Transcatheter Edge-to-Edge Repair for a Patient With Severe Mitral Regurgitation of Carpentier IIIa Classification.

Whether patients diagnosed with mitral regurgitation of Carpentier class IIIa (rheumatic origin) can possibly be treated with balloon mitral commissurotomy followed by transcatheter edge-to-edge repair remains unclear. Here, we report on such a case who was successfully treated with balloon mitral commissurotomy and then transcatheter edge-to-edge repair without aggravating mitral stenosis. (Level of Difficulty: Intermediate.).

A low-energy emulsification platform based on a Diet Coke-Mentos reaction-derived bubbly flow for formulating various emulsions as drug carriers.

The formulation of a drug using high-energy emulsification commonly causes drug deterioration. Exploiting the well-known Diet Coke-Mentos reaction (DCMR), a U-shaped tube reactor that can generate an eruption of bubbly flow that can serve as a low-energy emulsification platform, is proposed. The liquid in the U-tube reactor is a supersaturated solution of aqueous CO2, which mimics Diet Coke. When glass beads with rough surfaces, mimicking Mentos, are dropped into the carbonated water, an eruptive bubbly flow is spontaneously created, mediating effective emulsification at a compound water-oil interface. Experimental results demonstrate that DCMR-mediated bubbly flow may provide a versatile platform for the production of "oil-in-water" or "water-in-oil" droplets and Pickering emulsion composite particles as drug carriers. The DCMR-derived bubbly flow is generated without significant temperature elevation, so the activity of the drug to be emulsified is unaffected. In vivo results reveal the feasibility of using this low-energy emulsification platform to formulate an emulsion system that contains catalase, a temperature-sensitive oxidoreductase, to mitigate an experimentally formed paw inflammation in mice. The as-proposed emulsification platform is attractive for formulating numerous drug delivery systems on a small-scale in a customized manner to meet the needs of each individual for personalized medicine.

One-Year and Five-Year Outcomes of Transcatheter Aortic Valve Replacement or Surgical Aortic Valve Replacement in a Taiwanese Elderly Population.

BACKGROUND: The aim of our study was to provide real-world data on outcomes for elderly Taiwanese patients who underwent transcatheter aortic valve replacement or surgical aortic valve replacement in different risk groups. METHODS: From March 2011 through December 2021, 177 patients with severe aortic stenosis who were ≥70 years old and had undergone TAVI (transcatheter aortic valve implantation) or SAVR (surgical aortic valve replacement) in a single center were divided by STS score (<4%, 4-8% and >8%) into three different groups. Then, we compared their clinical characteristics, operative complications, and all-cause mortality. RESULTS: In all risk groups, there were no significant differences in in-hospital mortality, or 1-year and 5-year mortality between patients in the TAVI and SAVR groups. In all risk groups, patients in the TAVI group had shorter hospital stay and higher rate of paravalvular leakage than the SAVR group. After univariate analysis, BMI (body mass index) < 20 was a risk factor for higher 1-year and 5-year mortality. In the multivariate analysis, acute kidney injury was an independent factor for predicting worse outcomes in terms of 1-year and 5-year mortality. CONCLUSIONS: Taiwan elderly patients in all risk groups did not have significant differences in mortality rates between the TAVI and the SAVR group. However, the TAVI group had shorter hospital stay and higher rate of paravalvular leakage in all risk groups.

Migrating hook wire that travels to the heart via the bloodstream: A case report.

RATIONALE: This report documents the intracardiac migration of a hook wire in a 47-year-old male patient after computed tomography (CT)-guided percutaneous hook wire localization of pulmonary ground-glass opacities. PATIENT CONCERNS: The patient underwent CT-guided hook wire localization before video-assisted thoracoscopic surgery (VATS) wedge resection for a pulmonary nodule in the right upper lung field. However, the hook wire was not found in the specimen obtained from the wedge resection. A right upper lobectomy was performed to locate the hook wire; however, it was not found. DIAGNOSIS: A transesophageal echocardiogram was performed, and the hook wire was found in the left ventricle (LV). INTERVENTIONS: The patient subsequently underwent exploratory cardiotomy to remove the foreign body. The patient was admitted to the intensive care unit for postoperative care. OUTCOMES: Postoperatively, no complications were observed, and the patient was discharged from the hospital 7 days postoperatively. He received standard lung cancer treatment afterwards. LESSONS: The present case was unique because the hook wire migrated through the bloodstream from the pulmonary vein to the left atrium, before finally reaching the LV. Based on the patient preoperative CT images, the ground glass opacities were proximal to a 2.5 mm wide vein, which drained into the pulmonary vein. The proximity of the hook wire to a blood vessel was reportedly attributed to an increased risk of hook wire migration through the bloodstream. Hematogenous hook wire migration into the heart can result in fatal complications. Early diagnosis and timely removal of the hook wire are recommended to prevent the worsening of this complication.

