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Autoimmune hematological disorders are rare complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Diagnosis of immune thrombocytopenia (ITP) is challenging, especially after allo-HSCT, because various complications such as graft-versus-host disease, disease relapse, viral infection, thrombotic microangiopathy, and drug side effects can also cause thrombocytopenia. Assessment of reticulated platelets (RP) and plasma thrombopoietin (TPO) levels may be useful to distinguish between ITP and hypoplastic thrombocytopenia. ITP is generally characterized by an increased percentage of RP, and a normal or slightly increased plasma TPO level. We now report three cases of thrombocytopenia after allo-HSCT. RP% was elevated in these patients, as it is in primary ITP. However, in contrast to primary ITP, plasma TPO levels were high in two of three patients. Anti-αIIbβ3 and anti-GPIb/IX-specific direct IgG antibodies were detected as well, suggesting occurrence of immune-mediated platelet destruction in addition to bone marrow suppression in two patients. All three patients were successfully treated with corticosteroids and/or thrombopoietin receptor agonists (TPO-RAs). These results suggest that increased RP% and detection of glycoprotein-specific platelet autoantibodies are useful for the diagnosis of ITP after HSCT.

Background It remains unclear whether men have more favorable survival outcomes after out-of-hospital cardiac arrest (OHCA) than women. Methods We reviewed a total of 386,535 patients aged ≥ 18 years with OHCA who were included in the Japanese registry from 2013 to 2016. The study endpoints were the rates of 1-month survival and neurologically intact survival (Cerebral Performance Category Scale score = 1 or 2). Based on age, the reviewed patients were categorized into the following eight groups: 0.02). Moreover, after hierarchical propensity score matching, the survival outcomes did not significantly differ between both sexes (all P > 0.05). Conclusions No significant sex-specific differences were found in the rates of 1-month survival and neurologically intact survival after OHCA. Electronic supplementary material The online version of this article (10.1186/s13054-019-2547-x) contains supplementary material, which is available to authorized users.

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.

The purpose of this study was to clarify whether a gait analysis using an accelerometer could estimate gait independence. Eighty-six stroke patients and 21 healthy control subjects participated in this study. Stroke patients were identified as dependent or independent based on their gait ability. The acceleration of the trunk and bilateral thigh was measured using three wireless sensors during walking. The root mean square, gait regularity, and symmetry were calculated from the acceleration to estimate gait quality. ANCOVA showed that gait regularity of the trunk and bilateral thigh were significantly lowest in the dependent group, regardless of gait velocity. A logistic regression analysis showed that the regularity and root mean square of the anteroposterior acceleration of the unaffected thigh were the key factors for estimating gait independence. This study suggests that an acceleration-based gait analysis facilities gait independence estimation, and is a useful tool during the rehabilitation of stroke patients.

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.

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

The human gut harbours diverse microorganisms, and gut dysbiosis has recently attracted attention because of its possible involvement in various diseases. In particular, the lack of diversity in the gut microbiota has been associated with complications of haematopoietic stem cell transplantation (HSCT), such as infections, acute graft-versus-host disease and relapse of primary disease, which lead to a poor prognosis. However, few studies have serially examined the composition of the intestinal microbiota after HSCT. In this study, we demonstrated, using next-generation sequencing of the bacterial 16S ribosomal RNA gene, combined with uniFrac distance analysis, that the intestinal microbiota of patients undergoing allogeneic HSCT substantially differed from that of healthy controls and recipients of autologous transplants. Faecal samples were obtained daily throughout the clinical course, before and after transplantation. Notably, the proportions of Bifidobacterium and genera categorized as butyrate-producing bacteria were significantly lower in patients with allogeneic HSCT than in healthy controls. Furthermore, among allogeneic transplant recipients, a subgroup with a preserved microbiota composition showed a benign course, whereas patients with a skewed microbiota showed a high frequency of complications and mortality after transplantation. Thus, we conclude that the stability of intestinal microbiota is critically involved in outcomes of HSCT.

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.

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.

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.

