =0.008), resuscitated cardiac arrest (4% versus 30%; hazard ratio, 0.12 [95% CI, 0.01-1.15]; P =0.067), or hemodynamic deterioration (4% versus 30%; hazard ratio, 0.12 [95% CI, 0.01-1.15]; P =0.067)., Conclusions: In this study of CBT in patients with clot-in-transit, CBT or systemic thrombolysis was associated with a significantly lower rate of adverse clinical outcomes, including a lower rate of death compared with anticoagulation alone driven by the CBT group. CBT has the potential to improve outcomes. Further large-scale studies are needed to test these associations., Competing Interests: Dr Bangalore is on the Advisory Board of Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer, Merck, Reata, Inari, and Truvic. The other authors report no conflicts.

Background: In hemodynamically stable patients with acute pulmonary embolism (PE), the Composite Pulmonary Embolism Shock (CPES) score predicts normotensive shock. However, it is unknown if CPES predicts adverse clinical outcomes. The objective of this study was to determine whether the CPES score predicts in-hospital mortality, resuscitated cardiac arrest, or hemodynamic deterioration., Methods: Patients with acute intermediate-risk PE admitted from October 2016 to July 2019 were included. CPES was calculated for each patient. The primary outcome was a composite of in-hospital mortality, resuscitated cardiac arrest, or hemodynamic decompensation. Secondary outcomes included individual components of the primary outcome. The association of CPES with primary and secondary outcomes was evaluated., Results: Among the 207 patients with intermediate-risk PE (64.7% with intermediate-high risk PE), 29 (14%) patients had a primary outcome event. In a multivariable model, a higher CPES score was associated with a worse primary composite outcome (adjusted hazard ratio [aHR], 1.81 [95% CI, 1.29-2.54]; P =0.001). Moreover, a higher CPES score predicted death (aHR, 1.76 [95% CI, 1.04-2.96]; P =0.033), resuscitated cardiac arrest (aHR, 1.99 [95% CI, 1.17-3.38]; P =0.011), and hemodynamic decompensation (aHR, 1.96 [95% CI, 1.34-2.89]; P =0.001). A high CPES score (≥3) was associated with the worse primary outcome when compared with patients with a low CPES score (22% versus 2.4%; P =0.003; aHR, 6.48 [95% CI, 1.49-28.04]; P =0.012). CPES score provided incremental prognostic value for the prediction of primary outcome over baseline demographics and European Society of Cardiology intermediate-risk subcategories (global Χ 2 value increased from 0.63 to 1.39 to 13.69; P =0.005)., Conclusions: In patients with acute intermediate-risk PE, the CPES score effectively risk stratifies and prognosticates patients for the prediction of clinical events and provides incremental value over baseline demographics and European Society of Cardiology intermediate-risk subcategories., Competing Interests: Dr Bangalore participated in advisory board at Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer, Merck, REATA, Inari, Truvic, Argon. The other authors report no conflicts.

The popular formula Qiye Qingnian Powder, prescribed by Hua Tuo (BC145 - 208), is believed to "remove three kinds of worms, be conducive to the five main organs, keep fit, and prevent one's hair from turning gray". It is a representative formula in terms of "removing worms to prolong life" in traditional Chinese medicine. This paper focuses on "Qiye" in this formula, which plays an important role in removing worms, reviews its place in traditional Chinese medicine (TCM), Tibetan medicine, and Ayurvedic medicine and compares the concept of "removing worms" in Chinese and Ayurvedic medicine. It was found that the name and efficacy of Bhallātaka in Ayurvedic medicine is related to "Qiye". It was also indicated that by comparing the concept of "worms" and the understanding of "removing worms" in traditional Chinese medicine and Ayurvedic medicine, in the theory of traditional medicines worms are the causative factor of diseases. Traditional Chinese medicine has rich connotations which involved medicinal concepts of Buddhism and Taoism and the idea of "removing worms to prolong life" is a unique contribution of traditional Chinese medicine to human health.

