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Objective In Japan, immunosuppressive therapy (IST) with anti-thymocyte globulin (ATG), and cyclosporine A (CsA) is the standard of care in patients with aplastic anemia (AA) who are not indicated for stem-cell transplantation, although some patients may experience relapse. This study assessed the efficacy and safety of eltrombopag in combination with rabbit-ATG/CsA in IST-naive patients with non-severe or severe AA in Japan. Methods In this non-randomized, open-label, single-arm, phase II study, rabbit-ATG/CsA and eltrombopag were initiated on Days 1 and 15 (±3 days), respectively, and continued for ≥26 weeks; rabbit-ATG was given for 5 days (Days 1 to 5). The primary endpoint was the overall response rate (ORR) at Week 26. Patients Patients with AA who were IST-naive and ≤70 years old or between 71 and 75 years old based on the recommendation of the investigator were enrolled in Japan. Results Of the 11 enrolled patients, 10 started treatment with eltrombopag. The ORRs at Weeks 26 and 52 were 70.0% and 60.0%, respectively. The ORR at Week 26 was 100% (all 3 patients) in patients with non-severe AA and 57.1% (4/7) in patients with severe AA. Among transfusion-dependent patients, 66.7% (4/6) and 62.5% (5/8) became red blood cell- and platelet-transfusion independent, respectively. The most common adverse events were nausea and headache. No deaths or hematologic malignancies were reported. A cytogenetic abnormality was reported in one patient. Conclusion This study confirmed the clinical benefit of eltrombopag plus rabbit-ATG/CsA in IST-naive patients with non-severe or severe AA in Japan.

The relapse of acute lymphoblastic leukemia (ALL) usually involves the bone marrow, with the central nervous system being the most frequent extramedullary site. The relapse of ALL in the female genital organs, particularly the uterus, is markedly rare. We report such a patient who developed relapse in the bone marrow and uterus. The uterine lesion, which presented as abnormal uterine bleeding, consisted of a mass on MRI and proliferation of ALL cells on histology. MRI revealed a heterogeneous high-intensity mass (T2-WI/D-WI) with a diameter of 6.8 cm, a notable decrease in the apparent diffusion coefficient (ADC), and mild enhancement by contrast enhancement study. Histological findings of the uterine cervix demonstrated the infiltration of ALL. The patient achieved remission by allogeneic haplo-identical hematopoietic stem-cell transplantation, but died of complications of the transplantation. This case suggested that attention should be paid to the uterus as a site of extramedullary relapse. In addition, abnormal uterine bleeding, which is a common sign of hormonal imbalance and hormone replacement therapy after chemotherapy, may be an initial sign of extramedullary recurrence. To confirm uterine relapse as an intractable disease, the accumulation of more cases is required.

We believe that our report and further case reports on T‐cell chronic lymphocytic leukemia with genetic profile will contribute to the molecular classification of this rare but distinct disease.

Mixed chimerism (MC) and/or secondary graft failure (SGF) with recipient- or donor-type chimerism is a major obstacle in allogeneic transplantation for aplastic anemia (AA). From a registry database in Japan, patients with AA age >15 years who underwent a first allogeneic bone marrow or peripheral blood stem cell transplantation between 2000 and 2014 and achieved engraftment were included in this study. MC that did not require either granulocyte-colony stimulating factor (G-CSF) or transfusion support (group 1), MC (not SGF) that required G-CSF and/or transfusion support (group 2), SGF with MC or complete recipient-type chimerism (group 3), and SGF with complete donor-type chimerism (group 4) developed in 26, 16, 19, and 17 patients, respectively. The overall median duration of follow-up for survivors was 1727 days. The overall survival (OS) was 90.4% at 1 year and 83.5% at 5 years in patients without MC or SGF (n = 340), which was not different from the OS in groups 1 and 2. However, inferior OS was observed in group 3 (1 year, 52.1%; 5 years, 52.1%) and group 4 (1 year, 82.4%; 5 years, 56.3%). In multivariate analyses, the use of fludarabine (Flu) and the absence of irradiation in conditioning were associated with the development of SGF with MC or complete recipient-type chimerism, and the use of Flu in conditioning was associated with SGF with complete donor-type chimerism. In conclusion, the use of Flu may affect the occurrence of SGF with both recipient-type and donor-type chimerism.

Aim: Ventricular fibrillation (VF) cardiac arrest may consist of three time-sensitive phases: electrical, circulatory, and metabolic. However, the time boundaries of these phases are unclear. We aimed to determine the time boundaries of the three-phase model for VF cardiac arrest. Methods: We reviewed 20,741 out-of-hospital cardiac arrest cases with initial VF and presumed cardiac origin from the All-Japan Utstein-style registry between 2013 and 2017. The study endpoint was 1-month neurologically intact survival. The collapse-to-shock interval was defined as the time from collapse to the first shock delivery by emergency medical service personnel. The patients were divided into the bystander cardiopulmonary resuscitation (CPR, n = 11,606) and non-bystander CPR (n = 9135) groups. Results: In the bystander CPR group, the collapse-to-shock times that were associated with increased adjusted 1-month neurologically intact survival, compared with those in the non-bystander CPR group, ranged from 7 min (42.9% [244/4999] vs. 26.0% [119/458], adjusted odds ratio [aOR], 1.95; 95% confidence interval [CI], 1.44–2.63; P 17 min onward.

Exophiala dermatitidis is a dematiaceous fungus that is increasingly becoming the cause of fungal infection in immunocompromised patients. However, the risk factors and optimal treatment modality for E. dermatitidis infection are unknown to date. Herein, we present a fatal case of E. dermatitidis infection in an adult patient that developed after allogeneic hematopoietic stem cell transplantation for chronic active Epstein-Barr virus infection. The dematiaceous fungus caused a breakthrough fungemia despite prophylactic administration of micafungin. Although the patient was intensively treated with liposomal-amphotericin B and voriconazole, serum level of beta-D-glucan continuously increased, and the patient eventually died because of cerebral hemorrhage. An autopsy found multiple involvements of the fungal infection at the bilateral lungs, thoracic cavities, diaphragm, and thyroid. To the best of our knowledge, this is the first reported case of E. dermatitidis infection involving these tissues as determined via autopsy. This case highlights the importance of attention for Exophiala infection in immunocompromised individuals in those given antifungal therapy with echinocandins.

