Cardiovascular toxicity with CTLA-4 inhibitors in cancer patients: A meta-analysis.

Background: With the emergence of cytotoxic T lymphocyte-associated protein-4 (CTLA-4) inhibitors, the outcomes of patients with malignant tumors have improved significantly. However, the incidence of cardiovascular adverse events has also increased, which can affect tumor treatment. In this study, we evaluated the incidence and severity of adverse cardiovascular events caused by CTLA-4 inhibitors by analyzing reported trials that involved CTLA-4 inhibitor therapy. Methods: Randomized clinical trials published in English from January 1, 2013, to November 30, 2022, were searched using the Cochrane Library and PubMed databases. All included trials examined all grade and grades 3-5 cardiac and vascular adverse events. These involved comparisons of CTLA-4 inhibitors to placebo, CTLA-4 inhibitors plus chemotherapy to chemotherapy alone, CTLA-4 inhibitors combined with PD-1/PD-L1 inhibitors to PD-1/PD-L1 inhibitors alone, and CTLA-4 inhibitors plus target agent to PD-1/PD-L1 inhibitors plus target agent. The odds ratio (OR) and corresponding 95% confidence intervals (CIs) were calculated using the Mantel-Haenszel method. Results: Overall, 20 trials were included. CTLA-4 inhibitors significantly increased the incidence of all-grade cardiovascular toxicity (OR = 1.33, 95% CI: 1.00-1.75, p = 0.05). The incidence of all-grade cardiovascular toxicity increased in malignant tumor patients who received single-agent CTLA-4 inhibitors (OR = 1.73, 95% CI: 1.13-2.65, p = 0.01), as well as the incidence rate of grades 3-5 cardiovascular adverse events (OR = 2.00, 95% CI: 1.08-3.70, p = 0.03). Compared with the non-CTLA-4 inhibitor group, CTLA-4 inhibitors plus chemotherapy, PD-1/PD-L1 inhibitors, or target agent did not significantly affect the incidence of cardiac and vascular toxicity. The incidence of grades 3-5 cardiac failure, hypertension, pericardial effusion, myocarditis, and atrial fibrillation were much higher among patients exposed to CTLA-4 inhibitor, but the data were not statistically significant. Conclusion: Our findings suggest that the incidence rate of all cardiovascular toxicity and severe cardiovascular toxicity increased in patients who were administered CTLA-4 inhibitors. In addition, the risk of serious cardiovascular toxic events was independent of the type of adverse event. From these results, physicians should assess the benefits and risks of CTLA-4 inhibitors when treating malignancies.

Preparation and optimization of dummy molecularly imprinted polymer-based solid-phase extraction system for selective enrichment of p-toluene sulfonate esters genotoxic impurities.

Sulfonate esters, one class of genotoxic impurities (GTIs), have gained significant attention in recent years due to their potential to cause genetic mutations and cancer. In the current study, we employed the dummy template molecular imprinting technology with a dummy template molecule replacing the target molecule to establish a pretreatment method for samples containing p-toluene sulfonate esters. Through computer simulation and ultraviolet-visible spectroscopy analysis, the optimal functional monomer acrylamide and polymerization solvent chloroform were selected. Subsequently, a dummy template molecularly imprinted polymer (DMIP) was prepared by the precipitation polymerization method, and the polymer was characterized in morphology, particle size, and composition. The results of the adsorption and enrichment study demonstrated that the DMIP has high adsorption capability (Q = 7.88 mg/g) and favorable imprinting effects (IF = 1.37); Further, it could simultaneously adsorb three p-toluene sulfonate esters. The optimal adsorption conditions were obtained by conditional optimization of solid-phase extraction (SPE). A pH 7 solution was selected as the loading condition, the methanol/1 % phosphoric acid solution (20:80, v/v) was selected as the washing solution, and acetonitrile containing 10 % acetic acid in 6 mL was selected as the elution solvent. Finally, we determined methyl p-toluene sulfonate alkyl esters, ethyl p-toluene sulfonate alkyl esters, and isopropyl p-toluene sulfonate alkyl esters in tosufloxacin toluene sulfonate and capecitabine at the 10 ppm level (relative to 1 mg/mL active pharmaceutical ingredient (API) samples) by using DMIP-based SPE coupled with HPLC. This approach facilitated the selective enrichment of p-toluene sulfonate esters GTIs from complex API samples.

