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Objectives: Immunoglobulin A vasculitis/Henoch–Schönlein purpura (IgAV/HSP) is a major cause of vasculitis in children. It is often accompanied by nephritis (HSPN) and could progress to chronic kidney disease. Galactose‐deficient IgA1 was recently reported to be involved in the pathogenesis of HSPN, for which immunosuppressive drugs are considered key treatment. However, the involvement of immune cells in the development of HSPN remains unclear. Methods: We compared gene expressions of peripheral blood mononuclear cells (PBMCs) among healthy controls (n = 10), IgAV/HSP patients (n = 21) and HSPN patients (n = 8), which required nephritis development within 3 months of IgAV/HSP onset. Immunohistochemistry analysis and flow cytometry were performed to assess renal biopsy specimens and PBMCs, respectively. Serum CX3CL1 levels were measured by ELISA. Results: GNLY and GZMB expressions increased in HSPN patients, consistent with increased number of glomerular granulysin‐ and/or granzyme B‐positive cells demonstrated by immunohistochemistry analysis. Additionally, circulating cytotoxic T lymphocytes (CTLs) and natural killer (NK) cells were activated with the up‐regulated surface expressions of human leucocyte antigen DR (HLA‐DR) and CX3CR1 in HSPN patients with severe proteinuria. Renal biopsies demonstrated increased number of CD8+ cells and/or CD56+ cells and up‐regulated expression of glomerular CX3CL1, a specific ligand for CX3CR1, along with increased serum CX3CL1 level. Conclusion: Activated CTLs and NK cells play roles in the development of nephritis in IgAV/HSP patients and can be used as novel biomarkers for HSPN. [ABSTRACT FROM AUTHOR]

Background: Acute kidney injury (AKI) often occurs in pediatric patients who received allogeneic hematopoietic cell transplantation (HCT). We evaluated the risk and effect of HCT-related AKI in pediatric patients. Methods: We retrospectively studied the survival and renal outcome of 69 children 100 days and 1-year posttransplant in our institution in 2004–2016. Stage-3 AKI developed in 34 patients (49%) until 100 days posttransplant. Results: The 100-day overall survival (OS) rates of patients with stage-3 AKI were lower than those without it (76.5% vs. 94.3%, P = 0.035). The 1-year OS rates did not differ markedly between 21 post-100-day survivors with stage-3 AKI and 29 without it (80.8% vs. 87.9%, P = 0.444). The causes of 19 deaths included the relapse of underlying disease or graft failure (n = 11), treatment-related events (4), and second HCT-related events (4). Underlying disease of malignancy (crude hazard ratio (HR) 5.7; 95% confidence interval (CI), 2.20 to 14.96), > 1000 ng/mL ferritinemia (crude HR 4.29; 95% CI, 2.11 to 8.71), stem cell source of peripheral (crude HR 2.96; 95% CI, 1.22 to 7.20) or cord blood (crude HR 2.29; 95% CI, 1.03 to 5.06), and myeloablative regimen (crude HR 2.56; 95% CI, 1.24 to 5.26), were identified as risk factors for stage-3 AKI until 100 days posttransplant. Hyperferritinemia alone was significant (adjusted HR 5.52; 95% CI, 2.21 to 13.76) on multivariable analyses. Conclusions: Hyperferritinemia was associated with stage-3 AKI and early mortality posttransplant. Pretransplant iron control may protect the kidney of pediatric HCT survivors. [ABSTRACT FROM AUTHOR]

This article engages in a critical reflection on children's right to participation, focusing on their participation in three key spaces—streets, online spaces, and schools. These spaces are mentioned frequently in UN documents, yet the principle of protection tends to trump that of participation when it comes to children's activity in these spaces. Such treatment would not only underestimate the participatory dynamics of these spaces but also reinforce the dominant understanding of children as vulnerable, passive, and immature beings. By critically examining UNICEF's annual report, "The State of the World's Children," through a qualitative content analysis and drawing on recent counterexamples of children's activities in these spaces, this article reconceptualizes the participatory capacities of these spaces. [ABSTRACT FROM AUTHOR]

Background Human parvovirus B19 (B19V) causes glomerulopathy or microangiopathy, but not tubulopathy. We experienced an 11-year-old girl with spherocytosis who developed acute kidney injury on a primary infection of B19V. She presented with anuria, encephalopathy, thrombocytopenia, and coagulopathy, along with no apparent aplastic crisis. Methods Continuous hemodiafiltration, immunoglobulin, and intensive therapies led to a cure. Results A kidney biopsy resulted in a histopathological diagnosis of tubulointerstitial nephritis without immune deposits. The virus capsid protein was limitedly expressed in the tubular epithelial cells with infiltrating CD8-positive cells. Conclusions Viral and histopathological analyses first demonstrated B19-infected tubulointerstitial nephritis due to the aberrant viremia with hereditary spherocytosis. [ABSTRACT FROM AUTHOR]

Background: Pierson syndrome (PS) is a rare autosomal recessive disorder, characterized by congenital nephrotic syndrome and microcoria. Advances in renal replacement therapies have extended the lifespan of patients, whereas the full clinical spectrum of PS in infancy and beyond remains elusive. Case presentation: We present the case of a 12-month-old boy with PS, manifesting as the bilateral microcoria and congenital nephrotic syndrome. He was born without asphyxia, and was neurologically intact from birth through the neonatal period. Generalized muscle weakness and hypotonia were recognized from 3 months of age. The infant showed recurrent vomiting at age 5 months of age, and was diagnosed with gastroesophageal reflux and intestinal malrotation. Despite the successful surgical treatment, vomiting persisted and led to severely impaired growth. Tulobuterol treatment was effective in reducing the frequency of vomiting. Targeted sequencing confirmed that he had a compound heterozygous mutation in LAMB2 (NM_002292.3: p.Arg550X and p.Glu1507X). A search of the relevant literature identified 19 patients with severe neuro-muscular phenotypes. Among these, only 8 survived the first 12 months of life, and one had feeding difficulty with similar gastrointestinal problems. Conclusions: This report demonstrated that severe neurological deficits and gastrointestinal dysfunction may emerge in PS patients after the first few months of life. [ABSTRACT FROM AUTHOR]

In recent years, there has been a growing scholarly interest in conceptualising schools beyond their educational functions, as sites and agents of democracy. Yet this interest is often underpinned by a narrow conception of democracy, focusing solely on schools' public and social aspects. To capture the democratic potential of schools more fully, this article suggests adopting a deliberative systems approach, which conceptualises democracy as differentiated yet linked sites of democratic communications and views schools as one such site. Using this approach as a broader framework and drawing on the fieldwork conducted in two Japanese schools, this article identifies the condition under which schools can become a meaningful part of deliberative systems. It reveals that schools contribute to deliberative systems when they serve as a bridge between children's everyday practices and deliberative actions in the public space. In light of the findings, this article suggests conceptualising schools as a 'mediating space'. [ABSTRACT FROM AUTHOR]

