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ABSTRACT Ventricular assist device (VAD) infections are frequent causes of hospital readmission. The risk factors and optimal preventive strategies for such, including chronic suppressive antibiotics (CSA), remain uncertain. We performed a single-center, retrospective, observational cohort study assessing continuous flow VAD recipients who underwent implantation between 2008 and 2018 in Japan. From primary VAD infection (VADI), we followed the patients for recurrent infection, defined as relapsing VAD-specific (e.g., localized infections) or VAD-related (e.g., bacteremia) infections requiring hospital readmission. CSA was defined as the use of oral antimicrobial agents continued beyond initial antibiotic use until transplantation, VAD withdrawal, VADI recurrence, or death. Survival analysis was performed to identify risk factors for recurrent infection accounting for competing risks (e.g., deaths and transplants). Among 163 eligible patients, 76 patients had VADIs. The main causative organism in primary VADI was Staphylococcus aureus (63%, 48/76). Among them, 41 had recurrent infections, whereas 35 had none during the follow-up period (median, 335 days). Thirty-six patients received CSA for a median of 478 days. Although CSA was associated with a decreased risk of recurrent infection [adjusted sub-distribution hazard ratio (SHR), 0.40; 95% confidence interval (CI), 0.18–0.89; P = 0.03], this protective effect was observed only after primary VAD-specific infection (SHR, 0.28; 95% CI, 0.12–0.64; P < 0.01) but not after VAD-related infection. Surgical procedures during primary VADI were associated with an increased risk (SHR, 2.00; 95% CI, 1.10–3.66; P = 0.02). One patient had an adverse drug reaction. CSA may be an effective approach to limit relapsing VADIs following a primary VAD-specific infection with minimal adverse events.IMPORTANCEVentricular assist device infections (VADIs) are a significant complication leading to hospital readmissions. However, the risk factors and optimal preventive strategies for VADI remain unclear. This study investigated the effectiveness of chronic suppressive antibiotic therapy in patients with VADI. We found that the use of chronic suppressive antibiotic therapy was associated with a reduction in the risk of VADI recurrence with few adverse reactions. Our findings suggest the potential benefit of chronic suppressive antibiotics in preventing infections in selected cases. Our findings are relevant for the management of patients with ventricular assist devices awaiting heart transplantation, providing valuable insights for clinical practice.

Mesenchymal stem cell (MSC) transplantation has been explored for the clinical treatment of various diseases. However, the current two-dimensional (2D) culture method lacks a natural spatial microenvironment in vitro. This limitation restricts the stable establishment and adaptive maintenance of MSC stemness. Using natural polymers with biocompatibility for constructing stereoscopic MSC microenvironments may have significant application potential. This study used chitin-based nanoscaffolds to establish a novel MSC three-dimensional (3D) culture. We compared 2D and 3D cultured human umbilical cord-derived MSCs (UCMSCs), including differentiation assays, cell markers, proliferation, and angiogenesis. When UCMSCs are in 3D culture, they can differentiate into bone, cartilage, and fat. In 3D culture condition, cell proliferation is enhanced, accompanied by an elevation in the secretion of paracrine factors, including vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), Interleukin-6 (IL-6), and Interleukin-8 (IL-8) by UCMSCs. Additionally, a 3D culture environment promotes angiogenesis and duct formation with HUVECs (Human Umbilical Vein Endothelial Cells), showing greater luminal area, total length, and branching points of tubule formation than a 2D culture. MSCs cultured in a 3D environment exhibit enhanced undifferentiated, as well as higher cell activity, making them a promising candidate for regenerative medicine and therapeutic applications.

Abstract Tissue engineering combines cell biology and material science to construct tissues or organs for disease modeling, drug testing, and regenerative medicine. The cell sheet is a newly developed tissue engineering technology that has brought about scaffold-free tissue and shows great application potential. In this review, we summarized recent progress and future possibilities in preclinical research into and clinical applications of cell sheets fabricated by differing cell types from various sources for cardiac tissue repair, and the manufacturing strategies and promising application potential of 3D cell-dense tissue constructed from cell sheets. Special attention was paid to the mechanisms of mesenchymal stem cell (MSC) sheets in the prevention of myocardial ischemia and left ventricle remodeling. Comparing MSCs sheets with other types of cell sheets and 3D cardiac tissues, engineering tissues' potential safety and effectiveness concerns were also discussed.