Long-term results of robotic-assisted coronary artery bypass grafting with composite arterial grafts for multiple coronary anastomoses: 10-year experience.

Currently, robotic-assisted coronary artery bypass grafting (RACABG) is a feasible choice for myocardial revascularization. Acceptable outcomes have been reported for RACABG with single target vessels; however, the long-term benefits of multivessel RACABG with composite arterial grafts have rarely been studied. Therefore, our study investigated the long-term results of multivessel RACABG with composite arterial grafts by reviewing the clinical data of patients from Taichung Veterans General Hospital. From December 2005 to June 2015, 562 patients underwent robotic-assisted robotic minimally invasive direct coronary bypass (MIDCAB) at Taichung Veterans General Hospital. Two major composite arterial graft configurations (i.e., inverted T-graft and Y-graft) were used. Data regarding the short-term and long-term outcomes of robotic-assisted MIDCAB were obtained from the medical records. For data regarding long-term outcomes of the patients not followed up at our institution, telephone interviews were conducted in June 2019. The in-hospital mortality rate and complication rate were 2.5% and 17.6%, respectively. We completed the follow-up for 486 patients (86.4%), and postoperative coronary imaging-based evaluation performed for 157 patients. The 5-year and 10-year survival rates were 82.7% and 65.2%, respectively. The 5-year and 10-year major adverse cardiac and cerebral events-free survival rates were 86.9% and 70.9%, respectively. The 5-year patency rate of various coronary anastomoses was 85.1-100%. Our study revealed that multivessel robotic-assisted MIDCAB with composite arterial grafts provided acceptable long-term outcomes, irrespective of the composite graft configuration.

Concomitant Hepatectomy and Atrial Thrombectomy under Cardiopulmonary Bypass versus Staged Hepatectomy in the Treatment for Hepatocellular Carcinoma with Large Right Atrial Tumor Thrombi.

(1) Background: Hepatocellular carcinoma (HCC) with a large right atrium tumor thrombus (RATT) is a rare and critical presentation. Emergency hepatectomy and thrombectomy under cardiopulmonary bypass (CPB) is life-saving and potentially curative. The aim of this study is to propose an appropriate approach for this condition. (2) Methods: In period A (1998 to 2010, n = 7), hepatectomy and thrombectomy were concomitantly performed, and staged hepatectomy was performed in period B (2011 to 2018, n = 17). (3) Results: The median overall survival time (MOST) in the published studies was 14 months. Moreover, the blood loss, blood transfusion rate, length of ICU stays, and hospital costs were significantly reduced in period B. The MOSTs of patients in period A (n = 6) and period B (n = 17) were 14 vs. 18 months (p = 0.099). The median disease-free survival times (MDFTs) in period A (n = 6) and period B (n = 15) were 8 vs. 14 months (p = 0.073), while the MOSTs in period A and period B were 14 vs. 24 months (p = 0.040). (4) Conclusions: Emergency thrombectomy under CPB and staged hepatectomy 4-6 weeks later may be an appropriate approach for HCC with large RATT. However, the optimal waiting interval requires further investigation.

Catecholamine-Induced Secondary Takotsubo Syndrome in Children With Severe Enterovirus 71 Infection and Acute Heart Failure: A 20-year Experience of a Single Institute.