In Philosophy for Children (P4C), consensus-making is often regarded as something that needs to be avoided. P4C scholars believe that consensus-making would dismiss P4C's ideals, such as freedom, inclusiveness, and diversity. This paper aims to counteract such assumptions, arguing that P4C scholars tend to focus on a narrow, or universal, concept of "consensus" and dismiss various forms of consensus, especially what Niemeyer and Dryzek (2007) call meta-consensus. Meta-consensus does not search for universal consensus, but focuses on the process by which people achieve various non-universal forms of consensus, such as agreement on the value of opponents' normative view or agreement on the degree to which they accept opponents' view. This paper argues that such meta-consensus is a key part of what Clinton Golding (2009) calls "philosophical progress," which is the essential element that makes inquiry philosophical. In other words, without meta-consensus and philosophical progress, inquiry ends in merely conversation or antagonistic talk. Drawing on the example of P4C conducted with Japanese students, this paper shows how meta-consensus is achieved in the community of philosophical inquiry and how it contributes to make inquiry philosophical. [ABSTRACT FROM AUTHOR]

Aim: The target Geriatric Nutritional Risk Index (GNRI) for patients on chronic maintenance hemodialysis is unclear. We aimed to determine the relationship between the GNRI and independent walking ability in such patients. Methods: In the present retrospective cohort study, 90 patients receiving chronic maintenance hemodialysis were included. Logistic regression analyses were carried out to evaluate the relationship between the GNRI and independent walking ability. Receiver operating characteristic curve analysis was carried out to determine the cut‐off GNRI for predicting independent walking ability. Results: Multivariate logistic regression analysis showed significant differences in age (odds ratio [OR] 0.8, 95% confidence interval [CI] 0.6–0.9), creatinine generation rate percentage (OR 1.1, 95% CI 1.0–1.2), GNRI (OR 1.4, 95% CI 1.1–1.8; P < 0.01) and urea removal rate (OR 0.3, 95% CI 0.1–0.9; P < 0.05). The cut‐off GNRI for independent walking ability was 86.7 (area under the curve 0.80, sensitivity 92.1%, specificity 66.7%, positive hit ratio 86.6%, negative hit ratio 78.3%). The factors correlated with survival in the univariate analysis were the GNRI, equilibrated Kt/V, urea removal rate, clear space rate, salt intake amount (P < 0.01), number of days of hospitalization and %creatinine generation rate (P < 0.05). The Cox proportional hazard regression model showed an OR of 0.77 (95% CI 0.32–1.8) at a GNRI <86/GNRI ≥86. In the multivariate survival analysis, we observed no significant differences in any of the factors. Conclusions: GNRI was correlated with walking ability, which indicated that GNRI might predict future walking ability; also, a GNRI of 87 might be the target for maintaining walking ability. Geriatr Gerontol Int 2018; 18: 1556–1561. [ABSTRACT FROM AUTHOR]

Involvement of children in research processes requires various ethical considerations. In particular, while interviewing children, a researcher needs to take into consideration the power imbalance between a researcher and children as well as among children. This article suggests a possible way of mitigating potential risks, drawing on the idea and practice of the Community of Inquiry (CoI) as an interview method. CoI is the practice of group dialog for knowledge-making, where participants talk about a common topic by sharing their lived experiences in a cooperative manner. This article shows that CoI allows children to act as both interviewers and interviewees, which helps children in reflective knowledge-making while at the same time mitigating the ethical concerns of interviewing. To illustrate how CoI can help achieve these goals, this article draws on the empirical research conducted with a group of junior high school students in Japan. [ABSTRACT FROM AUTHOR]

This study aimed to determine the accuracy of the quick Sequential Organ Failure Assessment (qSOFA) score in predicting mortality among prehospital patients with and without infection. This single-center, retrospective, cross-sectional study was conducted among patients who arrived via the emergency medical services (EMS). We calculated the qSOFA score and Modified Early Warning Score (MEWS) from prehospital records. We identified patients as infected if they received intravenous antibiotics at the emergency department or within the first 24 hours. Receiver operating characteristic analysis was used to evaluate and compare the performance of the qSOFA score, each physiological parameter, and the MEWS in predicting admission and in-hospital mortality in patients with and without infection. Multivariate analysis was used to evaluate the qSOFA score and other risk factors. Out of 1574 prehospital patients, 47.1% were admitted and 3.2% died in the hospital. The performance of the qSOFA score in predicting in-hospital mortality in noninfected patients was 0.70, higher than for each parameter and the MEWS. The areas under the curve for the qSOFA+ model vs. the qSOFA- model was 0.77 vs. 0.68 for noninfected patients (p <0.05) and 0.71 vs. 0.68 for infected patients (p = 0.41). The likelihood ratio test comparing the qSOFA- and qSOFA+ groups demonstrated significant improvement for noninfected patients (p <0.01). Multivariate regression analysis for in-hospital mortality demonstrated that the qSOFA score is an independent prognosticator for in-hospital mortality, especially among noninfected patients (odds ratio, 3.60; p <0.01). In conclusion, the prehospital qSOFA score was associated with in-hospital mortality in noninfected patients and may be a beneficial tool for identifying deteriorating patients in the prehospital setting. [ABSTRACT FROM AUTHOR]

A 6-year-old boy was diagnosed with chromosomal abnormalities (48,XYY, + 21[11]/46,XY[19]) at 4 months of age after a physical examination revealed an undescended testis and a dwarf penis. He also had mild renal dysfunction and severe proteinuria, and kidney biopsy at 2 years of age revealed focal segmental glomerulosclerosis. Genetic analysis to investigate suspected WT1 gene abnormalities revealed a novel variant in NM_024426.6:exon10:c.1506 T > A (p.(Asp502Glu)). His kidney function deteriorated rapidly, leading to the induction of peritoneal dialysis at 5 years of age. Although this variant had not been previously reported, bilateral nephrectomy was performed to prevent any progression of the tumor. Histopathology showed all the glomeruli observed within the observation area to be completely sclerotic, while also showing evidence of embryonal hyperplasia. This case was not a hot spot for Denys-Drash syndrome, but it had a similar phenotype and pathology that could have been derived from a WT1 gene abnormality. [ABSTRACT FROM AUTHOR]

Objectives: Visualizing the needle tip using the short-axis (SA) ultrasound-guided central venous catheterization approach can be challenging. It has been suggested to start the process with the SA approach and then switch to the long-axis (LA); however, to our knowledge, this combination has not been evaluated. We compared the combined short- and long-axis (SLA) approach with the SA approach in a manikin study. Methods: We performed a prospective randomized controlled cross-over study in an urban emergency department and intensive care unit. Resident physicians in post-graduate years 1–2 performed a simulated ultrasound-guided internal jugular vein puncture using the SA and SLA approaches on manikins. Twenty resident physicians were randomly assigned to two equal groups: (1) one group performed punctures using the SA approach followed by SLA; and (2) the other performed the same procedures in the opposite order. We compared the success rate and procedure duration for the two approaches. Procedural success was defined as insertion of the guide-wire into the vein while visualizing the needle tip at the time of anterior wall puncture, without penetrating the posterior wall. Results: Six resident physicians (30%) performed both approaches successfully, while 12 (60%) performed the SLA approach, but not the SA, successfully. Those who performed the SA approach successfully also succeeded with the SLA approach. Two resident physicians (10%) failed to perform both approaches. The SLA approach had a significantly higher success rate than the SA approach (P < 0.001). The median (interquartile range) procedure duration was 59.5 [46.0–88.5] seconds and 45.0 [37.5–84.0] seconds for the SLA and SA approaches, respectively. The difference of the duration between the two procedures was 15.5 [0–28.5] seconds. There was no significant difference in duration between the two approaches (P = 0.12). Conclusions: Using the SLA approach significantly improved the success rate of internal jugular vein puncture performed by novice physicians on a manikin model, without increasing procedural duration. Further clinical trials are warranted to confirm the procedure’s utility in actual patients. Trial registration: UMIN Clinical Trials Registry [ABSTRACT FROM AUTHOR]

