Preventive Effects of Ramelteon, Suvorexant, and Lemborexant on Delirium in Hospitalized Patients With Physical Disease: A Retrospective Cohort Study.

BACKGROUND: New sleep-inducing drugs (eg, ramelteon, suvorexant, and lemborexant) have been shown to prevent delirium in high-risk groups. However, no single study has simultaneously evaluated the delirium-preventing effects of all novel sleep-inducing drugs in hospitalized patients. Therefore, this study aimed to clarify the relationship between sleep-inducing drugs and delirium prevention in patients hospitalized in general medical-surgical settings for nonpsychiatric conditions who underwent liaison interventions for insomnia. METHODS: This retrospective cohort study included patients treated in general medical-surgical settings for nonpsychiatric conditions with consultation-liaison psychiatry consult for insomnia. Delirium was diagnosed by fully certified psychiatrists using the Diagnostic and Statistical Manual of Mental Disorders 5 th edition. The following items were retrospectively examined from medical records as factors related to delirium development: type of sleep-inducing drugs, age, sex, and delirium risk factors. The risk factors of delirium development were calculated using adjusted odds ratios (aORs) via multivariate logistic regression analysis. RESULTS: Among the 710 patients analyzed, 257 (36.2%) developed delirium. Suvorexant (aOR, 0.61; 95% confidence interval [CI], 0.40-0.94; P = 0.02) and lemborexant (aOR, 0.23; 95% CI, 0.14-0.39; P < 0.0001) significantly reduced the risk of developing delirium. Benzodiazepines (aOR, 1.90; 95% CI, 1.15-3.13; P = 0.01) significantly increased this risk. Ramelteon (aOR, 1.30; 95% CI, 0.84-2.01; P = 0.24) and Z-drugs (aOR, 1.27; 95% CI, 0.81-1.98; P = 0.30) were not significantly associated with delirium development. CONCLUSIONS: The use of suvorexant and lemborexant may prevent delirium in patients with a wide range of medical conditions.

Arterial oxygen pressure during veno-venous extracorporeal membrane oxygenation may be increased by advancing the tip of the drainage cannula into the superior vena cava: a case report.

A simple and robust method for veno-venous extracorporeal membrane oxygenation (V-V ECMO) involves a drainage cannula into the inferior vena cava via the femoral vein (FV) and a reinfusion cannula into the right atrium (RA) via the internal jugular vein (IJV) (F-J configuration). However, with this method, the arterial oxygen (PaO2) is said to remain below 100 mmHg.Since recently, in our ICU, to prevent drainage failure, we apply a modification from the commonly practiced F-J configuration by advancing the tip of the drainage cannula inserted via the FV into the superior vena cava (SVC) and crossing the reinfusion cannula inserted via the IJV in the RA (F(SVC)-J(RA) configuration). We experienced that this modification can be associated with unexpectedly high PaO2 values, which here we investigated in detail.Veno-arteriovenous ECMO was induced in a 65-year-old male patient who suffered from repeated cardiac arrest due to acute respiratory distress syndrome. His chest X-ray images showed white-out after lung rest setting, consistent with near-absence of self-lung ventilation. Cardiac function recovered and the system was converted to F(SVC)-J(RA) configuration, after which both PaO2 and partial pressure of pulmonary arterial oxygen values remained high above 200 mmHg. Transesophageal echocardiography could not detect right-to-left shunt, and more efficient drainage of the native venous return flow compared to common F-J configuration may explain the increased PaO2.Although the F(SVC)-J(RA) configuration is a small modification of the F-J configuration, it seems to provide a revolutionary improvement in the ECMO field by combining robustness/simplicity with high PaO2 values.

Does Flexion Varus Osteotomy Improve Radiographic Findings Compared With Patients Treated in a Brace for Late-onset Legg-Calvé-Perthes Disease?

