Effectiveness and safety of a novel intravascular lithotripsy system for severe coronary calcification: CALCI-CRACK trial.

BACKGROUND: Intravascular lithotripsy is effective and safe for managing coronary calcification; however, available devices are limited, and complex lesions have been excluded in previous studies. This study aimed to investigate the effectiveness and safety of a novel intravascular lithotripsy system for severe calcification in a population with complex lesions. METHODS: CALCI-CRACK (ChiCTR2100052058) is a prospective, single-arm, multicenter study. The primary endpoint was the procedural success rate. Major safety endpoints included major adverse cardiovascular events (MACE) and target lesion failure (TLF) at 30 days and 6 months, and severe angiographic complications. Calcification morphology was assessed in the optical coherence tomography (OCT) subgroup. RESULTS: In total, 242 patients from 15 high-volume Chinese centers were enrolled, including 26.45% of patients with true bifurcation lesions, 3.31% with severely tortuous vessels, and 2.48% with chronic total occlusion, respectively. The procedural success rate was 95.04% (95% confidence interval 91.50-97.41%), exceeding the pre-specified performance goal of 83.4% (p<0.001). The 30-day and 6-month MACE rates were 4.13% and 4.55%, respectively. TLF rates at these time-points were 1.24% and 1.65%, respectively. Severe angiographic complications occurred in 0.42% of patients. In the OCT subgroup (n=93), 93.55% of calcified lesions were fractured, and minimal lumen area increased from 1.55 ± 0.55 mm2 to 4.91 ± 1.22 mm2 after stent implantation, with acute gain rate of 245 ± 102%. CONCLUSIONS: The novel intravascular lithotripsy system is effective and safe for managing severely calcified coronary lesions in a cohort that included true bifurcation lesions, severely tortuous vessels, and chronic total occlusion. (ChiCTR2100052058).

High-Throughput Manufacturing of Multimodal Epidermal Mechanosensors with Superior Detectability Enabled by a Continuous Microcracking Strategy.

Non-invasive human-machine interactions (HMIs) are expected to be promoted by epidermal tactile receptive devices that can accurately perceive human activities. In reality, however, the HMI efficiency is limited by the unsatisfactory perception capability of mechanosensors and the complicated techniques for device fabrication and integration. Herein, a paradigm is presented for high-throughput fabrication of multimodal epidermal mechanosensors based on a sequential "femtosecond laser patterning-elastomer infiltration-physical transfer" process. The resilient mechanosensor features a unique hybrid sensing layer of rigid cellular graphitic flakes (CGF)-soft elastomer. The continuous microcracking of CGF under strain enables a sharp reduction in conductive pathways, while the soft elastomer within the framework sustains mechanical robustness of the structure. As a result, the mechanosensor achieves an ultrahigh sensitivity in a broad strain range (GF of 371.4 in the first linear range of 0-50%, and maximum GF of 8922.6 in the range of 61-70%), a low detection limit (0.01%), and a fast response/recovery behavior (2.6/2.1 ms). The device also exhibits excellent sensing performances to multimodal mechanical stimuli, enabling high-fidelity monitoring of full-range human motions. As proof-of-concept demonstrations, multi-pixel mechanosensor arrays are constructed and implemented in a robot hand controlling system and a security system, providing a platform toward efficient HMIs.

Corrigendum: The effects of intermittent theta burst stimulation of the unilateral cerebellar hemisphere on swallowing-related brain regions in healthy subjects.

[This corrects the article DOI: 10.3389/fnhum.2023.1100320.].

The effects of intermittent theta burst stimulation of the unilateral cerebellar hemisphere on swallowing-related brain regions in healthy subjects.