Background Guidelines for cardiopulmonary resuscitation (CPR) recommend using the universal termination-of-resuscitation (TOR) rule to identify out-of-hospital cardiac arrest (OHCA) patients eligible for field termination of resuscitation, thus avoiding medically futile transportation to the hospital. However, in Japan, emergency medical services (EMS) personnel are forbidden from terminating CPR in the field and transport almost all patients with OHCA to hospitals. We aimed to develop and validate a novel TOR rule to identify patients eligible for field termination of CPR. Methods We analyzed 540,478 patients with OHCA from 2011 to 2015 using a Japanese registry. Main outcome measures were specificity and positive predictive value (PPV) of the newly developed TOR rule in predicting 1-month mortality after OHCA. Results Recursive partitioning analysis in the development group (n = 434,208) showed that EMS personnel could consider TOR if patients with OHCA met all of the following five criteria: (1) initial asystole, (2) arrest unwitnessed by a bystander, (3) age ≥81 years, (4) no bystander-administered CPR or automated external defibrillator use before EMS arrival, and (5) no return of spontaneous circulation after EMS-initiated CPR for 14 min. For patients meeting these criteria, specificity and PPV for predicting 1-month mortality were 99.2% [95% confidence interval (CI), 99.0–99.3%] and 99.7% (95% CI, 99.6–99.7%), respectively, for the development group and were 99.5% (95% CI, 99.3–99.7%) and 99.8% (95% CI, 99.7–99.9%), respectively, for the validation group. Implementation of this novel rule would reduce patient transports to hospitals by 10.6% in the development group and 10.4% in the validation group. Conclusions Having both high specificity and PPV of >99% for predicting 1-month mortality, our developed TOR rule may be applied in the field for Japanese patients with OHCA who meet all five criteria. Prospective validation studies and establishment of prehospital EMS protocol are required before implementing this rule.

Post-transplant lymphoproliferative disorder (PTLD) is a life-threatening complication of transplantation. In addition to reactivation of Epstein–Barr virus in immunocompromised patients, impaired tumor immunity is suggested to be a risk factor for PTLD. However, it remains unclear whether immune suppressive tumor-infiltrating lymphocytes (TILs) correlate with the occurrence or prognosis of PTLD. We analyzed TILs in 26 patients with PTLD to elucidate the clinicopathological significance of the expression of PD-1 and FoxP3, which are associated with exhausted T-cells and regulatory T-cells (Tregs), respectively. Numbers of PD-1+ TILs in the PTLD specimens were significantly higher in patients who developed PTLD early after transplantation (P = 0.0040), while numbers of FoxP3+ TILs were not (P = 0.184). There was no difference in overall response rate regardless of the expression of PD-1 or FoxP3. FoxP3high patients tended to have a shorter time to progression compared with FoxP3low patients, especially in the case of FoxP3high patients with diffuse large B-cell lymphoma-subtype PTLD (P = 0.011), while PD-1high patients did not. These results suggest that T-cell exhaustion may be mainly associated with PTLD development, while immune suppression by Tregs may be dominant in enhanced progression of PTLD following disease occurrence.

It remains unclear how specific innovations in allogeneic hematopoietic cell transplantation (HCT) attained over the past decades have contributed to improvement in transplantation outcomes. To address this question, we conducted a registry-based study of adults with acute myeloid leukemia in first or second complete remission who underwent allogeneic HCT between 1994 and 2013 from a sibling (N = 1600) or unrelated (N = 2113) donor matched at the antigen level for HLA-A, -B, and -DR. Preliminary analysis led us to focus on comparisons between the 1994–2006 and 2007–2013 periods. Significant improvement in survival was observed in the later cohort compared to the earlier cohort for unrelated HCT (P = 0.004), but not for related HCT (P = 0.767). The improvement in unrelated HCT was solely due to diminished non-relapse mortality (P = 0.001), while incidence of relapse did not change over time (P = 0.934). The percentage of patients receiving transplants from 8/8-matched unrelated donors was significantly higher in the later cohort (P

The quality of acute aortic syndrome (AAS) assessment by emergency medical service (EMS) and the incidence and prehospital factors associated with 1-month survival remain unclear.We retrospectively analyzed the data collected for 94,468 patients with non-traumatic medical emergency excluding out-of-hospital cardiac arrest during the period of 2011-2014.Of these transported by EMS, 22,075 had any of the AAS-related symptoms, and 330 had an EMS-assessed risk for AAS; of these, 195 received an in-hospital AAS diagnosis. Of the remaining 21,745 patients without EMS-assessed risk, 166 were diagnosed with AAS. Therefore, the sensitivity and specificity of our EMS-risk assessment for AAS was 54.0% (195/361) and 99.4% (21,579/21,714), respectively. EMS assessed the risk less frequently when patients were elderly and presented with dyspnea and syncope/faintness. Sign of upper extremity ischemia was rarely detected (6.9%) and absence of this sign was associated with lack of EMS-assessed risk. The calculation of modified aortic dissection detection risk score revealed that rigorous assessment based on this score may increase the EMS sensitivity for AAS. The 1-month survival rate was significantly higher in patients admitted to core hospitals with surgical teams for AAS than in those admitted to all other hospitals [87.5% (210/240) vs 69.4% (84/121); P0.01]. Multiple logistic regression analysis demonstrated that Stanford type A, Glasgow coma scale ≤14, and admission to core hospitals providing emergency cardiovascular surgery were associated with 1-month survival.Improvement of AAS survival is likely to be affected by rapid admission to appropriate hospitals providing cardiovascular surgery.