Abstract Aims The removal of left ventricular assist device (LVAD) after myocardial recovery can provide survival benefits with freedom from LVAD‐associated complications. However, in the absence of standardization, the weaning evaluation and surgical strategy differ widely among centres. Therefore, we analysed the experiences of LVAD explantation with our protocol in dilated cardiomyopathy (DCM) patients and investigated the validity of our weaning evaluation and surgical strategy from the perspective of optimal long‐term survival. Methods and results All LVAD explantation patients in our institution between May 2012 and May 2020 were enrolled. All patients were evaluated by our three‐phase weaning assessment: (i) clinical stability with improved cardiac function under LVAD support; (ii) haemodynamic stability shown by ramp‐loading and saline‐loading test; (iii) intraoperative pump‐off test. Explant surgery involved removal of the whole system including driveline, pump, sewing ring and outflow‐graft, and closure of an apical hole. Intra‐operative, peri‐operative, and post‐operative outcomes, including all‐cause mortality and LVAD associated major complications, were retrospectively analysed. A total of 12 DCM patients (DuraHeart, n = 2; EVAHEART, n = 2; HeartMate II, n = 6; HeartMate 3, n = 2) had myocardial recovery after a median 10 months [interquartile range (IQR); 6.3–15 months] support and qualified for our LVAD explantation study protocol [median age: 37 y, IQR; 34–41 years; 83% men]. The median left ventricular ejection fraction was 20% (IQR; 12–23%) at LVAD‐implantation and 54% (IQR: 45–55%) before LVAD explantation (P

Abstract Background Quadricuspid aortic valve is a rare congenital heart disease that may be associated with a different anatomical relationship between the coronary artery ostium and the commissure. Case presentation Herein, we report a case of a 59-year-old woman who underwent aortic valve replacement for a quadricuspid aortic valve with severe aortic regurgitation. Intraoperatively, the aortic valve had four cusps of almost equal size and the right coronary artery arose adjacent to the commissure between the right coronary cusp and one of the two non-coronary cusps. The annular stitches were placed in a non-everting mattress fashion with pledgets on the ventricular side, and stitches near the right coronary ostium were transitioned to the subannular ventricular myocardium to maintain the distance from the ostium. A one-step smaller-sized prosthesis was selected to avoid an oversized prosthetic valve potentially compressing the right coronary ostium. Conclusions When performing aortic valve replacement for a quadricuspid aortic valve, careful observation of the coronary location and means to avoid coronary ostium obstruction are essential.

Cardiac fibrosis is a hallmark of heart failure. Here the authors use single-cell RNA-sequencing, spatial transcriptomics, and genetic manipulations, to show that Htra3 regulates cardiac fibrosis by keeping fibroblasts quiescent and by degrading TGF-beta.

