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Supplemental Digital Content is available in the text., Background and importance Bystander cardiopulmonary resuscitation (CPR) and initial shockable rhythm are crucial predictors of survival after out-of-hospital cardiac arrest (OHCA). However, the relationship between dispatcher-assisted CPR (DA-CPR) and initial shockable rhythm is not completely elucidated. Objective To examine the association of DA-CPR with initial shockable rhythm and outcomes. Design, setting and participants This nationwide population-based observational study conducted in Japan included 59 688 patients with witnessed OHCA of cardiac origin after excluding those without bystander CPR. Patients were divided into DA-CPR (n = 42 709) and CPR without dispatcher assistance (unassisted CPR, n = 16 979) groups. Outcome measures and analysis The primary outcome measure was initial shockable rhythm, and secondary outcome measures were 1-month survival and neurologically intact survival. A Cox proportional hazards model adjusted for collapse-to-first-rhythm-analysis time and multivariable logistic regression models were used after propensity score (PS) matching to compare the incidence of initial shockable rhythm and outcomes, respectively. Main results Among all patients (mean age 76.7 years), the rates of initial shockable rhythm, 1-month survival and neurologically intact survival were 20.8, 10.7 and 7.0%, respectively. The incidence of initial shockable rhythm in the DA-CPR group (20.4%, 3462/16 979) was significantly higher than that in the unassisted CPR group (18.5%, 3133/16 979) after PS matching (P < 0.0001). However, no significant differences were found between the two groups with respect to the incidence of initial shockable rhythm in the Cox proportional hazards model [adjusted hazard ratio of DA-CPR for initial shockable rhythm compared with unassisted CPR, 0.99; 95% confidence interval (CI), 0.97–1.02, P = 0.56]. No significant differences were observed in the survival rates in the two groups after PS matching [10.8% (1833/16 979) vs. 10.3% (1752/16 979), P = 0.16] and neurologically intact survival rates [7.3% (1233/16 979) vs. 6.8% (1161/16 979), P = 0.13]. The multivariable logistic regression model showed no significant differences between the groups with regard to survival (adjusted odds ratio of DA-CPR compared with unassisted CPR: 1.00; 95% CI, 0.89–1.13, P = 0.97) and neurologically intact survival (adjusted odds ratio: 1.12; 95% CI, 0.98–1.29, P = 0.14). Conclusion DA-CPR after OHCA had the same independent association with the likelihood of initial shockable rhythm and 1-month meaningful outcome as unassisted CPR.

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.

A fibroepithelial stromal polyp is a benign soft tissue tumour that can occur in the vagina, vulva and uterine cervix. Magnetic resonance imaging (MRI) findings have been reported in patients with vulvar fibroepithelial stromal polyps, not in those with vaginal polyps. We present MRI findings of vaginal fibroepithelial stromal polyp in a postmenopausal female. A 1 to 2 cm firm vaginal mass arising from the left side of the vaginal wall with hypointense signal changes on T1W MRI was identified. A well-defined vaginal mass (1 cm diameter) was detected with inhomogeneous signal intensity on T2W images. However, a major portion had high signal intensity on diffusion-weighted images. A benign vaginal lesion with oedematous changes or myxoid degeneration was suspected. Vaginal resection was performed, and fibroepithelial stromal polyp was pathologically diagnosed. MRI may be a useful non-invasive modality for preoperatively diagnosing vaginal fibroepithelial stromal polyps.

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.

Background The International Liaison Committee on Resuscitation recommends that dispatchers provide instructions to perform compression-only cardiopulmonary resuscitation (CPR) to callers responding to adults with out-of-hospital cardiac arrest (OHCA). This study aimed to determine the optimal dispatcher-assisted CPR (DA-CPR) instructions for OHCA. Methods We analysed the records of 24,947 adult patients (aged ≥ 18 years) who received bystander DA-CPR after bystander-witnessed OHCA. Data were obtained from a prospectively recorded Japanese nationwide Utstein-style database for a 2-year period (2016–2017). Patients were divided into compression-only DA-CPR (n = 22,778) and conventional DA-CPR (with a compression-to-ventilation ratio of 30:2, n = 2169) groups. The primary outcome measure was 1-month neurological intact survival, defined as a cerebral performance category score of 1–2 (CPC 1–2). Results The 1-month CPC 1–2 rate was significantly higher in the conventional DA-CPR group than in the compression-only DA-CPR group (before propensity score (PS) matching, 7.5% [162/2169] versus 5.8% [1309/22778], p p p p Conclusion Within the limitations of this retrospective observational study, conventional DA-CPR with a compression-to-ventilation ratio of 30:2 was preferable to compression-only DA-CPR as an optimal DA-CPR instruction for coaching callers to perform bystander CPR for adult patients with bystander-witnessed OHCAs.