A conditioning regimen with fludarabine and myeloablative dose of busulfan (FLU/BU4) has been commonly used in allogeneic hematopoietic cell transplantation (allo-HCT). However, there are two major problems with this regimen: insufficient anti-leukemic effect, especially in advanced cases, and slow time to complete donor-type chimerism, especially T-cell chimerism. To overcome these issues, we designed a combination regimen with FLU (150 mg/m2), intravenous BU (12.8 mg/kg), and melphalan (100 mg/m2) (FLU/BU4/MEL) and conducted retrospective analyses of treatment outcomes at our institute. Forty-two patients with myeloid malignancies received allogeneic bone-marrow transplantation or peripheral blood stem-cell transplantation (allo-BMT/PBSCT) with FLU/BU4/MEL regimen. The median age of patients was 46.5 years (20–63 years). Thirteen patients (31%) did not achieve complete hematological remission at transplantation. All patients examined achieved complete whole and T-cell chimerism within 1 month after allo-HCT. The 4-year overall survival and disease-free survival rates were 66.0% [95% confidence interval (CI) 49.4–78.3%] and 59.5% (95% CI 43.2–72.6%) in all patients, and 49.4% (95% CI 19.7–73.6%) and 38.5% (95% CI 14.1–62.8%) in patients who were not in remission. In conclusion, FLU/BU4/MEL showed curative potential, even in patients with advanced myeloid malignancies, accompanied by achievement of rapid complete chimerism after allo-BMT/PBSCT.

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.

The present study involved 6 patients who had urgent surgery for acute cholecystitis(AC)complicated with gallbladder cancer(GBC)in our hospital from January 2014 to December 2016. We analyzed the clinical outcome of early surgery for AC complicated with GBC. According to Tokyo Guidelines 2013, the AC severity was classified as Mild 1 case, Moderate 5 cases. Only one patient was diagnosed with GBC before the operation for AC. The others were during or after the laparoscopic cholecystectomy. Histopathologically, all patients had Stage II disease or greater. Two patients had adjunctive radical operation with the wedge resection of the gallbladder bed, lymphadenectomy and bile duct resection, and they survived without recurrence for 28 months and 12 months, respectively. Of the 3 patients without any additional surgery, 2 patients died in several months after the operation. In consideration of the concurrence of GBC, early surgery for AC must be decided carefully.

Compared with 4-times-daily infusion of intravenous busulfan (ivBU4), the safety and efficacy of once-daily infusion of ivBU (ivBU1) has not been fully clarified. We have been routinely using ivBU1 in a conditioning regimen in adult patients with myeloid malignancy who undergo allogeneic hematopoietic stem cell transplantation. In this study, a total of 91 patients who received ivBU1 for 2 days (n = 18) or 4 days (n = 73) in our institutions were compared with 273 control patients who received ivBU4, who were matched for age, sex, performance status, disease risk, conditioning regimen, and donor type, selected from the database of the Japanese Society for Hematopoietic Cell Transplantation using optimal matching algorithms. One-year overall survival (56.8% versus 57.1%, P = .94), disease-free survival (51.6% versus 50.8%, P = .73), relapse rate (28.5% versus 26.2%, P = .94), nonrelapse mortality (19.9% versus 23.0%, P = .71), and the incidence of graft-versus-host disease were not significantly different between the ivBU1 and ivBU4 groups. In patients who received ivBU1, neutrophil recovery was slower (median days: 22 versus 17, P = .001), and the incidence of veno-occlusive disease was lower (2.6% versus 17.4%, P = .04). In conclusion, ivBU1 can be safely administered with clinical outcomes similar to those with ivBU4.

Purpose To investigate temporal variations in dispatcher-assisted and bystander-initiated resuscitation efforts and their association with survival after bystander-witnessed out-of-hospital cardiac arrests (OHCAs). Methods We retrospectively analyzed the neurologically favorable 1-month survival and the parameters related to dispatcher assisted cardiopulmonary resuscitation (DA-CPR) and bystander CPR (BCPR) for 227,524 OHCA patients between 2007 and 2013 in Japan. DA-CPR sensitivity for OHCAs, bystander's compliance to DA-CPR assessed by the proportion of bystanders who follow DA-CPR, and performance of BCPR measured by the rate of bystander-initiated CPR in patients without DA-CPR were calculated as indices of resuscitation efforts. Results Performance of BCPR was only similar to temporal variations in the survival (correlation between hourly paired values, R2 = 0.263, P = 0.01): a lower survival rate (3.4% vs 4.2%) and performance of BCPR (23.1% vs 30.8%) during night-time (22:00–5:59) than during non-night-time. In subgroup analyses based on interaction tests, all three indices deteriorated during night-time when OHCAs were witnessed by non-family (adjusted odds ratio, 0.73–0.82), particularly in non-elderly patients. The rate of public access defibrillation for these OHCAs markedly decreased during night-time (adjusted odds ratio, 0.49) with delayed emergency calls and BCPR initiation. Multivariable logistic regression analyses revealed that the survival rate of non-family-witnessed OHCAs was 1.83-fold lower during night-time than during non-night-time. Conclusions Dispatcher-assisted and bystander-initiated resuscitation efforts are low during night-time in OHCAs witnessed by non-family. A divisional alert system to recruit well-trained individuals is needed in order to improve the outcomes of night-time OHCAs witnessed by non-family bystanders.