Abstract Aims Heart transplantation (HT) is an effective therapeutic option for end‐stage heart failure. Infection is a major cause of morbidity and mortality after HT. Sarcopenia, defined as the loss of muscle mass and strength, is a common comorbidity in HT candidates with end‐stage heart failure. However, the effects of sarcopenia on the occurrence of post‐HT infections are not well understood. Therefore, we explored the association between the skeletal muscle mass and post‐transplant infections in adult HT recipients. Methods and results We retrospectively examined the records of 135 patients who underwent HT between August 2007 and November 2019 at our institution. Pre‐transplant computed tomography was used to calculate the skeletal muscle index (SMI) at the level of the third lumbar vertebra. Muscle wasting was defined as the SMI of the lowest sex‐based tertiles. The primary endpoint was infections within 6 months of HT. The study included 109 patients (80 men, mean age: 41.6 ± 12.0 years): 37 patients in the muscle wasting group and 72 patients in the non‐muscle wasting group. The mean SMI values in the muscle wasting and non‐muscle wasting groups were 29.9 ± 4.8 cm2/m2 and 40.7 ± 6.7 cm2/m2, respectively. Prior to HT, 108 (99.1%) patients were on left ventricular assist device support, and during that support, the rate of late right heart failure was significantly higher in the muscle wasting group than non‐muscle wasting group (P = 0.012). Sixteen infections occurred within 6 months of HT. The most common infection sites included the respiratory tract (n = 5) and the upper gastrointestinal tract (n = 5), followed by the urinary tract (n = 4). Overall, 10 patients experienced infections in the muscle wasting group (27.0%) and 6 in the non‐muscle wasting group (8.3%) (P = 0.009). Two patients in the muscle wasting group required intensive care unit admission, compared to none in the non‐muscle wasting group. Low skeletal muscle mass was associated with infections in the univariate and multivariate logistic regression models (hazard ratio: 3.68, 95% confidence interval: 1.19–11.3; P = 0.023). However, the duration of all‐cause mortality within 3 years did not differ between the groups (P = 0.56). Conclusions Low skeletal muscle mass is a predictor of post‐HT infections within 6 months of HT.

Cardiomyopathy develops through an interaction of genetic and environmental factors. The clinical manifestations of both dilated cardiomyopathy and hypertrophic cardiomyopathy are diverse, but genetic testing defines the causative genes in about half of cases and can predict clinical prognosis. It has become clear that cardiomyopathy is caused not only by single rare variants but also by combinations of multiple common variants, and genome-wide genetic research is important for accurate disease risk assessment. Single-cell analysis research aimed at understanding the pathophysiology of cardiomyopathy is progressing rapidly, and it is expected that genomic analysis and single-cell molecular profiling will be combined to contribute to more detailed stratification of cardiomyopathy.

Moderate to severe aortic insufficiency (AI) in patients who underwent continuous-flow left ventricular assist device (CF-LVAD) implantation is a significant complication. According to the INTERMACS registry analysis, at least mild AI occurs in 55% of patients at 6 months after CF-LVAD implantation and moderate to severe AI is significantly associated with higher rates of re-hospitalization and mortality. The clinical implications of these data may underscore consideration of prophylactic aortic valve replacement, or repair, at the time of CF-LVAD implantation, particularly with expected longer duration of support and in patients with preexisting AI that is more than mild. More crucially, even if a native aortic valve is seemingly competent at the time of VAD implantation, we frequently find de novo AI as time goes by, potentially due to commissural fusion in the setting of inconsistent aortic valve opening or persistent valve closure caused by CF-LVAD support, that alters morphological and functional properties of innately competent aortic valves. Therefore, close monitoring of AI is mandatory, as the prognostic nature of its longitudinal progression is still unclear. Clearly, significant AI during VAD support warrants surgical intervention at the appropriate timing, especially in patients of destination therapy. Nonetheless, such an uncertainty in the progression of AI translates to a lack of consensus regarding the management of this untoward complication. In practice, proposed surgical options are aortic valve replacement, repair, closure, and more recently transcatheter aortic valve implantation or closure. Transcatheter approach is of course less invasive, however, its efficacy in terms of long-term outcome is limited. In this review, we summarize the recent evidence related to the pathophysiology and surgical treatment of AI associated with CF-LVAD implantation.

Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyocyte disease characterized by intractable ventricular arrhythmia in the majority of affected patients. Some of these patients also manifest right ventricular dysfunction and heart failure symptoms. Fatal ventricular arrhythmia has been the primary cause of death in ARVC patients. However, increased early recognition of ARVC and improvement in arrhythmic risk stratification and treatment have dramatically improved survival. A small proportion of the patients are further complicated by left ventricular impairment at the late phase in addition to right heart failure, for whom only heart transplantation is the last resort. Because of the relative rarity of ARVC with biventricular failure, no consensus or guideline has been reported on how to effectively support these patients with a mechanical circulatory device. Herein, four ARVC patients with biventricular failure were presented who were successfully bridged to heart transplantation after long-term support by isolated continuous-flow LVAD.