Introduction: Placenta previa (PP) is one of the most significant risk factors for adherent placenta (AP). The aim of this study was to evaluate the diagnostic efficacy of a novel scoring system for predicting AP in pregnant women with PP. Methods: This prospective cohort study enrolled 175 women with PP. The placenta previa with adherent placenta score (PPAP score) is composed of 2 categories: (1) past history of cesarean section (CS), surgical abortion, and/or uterine surgery; and (2) ultrasonography and magnetic resonance imaging findings. Each category is graded as 0, 1, 2, or 4 points, yielding a total score between 0 and 24. When women with PP had PPAP score ≥8, they were considered to be at a high risk for AP and received placement of preoperative internal iliac artery occlusion balloon catheters. If they were found to have AP during CS, they underwent hysterectomy or placenta removal using advanced bipolar with balloon catheter occlusion. The predictive accuracy of PPAP score was evaluated. Results: In total, 23 of the 175 women with PP were diagnosed as having AP, histopathologically or clinically. Twenty-one of 24 women with PPAP score ≥8 had AP, whereas two of 151 women with PPAP score

Background The Glasgow prognostic score (GPS) has been reported as a sensitive prognostic marker for gastric cancer. This study aimed to investigate whether the GPS is equally applicable to patients with early-stage and advanced-stage gastric cancers. Methods Patients (n = 544) who underwent elective gastrectomy for gastric cancer between 2007 and 2015 were retrospectively studied. GPSs of 2, 1, and 0 were allocated to patients with both an elevated C-reactive protein level (> 1.0 mg/dL) and hypoalbuminemia (< 3.5 mg/dL), patients with only one of these abnormalities, and patients with neither abnormality, respectively. The prognostic factors relevant to patients with early-stage (pStage I, n = 304) and advanced-stage (pStage II, III, and IV, n = 240) gastric cancer were analyzed through univariate and multivariate analyses. Results In the early-stage group, only the serum carbohydrate antigen (CA) 19-9 level (P = 0.037) was a significant prognostic factor in the multivariate analysis; the GPS was not significant (P = 0.095). In the advanced-stage group, an American Society of Anesthesiologists physical status of 3 or 4 (P = 0.032), elevated carcinoembryonic antigen (CEA) (P = 0.043) and CA19-9 (P = 0.045) levels, a GPS 1 - 2 (P = 0.017), and type 4 tumor (P = 0.020) correlated significantly with worse overall survival. Conclusions GPS is a simple and useful prognostic score for patients with advanced-stage, but is not applicable to early-stage patients.

Aim: Among patients with paediatric out-of-hospital cardiac arrests (OHCAs), most have an initial non-shockable rhythm with poor outcomes. There is a subset who developed shockable rhythms. This study aimed to investigate the association between subsequent shock delivery and outcomes after paediatric OHCAs. Methods: We analysed records of 19,095 children (aged

Objectives: This study aimed to investigate the validity of gastric cancer surgery in elderly patients. Methods: A total of 544 patients who underwent elective gastrectomy for gastric cancer were divided into an elderly group (age ≥75 years, n = 171) and a control group (age n = 373). The clinicopathological data of the patients were reviewed. Results: The overall morbidity rate (26.3 vs. 16.1%, p = 0.005) and the incidence rate of anastomotic leakage (6.4 vs. 1.6%, p = 0.003) were significantly higher in the elderly group. The proportion of patients who had severe complications (≥grade IIIa) was relatively higher in the elderly group (10.5 vs. 5.7%); however, the difference was not significant (p = 0.074). A stage-matched survival analysis revealed no significant differences between the groups (stage I: p = 0.978; stage II: p = 0.964; stage III: p = 0.199). For the pathological stages II and III, the overall survival of the patients in the elderly group who received adjuvant chemotherapy for >3 months was significantly better than that of the patients who received it for ≤3 months or did not receive it (p = 0.023). Conclusions: An aggressive treatment strategy should be adopted in selected elderly patients with gastric cancer.

A 57-year-old female patient on hemodialysis with chronic renal failure due to chronic glomerular nephritis received deceased donor kidney transplantation. Induction immunosuppressive therapy was combination of tacrolimus, mycophenolate mofetil, everolimus, prednisolone, and basiliximab. She was diagnosed with secondary thrombotic microangiopathy (TMA) by clinical findings such as hemolytic anemia, thrombocytopenia and acute kidney injury not by pathological findings on the 4th post-operative date. Plasma exchange was performed with suspension of tacrolimus. General conditions recovered, and the graft function was preserved.

Background Bronchiolitis obliterans syndrome (BOS) is the term used for the progressive obliteration of small airways before the patient has had a confirmatory lung biopsy. It is also recognized as a transplant-related complication. There have been no reports of BOS during initial standard chemotherapy. Case presentation A 50-year-old woman with newly diagnosed follicular lymphoma grade 2, stage 3A, presented with hypoxia and progressive dyspnoea after the fifth cycle of R-CHOP. High-resolution computed tomography showed air trapping enhanced at the end-expiratory phase. Pulmonary function testing revealed severe obstructive and restrictive failure without bronchodilator response. We diagnosed BOS based on current criteria and treated the patient with glucocorticoids and cyclosporin. She was discharged home on oxygen therapy. However, soon after discharge, her respiratory symptoms deteriorated and she was hospitalized in a palliative care unit. She died of respiratory failure within a year of symptom onset. Conclusions This is the first case report to describe rapidly progressive BOS in a patient undergoing R-CHOP treatment, which strongly suggests the condition was caused by the chemotherapy. Although a pathological diagnosis was not obtained, the clinical diagnosis of BOS was important so that the patient could receive appropriate treatment and palliative care based on the prognosis of this incurable condition. Learning points R-CHOP chemotherapy may cause rapidly progressive bronchiolitis obliterans syndrome (BOS).When it is difficult to obtain a pathological diagnosis, a clinical diagnosis of BOS is important for early intervention and appropriate palliative care.

Various central nervous system (CNS) complications may occur after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which can result in severe clinical problems. Diagnosis is often difficult, as distinctive clinical symptoms may be absent and different neurological disorders may exhibit similar symptoms. Despite the fact that antibodies responding to brain cell surface antigens have become well recognized in several CNS disorders, cases of autoimmune CNS disorders after allo-HSCT have rarely been reported. Here, we report on a patient who developed encephalitis associated with antibodies against N-methyl-D-aspartate (NMDA)-type glutamate receptor (GluR) after allo-HSCT. To the best of our knowledge, this is the first report of the involvement of antibodies against NMDA-type GluR in post-transplantation encephalitis. Autoimmunity to NMDA-type GluR may have contributed to neurological complications after transplantation in unresolved cases.