Objective: We aimed to investigate the effects and mechanisms of swallowing-related brain regions using resting-state functional magnetic resonance imaging (rs-fMRI) in healthy subjects who underwent intermittent theta burst stimulation (iTBS) on dominant or non-dominant cerebellar hemispheres. Methods: Thirty-nine healthy subjects were randomized into three groups that completed different iTBS protocols (dominant cerebellum group, non-dominant cerebellum group and sham group). Before iTBS, the resting motor threshold (rMT) was measured by single-pulse transcranial magnetic stimulation (sTMS) on the cerebellar representation of the suprahyoid muscles, and the dominant cerebellar hemisphere for swallowing was determined. Forty-eight hours after elution, iTBS protocols were completed: in the dominant cerebellum group, iTBS was administered to the dominant cerebellar hemisphere, and the non-dominant cerebellar hemisphere was given sham stimulation; in the non-dominant cerebellum group, iTBS was administered to the non-dominant cerebellar hemisphere, and sham stimulation was delivered to the dominant cerebellar hemisphere; in the sham group, sham stimulation was applied to the cerebellum bilaterally. Rs-fMRI was performed before and after iTBS stimulation to observe changes in the fractional amplitude of low-frequency fluctuation (fALFF) in the whole brain. Results: Compared with baseline, the dominant cerebellum group showed increased fALFF in the ipsilateral cerebellum, and decreased fALFF in the ipsilateral middle temporal gyrus and contralateral precuneus after iTBS; the iTBS of the non-dominant cerebellum group induced increased fALFF in the ipsilateral superior frontal gyrus, the calcarine fissure and the surrounding cortex, and the contralateral inferior parietal lobule; and in the sham group, there was no significant difference in fALFF. Exploring the effects induced by iTBS among groups, the dominant cerebellum group showed decreased fALFF in the contralateral calcarine fissure, and surrounding cortex compared with the sham group. Conclusion: Intermittent theta burst stimulation of the dominant cerebellar hemisphere for swallowing excited the ipsilateral cerebellum, and stimulation of the non-dominant cerebellar hemisphere increased the spontaneous neural activity of multiple cerebrocortical areas related to swallowing. In conclusion, regardless of which side of the cerebellum is stimulated, iTBS can facilitate part of the brain neural network related to swallowing. Our findings provide supporting evidence that cerebellar iTBS can be used as a potential method to modulate human swallowing movement.

Gut-microbiome-based predictive model for ST-elevation myocardial infarction in young male patients.

Background: ST-segment elevation myocardial infarction (STEMI) in young male patients accounts for a significant proportion of total heart attack events. Therefore, clinical awareness and screening for acute myocardial infarction (AMI) in asymptomatic patients at a young age is required. The gut microbiome is potentially involved in the pathogenesis of STEMI. The aim of the current study is to develop an early risk prediction model based on the gut microbiome and clinical parameters for this population. Methods: A total of 81 young males (age < 44 years) were enrolled in this study. Forty-one young males with STEMI were included in the case group, and the control group included 40 young non-coronary artery disease (CAD) males. To identify the differences in gut microbiome markers between these two groups, 16S rRNA-based gut microbiome sequencing was performed using the Illumina MiSeq platform. Further, a nomogram and corresponding web page were constructed. The diagnostic efficacy and practicability of the model were analyzed using K-fold cross-validation, calibration curves, and decision curve analysis (DCA). Results: Compared to the control group, a significant decrease in tendency regarding α and ß diversity was observed in patients in the case group and identified as a significantly altered gut microbiome represented by Streptococcus and Prevotella. Regarding clinical parameters, compared to the control group, the patients in the case group had a higher body mass index (BMI), systolic blood pressure (SBP), triglyceride (TG), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) and low blood urea nitrogen (BUN). Additionally, BMI and SBP were significantly (p<0.05) positively correlated with Streptococcus and [Ruminococcus]. Further, BMI and SBP were significantly (p<0.05) negatively correlated with Prevotella and Megasphaera. A significant negative correlation was only observed between Prevotella and AST (p < 0.05). Finally, an early predictive nomogram and corresponding web page were constructed based on the gut microbiome and clinical parameters with an area under the receiver-operating characteristic (ROC) curve (AUC) of 0.877 and a C-index of 0.911. For the internal validation, the stratified K-fold cross-validation (K = 3) was as follows: AUC value of 0.934. The calibration curves of the model showed good consistency between the actual and predicted probabilities. The DCA results showed that the model had a high net clinical benefit for use in the clinical setting. Conclusion: In this study, we combined the gut microbiome and common clinical parameters to construct a prediction model. Our analysis shows that the constructed model is a non-invasive tool with potential clinical application in predicting STEMI in the young males.

The Effect of Repetitive Transcranial Magnetic Stimulation of Cerebellar Swallowing Cortex on Brain Neural Activities: A Resting-State fMRI Study.