Aim To determine the effectiveness of ventilations in bystander cardiopulmonary resuscitation (BCPR) and to identify the factors associated with ventilation-only BCPR. Methods From out-of-hospital cardiac arrest (OHCA) data prospectively collected from 2005 to 2011 in Japan, we extracted data for 210,134 bystander-witnessed OHCAs with complete datasets but no prehospital involvement of physician [no BCPR, 115,733; ventilation-only, 2093; compression-only, 61,075; and conventional (compressions+ventilations) BCPR, 31,233] and determined the factors associated with 1-month neurologically favourable survival using simple and multivariable logistic regression analyses. In 91,885 patients with known BCPR durations, we determined the factors associated with ventilation-only BCPR. Results The rate of survival in the no BCPR, ventilation-only, compression-only and conventional group was 2.8%, 3.9%, 4.5% and 5.0%, respectively. After adjustment for other factors associated with outcomes, the survival rate in the ventilation-only group was higher than that in the no BCPR group (adjusted OR; 95% CI, 1.29; 1.01–1.63), but lower than that in the compression-only (0.76; 0.59–0.96) or conventional groups (0.70; 0.55–0.89). Conventional CPR had the highest OR for survival in almost all OHCA subgroups. The adjusted OR (95% CI) for survival after dividing BCPR into ventilation and compression components was 1.19 (1.11–1.27) and 1.60 (1.51–1.69), respectively. Older guidelines, female sex, younger patient age, bystander-initiated CPR without instruction, early BCPR and short BCPR duration were associated with ventilation-only BCPR. Conclusions Ventilation is a significant component of BCPR, but alone is less effective than compression in improving neurologically favourable survival after OHCAs.

To investigate differences in chronological variations in characteristics and outcomes of out-of-hospital cardiac arrests (OHCAs) between elderly and non-elderly patients.We retrospectively analyzed bystander-witnessed OHCAs without prehospital involvement of physicians between January 2007 and December 2014 in Japan. We considered the following time periods: night-time (23:00-5:59) and non-night-time; we further divided non-night-time into dinnertime (18:00-20:29) and other non-night-time. Subsequently, we analyzed chronological variations in factors associated with OHCA survival using univariate and multivariable logistic regression analyses for unmatched and propensity-matched pairs, respectively.For elderly (≥65 years old, N = 201,073) and non-elderly (≥10,65 years old, N = 57,124) OHCA patients, survival rates were lower during night-time than during non-night-time (elderly, 2.8% vs 1.6%; non-elderly, 9.8% vs 7.7%). The trend for incidences of bystander-witnessed OHCA in the elderly showed three peaks associated with breakfast-time, lunchtime, and dinnertime. However, a transient but considerable decrease in survival rates was observed at dinnertime (1.9% at dinnertime and 3.0% during other non-night-time). OHCAs in the elderly at dinnertime were characterized by low proportions of presumed cardiac etiologies and shockable initial rhythm. However,even after adjusting for these and other factors associated with survival,survival rates were significantly lower at dinnertime than during other non-night-time for elderly OHCA patients (adjusted odds ratio, 1.29; 95% confidence interval, 1.18-1.41, with dinnertime as reference). This difference was significant even after propensity matching with significant augmentation in winter.Dinnertime, particularly in winter, is associated with lower survival in elderly OHCA patients.

A 67-year-old man was admitted with a 1-month history of spontaneous hematoma in his right back and severe anemia. He had suffered from rashes with blisters involving both legs for 10 years, which had shown worsening and extended to his entire body concurrently with the hematoma. APTT was markedly prolonged to 119 seconds, and Factor VIII:C and FVIII inhibitor levels were less than 1% and 153.1 BU/ml, respectively, confirming the diagnosis of acquired hemophilia A (AHA). Skin biopsy revealed his rashes to be caused by autoimmune bullous disease (ABD), and laboratory and physical findings showed that he also had autoimmune hypothyroidism (Hashimoto's disease). Recombinant FVIIa was effective for management of his bleeding; in addition, FVIII inhibitor reduction and FVIII:C recovery, in parallel with improvement of the skin lesions, were achieved by administering prednisolone and cyclophosphamide. To our knowledge, this is the first report of AHA associated with ABD and Hashimoto's disease.