Aim: This study investigated the value of regional cerebral oxygen saturation (rSO2) monitoring upon arrival at the hospital for predicting post-cardiac arrest intervention outcomes.Methods: We enrolled 1195 patients with out-of-hospital cardiac arrest of presumed cardiac cause from the Japan-Prediction of Neurological Outcomes in Patients Post-cardiac Arrest Registry. The primary endpoint was a good neurologic outcome (cerebral performance categories 1 or 2 [CPC1/2]) 90 days post-event.Results: A total of 68 patients (6%) had good neurologic outcomes. We found a mean rSO2 of 21%±13%. A receiver operating characteristic curve analysis indicated an optimal rSO2 cut-off of ≥40% for good neurologic outcomes (area under the curve 0.92, sensitivity 0.81, specificity 0.96). Good neurologic outcomes were observed in 53% (55/103) and 1% (13/1092) of patients with high (≥40%) and low (<40%) rSO2, respectively. Even without return of spontaneous circulation (ROSC) upon arrival at the hospital, 30% (9/30) of patients with high rSO2 had good neurologic outcomes. Furthermore, 16 patients demonstrating ROSC upon arrival at the hospital and low rSO2 had poor neurologic outcomes. Multivariate analyses indicated that high rSO2 was independently associated with good neurologic outcomes (odds ratio=14.07, P<0.001). Patients with high rSO2 showed favourable neurologic prognoses if they had undergone therapeutic hypothermia or coronary angiography (CPC1/2, 69% [54/78]). However, 24% (25/103) of those with high rSO2 did not undergo these procedures and exhibited unfavourable neurologic prognoses (CPC1/2, 4% [1/25]).Conclusion: rSO2 is a good indicator of 90-day neurologic outcomes for post-cardiac arrest intervention patients. [ABSTRACT FROM AUTHOR]

Aim: Our study aimed at filling the fundamental knowledge gap on the characteristics of regional brain oxygen saturation (rSO2) levels in out-of-hospital cardiac arrest (OHCA) patients with or without return of spontaneous circulation (ROSC) upon arrival at the hospital for estimating the quality of cardiopulmonary resuscitation and neurological prognostication in these patients.Methods: We enrolled 1921 OHCA patients from the Japan - Prediction of Neurological Outcomes in Patients Post-cardiac Arrest Registry and measured their rSO2 immediately upon arrival at the hospital by near-infrared spectroscopy using two independent forehead probes (right and left). We also assessed the percentage of patients with a good neurological outcome (defined as cerebral performance categories 1 or 2) 90 days post cardiac arrest.Results: After 90 days, 79 (4%) patients had good neurological outcomes and a median lower rSO2 level of 15% (15-20%). Compared to patients without ROSC upon arrival at the hospital, those with ROSC had significantly higher rSO2 levels (56% [39-65%] vs. 15% [15-17%], respectively; P<0.01), and significantly correlated right- and left-sided regional brain oxygen saturation levels (R=0.94 vs. 0.66, respectively). In both groups, the percentage of patients with a good 90-day neurological outcome increased significantly in proportion to their rSO2 levels upon arrival at the hospital (P<0.01).Conclusion: Our data indicate that measuring rSO2 levels might be effective for both monitoring the quality of resuscitation and neurological prognostication in patients with OHCA. [ABSTRACT FROM AUTHOR]

The authors report a case involving an elderly patient who experienced repetitive perioperative cardiac arrest caused by laryngomalacia. The patient underwent surgery under general anesthesia; however, 2 h after initial extubation, he experienced cardiopulmonary arrest. Return of spontaneous circulation was achieved by immediate resuscitation. Four hours later, a second extubation was performed without any neurological complications. However, 2 h later, he experienced cardiopulmonary arrest again. Immediately after the third extubation, 12 h after the second cardiopulmonary arrest, fiberoptic laryngoscopy revealed laryngomalacia. His respiratory condition stabilized after emergent tracheostomy. Laryngomalacia should be considered even in adult cases when signs of upper airway obstruction manifest after extubation. [ABSTRACT FROM AUTHOR]

Background: Although increasing staff numbers during shifts when emergency department (ED) crowding is severe can help meet patient demand, it remains unclear how different types of added staff, particularly junior residents, may affect crowding. Methods: To identify associations between types of staff and ED crowding, we conducted a cross-sectional, single-center study in the ED of a large, teaching hospital in Japan between January and December 2012. Patients who visited the ED during the study period were enrolled. We excluded (1) patients previously scheduled to visit the ED, and (2) neonates transferred from other hospitals. During the study period, 27,970 patients were enrolled. Types of staff analyzed were junior (first and second year) residents, senior (third to fifth year) residents, attending (board-certified) physicians, and nurses. A generalized linear model was applied to length of ED stay for all patients as well as admitted and discharged patients to quantify an association with the additional staff. Results: In the model, addition of one attending physician or senior resident was associated with decreased length of ED stay for total patients by 3.88 or 1.64 minutes, respectively (95% CI, 2.20–5.56 and 0.81–2.48 minutes); while additional nursing staff had no association. Surprisingly, however, one additional junior resident was associated with prolonged length of ED stay for total patients by 0.97 minutes (95% CI 0.37–1.57 minutes) and for discharged patients by 1.01 minutes (95% CI 0.45–1.59 minutes). Conclusion: Staffing adjustments aimed at alleviating ED crowding should focus on adding more senior staff during peak-volume shifts. [ABSTRACT FROM AUTHOR]

Study Objective: We compared the effects of execution of diagnostic tests in the emergency department (ED) and other common factors on the length of ED stay to identify those with the greatest impacts on ED crowding. Methods: Between February 2010 and January 2012, we conducted a cross-sectional, single-center study in the ED of a large, urban, teaching hospital in Japan. Patients who visited the ED during the study period were enrolled. We excluded (1) patients scheduled for admission or pharmaceutical prescription, and (2) neonates requiring intensive care transferred from other hospitals. Multivariate linear regression was performed on log-transformed length of ED stay in admitted and discharged patients to compare influence of diagnostic tests and other common predictors. To quantify the range of change in length of ED stay given a unit change of the predictor, a generalized linear model was used for each group. Results: During the study period, 55,285 patients were enrolled. In discharged patients, laboratory blood tests had the highest standardized β coefficient (0.44) among common predictors, and increased length of ED stay by 72.5 minutes (95% CI, 72.8–76.1 minutes). In admitted patients, computed tomography (CT) had the highest standardized β coefficient (0.17), and increased length of ED stay by 32.7 minutes (95% CI, 40.0–49.9 minutes). Although other common input and output factors were significant contributors, they had smaller standardized β coefficients in both groups. Conclusions: Execution of laboratory blood tests and CT had a stronger influence on length of ED stay than other common input and output factors. [ABSTRACT FROM AUTHOR]