Abstract In recent years, mesenchymal stem cells (MSCs) have been used to improve cardiac function and attenuate adverse ventricular remodeling of the ischemic myocardium through paracrine effects and immunoregulation functions. In combination with cell sheet technology, MSCs could be more easily transplanted to the ischemic area. The long-term retention of MSCs in the affected area was realized and significantly improved the curative effect. In this review, we summarized the research and the applications of MSC sheets to the treatment of ischemic heart tissue. At present, many types of MSCs have been considered as multipotent cells in the treatment of heart failure, such as bone marrow-derived mesenchymal stem cells (BM-MSCs), adipose-derived mesenchymal stem cells (AD-MSCs), umbilical cord-derived mesenchymal stem cells (UC-MSCs), and skeletal myoblasts (SMs). Since UC-MSCs have few human leukocyte antigen-II and major histocompatibility complex class I molecules, and are easy to isolate and culture, UC-MSC sheets have been proposed as a candidate for clinical applications to ischemic heart disease.

AimsWe compared hemodynamics and clinical events after heart transplantation (HTx) in patients stratified by the severity of residual pulmonary vascular resistance (PVR) after left ventricular assist device (LVAD) implantation for bridge to transplantation.MethodsWe retrospectively analyzed patients who had undergone HTx at the University of Tokyo Hospital. We defined the high PVR group as patients with PVR of >3 Wood Units (WU) as measured by right heart catheterization performed 1 month after LVAD implantation.ResultsWe included 85 consecutive HTx recipients, 20 of whom were classified in the high PVR group and 65 in the low PVR group. The difference in PVR between the two groups became apparent at 2 years after HTx (the high PVR group: 1.77 ± 0.41 WU, the low PVR group: 1.24 ± 0.59 WU, p = 0.0009). The differences in mean pulmonary artery pressure (mPAP), mean right arterial pressure (mRAP), and mean pulmonary capillary wedge pressure (mPCWP) tended to increase from the first year after HTx, and were all significantly higher in the high PVR group at 3 years after HTx (mPAP: 22.7 ± 9.0 mm Hg vs. 15.4 ± 4.3 mm Hg, p = 0.0009, mRAP: 7.2 ± 3.6 mm Hg vs. 4.1 ± 2.1 mm Hg, p = 0.0042, and mPCWP: 13.4 ± 4.5 mm Hg, 8.8 ± 3.3 mm Hg, p = 0.0040). In addition, pulmonary artery pulsatility index was significantly lower in the high PVR group than in the low PVR group at 3 years after HTx (2.51 ± 1.00 vs. 5.21 ± 3.23, p = 0.0033). The composite event including hospitalization for heart failure, diuretic use, and elevated intracardiac pressure (mRAP ≥ 12 mm Hg or mPCWP ≥ 18 mm Hg) between the two groups was significantly more common in the high PVR group. Residual high PVR was still an important predictor (hazard ratio 6.5, 95% confidence interval 2.0–21.6, and p = 0.0023) after multivariate Cox regression analysis.ConclusionOur study demonstrates that patients with residual high PVR under LVAD implantation showed the increase of right and left atrial pressure in the chronic phase after HTx.

Background: There are some patients with advanced heart failure (HF), for whom implantable left ventricular assist device (LVAD) or heart transplantation (HTx) should be considered. Some of them need to be transferred between hospitals. There are few reports on the interhospital transfer of patients with advanced HF and their subsequent clinical course.In this study, we investigated the characteristics and clinical course of patients transferred to a LVAD/HTx center, focusing on the distance between hospitals. Methods: We retrospectively examined 141 patients who were transferred to our hospital, considering the indications of LVAD implantation or HTx. We divided the patients into two groups: those referred