BACKGROUND: Legg-Calvé-Perthes disease (LCPD) is a childhood hip disease characterized by osteonecrosis of the femoral head. Because severe deformity of the femoral head can cause secondary osteoarthritis in adulthood, progressive collapse should be prevented in children with a necrotic epiphysis. The prognosis of patients with LCPD generally worsens as the age at disease onset increases, and the appropriate treatment for late-onset LCPD remains unclear. Based on the limited effect of nonoperative treatment using a nonweightbearing brace, flexion varus osteotomy (FVO) was introduced in 2010 as an initial treatment for late-onset LCPD in place of brace treatment, which we used in our institution before that time. QUESTIONS/PURPOSES: We asked, (1) Which treatment, FVO or a nonweightbearing brace, is associated with a lower likelihood of progressive femoral head collapse in children whose diagnosis of LCPD was made at the age of ≥ 8 years and who were followed for a minimum of 3 years after their intervention? (2) What proportion of patients in the brace group had surgery despite the treatment, and what percentage of children in the FVO group had a second operation to remove hardware and/or additional operations? METHODS: The initial treatment was applied in 181 patients with LCPD between 1995 and 2018 in our institution. Patients whose disease onset was at ≥ 8 years old (late-onset LCPD) with complete clinical and radiologic data were considered potentially eligible. In 2010, treatment for these patients changed from brace treatment to FVO for all patients. A total of 35% (42 of 121) of patients who were treated with a nonweightbearing brace between 1995 and 2009 and 40% (24 of 60) of patients who were treated with FVO between 2010 and 2018 were eligible. Among patients treated with a brace, 21% (nine of 42 patients) were excluded because of hospital transfer (three patients), short-term follow-up (three), the period from onset to the first visit was ≥ 7 months (two), and inability to use the brace because of mental incapacity (one patient). In patients treated with FVO, 12% (three of 24 patients) were excluded (two patients with a period from onset to the first visit ≥ 7 months and one with a comorbidity and multiple-epiphyseal dysplasia). Among the remaining patients, 79% (33 of 42 patients) were classified into the brace group and 88% (21 of 24 patients) were classified into the FVO group for analyses. There were no overlapping patients at the timepoint when the treatment strategy for late-onset LCPD changed. In the FVO group, subtrochanteric osteotomy with 35° to 40° of flexion and 15° to 20° of varus was performed using a locking compression plate for pediatric use. Patient demographics, radiographic parameters, and the assessment of femoral head deformity using the Stulberg classification were compared between the two groups. There was a greater proportion of boys than girls in both groups (brace: 88% and FVO: 86%), and there were no differences in the distribution of genders between the groups (p = 0.82). The right side was more frequently treated in the brace group, but there was no difference in laterality between the groups (brace: 58% right and FVO: 62% left; p = 0.16). There was no difference between groups in the median age at disease onset (9.0 years [range 8.0 to 12.5 years] in the brace group and 9.6 years [range 8.0 to 12.4 years] in the FVO group; p = 0.26). There was no difference between the groups in the period of treatment from onset (1.7 ± 1.9 months in the brace group and 1.5 ± 1.5 months in the FVO group; p = 0.73) or the follow-up period (6.7 ± 2.1 years in the brace group and 6.2 ± 2.1 years in the FVO group; p = 0.41). The LCPD stage at the first visit was assessed using the modified Waldenström classification. The intraobserver and interobserver values of the modified Waldenström classification, evaluated using kappa statistics, were excellent (kappa value 0.89 [95% CI 0.75 to 0.97]; p < 0.01) and good (kappa value 0.65 [95% CI 0.43 to 0.87]; p < 0.01). The radiographic degree of collapse at the maximum fragmentation stage was assessed using the lateral pillar classification. The intraobserver and interobserver reliabilities of the lateral pillar classification were excellent (kappa value 0.84 [95% CI 0.73 to 0.94]; p < 0.01) and excellent (kappa value 0.83 [95% CI 0.71 to 0.94]; p < 0.01). The degree of femoral head deformity at the most recent follow-up examination was compared between the groups in terms of the Stulberg classification, in which Classes I and II were classified as good and Classes III through V were classified as poor. The intraobserver and interobserver reliabilities of the Stulberg classification were good (kappa value 0.74 [95% CI 0.55 to 0.92]; p < 0.01) and good (kappa value 0.69 [95% CI 0.50 to 0.89]; p < 0.01). The evaluators were involved in the patients' clinical care as part of the treating team. RESULTS: Good radiographic results (Stulberg Class I or II) were obtained more frequently in the FVO group (76% [16 of 21 patients]) than in the brace group (36% [12 of 33 patients]), with an odds ratio of 5.6 (95% CI 1.7 to 18.5; p < 0.01). In the brace group, a subsequent femoral varus osteotomy was performed in 18% (six of 33) of patients with progressive collapse and hinge abduction, and implant removal surgery was performed approximately 1 year after the first procedure. This traditional varus osteotomy was occasionally performed in patients who were considered for conversion from nonoperative treatment before 2009 because FVO had not yet been introduced. In the FVO group, all patients (n = 21) had a second procedure to remove the implant at a mean of 10.5 ± 1.2 months postoperatively. Additional procedures were performed in 24% (five of 21) of patients, including a second FVO for progressive collapse (one patient), guided growth for a limb length discrepancy (one patient), and flexion valgus osteotomy for coxa vara in patients with a limb length discrepancy (three patients). CONCLUSION: Our historical control study found that FVO may increase the possibility of obtaining good radiographic results (Stulberg Class I or II) compared with brace treatment for patients with late-onset LCPD, although surgical interventions after the first and second implant removal procedures may be indicated. Surgeons can consider FVO if they encounter patients with late-onset LCPD, which is a challenging condition. A larger study with long-term follow-up is needed to confirm the efficacy of FVO. LEVEL OF EVIDENCE: Level III, therapeutic study.