Abstract: Renal hemangioblastoma (HB) is a rare subset of HBs arising outside of the central nervous system (CNS), with its molecular drivers remaining entirely unknown. There were no significant alterations detected in previous studies, including von Hippel-Lindau gene alterations, which are commonly associated with CNS-HB. This study aimed to determine the real molecular identity of renal HB and better understand its relationship with CNS-HB. A cohort of 10 renal HBs was submitted for next-generation sequencing technology. As a control, 5 classic CNS-HBs were similarly analyzed. Based on the molecular results, glycoprotein nonmetastatic B (GPNMB) immunohistochemistry was further performed in the cases of renal HB and CNS-HB. Mutational analysis demonstrated that all 10 renal HBs harbored somatic mutations in tuberous sclerosis complex 1 ( TSC1 , 5 cases), TSC2 (3 cases), and mammalian target of rapamycin (2 cases), with the majority classified as pathogenic or likely pathogenic. The CNS-HB cohort uniformly demonstrated somatic mutations in the von Hippel-Lindau gene. GPNMB was strong and diffuse in all 10 renal HBs and completely negative in CNS-HBs, reinforcing the molecular findings. Our study reveals a specific molecular hallmark in renal HB, characterized by recurrent TSC/mammalian target of rapamycin mutations, which defines it as a unique entity distinct from CNS-HB. This molecular finding potentially expands the therapeutic options for patients with renal HB. GPNMB can be considered for inclusion in immunohistochemical panels to improve renal HB identification., Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: Among patients with acute pulmonary embolism (PE) undergoing mechanical thrombectomy, the cardiac index (CI) is frequently reduced even among those without a clinically apparent shock. The purpose of this study is to describe the mixed venous-to-arterial carbon dioxide gradient (CO2 gap), a surrogate of perfusion adequacy, among patients with acute PE undergoing mechanical thrombectomy., Methods and Results: This was a single-centre retrospective study of consecutive patients with PE undergoing mechanical thrombectomy and simultaneous pulmonary artery catheterization over a 3-year period. Of 107 patients, 97 had simultaneous mixed venous and arterial blood gas measurements available. The CO2 gap was elevated (>6 mmHg) in 51% of the cohort and in 49% of patients with intermediate-risk PE. A reduced CI (≤2.2 L/min/m2) was associated with an increased odds [odds ratio = 7.9; 95% confidence interval (CI) 3.49-18.1, P < 0.001] for an elevated CO2 gap. There was an inverse relationship between the CI and the CO2 gap. For every 1 L/min/m2 decrease in the CI, the CO2 gap increased by 1.3 mmHg (P = 0.001). Among patients with an elevated baseline CO2 gap >6 mmHg, thrombectomy improved the CO2 gap, CI, and mixed venous oxygen saturation. When the CO2 gap was dichotomized above and below 6, there was no difference in the in-hospital mortality rate (9 vs. 0%; P = 0.10; hazard ratio: 1.24; 95% CI 0.97-1.60; P = 0.085)., Conclusion: Among patients with acute PE undergoing mechanical thrombectomy, the CO2 gap is abnormal in nearly 50% of patients and inversely related to the CI. Further studies should examine the relationship between markers of perfusion and outcomes in this population to refine risk stratification., Competing Interests: Conflict of interest: S.B.—advisory board—Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer, Merck, REATA, Inari, Truvic, and Argon. J.M.H.—funding from Inari Medical. The remaining authors report no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: The aim of this study was to compare the hemodynamic impact and clinical outcomes of saddle vs non-saddle pulmonary embolism (PE)., Methods: This was a retrospective analysis of clinical characteristics and outcomes among patients with saddle and non-saddle PE within a cohort referred for catheter-based thrombectomy (CBT) with invasive hemodynamic assessments. Patients who underwent CBT between August 2020 and January 2024 were included. The primary outcome was the proportion of patients with a low cardiac index (CI < 2.2 L/min/m²). Secondary outcomes included 30-day mortality, intensive care unit (ICU) length of stay (LOS), and hospital LOS., Results: A total of 107 patients (84 intermediate risk, 23 high-risk; mean age 58 years, 47.6% female) were included in the study, with 44 patients having saddle PE and 63 having non-saddle PE. There were no significant differences in baseline demographics and clinical characteristics between saddle and non-saddle PE, including rates of high-risk PE (25% vs 16%, P = .24), rates of RV dysfunction, pulmonary artery systolic pressure (55 vs 53 mm Hg, P = .74), mean pulmonary artery pressure (34 mm Hg vs 33 mm Hg), low cardiac index (56% vs 51%, P = .64), rates of normotensive shock (27% vs 20%, P = .44), or Composite Pulmonary Embolism Shock scores (4.5 vs 4.7, P = .25). Additionally, 30-day mortality (6% vs 5%, P = .69), ICU LOS, and hospital LOS were similar between the groups., Conclusions: Among patients undergoing CBT, there were no significant differences in invasive hemodynamic parameters or clinical outcomes between those with saddle and non-saddle PE.

Data comparing catheter-based thrombectomy (CBT) and catheter-directed thrombolysis (CDT) in acute pulmonary embolism are lacking. To address this, we performed a meta-analysis of prospective and retrospective studies of CBT and compared it to performance goal rates of mortality and major bleeding from a recently published network meta-analysis. When compared with performance goal for CDT based on historical studies, CBT was noninferior for all-cause mortality (6.0% vs 6.87%; P-value NI < .001), non-inferior and superior for major bleeding (4.9% vs 11%; P-value NI < .001 and P < .001 for superiority)., Competing Interests: Conflict of interest Dr. Bangalore- Advisory board- Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer, Merck, REATA, Inari, Truvic., (Copyright © 2024. Published by Elsevier Inc.)

Objectives: Clot-in-transit (CIT) in patients with pulmonary embolism (PE) has been associated with a high mortality rate and poor prognosis. The aim of this study was to evaluate the pooled efficacy of each of the 4 interventions (anticoagulation [AC] alone, systemic thrombolytic [ST] therapy, surgical thrombectomy, and catheter-based thrombectomy [CBT]) using mortality as the primary outcome., Methods: A time limited search until March 28, 2024 was conducted using PubMed (National Institutes of Health) and EMBASE (Elsevier) databases., Results: Thirteen studies (6 retrospective, 4 non-randomized prospective, and 3 pooled studies of case-reports) were included in the calculation of weighted proportion of mortality, including a total of 492 patients with CIT and PE with a mean age of 60.6 years; 50.1% were males. ST was the most frequently used treatment intervention (38.2%), followed by surgical thrombectomy (33.8%), AC alone (22.6%), and CBT (5.9%). The unweighted mortality was highest with AC alone 32.4% (36/111), followed by surgical thrombectomy 23.2% (38/164), CBT 20.7% (6/29), and ST 13.8% (26/188). The weighted mortality for AC alone was 35% (95% CI, 21% to 49%; 12 studies), surgical thrombectomy was 31% (95% CI, 16% to 47%; 12 studies), CBT was 20% (95% CI, 6% to 34%; 3 studies), and ST was 12% (95% CI, 5% to 19%; 12 studies)., Conclusions: In this meta-analysis of patients with CIT and PE, the highest mortality was observed with AC alone, followed by surgical thrombectomy, CBT, and ST therapy. However, there remains a need for randomized clinical trial data to determine the best treatment.

Purpose of Review: Although rare, the development of mechanical complications following an acute myocardial infarction is associated with a high morbidity and mortality. Here, we review the clinical features, diagnostic strategy, and treatment options for each of the mechanical complications, with a focus on the role of echocardiography., Recent Findings: The growth of percutaneous structural interventions worldwide has given rise to new non-surgical options for management of mechanical complications. As such, select patients may benefit from a novel use of these established treatment methods. A thorough understanding of the two-dimensional, three-dimensional, color Doppler, and spectral Doppler findings for each mechanical complication is essential in recognizing major causes of hemodynamic decompensation after an acute myocardial infarction. Thereafter, echocardiography can aid in the selection and maintenance of mechanical circulatory support and potentially facilitate the use of a percutaneous intervention., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Our study aims to present clinical outcomes of mechanical thrombectomy (MT) in a safety-net hospital., Methods: This is a retrospective study of intermediate or high-risk pulmonary embolism (PE) patients who underwent MT between October 2020 and May 2023. The primary outcome was 30-day mortality., Results: Among 61 patients (mean age 57.6 years, 47% women, 57% Black) analyzed, 12 (19.7%) were classified as high-risk PE, and 49 (80.3%) were intermediate-risk PE. Of these patients, 62.3% had Medicaid or were uninsured, 50.8% lived in a high poverty zip code. The prevalence of normotensive shock in intermediate-risk PE patients was 62%. Immediate hemodynamic improvements included 7.4 mmHg mean drop in mean pulmonary artery pressure (-21.7%, p < 0.001) and 93% had normalization of their cardiac index postprocedure. Thirty-day mortality for the entire cohort was 5% (3 patients) and 0% when restricted to the intermediate-risk group. All 3 patients who died at 30 days presented with cardiac arrest. There were no differences in short-term mortality based on race, insurance type, citizenship status, or socioeconomic status. All-cause mortality at most recent follow up was 13.1% (mean follow up time of 13.4 ± 8.5 months)., Conclusion: We extend the findings from prior studies that MT demonstrates a favorable safety profile with immediate improvement in hemodynamics and a low 30-day mortality in patients with acute PE, holding true even with relatively higher risk and more vulnerable population within a safety-net hospital., (© 2024 Wiley Periodicals LLC.)