The gene mutation occurring with transformation in lymphoplasmacytic lymphoma (LPL) /Waldenström macroglobulinemia (WM) has not been fully elucidated. Herein, we report a 61-year-old man with LPL/WM. In this case, the MYD88 gene mutation appeared with transformation to diffuse large B-cell lymphoma (DLBCL). Bone marrow biopsy revealed the involvement of CD20 positive small plasmacytoid lymphocytes, indicating LPL/WM. However, the samples taken from both the cervical lymph node and the pleural effusion provided a pathological diagnosis of DLBCL. All samples showed the same patterns of surface antigen expressions and immunoglobulin gene rearrangements. Therefore, these lymphomas had identical clonality and were regarded as transformation from LPL/WM to DLBCL. The MYD88

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.

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.

Background Population aging has rapidly progressed in Japan. However, few data exist regarding the characteristics of extremely elderly patients with out-of-hospital cardiac arrest (OHCA). We aimed to determine the prehospital predictors of one-month survival with favorable neurological outcomes (Cerebral Performance Category scale, category 1 or 2; CPC 1–2) in this population. Methods We investigated 23,520 OHCA patients aged ≥95 years from a prospectively recorded, nationwide, Utstein-style Japanese database between 2008 and 2012. The primary study endpoint was one-month CPC 1–2 after OHCA. Results The one-month CPC 1–2 rate was 0.27% (63/23,520). Only two variables were significantly associated with one-month CPC 1–2 in a multivariate logistic regression model: prehospital return of spontaneous circulation (ROSC) [adjusted odds ratio (aOR), 94.4; 95% confidential interval (CI), 50.1–191.7] and emergency medical service (EMS)-witnessed arrest (aOR, 5.1; 95% CI, 2.6–10.2). When stratified by these two predictors, the one-month CPC 1–2 rates were 20.2% (18/89) for patients who had both prehospital ROSC and EMS-witnessed arrest, 4.2% (33/783) for those who had prehospital ROSC without EMS-witnessed arrest, 0.28% (3/1065) for those who had EMS-witnessed arrest without prehospital ROSC, and 0.04% (9/21,583) for those who had neither predictor, respectively. Conclusions The crucial prehospital predictors for one-month CPC 1–2 in elderly OHCA patients aged ≥95 years in Japan were prehospital ROSC and EMS-witnessed arrest and the former was the predominant predictor.

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

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.

The rare central nervous system (CNS) infiltration of Waldenström macroglobulinemia (WM) is known as Bing-Neel syndrome (BNS). Furthermore, the transformation of WM into diffuse large B-cell lymphoma (DLBCL) is also unusual. Herein, we report a 69-year-old male with DLBCL transformed from BNS. In November 2008, the patient visited a prior hospital because of anemia and was diagnosed with WM. After receiving chemotherapy (R-CHOP), his serum immunoglobulin M (IgM) level decreased and then remained at approximately 2000 mg/dl for 3 years. In November 2011, he complained of visual impairment and photophobia in his left eye. Magnetic resonance imaging showed enlargement of the left optic nerve and cerebrospinal fluid examination indicated CNS infiltration of WM cells. Consequently, he was diagnosed with BNS. He thus received CNS targeted chemotherapy (R-MPV) and achieved a partial response. In May 2014, IgM was elevated and swelling of systemic lymph nodes was detected. Inguinal lymph node biopsy yielded a pathological diagnosis of DLBCL and the clonality of tumor cells between WM and DLBCL was confirmed by the allele-specific oligonucleotide polymerase chain reaction (ASO-PCR).

The standard conditioning regimen in allogeneic hematopoietic stem cell transplantation (HSCT) for aplastic anemia from a human leukocyte antigen (HLA)-identical sibling has been high-dose cyclophosphamide (CY 200 mg/kg). In the present study, results for 203 patients with aplastic anemia aged 16 years or older who underwent allogeneic HSCT from HLA-identical siblings were retrospectively analyzed using the registry database of Japan Society for Hematopoietic Cell Transplantation. Conditioning regimens were defined as a (1) high-dose CY (200 mg/kg or greater)-based (n = 117); (2) reduced-dose CY (100 mg/kg or greater, but less than 200 mg/kg)-based (n = 38); and (3) low-dose CY (less than 100 mg/kg)-based (n = 48) regimen. Patient age and the proportion of patients receiving fludarabine were significantly higher in the reduced- and low-dose CY groups than the high-dose CY group. Engraftment was comparable among the groups. Five-year overall survival (OS) tended to be higher in the low-dose CY group [93.0 % (95 % CI 85.1-100.0 %)] than the high-dose CY [84.2 % (95 % CI 77.1-91.3 %)] or reduced-dose CY groups [83.8 % (95 % CI 71.8-95.8 %); P = 0.214]. Age-adjusted OS was higher in the low-dose CY group than the high- and reduced-dose CY groups with borderline significance (P = 0.067). These results suggest that CY dose can safely be reduced without increasing graft rejection by adding fludarabine in allogeneic HSCT for aplastic anemia from an HLA-identical sibling.

