Novel Diagnostic and Therapeutic Approach to Antibody-Mediated Rejections in Heart Transplantation

Despite the improvement of immunosuppressive therapy in heart transplantation (HTx), antibody-mediated rejection (AMR) is still a great obstacle to prolong cardiac graft survival. Anti-donor-specific antibodies (DSAs), especially anti-donor human leukocyte antigen (HLA) antibody, lead to heart graft failure resulting in hemodynamic consequence and often in the recipient death. To prevent hyperacute rejection, prospective complement-dependent cytotoxicity test has been performed in every cardiac donor in Japan. But in other solid organ transplantations, flow cytometry crossmatch has been recently recommended to crossmatch to select the recipient in Japan as well as the world. However, flow cytometry is too sensitive to select the recipient, because not all DSAs determined by flow cytometry are cytotoxic to the cardiac graft. On the first complement classical pathway, alloantibodies bind to HLA antigens on cells of the graft and then recruit C1q, which is essential to make membrane attack complex and kill the cell. We review a role of the novel monitoring method of complement pathway regarding C1q in occurrence of AMR and its diagnostic and therapeutic significance in managing AMR in HTx

Ume (Japanese Apricot)-Induced Small Bowel Obstruction with Chronic Radiation Enteritis

Stricture formation is recognized as one of the complications of chronic radiation enteritis. Here, we present a case of a 73-year-old woman who presented with small bowel obstruction 16 years after pelvic irradiation for uterine cancer. Computed tomographic (CT) scan of the abdomen demonstrated a 1-cm foreign body in the terminal ileum. Laparotomy revealed a stone of ume (Japanese apricot) stuck in an ileal stricture, leading to complete impaction and perforation. She was successfully treated with ileocecal resection and ileocolic anastomosis without any complication. Pathological study revealed that the low compliance caused by fibrosis of the bowel wall prevented the small ume stone from passing through the irradiated ileum. Our case implies the specific risk of food-induced small bowel obstruction in patients with a history of pelvic irradiation

FOREVER22: the first bright galaxies with population III stars at redshifts z≃10−20z \simeq 10-20 and comparisons with JWST data

We study the formation of the first galaxies in overdense regions modelled by the FORmation and EVolution of galaxies in Extremely overdense Regions motivated by SSA22 (FOREVER22) simulation project. Our simulations successfully reproduce the star formation rates and the $M_{\rm UV}-M_{\rm star}$ relations of candidate galaxies at $z \sim 10-14$ observed by the James Webb Space Telescope (JWST). We suggest that the observed galaxies are hosted by dark-matter haloes with $M_{\rm h} \gtrsim 10^{10}~{\rm M_{\odot}}$ and are in short-period starburst phases. On the other hand, even simulated massive galaxies in overdense regions cannot reproduce the intense star formation rates and the large stellar masses of observed candidates at $z \sim 16$. Also, we show that the contribution of population III stars to the UV flux decreases as the stellar mass increases and it is a few percent for galaxies with $M_{\rm star} \sim 10^{7}~{\rm M_{\odot}}$. Therefore, a part of the observed flux by JWST could be the light from population III stars. Our simulations suggest that the UV flux can be dominated by population III stars and the UV-slope shows $\beta \lesssim -3$ if future observations would reach galaxies with $M_{\rm stars} \sim 10^{5}~{\rm M_{\odot}}$ at $z \sim 20$ of which the mass fraction of population III stars can be greater than 10 percent.Comment: 9 pages, 6 figures, accepted for publication in MNRA

Effect of scan length on densification and crystallographic texture formation of pure chromium fabricated by laser powder bed fusion

Processing of pure chromium (Cr) encounters substantial challenges due to its high melting point and intrinsic brittleness. Although laser powder bed fusion processing (LPBF) offers a novel processing approach by reaching the temperature required to melt pure Cr, the high ductile-to-brittle transformation temperature (DBTT) of pure Cr prevents the density of the as-built Cr component from reaching the level of industrial acceptance. This study focuses on raising the quality of the as-built pure Cr components to the industrial level while considering the effect of scan length on densification and crystallographic texture. It was found that short scan length induced by feature size improved the density of as-built specimens while strengthening the texture suggesting uniform heat distribution and lower thermal gradients as a result of short time intervals in scanning tracks and layers. It was discovered that cracking caused by residual stress was detrimental to densification due to the DBTT characteristic of pure Cr, which was localized at high-angle grain boundaries (HAGBs) with high misorientation. The decrease in density and misorientation of HAGBs owing to the increase in grain size and texture strength, respectively, improved the density of as-built Cr up to 97.6% and altered its mechanical properties. Therefore, these findings offer new insight into the LPBF processing of metals with high DBTT characteristics.Gokcekaya O., Ishimoto T., Todo T., et al. Effect of scan length on densification and crystallographic texture formation of pure chromium fabricated by laser powder bed fusion. Crystals, 11, 1, 1. https://doi.org/10.3390/cryst11010009