Purpose of Review: Targeting traditional cardiovascular risk factors is effective in reducing recurrent cardiovascular events, yet the presence of residual cardiovascular risk due to underlying systemic inflammation is a largely unaddressed opportunity. This review aims to comprehensively assess the evolving role of colchicine as a therapeutic approach targeting residual inflammatory risk in the context of those with coronary artery disease (CAD)., Recent Findings: Inflammation plays a significant role in promoting atherosclerosis, and targeting anti-inflammatory pathways has the potential to decrease cardiovascular events. Low-dose colchicine (0.5 mg/day orally), when added to guideline-directed medical care for CAD, safely decreases major adverse cardiovascular events (MACE) by 31% in stable atherosclerosis patients and 23% in those after recent myocardial infarctions. Meta-analyses of recent randomized control trials further support both the efficacy and safety of colchicine, particularly when added to other standard cardiovascular therapies, including statin therapy. The European Society of Cardiology and other national guidelines endorse the use of low-dose colchicine in patients across the spectrum of CAD. Recently, colchicine was FDA-approved in the United States as the first anti-inflammatory therapy for the reduction of cardiovascular events. In a period of a rising incidence of CAD across the globe, colchicine represents a unique opportunity to decrease MACE due to its large magnitude of benefits and general affordability. However, challenges with drug interactions must be addressed, especially in those regions where HIV, hepatitis, and tuberculosis are prevalent. Colchicine is safe and effective at reducing cardiovascular events across a broad spectrum of coronary syndromes. The ability to simultaneously target traditional risk factors and mitigate residual inflammatory risk marks a substantial advancement in cardiovascular prevention strategies, heralding a new era in the global battle against CAD., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Competing Interests: Declaration of competing interest Dr. Bangalore: Advisory board for Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer, Merck, REATA, Inari, Truvic. The remaining authors have no competing interests to declare.

Sexual dimorphism in traits of insects during the developmental stages could potentially be the direct or indirect result of sex-specific selection provided that genetic variation for sexual dimorphism is present. We investigated genetic variation in sexual dimorphism in a set of Drosophila melanogaster inbred lines for 2 traits: egg to adult development time and pupation site preference. We observed considerable genetic variation in sexual dimorphism among lines in both traits. The sexual dimorphic patterns remained relatively consistent across multiple trials, despite both traits being sensitive to environmental conditions. Additionally, we measured 2 sexually dimorphic adult morphological traits in 6 sampled lines and investigated correlations in the sexual dimorphism patterns with the 2 developmental traits. The abundance of genetic variation in sexual dimorphism for D. melanogaster developmental traits demonstrated in this study provides evidence for a high degree of evolvability of sex differences in preadult traits in natural populations., Competing Interests: Conflicts of interest. The authors declare no conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Genetics Society of America.)

Elucidating the quality markers(Q-markers) of traditional Chinese medicines is essential for understanding the mechanisms of action and promoting the rational use of traditional Chinese medicines as well as for developing traditional Chinese medicine-derived drugs. Studies have shown that surface plasmon resonance(SPR) is promising in this field. This study proposed a method based on pull-down with SPR chips to predict the Q-markers of Angong Niuhuang pills(AGNHP). Firstly, 71 main chemical components of AGNHP were analyzed by UPLC-Q-TOF-MS, and then network pharmacology was employed to predict the potential targets of AGNHP against stroke. Secondly, the STAT3 protein chip was constructed, and the extract of AGNHP was recovered by pull-down of the SPR system for STAT3 ligand. The potential active ingredients were collected, enriched, and identified as coptisine, palmatine, epiberberine, berberine, worenine, demethyleneberberine, jatrorrhizine, tetrahydrocoptisine, baicalein, and baicalin methyl ester. Next, the affinity constants of the 10 active ingredients were determined as 44.7, 44, 58.1, 51.3, 39.7, 32.1, 49.2, 69.1, 19.7, and 24.9 μmol·L~(-1), respectively. The molecular docking results showed that the 10 compounds could compete for binding with STAT3. This is the first report that SPR combined with UPLC-Q-TOF-MS is reliable and feasible for determining the active ingredients of AGNHP at the molecular level from complex systems. STAT3 could be used as a potential target for the biological quality evaluation of AGNHP.

Live streaming with goods is developing rapidly as an emerging platform economic model. Consumers can interact with the e-commerce platform in real-time and get a good shopping experience. This in turn generates value co-creation behaviors such as word-of-mouth communication. However, due to the lack of effective audit mechanisms on some platforms, the phenomenon of value co-destruction among them is becoming more and more common. This brings value loss to consumers, e-commerce platforms, and other multiple subjects. Based on the SOR model, this paper collects 212 sample data by using a questionnaire survey. The impact of live banding platform characteristics on consumers' value co-creation and value co-destruction behaviors is analyzed through multiple regression and other methods. The results show that platform information quality, functional quality, and interactive quality all positively affect consumers' value co-creation behavior and negatively affect value co-destruction behavior. Perceived value plays a mediating role, and promotional incentives enhance the positive relationship between platform features and perceived value. Therefore, if the live streaming bandwagon platform provides consumers with sufficiently rich, complete, and timely product information, responds quickly to consumer needs, and has high interaction quality. Consumers are more likely to exhibit value co-creation behavior. This study enriches the theoretical results of value co-creation and value co-destruction. It provides theoretical references for live streaming platforms to inhibit consumers' value co-destructive behaviors and promote value co-creation behaviors. In practice, it is pointed out that live streaming platforms should provide consumers with real information on all aspects of the products, update and improve the performance of the platform in a timely manner, and provide regular training to the staff., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Competing Interests: Disclosures Dr Bangalore was a participant in Advisory board—Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer, Merck, REATA, Inari, Truvic. Dr Sharp was a consultant to Medtronic, Boston Scientific, Recor Medical, Penumbra, Philips. Dr Sethi participated in Honoraria/consulting at Boston Scientific, Chiesi, Janssen, Inari, Penumbra, Terumo. Dr Giri received research funds to the institution and advisory boards for Boston Scientific, Edwards, Inari Medical, Recor Medical, and Abiomed. Honoraria from Cordis, Inari Medical, Abiomed.

