Multicentric Castleman disease (MCD) describes a heterogeneous group of disorders involving systemic inflammation, characteristic lymph node histopathology, and multi-organ dysfunction because of pathologic hypercytokinemia. Whereas Human Herpes Virus-8 (HHV-8) drives the hypercytokinemia in a cohort of immunocompromised patients, the etiology of HHV-8-negative MCD is idiopathic (iMCD). Recently, a limited series of iMCD cases in Japan sharing a constellation of clinical features, including thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O) has been described as TAFRO syndrome. Herein, we report clinicopathological findings on 25 patients (14 males and 11 females; 23 Japanese-born and two US-born), the largest TAFRO syndrome case series, including the first report of cases from the USA. The median age of onset was 50 years old (range: 23-72). The frequency of each feature was as follows: thrombocytopenia (21/25), anasarca (24/25), fever (21/25), organomegaly (25/25), and reticulin fibrosis (13/16). These patients frequently demonstrated abdominal pain, elevated serum alkaline phosphatase levels, and acute kidney failure. Surprisingly, none of the cases demonstrated marked hypergammoglobulinemia, which is frequently reported in iMCD. Lymph node biopsies revealed atrophic germinal centers with enlarged nuclei of endothelial cells and proliferation of endothelial venules in interfollicular zone. 23 of 25 cases were treated initially with corticosteroids; 12 patients responded poorly and required further therapy. Three patients died during the observation period (median: 9 months) because of disease progression or infections. TAFRO syndrome is a unique subtype of iMCD that demonstrates characteristic clinicopathological findings. Further study to clarify prognosis, pathophysiology, and appropriate treatment is needed.
For surgical treatment of the ruptured thoracic aortic aneurysm (TAA), it is important to control bleeding and to protect the brain, spinal cord, and myocardium. We have developed and performed a new procedure on 6 patients with a ruptured TAA, a true aneurysm in 3 patients and a type A dissection in the other 3.Cardiopulmonary bypass is installed with cannulations to the iliac artery and vein and to the common carotid arteries on both sides of the neck before the sternum is divided. For control of bleeding, venous drainage is accelerated, whereas cerebral perfusion is maintained via the carotid arteries. After insertion of the occlusion catheters into the descending aorta and the left subclavian artery following the aortotomy, the bypass flow to the iliac artery is increased.The arch replacement was performed in 4 patients and hemiarch replacement in two. Five patients are alive without neurologic deficits; one patient died of multi-organ failure on the 24th postoperative day.We conclude that our procedure may be advantageous for patients with a ruptured TAA, a large retrosternal aneurysm, or reoperation of the thoracic aorta.
The adoptive transfer of effector T cells combined with lymphodepletion has demonstrated promising antitumor effects in mice and humans, although the availability of tumor-specific T cells is limited. We and others have also demonstrated that the transfer of polyclonal naïve T cells induces tumor-specific effector T cells and enhances antitumor immunity after lymphodepletion. Because tumors have been demonstrated to induce immunosuppressive networks and regulate the function of T cells, obtaining a sufficient number of fully functional naïve T cells that are able to differentiate into tumor-specific effector T cells remains difficult. To establish culture methods to obtain a large number of polyclonal T cells that are capable of differentiating into tumor-specific effector T cells, naïve T cells were activated with anti-CD3 mAbs in vitro. These cells were stimulated with IL-2 and IL-7 for the CD8 subset or with IL-7 and IL-23 for the CD4 subset. Transfer of these hyperexpanded T cells after lymphodepletion showed significant antitumor efficacy, and tumor-specific effector T cells were primed from these expanded T cells in tumor-bearing hosts. Moreover, these ex vivo-expanded T cells maintained T cell receptor diversity and showed long-term persistence of memory against specific tumors. Further analyses revealed that combination therapy consisting of vaccination with dendritic cells that were co-cultured with irradiated whole tumor cells and the transfer of ex vivo-expanded T cells significantly enhanced antitumor immunity. These results indicate that the transfer of ex vivo-expanded polyclonal T cells can be combined with other immunotherapies and augment antitumor effects.
