The immunoreactive signature of monocyte-derived dendritic cells from patients with Down syndrome.

The clinical spectrum of Down syndrome (DS) ranges from congenital malformations to premature aging and early-onset senescence. Excessive immunoreactivity and oxidative stress are thought to accelerate the pace of aging in DS patients; however, the immunological profile remains elusive. We investigated whether peripheral blood monocyte-derived dendritic cells (MoDCs) in DS patients respond to lipopolysaccharide (LPS) distinctly from non-DS control MoDCs. Eighteen DS patients (age 2~47 years, 12 males) and 22 controls (age 4~40 years, 15 males) were enrolled. CD14-positive monocytes were immunopurified and cultured for 7 days in the presence of granulocyte-macrophage colony-stimulating factor and IL-4, yielding MoDCs in vitro. After the LPS-stimulation for 48 hours from days 7 to 9, culture supernatant cytokines were measured by multiplex cytokine bead assays, and bulk-prepared RNA from the cells was used for transcriptomic analyses. MoDCs from DS patients produced cytokines/chemokines (IL-6, IL-8, TNF-α, MCP-1, and IP-10) at significantly higher levels than those from controls in response to LPS. RNA sequencing revealed that DS-derived MoDCs differentially expressed 137 genes (74 upregulated and 63 downregulated) compared with controls. A gene enrichment analysis identified 5 genes associated with Toll-like receptor signaling (KEGG: hsa04620, p = 0.00731) and oxidative phosphorylation (hsa00190, p = 0.0173) pathways. MoDCs obtained from DS patients showed higher cytokine or chemokine responses to LPS than did control MoDCs. Gene expression profiles suggest that hyperactive Toll-like receptor and mitochondrial oxidative phosphorylation pathways configure the immunoreactive signature of MoDCs in DS patients.

WT1 exon 10 missense variant in a pediatric patient with focal segmental glomerulosclerosis with embryonal hyperplasia.

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.

Long-Term Renal Involvement in Association with Fontan Circulation.

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.

Medical and psychosocial outcomes in adolescents and young adults with childhood-onset end-stage kidney disease: a multicenter study in Japan.

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.

Depression and health-related quality of life in adolescents and young adults with childhood-onset end-stage kidney disease: a multicenter study in Japan.

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.

Maternal Chronic Disease and Congenital Anomalies of the Kidney and Urinary Tract in Offspring: A Japanese Cohort Study.

RATIONALE & OBJECTIVE: Several maternal chronic diseases have been reported as risk factors for congenital anomalies of the kidney and urinary tract (CAKUT) in offspring. However, these investigations used case-control designs, and cases with isolated genitourinary CAKUT were not distinguished from cases in which CAKUT were present with extrarenal congenital anomalies (complicated CAKUT). We examined the association of maternal diseases with isolated and complicated CAKUT in offspring using data from a prospective cohort study. STUDY DESIGN: A nationwide prospective birth cohort study. SETTING & PARTICIPANTS: 100,239 children enrolled in the Japan Environment and Children's Study between January 2011 and March 2014 at 15 research centers. Physicians' diagnoses in mothers and children were collected from medical record transcripts and questionnaires. EXPOSURES: Medical histories of maternal noncommunicable diseases, including obesity, hypertension, diabetes mellitus, kidney disease, hyperthyroidism, hypothyroidism, psychiatric disease, epilepsy, cancer, and autoimmune disease. OUTCOMES: CAKUT diagnosed during the first 3 years of life, classified as isolated or complicated. ANALYTICAL APPROACH: Multivariable Poisson regression with generalized estimating equations accounting for clustering by clinical center. RESULTS: Among the 100,239 children, 560 (0.6%) had CAKUT, comprising 454 (81%) isolated and 106 (19%) complicated forms. The risk of isolated CAKUT was increased in children of mothers who experienced kidney disease (adjusted risk ratio [RR], 1.80 [95% CI, 1.12-2.91]) or cancer (RR, 2.11 [95% CI, 1.15-3.86]). Furthermore, the risk of complicated CAKUT was increased in children of mothers with diabetes mellitus (RR, 3.04 [95% CI, 1.64-5.61]). LIMITATIONS: Lack of standardization or prespecification of clinical definitions, diagnostic criteria, measurements, and testing. Genetic testing was not performed. CONCLUSIONS: Isolated CAKUTs and complicated CAKUTs were associated with different maternal diseases. The results may inform clinical management of pregnancy and highlight potential differences in the genesis of isolated and complicated forms of CAKUT.