The primary objective of our study was to determine the proportion of intermediate-risk PE patients undergoing mechanical thrombectomy (MT) who achieved therapeutic anticoagulation (AC) at the time of the procedure. The salient findings of our study showed that only a minority of patients (14.3%) were in the therapeutic range by ACT at the time of MT (primary outcome). Furthermore, in this higher-risk PE cohort selected for MT, 18.2% of patients were subtherapeutic after initially reaching therapeutic AC, 43% experienced supratherapeutic AC at some point before MT, and less than half (43%) attained therapeutic AC at 6 hours, highlighting the necessity for optimizing anticoagulation practices in acute PE., Competing Interests: Conflict of interest Dr. Bangalore- Advisory board- Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer, Merck, REATA, Inari, Truvic, Argon., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Objective: To investigate the clinicopathological features, and molecular genetic alterations of metaplastic thymoma (MT). Methods: A total of ten MT cases, diagnosed from 2011 to 2021, were selected from the Department of Pathology of Jinling Hospital, Nanjing University Medical School, Nanjing, China for clinicopathological and immunohistochemical (IHC) examination and clinical follow-up. Fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and YAP1 C-terminus (YAP1-CT) IHC were performed to detect YAP1::MAML2 fusions. Results: There were four males and six females, ranging in age from 29 to 60 years (mean 50 years, median 54 years). Microscopically, all tumors showed a typical biphasic morphology consisting of epithelial components and gradually or abruptly transitioning spindle cell components. The two components were present in varying proportions in different cases. Immunophenotypically, the epithelial cells were diffusely positive for CKpan, CK5/6 and p63. The spindle cells were diffusely positive for vimentin and focally positive for EMA. TdT was negative in the background lymphocytes. Ki-67 proliferation index was less than 5%. YAP1 and MAML2 break-apart FISH analyses showed that all ten cases had narrow split signals with a distance of nearly 2 signal diameters and may be considered false-negative. Using YAP1::MAML2 fusion FISH assays, abnormal fusion signals were observed in all the ten cases. NGS demonstrated YAP1::MAML2 fusions in all eight cases with adequate nucleic acids; in two cases the fusions were detected by DNA sequencing and in eight cases by RNA sequencing. All ten cases of MT demonstrated loss of YAP1 C-terminal expression in epithelioid cells. Conclusions: MT is a rare and low-grade thymic tumor characterized by a biphasic pattern and YAP1::MAML2 fusions. Break-apart FISH assays may sometimes show false-negative results due to the proximity of YAP1 and MAML2, while YAP1 C-terminal IHC is a highly sensitive and specific marker for MT. Loss of YAP1 C-terminal expression can also be used to screen YAP1::MAML2 fusions for possible MT cases.

Competing Interests: Disclosures Dr Bangalore serves on the advisory board of Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer, Merck, Reata, Inari, and Truvic. The other authors report no conflicts.

In this study, we conducted molecular dynamic simulations to investigate the thermal expansion behavior of Janus MoSSe nanotubes. We focused on understanding how the intrinsic strain in these nanotubes affects their thermal expansion coefficient (TEC). Interestingly, we found that Janus MoSSe nanotubes with sulfur (S) on the outer surface (MoSeS) exhibit a different intrinsic strain compared to those with selenium (Se) on the outer surface (MoSSe). In light of this observation, we explored the influence of this intrinsic strain on the TEC of the nanotubes. Our results revealed distinct trends for the TEC along the radial direction (TEC- r ) and the axial direction (TEC- l x ) of the MoSSe and MoSeS nanotubes. The TEC- r of MoSeS nanotubes was found to be significantly greater than that of MoSSe nanotubes. Moreover, the TEC- l x of MoSeS nanotubes was smaller than that of MoSSe nanotubes. Further analysis showed that the TEC- r of MoSeS nanotubes decreased by up to 37% as the radius increased, while that of MoSSe nanotubes exhibited a slight increase with increasing radius. On the other hand, the TEC- l x of MoSeS nanotubes increased by as much as 45% with increasing radius, whereas that of MoSSe nanotubes decreased gradually. These opposite tendencies of the TECs with respect to the radius were attributed to the presence of intrinsic strain within the nanotubes. The intrinsic strain was found to play a crucial role in inducing thermally induced bending and elliptization of the nanotubes' cross-section. These effects are considered key mechanisms through which intrinsic strain influences the TEC. Overall, our study provides valuable insights into the thermal stability of Janus nanotubes. By understanding the relationship between intrinsic strain and the thermal expansion behavior of nanotubes, we contribute to the broader understanding of these materials and their potential applications., (© 2023 IOP Publishing Ltd.)