Background: Acute heart failure (AHF) is the major cause of death in children with severe enterovirus 71 (EV71) infection. This study aimed to report our clinical experience with EV71-related AHF, as well as to discuss its pathogenesis and relationship to Takotsubo syndrome (TTS). Methods: A total 27 children with EV71-related AHF between 1998 and 2018 were studied. The TTS diagnosis was based on the International Takotsubo Diagnostic Criteria. Results: Acute heart failure-related early death occurred in 10 (37%) of the patients. Sinus tachycardia, systemic hypertension, and pulmonary edema in 100, 85, and 81% of the patients, respectively, preceded AHF. Cardiac biomarkers were significantly increased in most patients. The main echocardiographic findings included transient and reversible left ventricular (LV) regional wall motion abnormality (RWMA) with apical ballooning. High concentrations of catecholamines either preceded or coexisted with AHF. Myocardial pathology revealed no evidence of myocarditis, which was consistent with catecholamine-induced cardiotoxic damage. Patients with EV71-related AHF who had received close monitoring of their cardiac function, along with early intervention involving extracorporeal life support (ECLS), had a higher survival rate (82 vs. 30%, p = 0.013) and better neurological outcomes (59 vs. 0%, p = 0.003). Conclusion: EV 71-related AHF was preceded by brain stem encephalitis-related hypercatecholaminemia, which resulted in a high mortality rate. Careful monitoring is merited so that any life-threatening cardiogenic shock may be appropriately treated. In view of the similarities in their clinical manifestations, natural course direction, pathological findings, and possible mechanisms, TTS and EV71-related AHF may represent the same syndrome. Therefore, we suggest that EV71-related AHF could constitute a direct causal link to catecholamine-induced secondary TTS.

A fast and facile platform for fabricating phase-change materials-based drug carriers powered by chemical Marangoni effect.

Emulsions of oil droplets as drug carriers are typically formulated by emulsification, which is complex and time-consuming and requires high energy input. To address these concerns, a fast and facile method for fabricating lipid-based oil droplets, using propulsive forces that arise from the chemical Marangoni effect, is developed for the oral delivery of lipophilic drugs, such as vitamin D. The oil droplets are prepared by solubilizing vitamin D in a phase-changeable fatty acid with the addition of ethanol as an oil phase, which is then deposited on a water bath. As a result of the differing surface tensions of water and ethanol (chemical energy), propulsive Marangoni forces are generated (kinetic energy), rapidly spreading the oil phase into many tiny oil droplets. To prevent their coalescence, the generated oil droplets are solidified by reducing their environmental temperature. Following oral administration, the fluidity of the solidified droplets increases at body temperature; they can be further emulsified into the vitamin D-containing micelles by intestinal bile salts. The micelles are then taken up by the intestinal epithelial cells, enabling their contained vitamin D to be absorbed into systemic circulation, improving its oral bioavailability.

Long-Term Outcomes and Risk Factors of Renal Failure Requiring Dialysis after Heart Transplantation: A Nationwide Cohort Study.

Acute kidney injury and renal failure are common after heart transplantation. We retrospectively reviewed a national cohort and identified 1129 heart transplant patients. Patients receiving renal replacement therapy after heart transplantation were grouped into the dialysis cohort. The long-term survival and risk factors of dialysis were investigated. Patients who had undergone dialysis were stratified to early or late dialysis for subgroup analysis. The mean follow-up was five years, the incidence of dialysis was 28.4% (21% early dialysis and 7.4% late dialysis). The dialysis cohort had higher overall mortality compared with the non-dialysis cohort. The hazard ratios of mortality in patients with dialysis were 3.44 (95% confidence interval (CI), 2.73-4.33) for all dialysis patients, 3.58 (95% CI, 2.74-4.67) for early dialysis patients, and 3.27 (95% CI, 2.44-4.36; all p < 0.001) for late dialysis patients. Patients with diabetes mellitus, chronic kidney disease, acute kidney injury, and coronary artery disease were at higher risk of renal failure requiring dialysis. Cardiomyopathy, hepatitis B virus infection, and hyperlipidemia treated with statins were associated with a lower risk of renal dysfunction requiring early dialysis. The use of Sirolimus and Mycophenolate mofetil was associated with a lower incidence of late dialysis. Renal dysfunction requiring dialysis after heart transplantation is common in Taiwan. Early and late dialysis were both associated with an increased risk of mortality in heart transplant recipients.

A self-doping conductive polymer hydrogel that can restore electrical impulse propagation at myocardial infarct to prevent cardiac arrhythmia and preserve ventricular function.