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.

A 45-year-old man with chronic active Epstein-Barr virus (EBV) infection (CAEBV) with natural killer cell type developed pulmonary arterial hypertension (PAH). After chemotherapy, he showed marked depression of the EBV DNA genome in the peripheral blood, but PAH sustained. He died of heart failure due to PAH, and the histo-pathological examination revealed pulmonary vascular abnormalities without lung disease on autopsy. Although the EBV DNA genome and the infiltrating lymphocytes were not detected in the lung, his clinical course suggested that his PAH might be caused by CAEBV. This is the first reported case of PAH associated CAEBV in an adult.

A 69-year-old man presented with lymph node swelling in the right inguinal region. A biopsy was made (LN1) and diagnosed as peripheral T-cell lymphoma. The lesion remitted completely over a period of about 51 months after combination chemotherapy, but erythematous papules, systemic lymphadenopathy, and fever of 38 degrees appeared. Skin (S1) and lymph nodes (LN2) were biopsied. Erythematous papules once disappeared spontaneously, but appeared again and were biopsied (S2). LN1 displayed the typical histologic and immunohistochemical features of Lennert lymphoma, i.e., diffuse proliferation of small to large lymphoid cells of CD3+, CD4+, CD8- immunophenotype accompanied by numerous clusters of epithelioid histiocytes. In LN2, the large cells with CD3+, CD4+, CD8- decreased in number, while numerous CD20+ large cells were discernible. Clonality analysis revealed the persistent presence of an identical T-cell clone in LN1 and LN2. Clonal bands of immunoglobulin heavy (IgH) chain gene were detected in LN2 but not in LN1. S1 and S2 showed diffuse proliferation of small to large lymphoid cells of CD20-, CD3+, CD4+, CD8- in the upper dermis, with obvious epidermotropism. Clonality analysis revealed the presence of a T-cell clone identical to LN1 and LN2 with no B-cell clone, indicating the recurrence of PTCL. In situ hybridization (ISH) for Epstein-Barr virus (EBV) genome revealed that positive signals in the nucleus of large B-lymphoid cells appeared only in LN2. Taken together, EBV-positive large B-cell lymphoma appeared transiently in the course of "Lennert lymphoma".

We have evaluated the antifungal activity of micafungin in serum by using the disk diffusion method with serum-free and serum-added micafungin standard curves. Serum samples from micafungin-treated patients have been shown to exhibit adequate antifungal activity, which was in proportion to both the applied dose and the actual concentration of micafungin measured by high-performance liquid chromatography. The antifungal activity of micafungin in serum was also confirmed with the broth microdilution method.

Objectives: FOLFIRI is one of the current standard first-line regimens for advanced colorectal cancer, but its administration is onerous. Because the replacement of 2-day-infusional 5-fluorouracil (5-FU) of FOLFIRI with oral tegafur-uracil/leucovorin (UFT/LV) would be highly beneficial for clinical management, we performed a phase I trial using oral UFT/LV and a pharmacokinetic evaluation. Methods: Treatment consisted of infusional irinotecan (100 mg/m 2 )/l-LV (15 mg/m 2 ) and a bolus injection of 5-FU (500 mg/m 2 ) on day 1, and oral UFT (300 mg as tegafur/m 2 /d)/LV (75 mg/d) on days 1-5 (level 1), days 1-7 (level 2), or days 1-10 (level 3). Cycles were repeated every 14 days. After determination of the recommended UFT/LV administration period, irinotecan was dose-escalated (level 4: 125 mg/m 2 ; level 5: 150 mg/m 2 ). Results: Nineteen patients were enrolled. One dose-limiting toxicity (DLT), grade 4 neutropenia lasting for ≥4 days was observed at level 2. At level 3, one DLT of treatment delay of ≥8 days occurred due to prolonged neutropenia, and 2 patients refused to continue the treatment because of prolonged grade 2 anorexia. Therefore, a 7-day administration of UFT/LV was recommended. No DLT was observed at levels 4 and 5. Pharmacokinetic evaluation suggested continuous exposure to 5-FU by means of oral UFT/LV administration in this combination. Conclusions: The recommended administration period was 7 days for oral UFT/LV, and the recommended dose of irinotecan was 150 mg/m 2 . A phase II study is ongoing to validate the clinical outcome.