Background: The optimal treatment strategy of patients with pulmonary embolism (PE) (especially those with intermediate risk) continues to evolve and remains controversial., Objectives: This study sought to compare the efficacy and safety of anticoagulation (AC) alone, catheter-directed thrombolysis (CDT), and systemic thrombolysis (ST) in patients with acute PE., Methods: PubMed and EMBASE were searched for randomized controlled trials or observational studies which compared outcomes of AC alone, CDT, and ST in acute PE. Efficacy outcome was all-cause mortality. Safety outcomes were major bleeding and intracranial hemorrhage (ICH)., Results: We identified 45 studies (17 randomized controlled trials, 2 prospective nonrandomized trials, and 26 retrospective observational trials), which included 81,705 patients. When compared with AC alone, CDT had lower mortality (OR: 0.55; 95% CI: 0.39-0.80) but higher major bleeding (OR: 1.84; 95% CI: 1.10-3.08) and numerically higher ICH (OR: 1.51; 95% CI: 0.75-3.04). ST was associated with no difference in mortality but higher major bleeding (OR: 2.16; 95% CI: 1.38-3.38) and ICH (OR: 2.26; 95% CI: 1.14-4.48) when compared with AC alone. The risk of mortality (OR: 2.05; 95% CI: 1.46-2.89) and ICH (OR: 1.50; 95% CI: 1.13-1.99) was higher with ST when compared with CDT. Findings were similar when analysis was restricted to trials of intermediate risk PE., Conclusions: In patients with acute PE, when compared with AC alone, CDT was associated with a lower mortality but higher risk of bleeding. Moreover, CDT had an enhanced safety profile when compared with ST., Competing Interests: Funding Support and Author Disclosures Dr Sharp has served as a consultant for Medtronic, Recor Medical, Boston Scientific, Penumbra, and Philips. Dr Sethi has served as a consultant/received honoraria from Boston Scientific, Inari, Terumo, Janssen, and Chiesi. Dr Bangalore has served on the advisory board for Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer, Merck, REATA, Inari, and Truvic. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Metaplastic thymoma is a rare thymic tumour characterized by Yes Associated Protein 1 (YAP1) and Mastermind Like Transcriptional Coactivator 2 (MAML2) gene fusions resulting from an intrachromosomal inversion of chromosome 11. Immunohistochemistry with an antibody directed against the C-terminus of YAP1 has shown loss of expression in YAP1-rearranged vascular neoplasms, poromas, and porocarcinomas. This study aimed to validate an anti-YAP1 C-terminal antibody as an ancillary immunohistochemical marker for the diagnosis of metaplastic thymoma., Materials and Methods: Ten metaplastic thymomas were selected for the current study. Fluorescence in situ hybridization (FISH), next-generation sequencing (NGS), and reverse transcription-polymerase chain reaction (RT-PCR) analyses were performed to detect YAP1::MAML2 fusions. We then performed immunohistochemistry to detect YAP1 C-terminus expression in 10 metaplastic thymomas, 50 conventional thymomas (10 each of type A thymoma, type AB thymoma, type B1 thymoma, type B2 thymoma, and type B3 thymoma) and seven thymic carcinomas., Results: All 10 cases showed narrow split signals with a distance of nearly two signal diameters and sometimes had false-negative results in YAP1 and MAML2 break-apart FISH (BA-FISH). Abnormal colocalized signals of the YAP1::MAML2 fusion were observed in all 10 cases using fusion FISH (F-FISH) assays. Eight of 10 cases with adequate nucleic acids were successfully sequenced and all showed YAP1::MAML2 fusions; in two cases the fusions were detected by both DNA and RNA sequencing and in six cases by RNA sequencing only. YAP1::MAML2 fusion transcripts were identified in four cases by RT-PCR. Metaplastic thymoma showed loss of YAP1 C-terminus expression in all 10 (100%) cases. All other thymic neoplasms showed retained YAP1 C-terminus expression., Conclusion: YAP1 C-terminus immunohistochemistry is a highly sensitive and specific ancillary marker that distinguishes metaplastic thymoma from its mimics. BA-FISH assays could not effectively detect YAP1::MAML2 fusions due to the proximity of the two genes. Loss of YAP1 C-terminus expression is a reliable surrogate for the detection of YAP1::MAML2 fusions in metaplastic thymoma., (© 2023 John Wiley & Sons Ltd.)

Discrepancy between computed tomography (CT) and transthoracic echocardiography (TTE) regarding pericardial effusion (PEff) size is common, but there is limited data regarding the correlation between these 2 imaging methods. The aim of this study is to examine the real-world concordance of observed PEff size between CT and TTE. We performed a retrospective analysis of all imaging reports available from 2013 to 2019 and identified patients with a PEff who underwent both a chest CT and TTE within a 24-hour period. We evaluated the agreement between CT and TTE in assessing PEff size. Of 1,118 patients included in the study, mean age was 66 (±17 years) and 54% were female. The median time interval between the 2 studies was 9.4 hours (interquartile range 3.5 to 16.6). Patients within a half-grade or full-grade of agreement were 71.9% and 97.2%, respectively. The mean difference in grade of agreement (TTE minus CT) between the 2 imaging methods was -0.1 (±0.6, p <0.0001). CT was more likely to report a higher grade (i.e. larger PEff size) when compared with TTE (261 patients vs 157 patients, p <0.001). The weighted kappa was 0.73 (95% confidence interval 0.69 to 0.76). After excluding patients with trace/no effusion, 42.3% and 94.1% of patients' studies were within a half-grade or full-grade of agreement, respectively. Of the 18 patients who had large discrepancies, 9 patients had loculated effusions, 2 patients had large pleural effusions, and 6 patients had suboptimal TTEs images. In conclusion, TTE and CT showed relatively strong agreement in estimation of PEff size, with CT sizes larger than TTE, on average. Large discrepancies in size may be related to reduced image quality, large pleural effusions, and loculated PEff., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Published by Elsevier Inc.)

Competing Interests: Disclosures Dr Bangalore serves on the advisory board of Abbott Vascular, Boston Scientific, Biotronik, Amgen, Pfizer, Merck, REATA, Inari, and Truvic. The other author reports no conflicts.