Abnormal stenosis of a drainage cannula due to excessive negative pressure during venovenous extracorporeal membrane oxygenation management: a case report.

We report a case in which excessive negative pressure may have been applied to the proximal side hole of a drainage cannula during venovenous extracorporeal membrane oxygenation (V-V ECMO), resulting in abnormal stenosis of the drainage cannula. V-V ECMO was introduced in a 71-year-old male patient who was transferred from another hospital for severe respiratory failure associated with varicella pneumonia and acute respiratory distress syndrome. Drainage was performed using a PCKC-V™ 24Fr (MERA, Japan) cannula via the right femoral vein with the tip of the cannula near the level of the diaphragm under fluoroscopy. Reinfusion was performed via the right internal jugular vein. Due to poor systemic oxygenation, the drainage cannula was withdrawn caudally and refixed to reduce the effect of recirculation. Two days later, drainage pressure dropped rapidly, and frequent ECMO flow interruption occurred due to poor drainage. An abdominal X-ray revealed abnormal stenosis of the proximal side hole site of the drainage cannula. We diagnosed that the drainage cannula was damaged, and it was replaced with another, namely a Medtronic Bio-Medicus™ 25 Fr (GETINGE, Sweden) cannula. However, the removed drainage cannula was not damaged, suggesting that the cannula was temporarily stenosed by momentary excessive negative pressure. In a multi-stage drainage cannula, the main drainage site is the proximal side hole, with little negative pressure applied at the apical foramen in a mock experimental ex vivo drainage test in a water tank. Hence, improvement of a multi-stage drainage cannula is recommended, such as adequate reinforcement of the side hole site with a wire.

A Novel Method for Assessing the 3-dimensional Morphology of Cartilaginous Acetabulum Via Childhood Magnetic Resonance Imaging.

BACKGROUND: Periarticular cartilage is abundant in children, making evaluations of 3-dimensional (D) cartilaginous acetabular morphology using x-ray or computed tomography (CT) difficult. The study aimed to visualize the 3D cartilaginous acetabular morphology in normal children and patients with pediatric developmental dysplasia of the hip (DDH). METHODS: Magnetic resonance imaging (MRI) of 17 female children without acetabular dysplasia at 7.5 years and CT of 33 normal female adolescents with mature bones at 14.6 years were used as controls. Subjects were 26 female patients with unilateral DDH who underwent angulated Salter innominate osteotomy (A-SIO) at 5.5 years. Preoperative and postoperative MRIs were performed at 5.2 and 7.0 years, respectively. The MRI sequence was 3D-MEDIC. The medial intersection (point A) of the line connecting the centers of the bilateral femoral head and the femoral head were defined as point zero. The 3D coordinates (X, Y, Z) of the cartilaginous acetabular edge (point C) from anterior to posterior were calculated. Subsequently, a 3D scatter plot was created using 3D graph software. The subjects were divided into 6 groups, including control MRI, control CT, unaffected DDH before and after A-SIO, and affected DDH before and after A-SIO. The femoral head coverage ratio (FHCR: AC/AB) was used to quantify coverage and was compared in each group. RESULTS: In the control MRI group, the acetabular coverage was small anteriorly, largest anterolaterally, and gradually decreased posteriorly, similar to the bony acetabulum in adolescents. In the affected DDH before A-SIO group, the coverage was significantly lower than that of the control MRI and unaffected DDH groups. After A-SIO, the morphology improved beyond the unaffected DDH and the control MRI group. CONCLUSIONS: The global defect of the cartilaginous acetabulum in the affected DDH group was significantly improved to normal morphology after A-SIO. Evaluating the cartilaginous acetabulum using MRI was useful for assessing hip morphology in childhood. LEVEL OF EVIDENCE: Level III-retrospective comparative study.

Investigation of factors affecting COVID-19 pancreatic injury: a single-center, retrospective study.

Pancreatic injury is considered an organ-related complication in patients with coronavirus disease 2019 (COVID-19). However, it is unclear whether COVID-19 status affects pancreatic injury. This retrospective study aimed to determine whether COVID-19 affects the occurrence of pancreatic injuries. Consecutive patients diagnosed with sepsis admitted to the ICU between March 2020 and September 2021 were included. The primary endpoint was a pancreatic injury, which was defined as amylase or lipase levels > 3 times the upper limit of the normal range. Among the 177 patients included in the analysis, 40 (23%) were COVID-19 patients, and 54 (31%) had pancreatic injuries. Of these three patients, acute pancreatitis was diagnosed based on computed tomography. The pancreatic injury was significantly more common among COVID-19 patients (75 vs. 18%, p < 0.001). Multivariate analysis showed that COVID-19 and steroid use were independent risk factors for pancreatic injury (Odds Ratio (OR) 4.79 [95% confidence interval (CI) 1.48-15.5], p = 0.009; OR 4.02 [95% CI 1.42-11.4], p = 0.009). This study revealed that the proportion of pancreatic injury in septic patients with COVID-19 was significantly higher than in those without COVID-19. It may be difficult to diagnose pancreatitis based on amylase and lipase levels in COVID-19 patients.