Objective: The effects and possible mechanisms of cerebellar high-frequency repetitive transcranial magnetic stimulation (rTMS) on swallowing-related neural networks were studied using resting-state functional magnetic resonance imaging (rs-fMRI). Method: A total of 23 healthy volunteers were recruited, and 19 healthy volunteers were finally included for the statistical analysis. Before stimulation, the cerebellar hemisphere dominant for swallowing was determined by the single-pulse TMS. The cerebellar representation of the suprahyoid muscles of this hemisphere was selected as the target for stimulation with 10 Hz rTMS, 100% resting motor threshold (rMT), and 250 pulses, with every 1 s of stimulation followed by an interval of 9 s. The motor evoked potential (MEP) amplitude of the suprahyoid muscles in the bilateral cerebral cortex was measured before and after stimulation to evaluate the cortical excitability. Forty-eight hours after elution, rTMS was reapplied on the dominant cerebellar representation of the suprahyoid muscles with the same stimulation parameters. Rs-fMRI was performed before and after stimulation to observe the changes in amplitude of low-frequency fluctuation (ALFF) and regional homology (ReHo) at 0.01-0.08 Hz, 0.01-0.027 Hz, and 0.027-0.073 Hz. Results: After cerebellar high-frequency rTMS, MEP recorded from swallowing-related bilateral cerebral cortex was increased. The results of rs-fMRI showed that at 0.01-0.08 Hz, ALFF was increased at the pons, right cerebellum, and medulla and decreased at the left temporal lobe, and ReHo was decreased at the left insular lobe, right temporal lobe, and corpus callosum. At 0.01-0.027 Hz, ALFF was decreased at the left temporal lobe, and ReHo was decreased at the right temporal lobe, left putamen, and left supplementary motor area. Conclusion: Repetitive transcranial magnetic stimulation of the swallowing cortex in the dominant cerebellar hemisphere increased the bilateral cerebral swallowing cortex excitability and enhanced pontine, bulbar, and cerebellar spontaneous neural activity, suggesting that unilateral high-frequency stimulation of the cerebellum can excite both brainstem and cortical swallowing centers. These findings all provide favorable support for the application of cerebellar rTMS in the clinical practice.

A Novel Strategy to Simplify the Procedures in Treating Complicated Coronary Bifurcation Lesions: From a Bench Test to Clinical Application.

Background: Although provisional stenting strategy based on jailed balloon side branch (SB) protection could be useful for high-risk bifurcation lesion in certain clinical scenarios, its complexity still gives rise to procedure complications. We proposed a novel strategy, the jailed balloon proximal optimization technique (JB-POT), to simplify the procedures in treating complex coronary bifurcation lesions (CBLs). The present study was designed to verify the safety and efficacy of JB-POT under bench testing and clinical circumstances. Methods: After a stent was deployed in main vessel (MV) with a balloon jailed in SB, POT and post-dilation of the stent were performed without retrieving the jailed balloon. A re-POT was performed 2 mm away from SB branching point to minimize proximal stent malapposition. The JB-POT procedure was performed on 10 samples of a silicone bifurcation bench model, and optical coherence tomography (OCT) was utilized to evaluate stent deployment. From December 2018 to July 2021, a total of 28 consecutive patients with true CBLs treated with JB-POT were enrolled. Immediate procedure results were observed, and clinical follow-ups were performed. Results: The bench test showed that JB-POT did not induce significant stent malapposition, underexpansion or distortion, as indexed by the malapposition rate, minimum stent area (MSA), eccentricity index and symmetry index determined through OCT. Under clinical circumstances, JB-POT did not induce significant malapposition, underexpansion or distortion. Among the 30 lesions, there was no primary endpoint event defined as SB occlusion, need to rewire the SB with a polymer-covered guide wire, or failure to retrieve a jailed wire or balloon. One rewiring event and 0 double stenting events occurred as secondary endpoint events. One patient died of heart failure in the 8th month after discharge. Conclusions: The JB-POT protocol, which tremendously simplifies the current standard provisional stenting procedure in complicated bifurcation lesions, shows acceptability in safety and efficacy. Hence, it might become an applicable strategy for treating high-risk bifurcation lesions, especially those with multiple risked SBs.