Mucopolysaccharidosis type II (MPS II) is caused by deficiency of lysosomal enzyme iduronate-2-sulfatase. Insufficient activity of the enzyme results in accumulation of glycosaminoglycans leading to progressive multisystem pathologies. MPS II is less likely to be complicated by kidney and urinary tract problems. We report a boy with MPS II, who developed left hydronephrosis. His hydronephrosis improved after starting enzyme replacement therapy. It was suggested that MPS II was closely associated with the pathogenesis of hydronephrosis. [ABSTRACT FROM AUTHOR]

Abstract: Aim: To investigate the association between regional brain oxygen saturation (rSO2) at hospital arrival and neurological outcomes at 90 days in patients with out-of-hospital cardiac arrest (OHCA). Methods: The Japan-Prediction of neurological Outcomes in patients post cardiac arrest (J-POP) registry is a prospective, multicenter, cohort study to test whether rSO2 predicts neurological outcomes after OHCA. We measured rSO2 in OHCA patients immediately after hospital arrival using a near-infrared spectrometer placed on the forehead with non-blinded fashion. The primary endpoint was “neurological outcomes” at 90 days after OHCA. Results: EMS providers are not permitted to terminate CPR in the field in Japan, and so most patients with OHCA who are treated by EMS personnel are transported to emergency hospitals. Among 1017 OHCA patients, 672 patients including 52 comatose patients with pulses detectable (8%) and 620 cardiac arrest patients (92%) at hospital arrival were enrolled prospectively and consecutively. Twenty-nine patients with good neurological outcome had a significantly higher value of rSO2 at hospital arrival than 643 patients with poor neurological outcome (mean [±SD] 55.6±20.8% vs. 19.7±11.0%, p <0.001). Receiver operating curve analysis indicated an optimal rSO2 cutoff point of >42% for predicting good neurological outcome, with sensitivity 0.79 (95% confidence interval [CI], 0.60–0.92), specificity 0.95 (95% CI, 0.93–0.96), positive predictive value, 0.41 (95% CI, 0.28–0.55), negative predictive value, 0.99 (95% CI, 0.98–1.00), and area under the curve 0.90 (95% CI, 0.88–0.92). Conclusion: The rSO2 at hospital arrival can predict good neurological outcome at 90 days after OHCA. [Copyright &y& Elsevier]

Abstract: Background: Few prospective cohort studies have examined the relationship between reduced left ventricular ejection fraction (LVEF) and other comorbidities for precise risk stratification of sudden cardiac death (SCD) after coronary revascularization. Methods: We analyzed 9877 consecutive patients who underwent first elective percutaneous coronary intervention (PCI) (n =6878) and coronary artery bypass grafting (CABG) (n =2999) between 2000 and 2002 at 30 institutions registered under the CREDO-Kyoto registry. Results: During the long-term follow-up (median follow-up period=42.8 months), 906 patients (9.4%) died; death from cardiovascular causes was observed in 517 (5.7%) patients; cardiac death, in 376 (3.9%) patients; and SCD, in 140 (1.5%) patients. The rates of SCD were 0.5%, 0.9%, and 1.3% at 1, 2, and 3 years of follow-up, respectively. Multivariate analyses indicated that dialysis (hazard ratio=2.51), chronic obstructive pulmonary disease (hazard ratio=2.04), congestive heart failure (hazard ratio=1.63), reduced LVEF (LVEF≤30%; hazard ratio=1.55), chronic total occlusion of coronary artery (hazard ratio=1.38), diabetes with insulin therapy (hazard ratio=1.33), chronic renal disease (hazard ratio=1.29), and peripheral artery disease (hazard ratio=1.27) were independent predictors of SCD. Conclusions: The method of revascularization had no influence on the incidence of SCD, and the adjusted hazard ratio of reduced LVEF was smaller than that observed in dialysis, chronic obstructive pulmonary disease, and congestive heart failure. This indicated that the risk of SCD depends on multiple variables in addition to LVEF. [ABSTRACT FROM AUTHOR]

Abstract: Background: Limited data are available on long-term mortality and morbidity of patients with chronic obstructive pulmonary disease (COPD) and ischemic heart disease. We examined how COPD affects long-term mortality and morbidity after undergoing percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). Methods: We analyzed 9877 consecutive patients who underwent their first elective PCI (n =6878) and CABG (n =2999) in 2000–2002 at 30 institutions listed in the CREDO–Kyoto registry. Results: COPD was diagnosed in 240 patients (2.4%). In-hospital mortality (1.3% vs. 1.2%, p =0.972) did not differ between patients with and without COPD. During long-term follow-up (42. 8 month s), 906 patients (9.4%) died, 517 (5.3%) of whom died of cardiovascular death and 376 (3.9%), of cardiac death. At 3 years, the unadjusted survival rate and the rates of freedom from cardiovascular death and cardiac death were 92.1%, 95.3%, and 96.5% in the total population and 82.8%, 91.7%, and 92.1% in patients with COPD respectively. Log-rank test indicated that COPD was associated with higher incidence of all-cause mortality (p <0.0001), cardiovascular death (p =0.0002), and cardiac death (p <0.0001). Multivariate analyses indicated that COPD was an independent predictor of all-cause mortality (hazard ratio 1.36, p =0.0003), cardiovascular death (hazard ratio 1.28, p =0.0407), and cardiac death (hazard ratio 1.48, p =0.003). Conclusions: COPD is an independent risk factor for long-term cardiac and cardiovascular mortality in patients with ischemic heart disease. [ABSTRACT FROM AUTHOR]

In spite of the progress made in acute angiographic evaluation and obtaining durable reperfusion of acute myocardial infarction (AMI) in the past two decades, cardiac free wall rupture (FWR) is still one of the causes of mortality following AMI. In this study, we evaluated the role of thrombolysis in the risk of FWR in AMI patients treated with acute percutaneous coronary intervention (PCI). Among 3,786 consecutive AMI patients seen between 1985 and 2003, 3,066 patients were treated by primary PCI or rescue PCI, with or without additional thrombolysis. FWR occurred in 24 of 3,066 patients (0.8%) treated by PCI; female gender (1.4% vs 0.6%, P = 0.001), age >75 years, (1.4% vs 0.6%, P = 0.001) left main coronary artery (LMCA)-related infarction, (4.5% vs all other arteries, P = 0.015), and thrombolytic use (3.1% vs 0.4%, P < 0.001) were all associated with higher rates of FWR by univariate analysis. In patients treated with PCI and thrombolysis, FWR occurred in 2.7% with optimal PCI results but in only 4.9% if PCI was unsuccessful (P = NS). The incidence of FWR in patients with optimal PCI without thrombolysis was 0.4% (P < 0.001). Multivariable analysis identified thrombolytic use (odds ratio [OR]: 8.49, 95% confidence interval [CI]: 3.66–19.7, P < 0.001), LMCA-related infarction (OR: 7.06, 95% CI: 1.89–26.4, P = 0.004), and female gender (OR: 3.02, 95% CI: 1.27–7.21, P = 0.013) as independent predictors of FWR. Thrombolysis is one of the contributing causes of FWR in AMI patients undergoing PCI, even when PCI is successful. (J Interven Cardiol 2005;18:167–172) [ABSTRACT FROM AUTHOR]