Objectives Eltrombopag, a thrombopoietin-receptor agonist, stimulates hematopoiesis in patients with acquired aplastic anemia (AA). Cytomorphologic changes in bone marrow after eltrombopag administration are still unclear. This study examined the effect of eltrombopag on cytomorphologic findings using data from prior phase 2 studies (E1201 and E1202). Methods Microscopic examinations were performed in 31 patients with AA (E1201 [n = 21], E1202 [n = 10]). The relationship between hematologic improvement and morphologic findings was also investigated. Results In 5 patients (E1201 [n = 3], E1202 [n = 2]), the bone marrow blast count increased after initiation of eltrombopag treatment compared with screening values. The blast count was less than 5%, and the increase in bone marrow blasts was transient in all 4 patients who had bone marrow examinations at follow-up. In 8 patients (E1201 [n = 5], E1202 [n = 3]), dysplastic forms of megakaryocytes were found in the bone marrow following treatment initiation. Dysmegakaryopoiesis of 10% or more was found in 3 patients. None of the patients revealed micromegakaryocytes. Ten patients showed an increase in bone marrow blasts and/or dysmegakaryopoiesis following treatment initiation. Nine of 10 patients showed hematologic improvement in 1 or more lineages. Conclusions Dysmegakaryopoiesis without micromegakaryocytes and a transient increase of less than 5% in bone marrow blast count may be signs of hematologic improvement with eltrombopag for patients with AA.

As asphyxial cardiac arrest is more common than cardiac arrest from a primary cardiac event in paediatric cardiac arrest, effective ventilation is important during paediatric cardiopulmonary resuscitation (CPR). We aimed to determine optimal dispatcher-assisted CPR instructions for bystanders after paediatric out-of-hospital cardiac arrest (OHCA).We analysed the records of 8172 children who received bystander dispatcher-assisted CPR. Data were obtained from an All-Japan Utstein-style registry from 2005 to 2017. Patients were divided into conventional CPR and compression-only CPR groups. The primary study endpoint was 1-month neurologically intact survival, defined as a Cerebral Performance Category score of 1 or 2 (CPC 1-2).The 1-month CPC 1-2 rate was significantly higher in the dispatcher-assisted conventional CPR group than in the dispatcher-assisted compression-only CPR group (before propensity score matching, 5.7% [175/3077] vs. 3.1% [160/5095], p 0.0001, adjusted odds ratio 2.48, 95% confidence interval 1.19-3.22; after propensity score matching, 6.0% [156/2618] vs. 2.6% [69/2618], p 0.0001, adjusted odds ratio 2.42, 95% confidence interval 1.76-3.32). In most subgroup analyses after matching, dispatcher-assisted conventional CPR had a higher CPC 1-2 rate than dispatcher-assisted compression-only CPR; however, CPC 1-2 rates were similar between the two groups for patients with an initial shockable rhythm, those with total prehospital CPR time ≥ 20 min, those receiving public access defibrillation, advanced airway management, or adrenaline administration.Within the limitations of this retrospective observational study, dispatcher-assisted conventional CPR was preferable to dispatcher-assisted compression-only CPR as optimal CPR instructions for coaching callers to perform bystander CPR.

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.

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.

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.

Aim: Trends in neurologically intact survival after paediatric out-of-hospital cardiac arrest (OHCA) remain unclear. In the present study, we aimed to determine trends in 1-month neurologically intact survival after paediatric OHCA over time. Methods: We reviewed the data of 5461 children (aged < 18 years) who experienced bystander-witnessed OHCA and were included in the nationwide Japanese registry from 2005 to 2017. Patients were divided into three groups according to study period: 2005–2010, 2011–2015, and 2016–2017. We analysed the trends in 1-month neurologically intact survival rates over time. Results: The risk-adjusted odds of 1-month neurologically intact survival (odds ratio, 1.86; 95% confidence interval, 1.41–2.44) were significantly improved by 2016–2017 compared with baseline. Similar improvements in 1-month neurologically intact survival rates were observed with both standard bystander cardiopulmonary resuscitation (CPR) with rescue breaths and chest compression-only bystander CPR (P for trend < 0.05 and < 0.001, respectively). In the subgroup analyses by aetiology, the 1-month neurologically intact survival rate in patients with OHCA of non-traumatic origin significantly increased from 11.8%–15.1% to 19.7% (P for trend < 0.001) but not in those with OHCA of traumatic origin (from 4.9% to 3.4% to 4.1%; P for trend = 0.29). Conclusion: The 1-month neurologically intact survival rate significantly increased from 2005 to 2017 in Japanese children with bystander-witnessed OHCA, regardless of bystander CPR type; This increase was noted in patients with OHCA of non-traumatic origin but not in those with OHCA of traumatic origin.

