Association of 18F- fluorodeoxyglucose uptake with the expression of metabolism-related molecules in papillary thyroid cancer.

OBJECTIVES: 18F-fluorodeoxyglucose positron emission tomography-computed tomography (18F-FDG-PET/CT) is a diagnostic imaging method that is based on the Warburg effect, which is the increased uptake of glucose through aerobic glycolysis in cancer cells. The diagnostic value of 18F-FDG-PET/CT for thyroid cancer is controversial. However, uptake of 18F-FDG and the corresponding maximum standardized uptake value (SUVmax) is expected to reflect the metabolic status of cancer cells. In the present study, we sought to determine the relationship between 18F-FDG uptake and tumor metabolism- associated factors. METHODS: This was a single-center retrospective study. In the present study, SUVmax was compared with the expression of hexokinase 2 (HK2), glucose transporter 1 (GLUT1), vascular endothelial growth factor (VEGF), and glutaminase 1 (GLS1) in 41 patients with thyroid cancer. RESULTS: GLS1 expression was found to be moderately correlated with SUVmax (p < 0.001, r = 0.51), whereas HK2 and VEGF expression were weakly correlated (p = 0.011, r = 0.28, p = 0.008, r = 0.29, respectively) and GLUT1 did not correlate with SUVmax (p = 0.62, r = 0.06). CONCLUSION: Our findings suggest 18F-FDG PET/CT reflects GLS1 expression in thyroid cancer and could be used to select suitable candidates for GLS1 inhibitor treatment.

Challenges in decision-making support processes regarding living kidney donation: A qualitative study.

BACKGROUND: Previous studies on decision-making of living kidney donors have indicated issues regarding donors' autonomy is inherent in decision-making to donate their kidney. Establishing effective decision-making support that guarantees autonomy of living kidney donor candidates is important. OBJECTIVES: The aim of this study was to identify the difficulties in the decision-making support when clinical transplant coordinators advocating for the autonomy of donor candidates of living donor kidney transplantation and to identify the methods to deal with these difficulties. DESIGN: A qualitative descriptive study. PARTICIPANTS: Ten clinical transplant coordinators supporting living kidney donors. APPROACH: Semi-structured interviews were conducted using an interview guide. The modified grounded theory approach was utilised to analyse. RESULTS: Three categories related to difficulties were as follows: issues inherent to the interaction between coordinators, donor candidates and their families; issues regarding the environment and institutional background in which coordinators operate; and emotional labour undertaken by coordinators in the decision-making support process. Additionally, five categories related to methods were as follows: assessing the autonomy of donor candidates based on the coordinators nursing experience; interventions for the donor candidates and their family members based on the coordinators nursing experience; smooth coordination with medical staff; clarifying and asserting their views as coordinators; and readiness to protect the donor candidates. CONCLUSION: The involvement of highly experienced coordinators with excellent and assertive communication skills as well as the ability to reflect on their own practices is essential. Moreover, we may need to fundamentally review the transplant community, where power domination is inherent.

Left ventricular assist device temporary explantation as a strategy for infection control in a pediatric patient.

We report a case of temporary Berlin Heart EXCOR® explantation in a pediatric patient with idiopathic dilated cardiomyopathy who suffered an uncontrollable inflow cannulation site infection while on bridge-to-transplantation. Despite failure to thrive and catheter-related infections, once free of the device, the patient was cured of infection using systemic antibiotics and surgical debridement. The patient underwent EXCOR® reimplantation after four months, and is awaiting heart transplantation in stable condition. A life-threatening ventricular assist device-related infection may require device explantation under conditions that may not fulfill conventional explantation criteria despite risks. Temporary explantation can be an effective strategy if isolated systolic dysfunction is managed carefully.

Performance of GPT-4V in Answering the Japanese Otolaryngology Board Certification Examination Questions: Evaluation Study.