Few studies have compared the sensitivities of autopsy and post mortem computed tomography (PMCT) in detecting rib fractures caused by cardiopulmonary resuscitation (CPR). We aimed to compare the characteristics between both modalities for accurately detecting CPR-related rib fractures. This single-centre observational study included adult patients with autopsy records and PMCT scans at our institution from January 2013 to March 2019. CPR-related rib fractures were evaluated using autopsy and PMCT findings. In 62 patients enrolled, 339 rib fractures were detected on autopsy and/or PMCT (222 fractures on both PMCT and autopsy, 69 on PMCT alone, and 50 on autopsy alone). The agreement of detection for both modalities was substantial (kappa coefficient, 0.78). In the logistic regression model, incomplete fractures detected by PMCT and age <75 years were significantly associated with findings that were negative on autopsy but positive on PMCT, while rib number (ribs 1–3 and 7–12) and fracture location (posterolateral and paravertebral) were significantly associated with negative PMCT findings but positive autopsy findings. Autopsy and PMCT showed complementary roles, and are thus necessary in accurately detecting CPR-related rib fractures. Combining both modalities may contribute to improved CPR quality and better understanding of discrepancy in characteristics between the two modalities. [ABSTRACT FROM AUTHOR]

Multiorgan dysfunction is a concern of Fontan patients. To clarify the pathophysiology of Fontan nephropathy, we characterize renal disease in the long-term observational study. Medical records of 128 consecutive Fontan patients [median age: 22 (range 15–37) years old] treated between 2009 and 2018 were reviewed to investigate the incidence of nephropathy and its association with other clinical variables. Thirty-seven patients (29%) showed proteinuria (n = 34) or < 90 mL/min/1.73 m2 of estimated glomerular filtration rate (eGFR) (n = 7), including 4 overlapping cases. Ninety-six patients (75%) had liver dysfunction (Forns index > 4.21). Patients with proteinuria received the Fontan procedure at an older age [78 (26–194) vs. 56 (8–292) months old, p = 0.02] and had a higher cardiac index [3.11 (1.49–6.35) vs. 2.71 (1.40–4.95) L/min/m2, p = 0.02], central venous pressure [12 (7–19) vs. 9 (5–19) mmHg, p < 0.001], and proportion with > 4.21 of Forns index (88% vs. 70%, p = 0.04) than those without proteinuria. The mean renal perfusion pressure was lower in patients with a reduced eGFR than those without it [55 (44–65) vs. 65 (45–102) mmHg, p = 0.03], but no other variables differed significantly. A multivariable analysis revealed that proteinuria was associated with an increased cardiac index (unit odds ratio 2.02, 95% confidence interval 1.12–3.65, p = 0.02). Seven patients with severe proteinuria had a lower oxygen saturation than those with no or mild proteinuria (p = 0.01, 0.03). Proteinuria or a decreased eGFR differentially occurred in approximately 30% of Fontan patients. Suboptimal Fontan circulation may contribute to the development of proteinuria and reduced eGFR. [ABSTRACT FROM AUTHOR]

Background: Early dumping syndrome characterized by palpitation, dizziness, cold sweat, feebleness, and abdominal symptoms, occurs within 30 minutes after meals in patients who have undergone gastrectomy. This case report describes the case of a patient who presented with severe distributive shock due to early dumping syndrome; he recovered within a few hours after massive fluid infusion and vasopressor administration.Case Presentation: Our patient was a 68-year-old Japanese man who underwent total gastrectomy for gastric cancer and was diagnosed as having late dumping syndrome. On admission, he developed severe shock and was treated with massive fluid administration. Based on the history of the present illness, past medical history, normal findings of blood chemistry test, transient course, and Sigtad score, which helps diagnose dumping syndrome, early dumping syndrome was considered the cause of severe distributive shock.Conclusions: Early dumping syndrome can cause severe shock requiring massive fluid infusion and vasopressor administration. It should be considered a cause of severe distributive shock in patients who have undergone gastrectomy. [ABSTRACT FROM AUTHOR]

Background: Although median sternotomy is standard during cardiac surgery, the procedure is associated with a risk of injury to mediastinal organs. Here, we discuss two cases of tracheal injury following median sternotomy during cardiac surgery.Case Presentation: Ventilation failure occurred in a 78-year-old Japanese man and a 71-year-old Japanese man after median sternotomy, and tracheal injury was identified. The sites of injury were directly repaired and covered with mediastinal fat tissue, following which ventilation was successful. The burn-like deposits observed at the site of tracheal injury and on the removed endotracheal tube support the notion that the injuries in our patients were caused by electrocautery prior to median sternotomy. In one case, short sternotracheal distance may have contributed to tracheal injury during post-sternal manipulation. In both cases, the relative inexperience of both surgeons also supports the suspected cause of injury.Conclusions: Tracheal injury represents a potential complication following median sternotomy, especially when performed by inexperienced surgeons or in cases of short sternotracheal distance. Anesthesiologists should consider this rare yet potentially lethal complication. [ABSTRACT FROM AUTHOR]

Abstract In the treatment of severe infections in critical care settings, the selection of initial empirical antimicrobials affects patient outcomes and antimicrobial overuse. The application of a comprehensive treatment guidance might facilitate appropriate antimicrobial selection. Therefore, we developed such an antimicrobial guidance for use in emergency and critical care center and verified its efficacy. We retrospectively analyzed the data of 195 patients (96 patients before guidance introduction [control group] and 99 after guidance introduction [intervention group]) who were ultimately diagnosed with bacteremia to assess the effects of the guidance (the intervention). The appropriateness of the empirical therapy was greater in the intervention than in the control group (96% vs. 90%, respectively; P = 0.10). Moreover, the rate of carbapenem use was significantly lower in the intervention than in the control group (6% vs. 20%, respectively; P < 0.01). The control and intervention groups had similar 28-day survival rates of 81% and 85%, respectively; P = 0.50). These findings imply that introducing an empirical antimicrobial guidance in emergency outpatient and emergency intensive care settings could improve antimicrobial stewardship without affecting patient mortality. The data of this study can be used as a reference for establishing the study design of a large-scale prospective trial, aimed at verifying guidance efficacy. [ABSTRACT FROM AUTHOR]

Background: Patient survival and physical outcomes among children with end-stage kidney disease (ESKD) have significantly improved, and recent research has focused on long-term depression symptoms and health-related quality of life (HRQOL). However, no studies have been conducted among adolescents and young adults with childhood-onset ESKD in Japan. Methods: This multicenter study included 45 adolescents and young adults aged 16–39 years who developed ESKD at age < 20 years. Depression symptoms were measured using the Beck Depression Inventory (BDI)-II. The Short Form-36 Health Survey (SF-36) was used to assess HRQOL. Factors associated with depression and HRQOL were analyzed. Results: Depression (BDI-II score ≥ 14) was observed in 13 (29%) patients. Patient's SF-36 physical component summary (PCS) and mental component summary (MCS) scores were comparable with those for the general population. Lower estimated glomerular filtration rate, higher BDI-II scores, and lower body mass index were associated with lower PCS scores. BDI-II scores were negatively correlated with MCS scores. We observed a trend that unemployment was associated with lower MCS scores. Conclusions: Depression is frequently observed among adolescents and young adults with childhood-onset ESKD. Regular screening for psychosocial concerns, maintaining stable graft functions, and achieving optimal nutritional status may contribute to improved well-being among these patients. [ABSTRACT FROM AUTHOR]