Abstract Heart transplantation is an effective therapy for patients with end‐stage heart failure. In some cases, Takotsubo syndrome (TTS) was seen in the donor heart. We report a case of TTS in a 40‐year‐old woman with a history of epileptic seizures who underwent heart transplantation from a donor with TTS. The donor was brain‐dead due to severe hypoxic encephalopathy during cardiac arrest with TTS. Fifteen months after heart transplantation, she was readmitted for epileptic seizures. Electrocardiogram showed T‐wave inversion, and transthoracic echocardiography showed apical ballooning. Coronary angiography was normal, and endomyocardial biopsy was negative for rejection. Iodine‐123 metaiodobenzylguanidine imaging demonstrated a low heart‐to‐mediastinum ratio and high washout rate. Eighteen days after admission, recovery of left ventricular dysfunction was confirmed, and she was diagnosed with TTS triggered by epileptic seizures. It is important to recognize the risk of recurrent TTS in heart transplantation patients from a donor with TTS.

Abstract Aims Nephrotoxicity of calcineurin inhibitors (CNIs) is associated with adverse events in patients undergoing heart transplant (HTx), although studies directly comparing tacrolimus (TAC) versus cyclosporin A (CsA), especially in combination with everolimus and low‐dose CNIs approach, are limited. Thus, we sought to investigate the associations of TAC and CsA with clinical outcomes in HTx recipients, with specific focus on renal function. Methods and results From August 2007 to February 2017, 72 consecutive patients (39 treated with TAC vs. 33 with CsA) receiving de novo HTx in a single transplant centre were retrospectively evaluated. We used the instrumental variable method to account for unmeasured confounding. The study outcomes were percentage change in estimated glomerular filtration rates (eGFR) (safety endpoint) and biopsy‐proven acute rejection (efficacy endpoint) within the first year after HTx. The enrolled patients (median age 40 years) were predominantly men (68%). There were no significant differences in baseline characteristics, including eGFR (64.8 [45.7–96.4] mL/min/1.73 m2 in TAC vs. 65.6 [57.9–83.0] mL/min/1.73 m2 for CsA; P = 0.48), other than sex (male, 49% for TAC vs. 91% for CsA; P

Background: Implantable continuous-flow left ventricular assist device (LVAD) improve renal function in advanced heart failure. However, the long-term effects of LVAD on renal function have not been investigated thoroughly. We aimed to assess long-term renal function in patients with LVAD support and to identify predictors for late deterioration in renal function (LDRF). Methods: One hundred patients underwent LVAD implantation as a bridge to transplant at the University of Tokyo Hospital between May 2011 and December 2018. We assessed renal function at intervals (preoperative, 1, 6, 12, 18, 24 and 30 months after LVAD implantation). We divided patients into two groups: “with LDRF,” whose renal function at 30 months had decreased by >25% compared with preoperatively (n = 14), and “without LDRF” (n = 55). Results: Renal function improved at 1 month, returned to preoperative levels at 6 months, and remained there up to 30 months after LVAD implantation. However, renal function impairment became evident in patients with LDRF 18 months after LVAD implantation. A ratio of right atrial pressure/pulmonary artery wedge pressure > 0.57 and left ventricular dimension diastole ≤ 67 mm were preoperative independent risk factors for LDRF. In addition, the incidence of perioperative acute kidney injury, ventricular arrhythmia, aortic insufficiency, and late right ventricular failure was significantly higher in patients with LDRF. Conclusion: LDRF after LVAD implantation corresponded to several risk factors, including a small left ventricle and LVAD-related complications, such as right ventricular failure.

This study aimed to investigate the outcomes of surgical interventions for symptomatic moderate-to-severe aortic regurgitation (AR), including aortic valve replacement (AVR) and repair (AVP), in 184 patients who underwent continuous flow-left ventricular assist device (Cf-LVAD) implantation as a bridge-to-transplant (BTT) between November 2007 and April 2020. Ten patients (median age, 34 (25–41) years; 60% men) underwent surgical interventions (AVR, n = 6; AVP, n = 4) late after cf-LVAD implantation. The median duration after the device implantation was 34 (24–44) months. Three patients required additional tricuspid valve repair. Aortic valve suturing resulted in severe recurrent AR 6 months postoperatively, due to leaflet cutting in one patient. Seven patients with AVR survived without regurgitation during the study period, except for one non-survivor complicated by liver failure due to postoperative right heart failure. Therefore, six patients after AVP (n = 4) and AVR (n = 2) underwent successful heart transplantation 7 (4–13) months after aortic intervention. Kaplan–Meier analysis showed no significant difference in overall survival through 5 years after cf-LVAD implantation, regardless of the surgical AV intervention chosen (log-rank test, p = 0.86). In conclusion, surgical interventions (AVR or AVP) for patients with an ongoing cf-LVAD are safe, effective, and viable options.