Soft tissue perineurioma is an uncommon benign peripheral nerve sheath tumor, although it is the most common subtype of perineuriomas. We present a case of soft tissue perineurioma in the left groin of a 48-year-old man. Precontrast computed tomography showed a homogeneous hypodense mass that showed faint enhancement. The mass appeared with hypointensity on T1-weighted magnetic resonance (MR) images and heterogeneous hyperintensity on T2-weighted MR images. Slight contrast uptake was noted on enhanced T1-weighted MR images with fat suppression. Although these CT and MR imaging findings were nonspecific, the overall imaging features are similar to those of schwannomas.

To report the efficacy of intravitreal chemotherapy for primary intraocular lymphoma (PIOL).Retrospective, noncomparative interventional case reports are presented for six patients (ten eyes; mean age, 58.8 years) with pathologically confirmed PIOL who participated in this study and were treated at our hospital with intravitreal injections of methotrexate (MTX) between January 2004 and February 2007. Intravitreal injections of MTX (400 microg MTX/50 microl Opeguard-MA) were administered once or twice weekly for 1 month followed by ten monthly injections. Interleukin-10 (IL-10) and IL-6 were measured in the vitreous before and after injections to determine tumor activity.All eyes were clinically cleared of malignant cells. One eye lost vision. After intravitreal chemotherapy, the vitreous IL-10 concentration reached barely detectable levels.Intravitreal chemotherapy achieves clinical remission and preserves vision in patients with PIOL.

In epithelia, tight junctions (TJs) create a primary barrier to the diffusion of solutes through the paracellular pathway. Although TJ-related molecules are present in the epidermis, the precise mechanisms underlying TJ functions in this tissue remain unclear. In this study, we use an ultraviolet (UV) B-irradiated murine skin model, in which the epidermal barrier function has been perturbed, to demonstrate a correlation between the expression patterns of TJ-related molecules and the epidermal permeability of TJs. Occludin remained localized in the upper epidermis, regardless of UVB irradiation (0.15 J per cm(2)). ZO-1 was localized in the upper portion of normal epidermis, and within 3-4 days of UVB irradiation, it was expressed throughout the upper epidermis and their expression coincided with epidermal thickening. Protein expression of claudin-1 and occludin did not alter until 3 and 4 days after UVB irradiation, respectively and thereafter expression remained elevated above pre-irradiation levels. An in vivo epidermal permeability assay revealed that tight junction-barrier function was perturbed by UVB irradiation, whereby biotinylated markers clearly permeated the stratum granulosum 3-5 days after irradiation. These results suggest that TJ-related molecules play important roles in epidermal barrier function in murine skin and show that changes in their expression patterns are associated with epidermal barrier perturbation after UVB irradiation. Specifically, it appears that epidermal barrier recovery is accelerated by the increased production and dense localization of occludin in the cell-cell contact region of the stratum granulosum.

The purpose of the present study was to determine the diagnostic accuracy of non-enhanced CT and contrast-enhanced CT in integrated PET/CT studies for preoperative nodal staging of rectal cancer.Retrospective analysis was performed in 53 patients with pathologically proven rectal cancer who had been referred for preoperative staging. All patients underwent integrated PET/CT consisting of non-enhanced and contrast-enhanced CT followed by whole-body fluorine-18-fluorodeoxyglucose ([(18)F]FDG) PET. Both non-enhanced and contrast-enhanced PET/CT images were evaluated separately by two observers in consensus. The reference standard was histopathologic results. For nodal staging of rectal cancer, we compared diagnostic accuracy on a per-patient basis between the two modalities.Nodal staging was correctly determined with non-enhanced studies in 37 patients (70%) and with contrast-enhanced studies in 42 patients (79%). On a per-patient basis, sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of regional lymph node staging were 85%, 68%, 83%, 72%, and 79%, respectively, with contrast-enhanced studies, and 85%, 42%, 73%, 62%, and 70%, respectively, with non-enhanced studies. The difference in the accuracy of nodal staging between the two modalities was not significant (p = 0.063). Compared with non-enhanced studies, contrast-enhanced studies determined more correctly the status of pararectal lymph nodes (p = 0.002), internal iliac lymph nodes (p = 0.004), and obturator lymph nodes (p0.0001).Contrast-enhanced PET/CT is superior to non-enhanced PET/CT for precise definition of regional nodal status in rectal cancer.