Following myocardial infarction (MI), necrotic cardiomyocytes (CMs) are replaced by fibroblasts and collagen tissue, causing abnormal electrical signal propagation, desynchronizing cardiac contraction, resulting in cardiac arrhythmia. In this work, a conductive polymer, poly-3-amino-4-methoxybenzoic acid (PAMB), is synthesized and grafted onto non-conductive gelatin. The as-synthesized PAMB-G copolymer is self-doped in physiological pH environments, making it an electrically active material in biological tissues. This copolymer is cross-linked by carbodiimide to form an injectable conductive hydrogel (PAMB-G hydrogel). The un-grafted gelatin hydrogel is prepared in a similar manner as a control. Both test hydrogels not only provide an optimal matrix for CM adhesion and growth but also maintain CM morphology and functional proteins. The conductivity of PAMB-G hydrogel is ca. 12 times higher than that of gelatin hydrogel. Microelectrode array analyses reveal that a heart placed on the PAMB-G hydrogel has a higher field potential amplitude than that placed on the gelatin hydrogel and can pass current from one heart to excite another heart at a distance. The injection of PAMB-G hydrogel into the scar zone following an MI in a rat heart improves electrical impulse propagation over that in a heart that has been treated with gelatin hydrogel, and synchronizes heart contraction, leading to preservation of the ventricular function and reduction of cardiac arrhythmia, demonstrating its potential for use in treating MI.

An in situ slow-releasing H2S donor depot with long-term therapeutic effects for treating ischemic diseases.

Therapeutic angiogenesis is essential for rescuing necrotic tissues in cases of ischemic disease. The exogenous hydrogen sulfide (H2S) donor, diallyl trisulfide (DATS), has been investigated as a therapeutic agent that promotes angiogenesis. However, the short half-life of generated H2S limits its therapeutic efficacy. In an attempt to overcome this difficulty, a poly(D,L-lactic-co-glycolic acid) microparticle system that contains DATS (DATS@MPs) is prepared as an in situ depot for the controlled release of H2S, providing slow release and long-term effectiveness. The results of in vitro investigations indicate that the slow-released DATS from the DATS@MPs depot yields a longer intracellular production of H2S than that from a free DATS depot. The intracellular generation of H2S favors the translocation of the transcription factor, Nrf2, from the cytosol to nuclei, potentially upregulating the gene expressions of antioxidant enzymes, ultimately increasing cellular resistance to oxidative stress. Intramuscular injection of the slow-releasing H2S donor depot DATS@MPs in an ischemic limb that is experimentally generated in a mouse model promotes therapeutic angiogenesis and protects cells from apoptosis and tissues from necrosis, ultimately salvaging the limb. These analytical results reveal that DATS@MPs is potentially useful in H2S-based therapy for treating ischemic diseases.

Long-Term Outcomes in Coronary Artery Bypass Graft Patients Using Internal Thoracic Artery with Ipsilateral Arteriovenous Shunt for Hemodialysis.

BACKGROUND: The goal of this study was to evaluate the long-term results of coronary artery bypass grafting (CABG) using internal thoracic artery (ITA) grafts in hemodialysis (HD) patients with arteriovenous (AV) fistulae or AV grafts involving the ipsilateral or contralateral brachial artery or radial artery. METHODS: From March 2007 to May 2017, 76 end-stage renal disease (ESRD) patients with an upper limb AV fistula or graft for HD underwent CABG at a single center. Group A included 23 patients who underwent CABG using an ITA graft ipsilateral to the AV vascular access (AVVA); Group B included 22 patients who underwent CABG using a contralateral ITA with AVVA; and Group C included 29 patients who underwent CABG with AVVA without the use of an ITA graft. The primary end-point was death from any cause. RESULTS: The average follow-up period was 34.4 ± 26.9 months. Death from any cause occurred in 6 (26.09%) patients in Group A, 8 (36.36%) patients in Group B, and 17 (58.62%) patients in Group C (log-rank p = 0.04). There was no significant difference in death rate between Groups A and B. The risk of death was lower in the patients with CABG using an ITA graft (ITA CABG) compared to the patients without ITA CABG [HR 0.41 (95% CI, 0.20-0.84), p = 0.015]. CONCLUSIONS: The HD patients who underwent CABG with an ipsilateral location of the ITA and AVVA did not have an increased risk of death compared to the patients who underwent CABG with a contralateral location of the ITA and AVVA. In addition, the use of ITA in CABG resulted in better outcomes in the HD patients.