Impact of hyperuricemia and chronic kidney disease on the prevalence and mortality of cardiovascular disease in cancer survivors.

BACKGROUND: The risks of cardiovascular disease (CVD) and CVD mortality are prevalent among cancer survivors (CS) population. The 2022 ESC Guidelines on cardio-oncology have recommended that modifying cardiovascular risk factors (CVRF) could potentially improve long-term outcomes in CS. OBJECTIVES: To identify the independent and joint chronic kidney disease (CKD) associations of hyperuricemia with the incidence of CVD and mortality outcomes among CS. METHODS: Utilizing data from the US National Health and Nutrition Examination Survey spanning 2005-2018, we assessed the risk of CVD through weighted multivariable logistic regression and restricted cubic spline (RCS) regression. Additionally, all-cause and CVD-related mortality were evaluated using weighted multivariable Cox regression and Kaplan-Meier analysis. Subgroup analysis was conducted to further elucidate the interplay between hyperuricemia, CKD, and mortality within the CS population. RESULTS: A total of 3276 CS participants were enrolled in this study. Results showed that hyperuricemia was positively related to the incidence of CVD (OR [95% CI] = 1.86 [1.24, 2.81], p = 0.004). RCS analysis further demonstrated that uric acid levels ≥345 µmol/L positively correlated with CVD incidence (p value for nonlinearity = 0.0013). However, the association between hyperuricemia and CVD mortality, as well as all-cause mortality did not reach statistical significance in the fully adjusted model (HR = 1.48, 95% CI: 0.92-2.39, p = 0.11; HR = 1.11, 95% CI:0.92, 1.34, p = 0.28, respectively). Among CS participants with CKD, hyperuricemia could increase risks of all-cause (HR [95% CI] = 1.39 [1.08, 1.11], p = 0.02) and CVD mortality (HR [95% CI] =2.17 [1.29, 3.66], p = 0.004) after adjusting for sex, age, and ethnicity. CONCLUSIONS: In the CS population, hyperuricemia was positively associated with the incidence of CVD. In addition, CKD might be an intermediate variable among the CS population that mediated the effects of hyperuricemia on mortality.

Safety and efficacy of day anterior cervical discectomy and fusion procedure for degenerative cervical spondylosis: a retrospective analysis.

OBJECTIVE: Our study aimed to develop a day anterior cervical discectomy and fusion (ACDF) procedure to treat degenerative cervical spondylosis (DCS). The goal was to analyze its clinical implications, safety, and early effects to provide a better surgical option for eligible DCS patients. METHODS: A retrospective analysis was performed to identify DCS patients who underwent day ACDF from September 2022 to August 2023. The operative time, intraoperative blood loss, postoperative drainage, preoperative and postoperative visual analog scale (VAS) scores, neck disability index (NDI) scores, Japanese Orthopedic Association (JOA) scores, JOA recovery rate (RR), incidence of dysphagia-related symptoms, 30-day hospital readmission rate, and incidence of other complications were recorded to evaluate early clinical outcomes. Radiography was performed to assess the location of the implants, neurological decompression, and cervical physiological curvature. RESULTS: All 33 patients (23 women and 10 men) underwent successful surgery and experienced significant symptomatic and neurological improvements. Among them, 26 patients underwent one-segment ACDF, 5 underwent two-segment ACDF, and 2 underwent three-segment ACDF. The average operative time was 71.1 ± 20.2 min, intraoperative blood loss was 19.1 ± 6.2 mL, and postoperative drainage was 9.6 ± 5.8 mL. The preoperative VAS and NDI scores improved postoperatively (7.1 ± 1.2 vs. 3.1 ± 1.3 and 66.7% ± 4.8% vs. 24.1% ± 2.5%, respectively), with a significant difference (P < 0.01). Moreover, the preoperative JOA scores improved significantly postoperatively (7.7 ± 1.3 vs. 14.2 ± 1.4; P < 0.01) with an RR of 93.9% in good or excellent. Postoperative dysphagia-related symptoms occurred in one patient (3.0%). During the follow-up period, no patient was readmitted within 30 days after discharge; however, an incisional hematoma was reported in one patient on the 6th day after discharge, which was cured by pressure dressing. The postoperative radiographs revealed perfect implant positions and sufficient nerve decompression in all patients. Furthermore, the preoperative cervical physiological curvature improved significantly after the operation (14.5° ± 4.0° vs. 26.3° ± 5.4°; P < 0.01). CONCLUSIONS: Day ACDF has good safety and early clinical efficacy, and it could be an appropriate choice for eligible DCS patients.

