Nafamostat Mesylate for the Hypercoagulable State of SARS-CoV-2 With Renal Replacement Therapy: A Case Report.

Being a dialysis patient is one of the risks for severe coronavirus disease 2019 (COVID-19) cases. In addition, there have been many reports of coagulation abnormalities in severe COVID-19 cases; these also make dialysis management more difficult. In this study, we report a case of severe COVID-19 in a hemodialysis patient who had coagulation in the dialysis circuit with unfractionated heparin (UFH), which could be managed without intracircuit obstruction when nafamostat mesylate (NM) was used in combination with unfractionated heparin.

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.

The Effectiveness of Deflux® Treatment for Vesicoureteral Reflux Following Pediatric Renal Transplantation: A Single-Institution Challenging Experience.

PURPOSE: To validate the effectiveness of Deflux® treatment for vesicoureteral reflux (VUR) following pediatric renal transplantation (RT), based on our single-institution experience. METHOD: A retrospective study was conducted using the medical records of pediatric patients who underwent Deflux® treatment for VUR after RT from April 2008 to March 2022. RESULTS: Sixty-eight pediatric patients underwent RT. VUR was subsequently detected in 22 (32 %) of these patients. Seven of the 22 patients (32 %) underwent Deflux® treatment to avoid renal dysfunction due to urinary infection (UTI). The median age at the time of RT was 4 years (range:2-12). All 7 patients had urinary UTIs before Deflux® treatment. The median estimated glomerular filtration rate (eGFR) before Deflux® treatment was 67 ml/min/1.73 m2 (range:42-138 ml/min/1.73 m2). After Deflux® treatment, VUR was downgraded in three cases (43 %). Four patients (57 %) experienced postoperative UTI, two of who underwent a second Deflux® treatment, one underwent submuscular tunnel reconstruction, and the other one experienced UTI without VUR after 1st Deflux® treatment but did not reoccur. All seven patients continued prophylactic medication after Deflux® treatment, without any history of recurrent UTIs during the observation period after treatment (median 37 months [range 7-86 months]). Furthermore, the eGFRs did not significantly decrease after Deflux® treatment (median eGFR 58 ml/min/1.73 m2 [range:33-99 ml/min/1.73 m2], p > 0.1). CONCLUSION: Deflux® treatment for VUR after RT is technically challenging because the new ureteral orifice is ventrally anastomosed at the bladder. We believe our results indicate the possibility of reducing the frequency of UTIs and contributing to preservation of the renal function after RT. TYPE OF STUDY: Retrospective Study. LEVEL OF EVIDENCE: Level III.

Critical diseases in neonates after discharge home from birth hospital: A retrospective study from a tertiary hospital in Japan.

INTRODUCTION: To establish actionable neonatal screening during the first month of life, we investigated critical diseases in seemingly healthy newborns discharged from birth hospitals. METHODS: 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. RESULTS: 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 %). CONCLUSION: 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.

Investigation of Mechanical Thrombectomy in Elderly Patients over 85 Years Old: A Multicenter Study.

In Japan, which has a super-aging society, there are increasing opportunities to perform mechanical thrombectomy for the elderly; however, there is no recorded evidence of thrombectomy for the elderly. This study examined the usefulness of thrombectomy in the elderly. We retrospectively analyzed patient data using a multicenter acute ischemic stroke registry (NGT-FAST). We examined outcomes in patients 75 years and older who underwent thrombectomies between January 1, 2021, and December 31, 2021. The patients were divided into two groups: the 75-84-year-old group and the 85+-year-old group. There was no difference in the pretreatment National Institutes of Health Stroke Scale score or Alberta Stroke Program Early Computed Tomography Score between the two groups, but the 85+-year-old group had a significantly lower rate of pre-stroke modified Rankin Scale (mRS) score of 0-2. There were no differences in time from onset to treatment or effective recanalization rate, but complications tended to be more common in the 85+-year-old group. The number of patients with a good outcome at discharge (an mRS score of 0-3) was significantly lower in the 85+-year-old group than in the 75-84-year-old group. In addition, 90.9% of patients in the 85+-year-old group with a pre-stroke mRS score of 3 deteriorated after treatment. The pre-stroke mRS score is very important in determining the indication for thrombectomy in the elderly because their preoperative condition is more likely to influence the outcome than that of younger patients.

Prenatal metal levels and congenital anomalies of the kidney and urinary tract: The Japan Environment and Children's Study.