Background/Introduction Shockable rhythm after cardiac arrest is highly expected after early initiation of bystander cardiopulmonary resuscitation (CPR) owing to increased coronary perfusion. However, the relationship between bystander CPR and initial shockable rhythm in patients with out-of-hospital cardiac arrest (OHCA) remains unclear. We hypothesized that chest-compression-only CPR (CC-CPR) before emergency medical service (EMS) arrival has an equivalent effect on the likelihood of initial shockable rhythm to the standard CPR (chest compression plus rescue breathing [S-CPR]). Purpose We aimed to examine the rate of initial shockable rhythm and 1-month outcomes in patients who received bystander CPR after OHCA. Methods The study included 59,688 patients (age, ≥18 years) who received bystander CPR after an OHCA with a presumed cardiac origin witnessed by a layperson in a prospectively recorded Japanese nationwide Utstein-style database from 2013 to 2017. Patients who received public-access defibrillation before arrival of the EMS personnel were excluded. The patients were divided into CC-CPR (n=51,520) and S-CPR (n=8168) groups according to the type of bystander CPR received. The primary end point was initial shockable rhythm recorded by the EMS personnel just after arrival at the site. The secondary end point was the 1-month outcomes (survival and neurologically intact survival) after OHCA. In the statistical analyses, a Cox proportional hazards model was applied to reflect the different bystander CPR durations before/after propensity score (PS) matching. Results The crude rate of the initial shockable rhythm in the CC-CPR group (21.3%, 10,946/51,520) was significantly higher than that in the S-CPR group (17.6%, 1441/8168, p Conclusions Compared with S-CPR, the CC-CPR before EMS arrival had an equivalent multivariable-adjusted association with the likelihood of initial shockable rhythm in the patients with OHCA due to presumed cardiac causes that was witnessed by a layperson. Funding Acknowledgement Type of funding source: None

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

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

Although white esophagus is an extremely rare disease, careful diagnosis and intensive treatment are required because of a relationship with black esophagus. Further case accumulation including duodenal and jejunum lesion is needed.

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 The effects of prehospital epinephrine administration in combination with the quality of cardiopulmonary resuscitation (CPR) on neurological outcomes in out-of-hospital cardiac arrest (OHCA) patients with non-shockable rhythm remains unclear. Purpose This study aimed to elucidate the effects of prehospital epinephrine administration in combination with the quality of CPR on neurologically intact survival in OHCA patients with non-shockable rhythm. Methods We analysed 118,732 adult OHCA patients with non-shockable rhythm from the All-Japan OHCA registry between 2011 and 2016 (29,989 emergency medical service [EMS]-witnessed arrests with EMS-initiated CPR [high-quality CPR] and 88,743 bystander-witnessed arrests with bystander-initiated CPR continued by EMS providers [low-quality CPR]). Patients who achieved prehospital return of spontaneous circulation without prehospital epinephrine administration were excluded. The primary outcome measure was 1-month neurologically intact survival (cerebral performance category 1 or 2; CPC 1–2). Time from collapse to prehospital epinephrine administration for patients with prehospital epinephrine administration, or to hospital arrival for patients without prehospital epinephrine administration was calculated and adjusted collectively in multivariate logistic regression analysis for 1-month CPC 1–2. Results Multivariate logistic regression analysis revealed that the time from collapse to prehospital epinephrine administration or to hospital arrival was negatively associated with 1-month CPC 1–2 (adjusted odds ratio [OR] 0.95 per 1-minute increment, 95% confidence interval [CI] 0.94–0.96). Compared with bystander-witnessed arrests without prehospital epinephrine administration, EMS-witnessed arrests with or without prehospital epinephrine administration were significantly associated with increased chances of 1-month CPC 1–2 (adjusted OR 2.04, 95% CI 1.50–2.75 and adjusted OR 1.97, 95% CI 1.57–2.48, respectively). Prehospital epinephrine administration was significantly associated with an increased chance of 1-month CPC 1–2 among bystander-witnessed arrests (adjusted OR 1.57, 95% CI 1.24–1.98), but not among EMS-witnessed arrests. EMS-witnessed arrests without prehospital epinephrine administration were significantly associated with an increased chance of 1-month CPC 1–2 compared with bystander-witnessed arrests with prehospital epinephrine administration (adjusted OR 1.26, 95% CI 1.01–1.56). Conclusions High-quality CPR is crucial for increasing neurologically intact survival in OHCA patients with non-shockable rhythm. The additional beneficial effects of prehospital epinephrine administration were observed only among OHCA patients with low-quality CPR.