[F-18]-fluorodeoxy-D-glucose (18FDG) positron emission tomography (PET) is a sensitive modality for detecting malignant lesions. The purpose of the present study was to describe unknown bone and soft tissue lesions in adults identified at cancer screening using PET.A total of 4283 individuals of more than or equal to 40 years of age were enrolled. All individuals underwent scans from the base of the skull to proximal thigh. The images were reviewed and a consensus was reached by two board-certified radiologists and a nuclear medicine specialist for the diagnoses. Diagnoses of the lesions were confirmed by histological examination, typical radiologic findings, obvious progression in number and/or size of the lesion on follow-up examinations, and medical examination of interview.Unsuspected focal abnormality in the bone and soft tissue were found in 62 individuals (1.4%). The mean size of the lesion was 26 mm (range, 6-155 mm). There were 29 bone lesions (47%) and 33 soft tissue lesions (53%). A malignant lesion was found in one case (1.6%) and histologic diagnosis was primary non-Hodgkin lymphoma of the vertebra. Other major diagnoses were healing bone (n = 11, 18%) and benign cystic lesions of bone and soft tissue (n = 9, 15%), and brown fat of soft tissue (n = 4, 6%).Unsuspected bone and soft tissue lesions of a wide variation of pathologic and clinical diagnoses were encountered at cancer screening using PET. Correlation with clinical history and other imaging findings is essential in the differential diagnosis.

The purpose of this study was to determine whether a lateral wedge insole reduces the external knee adduction moment during slope walking. Twenty young, healthy subjects participated in this study. Subjects walked up and down a slope using 2 different insoles: a control flat insole and a 7° lateral wedge insole. A three-dimensional motion analysis system and force plate were used to examine the knee adduction moment, the ankle valgus moment, and the moment arm of the ground reaction force to the knee joint center in the frontal plane. The lateral wedge insole significantly decreased the moment arm of the ground reaction force, resulting in a reduction of the knee adduction moment during slope walking, similar to level walking. The reduction ratio of knee adduction moment by the lateral wedge insole during the early stance of up-slope walking was larger than that of level walking. Conversely, the lateral wedge insole increased the ankle valgus moment during slope walking, especially during the early stance phase of up-slope walking. Clinicians should examine the utilization of a lateral wedge insole for knee osteoarthritis patients who perform inclined walking during daily activity, in consideration of the load on the ankle joint.

Recent studies have revealed the crucial role of the niche which supports B-lymphocyte differentiation from hematopoietic stem cells. In this study, we aimed to identify a novel regulator of B lymphopoiesis secreted in the specific niche using the signal sequence trap method. Among the identified proteins from MS5 stromal cells, expression of pleiotrophin, placental proliferin 2, and osteoblast stimulating factor 5 (OSF-5) was dominantly high in several stromal cell lines. We found that OSF-5 suppressed early B lymphopoiesis in transgenic mice producing the target protein. The number of pre-B and immature B cells was reduced by more than half compared with control in the transgenic mice. In vitro studies showed that a secreted variant of OSF-5 inhibited the proliferation and colony formation of pre-B cells, whereas cell-intrinsic form had no influence on B lymphopoiesis. The main components of the B-lymphopoietic niche, osteoblasts in mice and mesenchymal cells in humans, are primary producers of OSF-5. These results define a novel mechanism of B lymphopoiesis in bone marrow. In the specific niche, B-lymphocyte differentiation is fine-tuned by negative regulators as well as supportive factors.

We report the computed tomography (CT) and magnetic resonance imaging (MRI) features of a 10-year-old boy with low-grade fibromyxoid sarcoma (LGFMS) in the shoulder and correlate them with the clinicopathological features. LGFMS, a rare soft tissue sarcoma with bland histological features and paradoxically aggressive behavior, tends to occur in superficial regions and in children more than previously recognized. To date, few imaging studies have been reported, particularly in pediatric patients. In this case, precontrast CT showed a low- to isodensity mass and punctate calcification. On contrast-enhanced CT, heterogeneous enhancement was seen. MRI findings correlated well with the pathological features of the tumor. The myxoid area showed high signal intensity on T2-weighted MR images and heterogeneous enhancement after administration of contrast material; the hypercellular area demonstrated lower signal intensity on T2-weighted MR images and slight enhancement.

Diaphyseal medullary stenosis (DMS) is an extremely rare hereditary bone dysplasia, which was first described by Arnold in 1973. DMS has a high incidence of pleomorphic malignant fibrous histiocytoma (MFH). In this paper, we report the imaging findings of DMS with pleomorphic MFH of the bone, mainly describing 99mTc hydroxymethylenediphosphonate (HMDP) and thallium-201 (201Tl) chloride scintigraphy findings. On 99mTc HMDP scintigraphy, focal increased uptake area of the right femur corresponded to the area of bone marrow invasion of the tumor and bone infarction. The mechanism of the uptake of 99mTc HMDP to the extraosseous lesion was not clear. On 201Tl chloride scintigraphy, the increased uptake of the periphery of the mass seemed to reflect the aggressiveness of invasion and the cellularity.