Introduction: The definitive treatment for severe heart failure is transplantation. However, only a small number of heart transplants are performed each year due to donor shortages. Therefore, novel treatment approaches based on artificial organs or regenerative therapy are being developed as alternatives. We have developed a technology known as cell sheet-based tissue engineering that enables the fabrication of functional three-dimensional (3D) tissue. Here, we report a new technique for engineering human cardiac tissue with perfusable blood vessels. Our method involved the layering of cardiac cell sheets derived from human induced pluripotent stem cells (hiPSCs) on a vascular bed derived from porcine small intestinal tissue. Methods: For the vascular bed, a segment of porcine small intestine was harvested together with a branch of the superior mesenteric artery and a branch of the superior mesenteric vein. The small intestinal tissue was incised longitudinally, and the mucosa was resected. Human cardiomyocytes derived from hiPSCs were co-cultured with endothelial cells and fibroblasts on a temperature-responsive dish and harvested as a cardiac cell sheet. A triple-layer of cardiac cell sheets was placed onto the vascular bed, and the resulting construct was subjected to perfusion culture in a bioreactor system. Results: The cardiac tissue on the vascular bed pulsated spontaneously and synchronously after one day of perfusion culture. Electrophysiological recordings revealed regular action potentials and a beating rate of 105 ± 13/min (n = 8). Furthermore, immunostaining experiments detected partial connection of the blood vessels between the vascular bed and cardiac cell sheets. Conclusions: We succeeded in engineering spontaneously beating 3D cardiac tissue in vitro using human cardiac cell sheets and a vascular bed derived from porcine small intestine. Further development of this method might allow the fabrication of functional cardiac tissue that could be used in the treatment of severe heart failure. Keywords: Cardiac cell sheet, Vascular bed, Perfusion culture, hiPSCs, Angiogenesis

This report presents a new hybrid lead extraction technique combined with transatrial laser lead extraction and surgical removal of calcified lesions in a 50-year-old man with superior vena cava syndrome and bilateral subclavian vein occlusion caused by an abandoned lead, which had been infected for 11 years. (Level of Difficulty: Intermediate.)

Concomitant heart failure is associated with poor clinical outcome in dialysis patients. The arteriovenous shunt, created as vascular access for hemodialysis, increases ventricular volume-overload, predisposing patients to developing cardiac dysfunction. The integral function of mitochondrial respiration is critically important for the heart to cope with hemodynamic overload. The involvement, however, of mitochondrial activity or reactive oxygen species (ROS) in the pathogenesis of ventricular-overload-induced heart failure has not been fully elucidated.We herein report that disorganization of mitochondrial respiration increases mitochondrial ROS production in the volume-overloaded heart, leading to ventricular dysfunction. We adopted the murine arteriovenous fistula (AVF) model, which replicates the cardinal features of volume-overload-induced ventricular dysfunction. Enzymatic assays of cardiac mitochondria revealed that the activities of citrate synthase and NADH-quinone reductase (complex Ⅰ) were preserved in the AVF heart. In contrast, the activity of NADH oxidase supercomplex was significantly compromised, resulting in elevated ROS production. Importantly, the antioxidant N-acetylcysteine prevented the development of ventricular dilatation and cardiac dysfunction, suggesting a pathogenic role for ROS in dialysis-related cardiomyopathy. A cardioprotective effect was also observed in metformin-treated mice, illuminating its potential use in the management of heart failure complicating diabetic patients on dialysis. Keywords: Heart failure, Volume-overload, ROS, N-acetylcysteine, Metformin