Background: Adolescents and young adults face various socio-emotional and behavioral challenges that can affect their medical and psychosocial outcomes. Pediatric patients with end-stage kidney disease (ESKD) often have extra-renal manifestations, including intellectual disability. However, limited data are available regarding the impact of extra-renal manifestations on medical and psychosocial outcomes among adolescents and young adults with childhood-onset ESKD. Methods: Patients born between January 1982 and December 2006 that had developed ESKD in 2000 and later at age < 20 years were enrolled in this multicenter study in Japan. Data for patients' medical and psychosocial outcomes were retrospectively collected. Associations between extra-renal manifestations and these outcomes were analyzed. Results: In total, 196 patients were analyzed. The mean age at ESKD was 10.8 years, and at last follow-up was 23.5 years. The first modality of kidney replacement therapy was kidney transplantation, peritoneal dialysis, and hemodialysis in 42, 55 and 3% of patients, respectively. Extra-renal manifestations were documented in 63% of patients and 27% had intellectual disability. Baseline height at kidney transplantation and intellectual disability significantly impacted final height. Six (3.1%) patients died, of which five (83%) had extra-renal manifestations. Patients' employment rate was lower than that in the general population, especially among those with extra-renal manifestations. Patients with intellectual disability were less likely to be transferred to adult care. Conclusions: Extra-renal manifestations and intellectual disability in adolescents and young adults with ESKD had considerable impacts on linear growth, mortality, employment, and transfer to adult care. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 19-year-old man with end-stage renal failure secondary to bilateral hypoplastic kidney received. The patient complained of dyspnea three months after starting peritoneal dialysis (PD). The article also discusses the diagnosis and treament of hydrothorax secondary to pleuroperitoneal communication (PPC).

Aim: Target temperature management (TTM) is used in comatose post-cardiac arrest patients, but the recommended temperature range is wide. This study aimed to assess the effectiveness of TTM at 32-34 °C while considering the degree of cerebral injury and cerebral circulation, as assessed by regional cerebral oxygen saturation (rSO2).Methods: This is a secondary analysis of prospectively collected registry data from comatose patients who were transferred to 15 hospitals in Japan after out-of-hospital cardiac arrest (OHCA) from 2011 to 2013. The primary outcome was all-cause mortality at 90 days after OHCA, and the secondary outcome was favorable neurological outcomes as evaluated according to the Cerebral Performance Category. We monitored rSO2 noninvasively with near-infrared spectroscopy, which could assess cerebral perfusion and the balance of oxygen delivery and uptake.Results: We stratified 431 study patients into three groups according to rSO2 on hospital arrival: rSO2 ≤40% (n = 296), rSO2 41-60% (n = 67), and rSO2 ≥61% (n = 68). Propensity score analysis revealed that TTM at 32-34 °C decreased all-cause mortality in patients with rSO2 41-60% (average treatment effect on treated [ATT] by propensity score matching [PSM] -0.51, 95%CI -0.70 to -0.33; ATT by inverse probability of treatment weighting [IPW] -0.52, 95%CI -0.71 to -0.34), and increased favorable neurological outcomes in patients with rSO2 41-60% (ATT by PSM 0.50, 95%CI 0.32-0.68; ATT by IPW 0.52, 95%CI 0.35-0.69).Conclusion: TTM at 32-34 °C effectively decreased all-cause mortality in comatose OHCA patients with rSO2 41-60% on hospital arrival in Japan. [ABSTRACT FROM AUTHOR]

Background: Long durational chest compression (CC) deteriorates cardiopulmonary resuscitation (CPR) quality. The appropriate number of CC personnel for minimizing rescuer’s fatigue is mostly unknown. Objective: We determined the optimal number of personnel needed for 30-min CPR in a rescue-team. Methods: We conducted a randomized, manikin trial on healthcare providers. We divided them into Groups A to D according to the assigned different rest period to each group between the 2 min CCs. Groups A, B, C, and D performed CCs at 2, 4, 6, and 8 min rest period. All participants performed CCs for 30 min with a different rest period; participants allocated to Groups A, B, C, and D performed, eight, five, four, and three cycles, respectively. We compared a quality change of CCs among these groups to investigate how the assigned rest period affects the maintenance of CC quality during the 30-min CPR. Results: This study involved 143 participants (male 58 [41%]; mean age, 24 years,) for the evaluation. As participants had less rest periods, the quality of their CCs such as sufficient depth ratio declined over 30-min CPR. A significant decrease in the sufficient CC depth ratio was observed in the second to the last cycle as compared to the first cycle. (median changes; A: −4%, B: −3%, C: 0%, and D: 0% p < 0.01). Conclusions: A 6 min rest period after 2 min CC is vital in order to sustain the quality of CC during a 30-min CPR cycle. At least four personnel may be needed to reduce rescuer's fatigue for a 30-min CPR cycle when the team consists of men and women. [ABSTRACT FROM AUTHOR]

Background: Recurrence of SRNS is a major challenge in KT. Several clinical factors, including initial steroid sensitivity, have been associated with increased post‐transplant SRNS recurrence risk. However, conflicting data have been reported, possibly due to the heterogeneous pathophysiology of SRNS and the lack of genetic testing of SRNS patients. Furthermore, the response to immunosuppressive therapies has not been evaluated. Methods: Seventy patients aged 1–15 years at SRNS onset who underwent KT between 2002 and 2018 were enrolled. Patients with secondary, familial, syndromic, and genetic forms of SRNS and those who were not treated with steroid were excluded. This study aimed to assess the risk factors for post‐transplant recurrence, including treatment responses to initial steroid therapy and additional therapies with immunosuppressive agents, rituximab, plasmapheresis, and/or LDL‐A. Results: Data from 36 kidney transplant recipients were analyzed. Twenty‐two (61%) patients experienced post‐transplant SRNS recurrence, while 14 patients did not. The proportion of patients who achieved complete or partial remission with initial steroid therapy and/or additional therapies with immunosuppressive agents, rituximab, plasmapheresis, and/or LDL‐A was significantly higher in the SRNS recurrence group (19/22, 86%) than in the group without SRNS recurrence (6/14, 43%; p =.01). Conclusion: This study suggests that the response to steroid treatment, other immunosuppressive agents, rituximab, plasmapheresis, and/or LDL‐A may predict post‐transplant SRNS recurrence. [ABSTRACT FROM AUTHOR]