Aggregation of monoclonal immunoglobulin can lead to organ damage. However, the necessity of invasive examination such as biopsy has hampered better understanding of the pathophysiology. Corneal crystalline deposition is a rarely reported but known ocular manifestation of multiple myeloma. It is unclear whether the cornea is a common target of monoclonal immunoglobulin deposition. We conducted a prospective clinical case-control study to objectively quantify monoclonal gammopathy-associated corneal changes as well as any therapeutic response. Using an ophthalmic Scheimpflug camera imaging for noninvasive corneal assessments, we quantified densitometry values in 30 patients. Although none had crystalline keratopathy, corneal transparency in monoclonal gammopathy patients was significantly impaired compared to that in age-matched controls, based on noninvasive Scheimpflug camera imaging. Furthermore, treatment for multiple myeloma seemed to eradicate the diffuse aggregation of monoclonal proteins. Our results indicate that exposure to monoclonal immunoglobulin may induce the accumulation of monoclonal immunoglobulin in the cornea, and ophthalmic examinations such as corneal densitometry measurements with a Scheimpflug camera may be useful for noninvasive evaluation of monoclonal immunoglobulin deposition diseases.

Purpose To investigate the impacts of emergency calls made using mobile phones on the quality of dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) and survival from out-of-hospital cardiac arrests (OHCAs) that were not witnessed by emergency medical service (EMS). Methods In this prospective study, we collected data for 2530 DA-CPR-attempted medical emergency cases (517 using mobile phones and 2013 using landline phones) and 2980 non-EMS-witnessed OHCAs (600 using mobile phones and 2380 using landline phones). Time factors and quality of DA-CPR, backgrounds of callers and outcomes of OHCAs were compared between mobile and landline phone groups. Results Emergency calls are much more frequently placed beside the arrest victim in mobile phone group (52.7% vs. 17.2%). The positive predictive value and acceptance rate of DA-CPR in mobile phone group (84.7% and 80.6%, respectively) were significantly higher than those in landline group (79.2% and 70.9%). The proportion of good-quality bystander CPR in mobile phone group was significantly higher than that in landline group (53.5% vs. 45.0%). When analysed for all non-EMS-witnessed OHCAs, rates of 1-month survival and 1-year neurologically favourable survival in mobile phone group (7.8% and 3.5%, respectively) were higher than those in landline phone group (4.6% and 1.9%; p, Embargo Period 12 months

To compare the factors associated with survival after out-of-hospital cardiac arrests (OHCAs) among three time-distance areas (defined as interquartile range of time for emergency medical services response to patient's side).From a nationwide, prospectively collected data on 716,608 OHCAs between 2007 and 2012, this study analyzed 193,914 bystander-witnessed OHCAs without pre-hospital physician involvement.Overall neurologically favourable 1-month survival rates were 7.4%, 4.1% and 1.7% for close, intermediate and remote areas, respectively. We classified BCPR by type (compression-only vs. conventional) and by dispatcher-assisted CPR (DA-CPR) (with vs. without); the effects on time-distance area survival were analyzed by BCPR classification. Association of each BCPR classification with survival was affected by time-distance area and arrest aetiology (p0.05). The survival rates in the remote area were much higher with conventional BCPR than with compression-only BCPR (odds ratio; 95% confidence interval, 1.26; 1.05-1.51) and with BCPR without DA-CPR than with BCPR with DA-CPR (1.54; 1.29-1.82). Accordingly, we classified BCPR into five groups (no BCPR, compression-only with DA-CPR, conventional with DA-CPR, compression-only without DA-CPR, and conventional without DA-CPR) and analyzed for associations with survival, both cardiac and non-cardiac related, in each time-distance area by multivariate logistic regression analysis. In the remote area, conventional BCPR without DA-CPR significantly improved survival after OHCAs of cardiac aetiology, compared with all the other BCPR groups. Other correctable factors associated with survival were short collapse-to-call and call-to-first CPR intervals.Every effort to recruit trained citizens initiating conventional BCPR should be made in remote time-distance areas.

Late-onset noninfectious pulmonary complication after allogenic hematopoietic stem cell transplantation is an important contributing factor associated with high rate morbidity and mortality. We report a case with pleuroparenchymal fibroelastosis (PPFE) occurred after allogenic bone marrow transplantation. The onset was infiltrative shadows in upper lobes, and the haziness spread gradually throughout the lungs with recurrent episodes of pneumothorax in both lungs. Progressive respiratory failure in course of adrenocortical steroid administration eventually caused death. Histological examination in general autopsy showed patchy subpleural fibrosis predominantly distributed in the upper lobes with substantial density rise of elastic fibers in the subpleural area, consistent with the diagnosis of PPFE. PPFE after allogenic transplantation has been seldom reported to date, but it is one of the most important histological components of late-onset noninfectious pulmonary complication after allogenic transplantation characterized by recurrent pneumothorax. Retrospective analysis in our case indicates early diagnosis may be possible by histological evaluation of elastic fibers in lung specimen when pneumothorax is treated surgically. This case suspects that it is important for hematologist and pathologist to aware this progressive disease along with information of histological characteristics, therefore, leading to the establishment of therapeutic strategies and the improvement of poor prognosis.