Single-injecting, bioinspired nanocomposite hydrogel that can recruit host immune cells in situ to elicit potent and long-lasting humoral immune responses.

Vaccination is an effective medical intervention for preventing disease. However, without an adjuvant, most subunit vaccines are poorly immunogenic. This work develops a bioinspired nanocomposite hyaluronic acid hydrogel system that incorporates N-trimethyl chitosan nanoparticles (TMC/NPs) that carry a model subunit vaccine ovalbumin (OVA) that can elicit a potent and prolonged antigen-specific humoral response. Experimental results indicate that the nanocomposite hydrogel system (NPs-Gel) can retain a large proportion of its TMC/NPs that are bonded by covalent/electrostatic interactions and extend the release of the encapsulated OVA, enabling their localization at the site of hydrogel injection. The positively charged TMC/NPs can be effectively internalized by dendritic cells, significantly augmenting their maturation, suggesting that TMC can function as an adjuvant-based OVA delivery system. Upon subcutaneous implantation in mice, the NPs-Gel acts as an in situ depot that recruits and concentrates immune cells. The TMC/NPs that do not have any specific interactions with the hydrogel network are released rapidly and internalized by the neighboring immune cells, providing a priming dose, while those retained inside the NPs-Gel are ingested by the recruited and concentrated immune cells over time, acting as a booster dose, eliciting high titers of OVA-specific antibody responses. These experimental results suggest particulate vaccines that are integrated in such a bioinspired hydrogel system may be used as single-injection prime-boost vaccines, enabling effective and persistent humoral immune responses.

Sinus Venosus Interatrial Communication, Anomalous Pulmonary Venous Return, Pulmonary Artery Aneurysm With Left Main Compression: Complex Case With Complex Management.

A young female patient was referred for pulmonary arterial hypertension (PAH). Catheterization revealed a large sinus venosus interatrial communication (SVIAC), partial anomalous pulmonary venous return (PAPVR), pulmonary vascular resistance (PVR) 15 Wood units, and bidirectional shunting. She was then put on target medication for PAH. Two years later, she had angina and underwent computed tomography examination, which showed pulmonary arterial aneurysm compressing the left main coronary. Coronary stenting was performed, which successfully relieved the compression and angina. Meanwhile, PVR lowered to 3.5 Wood units after medical therapy. Surgical correction for SVIAC and PAPVR was done successfully 5 years after diagnosis.

Effect of Retrograde Cerebral Protection Strategy on Outcome of Patients with Stanford Type A Aortic Dissection.

BACKGROUND: Neurological complications are an important concern in the repair of type A aortic dissection. Supra-aortic involvement is considered to be an important risk factor for neurological injuries. However, the optimal brain protection strategy still remains controversial. The aim of the present study was to assess the efficacy and short-term results of retrograde cerebral protection techniques in the treatment of acute type A aortic dissection. METHODS: Between 2005 and 2013, 185 patients who underwent repair of acute type A aortic dissection were enrolled in this study, all of whom received retrograde cerebral perfusion. The patients were divided into two group: 102 patients who had at least one carotid artery involved as the carotid dissection group, and 83 patients who had no carotid artery involvement as the non-carotid dissection group. RESULTS: The mean age of the patients was 57.8 years and 69% were male. The 30-day mortality rate was 10.3%, and the overall in-hospital mortality rate was 11.9%. Eight patients (4.3%) developed new permanent neurological deficits (PNDs) including two in the non-carotid dissection group and six in the carotid dissection group. Although new PND was milder in the carotid dissection group, there was no significant difference (p = 0.248). The proportion of patients who received a coronary artery bypass graft was significantly higher in the carotid dissection group (1 vs. 8, p = 0.037). CONCLUSIONS: According to our study, the retrograde cerebral perfusion technique is an easy and safe procedure, especially for patients with concomitant carotid dissection.

Enhancement of cell adhesion, retention, and survival of HUVEC/cbMSC aggregates that are transplanted in ischemic tissues by concurrent delivery of an antioxidant for therapeutic angiogenesis.