Background Data on the effects of witness status and time from an emergency call to initiation of cardiopulmonary resuscitation (CPR) by emergency medical service (EMS) providers on neurological outcome in out-of-hospital cardiac arrest (OHCA) patients with non-shockable rhythm according to the first documented rhythm are limited. Purpose We aimed to determine the effects of witness status and time from an emergency call to CPR initiation by EMS providers on neurologically intact survival in OHCA patients according to the type of non-shockable rhythm (pulseless electrical activity [PEA] and asystole). Methods We analysed the records of 583,431 adult OHCA patients with non-shockable rhythm (191,905 bystander-witnessed arrest and 391,526 unwitnessed arrest). Data were derived from the prospectively recorded All-Japan OHCA registry between 2011 and 2016. Call to EMS-CPR interval was defined as the time from an emergency call to CPR initiation by EMS providers. The primary outcome was 1-month neurologically intact survival (cerebral performance category 1 or 2; CPC 1–2) and secondary outcome was presence of PEA. Results The rates of 1-month CPC 1–2 were 1.21% (2,326/191,905) for bystander-witnessed arrest and 0.24% (959/391,526) for unwitnessed arrest. When divided into 4 groups based on witness status and initial documented rhythm, these rates were 2.42% (1,869/77,190) for bystander-witnessed arrest with PEA (group A), 0.40% (457/114,715) for bystander-witnessed arrest with asystole (group B), 1.51% (679/44,926) for unwitnessed arrest with PEA (group C) and 0.08% (280/346,600) for unwitnessed arrest with asystole (group D). Multivariate logistic regression analysis revealed each 1-min delay of Call to EMS-CPR interval to be significantly associated with decreased chances of 1-month CPC 1–2 for groups A, B and D (adjusted odds ratio [OR]: 0.95, 0.91 and 0.96, respectively; 95% confidence interval [CI]: 0.93–0.96, 0.88–0.94 and 0.93–0.99, respectively). However, for group C, there was no significant relationship between these variables (adjusted OR: 1.00; 95% CI: 0.98–1.02). The proportion of PEA was 40.2% (77,190/191,905) for bystander-witnessed arrest and 11.5% (44,926/391,526) for unwitnessed arrest. Multivariate logistic regression analysis revealed that, as Call to EMS-CPR interval lengthened (per 1-min delay), the number of OHCA patients with PEA decreased for bystander-witnessed arrest (adjusted OR: 0.94; 95% CI: 0.93–0.94) and for unwitnessed arrest (adjusted OR: 0.96; 95% CI: 0.96–0.97). Conclusions The 1-month CPC 1–2 rate differed by witness status and initial documented rhythm in OHCA patients with non-shockable rhythm. Shortening of Call to EMS-CPR interval is crucial for improving 1-month CPC 1–2 rate and sustaining PEA, particularly in bystander-witnessed arrest.

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.

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.

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

BACKGROUND There is sparse data regarding the survival and neurological outcome of elderly patients with out-of-hospital cardiac arrest (OHCA). METHODS AND RESULTS OHCA patients (334,730) aged ≥75 years were analyzed using a nationwide, prospective, population-based Japanese OHCA database from 2008 to 2012. The overall 1-month survival with favorable neurological outcome (Cerebral Performance Category Scale, category 1 or 2; CPC 1-2) rate was 0.88%. During the study period, the annual 1-month CPC 1-2 rate in whole OHCA significantly improved (0.73% to 0.96%, P for trend

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.

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.

Upslope and downslope walking are basic activities necessary for normal daily living in community, and they impose greater joint load on the lower extremities than during level walking. Thus, the purpose of this study was to quantify the resultant and shear forces in the hip and knee joints during slope walking.Twelve healthy volunteers were evaluated when walking under level and 10° up- and downslope conditions. Three-dimensional gait analysis was conducted using a 7-camera optoelectronic motion analysis system combined with a force plate to measure ground reactive force. Joint forces in the hip and knee joints were estimated using musculoskeletal model simulation.Results showed that the resultant hip force was increased significantly to 117.2% and 126.9%, and the resultant knee force was increased to 133.5% and 144.5% in up- and downslope walking, respectively, compared to that of level walking. Furthermore, increased shear force in the hip and knee joints was noted during both slope walking conditions.This information may be beneficial for therapists advising elderly people or patients with osteoarthrosis on an appropriate gait pattern, gait assistive devices, or orthoses according to their living environment.

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.