Impact of Selected Initial Titration Schedules on Safety and Long-Term Effectiveness of Lamotrigine for the Treatment of Mood Disorders.

PURPOSE: Lamotrigine (LTG) is used for treatment of mood disorders, but it is associated with the risk of rash occurrence in the initial administration phase. Although slow titration reduces this risk, its effectiveness in the treatment of mood disorders has not been verified. The effects of titration method on the safety and effectiveness of LTG for the treatment of mood disorders were examined in this study. METHODS: This retrospective cohort study included 312 patients with mood disorders who underwent initiation of LTG therapy. Data regarding baseline demographics, titration schedules, concomitant medications, and time to and cause of discontinuation of LTG were collected. A multivariate analysis was used to evaluate the effects of the titration schedules. The 12-month effectiveness was also evaluated. RESULTS: The 12-month discontinuation rate of LTG was 16.7%. The most frequent cause of discontinuation was development of a rash (47.7%, n = 312). Fast titration (adjusted odds ratio, 8.15) significantly increased the risk of rash development, and slow titration (adjusted odds ratio, 0.29) significantly decreased this risk. The time to all-cause discontinuation was not significantly different between the slow and standard titration groups (n = 303). After 12 months of treatment, the condition of 46.7% patients were rated much or very much improved using CGI-C. CONCLUSIONS: Although slow titration of LTG reduces the occurrence of a rash, it is not more effective than standard titration in the long term. Optimizing the initial LTG titration schedule for patients with mood disorders is challenging.

Clinical Utility of Semistructured Interview and Scales to Assess Withdrawal Syndromes With Dose Reduction or Discontinuation of Selective Serotonin Reuptake Inhibitors or Serotonin Norepinephrine Reuptake Inhibitors.

BACKGROUND: Withdrawal syndromes can occur after dose reduction or discontinuation of selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). Few measurement instruments are available to assess them: Diagnostic Clinical Interview for Drug Withdrawal 1-New Symptoms of SSRI and SNRI (DID-W1) and Discontinuation Emergent Signs and Symptoms (DESS) checklist. We assessed their interrater reliability, verified the percent agreement between the two, and tested DESS sensitivity and specificity on the basis of the diagnoses formulated via the DID-W1. METHODS: One-hundred thirty-four subjects who referred for withdrawal at 3 outpatient facilities were enrolled and assessed via the DESS and the DID-W1. Percent agreement and Cohen κ were calculated to measure DID-W1 and DESS interrater reliability, as well as the agreement between DID-W1 and DESS items. Sensitivity and specificity of DESS were derived from the identification of true-positive, false-negative, true-negative, and false-positive on the DID-W1. RESULTS: Both tools showed excellent interrater reliability (DID-W1 Cohen κ = 0.958; DESS Cohen κ = 0.81-1). The degree of agreement between DID-W1 and DESS items was poor or fair (Cohen κ < 0.40) for some items and moderate (Cohen κ = 0.41-0.60) for others. Sensitivity and specificity of DESS were 0.937 (true-positive = 60, false-negative = 4) and 0.285 (true-negative = 20, false-positive = 50), respectively. CONCLUSIONS: DID-W1 was a reliable method to identify and diagnose withdrawal syndromes. The DESS checklist showed to be a useful tool for detecting withdrawal SSRI/SNRI symptoms when the aim is to achieve high sensitivity to identify true positives.

Hyperchloremia and Postoperative Acute Kidney Injury in Adult Cardiac Patients: A Propensity-Matched Cohort Study.

OBJECTIVES: Hyperchloremia is a potential risk factor for acute kidney injury (AKI) in critically ill patients. However, the relationship between hyperchloremia and postoperative AKI in adult patients undergoing cardiovascular surgery with cardiopulmonary bypass (CPB) remains unclear. The authors aimed to determine whether postoperative hyperchloremia was associated with postoperative AKI in these populations. OBJECTIVES: Retrospective, single-center study. SETTING: Tertiary care hospital. PARTICIPANTS: Adult patients who underwent cardiovascular surgery with CPB. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Patients with and without postoperative hyperchloremia were matched (1:1). The primary outcome was the rate of postoperative AKI diagnosed using the Kidney Disease: Improving Global Outcomes consensus criteria. Postoperative hyperchloremia was defined as postoperative serum chloride levels of >110 mmol/L during the first 48 hours. An increase in serum chloride levels (Δ[Cl-]) was defined as the difference between the preoperative and maximum postoperative serum chloride levels during the first 48 hours ([Cl-]max). Propensity-score matching and univariate and multivariate logistic regression analyses were employed. A total of 323 patients were included. Propensity-score matching selected 55 pairs for the final comparison. The incidence of postoperative AKI did not differ between the two groups (47% v 46%, p = 1.0). In the multivariate logistic regression analysis, Δ[Cl-] was associated independently with the development of postoperative AKI (odds ratio, 1.13; 95% confidence interval, 1.06-1.21; p < 0.001). CONCLUSIONS: Exposure to postoperative hyperchloremia was not associated with postoperative AKI in adult patients undergoing cardiovascular surgery with CPB. However, an increase in the serum chloride level might be associated with postoperative AKI.