The case of a patient with left ventricular assist device (LVAD)-associated endocarditis involving multiple clones of Staphylococcus aureus is presented. Different clones with distinct colony morphology were identified from blood cultures collected on the same day and showed diverse antimicrobial resistance patterns. In addition, a difference in antimicrobial susceptibility was observed even within an identical clone recovered 400 days apart due to the loss of SCCmec for methicillin and modification of the 23S rRNA target site for linezolid during a long-term treatment course. Keywords: Staphylococcus aureus, Left ventricular assist device, Linezolid resistance, Endocarditis, Whole-genome sequencing

Abstract Background Continuous-flow left ventricular assist devices (LVADs) improve survival and morbidity in patients with stage D heart failure. Management of LVADs for longer durations is necessary in some clinical settings, and a better understanding of the hemodynamics of patients using LVADs is warranted. Arrhythmia, including atrial (AA) and ventricular (VAs) arrhythmias, is a modifying factor of hemodynamics that is highly prevalent among patients with LVADs. However, the clinical impact of arrhythmias in various clinical settings in patients with LVAD, in which the hemodynamic load is likely to present as worsening of right heart failure, remains to be completely elucidated. Case presentation We describe the case of a patient under sustained ventricular fibrillation for extraordinarily long duration who was stabilized using LVAD support and in whom newly developed atrial fibrillation led to a significant worsening of right heart failure while using an LVAD. Conclusion This case demonstrates the substantial clinical impact of AAs in the management of right heart failure using an LVAD.

BackgroundLittle evidence has been presented about the association between previous atopic/allergic disease and graft rejection after solid organ transplantation. Thus, we present a case wherein acute cellular rejection (ACR) after heart transplantation (HTx) was noted along with exacerbation of atopic disease.Case SummaryA 32-year-old man was admitted at our hospital for regular monitoring of graft rejection. He had undergone heart transplant 3 years prior due to dilated cardiomyopathy. Echocardiogram revealed good biventricular function, and no abnormal findings were found in blood sampling tests. However, biopsy showed moderate ACR [Grade 2R(ISHLT 2004)/3A(ISHLT 1990)], which required twice-repeated steroid pulses with intensified immunosuppression. Meanwhile, his atopic dermatitis, which was diagnosed before having heart failure, was getting worse for the past 6 months. The exacerbation of atopic dermatitis was presumed to be related to the development of the intractable cellular rejection.DiscussionThis case suggested the association of atopic disease and graft rejection after HTx. We examined 76 patients from a cohort of previous studies who underwent HTx at our hospital, which suggested that patients with atopic/allergic disorders such as atopic dermatitis and asthma tended to have a significantly higher frequency of moderate rejection than non-allergic patients. (p = 0.012; Fisher’s exact test). Our case also suggests that exacerbation of atopic dermatitis might cause graft rejection of the transplanted organ, so that it is important to carefully evaluate the risk of graft rejection if there is a previous history of atopic/allergic disease.

Mesenchymal stem cell (MSC) transplantation, in particular allogeneic transplantation, is a promising therapy for a variety of diseases. However, before performing allograft treatment it is necessary to find suitable donors, establish culture methods that maintain cell quality, and reduce cell production costs. Here, we present a new method of producing allogeneic MSCs combining human umbilical cord-derived mesenchymal stem cells (UCMSCs) and chitin-based polysaccharide fibers (Cellhesion® MS). UCMSC numbers significantly increased, and cells grew as dispersed spheres on Cellhesion® MS. Subsequent biological analyses showed that the expression levels of stemness-related and migration-related genes were significantly upregulated, including octamer-binding transcription factor 4 (OCT4), Nanog homeobox (NANOG), and C-X-C chemokine receptor type 4 (CXCR4). The secretion levels of paracrine factors such as prostaglandin E2 (PGE2), TNFα-stimulating gene (TSG)-6, fibroblast growth factor 2 (bFGF), and Angiogenin (Ang) from UCMSCs using Cellhesion® MS were significantly higher than with microcarrier and U-bottom plate culture. In addition, culture supernatant from UCMSCs with Cellhesion® MS had better angiogenic potential than that from monolayer cultured UCMSCs. Furthermore, we succeeded in a scaled-up culture of UCMSCs with Cellhesion® MS using a closed culture bag. Therefore, Cellhesion® MS is a key material for producing high-quality UCMSCs in a three-dimensional (3D) culture system.