A recurring obstacle in cell-base strategies for treating ischemic diseases is the significant loss of viable cells that is caused by the elevated levels of regional reactive oxygen species (ROS), which ultimately limits therapeutic capacity. In this study, aggregates of human umbilical vein endothelial cells (HUVECs) and cord-blood mesenchymal stem cells (cbMSCs), which are capable of inducing therapeutic angiogenesis, are prepared. We hypothesize that the concurrent delivery of an antioxidant N-acetylcysteine (NAC) may significantly increase cell retention following the transplantation of HUVEC/cbMSC aggregates in a mouse model with hindlimb ischemia. Our in vitro results demonstrate that the antioxidant NAC can restore ROS-impaired cell adhesion and recover the reduced angiogenic potential of HUVEC/cbMSC aggregates under oxidative stress. In the animal study, we found that by scavenging the ROS generated in ischemic tissues, NAC is likely to be able to establish a receptive cell environment in the early stage of cell transplantation, promoting the adhesion, retention, and survival of cells of engrafted aggregates. Therapeutic angiogenesis is therefore enhanced and blood flow recovery and limb salvage are ultimately achieved. The combinatory strategy that uses an antioxidant and HUVEC/cbMSC aggregates may provide a new means of boosting the therapeutic efficacy of cell aggregates for the treatment of ischemic diseases.

Multimodality noninvasive imaging for assessing therapeutic effects of exogenously transplanted cell aggregates capable of angiogenesis on acute myocardial infarction.

Although the induction of neovascularization by cell-based approaches has demonstrated substantial potential in treating myocardial infarction (MI), the process of cell-mediated angiogenesis and its correlation with therapeutic mechanisms of cardiac repair remain elusive. In this work, three-dimensional (3D) aggregates of human umbilical vein endothelial cells (HUVECs) and cord-blood mesenchymal stem cells (cbMSCs) are constructed using a methylcellulose hydrogel system. By maximizing cell-cell and cell-ECM communications and establishing a hypoxic microenvironment in their inner cores, these cell aggregates are capable of forming widespread tubular networks together with the angiogenic marker αvß3 integrin; they secret multiple pro-angiogenic, pro-survival, and mobilizing factors when grown on Matrigel. The aggregates of HUVECs/cbMSCs are exogenously engrafted into the peri-infarct zones of rats with MI via direct local injection. Multimodality noninvasive imaging techniques, including positron emission tomography, single photon emission computed tomography, and echocardiography, are employed to monitor serially the beneficial effects of cell therapy on angiogenesis, blood perfusion, and global/regional ventricular function, respectively. The myocardial perfusion is correlated with ventricular contractility, demonstrating that the recovery of blood perfusion helps to restore regional cardiac function, leading to the improvement in global ventricular performance. These experimental data reveal the efficacy of the exogenous transplantation of 3D cell aggregates after MI and elucidate the mechanism of cell-mediated therapeutic angiogenesis for cardiac repair.

An AS1411 aptamer-conjugated liposomal system containing a bubble-generating agent for tumor-specific chemotherapy that overcomes multidrug resistance.

Recent research in chemotherapy has prioritized overcoming the multidrug resistance (MDR) of cancer cells. In this work, liposomes that contain doxorubicin (DOX) and ammonium bicarbonate (ABC, a bubble-generating agent) are prepared and functionalized with an antinucleolin aptamer (AS1411 liposomes) to target DOX-resistant breast cancer cells (MCF-7/ADR), which overexpress nucleolin receptors. Free DOX and liposomes without functionalization with AS1411 (plain liposomes) were used as controls. The results of molecular dynamic simulations suggest that AS1411 functionalization may promote the affinity and specific binding of liposomes to the nucleolin receptors, enhancing their subsequent uptake by tumor cells, whereas plain liposomes enter cells with difficulty. Upon mild heating, the decomposition of ABC that is encapsulated in the liposomes enables the immediate activation of generation of CO2 bubbles, creating permeable defects in their lipid bilayers, and ultimately facilitating the swift intracellular release of DOX. In vivo studies in nude mice that bear tumors demonstrate that the active targeting of AS1411 liposomes can substantially increase the accumulation of DOX in the tumor tissues relative to free DOX or passively targeted plain liposomes, inhibiting tumor growth and reducing systemic side effects, including cardiotoxicity. The above findings indicate that liposomes that are functionalized with AS1411 represent an attractive therapeutic alternative for overcoming the MDR effect, and support a potentially effective strategy for cancer therapy.