Response to steroid and immunosuppressive therapies may predict post-transplant recurrence of steroid-resistant nephrotic syndrome.

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.

Factors influencing the length of emergency room stay and hospital stay in non-fatal bicycle accidents: A retrospective analysis.

PURPOSE: Lengthy hospitalization places a burden on patients and healthcare resources. However, the factors affecting the length of hospital stay (LHoS) and length of emergency room stay (LERS) in non-fatal bicycle accidents are currently unclear. We investigated these factors to inform efforts to minimize hospitalization. METHODS: We performed a retrospective analysis of data from non-fatal injured bicyclists admitted to the Emergency and Critical Care Center at Kyoto Medical Center between January 2012 and December 2016. We measured LHoS, LERS, mechanism of injury, head injury prevalence, polytrauma, operations performed, injury severity score (ISS), abbreviated injury scale (AIS) score, maximum AIS score, and trauma and injury severity score probability of survival. We conducted multiple regression analysis to determine predictors of LHoS and LERS. RESULTS: Within the study period, 82 victims met the inclusion and exclusion criteria and were included. Mean age was (46.0 ± 24.7) years. Overall mean LHoS was (16.8 ± 25.2) days, mean LERS was (10.6 ± 14.7) days, median ISS was 9 (interquartile range (IQR): 3-16), median maximum AIS was 3 (IQR: 1-4), and median trauma and injury severity score probability of survival was 98.0% (IQR: 95.5%-99.6%). Age, maximum AIS, ISS, and prevalence of surgery were significantly greater in long LHoS and LERS group compared with short LHoS and LERS group (p < 0.05). Performance of surgery independently explained LHoS (p = 0.0003) and ISS independently explained LERS (p = 0.0009). CONCLUSION: Surgery was associated with long hospital stays and ISS was associated with long emergency room stays. To improve the quality life of the bicyclists, preventive measures for reducing injury severity or avoiding injuries needing operation are required.

Gastrointestinal symptoms as an extended clinical feature of Pierson syndrome: a case report and review of the literature.

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.

Molecular mechanisms determining severity in patients with Pierson syndrome.

Null variants in LAMB2 cause Pierson syndrome (PS), a severe congenital nephrotic syndrome with ocular and neurological defects. Patients' kidney specimens show complete negativity for laminin ß2 expression on glomerular basement membrane (GBM). In contrast, missense variants outside the laminin N-terminal (LN) domain in LAMB2 lead to milder phenotypes. However, we experienced cases not showing these typical genotype-phenotype correlations. In this paper, we report six PS patients: four with mild phenotypes and two with severe phenotypes. We conducted molecular studies including protein expression and transcript analyses. The results revealed that three of the four cases with milder phenotypes had missense variants located outside the LN domain and one of the two severe PS cases had a homozygous missense variant located in the LN domain; these variant positions could explain their phenotypes. However, one mild case possessed a splicing site variant (c.3797 + 5G>A) that should be associated with a severe phenotype. Upon transcript analysis, this variant generated some differently sized transcripts, including completely normal transcript, which could have conferred the milder phenotype. In one severe case, we detected the single-nucleotide substitution of c.4616G>A located outside the LN domain, which should be associated with a milder phenotype. However, we detected aberrant splicing caused by the creation of a novel splice site by this single-base substitution. These are novel mechanisms leading to an atypical genotype-phenotype correlation. In addition, all four cases with milder phenotypes showed laminin ß2 expression on GBM. We identified novel mechanisms leading to atypical genotype-phenotype correlation in PS.

Osborn Wave Is Related to Ventricular Fibrillation and Tachycardia in Hypothermic Patients.