Current status of antimicrobial prophylaxis during extracorporeal membrane oxygenation in Japan: a national survey.

Infection during extracorporeal membrane oxygenation (ECMO) is a common complication that leads to increased mortality. Thus, antimicrobial prophylaxis during ECMO is often performed to prevent of nosocomial infections. However, the current status of antimicrobial prophylaxis during ECMO in Japan is unclear. Therefore, we conducted a national survey of members of the Japanese Society of Intensive Care Medicine (JSICM) to clarify the current status of antimicrobial prophylaxis during ECMO in intensive care units. An 11-question survey was devised to assess antimicrobial prophylaxis and surveillance practices during ECMO. A total of 253 hospitals responded. Of these, 235 hospitals were the JSICM-certified hospitals, and the response rate was 64%. A total of 96 hospitals (39%) administered antimicrobial prophylaxis during ECMO, and 17% of hospitals had a standardized protocol for antimicrobial prophylaxis during ECMO. Of these 96 hospitals, 79% used single agents. First-generation cephalosporins were the most commonly used (54%), followed by penicillins or penicillin-derived combinations (24%), second-generation cephalosporins (7%), and anti-methicillin-resistant Staphylococcus aureus agents (6%). In conclusion, our survey revealed 39% of hospitals administered antimicrobial prophylaxis during ECMO in Japan. First-generation cephalosporins were the agents most commonly used.

Hip Prognosis in Patients With Congenital Diastasis of the Pubic Symphysis.

BACKGROUND: Congenital diastasis of the pubic symphysis (CDPS) is a rare musculoskeletal malformation in the exstrophy-epispadias complex that is potentially associated with the development of hip dysplasia. The purpose of this study was to investigate the incidence and prognostic factors of hip dysplasia in patients with CDPS. METHODS: Fifty-four hips in 27 patients with CDPS initially evaluated between 1983 and 2016 were retrospectively reviewed. The mean age at the first visit was 2.3 (0 to 8) years. The mean follow-up duration was 10.5 (1 to 36) years. Patient characteristics at the first visit, the clinical course at the most recent follow-up, and radiologic parameters on pubic malformation and hip dysplasia during at least 2 time points (first visit or age 1, and either the most recent visit or before hip surgery) were evaluated. Prognostic factors associated with the development of hip dysplasia were analyzed using univariate/multivariate analysis. The Kaplan-Meier survival curves were generated and compared based on these factors. RESULTS: Nine of 27 patients (33%) and 13 of 54 hip joints (24%) with CDPS developed hip dysplasia. Paraplegia (odds ratio, 10.0; 95% confidence interval, 1.7-76.6) and center-edge angle of <5 degrees at the first visit or age 1 (P<0.001) were independent predictors of the development of hip dysplasia. Patients with CDPS and either paraplegia or center-edge angle <5 degrees at the first visit or age 1 were significantly more likely to develop hip dysplasia than other patients (hazard ratio, 29.3; 95% confidence interval, 3.4-250). CONCLUSIONS: Approximately one third of patients with CDPS develop hip dysplasia. Paraplegia and center-edge angle of <5 degrees at the first visit are independent risk factors. LEVEL OF EVIDENCE: Level III.

Cefepime-induced encephalopathy in a COVID-19 patient: a case report.

Prolonged neurological symptoms such as "brain fog" and cognitive impairment have occurred after coronavirus disease 2019 (COVID-19) infection. In this report, we describe impaired consciousness caused by cefepime hydrochloride (CFPM) in a patient with cognitive sequalae of COVID-19. A 56-year-old male patient was diagnosed with penile abscess after COVID-19 infection, and a blood culture detected two drug-resistant Pseudomonas aeruginosa strains. Therefore, CFPM 2 g × twice/day was administered on day 71 after intensive care unit admission. Approximately 48 h after CFPM administration, the patient showed disturbances in consciousness. Contrast-enhanced computed tomography, magnetic resonance imaging, and spinal fluid examination revealed no obvious abnormalities. Therefore, CFPM-induced neurotoxicity was suspected. CFPM was discontinued and ceftazidime 2 g × three times/day was initiated. The patient's consciousness improved 30 h after the final administration of CFPM. Serum CFPM concentrations were 14.2, 21.7, 21.7, and 11.9 µg/mL on days 1, 2, and 3 after the initiation of CFPM and on the day after CFPM was discontinued, respectively. In conclusion, intensivists should pay attention to new neurological symptoms such as CFPM-induced encephalopathy in patients with prolonged neurological symptoms after COVID-19 infection.