Novel predictors of stent under-expansion regarding calcified coronary lesions assessed by optical coherence tomography.

A previous calcium scoring system using circumferential angle, thickness, and length of coronary calcium by OCT could assist in predicting stent under-expansion. However, this scoring system only reflects the calcification distribution within a single cross-section and fails to consider the lumen's original size. The current study aims to investigate whether novel parameters to quantify calcium lesions, including calcium burden, area, and volume assessed by optical coherence tomography (OCT), could predict stent under-expansion related to calcium lesions. Consecutive patients admitted between March 10th to October 19th 2021 with calcified coronary lesions undergoing percutaneous coronary intervention (PCI) with OCT guidance were screened for inclusion. The calcium burden, area, and volume of the target lesions were measured using OCT at pre-PCI. After successful stent implantation, stent expansion at the corresponding lesions was also measured by OCT. A total of 125 patients who underwent OCT-guided PCI were included in this study. While the calcium grades by angiography failed to show a significant correlation with stent expansion, maximum and average calcium burden, maximum calcium area, and calcium volume exhibited a moderate correlation with stent expansion. According to the receiver operating characteristic curves, the optimal cutoffs of calcium volume and area for predicting stent under-expansion were 4.37 mm3 and 2.48 mm2 , respectively. Calcium burden, area, and volume by OCT are more favorable predictors of stent under-expansion given its better performance than calcium grades by angiography. Using cutoffs of calcium area and volume could identify high-risk patients of under-expansion and might guide future clinical practice.

Bakuchiol Alleviates Hyperglycemia-Induced Diabetic Cardiomyopathy by Reducing Myocardial Oxidative Stress via Activating the SIRT1/Nrf2 Signaling Pathway.

Bakuchiol (BAK), a monoterpene phenol reported to have exerted a variety of pharmacological effects, has been related to multiple diseases, including myocardial ischemia reperfusion injury, pressure overload-induced cardiac hypertrophy, diabetes, liver fibrosis, and cancer. However, the effects of BAK on hyperglycemia-caused diabetic cardiomyopathy and its underlying mechanisms remain unclear. In this study, streptozotocin-induced mouse model and high-glucose-treated cell model were conducted to investigate the protective roles of BAK on diabetic cardiomyopathy, in either the presence or absence of SIRT1-specific inhibitor EX527, SIRT1 siRNA, or Nrf2 siRNA. Our data demonstrated for the first time that BAK could significantly abate diabetic cardiomyopathy by alleviating the cardiac dysfunction, ameliorating the myocardial fibrosis, mitigating the cardiac hypertrophy, and reducing the cardiomyocyte apoptosis. Furthermore, BAK achieved its antifibrotic and antihypertrophic actions by inhibiting the TGF-ß1/Smad3 pathway, as well as decreasing the expressions of fibrosis- and hypertrophy-related markers. Intriguingly, these above effects of BAK were largely attributed to the remarkable activation of SIRT1/Nrf2 signaling, which eventually strengthened cardiac antioxidative capacity by elevating the antioxidant production and reducing the reactive oxygen species generation. However, all the beneficial results were markedly abolished with the administration of EX527, SIRT1 siRNA, or Nrf2 siRNA. In summary, these novel findings indicate that BAK exhibits its therapeutic properties against hyperglycemia-caused diabetic cardiomyopathy by attenuating myocardial oxidative damage via activating the SIRT1/Nrf2 signaling.

Anterior wall myocardial infarction in a 16-year-old man caused by coronary artery aneurysm during the outbreak of COVID-19.