Abstract Background Endoscopic submucosal dissection (ESD) can be used as a less invasive treatment option for superficial esophageal cancer involving the muscularis mucosae (T1a-MM) or upper third of the submucosa (T1b-SM1). Additional treatment after ESD is needed to prevent lymph node metastasis. However, the efficacy of radiotherapy following ESD has not been well evaluated. Moreover, the clinical outcomes of patients with large mucosal defects of the esophagus who received radiotherapy after ESD have not been reported. This study aimed to clarify the efficacy of additional radiotherapy following ESD for esophageal squamous cell cancer involving T1a-MM or T1b-SM1. Methods We analyzed twenty-seven patients with pathologically confirmed T1a-MM or T1b-SM1 esophageal squamous cell cancer treated by ESD. Thirteen patients received additional radiotherapy (RT group), and the remaining patients did not (non-RT group). Locoregional control (LRC), overall survival, cause-specific survival, and adverse events including treatment-related esophageal strictures were evaluated. Results The three-year LRC was significantly better for the RT than the non-RT group (100% vs. 57.8%, respectively; p = 0.022). Chemotherapy following ESD did not improve LRC. Multivariate analysis showed that radiotherapy was an independent prognostic factor for better LRC (p = 0.0022). Contrary to the results in LRC, overall and cause-specific survival were not significantly different between the RT and non-RT groups. A subgroup analysis of patients with mucosal defects involving ≥ 3/4 of the esophageal circumference after ESD showed that LRC of the RT group was better than that of the non-RT group (p = 0.049). Treatment-related esophageal strictures were observed in 2 of 6 patients in the RT group with large mucosal defects after ESD. No patients with mucosal defects involving less than 3/4 of the circumference after ESD developed treatment-related strictures. Conclusions Radiotherapy after ESD contributed to better LRC in esophageal squamous cell cancer involving pT1a-MM and pT1b-SM1. Esophageal strictures were observed in some patients with large mucosal defects after ESD. Despite leading to better LRC, radiotherapy after ESD should be undertaken after careful consideration for patients with large mucosal defects after ESD.

Abstract Background Fulminant myocarditis is a life-threatening disease, and myocardial damage expands the right ventricle as well as the left ventricle in some cases. There is a mortality rate of over 40% in patients with fulminant myocarditis who need mechanical circulatory support by peripheral venoarterial extracorporeal membrane oxygenation. Case presentation We report a case of a 27-year-old Japanese woman who was successfully bridged to recovery by using a biventricular assist device. She was diagnosed with fulminant myocarditis, and peripheral venoarterial extracorporeal membrane oxygenation was established on the same day. Her left ventricular ejection fraction rapidly decreased from 40% to 5% in 3 days and weaning from venoarterial extracorporeal membrane oxygenation was deemed difficult. Therefore, we performed a ventricular assist device implantation on day 4. A left ventricular assist device was implanted first. However, adequate blood flow did not circulate to the left side of her heart because of right-sided heart failure. Thus, an additional implant of a right ventricular assist device was performed during the operation. Her left ventricular ejection fraction recovered to 50% on day 10. The biventricular assist device was successfully removed on day 14. She has not experienced worsening of biventricular function during her follow-ups for 4 years. Conclusions Ventricular assist device therapy should be considered if there is no improvement in cardiac function in patients with fulminant myocarditis regardless of several days of support by venoarterial extracorporeal membrane oxygenation. A right ventricular assist device should always be implemented when necessary because biventricular involvement is not uncommon in fulminant myocarditis.