A case of spontaneous rectus sheath hematoma induced by lateral semi-prone positional changes during extracorporeal membrane oxygenation.

Spontaneous abdominal wall hematomas are relatively rare and mainly attributed to anticoagulation and severe cough. Despite the high incidence of anticoagulation-related bleeding complications, there are no reports of spontaneous abdominal wall hematomas during extracorporeal membrane oxygenation (ECMO). We report a case of a spontaneous rectus sheath hematoma caused by alternation of the lateral semi-prone position during ECMO in a 76-year-old female patient with severe acute respiratory distress syndrome. Unfractionated heparin 12,000-14,000 units/day was administered for anticoagulation during ECMO. From Day 6 of ECMO, the patient who was under deep sedation was alternately placed in the left and right lateral semi-prone positions every 4 h, for approximately 20 h per day. On Day 12 of ECMO, the patient developed hypotension with anemia and a palpable mass in the right lower abdomen. Abdominal ultrasonographic imaging revealed a huge echo-free space centered in the right lower abdomen. Emergency contrast-enhanced computed tomography (CT) scanning showed extravasation from the superior and inferior epigastric arteries as well as a rectus sheath hematoma. Despite no apparent contrast leakage, an inferior epigastric artery embolization was undertaken because the patient was on ECMO. On Day 13 after ECMO initiation, ECMO and anticoagulation were discontinued. On CT scanning a week later, the hematoma had reduced. In conclusion, spontaneous abdominal wall hematoma is a rare and important complication that might occur during ECMO. Thus, careful physical examination should be routinely conducted when the patient is semi-prone during ECMO.

A longitudinal study for the prediction of the mature acetabular morphology using childhood magnetic resonance imaging.

BACKGROUND: Although acetabular dysplasia is a common etiology of osteoarthritis of the hip regardless of the history of developmental dysplasia of the hip (DDH), whether or not corrective surgeries are beneficial for the childhood asymptomatic acetabular dysplasia remains controversial due to a lack of evidence. We conducted a longitudinal study to compare the cartilaginous morphology on childhood magnetic resonance imaging (MRI) and the mature hip morphology of the same patient and to assess the predictive indicators for future acetabular dysplasia. METHODS: A total of 92 unaffected hips (47 unilateral DDH and 45 unilateral Legg-Calvé-Perthes disease) were reviewed for X-ray and MRI findings on childhood (mean age: 6.0 years) and X-ray findings from a skeletally mature age with a mean follow-up period of 15.1 years. The following parameters were measured and compared: the immature-acetabular index (AI) and center edge angle (CE) on immature X-ray; the cartilage- and bone- AI, CE, Sharp and acetabular head index (AHI) on childhood MRI; and the mature-acetabular roof obliquity (ARO), CE, Sharp and AHI on skeletally mature X-ray. The prognostic factors on childhood MRI for acetabular dysplasia, defined by a CE of <20° on skeletally mature X-ray were also assessed. RESULTS: Positive correlations were shown between the cartilage-AI and mature-ARO (7.6°/6.3°; r = 0.44), the cartilage-CE and mature-CE (27.8°/28.0°; r = 0.62), the cartilage-Sharp and mature-Sharp (44.4°/41.8°; r = 0.52) and the cartilage-AHI and mature-AHI (78.7%/80.3%; r = 0.46). A multivariate analysis indicated cartilage-CE to be an independent predictor for acetabular dysplasia with a cut-off value of 22°. Children with a cartilage-CE <22° developed more frequently acetabular dysplasia compared to the others (52.4% vs. 1.4%). CONCLUSIONS: Childhood MRI findings are useful for the prediction of acetabular dysplasia without a DDH history. Children with a cartilage-CE ≥23° are likely to achieve a non-dysplastic hip without the need for surgical intervention.

Effects of Thrombomodulin in Reducing Lethality and Suppressing Neutrophil Extracellular Trap Formation in the Lungs and Liver in a Lipopolysaccharide-Induced Murine Septic Shock Model.