Background: Uveitis is an eye disease with a high rate of blindness, whose pathogenesis is not completely understood. Si-Ni-San (SNS) has been used as a traditional medicine to treat uveitis in China. However, its mechanism of action remains unclear. This study explored the potential mechanisms of SNS in the treatment of uveitis through network pharmacology and bioinformatics., Methods: Using R language and Perl software, the active components and predicted targets of SNS, as well as the related gene targets of uveitis, were mined through the Traditional Chinese Medicine Systems Pharmacology, Therapeutic Target, Gene Expression Omnibus, GeneCards, and DrugBank databases. The network diagram of active components and intersection targets was constructed using Cytoscape software and the String database. The CytoNCA plug-in was used to conduct topological analysis on the network diagram and screen out the core compounds and key targets. The genes were analyzed for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment. Chemoffice, Pymol, AutoDock, and Vina were used to analyze the molecular docking of key targets and core compounds of diseases through the PubChem database., Results: JUN, RELA, and MAPK may play important roles in the treatment of uveitis by SNS. Kyoto encyclopedia of genes and genomes pathway enrichment analysis showed that core genes were mainly concentrated in MAPK, toll-like receptor, tumor necrosis factor, and nucleotide oligomerization domain-like receptor signaling pathways. In addition, molecular docking results showed that the bioactive compounds (kaempferol, luteolin, naringin, and quercetin) exhibited good binding ability to JUN, RELA, and MAPK., Conclusion: Based on these findings, SNS exhibits multi-component and multi-target synergistic action in the treatment of uveitis, and its mechanism may be related to anti-inflammatory and immune regulation., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: In patients with tricuspid valve infective endocarditis, percutaneous debulking is a treatment option. However, the outcomes of this approach are less well known., Methods: We performed a retrospective analysis of all patients who underwent percutaneous vegetation debulking for tricuspid valve infective endocarditis from August 2020 to November 2022 at a large academic tertiary care public hospital. The primary efficacy outcome was procedural success defined by clearance of blood cultures. The primary safety outcome was any procedural complication. For the composite outcome of in-hospital mortality or heart block, outcomes were compared (sequential noninferiority and superiority) with published surgical outcomes data., Results: Of the 29 patients with tricuspid valve infective endocarditis who underwent percutaneous debulking, the average age was 41.3±10.1 years, all patients had septic pulmonary emboli with 27 (93.1%) patients having cavitary lung lesions before the procedure. For the efficacy outcomes, 28 patients (96.6%) had clearance of cultures after their procedure, mean white blood cell count significantly decreased from 16.8±1.4×10 3 to 12.6±1.0×10 3 per µL ( P <0.01), and mean body temperature significantly decreased from 99.8F ±0.30 to 98.3F ±0.20 ( P <0.001) post-procedure. For safety outcomes, there were no procedural complications (0%). Two patients (6.9%) died during the follow-up period, both during the index hospitalization due to severe necrotizing pneumonia. When compared with published data on surgical outcomes, percutaneous debulking was noninferior and superior for the composite of in-hospital death or heart block (noninferiority, P <0.001; superiority, P =0.016)., Conclusions: Percutaneous debulking is feasible, effective, and safe in treating patients with tricuspid valve infective endocarditis refractory to medical therapy.

The Ras GTPase-activating protein SYNGAP1 plays a central role in synaptic plasticity, and de novo SYNGAP1 mutations are among the most frequent causes of autism and intellectual disability. How SYNGAP1 is regulated during development and how to treat SYNGAP1-associated haploinsufficiency remain challenging questions. Here, we characterize an alternative 3' splice site (A3SS) of SYNGAP1 that induces nonsense-mediated mRNA decay (A3SS-NMD) in mouse and human neural development. We demonstrate that PTBP1/2 directly bind to and promote SYNGAP1 A3SS inclusion. Genetic deletion of the Syngap1 A3SS in mice upregulates Syngap1 protein and alleviates the long-term potentiation and membrane excitability deficits caused by a Syngap1 knockout allele. We further report a splice-switching oligonucleotide (SSO) that converts SYNGAP1 unproductive isoform to the functional form in human iPSC-derived neurons. This study describes the regulation and function of SYNGAP1 A3SS-NMD, the genetic rescue of heterozygous Syngap1 knockout mice, and the development of an SSO to potentially alleviate SYNGAP1-associated haploinsufficiency., Competing Interests: Declaration of interests A provisional patent on splice-switching oligonucleotides described in this study has been filed on behalf of X.Z. and R.Y., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: The contribution of chronotropic incompetence to reduced exercise tolerance after a heart transplant is well known, but its role as a prognostic marker of post-transplant mortality is unclear. The aim of this study is to examine the relationship between post-transplant heart rate response (HRR) and survival., Methods: We performed a retrospective analysis of all adult heart transplant recipients at the University of Pennsylvania between the years 2000 and 2011 who underwent a cardiopulmonary exercise test (CPET) within a year of transplant. Follow-up time and survival status were observed through October 2019, using data merged from the Penn Transplant Institute. HRR was calculated by subtracting the resting HR from the peak exercise HR. The association between HRR and mortality was analyzed using Cox proportional hazard models and Kaplan-Meier analysis. The optimal cut-off point for HRR was generated by Harrell's C statistic. Patients with submaximal exercise tests were excluded, defined by a respiratory exchange ratio (RER) cut-off of 1.05., Results: Of 277 patients with CPETs performed within a year post-transplant, 67 were excluded for submaximal exercise. In the 210 included patients, the mean follow-up time was 10.9 years (Interquartile range (IQR) 7.8-14). Resting HR and peak HR did not significantly impact mortality after adjusting for covariates. In a multivariable linear regression analysis, each 10-beat increase in heart rate response was associated with a 1.3 mL/kg/min increase in peak V O 2 and a 48 s increase in the total exercise time. Each beat/min increase in HRR was associated with a 3% reduction in the hazard of mortality (HR 0.97; 95% CI 0.96-0.99, p = 0.002). Using the optimal cut-off point generated by Harrell's C statistic, survival was significantly higher in patients with an HRR > 35 beats/min compared to those with an HRR < 35 beats/min (log rank p = 0.0012)., Conclusion: In heart transplant patients, a low HRR is associated with increased all-cause mortality and decreased exercise capacity. Additional studies are needed to validate whether targeting HRR in cardiac rehabilitation may improve outcomes.