BACKGROUND: Prenatal exposure to metal elements has been reported as a potential risk factor for congenital malformation. However, studies on the relationship with congenital anomalies of the kidney and urinary tract (CAKUT) are very scarce. METHODS: Participants of a prospective cohort from the Japan Environment and Children's Study, conducted at 15 research centers, were recruited between January 2011 and March 2014. The exposure factors were concentrations of lead (Pb), cadmium (Cd), mercury (Hg), selenium (Se), and manganese (Mn) measured from maternal whole blood in the second or third trimester. The primary outcome was CAKUT diagnosed during the first three years of life, which was classified into isolated cases and complicated cases accompanied by extrarenal congenital defects. To conduct a nested case-control design within the cohort, we selected 351 isolated cases with 1404 matched controls, and 79 complicated cases with 316 matched controls. RESULTS: A logistic regression model was used to examine the associations between individual metal concentrations and each subtype of CAKUT. A higher level of Se was associated with an increased risk of isolated CAKUT (adjusted odds ratio [95 % confidence interval]: 3.22 [1.33-7.77]). Meanwhile, higher levels of Pb and Mn were associated with a reduced risk of the complicated subtype (0.46 [0.24-0.90] and 0.33 [0.15-0.73], respectively). A Bayesian kernel machine regression model accounting for mixed effects of multiple metals further demonstrated that a higher level of Mn alone was significantly associated with a reduced occurrence of the complicated subtype. CONCLUSIONS: Using a stringent statistical approach, the present study demonstrated that a higher Mn concentration in the maternal blood was associated with a lower risk of complicated CAKUT in offspring. Further cohort and experimental studies are needed to verify the clinical impact of this finding.

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.

Impact on outcomes of measuring lactates prior to ICU in unselected heterogeneous critically ill patients: A propensity score analysis.

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.

Case Report: Juvenile Myelomonocytic Leukemia Underlying Ornithine Transcarbamylase Deficiency Safely Treated Using Hematopoietic Stem Cell Transplantation.

Background: Juvenile myelomonocytic leukemia (JMML), which is predominantly found in infants, is a clonal abnormality of pluripotent hematopoietic stem cells and presents with the symptoms of both myeloproliferative tumors and myelodysplastic syndromes. Estimates have shown that ~20 cases of JMML occur annually in Japan. Ornithine transcarbamylase deficiency (OTCD), the most common among all urea cycle disorders (UCDs), occurs in 1 of 80,000 people in Japan. Case Presentation: A 10-month-old infant who had fever, vomiting, and diarrhea for 2 days was referred to our hospital for the following abnormalities in blood tests: white blood cell count, 48,200/µL; hemoglobin, 9.0 g/dL; and platelet count, 135,000/µL. Bone marrow examination showed a nucleated cell count of 396,000/mm3 and blast cell count of 5.0%, as well as decreased mature granulocyte count and slightly myeloperoxidase stain-negative blasts but no monoclonal cell proliferation on May-Giemsa staining. Colony assay showed the proliferation of spontaneous colony and high sensitivity to granulocyte-macrophage colony-stimulating factor. Genetic analysis of peripheral blood mononuclear cells showed that the patient was positive for neuroblastoma RAS (NRAS) mutation. The patient was ultimately diagnosed with JMML. Approximately 170 days after his first hematopoietic stem cell transplantation (HSCT), the patient's JMML relapsed. Shortly after the recurrence, nausea, vomiting, hyperventilation, and decreased vitality were observed, followed by a decrease in the level of consciousness. The patient's ammonia level was 472 µmol/L. A test for seven different genetic mutations for the UCD showed the presence of c. 119G>A (amino acid change p. Arg40His). As such, late-onset OTCD was added to his diagnosis. Administration of sodium phenylacetate, l-arginine hydrochloride, and carnitine was continued following the diagnosis of OTCD, after which hyperammonemia was not observed. Regarding JMML relapse, HSCT was performed on day 405 after the first transplantation. Conclusion: Hyperammonemia should be considered a differential diagnosis when unexplained and non-specific symptoms occur during the treatment of hematologic malignancies. Patients should be tested for UCD as a cause of hyperammonemia, and treatment for hyperammonemia should be continued until the cause is identified. The patient shows normal developmental progress, has an intact neurological status, and has not experienced another hyperammonemia attack. His JMML has remained in remission for over 3 years.

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.

Factors Associated With Height Among Pediatric Kidney Transplant Recipients Aged ≤16 Years: A Retrospective, Single-Center Cohort Study of 60 Transplants.