BACKGROUND: The Osborn wave (OW) is often observed in hypothermic patients; however, whether OW in hypothermic patients is related to the development of fatal ventricular arrhythmia, including ventricular fibrillation (VF) and pulseless ventricular tachycardia (VT), remains undetermined. This study aimed to estimate the association between OW and the incidence of fatal ventricular arrhythmias.Methods and Results: This retrospective study used the Japanese Accidental Hypothermia Network registry database and included 572 hypothermic patients. Patients were divided into the OW group (those with OW) and non-OW group (those without OW). The relationship between the development of fatal arrhythmias and presence of OW was assessed using the chi-squared test. All patients who developed VF/VT (n=10) had OW on electrocardiogram upon hospital arrival. The presence of OW had a sensitivity of 100%, specificity of 47.8%, positive predictive value of 4.0%, and negative predictive value of 100% for VF/VT development. The in-hospital mortality rate was 22.3% in the OW group and 21.2% in the non-OW group (P=0.781). CONCLUSIONS: OW was observed in all hypothermic patients with VF/VT. The occurrence of ventricular arrhythmias is highly unlikely in the absence of OW on the electrocardiogram. Although the presence of OW might be used to predict these fatal arrhythmias in hypothermic patients, there was no association between the presence of OW and in-hospital mortality.

Hyperferritinemia and acute kidney injury in pediatric patients receiving allogeneic hematopoietic cell transplantation.

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.

Dynamic Needle Tip Positioning for Ultrasound-Guided Placement of a Peripherally Inserted Central Catheter in Pediatric Patients.

OBJECTIVE: Although a few studies have reported the efficacy of ultrasound-guided peripherally inserted central catheter placement for pediatric patients, the procedure still is challenging. Ultrasound-guided dynamic needle tip positioning technique is useful for vascular catheterization. There have been no reports on using dynamic needle tip positioning for peripherally inserted central catheter placement. The authors assessed the rate of successful peripherally inserted central catheter placement with dynamic needle tip positioning. DESIGN: Case series. SETTING: Single tertiary institution. PARTICIPANTS: Forty patients <5 years old who were admitted to the pediatric intensive care unit after cardiac surgeries and required peripherally inserted central catheter placement. INTERVENTIONS: Peripherally inserted central catheter placement was performed under ultrasound guidance with dynamic needle tip positioning. The authors recorded the first attempt and overall success rates of peripherally inserted central catheter and outer cannula placement, time needed for outer cannula and peripherally inserted central catheter placement, and number of attempts. MEASUREMENTS AND MAIN RESULTS: The first attempt and overall success rates of peripherally inserted central catheter placement were 85% (n = 34) and 97.5% (n = 39), respectively. The first attempt and overall success rates of outer cannula placement were 87.5% (n = 35) and 100% (n = 40), respectively. Time needed for outer cannula placement was 59.5 (interquartile range 40.5-80.5) seconds and for peripherally inserted central catheter placement was 112.5 (interquartile range 91.5-159.5) seconds. The number of attempts was 1 (interquartile range 1-1 [range 1-5]). CONCLUSIONS: In pediatric patients, ultrasound-guided peripherally inserted central catheter placement using dynamic needle tip positioning attained a high success rate.

Superiority of Dynamic Needle Tip Positioning for Ultrasound-Guided Peripheral Venous Catheterization in Patients Younger Than 2 Years Old: A Randomized Controlled Trial.