Objective: To derive the Chinese medicine (CM) syndrome classification and subgroup syndrome characteristics of ischemic stroke patients., Methods: By extracting the CM clinical electronic medical records (EMRs) of 7,170 hospitalized patients with ischemic stroke from 2016 to 2018 at Weifang Hospital of Traditional Chinese Medicine, Shandong Province, China, a patient similarity network (PSN) was constructed based on the symptomatic phenotype of the patients. Thereafter the efficient community detection method BGLL was used to identify subgroups of patients. Finally, subgroups with a large number of cases were selected to analyze the specific manifestations of clinical symptoms and CM syndromes in each subgroup., Results: Seven main subgroups of patients with specific symptom characteristics were identified, including M3, M2, M1, M5, M0, M29 and M4. M3 and M0 subgroups had prominent posterior circulatory symptoms, while M3 was associated with autonomic disorders, and M4 manifested as anxiety; M2 and M4 had motor and motor coordination disorders; M1 had sensory disorders; M5 had more obvious lung infections; M29 had a disorder of consciousness. The specificity of CM syndromes of each subgroup was as follows. M3, M2, M1, M0, M29 and M4 all had the same syndrome as wind phlegm pattern; M3 and M0 both showed hyperactivity of Gan (Liver) yang pattern; M2 and M29 had similar syndromes, which corresponded to intertwined phlegm and blood stasis pattern and phlegm-stasis obstructing meridians pattern, respectively. The manifestations of CM syndromes often appeared in a combination of 2 or more syndrome elements. The most common combination of these 7 subgroups was wind-phlegm. The 7 subgroups of CM syndrome elements were specifically manifested as pathogenic wind, pathogenic phlegm, and deficiency pathogens., Conclusions: There were 7 main symptom similarity-based subgroups in ischemic stroke patients, and their specific characteristics were obvious. The main syndromes were wind phlegm pattern and hyperactivity of Gan yang pattern., (© 2022. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: We report on the clinical course and management of patients supported with durable implantable LVADs who developed outflow graft obstructions at a large academic center., Methods: We performed a retrospective review of patients receiving LVAD support from 2012 through 2020. Patients who developed an outflow graft obstruction diagnosed by computed tomography angiography (CTA) or angiogram were identified, and patient characteristics and outcomes were reported., Results: Of the 324 patients supported by LVAD at our institution, 11 patients (3.4%) were diagnosed with outflow graft obstructions. The most common presentation was low flow alarms, which was present in 10/11 patients, and the remaining patient presented with lightheadedness. Patients had minimal LDH elevation with 8/11 presenting with less than 2-fold the upper limit of normal. Transthoracic echocardiograms were not diagnostic, but CTA enabled non-invasive diagnoses in 8/11 of the patients. Three patients with extrinsic compression of the outflow graft successfully underwent endovascular stent placement, and three patients with outflow cannula kinks received supportive care. Of the five patients diagnosed with intraluminal thromboses, one received a heart transplant, one underwent an outflow graft revision, and three received supportive care due to comorbidities., Conclusion: Outflow graft obstructions remain a rare, but serious complication. The true prevalence of this entity is likely underestimated due to the non-specific clinical presentation. CTA is a pivotal non-invasive diagnostic step. Patients with external compression were successfully treated with endovascular stenting.

Background: This study aims to investigate the value of myocardial work (MW) parameters during the isovolumic relaxation (IVR) period in patients with left ventricular diastolic dysfunction (LVDD)., Methods: This study prospectively recruited 448 patients with risks for LVDD and 95 healthy subjects. An additional 42 patients with invasive measurements of left ventricular (LV) diastolic function were prospectively included. The MW parameters during IVR were noninvasively measured using EchoPAC., Results: The total myocardial work during IVR (MW IVR ), myocardial constructive work during IVR (MCW IVR ), myocardial wasted work during IVR (MWW IVR ), and myocardial work efficiency during IVR (MWE IVR ) of these patients were 122.5 ± 60.1 mmHg%, 85.7 ± 47.8 mmHg%, 36.7 ± 30.6 mmHg%, and 69.4 ± 17.8%, respectively. The MW during IVR was significantly different between patients and healthy subjects. For patients, MWE IVR and MCW IVR were significantly correlated with the LV E/e' ratio and left atrial volume index, MWE IVR exhibited a significant correlation with the maximal rate of decrease in LV pressure (dp/dt per min) and tau, and the MWE IVR corrected by IVRT also exhibited a significant correlation with tau., Conclusions: MW during IVR significantly changes in patients with risks for LVDD, and is correlated to LV conventional diastolic indices, including dp/dt min and tau. Noninvasive MW during IVR may be a promising tool to evaluate the LV diastolic function., (© 2023. The Author(s).)

Mass spectrometry (MS)-based metabolic profiling of the endophytic fungus Chaetomium nigricolor F5 guided the isolation of five novel cytochalasans, chamisides B-F ( 1-5 ), and two known ones, chaetoconvosins C and D ( 6 and 7 ). Their structures including stereochemistry were unambiguously determined by MS, nuclear magnetic resonance, and single-crystal X-ray diffraction analyses. Compounds 1-3 share a new 5/6/5/5/7-fused pentacyclic skeleton in cytochalasans and are appropriately proposed to be the key biosynthetic precursors of co-isolated cytochalasans with a 6/6/5/7/5, 6/6/5/5/7, or 6/6/5 ring system. Remarkably, compound 5 with a relatively flexible side chain showed promising inhibition activity against the cholesterol transporter protein Niemann-Pick C1-like 1 (NPC1L1), expanding the function of cytochalasans.

Background: Decreased peak oxygen consumption during exercise (peak Vo 2 ) is a well-established prognostic marker for mortality in ambulatory heart failure. After heart transplantation, the utility of peak Vo 2 as a marker of post-transplant survival is not well established., Methods and Results: We performed a retrospective analysis of adult heart transplant recipients at the Hospital of the University of Pennsylvania who underwent cardiopulmonary exercise testing within a year of transplant between the years 2000 to 2011. Using time-to-event models, we analyzed the hazard of mortality over nearly two decades of follow-up as a function of post-transplant percent predicted peak Vo 2 (%Vo 2 ). A total of 235 patients met inclusion criteria. The median post-transplant %Vo 2 was 49% (IQR 42 to 60). Each standard deviation (±14%) increase in %Vo 2 was associated with a 32% decrease in mortality in adjusted models (HR 0.68, 95% CI 0.53 to 0.87, p = 0.002). A %Vo 2 below 29%, 64% and 88% predicted less than 80% survival at 5, 10, and 15 years, respectively., Conclusions: Post-transplant peak Vo 2 is a highly significant prognostic marker for long-term post-transplant survival. It remains to be seen whether decreased peak Vo 2 post-transplant is modifiable as a target to improve post-transplant longevity.

Background: Knee osteoarthritis (KOA) is a chronic musculoskeletal disease affecting the entire joint. Exercise therapy is the core treatment plan for non-surgical treatment of KOA, and tele-rehabilitation is also applied to KOA, but there is a lack of research on the comparison of pain and function recovery between different exercise methods combined Internet respectively. The study aims to compare the effects of power cycling and quadriceps training combined with online guidance separately on KOA mitigation of pain, recovery of function, quality of life, and adherence of participants in the community, compared to the control group., Methods: This study is a single-blind, 12-week parallel randomized controlled trial. Seventy-two participants aged ≥ 50 years with KOA will be randomized into either the power cycling group, the quadriceps group or the control group. The intervention will be performed three times per week during 12 weeks. Outcome measures will be assessed at baseline, and at 4, 8, and 12 weeks after allocation. The primary outcome will be self-reported pain, assessed with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale. Secondary outcomes will include mitigation of knee pain, quality of life, improvement of functional physical performance, adherence of participants., Discussion: By summarizing the study's strengths and limitations, this trial results may guide tele-rehabilitation of KOA in the community.Trial registration: The study was registered in the clinical trial registry ChiCTR2200059255, 27/04/2022., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