Background: Elevated blood lactate levels were reported as effective predictors of clinical outcome and mortality in ICU. However, there have been no studies simply comparing the timing of measuring lactates before vs. after ICU admission. Methods: A total of 19,226 patients with transfer time ≤ 24 hr were extracted from the Medical Information Mart for Intensive Care IV database (MIMIC-IV). After 1:1 propensity score matching, the patients were divided into two groups: measuring lactates within 3 hr before (BICU group, n = 4,755) and measuring lactate within 3 hr after ICU admission(AICU group, n = 4,755). The primary and secondary outcomes were hospital mortality, hospital 28-day mortality, ICU mortality, ICU length of stay (LOS), hospital LOS, and restricted mean survival time (RMST). Results: Hospital, hospital 28-day, and ICU mortality were significantly higher in AICU group (7.0% vs.9.8%, 6.7% vs. 9.4%, and 4.6% vs.6.7%, respectively, p<0.001 for all) Hospital LOS and ICU LOS were significantly longer in AICU group (8.4 days vs. 9.0 days and 3.0 days vs. 3.5 days, respectively, p<0.001 for both). After adjustment for predefined covariates, a significant association between the timing of measuring lactate and hospital mortality was observed in inverse probability treatment weight (IPTW) multivariate regression, doubly robust multivariate regression, and multivariate regression models (OR, 0.96 [95%CI, 0.95-0.97], OR 0.52 [95%CI, 0.46-0.60], OR 0.66 [95%CI, 0.56-0.78], respectively, p<0.001 for all), indicating the timing as a significant risk-adjusted factor for lower hospital mortality. The difference (BICU-AICU) of RMST at 28- days after ICU admission was 0.531 days (95%CI, 0.002-1.059, p<0.05). Placement of A-line and PA-catheter, administration of intravenous antibiotics, and bolus fluid infusion during the first 24-hr in ICU were significantly more frequent and faster in the BICU vs AICU group (67.6% vs. 51.3% and 126min vs.197min for A-line, 19.6% vs.13.2% and 182min vs. 274min for PA-catheter, 77.5% vs.67.6% and 109min vs.168min for antibiotics, and 57.6% vs.51.6% and 224min vs.278min for bolus fluid infusion, respectively, p<0.001 for all). Additionally, a significant indirect effect was observed in frequency (0.19879 [95% CI, 0.14061-0.25697] p<0.001) and time (0.07714 [95% CI, 0.22600-0.13168], p<0.01) of A-line replacement, frequency of placement of PA-catheter (0.05614 [95% CI, 0.04088-0.07140], p<0.001) and frequency of bolus fluid infusion (0.02193 [95%CI, 0.00303-0.04083], p<0.05). Conclusions: Measuring lactates within 3 hr prior to ICU might be associated with lower hospital mortality in unselected heterogeneous critically ill patients with transfer time to ICU ≤ 24hr, presumably due to more frequent and faster therapeutic interventions. [ABSTRACT FROM AUTHOR]

To establish actionable neonatal screening during the first month of life, we investigated critical diseases in seemingly healthy newborns discharged from birth hospitals. This retrospective study enrolled previously healthy full-term infants who visited our hospital, a tertiary hospital in Japan, from home between 5 and 28 days after birth from 2009 to 2018. Infants with known perinatal or congenital diseases, positive newborn screening results, or accidental injuries were excluded. Data were collected from electronic medical records, including principal diagnosis, clinical details, and prognosis at 18 months of age. Ninety-seven (58 %) of 168 eligible neonates were admitted to the hospital, and 71 (42 %) were not. The median admission rate in patients with disease onset at ≤14 days after birth (80 %) was significantly higher than that in patients with disease onset at ≥15 days (42 %). Among 45 patients who received intensive medical care, 5 died and 10 developed neurodevelopmental sequelae. Four of 5 patients died by 100 days. Among 25 diseases treated in intensive care unit, 17 (68 %) diseases had a prevalence of <1 per 2000 live births. The commonly used diagnostic methods were imaging (n = 58, 35 %) and physical examination (n = 34, 20 %). Critical diseases due to rare and heterogeneous causes in ostensibly healthy newborns occurred predominantly in the first two weeks of life. Optimal newborn screening and health check-up protocols may benefit from the wide spectrum of life-threatening diseases occurring in home after birth. • Newborns have the highest mortality rate among children. • There are few data on neonatal-onset diseases in seemingly healthy infants. • Ostensibly healthy newborns have suffered from rare and diverse critical diseases. • Neonatal screening and health check-ups must target these diseases. [ABSTRACT FROM AUTHOR]

Background: Hypokalemic periodic paralysis (HypoPP) is an autosomal dominant disease characterized by the episodic weakness of skeletal muscles and hypokalemia. More than half patients with HypoPP carry mutations in CACNA1S, encoding alpha‐1 subunit of calcium channel. Few reports have documented the non‐neuromuscular phenotypes of HypoPP. Methods: The proband is a Japanese woman who developed HypoPP at 6 years of age. An excessive insulin secretion with the oral glucose tolerance test rationalized that she had experienced frequent attacks of paralysis on high‐carbohydrate diets. Results: Voglibose and acetazolamide effectively controlled her paralytic episodes. Her 8‐year‐old son and 2‐year‐old daughter started showing the paralytic symptoms from 4 and 2 years of age, respectively. Laboratory tests revealed high concentrations of creatinine kinase in serum and elevated renin activities in plasma of these children. The targeted sequencing confirmed that these three patients had an identical heterozygous mutation (p.V876E) in CACNA1S. Conclusion: Our data indicate that the p.V876E mutation in CACNA1S contributes to the early onset of neuromuscular symptoms and unusual clinical phenotypes of HypoPP. [ABSTRACT FROM AUTHOR]

B Learning Objectives: b Several studies have reported the effectiveness of extracorporeal cardiopulmonary resuscitation (ECPR) after out-of-hospital cardiac arrest (OHCA). Among 3,086 consecutive OHCA patients, 1,921 adult patients whose rSO2 was measured with near-infrared spectroscopy were enrolled according to the registry protocol. B Conclusions: b The rSO2 value upon hospital arrival can be a good predictor of 90-day neurological outcome of patients treated with ECPR after OHCA. [Extracted from the article]

Abstract Introduction Upshaw-Schulman syndrome (USS) is a congenital form of thrombotic thrombocytopenic purpura (TTP) associated with loss-of-function mutations in the ADAMTS13 gene, possibly leading to aberrant complement activation and vascular injury. However, USS is extremely rare, and there have been no systematic studies correlating histopathological severity with local ADAMTS13 expression and complement activation. Materials and methods Here, we compared histopathological features, ADAMTS13 immunoreactivity, and immunoreactivity of complement proteins C4d and C5b-9 among renal biopsy tissues from five USS cases, ten acquired TTP cases, and eleven controls. Results Pathological analysis revealed chronic glomerular sclerotic changes in the majority of USS cases (4 of 5), with minor glomerular pathology in the remaining case. In two of these four severe cases, more than half of the glomerular segmental sclerosis area was localized in the perihilar region. The average number of ADAMTS13-positive cells per glomerulus was significantly lower in USS cases than controls (p < 0.05). Conversely, C4d staining was significantly more prevalent in the glomerular capillary walls of USS cases than controls (p < 0.05), while C5b-9 staining did not differ significantly among groups. Conclusions These findings suggest that the severity of glomerular injury in USS is associated with deficient ADAMTS13 expression and local complement activation, particularly in vascular regions with higher endothelial shear stress. We suggest that C4d immunostaining provides evidence for complement-mediated glomerular damage in USS. Highlights • Upshaw-Schulman syndrome (USS) is a congenital thrombotic thrombocytopenic purpura with mutations in the ADAMTS13 gene. • In USS cases, glomerular segmental sclerosis was predominantly localized in the perihilar region. • The severity of glomerular injury in USS may be associated with deficient ADAMTS13 expression and complement activation. [ABSTRACT FROM AUTHOR]