PURPOSE To evaluate the interobserver variability and diagnostic performance of a developed magnetic resonance imaging (MRI)-based scoring system for invasive placenta previa. MATERIALS AND METHODS Prenatal MR images of 70 women were retrospectively evaluated, 18 of whom were diagnosed with invasive placenta. The six MR features (dark band on T2 -weighted images, intraplacental abnormal vascularity, placental bulge, heterogeneous placenta, myometrial thinning, and placental protrusion sign) were scored on 5-point Likert scale separately, and the cumulative radiological score (CRS) was defined as the sum of each score. Two more experienced radiologists (readers A and B) and two less experienced residents (readers C and D) calculated the CRS. Interobserver variability was assessed by measuring the intraclass correlation coefficient. Diagnostic performance was evaluated by means of receiver operating characteristic (ROC) analysis. RESULTS Interobserver variability for CRS was excellent for the more experienced radiologists (0.85), and good for all readers (0.72) and the less experienced residents (0.66). The area under the ROC curve (Az) and accuracy (Acc) for CRS were significantly higher or equivalent to those of other MR features for all readers (Az and Acc for reader A; CRS, 0.92, 91.4%; intraplacental T2 dark band, 0.83, P = 0.009, 81.4%, P = 0.03; intraplacental abnormal vascularity, 0.9, P = 0.3, 90.0%, P = 1.00; placental bulge, 0.81, P = 0.0008, 80.0%, P = 0.02; heterogeneous placenta, 0.85, P = 0.11, 74.3%, P = 0.002; myometrial thinning, 0.84, P = 0.06, 60.0%, P < 0.0001; placental protrusion sign, 0.81, P = 0.01, 81.4%, P = 0.26). CONCLUSION This developed MRI-based scoring system demonstrated excellent or good interobserver variability, and good diagnostic performance for invasive placenta previa. J. Magn. Reson. Imaging 2016;44:573-583.

We analyzed data from 64,539 consecutive patients in the Japanese national transplant registry, including 40,195 after allogeneic hematopoietic stem cell transplantation (HSCT), 24,215 after autologous HSCT and 129 after syngeneic HSCT, of whom 299 developed Epstein-Barr virus-positive post-transplant lymphoproliferative disorder (PTLD). The probability of developing PTLD at 2 years post-HSCT was .79% after allogeneic transplantation, .78% after syngeneic transplantation, and .11% after autologous transplantation. The following variables were identified as risk factors after allogeneic HSCT in multivariate analysis: antithymocyte globulin (ATG) use in a conditioning regimen, ATG use for acute graft-versus-host disease (GVHD) treatment, donor other than an HLA-matched related donor, aplastic anemia, second or subsequent allogeneic HSCT, the most recent year of transplantation, and acute GVHD. The probability at 2 years increased particularly after 2009 (1.24%) than before 2009 (.45%). To stratify the risk of PTLD before allogeneic HSCT, we developed a novel 5-point scoring system based on 3 pretransplant risk factors: ATG use in a conditioning regimen (high dose, 2 points; low dose, 1 point), donor type (HLA-mismatched related donor, 1 point; unrelated donor, 1 point; cord blood, 2 points), and aplastic anemia (1 point). Patients were classified into 4 risk groups according to the summed points: low risk (0 or 1 point), intermediate risk (2 points), high risk (3 points), and very high risk (4 or 5 points) groups, with probabilities at 2 years of .3%, 1.3%, 4.6%, and 11.5%, respectively. Our scoring system is useful for predicting patients at high risk for PTLD. Careful observation and close monitoring of Epstein-Barr virus reactivation are warranted for these high-risk patients.

Objectives: This study aimed to investigate the validity of laparoscopic gastric cancer surgery in elderly patients. Methods: A total of 202 patients who underwent laparoscopic gastrectomy for gastric cancer between January 2007 and December 2016 were divided into an elderly group (age ≥75 years, n = 36) and a control group (age < 75 years, n = 166). The patients’ clinicopathological data were reviewed. Results: The overall morbidity rate was relatively higher in the elderly group (16.7 vs. 11.4%, p = 0.389), whereas the incidence of serious complications ≥grade III according to the Clavien-Dindo classification did not increase significantly in the elderly group (8.3 vs. 7.8%, p = 0.920). Univariate and multivariate analyses revealed that age ≥75 years was not a significant predictive factor of postoperative morbidity (p = 0.568). There was no significant difference in the 5-year overall survival rate of patients with pathological stage I gastric cancer between the groups (97.1 vs. 96.1%, p = 0.704; hazard ratio, 0.669; 95% confidence interval, 0.036–3.692). Conclusions: Laparoscopic gastrectomy has an acceptable morbidity rate in elderly patients, and the long-term outcome of patients with stage I gastric cancer was similar to that of the control group.

Background The diagnosis of granulomatous amoebic encephalitis is challenging for clinicians because it is a rare and lethal disease. Previous reports have indicated that Acanthamoeba with some specific genotypes tend to cause the majority of human infections. We report a case of granulomatous amoebic encephalitis caused by Acanthamoeba spp. with genotype T18 in an immunodeficient patient in Japan after allogenic bone marrow transplantation, along with the morphological characteristics and genetic analysis. Case presentation A 52-year old man, who had undergone allogenic bone marrow transplantation, suffered from rapid-growing brain masses in addition to pneumonia and died within 1 month from the onset of the symptoms including fever, headache and disorientation. Infection with Acanthamoeba in the brain and lung was confirmed by histological evaluation; immunohistochemical staining and polymerase chain reaction analysis using autopsy samples also indicated the growth of Acanthamoeba in the brain. Gene sequence analysis indicated that this is the second documented case of infection with Acanthamoeba spp. with genotype T18 in a human host. Postmortem retrospective evaluation of cerebrospinal fluid sample in our case, as well as literature review, indicated that some cases of granulomatous amoebic encephalitis caused by Acanthamoeba may be diagnosable by cerebrospinal fluid examination. Conclusion This case indicates that Acanthamoeba spp. with genotype T18 can also be an important opportunistic pathogen. For pathologists as well as physicians, increased awareness of granulomatous amoebic encephalitis is important for improving the poor prognosis along with the attempt to early diagnosis with cerebrospinal fluid.