A case report of right bundle branch block and junctional beats during ablation at the right ventricle outflow tract: metallic occluder's unanticipated effect.

Background: Previously, ablation at the outflow tract was considered to be safe and rarely affected the His-Purkinje system due to their spatial distance. However, we have reported a case of right bundle branch block (RBBB) and junctional beats that were recorded during radiofrequency catheter ablation in a patient who had a history of peri-membranous ventricular septal defect (pmVSD) closure and the implantation of a metallic occluder. Case summary: A 16-year-old girl with a metallic occluder for peri-membranous ventricular septum defect underwent an ablation procedure for premature ventricular complexes. During the ablation at the right ventricular outflow tract (RVOT), RBBB and junctional beats were recorded. His bundle potentials and the high-frequency potential generated by electrical interference were observed when mapping the margin of the occluder. To ensure safety, we attempted ablation at the right coronary cusp in the left ventricular outflow tract, which eventually proved to be successful, presenting an alternative ablation strategy. Conclusion: This is a rare report of RBBB and junctional beats observed during ablation at RVOT in a patient with pmVSD and a metallic occluder. The observed damage to the His-Purkinje system may be attributed to uncontrolled radiofrequency energy heating up caused by the metallic device. This case emphasizes the importance of thorough electroanatomic and activation mapping prior to starting the ablation procedure, especially in complicated cases. Furthermore, it suggests that ablation at a relatively remote position is both feasible and relatively safe for patients with occluder devices.

Renal clearable magnetic nanoparticles for magnetic resonance imaging and guided therapy.

Magnetic resonance imaging (MRI) is a non-invasive, radiation-free imaging technique widely used for disease detection and therapeutic evaluation due to its infinite penetration depth. Magnetic nanoparticles (MNPs) have unique magnetic and physicochemical properties, making them ideal as contrast agents for MRI. However, the in vivo toxicity of MNPs, resulting from metal ion leakage and long-term accumulation in the reticuloendothelial system (RES), limits their clinical application. To overcome these challenges, there is considerable interest in the development of renal-clearable MNPs that can be completely cleared through the kidney, reducing retention time and potential toxic risks. In this review, we provide an overview of recent advancements in the development of renal-clearable MNPs for disease imaging and treatment. We discuss the factors influencing renal clearance, summarize the types of renal-clearable MNPs, their synthesis methods, and biomedical applications. This review aims to offer comprehensive information for the design and clinical translation of renal-clearable MNPs. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Diagnostic Tools > Biosensing.

Muscle quality index and cardiovascular disease among US population-findings from NHANES 2011-2014.

BACKGROUND AND OBJECTIVE: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in the United States. However, current evidence on the association between muscle quality and CVD is limited. This study investigates the potential association between the muscle quality index (MQI) and the prevalence of CVD and CVD-related mortality. METHODS: Participants were selected from the National Health and Nutrition Examination Survey (NHANES) 2011-2014. Data on mortality and causes of death were obtained from the National Death Index (NDI) records through December 31, 2019. Statistical analysis used in this study, including weighted multivariable linear and logistic regression, cox regression and Kaplan-Meier (K-M) analysis, to estimate the association between MQI and all-cause mortality as well as CVD mortality. In addition, subgroup analysis was used to estimate the association between MQI and CVD subtypes, such as heart attack, coronary heart disease, angina, congestive heart failure, and stroke. RESULTS: A total of 5,053 participants were included in the final analysis. Weighted multivariable linear regression models revealed that a lower MQI.total level was independently associated with an increased risk of CVD development in model 3, with t value =-3.48, 95%CI: (-0.24, -0.06), P = 0.002. During 5,053 person-years of 6.92 years of follow-up, there were 29 deaths from CVD. Still, the association between MQI.total and CVD mortality, as well as all-cause mortality did not reach statistical significance in the fully adjusted model (HR = 0.58, 95% CI: 0.21-1.62, P = 0.30; HR = 0.91, 95% CI:0.65,1.28, P = 0.59, respectively). Subgroup analysis confirmed that MQI.total was negatively associated with congestive heart failure (OR = 0.35, 95% CI = 0.18,0.68, P = 0.01). CONCLUSION: This study highlights the potential of MQI as a measure of muscle quality, its negative correlation with congestive heart failure (CHF). However, MQI was not very useful for predicting the health outcomes such as CVD and mortality. Therefore, more attention should be paid to the early recognition of muscle weakness progression in CHF. Further studies are needed to explore more effective indicator to evaluate the association between muscle quality and health outcomes.