BACKGROUND: Artificial intelligence models can learn from medical literature and clinical cases and generate answers that rival human experts. However, challenges remain in the analysis of complex data containing images and diagrams. OBJECTIVE: This study aims to assess the answering capabilities and accuracy of ChatGPT-4 Vision (GPT-4V) for a set of 100 questions, including image-based questions, from the 2023 otolaryngology board certification examination. METHODS: Answers to 100 questions from the 2023 otolaryngology board certification examination, including image-based questions, were generated using GPT-4V. The accuracy rate was evaluated using different prompts, and the presence of images, clinical area of the questions, and variations in the answer content were examined. RESULTS: The accuracy rate for text-only input was, on average, 24.7% but improved to 47.3% with the addition of English translation and prompts (P<.001). The average nonresponse rate for text-only input was 46.3%; this decreased to 2.7% with the addition of English translation and prompts (P<.001). The accuracy rate was lower for image-based questions than for text-only questions across all types of input, with a relatively high nonresponse rate. General questions and questions from the fields of head and neck allergies and nasal allergies had relatively high accuracy rates, which increased with the addition of translation and prompts. In terms of content, questions related to anatomy had the highest accuracy rate. For all content types, the addition of translation and prompts increased the accuracy rate. As for the performance based on image-based questions, the average of correct answer rate with text-only input was 30.4%, and that with text-plus-image input was 41.3% (P=.02). CONCLUSIONS: Examination of artificial intelligence's answering capabilities for the otolaryngology board certification examination improves our understanding of its potential and limitations in this field. Although the improvement was noted with the addition of translation and prompts, the accuracy rate for image-based questions was lower than that for text-based questions, suggesting room for improvement in GPT-4V at this stage. Furthermore, text-plus-image input answers a higher rate in image-based questions. Our findings imply the usefulness and potential of GPT-4V in medicine; however, future consideration of safe use methods is needed.

Impaired Relaxation in Induced Pluripotent Stem Cell-Derived Cardiomyocytes with Pathogenic TNNI3 Mutation of Pediatric Restrictive Cardiomyopathy.

BACKGROUND: Restrictive cardiomyopathy (RCM) is characterized by impaired diastolic function with preserved ventricular contraction. Several pathogenic variants in sarcomere genes, including TNNI3, are reported to cause Ca2+ hypersensitivity in cardiomyocytes in overexpression models; however, the pathophysiology of induced pluripotent stem cell (iPSC)-derived cardiomyocytes specific to a patient with RCM remains unknown. METHODS AND RESULTS: We established an iPSC line from a pediatric patient with RCM and a heterozygous TNNI3 missense variant, c.508C>T (p.Arg170Trp; R170W). We conducted genome editing via CRISPR/Cas9 technology to establish an isogenic correction line harboring wild type TNNI3 as well as a homozygous TNNI3-R170W. iPSCs were then differentiated to cardiomyocytes to compare their cellular physiological, structural, and transcriptomic features. Cardiomyocytes differentiated from heterozygous and homozygous TNNI3-R170W iPSC lines demonstrated impaired diastolic function in cell motion analyses as compared with that in cardiomyocytes derived from isogenic-corrected iPSCs and 3 independent healthy iPSC lines. The intracellular Ca2+ oscillation and immunocytochemistry of troponin I were not significantly affected in RCM-cardiomyocytes with either heterozygous or homozygous TNNI3-R170W. Electron microscopy showed that the myofibril and mitochondrial structures appeared to be unaffected. RNA sequencing revealed that pathways associated with cardiac muscle development and contraction, extracellular matrix-receptor interaction, and transforming growth factor-ß were altered in RCM-iPSC-derived cardiomyocytes. CONCLUSIONS: Patient-specific iPSC-derived cardiomyocytes could effectively represent the diastolic dysfunction of RCM. Myofibril structures including troponin I remained unaffected in the monolayer culture system, although gene expression profiles associated with cardiac muscle functions were altered.