Staphylococcus aureus as a pathogen in human gestational membranes, a rather rare phenomenon, has recently been the focus of several researches. S. aureus forms biofilms on these membranes and potentially causes chorioamnionitis in pregnant women. We report a case of persistent methicillin-resistant S. aureus (MRSA) bacteremia owing to placental infection, causing chorioamnionitis and preterm birth. A 29-year-old Japanese woman at the 27th gestational week was diagnosed with acute promyelocytic leukemia and underwent all-trans retinoic acid therapy. Soon after hospitalization, the patient presented with persistent MRSA bacteremia of unknown origin. Despite various antimicrobial therapies, she experienced 12 MRSA bacteremia episodes over 6 weeks. However, after child birth, MRSA bacteremia disappeared without any complications. A pathologic examination of her placenta revealed placenta abscess, resulting in a diagnosis of MRSA-associated chorioamnionitis. Molecular analysis proved that a single MRSA strain (SCCmec Type IVa), which tested negative for Panton-Valentine leukocidin and toxic shock syndrome toxin-1, caused the obstinate infection. We should be aware that persistent MRSA bacteremia in pregnant women can originate from placental abscess.

Background Elderly patients have a high risk of adverse outcomes after surgery. Therefore, it is essential to determine the predictive factors for postoperative morbidity in elderly patients undergoing gastric cancer surgery. Methods A total of 544 patients who underwent elective gastrectomy for gastric cancer at Yodogawa Christian Hospital between January 2007 and December 2015 were divided into the elderly group (age ≥70 years, n=282) and a control group (age

Thrombocytopenia during pregnancy has many different causes, but Mycoplasma pneumoniae is not usually considered one of the several pathogens that induce thrombocytopenia. Herein, we present a case of severe thrombocytopenia that was associated with M. pneumoniae during pregnancy. The patient experienced fever, cough, and cytopenia with M. pneumoniae-specific IgM antibody increasing from 40-fold to 160-fold during the 2 weeks of illness. A diagnosis was made after excluding other diseases that cause thrombocytopenia. The patient was successfully treated with azithromycin hydrate, and she delivered a healthy newborn without any complications. Pregnant women who are infected with M. pneumoniae during pregnancy may develop severe and fatal thrombocytopenia. Prompt diagnosis and initiation of treatment lead to early recovery.

Allogeneic hematopoietic stem cell transplantation (HSCT) has largely improved the prognosis of leukemia patients. However, relapse is still a major concern. One promising option for the prevention of relapse is vaccination therapy. The post allogeneic HSCT period provides a unique platform for vaccination, because tumor burden is minimal, lymphopenic condition allows for rapid expansion of cytotoxic T cells (CTLs), donor-derived CTLs are not exhausted and inflammatory condition is caused by allo reactions. Tumor cells, dendritic cells and peptides have been used as vaccines targeting leukemia-associated antigens or minor histocompatibility antigens. Clinical trials with several types of vaccines for post-HSCT patients showed that the vaccination induced immunological response and might benefit patients with minimal residual disease, while their effect in patients with advanced disease were limited. To enhance the effect, vaccination in combination with other immune-modulatory drugs such as checkpoint antibodies is now being considered.

Purpose To investigate the fusion of pelvic magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (PET) for assessment of locoregional extension and nodal staging of cervical cancer. Methods PET/computed tomography (CT), MRI, and non-fused and fusion of PET and MRI for assessing the extent of the primary tumor and metastasis to nodes were evaluated. Results Accuracy for T-status was 83.3% for fused and non-fused PET/MRI and MRI proved significantly more accurate than PET/CT (53.3%) ( P =.0077). Sensitivity, specificity, and accuracy for nodal metastasis were 92.3%, 88.2%, and 90.0% for fused PET/MRI and PET/contrast-enhanced CT; 84.6%, 94.1%, and 90.0% for non-fused PET/MRI; and 69.2%, 100%, and 86.7% for MRI. Conclusion Fused PET/MRI combines the individual advantages of MRI and PET.

Although the prognosis of leukemia patients after allogeneic hematopoietic stem cell transplantation (HSCT) has greatly improved, relapse is still a major cause of death after HSCT. Cancer vaccines may have the potential to enhance the graft-versus-leukemia (GVL) effect. The post-allogeneic HSCT period provides a unique platform for vaccination, because (I) tumor burden is minimal, (II) lymphopenia allows for rapid expansion of cytotoxic T cells (CTLs), (III) donor-derived CTLs are not exhausted, (IV) inflammation is caused by alloreactions, and (V) the abundance of regulatory T cells is low due to their late recovery. Tumor cell lysates, dendritic cells (DCs), and peptides derived from leukemia-associated antigens (LAAs) have been used as vaccines. Clinical trials with several types of vaccines for post-HSCT patients revealed that the vaccination induced an immunological response and might benefit patients with minimal residual disease; however, the efficacy of this approach must be examined in randomized studies. In addition, it is important to consider the combination of cancer vaccine with checkpoint antibodies, recently shown to be useful in treating leukemia relapse after HSCT.

We report the case of a 44-year-old woman with Masaoka stage IV, World Health Organization type B1 thymoma associated with pure red cell aplasia, thrombocytopenia, and myasthenia gravis, which occurred during preoperative chemotherapy with high-dose methylprednisolone. Noninvasive positive-pressure ventilation, intravenous immunoglobulin infusion, and methylprednisolone pulse therapy were performed for the myasthenic crisis. Disseminated thymoma was markedly reduced after these treatments, and macroscopic complete resection was performed after achieving control of pure red cell aplasia, myasthenia gravis, and thrombocytopenia using cyclosporine A. Chemotherapy, including high-dose methylprednisolone, may carry a risk of myasthenic crisis, although the regimen is effective against lymphocyte-rich thymoma.

Purpose To investigate the diagnostic value of retrospective fusion of pelvic MRI and 18F-fluorodeoxyglucose (18F-FDG) PET images for assessment of locoregional extension and nodal staging of endometrial cancer. Materials and methods Thirty patients with biopsy-proven endometrial cancer underwent preoperative contrast-enhanced PET/CT (PET/ceCT) and pelvic dynamic contrast-enhanced MRI for initial staging. Diagnostic performance of PET/ceCT, contrast-enhanced MRI, and retrospective image fusion from PET and MRI (fused PET/MRI) for assessing the extent of the primary tumor (T stage) and metastasis to regional LNs (N stage) was evaluated by two experienced readers. Histopathological and follow-up imaging results were used as the gold standard. The McNemar test was employed for statistical analysis. Results Fused PET/MRI and MRI detected 96.7% of the primary tumors, whereas PET/ceCT detected 93.3%. Accuracy for T status was 80.0% for fused PET/MRI, and MRI proved significantly more accurate than PET/ceCT, which had an accuracy of 60.0% (p = 0.041). Patient-based sensitivity, specificity and accuracy for detecting pelvic nodal metastasis were 100%, 96.3% and 96.7% for both fused PET/MRI and PET/ceCT, and 66.7%, 100% and 96.7% for MRI, respectively. These three parameters were not statistically significant (p = 1). Conclusion Fused PET/MRI, which complements the individual advantages of MRI and PET, is a valuable technique for assessment of the primary tumor and nodal staging in patients with endometrial cancer.