'Single-shot' pulmonary vein isolation using a novel lotos pulsed field ablation catheter: a pre-clinical evaluation of feasibility, safety, and 30-day efficacy.

AIMS: Pulsed field ablation (PFA) is emerging as a non-thermal, tissue-specific technique for pulmonary vein isolation (PVI) in atrial fibrillation therapy. This pre-clinical study aims to investigate the feasibility and safety of PVI using a novel PFA system including a nanosecond-scale PFA generator, a novel lotos PFA catheter, and a customized 12 Fr steerable sheath. METHODS AND RESULTS: A total of 11 Yorkshire swine were included in this study, with 4 in the acute cohort and 7 in the chronic cohort. Under general anaesthesia, transseptal puncture and pulmonary vein (PV) angiography was initially performed. The PFA catheter was navigated to position at the right and left PV antrum after the electroanatomic reconstruction of the left atrium. Biphasic PFA applications were performed on PVs in both the spindle-shaped and the lotos-shaped poses. Pulmonary vein isolation and PFA-associated safety were assessed 30 min after ablation in both cohorts and 30 days later in the chronic cohort. Detailed necropsy and histopathology were performed. Additional intracardiac echocardiography and coronary angiogram were evaluated for safety. All target PVs (n = 20) were successfully isolated on the first attempt. No spasm of coronary artery or microbubble was seen during the procedure. Eleven of 12 PVs (91.6%) remained in isolation at the 30-day invasive study. No evidence of PV stenosis was observed in any targets. However, transient diaphragm capture occurred in 17.6%. Histopathological examinations showed no evidence of collateral injury. CONCLUSION: This study provides scientific evidence demonstrating the safety and efficacy of the novel PFA catheter and system for single-shot PVI, which shows great potential.

Ultrasmall PtMn nanoparticles as sensitive manganese release modulator for specificity cancer theranostics.

Manganese-based nanomaterials (Mn-nanomaterials) hold immense potential in cancer diagnosis and therapies. However, most Mn-nanomaterials are limited by the low sensitivity and low efficiency toward mild weak acidity (pH 6.4-6.8) of the tumor microenvironment, resulting in unsatisfactory therapeutic effect and poor magnetic resonance imaging (MRI) performance. This study introduces pH-ultrasensitive PtMn nanoparticles as a novel platform for enhanced ferroptosis-based cancer theranostics. The PtMn nanoparticles were synthesized with different diameters from 5.3 to 2.7 nm with size-dominant catalytic activity and magnetic relaxation, and modified with an acidity-responsive polymer to create pH-sensitive agents. Importantly, R-PtMn-1 (3 nm core) presents "turn-on" oxidase-like activity, affording a significant enhancement ratio (pH 6.0/pH 7.4) in catalytic activity (6.7 folds), compared with R-PtMn-2 (4.2 nm core, 3.7 folds) or R-PtMn-3 (5.3 nm core, 2.1 folds), respectively. Moreover, R-PtMn-1 exhibits dual-mode contrast in high-field MRI. R-PtMn-1 possesses a good enhancement ratio (pH 6.4/pH 7.4) that is 3 or 3.2 folds for T1- or T2-MRI, respectively, which is higher than that of R-PtMn-2 (1.4 or 1.5 folds) or R-PtMn-3 (1.1 or 1.2 folds). Moreover, their pH-ultrasensitivity enabled activation specifically within the tumor microenvironment, avoiding off-target toxicity in normal tissues during delivery. In vitro studies demonstrated elevated intracellular reactive oxygen species production, lipid peroxidation, mitochondrial membrane potential changes, malondialdehyde content, and glutathione depletion, leading to enhanced ferroptosis in cancer cells. Meanwhile, normal cells remained unaffected by the nanoparticles. Overall, the pH-ultrasensitive PtMn nanoparticles offer a promising strategy for accurate cancer diagnosis and ferroptosis-based therapy.