Background: We evaluated whether color Doppler ultrasound (US) had diagnostic accuracy equal to dynamic computed tomography (CT) and whether performing dynamic CT and Doppler US together would be more informative in preoperative diagnosis of renal solid tumors. Methods: A total of 110 renal solid tumors smaller than 7 cm were evaluated with dynamic CT and Doppler US. We compared the enhancement and the color flow patterns with the histopathological subtypes. Results: Eighty-seven (95.6%) of 91 clear cell carcinomas showed rich enhancement in the cortical nephrographic phase (CNP) and 82 (90.1%) of them had color flow in the Doppler US. Of the total of 110 tumors, nine (8.1%) did not show color flow in spite of rich enhancement in the CNP. Conversely, eight (7.2%) of the 110 tumors showed color flow in spite of poor enhancement, including two chromophobe cell carcinomas and two metastatic renal tumors. Conclusions: The enhancement pattern in dynamic CT and the color flow pattern in Doppler US were different among the subtypes of RCC. Color Doppler US had diagnostic accuracy equal to dynamic CT in most patients with renal solid tumors. Although Doppler US may play a unique role in the diagnosis of some renal parenchymal solid tumors, it is sufficient to perform dynamic CT alone for diagnosis of clear cell carcinoma.

Aim: To study the clinicopathologic characteristics of hepatic nodular lesions with high attenuation (increased portal blood flow) compared with surrounding hepatic parenchyma on computed tomography (CT) during arterial portography (CTAP). Methods : For six lesions found in six patients demonstrated as a high-attenuated mass by CTAP, CT during hepatic arteriography (CTHA; n = 3 patients), digital subtraction hepatic arteriography (n = 6) and conventional helical CT (n = 6) were evaluated retrospectively and compared with histopathologic findings (n = 4). Pathologic diagnosis was atypical adenomatous hyperplasia, nodule-in-nodule hepatocellular carcinoma (HCC) in one resected lesion each and overt HCC in two biopsied lesions. Two patients did not undergo any therapy and were followed up. Results : The average size of lesions was 2.2 cm (range 1.2–3.5 cm). The CTAP revealed high attenuation in all six lesions; entirely within the lesion (n = 4 lesions) or peripherally with a central low attenuation (n = 2). In contrast, CTHA showed low attenuated lesions; entirely within the mass (n = 2) or peripherally with a central high-attenuated spot (n = 1). Hepatic arteriogram revealed only two hypervascular lesions; entirely and partially in one each. In the arterial phase of helical CT, all but one lesion were iso- or hypo-attenuated. In two patients who were followed up to 39 and 55 months without therapy, neither tumor growth nor hemodynamic change of the lesion was recognized on CT. Conclusions: Even though the incidence of hepatic nodular lesions demonstrated as high attenuating on CTAP is low, all but one lesion in the current series showed iso- or hypo-attenuation on CTHA and/or helical CT, suggesting the hemodynamics are reciprocal between CTAP and CTHA. One exceptional lesion that showed high attenuation on both CTAP and conventional CT was pathologically advanced HCC. Based on the follow-up study of two untreated patients, this kind of lesion with high attenuation on CTAP seems to grow slowly. © 2002 Blackwell Publishing Asia Pty Ltd

Introduction The prognostic significance of conversion from nonshockable to shockable rhythms in patients with initial nonshockable rhythms who experience out-of-hospital cardiac arrest (OHCA) remains unclear. We hypothesized that the neurological outcomes in those patients would improve with subsequent shock delivery following conversion to shockable rhythms and that the time from initiation of cardiopulmonary resuscitation by emergency medical services personnel to the first defibrillation (shock delivery time) would influence those outcomes. Methods We analyzed the data of 569,937 OHCA adults with initial nonshockable rhythms. The data were collected in a nationwide Utstein-style Japanese database between 2005 and 2010. Patients were divided into subsequently shocked (n =21,944) and subsequently not-shocked (n =547,993) cohorts. The primary study endpoint was 1-month favorable neurological outcome (Cerebral Performance Categories scale, category 1 or 2). Results In the subsequently shocked cohort, the ratio of 1-month favorable neurological outcome was significantly higher than that in the subsequently not-shocked cohort (1.79% versus 0.60%, P