Review: An increased number of rescuers may improve the survival rate from out-of-hospital cardiac arrests (OHCAs). The majority of OHCAs occur at home and are handled by family members. Materials and methods: Data from 5078 OHCAs that were witnessed by citizens and unwitnessed by citizens or emergency medical technicians from January 2004 to March 2010 were prospectively collected. The number of rescuers was identified in 4338 OHCAs and was classified into two (single rescuer (N = 2468) and multiple rescuers (N = 1870)) or three (single rescuer, two rescuers (N = 887) and three or more rescuers (N = 983)) groups. The backgrounds, characteristics and outcomes of OHCAs were compared between the two groups and among the three groups. Results: When all OHCAs were collectively analysed, an increased number of rescuers was associated with better outcomes (one-year survival and one-year survival with favourable neurological outcomes were 3.1% and 1.9% for single rescuers, 4.1% and 2.0% for two rescuers, and 6.0% and 4.6% for three or more rescuers, respectively (p = 0.0006 and p < 0.0001)). A multiple logistic regression analysis showed that the presence of multiple rescuers is an independent factor that is associated with one-year survival (odds ratio (95% confidence interval): 1.539 (1.088-2.183)). When only OHCAs that occurred at home were analysed (N = 2902), the OHCAs that were handled by multiple rescuers were associated with higher incidences of bystander CPR but were not associated with better outcomes. Conclusions: In summary, an increased number of rescuers improves the outcomes of OHCAs. However, this beneficial effect is absent in OHCAs that occur at home. © 2012 Elsevier Ireland Ltd. All rights reserved.

A 73-year-old male was admitted to our institution with complaints of nausea, vomiting, and abdominal distension. Plain abdominal computed tomography (CT) suggested intussusception in the jejunum. Enhanced abdominal CT revealed the 'target-like' sign and ultrasonography revealed the 'multiple concentric ring' sign; therefore, a diagnosis of entero-enteric intussusception was made. The small intestinal obstruction and cause of the intussusception were not evident. The patient was treated conservatively with fasting and transfusion therapy to prevent intestinal obstruction. However, with no spontaneous resolution of intussusception, surgical treatment was decided. The operative findings revealed a jejunal tumor about 30 cm from the Treiz ligament, and the jejunum including the tumor with a 5 cm margin were partially resected. The resected tumor was a 35 × 50 mm soft mass spreading laterally with nodules. The pathological examinations revealed tubulovillous adenocarcinoma in the adenoma. Intussusception is rare in adults compared to children. About 45 % of cases of intussusception in adults are due to small intestinal tumors such as malignant lymphoma or lipoma, but a tubulovillous adenocarcinoma with adenoma is a rare cause of intussusception. We present a rare case of jejunal tubulovillous adenocarcinoma in adenoma presenting with entero-enteric intussusception.

Plasma cell leukemia (PCL) is an aggressive variant of multiple myeloma characterized by a high level of plasma cells circulating in the peripheral blood. The prognosis of PCL patients treated with conventional chemotherapy remains poor. Some reports have suggested that both bortezomib and lenalidomide are effective in treating PCL. We herein report a case of primary PCL in which the patient achieved stringent complete remission after receiving combination chemotherapy with reduced-dose bortezomib, lenalidomide and dexamethasone (VRd). This regimen was very effective, and no severe adverse events were observed. A reduced-dose VRd regimen can be considered in PCL patients.

This study evaluated the effect of foot progression angle on the reduction in knee adduction moment caused by a lateral wedged insole during walking. Twenty healthy, young volunteers walked 10 m at their comfortable velocity wearing a lateral wedged insole or control flat insole in 3 foot progression angle conditions: natural, toe-out, and toe-in. A 3-dimensional rigid link model was used to calculate the external knee adduction moment, the moment arm of ground reaction force to knee joint center, and the reduction ratio of knee adduction moment and moment arm. The result indicated that the toe-out condition and lateral wedged insole decreased the knee adduction moment in the whole stance phase. The reduction ratio of the knee adduction moment and the moment arm exhibited a close relationship. Lateral wedged insoles decreased the knee adduction moment in various foot progression angle conditions due to decrease of the moment arm of the ground reaction force. Moreover, the knee adduction moment during the toe-out gait with lateral wedged insole was the smallest due to the synergistic effect of the lateral wedged insole and foot progression angle. Lateral wedged insoles may be a valid intervention for patients with knee osteoarthritis regardless of the foot progression angle.

For patients chronically infected with hepatitis C virus (HCV), mutations in the non-structural 5A (NS5A) gene are important predictive factors for the response to interferon (IFN) therapy. In the present study, factor analysis of the therapeutic response of patients following pegylated IFN and ribavirin combination therapy was assessed in a multicenter study. Chronic HCV-infected patients with genotype 1b and high viral load (n=96, mean age 56.5 years; 59 males, 68 females) treated with pegylated IFN-α-2b and ribavirin combination therapy were enrolled. This study was conducted at Kobe University Hospital and 25 affiliated hospitals in Hyogo prefecture. Sixty-five patients (68%) completed treatment with both pegylated IFN and ribavirin at >80% of the weight-based scheduled dosages. Patients who reduced or terminated therapy were frequently aged women (mean age 60.8 years; 11 males, 17 females). Overall, a sustained viral response (SVR) was achieved in 42 (44%) patients out of 96. Based on per-protocol-based (PPB) analysis, the SVR rate in patients with ≥6 amino acid (aa) mutations in the IFN resistance-determining region (IRRDR) (75%) or ≥1 aa mutation in the IFN sensitivity-determining region (ISDR) (61%) was significantly higher than that in patients with