GSH/APE1 Cascade-Activated Nanoplatform for Imaging Therapy Resistance Dynamics and Enzyme-Mediated Adaptive Ferroptosis.

Ferroptosis, as a type of programmed cell death process, enables effective damage to various cancer cells. However, we discovered that persistent oxidative stress during ferroptosis can upregulate the apurinic/apyrimidinic endonuclease 1 (APE1) protein that induces therapeutic resistance ("ferroptosis resistance"), resulting in an unsatisfactory treatment outcome. To address APE1-induced therapeutic resistance, we developed a GSH/APE1 cascade activated therapeutic nanoplatform (GAN). Specifically, the GAN is self-assembled by DNA-functionalized ultrasmall iron oxide nanoparticles and further loaded with drug molecules (drug-GAN). GSH-triggered GAN disassembly can "turn on" the catalysis of GAN to induce efficient lipid peroxidation (LPO) for ferroptosis toward the tumor, which could upregulate APE1 expression. Subsequently, upregulated APE1 can further trigger accurate drug release for overcoming ferroptosis resistance and inducing the recovery of near-infrared fluorescence for imaging the dynamics of APE1. Importantly, adaptive drug release can overcome the adverse effects of APE1 upregulation by boosting intracellular ROS yield and increasing DNA damage, to offset APE1's functions of antioxidant and DNA repair, thus leading to adaptive ferroptosis. Moreover, with overexpressed GSH and upregulated APE1 in the tumor as stimuli, the therapeutic specificity of ferroptosis toward the tumor is greatly improved, which minimized nonspecific activation of catalysis and excessive drug release in normal tissues. Furthermore, a switchable MRI contrast from negative to positive is in sync with ferroptosis activation, which is beneficial for monitoring the ferroptosis process. Therefore, this adapted imaging and therapeutic nanoplatform can not only deliver GSH/APE1-activated lipid peroxide mediated adaptive synergistic therapy but also provided a switchable MRI/dual-channel fluorescence signal for monitoring ferroptosis activation, drug release, and therapy resistance dynamics in vivo, leading to high-specificity and high-efficiency adaptive ferroptosis therapy.

Emerging biomedical imaging-based companion diagnostics for precision medicine.

The tumor heterogeneity, which leads to individual variations in tumor microenvironments, causes poor prognoses and limits therapeutic response. Emerging technology such as companion diagnostics (CDx) detects biomarkers and monitors therapeutic responses, allowing identification of patients who would benefit most from treatment. However, currently, most US Food and Drug Administration-approved CDx tests are designed to detect biomarkers in vitro and ex vivo, making it difficult to dynamically report variations of targets in vivo. Various medical imaging techniques offer dynamic measurement of tumor heterogeneity and treatment response, complementing CDx tests. Imaging-based companion diagnostics allow for patient stratification for targeted medicines and identification of patient populations benefiting from alternative therapeutic methods. This review summarizes recent developments in molecular imaging for predicting and assessing responses to cancer therapies, as well as the various biomarkers used in imaging-based CDx tests. We hope this review provides informative insights into imaging-based companion diagnostics and advances precision medicine.

Prevalence and incidence of heart failure among community in China during a three-year follow-up.