Lymph node metastasis regulation by peritumoral tonsillar tissue mitochondria-related pathway activation in oropharyngeal cancer.

Immune-related gene expression profiles of peritumoral tonsillar tissues are modified by oropharyngeal cancer (OPC) nodal status. This study explored immunometabolism and immune cell count alterations in peritumoral tonsillar tissue according to OPC nodal status. Microarray data analysis of 27 peritumoral tonsillar tissue samples, using a newly generated mitochondrial metabolism-related gene set comprised of 948 genes, detected 228 differentially expressed genes (DEGs) (206 up- and 22 downregulated) in metastasis-negative cases compared to metastasis-positive ones. REACTOME pathway analysis of the 206 upregulated genes revealed the Toll-like receptor 4 cascade were most enriched. Immune cell proportion analysis using the CIBERSORTx algorithm revealed a significantly higher rate of naïve B cells, but lower rates of regulatory T cells and resting natural killer cells in metastasis-negative cases. Digital spatial profiling of the 6 OPC tissues detected 9 DEGs in the lymphoid regions, in contrast, no DEGs were identified in tumor regions according to nodal status. Cancer cell nests and pair matched normal epithelia mitochondrial DNA (mtDNA) from 5 OPC tissues were analyzed by next generation sequencing for variant detection. However, no significant mtDNA variation was found. This study identified mitochondria-related immune cell transcriptional programs and immune cell profiles associated with OPC lymphatic spread in peritumoral tonsil tissue, further evaluation of which will elucidate targetable immune mechanisms associated with OPC lymphatic dissemination.

Efficacy of tokishakuyakusan and mecobalamin on post-infectious olfactory dysfunction: A prospective multicenter study.

OBJECTIVE: To determine if tokishakuyakusan (TSS) is effective for treating post-infectious olfactory dysfunction (PIOD) compared with vitamin B12 (mecobalamin). METHODS: We conducted a randomized, nonblinded clinical trial. Patients with PIOD enrolled in 17 hospitals and clinics from 2016 to 2020 were randomly divided into two groups, and we administered TSS or mecobalamin for 24 weeks. Their olfactory function was examined using interviews and T&T olfactometry. The improvement of olfactory dysfunction was assessed following the criteria of the Japanese Rhinologic Society. RESULTS: Overall, 82 patients with PIOD were enrolled in this study. In the TSS and mecobalamin groups, 39 patients completed the medication regimen. In the TSS and mecobalamin groups, olfactory dysfunction was significantly improved based on self-reports and olfactory test results. The improvement rate of olfactory dysfunction was 56% in the TSS group and 59% in the mecobalamin group. Early intervention within 3 months produced a better prognosis than the treatment initiated after 4 months. Furthermore, age and sex differences were not observed. Both medications produced no severe adverse events. CONCLUSION: The present study showed that TSS and mecobalamin might be useful for treating PIOD.

Peritumoral SPARC expression induced by exosomes from nasopharyngeal carcinoma infected Epstein-Barr virus: A poor prognostic marker.

Epstein-Barr virus (EBV)-associated nasopharyngeal carcinoma (NPC) cells have high metastatic potential. Recent research has revealed that the interaction of between tumor cells and the surrounding stroma plays an important role in tumor invasion and metastasis. In this study, we showed the prognostic value of expression of SPARC, an extracellular matrix protein with multiple cellular functions, in normal adjacent tissues (NAT) surrounding NPC. In the immunohistochemical analysis of 51 NPC biopsy specimens, SPARC expression levels were significantly elevated in the NAT of EBER (EBV-encoded small RNA)-positive NPC compared to that in the NAT of EBER-negative NPC. Moreover, increased SPARC expression in NAT was associated with a worsening of overall survival. The enrichment analysis of RNA-seq of publicly available NPC and NAT surrounding NPC data showed that high SPARC expression in NPC was associated with epithelial mesenchymal transition promotion, and there was a dynamic change in the gene expression profile associated with interference of cellular proliferation in NAT, including SPARC expression. Furthermore, EBV-positive NPC cells induce SPARC expression in normal nasopharyngeal cells via exosomes. Induction of SPARC in cancer-surrounding NAT cells reduced intercellular adhesion in normal nasopharyngeal structures and promoted cell competition between cancer cells and normal epithelial cells. These results suggest that epithelial cells loosen their own binding with the extracellular matrix as well as stromal cells, facilitating the invasion of tumor cells into the adjacent stroma by activating cell competition. Our findings reveal a new mechanism by which EBV creates a pro-metastatic microenvironment by upregulating SPARC expression in NPC.