BACKGROUND: Coronary artery aneurysm (CAA) is a potential cause of infarction. During the outbreak of coronavirus disease 2019 (COVID-19), home isolation and activity reduction can lead to hypercoagulability. Here, we report a case of sudden acute myocardial infarction caused by large CAA during the home isolation. CASE PRESENTATION: During the outbreak of coronavirus disease 2019 (COVID-19),a 16-year-old man with no cardiac history was admitted to CCU of Tang du hospital because of severe chest pain for 8 h. The patient reached the hospital its own, his electrocardiogram showed typical features of anterior wall infarction, echocardiography was performed and revealed local anterior wall dysfunction, but left ventricle ejection fraction was normal, initial high-sensitivity troponin level was 7.51 ng/mL (<1.0 ng/mL). The patient received loading dose of aspirin and clopidogrel bisulfate and a total occlusion of the LAD was observed in the emergency coronary angiography (CAG). After repeated aspiration of the thrombus, TIMI blood flow reached level 3. Coronary artery aneurysm was visualized in the last angiography. No stent was implanted. Intravascular ultrasound (IVUS) was performed and the diagnosis of coronary artery aneurysm was further confirmed. The patient was discharged with a better health condition. CONCLUSIONS: Coronary artery aneurysm is a potential reason of infarction, CAG and IVUS are valuable tools in diagnosis in such cases, during the outbreak of coronavirus disease 2019 (COVID-19), home isolation and activity reduction can lead to hypercoagulability, and activities at home should be increased in the high-risk patients.

Taurine protects against cardiac dysfunction induced by pressure overload through SIRT1-p53 activation.

BACKGROUND: Heart failure (HF) is an epidemic disease with increased incidence annually. It has been reported that taurine can improve cardiac function. This study investigated the cardioprotective effects of taurine in pressure-loaded HF mice and elucidated the possible mechanism. METHODS: HF models were established by transverse aortic constriction (TAC). Animals were treated with either taurine for 9 weeks and/or the SIRT1 inhibitor EX527 (5 mg/kg/day, every 2days) after TAC operation. Cardiac function and geometry were revealed by echocardiography. Myocardial hypertrophy and fibrosis were assessed using Fluorescent wheat germ agglutinin (WGA) staining and Masson's trichrome staining. Western blot and RT-PCR were performed to elucidate the expression of target proteins and genes respectively. Apoptosis in cardiomyocytes was detected by TUNEL staining. Myocardial oxidative stress was assessed by detecting the concentration of myocardial super oxidative dismutase (SOD) and malonyldialdehyde (MDA) and reactive oxygen species (ROS). Taurine concentrations and NAD+/NADH ratio were determined by taurine and NAD+/NADH assay kit. RESULTS: Taurine notably relieved cardiac dysfunction after TAC. The mechanisms were attributed to reduced myocyte hypertrophy and fibrosis, and alleviated apoptosis and oxidative stress. Meanwhile, taurine increased NAD+/NADH ratio，promoted the expression of SIRT1 and suppressed p53 acetylation. However, EX-527(inhibitor of SIRT1) decreased NAD+/NADH ratio and increased acetyl-p53 levels, and abolished the cardioprotective effects of taurine on mice subjected to TAC and increased apoptosis and oxidative stress. CONCLUSION: The mechanism responsible for cardiac-protective effects of taurine in HF induced by pressure overload is associated with the activation of the SIRT1-p53 pathway.

Effect of Low-Frequency rTMS and Intensive Speech Therapy Treatment on Patients With Nonfluent Aphasia After Stroke.

BACKGROUND: To observe the effect of low-frequency repetitive transcranial magnetic stimulation (rTMS) on patients with nonfluent aphasia after stroke. MATERIALS AND METHODS: Thirty patients were divided into control, rTMS, and 2 times a day low-frequency rTMS (2rTMS) groups, and all 3 groups had intensive speech therapy (ST). Patients were assessed by western aphasia battery (WAB) scale. The spontaneous language, listening comprehension, retelling, and naming were scored, respectively. The expression of brain-derived neurotrophic factor (BDNF) in peripheral blood was detected by enzyme-linked immunosorbent assay. RESULTS: There was significant difference in aphasia quotient after treatment in the 3 groups. The values of the 4 dimensions in the WAB score of the rTMS group were higher than those in the control group. The WAB scores in the 2rTMS group were higher than those in the rTMS group. After 2 weeks treatment, the BDNF levels in the rTMS group and the 2rTMS group were significantly higher than those in the control group. Four weeks later, the 2rTMS group was significantly increased compared with the control group and the rTMS group. CONCLUSIONS: Low-frequency rTMS combined with conventional ST treatment can effectively improve the language function of patients with nonfluent aphasia after stroke. Two times a day low-frequency rTMS therapy combined with conventional ST treatment can improve the language function of patients with nonfluent aphasia after stroke more effectively and it also promote the expression of BDNF more effectively, thereby improving nerve repair and protecting brain tissue.