IntroductionThis study aimed to examine the factors associated with cytomegalovirus (CMV) antigenemia and the time of onset of CMV antigenemia among patients with rheumatic diseases.MethodsA single-center, retrospective, observational study was conducted in our institution from January 2009 to December 2017. This study included patients with rheumatic diseases who had at least one CMV antigen measurement. Multivariate analysis and receiver operating characteristic analysis was performed.ResultsA total of 249 patients underwent CMV antigenemia assay, and 84 (33.7%) patients tested positive. When the association between CMV antigenemia and possible associated factors was investigated, multivariate analysis showed that daily steroid dose increased the odds of having CMV [odds ratio 16.25, 95% confidence interval (CI), 5.360–49.253]. In this study, the cutoff value of daily steroid dose found in this study (0.45 mg/kg/day) was reasonable in clinical practice, and the area under the curve of the steroid dose was 0.838 [95% CI 0.781–0.882], which was the largest of the known indicators. Moreover, the median time from the start of immunosuppressive therapy to the onset of CMV antigenemia was 30 (interquartile range, 21–44) days, and most of the daily steroid users (85.7%) developed CMV antigenemia within 60 days.ConclusionsThe daily steroid dose is the most important factor associated with CMV antigenemia. Therefore, monitoring and treatment strategies based on the steroid dose, especially in the initial 2 months, are important.
Abstract Multicentric Castleman disease (MCD) is a heterogeneous lymphoproliferative disorder. It is characterized by inflammatory symptoms, and interleukin (IL)-6 contributes to the disease pathogenesis. Human herpesvirus 8 (HHV-8) often drives hypercytokinemia in MCD, although the etiology of HHV-8-negative MCD is idiopathic (iMCD). A distinct subtype of iMCD that shares a constellation of clinical features including thrombocytopenia (T), anasarca (A), fever (F), reticulin fibrosis (R), and organomegaly (O) has been reported as TAFRO-iMCD, however the differences in cytokine profiles between TAFRO-iMCD and iMCD have not been established. We retrospectively compared levels of serum interferon γ-induced protein 10 kDa (IP-10), platelet-derived growth factor (PDGF)-AA, interleukin (IL)-10, and other cytokines between 11 cases of TAFRO-iMCD, 6 cases of plasma cell type iMCD, and 21 healthy controls. During flare-ups, patients with TAFRO-iMCD had significantly higher serum IP-10 and tended to have lower PDGF-AA levels than the other 2 groups. In addition, serum IL-10, IL-23, and vascular endothelial growth factor-A were elevated in both TAFRO-iMCD and iMCD. Elevated serum IP-10 is associated with inflammatory diseases including infectious diseases. There was a strong correlation between high serum IP-10 and the presence of TAFRO-iMCD, suggesting that IP-10 might be involved in the pathogenesis of TAFRO-iMCD.
A 53-year-old man with an asymptomatic anterior mediastinal tumor undergoing hemodialysis was referred to our institution. He was diagnosed with thymic basaloid carcinoma based on the findings of a chest tomography-guided biopsy and successfully treated with carboplatin (300 mg/m2/day) and paclitaxel (200 mg/m2/day) on day 1 for six three-week cycles. To our knowledge, this is the first report regarding the efficiency of a carboplatin dose-definition method based on the body surface area with paclitaxel in a hemodialysis patient. This report may therefore be useful for treating hemodialysis patients who are candidates for carboplatin and paclitaxel therapy.
Background Each of the currently available (1→3)-β-D-glucan (BDG) measurement kits follows a different measurement method and cut-off value. Comparisons of diagnostic performance for invasive fungal infections (IFIs) are desirable. Additionally, ecological considerations are becoming increasingly important in the development of new measurement kits. Methods The plasma BDG levels in clinical samples were measured using the following currently available kits: the Fungitec G test MKII, the Fungitec G test ES, Fungitell, the β-Glucan test Wako, and the newly developed Wako kit (Wako-Eu). Wako-Eu uses a pre-treatment solution that conforms to European regulations for the registration, evaluation, authorisation, and restriction of chemicals. The values obtained for the samples using each kit were studied and compared. Results Of the 165 patients evaluated, 12 had IFIs, including pneumocystis pneumonia, aspergillosis, and candidiasis. BDG values obtained using the kits were moderately correlated with each other. Clinical diagnoses of the evaluated cases indicated that 21 false positives were diagnosed by at least one kit. The sensitivity of the Fungitell kit was relatively low, but those of the other four were over 90%. The specificity was above 90% for all kits. For positive predictive value, the Wako and the Wako-Eu methods were superior to the others owing to fewer false positive results. Conclusions The newly developed Wako-Eu method, which considers ecological concerns, shows diagnostic performance equivalent to that of its predecessor. To improve the diagnostic accuracy of IFIs, it is necessary to interpret the results carefully, giving due consideration to the characteristics of each measurement kit.