Diagnostic Intravascular Imaging Modalities for Cardiac Allograft Vasculopathy

Cardiac allograft vasculopathy (CAV) is one of the major factors limiting long-term survival after heart transplantation (HTX). Typically, concentric vascular thickening and fibrosis with marked intimal proliferation are found in CAV. Most of HTX patients often remain free from symptoms of typical angina. Therefore, surveillance diagnostic exams are often performed. The gold standard of diagnosing CAV is coronary angiography (CAG). However, CAG can often be a less sensitive modality for the detection of diffuse concentric lesions. Intravascular ultrasound (IVUS) is helpful for direct imaging of vessel walls and provides useful information about coronary intimal thickening; however, it is difficult to evaluate plaque morphology in detail. Optimal coherence tomography (OCT), which delivers high resolution of 10 μm, can provide more details on plaque morphology than conventional imaging modalities. Recently, OCT imaging revealed new insight in CAV such as the development of atherosclerotic lesions and complicated coronary lesions. We review the pathogenesis, clinical features, diagnosis of CAV, with a particular focus on diagnostic intravascular imaging modalities

Induction Therapy in the Current Immunosuppressive Therapy

The current immunosuppressive therapy including calcineurin inhibitors, mycophenolate mofetil, and steroids, has substantially suppress rejections and improved clinical outcomes in heart transplant (HTx) recipients. Nevertheless, the management of drug-related nephrotoxicity, fatal acute cellular rejection (ACR), antibody-mediated rejection and infections remains challenging. Although previous some studies suggested that perioperative induction immunosuppressive therapy may be effective for the suppressing ACR and deterioration of renal function, increased incidence of infection and malignancy was concerned in recipients with induction immunosuppressive therapy. The international society of heart and lung transplantation (ISHLT) guidelines for the care of heart transplant recipients do not recommend routine use of induction immunosuppressive therapy, except for the patients with high risk of acute rejection or renal dysfunction, however, appropriate therapeutic regimen and indication of induction immunosuppressive therapy remains unclear in HTx recipients. We review current evidence of induction immunosuppressive therapy in HTx recipients, and discuss the appropriate therapeutic regimen and indication of induction therapy

Effects of transcutaneous electrical nerve stimulation on physical symptoms in advanced cancer patients receiving palliative care

Transcutaneous electrical nerve stimulation (TENS) is primarily used for pain, butmight be useful for various other physical symptoms, including nausea, fatigue,dyspnea, and constipation. However, few studies have used TENS for treating thephysical symptoms of patients with advanced cancer. In this crossover trial, we assessthe effects of TENS on pain and other physical symptoms in 20 in-patients withadvanced cancer receiving palliative care. For 5-day phases between wash out periodsof 5 days, patients received TENS or non-TENS. TENS was delivered at four points: thecenter of the back for mainly nausea and dyspnea, on the back at the same dermatomallevel as the origin of the pain (100 Hz), and on both ankle joints for constipation (10Hz). The intensity of pain and the total opioid dose used during phases were recorded.Physical symptoms were evaluated using the European Organization for Research andTreatment of Cancer (EORTC) Quality of Life Questionnaire Core 15 Palliative Care(QLQ-C15-PAL). Hematological and biochemical data were recorded before and afterthe TENS phase. The average pain and total number of opioid rescue doses weresignificantly reduced by TENS. TENS tended to improve nausea and appetite loss, butnot constipation. There were no effects on hematological and biochemical parameters.Use of TENS could safely improve pain, nausea, and appetite loss in patients withadvanced cancer. Although it cannot be used as a substitute for opioids and otherpharmaceutical treatment, it may be useful to support palliative care