Development of new colloid osmotic pressure measurement method using ultrafiltration membrane during cardiopulmonary bypass.

BACKGROUND: Clinical practice of measuring colloid osmotic pressure (COP) was abandoned after correcting hypoosmolarity did not improve overall patient outcomes. However, the use of albumin and colloidal solutions has contributed to maintaining intraoperative and postoperative fluid balance at lower levels. Reduced perioperative fluid balance is consistently reported to have positive effects on clinical outcomes. Priming solutions for cardiopulmonary bypass typically include colloids; however, the optimal type of priming solution has not yet been determined. Stricter COP management may further improve postoperative courses. To achieve this, the widespread adoption of a measurement method suitable for COP monitoring during cardiopulmonary bypass is required. METHODS: A test circuit was made which measured COP using an ultrafiltration membrane method based on the changes in hydrostatic pressure that occurs across a semipermeable membrane. We then compared the measurements obtained using this method with colloidal osmometer measurements. RESULTS: COP measurements were obtained for a total of 100 tests (10 times each for 10 test solutions). The evaluation parameters included simultaneous reproducibility, correlation with the colloid osmometer, and measurement time. The results demonstrated high accuracy of the ultrafiltration membrane method, simultaneous reproducibility within 3%, a high positive correlation with the colloid osmometer (correlation coefficient: R2 = 0.99; p < 0.01), and equal time required for measurement. CONCLUSION: Measuring COP using ultrafiltration membranes solves problems within existing measurement methods. Although further improvements in the method are necessary, it has implications for future research and clinical applications.

Predicting postoperative delirium after cardiovascular surgeries from preoperative portable electroencephalography oscillations.

Introduction: Postoperative delirium (POD) is common and life-threatening, however, with intensive interventions, a potentially preventable clinical syndrome. Although electroencephalography (EEG) is a promising biomarker of delirium, standard 20-leads EEG holds difficulties for screening usage in clinical practice. Objective: We aimed to develop an accurate algorithm to predict POD using EEG data obtained from portable device. Methods: We recruited 128 patients who underwent scheduled cardiovascular surgery. Cognitive function assessments were conducted, and portable EEG recordings were obtained prior to surgery. Results: Among the patients, 47 (36.7%) patients with POD were identified and they did not significantly differ from patients without POD in sex ratio, age, cognitive function, or treatment duration of intensive care unit. However, significant differences were observed in the preoperative EEG power spectrum densities at various frequencies, especially gamma activity, between patients with and without POD. POD was successfully predicted using preoperative EEG data with a machine learning algorithm, yielding accuracy of 86% and area under the receiver operating characteristic curve of 0.93. Discussion: This study provides new insights into the objective and biological vulnerability to delirium. The developed algorithm can be applied in general hospitals without advanced equipment and expertise, thereby enabling the reduction of POD occurrences with intensive interventions for high-risk patients.

Development of postoperative delirium prediction models in patients undergoing cardiovascular surgery using machine learning algorithms.