BACKGROUND: Epidemiological surveys on heart failure (HF) in Chinese community are relatively lacking. This study aimed to estimate the prevalence and incidence of HF among community residents in southern China. METHODS: Baseline data of this prospective study was collected from 2015 to 2017 among 12,013 permanent residents aged ≥ 35 years in Guangzhou, China. The same survey process was carried out for individuals aged ≥ 65 years after a three-year follow-up. RESULTS: The overall prevalence of HF in community residents aged ≥ 35 years was 1.06%. Male had significantly higher risk of HF prevalence [odds ratio (OR) = 1.50, P = 0.027]. The gender-adjusted risk of HF was 1.48 times higher per 10 years aging. HF prevalence was statistically associated with atrial fibrillation, valvular heart disease, hypertension and chronic obstructive pulmonary disease after adjusting for age and gender (OR = 8.30, 5.17, 1.11, 2.28, respectively; all P < 0.05). HF incidence in individuals aged ≥ 65 years were 847 per 100,000 person-years. Baseline atrial fibrillation, valvular heart disease, and diabetes mellitus were risk factors for HF incidence for individuals aged ≥ 65 years adjusting for age and gender (OR = 5.05, 3.99, 2.11, respectively; all P < 0.05). Besides, residents with new-onset atrial fibrillation and myocardial infarction were at significantly higher risk of progression to HF (OR = 14.41, 8.54, respectively; all P < 0.05). CONCLUSIONS: Both pre-existing and new-onset cardiovascular diseases were associated with HF incidence in southern China. Management of related cardiovascular diseases may be helpful to reduce the incidence of HF.

Dynamic-Reversible MRI Nanoprobe for Continuous Imaging Redox Homeostasis in Hepatic Ischemia-Reperfusion Injury.

Hepatic ischemia-reperfusion (I/R) injury accompanied by oxidative stress is responsible for postoperative liver dysfunction and failure of liver surgery. However, the dynamic non-invasive mapping of redox homeostasis in deep-seated liver during hepatic I/R injury remains a great challenge. Herein, inspired by the intrinsic reversibility of disulfide bond in proteins, a kind of reversible redox-responsive magnetic nanoparticles (RRMNs) is designed for reversible imaging of both oxidant and antioxidant levels (ONOO-/GSH), based on sulfhydryl coupling/cleaving reaction. We develop a facile strategy to prepare such reversible MRI nanoprobe via one-step surface modification. Owing to the significant change in size during the reversible response, the imaging sensitivity of RRMNs is greatly improved, which enables RRMNs to monitor the tiny change of oxidative stress in liver injury. Notably, such reversible MRI nanoprobe can non-invasively visualize the deep-seated liver tissue slice by slice in living mice. Moreover, this MRI nanoprobe can not only report molecular information about the degree of liver injury but also provide anatomical information about where the pathology occurred. The reversible MRI probe is promising for accurately and facilely monitoring I/R process, accessing injury degree and developing powerful strategy for precise treatment.

High-Power, Short-Duration Ablation under the Guidance of Relatively Low Ablation Index Values for Paroxysmal Atrial Fibrillation: Long-Term Outcomes and Characteristics of Recurrent Atrial Arrhythmias.

OBJECTIVE: The purpose of this study was to evaluate the difference in effectiveness and safety of high-power, short-duration (HPSD) radiofrequency catheter ablation (RFA) guided by relatively low ablation index (AI) values and conventional RFA in paroxysmal atrial fibrillation (PAF) patients. METHODS: The HPSD RFA strategy (40-50 W, AI 350-400 for anterior, 320-350 for posterior wall; n = 547) was compared with the conventional RFA strategy (25-40 W, without AI; n = 396) in PAF patients who underwent their first ablation. Propensity-score matching analyses were used to compare the outcomes of the two groups while controlling for confounders. RESULTS: After using propensity-score matching analysis, the HPSD group showed a higher early recurrence rate (22.727% vs. 13.636%, p = 0.003), similar late recurrence rate, and comparable safety (p = 0.604) compared with the conventional group. For late recurrent atrial arrhythmia types, the rate of regular atrial tachycardia was significantly higher in the HPSD group (p = 0.013). Additionally, the rate of chronic pulmonary vein reconnection and non-pulmonary vein triggers during repeat procedures was similar in both groups. CONCLUSIONS: For PAF patients, compared with the conventional RFA strategy, the HPSD RFA strategy at relatively low AI settings had a higher early recurrence rate, similar long-term success rate, and comparable safety.