OBJECTIVES: This study evaluated whether the dynamic needle tip positioning technique increased the success rate of ultrasound-guided peripheral venous catheterization in pediatric patients with a small-diameter vein compared with the static ultrasound-guided technique. DESIGN: Randomized controlled study. SETTING: Single institution, Osaka Women's and Children's Hospital. PATIENTS: The study population included 60 pediatric patients less than 2 years old who required peripheral venous catheterization in the PICU. INTERVENTIONS: Patients were randomly divided into the dynamic needle tip positioning (n = 30) or static group (n = 30). Each group received ultrasound-guided peripheral venous catheterization with or without dynamic needle tip positioning, respectively. The Fisher exact test, Kaplan-Meier curve plots, log-rank tests, and Mann-Whitney U test were used in the statistical analysis. MEASUREMENTS AND MAIN RESULTS: The first-attempt success rate was higher in the dynamic needle tip positioning group than in the static group (86.7% vs 60%; p = 0.039; relative risk = 1.44; 95% CI, 1.05-2.0). The overall success rate within 10 minutes was higher in the dynamic needle tip positioning group than in the static group (90% vs 63.3%; p = 0.03; relative risk = 1.42; 95% CI, 1.06-1.91). Significantly fewer attempts were made in the dynamic needle tip positioning group than in the static group (median [interquartile range, range] = 1 [1-1, 1-2] vs 1 [1-2, 1-3]; p = 0.013]). The median (interquartile range) catheterization times were 51.5 seconds (43-63 s) and 71.5 seconds (45-600 s) in the dynamic needle tip positioning and static groups, respectively (p = 0.01). CONCLUSIONS: Dynamic needle tip positioning increased the first-attempt and overall success rates of ultrasound-guided peripheral venous catheterization in pediatric patients less than 2 years old.

Combined Approach Versus 2 Conventional Approaches in Ultrasound-Guided Central Venous Catheterization: A Randomized Controlled Trial.

OBJECTIVE: The authors compared the occurrence of posterior wall puncture using the short-axis out-of-plane and long-axis in-plane approaches with that using the combined short-axis-and-long-axis approach that the authors previously showed to be effective in observational and manikin studies. DESIGN: Randomized controlled study. SETTING: Single tertiary institution. PARTICIPANTS: One hundred twenty patients who underwent cardiac or vascular surgery under general anesthesia. INTERVENTIONS: The patients were divided randomly into combined short-axis-and-long-axis (n = 40), short-axis out-of-plane (SA-OOP) (n = 40), and long-axis in-plane (LA-IP) (n = 40) groups and received ultrasound-guided central venous catheterization at the right internal jugular vein. MEASUREMENTS AND MAIN RESULTS: Successful guidewire insertion without posterior wall puncture was performed in 40 patients (100%) in the combined short-axis-and-long-axis approach group, 28 (70%) in the short-axis out-of-plane approach group, and 38 (95%) in the LA-IP approach group (combined short-axis-and-long-axis v SA-OOP, p = 0.0002 [relative risk = 1.43; 95% CI: 1.17-1.75]; combined short-axis-and-long-axis v LA-IP, p = 0.49 [relative risk = 1.05; 95% CI: 0.98-1.13]). Procedure durations were 28.5 (24.1-36.4) seconds in the combined short-axis-and-long-axis group, 31.7 (24.4-40.6) seconds in the SA-OOP group, and 24.3 (20.8-32.1) seconds in the long-axis in-plane group (combined short-axis-and-long-axis v SA-OOP, p = 0.53; combined short-axis-and-long-axis v LA-IP, p = 0.044). CONCLUSION: The combined short-axis-and-long-axis approach for ultrasound-guided central venous catheterization had a lower posterior wall puncture rate than the SA-OOP approach, but there was no significant difference with the long-axis in-plane approach.

Comparing Combined Short-Axis and Long-Axis Ultrasound-Guided Central Venous Catheterization With Conventional Short-Axis Out-of-Plane Approaches.