Associations between delirium and postoperative adverse events in cardiovascular surgery have been reported and the preoperative identification of high-risk patients of delirium is needed to implement focused interventions. We aimed to develop and validate machine learning models to predict post-cardiovascular surgery delirium. Patients aged ≥ 40 years who underwent cardiovascular surgery at a single hospital were prospectively enrolled. Preoperative and intraoperative factors were assessed. Each patient was evaluated for postoperative delirium 7 days after surgery. We developed machine learning models using the Bernoulli naive Bayes, Support vector machine, Random forest, Extra-trees, and XGBoost algorithms. Stratified fivefold cross-validation was performed for each developed model. Of the 87 patients, 24 (27.6%) developed postoperative delirium. Age, use of psychotropic drugs, cognitive function (Mini-Cog < 4), index of activities of daily living (Barthel Index < 100), history of stroke or cerebral hemorrhage, and eGFR (estimated glomerular filtration rate) < 60 were selected to develop delirium prediction models. The Extra-trees model had the best area under the receiver operating characteristic curve (0.76 [standard deviation 0.11]; sensitivity: 0.63; specificity: 0.78). XGBoost showed the highest sensitivity (AUROC, 0.75 [0.07]; sensitivity: 0.67; specificity: 0.79). Machine learning algorithms could predict post-cardiovascular delirium using preoperative data.Trial registration: UMIN-CTR (ID; UMIN000049390).

Impact of complete revascularization in coronary artery bypass grafting for ischemic cardiomyopathy.

Objective: In patients with ischemic cardiomyopathy, coronary artery bypass grafting ensures better survival than medical therapy. However, the long-term clinical impact of complete revascularization remains unclear. This observational study aimed to evaluate the effects of complete revascularization on long-term survival and left ventricular functional recovery in patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting. Methods: We retrospectively reviewed outcomes of 498 patients with ischemic cardiomyopathy who underwent complete (n = 386) or incomplete (n = 112) myocardial revascularization between 1993 and 2015. The baseline characteristics were adjusted using inverse probability of treatment weighting to reduce the impact of treatment bias and potential confounding. The mean follow-up duration was 77.2 ± 42.8 months in survivors. Results: The overall 5-year survival rate (complete revascularization, 72.5% vs incomplete revascularization, 57.9%, P = .03) and freedom from all-cause death and/or readmission due to heart failure (54.5% vs 40.1%, P = .007) were significantly greater in patients with complete revascularization than those with incomplete revascularization. After adjustments using inverse probability of treatment weighting, the complete revascularization group demonstrated a lower risk of all-cause death (hazard ratio, 0.61; 95% confidence interval, 0.43-0.86; P = .005) and composite adverse events (hazard ratio, 0.59; 95% confidence interval, 0.44-0.79; P < .001) and a greater improvement in the left ventricular ejection fraction 1-year postoperatively (absolute change: 11.0 ± 11.9% vs 8.3 ± 11.4%, interaction effect P = .05) than the incomplete revascularization group. Conclusions: In patients with ischemic cardiomyopathy undergoing coronary artery bypass grafting, complete revascularization was associated with better long-term outcomes and greater left ventricular functional recovery and should be encouraged whenever possible.

Pseudoaneurysm after aortopulmonary window repair and bilateral lung transplantation for eisenmenger syndrome: a case report.

BACKGROUND: Aortopulmonary window (APW) is a rare congenital cardiac anomaly characterized by communication between the main pulmonary artery and ascending aorta. There are various surgical techniques, and the short- and long-term results are excellent if the surgical repair is performed early in life. To our knowledge, there have been no reports of pseudoaneurysm after APW repair. Herein, we present a case of a 30-year-old woman with an ascending aortic pseudoaneurysm found at the site of APW repair nine months after the APW repair and bilateral lung transplantation. CASE PRESENTATIONS: A 30-year-old woman presented with APW and Eisenmenger syndrome. The patient underwent APW repair and bilateral lung transplantation. We transected the communication between the aorta and pulmonary artery and closed the aortic side directly with strips of felts. Nine months after the surgery, the patient complained of chest pain. Cardiac computed tomography revealed an ascending aortic pseudoaneurysm at the anastomotic site. Emergent graft replacement of the ascending aorta was performed and the postoperative course was uneventful. CONCLUSIONS: We have presented a case of a pseudoaneurysm at the anastomotic site after APW repair and bilateral lung transplantation. The choice of surgical technique should be based on the patient's background requiring lung transplantation, and in these cases close postoperative follow-up is required.