Comparison of Effectiveness and Safety between High-Power Short-Duration Ablation and Conventional Ablation for Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Aim: We aimed to evaluate the effectiveness and safety between high-power short-duration (HPSD) radiofrequency ablation (RFA) and conventional RFA in patients with atrial fibrillation (AF). Methods: Studies comparing HPSD and traditional applications in patients undergoing initial catheter ablation for atrial fibrillation from inception through December 2021 were searched on Pubmed, Medline, Cochrane, and Clinicaltrials.gov. Results: The meta-analysis included seventeen studies with a total of 4934 patients. HPSD group decreased procedure duration (mean difference (MD) -38.28 min, P < 0.001), RF duration (MD -20.51 min, P < 0.001), fluoroscopy duration (MD -5.19 min, P < 0.001), and acute pulmonary vein reconnection (Odds ratio (OR) 0.40, P < 0.001), while improving the freedom from atrial arrhythmia at one year (OR 1.48, 95% confidence interval (CI) 1.12-1.94, P=0.005) and rates of first-pass isolation (OR 8.92, P=0.001). Compared with the conventional group, freedom from atrial arrhythmia at one-year follow-up was higher in the HPSD group without the guidance of AI/LSI (OR 1.66, P=0.01) and studies with a power setting of 40-50 W (OR 1.93, P=0.002). Nevertheless, the two groups had similar effectiveness with a power setting of 50 W in the HPSD RFA (OR 1.10, P=0.52). There was no difference in complications between the two groups (P=0.71). Conclusion: HPSD RFA was associated with shorter procedure duration, higher freedom from atrial arrhythmia, and comparable safety compared to conventional RFA.

Ternary Alloy PtWMn as a Mn Nanoreservoir for High-Field MRI Monitoring and Highly Selective Ferroptosis Therapy.

Ferroptosis exhibits potential to damage drug-resistant cancer cells. However, it is still restricted with the "off-target" toxicity from the undesirable leakage of metal ions from ferroptosis agents, and the lack of reliable imaging for monitoring the ferroptosis process in living systems. Herein, we develop a novel ternary alloy PtWMn nanocube as a Mn reservoir, and further design a microenvironment-triggered nanoplatform that can accurately release Mn ions within the tumor to increase reactive oxygen species (ROS) generation, produce O2 and consume excess glutathione for synergistically enhancing nonferrous ferroptosis. Moreover, this nanoplatform exerts a responsive signal in high-field magnetic resonance imaging (MRI), which enables the real-time report of Mn release and the monitoring of ferroptosis initiation through the signal changes of T1 -/T2 -MRI. Thus, our nanoplatform provides a novel strategy to store, deliver and precisely release Mn ions for MRI-guided high-specificity ferroptosis therapy.

Recent development of a magneto-optical nanoplatform for multimodality imaging of pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer. Given its inconspicuous and atypical early symptoms and hidden location, most patients have already reached the terminal stage before diagnosis. At present, the diagnosis of PDAC mainly depends on serological and imaging examinations. However, serum tests cannot identify specific tumor locations and each imaging technology has its own defects, bringing great challenges to the early diagnosis of PDAC. Therefore, it is of great significance to find new strategies for the early and accurate diagnosis of PDAC. In recent years, a magneto-optical nanoplatform integrating near infrared fluorescence, photoacoustic, magnetic resonance imaging, etc. has attracted widespread attention, giving full play to the complementary advantages of each imaging modality. Herein, we summarize the recent advances of imaging modalities in the diagnosis of pancreatic cancer, and then discuss in detail the construction and modification of magneto or/and optical probes for multimodal imaging, and advances in early diagnosis using the combination of various imaging modalities, which can provide potential tools for the early diagnosis or even intraoperative navigation and post-treatment follow-up of PDAC patients.

Row and Column Structure-Based Biclustering for Gene Expression Data.

Due to the development of high-throughput technologies for gene analysis, the biclustering method has attracted much attention. However, existing methods have problems with high time and space complexity. This paper proposes a biclustering method, called Row and Column Structure-based Biclustering (RCSBC), with low time and space complexity to find checkerboard patterns within microarray data. First, the paper describes the structure of bicluster by using the structure of rows and columns. Second, the paper chooses the representative rows and columns with two algorithms. Finally, the gene expression data are biclustered on the space spanned by representative rows and columns. To the best of our knowledge, this paper is the first to exploit the relationship between the row/column structure of a gene expression matrix and the structure of biclusters. Both the synthetic datasets and the real-life gene expression datasets are used to validate the effectiveness of our method. It can be seen from the experiment results that the RCSBC outperforms the state-of-the-art algorithms both on clustering accuracy and time/space complexity. This study offers new insights into biclustering the large-scale gene expression data without loading the whole data into memory.