Nephrogenic systemic fibrosis is a progressive, potentially fatal, multiorgan-system fibrosing disease related to exposure of patients with renal failure to gadolinium-based contrast agents used in magnetic resonance imaging. Between 1997 and 2007, more than 500 cases of nephrogenic systemic fibrosis in patients with severe renal insufficiency (glomerular filtration rate less than 30 mL/min/1.73 m(2)) were reported, and no known cases of nephrogenic systemic fibrosis have occurred in patients with a glomerular filtration rate of more than 30 mL/min/1.73 m(2) without acute kidney injury. Additional major risk factors are use of high-dose and specific gadolinium-based contrast agents, a pro-inflammatory state. Although the mechanism of nephrogenic systemic fibrosis is unclear and there is no consistently-effective therapy, nephrogenic systemic fibrosis is an entity that can be eliminated by observing recent recommended guidelines for gadolinium-based contrast agents and nephrogenic systemic fibrosis. This article reviews current knowledge about nephrogenic systemic fibrosis and focuses mainly on how to prevent it.

We have recently reported that the outcome of acute myeloid leukemia (AML) patients with t(6;9)(p23;q34) who underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) was comparable to that of patients with a normal karyotype. We performed a further analysis regarding the prognostic factors for t(6;9)(p23;q34) AML patients who underwent a HSCT. Seven pediatric patients and 57 adult patients, transplanted between 1996 and 2007, were assessed in this study. The overall survival (OS) of the pediatric patients tended to be better than the OS of the adults, although there were no statistically significant differences. The present study focused on the adult patients revealed that the disease status at HSCT was the sole prognostic factor affecting the OS identified in the univariate analysis. A multivariate analysis showed that the disease status at HSCT and M2 in the FAB classification were extracted as the significant variables affecting the OS. The patients who were not in remission at HSCT and had non-FAB-M2 showed a poorer outcome; 6 deaths in the 9 patients were due to a relapse of the AML. These findings suggest that novel therapeutic approaches might be needed for patients with these poor prognostic factors., 発行後6か月より全文公開

Acute myeloid leukemia (AML) with t(6;9)(p23;q34) is well known to have a poor prognosis treated with chemotherapy and autotransplantation. The presence of this karyotype is an indicator for allogeneic hematopoietic stem cell transplantation (HSCT); however, the impact of t(6;9)(p23;q34) on the HSCT outcome remains unclear. We conducted a matched-pair analysis of de novo AML patients with and without t(6;9)(p23;q34) using data obtained from the Japanese HSCT data registry. A total of 57 patients with t(6;9)(p23;q34) received transplants between 1996 and 2007, and 171 of 2056 normal karyotype patients matched for age, disease status at HSCT and graft source were selected. The overall survival, disease-free survival, cumulative incidence of relapse and the non-relapse mortality in t(6;9)(p23;q34) patients were comparable to those for normal karyotype patients. A univariate analysis showed that t(6;9)(p23;q34) had no significant impact on the overall survival. These findings suggest that allogeneic HSCT may overcome the unfavorable impact of t(6;9)(p23;q34) as an independent prognostic factor. © 2012 Macmillan Publishers Limited All rights reserved.

Contrast-induced nephropathy (CIN) is a serious complication resulting from the use of iodinated contrast medium (CM) with potentially high morbidity and mortality. Patients with pre-existing renal insufficiency appear to be at higher risk of CIN. To prevent CIN among patients undergoing contrast-enhanced computed tomography, every effort is required, including routine identification of at-risk patients, the use of appropriate hydration regimens, withdrawal of nephrotoxic drugs, selection of low-osmolality CM or iso-osmolar CM, and using the minimum volume of CM possible.

To evaluate the diagnostic value of integrated 18F-fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT) to discriminate malignant from benign ovarian tumors.One hundred and eight women suspected of having ovarian cancer underwent preoperative FDG-PET/CT scans. FDG uptake was quantified by calculating the maximum standardized uptake value (SUV max) of each tumor. The receiver operating characteristic curve was drawn to determine the optimal cut-off values of SUV max that would best discriminate between benign and malignant tumors. Histopathologic results served as the reference standard. We assessed the association between SUV max and with International Federation of Gynecology and Obstetrics stage in borderline and malignant tumors, using one-factor analysis of variance and an unpaired t test with Bonferoni correction.The SUV max of benign (n=26), borderline (n=12) and malignant (n=73) lesions was 2.00 ± 1.02, 2.72 ± 1.04, and 7.55 ± 4.29, respectively. Although there were significant differences between benign and malignant, and borderline and malignant lesions (P0.0001), there was no significant difference between benign and borderline lesions. Using an SUV max cutoff of 2.55, the sensitivity, specificity and accuracy of FDG-PET/CT scanning to detect malignant or borderline tumors were 82.4, 76.9, and 81.1%, respectively. The SUV max of stage I (n=35), stage II (n=8), stage III (n=34) and stage IV (n=8) was 3.59 ± 2.32, 5.18 ± 1.34, 8.72 ± 2.69, and 15.05 ± 3.77, respectively, and significant differences were observed between SUV max values and the various International Federation of Gynecology and Obstetrics stage (P0.0001).FDG-PET/CT scanning has a high diagnostic value in differentiating between malignant and benign tumors, and a low diagnostic value in differentiating between borderline and benign tumors.

The aim of this study was to examine the dexterity of both lower extremities in patients with stroke. Twenty patients with stroke and 20 age-matched control subjects participated in this study. To determine the dexterity of the lower extremities, we examined the ability to control muscle force during submaximal contractions in the knee extensor muscles using a force tracking task. The root mean square errors were calculated from the difference between the target and response force. The root mean square error was significantly greater in the affected limb of patients with stroke compared with those of the unaffected limb and the control subjects, and in the unaffected limb compared with that of the control subjects. Furthermore, the root mean square error of the affected limb was related significantly to motor function as determined by Fugl-Myer assessment. These results demonstrate impairment of the dexterity of both the affected and the unaffected lower extremities in patients with stroke.