Risk factors for atrial arrhythmia recurrence after atrial arrhythmia surgery with pulmonary valve replacement.

Objectives: Atrial arrhythmias are a significant cause of late morbidity and mortality in patients after tetralogy of Fallot repair. However, reports on their recurrence following atrial arrhythmia surgery are limited. We aimed to identify the risk factors for atrial arrhythmia recurrence after pulmonary valve replacement (PVR) and arrhythmia surgery. Methods: We reviewed 74 patients with repaired tetralogy of Fallot who underwent PVR for pulmonary insufficiency at our hospital between 2003 and 2021. Twenty-two patients (mean age, 39 years) underwent PVR and atrial arrhythmia surgery. A modified Cox-maze III was performed in 6 patients with chronic atrial fibrillation, and a right-sided maze was performed in 12 with paroxysmal atrial fibrillation, 3 with atrial flutter, and 1 with atrial tachycardia. Atrial arrhythmia recurrence was defined as any documented sustained atrial tachyarrhythmia requiring intervention. The influence of preoperative parameters on recurrence was assessed with the Cox proportional-hazards model. Results: The median follow-up period was 9.2 years (interquartile range, 4.5-12.4). Cardiac death and redo-PVR due to prosthetic valve dysfunction were not observed. Eleven patients had atrial arrhythmia recurrence after discharge. Atrial arrhythmia recurrence-free rates were 68% at 5 years and 51% at 10 years after PVR and arrhythmia surgery. Multivariable analysis revealed that right atrial volume index (hazard ratio, 1.04; 95% confidence interval, 1.01-1.08, P = .009) was a significant risk factor for atrial arrhythmia recurrence after arrhythmia surgery and PVR. Conclusions: Preoperative right atrial volume index was associated with atrial arrhythmia recurrence, which may assist in planning the timing of atrial arrhythmia surgery and PVR.

Immune-Related Gene Expression Profile at Peritumoral Tonsillar Tissue Is Modified by Oropharyngeal Cancer Nodal Status.

Secondary lymphoid organs, such as lymph nodes and tonsils, serve as an interface between the immune system and tumor cells as an initial antigen-presentation site, crucial in antitumor immune response and disease progression. In oropharyngeal cancers originating from palatine tonsils, it was hypothesized that characterizing the immunologic process occurring in the peritumoral tonsil tissue would elucidate immune mechanisms of the lymphatic spread of the disease. A total of 33 patients were enrolled and divided into two cohorts. In Cohort 1 (6 patients), gene expression profiles at the peritumoral lymph regions and tumor regions were analyzed using the whole-transcriptome atlas. In the peritumoral lymph regions, 237 genes were up-regulated in metastasis-negative cases compared with metastasis-positive ones, but only 1 gene was up-regulated in tumor regions. In Cohort 2 (27 patients), microarray analysis of peritumoral tonsil tissue revealed 192 up-regulated genes. Gene ontology analysis revealed the significantly enriched Gene Ontology terms associated with T-cell activation; top 10 hub genes, as ranked by degree, were PTPRC, TLR4, CD80, CD40, STAT3, CD28, CD40LG, CD44, CCR7, and IL7R. Gene set enrichment analysis combined with principal component analysis were used to effectively classify patients as lymph node metastasis positive or negative. These findings suggest peritumoral tonsils as a potential target for investigating the immune mechanisms associated with the lymphatic spread of the disease in oropharyngeal cancers.