OBJECTIVES: The aim of this study was to describe the factors associated with growth before and after kidney transplant. MATERIALS AND METHODS: We retrospectively reviewed 60 pediatric patients with end-stage kidney disease aged ≤16 years who underwent kidney transplant at our facility between November 2001 and March 2018. Height standard deviation score and possible associated factors were also compared. RESULTS: Among the 60 patients, median age was 11 years (interquartile range, 5.3-14 years), and 24 (40%) were female. All patients were alive during the observational period. The 2-, 5-, and 15-year graft survival rates were 96.7%, 94.4%, and 77.8%, respectively. Mean height standard deviation score for preoperative kidney transplant was -2.1 ± 1.5. Duration of dialysis (months) was associated with preoperative height standard deviation score (ß = -0.020; standard error = 0.006; t = -3.23; P = .002).Higher age andepisode of rejection were significant factors for loss of catch-up growth (P < .001 and P = .023, respectively). In total, 26 patients (43.3%) and 19 patients (31.7%) had short stature preoperatively and at 2 years after kidney transplant, respectively. Although 23 patients (38.3%) presented with catch-up growth after kidney transplant, 14 (53.9%) remained with short stature even 2 years after kidney transplant.Height standard deviation score 2 years after kidney transplant was associated with age, preoperative height standard deviation score, and episodes of rejection (P = .032, P < .001, and P = .005, respectively). CONCLUSIONS: Our study suggests that, although kidney transplant results in catch-up growth in pediatric patients, short stature often persists even 2 years after kidney transplant and is affected by age, preoperative height standard deviation score, and episodes of rejection.

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.

Pharmacokinetics of duloxetine self-administered in overdose with quetiapine and other antipsychotic drugs in a Japanese patient admitted to hospital.

BACKGROUND: Combinations of antidepressant duloxetine (at doses of 40-60 mg/day) and other antipsychotics are frequently used in clinical treatment; however, several fatal and nonfatal cases of duloxetine overdose have been documented. We experienced a patient who had taken an overdose of duloxetine (780 mg) in combination with other drugs in a suicide attempt. CASE PRESENTATION: The patient was a 37-year-old man (body weight, 64 kg) with a history of gender identity disorder and depression. He intentionally took an overdose of duloxetine in combination with three other antipsychotic drugs (18 mg flunitrazepam, 850 mg quetiapine, and 1100 mg trazodone) and was emergently admitted to Kyoto Medical Center. The patient's plasma concentration of duloxetine during ambulance transport was 57 ng/ml, and the level was still as high as 126 ng/mL at 32 h after administration. Duloxetine disappeared most slowly from plasma, in contrast to quetiapine, which was the fastest to clear among the four medicines determined in this patient. The observed concentrations of duloxetine in this overdose patient were generally within the 95% confidence intervals of the plasma concentration curves predicted using a physiologically based pharmacokinetic (PBPK) model. CONCLUSION: Even if more than 1 h (the generally recommended period) has passed after administration of duloxetine in such overdose cases, gastric lavage and/or administration of activated charcoal may be effective in clinical practice up to 6 h because of the typically slow elimination behavior illustrated by the PBPK model. Pharmacokinetic profiles visualized using PBPK modeling can inform treatment decisions in cases of drug overdose for medicines such as duloxetine in emergency clinical practice.

Involvement of activated cytotoxic T lymphocytes and natural killer cells in Henoch-Schönlein purpura nephritis.

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.

Both Autopsy and Computed Tomography Are Necessary for Accurately Detecting Rib Fractures Due to Cardiopulmonary Resuscitation.

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.

Pharmacokinetics of anticoagulant edoxaban in overdose in a Japanese patient transported to hospital.

BACKGROUND: The anticoagulant edoxaban is used clinically at doses of 30-60 mg/day; however, we experienced a patient who had taken an overdose of edoxaban of 750 mg. We investigated the pharmacokinetics of edoxaban in this patient by using liquid chromatography-tandem spectrometry to estimate the follow-up period in emergency clinical practice with this medicine. CASE PRESENTATION: The patient was a 57-year-old woman (body weight, 69 kg) who had taken a single oral dose of 750 mg of edoxaban in a suicide attempt. She was emergently admitted to Kyoto Medical Center. The patient's edoxaban plasma concentrations during ambulance transport (8 h after oral administration) were ~ 4900 ng/ml, and the concentration gradually decreased to ~ 10 ng/mL and to detectable but unmeasurable levels of ~ 1.0 ng/mL at 60 h and 100 h, respectively. The linear range of the relationship between the dose and plasma concentration was assumed to have been exceeded during the first 8 h; however, the measured elimination rate of edoxaban was similar to that visualized curves predicted by a simplified physiologically based pharmacokinetic model previously established. CONCLUSION: Simplified physiologically based pharmacokinetic models for creating visualized curves have proven to be useful not only during drug discovery or chemical risk assessment but also in cases of medical poisoning. We used a physiologically based pharmacokinetic model previously established for edoxaban to predict the pharmacokinetics in the current case. It is hoped that the results of this study, which encompass drug monitoring data in the patient and visualized pharmacokinetic prediction, will serve as an index when setting the treatment and follow-up period in cases of drug overdose for medicines such as edoxaban in emergency clinical practice.

Parvovirus B19-Infected Tubulointerstitial Nephritis in Hereditary Spherocytosis.

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.