The relationship between folic acid and S -adenosylhomocysteine (SAH) is controversial. This study aims to explore the effect of different doses of folic acid supplementation on SAH levels in hypertensive patients and the modification of methylene-tetrahydrofolate reductase (MTHFR) C677T gene polymorphism. A randomized, double-blind, controlled clinical trial was conducted. Hypertensive patients aged 45-75 years without a history of stroke and cardiovascular disease were selected, who were randomly assigned to one of 8 dose groups. This trial has been registered with Trial Number: ChiCTR1800016135. In the total population, folic acid supplementation of 0.4-2.0 mg/day had no effect on SAH level (β = 0.47, 95% CI: -0.86-1.79, p  = 0.491), while folic acid supplementation of 2.4 mg/day significantly increased SAH level (β = 1.93, 95% CI: 0.22-3.64, p  = 0.027). Stratified analysis found that MTHFR C677T genotype CC supplemented with 2.4 mg/day folic acid had no effect on SAH level (β = 0.30, 95% CI: -2.74-3.34, p  = 0.847), while CT and TT genotype supplemented with 2.4 mg/day folic acid showed a significant increase in SAH level (CT: β = 2.98, 95% CI: 0.34-5.62, p  = 0.027; TT: β = 3.00, 95% CI: -0.51-6.51, p  = 0.095; CT combined with TT: β = 2.99, 95% CI: 0.90-5.09, p  = 0.005). In conclusion, supplementation of 2.4 mg/day folic acid can lead to increased SAH levels, especially in MTHFR C677T genotype CT and TT., Competing Interests: No potential conflicts of interest were disclosed., (Copyright © 2022 JCBN.)

Background: Several TSC1/2- or MTOR -mutated eosinophilic renal tumor subsets are emerging, including eosinophilic solid and cystic renal cell carcinoma (ESC RCC), eosinophilic vacuolated tumors (EVTs) and low-grade oncocytic tumors (LOTs). "Unclassified renal tumors with TSC/MTOR mutations" ( TSC -mt RCC-NOS) do not meet the criteria for other histomolecular subtypes. Whether these tumors represent a continuum of 1 TS C/ MTOR -mutation-associated disease is unknown., Design: We evaluated the clinicopathologic and IHC profiles of 39 eosinophilic renal tumors with targeted DNA sequencing-confirmed TSC/MTOR mutations. Twenty-eight of these, plus 6 ChRCC, 5 RO, 5 ccRCC, 7 MiT RCC and 6 normal renal tissues, were profiled transcriptionally by RNA-seq., Results: The 39 cases were reclassified based on morphological and IHC features as ESC RCC (12), EVT (9), LOT, (8) and TSC -mt RCC-NOS (10). The mutation profiles demonstrated consistency; ESC RCCs (12/12) had TSC mutations, and most LOTs (7/8) had MTOR mutations. Ten TSC -mt RCC-NOSs exhibited heterogeneous morphology, arising a differential diagnosis with other renal tumors, including MiT RCC, PRCC and epithelioid PEComa. RNA sequencing-based clustering segregated ESC RCC, EVT and LOT from each other and other renal tumors, indicating expression profile-level differences. Most TSC- mt RCC-NOSs (6/7) formed a mixed cluster with ESC RCC, indicating similar expression signatures; one TSC- mt RCC-NOS with unusual biphasic morphology clustered with EVT., Conclusions: We expanded the TSC/MTOR -associated eosinophilic renal tumor morphologic spectrum, identified gene mutation characteristics, and highlighted differential diagnosis challenges, especially with MiT RCC. ESC RCC, EVT, and LOT having distinct expression profiles. TSC -mt RCC-NOS may cluster with recognized TSC/MTOR -associated entities., Competing Interests: Conflicts of Interest and Source of Funding: This work was supported by grants from the National Natural Science Foundation of China (81872095 to Q.R., 81802557 to Q.-y. X. and 82103192 to R.F.) and Zhejiang Provincial Natural Science Foundation (LY21H160052 to Ming Zhao). For the remaining authors none were declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Melanoma is the most lethal skin malignant tumor with a short survival once stepping into the metastatic status and poses a therapeutic challenge. Apatinib (a tyrosine kinase inhibitor) is a promising antiangiogenic agent for the treatment of metastatic melanoma. However, antiangiogenic monotherapy is prone to acquired drug resistance and has a limited therapeutic effect. The persistence dependence of glycolytic metabolism in antiangiogenic therapy-resistant cells provides evidence that glycolysis inhibitors may enhance the effect of antiangiogenic therapy. So, this study aimed to investigate whether WZB117 (a specific GLUT1 inhibitor) could enhance the anti-tumor effect of apatinib against melanoma and its potential mechanisms. Methods: We investigated the anti-tumor effects of apatinib alone or in combination with WZB117 on human melanoma cell lines (A375 and SK-MEL-28). The MTT assay determined cell viability and the half-maximal inhibitory concentration (IC50). Multiple drug effect/combination indexes (CI) analysis was conducted to assess interactions between apatinib and WZB117. Signal transducer and activator of transcription 3 (STAT3) pathway measured by western blotting and immunofluorescence staining. RNA expression analyses were performed using the reverse transcription-quantitative PCR method. Results: Apatinib and WZB117 showed dose and time-dependent growth inhibitory effects in both melanoma cells. The IC50 of apatinib at 48 h in A375 and SK-MEL-28 cells was 62.58 and 59.61 μM, respectively, while the IC50 of WZB117 was 116.85 and 113.91 μM, respectively. The CI values of the two drugs were 0.538 and 0.544, respectively, indicating a synergistic effect of apatinib combined with WZB117. We also found that glucose consumption and lactate production were suppressed by apatinib plus WZB117 in a dose-dependent manner, paralleled by reducing glycolytic enzyme pyruvate kinase M2 (PKM2). The potential mechanism of the combination was to suppress the phosphorylation of STAT3. Knockdown of STAT3 by siRNA inhibited the expression of PKM2, while the activation of STAT3 by IL-6 increased the expression of PKM2. The effects of IL-6 were attenuated by apatinib combined with WZB117 treatment. Conclusion: WZB117 enhanced the anti-tumor effect of apatinib against melanoma via modulating glycolysis by blocking the STAT3/PKM2 axis, which suggested the combination of apatinib with WZB117 could be a potential therapeutic candidate for melanoma., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Li, Liu, Deng and Jiang.)