Minimally Interrupted Non-Vitamin K Antagonist Oral Anticoagulants vs. Bridging Therapy and Uninterrupted Vitamin K Antagonists During Atrial Fibrillation Ablation: A Retrospective Single-Center Study.

Objectives: Although the latest international guidelines recommend the use of uninterrupted non-vitamin K antagonist oral anticoagulants (NOAC) during atrial fibrillation (AF) ablation, it does not reflect current clinical practice, as most centers still use a minimally interrupted NOAC strategy. The purpose of this study was to evaluate the safety and effectiveness of minimally interrupted NOAC compared with bridging therapy and uninterrupted vitamin K antagonist (VKA) for nonvalvular AF ablation. Patients and Methods: A total of 4520 patients who underwent AF ablation between January 2010 and December 2018 were included in the analysis. According to their periprocedural anticoagulation strategies, patients were divided into three groups: Bridging heparin group (n = 1848); Uninterrupted VKA group (n = 796) and Minimally interrupted NOAC group (Total n = 1876; dabigatran: n = 865; rivaroxaban, n = 1011). A combined complication endpoint (CCE) as composed of any bleeding complications and thromboembolic events was analyzed. Results: Rates of thromboembolisms were similar among the three groups (0.22% for Bridging heparin group, 0.25% for Uninterrupted VKA group, and 0.11% for Minimally interrupted NOAC group, p = 0.626). There was a significant difference among the three groups for the incidence of overall bleeding events (8.50% for Bridging heparin group, 4.52% for Uninterrupted VKA group, and 2.67% for Minimally interrupted NOAC group, p < 0.001). A significant difference of CCE rates was shown in the Minimally interrupted NOAC group as compared with the Uninterrupted VKA group (2.77 vs. 4.77%, p = 0.008) and the Bridging heparin group (2.77 vs. 8.71%, p < 0.001). There was no significant difference in CCE rates among the different NOACs (dabigatran 2.89% vs. rivaroxaban 2.67%, p = 0.773). Conclusions: In patients undergoing AF ablation, minimally interrupted NOACs during the periprocedural period appears safer and equally effective when compared to the bridging heparin and uninterrupted VKA therapy.

Long-term follow-up of fibular graft for the reconstruction of bone defects.

The use of fibular graft for the reconstruction of bone defects has been demonstrated to be a reliable method. The aim of this study was to assess the clinical outcome of graft union, functional outcome (hypertrophy of the graft bones) and complications of both non-vascularized and vascularized grafts.From 1981 to 2015, 10 patients were treated using non-vascularized fibular graft or free vascularized fibular graft. The outcomes were bony union time, graft hypertrophy and complications based on radiograph and functional outcomes according to the Musculoskeletal Tumor Society (MSTS) score. Mobility of the ankle at the donor site was evaluated using the Kofoed ankle score system.This study included 10 patients with an average follow-up of 6.8 years. The union rate for all patients was 100%. The mean union time was 21.3 weeks for vascularized fibular grafts and 30.5 weeks for non-vascularized fibular grafts (P = .310). There was a significant difference between the upper limbs and the lower limbs regarding hypertrophy of the grafts in 5 patients (P = .003). The mean MSTS score in 10 patients was 84% (range 53%-97%). Stress fracture of the graft occurred in 1 patient. Donor site complications, including valgus deformity and length discrepancy, between 2 legs occurred in 2 patients who were under 18 years of age at the time of operation (P = .114). The mean Kofoed score was 96.8 (range 88-100).A greater increase in hypertrophy of grafts was observed with reconstruction in the lower limbs. There was no difference in MSTS score between these 2 types of grafts. Children were more likely to experience the valgus deformity at the donor site after harvesting the fibula. Keeping at least the distal 1/4 of the fibula intact during the surgery is a valid means of ensuring ankle stability at the donor site, and children should be considered for prophylactic distal tibiofibular synostosis creation to prevent the valgus deformity of the ankle at the donor site.