Background: Extracorporeal membrane oxygenation is an established life-saving procedure for severe acute respiratory failure due to various causes. In general, the duration of extracorporeal membrane oxygenation ranges from 1 to 2 weeks, with withdrawal recommended if no improvement is noted. We report a successful case of long-term extracorporeal membrane oxygenation management for respiratory failure due to invasive pulmonary Aspergillus infection.Case Presentation: A 64-year-old Asian man with no previous underlying medical conditions was transferred to our hospital for fever and dyspnea. On admission, he presented with bilateral diffuse infiltration shadow on X-ray and chest computed tomography readings, and severe hypoxemia with a partial pressure of oxygen in arterial blood/fraction of inspired oxygen ratio of 55. He was intubated and underwent mechanical ventilation. A bronchial-alveolar lavage was performed prior to administration of antibiotics, and as the bacterial culture was positive for Aspergillus fumigatus, antifungal treatment was then initiated. His respiratory status deteriorated on the 11th admission day, with no improvement on any mechanical ventilator settings. Venous-venous extracorporeal membrane oxygenation was introduced. Extracorporeal membrane oxygenation was used for an extended period of time, with respiratory improvement delayed until the 39th admission day. Extracorporeal membrane oxygenation discontinuation was possible on the 44th day, and he was removed from the ventilator on the 64th day.Conclusions: Long-term extracorporeal membrane oxygenation might be considered if the primary causes of respiratory failure necessitating extracorporeal membrane oxygenation can be expected to be resolved, such as in the case of effective antimicrobial therapy for a definite pathogen. Our case indicates that extracorporeal membrane oxygenation can be used during treatment of respiratory failure due to invasive aspergillosis for the recommended treatment duration of 4 to 8 weeks. [ABSTRACT FROM AUTHOR]

CAKUT are the most frequent causes of ESRD in children. Mutations in the gene encoding HNF1B, a transcription factor involved in organ development and maintenance, cause a multisystem disorder that includes CAKUT, diabetes, and liver dysfunction. Here, we describe the case of a patient with renal hypodysplasia who developed NODAT presenting with liver dysfunction. The NODAT was initially thought to be steroid and FK related. However, based on the patient's clinical features, including renal hypodysplasia and recurrent elevations of transaminase, screening for an HNF1B mutation was performed. Direct sequencing identified a novel splicing mutation of HNF1B, designated c.344 + 2T>C. Because CAKUT is the leading cause of ESRD in children and HNF1B mutations can cause both renal hypodysplasia and diabetes, HNF1B mutations may account for a portion of the cases of NODAT in pediatric patients who have undergone kidney transplantation. NODAT is a serious and major complication of solid organ transplantation and is associated with reduced graft survival. Therefore, for the appropriate management of kidney transplantation, screening for HNF1B mutations should be considered in pediatric patients with transplants caused by CAKUT who develop NODAT and show extra-renal symptoms. [ABSTRACT FROM AUTHOR]

Abstract: Aim To investigate the association between regional brain oxygen saturation (rSO2) on hospital arrival and neurological outcomes at hospital discharge in patients with out-of-hospital cardiac arrest (OHCA). Methods A prospective cohort study was conducted, registering 179 patients with OHCA who were referred to Senri Critical Care Medical Centre between April 2009 and June 2010. Of these patients, 92 met the inclusion criteria. The primary end point was “neurological outcomes” at hospital discharge according to the “Utstein style” guidelines. Results The overall rate of good neurological outcome at hospital discharge was 14% (n =13). Sixty-one patients with rSO2 ≤25% showed poor neurological outcome in the receiver operating curve analysis (optimal cut-off point, 25%; sensitivity, 0.772; specificity, 1.000; positive predictive value, 1.000; area under the curve (AUC), 0.919; p <0.0001). The AUC for rSO2 was greater than that for base excess (p =0.0461) or lactate (p =0.0128) measured on hospital arrival. Since rSO2 >40% was previously collated with good neurological outcome after cardiovascular surgery, we categorised our patients into three groups in a post hoc analysis: patients with rSO2 ≤25% (n =61); patients with rSO2 26–40% (n =9) and patients with rSO2 >40% (n =22). Patients with good neurological outcome were as follows: 0 (0%)/61 with rSO2 ≤25%; two (22.2%)/9 with rSO2 26–40% and 11 (50.0%)/22 with rSO2 >40% (p <0.0001). Conclusion rSO2 on hospital arrival may help predict neurological outcomes at hospital discharge in patients with OHCA. [Copyright &y& Elsevier]

The oxidation of a redox-active tyrosine residue YZ in photosystem II (PSII) is coupled with proton transfer to a hydrogen-bonded D1-His190 residue. Because of the apparent proximity of YZ to the water-oxidizing complex and its redox activity, it is believed that YZ plays a significant role in water oxidation in PSII. We investigated the g-anisotropy of the tyrosine radical YZ∙ to provide insight into the mechanism of YZ∙ proton-coupled electron transfer in Mn-depleted PSII. The anisotropy was highly resolved by electron paramagnetic resonance spectroscopy at the W-band (94.9 GHz) using PSII single crystals. The gX-component along the phenolic C-O bond of YZ∙ was calculated by density functional theory (DFT). It was concluded from the highly resolved g-anisotropy that YZ loses a phenol proton to D1-His190 upon tyrosine oxidation, and D1-His190 redonates the same proton back to YZ∙ upon reduction. [ABSTRACT FROM AUTHOR]

Objectives: This study describes a novel heterozygous gain-of-function mutation in the cardiac sodium (Na+) channel gene, SCN5A, identified in a Japanese family with lone atrial fibrillation (AF). Background: SCN5A mutations have been associated with a variety of inherited arrhythmias, but the gain-of-function type modulation in SCN5A is associated with only 1 phenotype, long-QT syndrome type 3 (LQTS3). Methods: We studied a Japanese family with autosomal dominant hereditary AF, multiple members of which showed an onset of AF or frequent premature atrial contractions at a young age. Results: The 31-year-old proband received radiofrequency catheter ablation, during which time numerous ectopic firings and increased excitability throughout the right atrium were documented. Mutational analysis identified a novel missense mutation, M1875T, in SCN5A. Further investigations revealed the familial aggregation of this mutation in all of the affected individuals. Functional assays of the M1875T Na+ channels using a whole-cell patch-clamp demonstrated a distinct gain-of-function type modulation; a pronounced depolarized shift (+16.4 mV) in V1/2 of the voltage dependence of steady-state inactivation; and no persistent Na+ current, which is a defining mechanism of LQTS3. These biophysical features of the mutant channels are potentially associated with increased atrial excitability and normal QT interval in all of the affected individuals. Conclusions: We identified a novel SCN5A mutation associated with familial AF. The mutant channels displayed a gain-of-function type modulation of cardiac Na+ channels, which is a novel mechanism predisposing to increased atrial excitability and familial AF. This is a new phenotype resulting from the SCN5A gain-of-function mutations and is distinct from LQTS3. [Copyright &y& Elsevier]