Changes in Transcutaneous Oxygen Pressure in the Lower Limb Associated with the Use of Elastic Compression Stockings.

Objective: Elastic compression stockings are used to prevent venous thrombosis in postsurgical patients. However, they have been associated with skin complications, such as medical device-related pressure ulcers. This study aimed to assess the effect of elastic compression stockings on the skin tissue status of the lower limbs. Methods: Transcutaneous oxygen pressure (TcPO2) was measured in the anterior tibia and corresponding soft skin of healthy subjects before, during, and after continuous use of elastic stockings for 30 min. Results: Wearing elastic stockings significantly reduced TcPO2 in the skin of the anterior tibia, and removal of the stockings restored TcPO2 values. Both individuals who exercised regularly and men had lower TcPO2 at all measurement points than both individuals who did not exercise and women. Older subjects (50-60 years) had reduced TcPO2 in the sural region than younger ones (20-30 years). Conclusion: The use of elastic compression stockings caused an early decrease of TcPO2 in healthy subjects. Clinical patients were predicted to be at a high risk of wounding.

Cardiomyocyte deoxyribonucleic acid damage and cardiac recovery in paediatric dilated cardiomyopathy.

OBJECTIVES: The goal of this study was to identify the clinical significance of the deoxyribonucleic acid (DNA) damage response marker, phosphorylated H2A histone variant X, on the bridge to recovery in low-weight paediatric patients with dilated cardiomyopathy (DCM) after having a Berlin Heart EXCOR implanted. METHODS: Consecutive paediatric patients with DCM who had an EXCOR implanted for DCM at our hospital between 2013 and 2021 were reviewed. Patients were classified into 2 groups according to the degree of DNA damage in the left ventricular cardiomyocytes-the low DNA damage group and the high DNA damage group-using the median value as the threshold. We examined and compared the preoperative factors and histologic findings associated with cardiac functional recovery following the explant procedure in the 2 groups. RESULTS: Competing outcome analysis of 18 patients (median body weight, 6.1 kg) showed that the incidence of an EXCOR explant was 40% at 1 year after the implant procedure. Serial echocardiography revealed significant left ventricular functional recovery in the low DNA damage group 3 months after the implant. The univariable Cox proportional hazards model revealed that the percentage of phosphorylated H2A histone variant X-positive cardiomyocytes was the significant factor associated with cardiac recovery and the EXCOR explant (hazard ratio, 0.16; 95% confidence interval, 0.027-0.51; P = 0.0096). CONCLUSIONS: The degree of DNA damage response to the EXCOR implant may aid in predicting the bridge to recovery with EXCOR among low-weight paediatric patients with DCM.

Mitochondrial Transfer Induced by Adipose-Derived Mesenchymal Stem Cell Transplantation Improves Cardiac Function in Rat Models of Ischemic Cardiomyopathy.

Although mesenchymal stem cell transplantation has been successful in the treatment of ischemic cardiomyopathy, the underlying mechanisms remain unclear. Herein, we investigated whether mitochondrial transfer could explain the success of cell therapy in ischemic cardiomyopathy. Mitochondrial transfer in co-cultures of human adipose-derived mesenchymal stem cells and rat cardiomyocytes maintained under hypoxic conditions was examined. Functional recovery was monitored in a rat model of myocardial infarction following human adipose-derived mesenchymal stem cell transplantation. We observed mitochondrial transfer in vitro, which required the formation of cell-to-cell contacts and synergistically enhanced energy metabolism. Rat cardiomyocytes exhibited mitochondrial transfer 3 days following human adipose-derived mesenchymal stem cell transplantation to the ischemic heart surface post-myocardial infarction. We detected donor mitochondrial DNA in the recipient myocardium concomitant with a significant improvement in cardiac function. Mitochondrial transfer is vital for successful cell transplantation therapies and improves treatment outcomes in ischemic cardiomyopathy.