Neutrophil extracellular trap (NET) formation, an innate immune system response, is associated with thrombogenesis and vascular endothelial injury. Circulatory disorders due to microvascular thrombogenesis are one of the principal causes of organ damage. NET formation in organs contributes to the exacerbation of sepsis, which is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. We have previously reported that recombinant human soluble thrombomodulin (rTM) reduces lipopolysaccharide (LPS)-induced NET formation in vitro. Here, we aimed to show that thrombomodulin (TM)-mediated suppression of NET formation protects against organ damage in sepsis. Mice were injected intraperitoneally (i.p.) with 10 mg/kg LPS. rTM (6 mg/kg/day) or saline was administered i.p. 1 h after LPS injection. In the LPS-induced murine septic shock model, extracellular histones, which are components of NETs, were observed in the liver and lungs. In addition, the serum cytokine (interleukin-1ß (IL-1ß), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), macrophage chemotactic protein-1 (MCP-1), and interleukin-10 (IL-10)) levels were increased. The administration of rTM in this model prevented NET formation in the organs and suppressed the increase in the levels of all cytokines except IL-1ß. Furthermore, the survival rate improved. We provide a novel role of TM in treating inflammation and NETs in organs during sepsis.

Role of Thrombospondin-1 in Mechanotransduction and Development of Thoracic Aortic Aneurysm in Mouse and Humans.

RATIONALE: Abnormal mechanosensing of smooth muscle cells (SMCs) resulting from the defective elastin-contractile units has been suggested to drive the formation of thoracic aortic aneurysms; however, the precise molecular mechanism has not been elucidated. OBJECTIVE: The aim of this study was to identify the crucial mediator(s) involved in abnormal mechanosensing and propagation of biochemical signals during the aneurysm formation and to establish a basis for a novel therapeutic strategy. METHODS AND RESULTS: We used a mouse model of postnatal ascending aortic aneurysms ( Fbln4SMKO; termed SMKO [SMC-specific knockout]), in which deletion of Fbln4 (fibulin-4) leads to disruption of the elastin-contractile units caused by a loss of elastic lamina-SMC connections. In this mouse, upregulation of Egr1 (early growth response 1) and angiotensin-converting enzyme leads to activation of Ang II (angiotensin II) signaling. Here, we showed that the matricellular protein, Thbs1 (thrombospondin-1), was highly upregulated in SMKO ascending aortas and in human thoracic aortic aneurysms. Thbs1 was induced by mechanical stretch and Ang II in SMCs, for which Egr1 was required, and reduction of Fbln4 sensitized the cells to these stimuli and led to higher expression of Egr1 and Thbs1. Deletion of Thbs1 in SMKO mice prevented the aneurysm formation in ≈80% of DKO (SMKO;Thbs1 knockout) animals and suppressed Ssh1 (slingshot-1) and cofilin dephosphorylation, leading to the formation of normal actin filaments. Furthermore, elastic lamina-SMC connections were restored in DKO aortas, and mechanical testing showed that structural and material properties of DKO aortas were markedly improved. CONCLUSIONS: Thbs1 is a critical component of mechanotransduction, as well as a modulator of elastic fiber organization. Maladaptive upregulation of Thbs1 results in disruption of elastin-contractile units and dysregulation of actin cytoskeletal remodeling, contributing to the development of ascending aortic aneurysms in vivo. Thbs1 may serve as a potential therapeutic target for treating thoracic aortic aneurysms.

Scooping Rice Into a Glass and Putting a Cell Phone in the Refrigerator: Action Slips in an Individual With a Diffuse Axonal Injury.

A 39-year-old man with a diffuse axonal injury self-presented to the cognitive function clinic of the Ashikaga Red Cross Hospital complaining of behavioral errors in his daily life, such as scooping hot rice into a glass instead of a bowl or forgetting to turn off the gas stove after cooking. This type of error has been referred to as an action slip-a form of unintentional behavioral error that occurs when an individual attempts to perform an automatic and/or familiar task. In this case, action slips occurred nine times a day on average and had a serious and long-term impact on the man's daily quality of life. To reduce the impact of action slips, we created a one-on-one cognitive intervention that used a combination of mnemonic strategies, such as verbalizing his actions as he carried them out, and external aids, including a waist pouch, a voice-controlled artificial intelligence (AI) speaker, and an AI key finder. After 3 years of intervention, the man reported some improvement in his daily activities and a reduction in the number of action slips. Thus, intervention strategies for individuals with a diffuse axonal injury may benefit from targeting action slips. To our knowledge, this is the first detailed description of action slips in an individual with a diffuse axonal injury.

In vitro Evaluation of Linezolid and Doripenem Clearance with Different Hemofilters.