OBJECTIVE: Visualizing the needle tip using the short-axis out-of-plane (SA-OOP) ultrasound-guided central venous catheterization approach is difficult and results in posterior wall puncture (PWP). To improve needle tip visualization in the long-axis view, combining the SA-OOP and the long-axis in-plane approaches has been suggested. The authors, who previously reported on the utility of this technique using a manikin model, examined the feasibility of this novel method (referred to as the combined short-axis and long-axis [CSLA] approach) and compared the CSLA approach with the SA-OOP approach in humans for the present study. DESIGN: Prospective observational study. SETTING: Single institution, Rakuwakai Otowa Hospital. PARTICIPANTS: Patients undergoing cardiac or vascular surgeries. INTERVENTIONS: The CSLA and SA-OOP approaches were used for ultrasound-guided right jugular venous puncture. The puncturing procedures were determined arbitrarily preoperatively without consideration of the patient's neck anatomy and were based on the operator's preference without randomization. MEASUREMENTS AND MAIN RESULTS: The study comprised 100 patients. Successful guidewire insertion without PWP was performed in 48 patients (96%) in the CSLA approach group and 33 (66%) in the SA-OOP approach group; the rate was significantly higher in the CSLA approach group (p = 0.0001). The procedural durations were 27.5 (range 17.0-122.0) seconds in the CSLA approach group and 25.0 (range 15.0-158.0) seconds in the SA-OOP approach group (p = 0.19). CONCLUSIONS: This study showed that the CSLA approach to ultrasound-guided central venous catheterization might help prevent PWP.

Dynamic Needle Tip Positioning for Ultrasound-Guided Arterial Catheterization in Infants and Small Children With Deep Arteries: A Randomized Controlled Trial.

OBJECTIVE: Arterial catheterization for infants and small children is technically challenging. This study evaluated whether the dynamic needle tip positioning (DNTP) technique improved the success rate of ultrasound-guided radial artery catheterization in patients with a radial artery depth ≥4 mm compared with the conventional ultrasound-guided technique. DESIGN: Randomized controlled study. SETTING: Single institution, Osaka Women's and Children's Hospital. PARTICIPANTS: Patients (n = 40; age <3 years) with artery depth ≥4 mm. INTERVENTIONS: Patients were divided randomly into 2 groups. The DNTP group received ultrasound-guided radial artery catheterization with DNTP; the conventional group received catheterization without DNTP. MEASUREMENTS AND MAIN RESULTS: First-attempt success rates were 85% and 50% in the DNTP and conventional groups, respectively (p = 0.018; relative risk = 1.7; 95% CI: 1.06-2.73). Overall success rates within 10 minutes were 95% and 60% in the DNTP and conventional groups, respectively (p = 0.008; relative risk = 1.58; 95% CI: 1.09-2.3). Posterior wall puncture rates were 5% and 50% in the DNTP and conventional groups, respectively (p = 0.0014; relative risk = 0.1; 95% CI: 0.014-0.71). Significantly fewer attempts were made in the DNTP group (median = 1 v 1.5; p = 0.01). The median catheterization times were 38 seconds (34-55.5) and 149 seconds (49.5-600) in the DNTP and conventional groups, respectively (p = 0.0003). CONCLUSION: Dynamic needle tip positioning improved first-attempt and overall success rates of ultrasound-guided radial artery catheterization in pediatric patients with a radial artery depth ≥4 mm.

Implementation of an empirical antimicrobial protocol in a critical care setting: A single-center retrospective observational cohort study in bacteremic patients.

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.

A childhood-onset intestinal toxemia botulism during chemotherapy for relapsed acute leukemia.

BACKGROUND: Botulism is a potentially fatal infection characterized by progressive muscle weakness, bulbar paralysis, constipation and other autonomic dysfunctions. A recent report suggested that cancer chemotherapy might increase the risk for the intestinal toxemia botulism in both adults and children. CASE PRESENTATION: We report a 5-year-old boy, who developed general muscle weakness, constipation, ptosis and mydriasis during the third induction therapy for relapsed acute myeloid leukemia. He had recent histories of multiple antibiotic therapy for bacteremia and intake of well water at home. Repeated bacterial cultures identified Clostridium botulinum producing botulinum neurotoxin A. Botulinum toxin A was isolated from his stools at 17, 21, and 23 days after the onset. Symptoms were self-limiting, and were fully recovered without anti-botulinum toxin globulin therapy. CONCLUSION: This is the second report of a pediatric case with cancer chemotherapy-associated intestinal toxemia botulism. Our case provides further evidence that the immunocompromised status due to anti-cancer treatments increases the risk for the development of botulism at all ages in childhood.

Repetitive postoperative extubation failure and cardiac arrest due to laryngomalacia after general anesthesia in an elderly patient: a case report.

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.