INTRODUCTION: Renal replacement therapy (RRT) is widely used in the treatment of septic acute kidney injury. However, little is known about how the adsorption properties of hemofilters used in RRT affect antibiotic concentration. Because a cytokine-adsorption membrane is frequently used in RRT, it is important to determine the antibiotic adsorption capacity of this membrane. OBJECTIVE: The present study aimed to investigate the antibiotic adsorption capacity of different hemofilter membranes by in vitro experiments using 2 antibacterial agents (linezolid and doripenem). METHODS: We performed experimental hemofiltration in vitro using polyacrylonitrile (AN69ST), polymethylmethacrylate (PMMA), and polysulfone (PS) hemofilters for 1,440 min. The test solution was a 1,000-mL substitution fluid containing 30 µg/mL linezolid and 120 µg/mL doripenem. We measured drug concentrations at the inlet, outlet, and filtrate ports of the hemofilters for 1,440 min and calculated the sieving coefficient (SC) and adsorption rate (Ra) of the drugs onto the hemofilters. RESULTS: The amount of linezolid adsorbed onto AN69ST, PMMA, and PS membranes was decreased relative to that in the control group at 15 min (p < 0.05). However, no SC for linezolid was obtained thereafter. The Ra of linezolid onto AN69ST, PMMA, and PS membranes was higher than that in the control group (p < 0.05). In contrast, no significant differences were observed in the concentrations and Ra values of doripenem adsorbed onto AN69ST, PMMA, and PS membranes compared with those in the control group. CONCLUSIONS: Doripenem was not adsorbed onto PMMA, PS, and AN69ST membranes. Linezolid was adsorbed onto PMMA, PS, and AN69ST membranes, but only temporarily, and this did not affect drug bioavailability.

Involvement of ionic interactions in cytokine adsorption of polyethyleneimine-coated polyacrylonitrile and polymethyl methacrylate membranes in vitro.

Polyethyleneimine-coated polyacrylonitrile (AN69ST) and polymethyl methacrylate (PMMA) membranes are effective cytokine-adsorbing hemofilters; however, the cytokine-adsorption mechanism remains elusive. This study investigated the involvement of ionic interactions in cytokine adsorption to a negatively charged AN69ST membrane and neutral-charged PMMA membrane. Experimental hemofiltration was performed for 30 min in a closed-loop circulation system using AN69ST and PMMA hemofilters. Tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-8 concentrations in the test solutions were measured at baseline and at 10 min and 30 min into hemofiltration. To investigate the involvement of ionic interactions in cytokine adsorption, cytokine clearance (CL) was calculated at 10 min into hemofiltration and with three types of solutions at various pH levels (7.6, 7.2, and 6.8). During AN69ST hemofiltration, the CLs of TNF-α, IL-6, and IL-8 were 38 ± 6 mL/min, 23 ± 7 mL/min, and 78 ± 3 mL/min, respectively, demonstrating a relationship with their respective isoelectric points. During PMMA hemofiltration, the CL of IL-6 peaked at 31 ± 76 mL/min, with no relationship observed between the CL and isoelectric point. When the pH of the test solution shifted from 7.6 to 6.8, the CLs of TNF-α, IL6, and IL-8 increased in the AN69ST hemofilter; whereas, no such trend was observed in the PMMA hemofilter. These results indicated that Ionic interactions play a role in cytokine adsorption by the AN69ST membrane but not the PMMA membrane and highlight the clinical relevance of this finding, as well as the potential practical applications for further hemofilter design.

MicroRNA-33 Controls Adaptive Fibrotic Response in the Remodeling Heart by Preserving Lipid Raft Cholesterol.

RATIONALE: Heart failure and atherosclerosis share the underlying mechanisms of chronic inflammation followed by fibrosis. A highly conserved microRNA (miR), miR-33, is considered as a potential therapeutic target for atherosclerosis because it regulates lipid metabolism and inflammation. However, the role of miR-33 in heart failure remains to be elucidated. OBJECTIVE: To clarify the role of miR-33 involved in heart failure. METHODS AND RESULTS: We first investigated the expression levels of miR-33a/b in human cardiac tissue samples with dilated cardiomyopathy. Increased expression of miR-33a was associated with improving hemodynamic parameters. To clarify the role of miR-33 in remodeling hearts, we investigated the responses to pressure overload by transverse aortic constriction in miR-33-deficient (knockout [KO]) mice. When mice were subjected to transverse aortic constriction, miR-33 expression levels were significantly upregulated in wild-type left ventricles. There was no difference in hypertrophic responses between wild-type and miR-33KO hearts, whereas cardiac fibrosis was ameliorated in miR-33KO hearts compared with wild-type hearts. Despite the ameliorated cardiac fibrosis, miR-33KO mice showed impaired systolic function after transverse aortic constriction. We also found that cardiac fibroblasts were mainly responsible for miR-33 expression in the heart. Deficiency of miR-33 impaired cardiac fibroblast proliferation, which was considered to be caused by altered lipid raft cholesterol content. Moreover, cardiac fibroblast-specific miR-33-deficient mice also showed decreased cardiac fibrosis induced by transverse aortic constriction as systemic miR-33KO mice. CONCLUSION: Our results demonstrate that miR-33 is involved in cardiac remodeling, and it preserves lipid raft cholesterol content in fibroblasts and maintains adaptive fibrotic responses in the remodeling heart.