Use of preoperative haemostasis and ABO blood typing tests in children: a retrospective observational study using a nationwide claims database in Japan.

OBJECTIVES: To describe the prevalence and factors associated with preoperative haemostasis and ABO blood typing tests for children because these tests might represent low-value care. DESIGN: A retrospective observational study. SETTING: Nationwide insurance claims database in Japan. PARTICIPANTS: Patients aged 1-17 years who underwent common non-cardiac surgeries between April 2012 and March 2018 were included. Patients with high-risk comorbidities for bleeding (n=175) and those with multiple eligible surgeries were excluded (n=2121). MAIN OUTCOME MEASURES: We described the proportions of each preoperative test performed within 60 days before an index surgery, including platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT) and ABO blood typing tests. We also explored the associations between patient-level and institutional-level factors and any preoperative tests, using multilevel logistic regression analysis. RESULTS: We included 13 018 patients (median (IQR) age, 5.2 (2.9-7.7) years; 8276 (63.6%) boys) from 1499 institutions. The overall proportion of each test was as follows: platelet count, 78.6%; PT, 54.4%; aPTT, 56.4% and ABO blood typing tests, 50.4%. The proportion of patients undergoing any preoperative tests in the overall sample was 79.3%. Multilevel logistic regression analysis indicated that preoperative tests were associated with type of anaesthesia (general anaesthesia: adjusted OR 7.06; 95% CI 4.94 to 10.11), type of surgery (tonsillectomy: adjusted OR 3.45; 95% CI 2.75 to 4.33) and surgical setting (inpatient procedure: adjusted OR 5.41; 95% CI 3.83 to 7.66). There was one postoperative transfusion event (0.008%) in the entire cohort and 37 postoperative reoperation events for surgical bleeding after tonsillectomy (0.90%). CONCLUSIONS: In the largest Japanese cohort reported to date, preoperative haemostasis and ABO blood typing tests were performed in a majority of children prior to common paediatric surgeries. Preoperative tests were associated with anaesthesia, surgical type and surgical setting.

Use of low-dose ß1-blocker for sinus tachycardia in patients with catecholamine support following cardiovascular surgery: a retrospective study.

BACKGROUND: Sinus tachycardia coupled with high-dose catecholamine is common after cardiopulmonary bypass (CPB). The present study assessed the hemodynamic efficacy and safety of combination therapy using low-dose ß1-selective adrenergic blocker (landiolol) and inotropes. METHODS: This was a retrospective, single center, self-comparison study at post-anesthesia care unit within a tertiary care center. The study included adults who underwent cardiac surgery with CPB and received landiolol between April 2007 and November 2011. We assessed hemodynamic data prior to and 1 h after initiation of landiolol therapy. RESULTS: We evaluated 11 patients who were administered 2.6 ± 1.3 µg/kg/min (mean ± SD) landiolol with sinus tachycardia and received catecholamine therapy after on-pump cardiovascular surgery. Landiolol administration led to a significant reduction in heart rate (HR; 112.4 ± 5.8 vs 126.0 ± 7.6 beats/min, p < 0.001), and a significant increase in stroke volume index (SVI) assessed by pulmonary artery catheterization (22.4 ± 5.4 vs. 18.9 ± 4.2 mL/m2, p = 0.04). Only one patient showed no HR reduction, whereas seven patients showed decreased HR and increased SVI (64, 95% confidence interval: 30-98%). Moreover, all five patients who received high-dose catecholamine support showed improved hemodynamics. In terms of safety, no patients required cessation of landiolol therapy. CONCLUSIONS: Low-dose landiolol therapy may safely decrease HR and improve hemodynamics among patients with sinus tachycardia receiving catecholamine treatment after cardiovascular surgery. TRIAL REGISTRATION: This study is retrospective. Registration number: 11. Duration of registration: April 2007~November 2011.

[A Case of Persistent Dysesthesia after Uneventful Spinal Anesthesia with Bupivacaine].

We report a case of persistent dysesthesia lasting over a year in a patient after uneventful spinal anes- thesia with bupivacaine. A 67-year-old woman received spinal anesthesia for transurethral resection of bladder tumor. The surgery was performed in lithotomy position taking 20 min. Dysesthesia was found in her left lower limb postoperatively. Postoperative magnetic resonance imaging (MRI) revealed lumbar spinal canal stenosis at the L4-5 level, but she did not have any neurological deficits preoperatively. In spite of conser- vative treatment, the dysesthesia persisted for a year. We suspect that neurological symptoms were potentially caused by the interaction of local anesthetic toxicity and lumbar spinal canal stenosis. This case emphasizes the importance of thorough consultation on potential neurological complications following spinal anesthesia including the possibility for prolonged sequelae. In addition an early imaging examination during follow up is quite informative in assessing the situation appropriately.

Surgical Resection of a Ruptured Pancreaticoduodenal Artery Aneurysm.

BACKGROUND: Ruptured aneurysms of the pancreaticoduodenal artery result in fatal hemorrhage and high mortality. Therefore, prompt diagnosis and treatment are required, but there are sometimes problems differentiating this specific diagnosis from other abdominal pathologies. CASE REPORT: We encountered a rare case of a ruptured pancreaticoduodenal artery aneurysm with an atypical clinical presentation that simulated acute pancreatitis. A 71-year-old woman was admitted to the emergency department with abdominal pain in the left upper quadrant, a slightly elevated level of pancreatic amylase, and cholelithiasis on ultrasonography. With persistent pain and progressively decreasing hemoglobin level, computed tomography with contrast showed fluid collection in the subphrenic space, a retroperitoneal hematoma, and a pancreaticoduodenal artery aneurysm that appeared to originate from a branch of the SMA. Urgent angiography indicated spontaneous rupture of a pancreaticoduodenal artery aneurysm. Emergent surgery was undertaken, and a simple aneurysmectomy was successfully performed. The patient's recovery was unremarkable. The prompt diagnosis of a pancreaticoduodenal artery aneurysm was difficult because the initial symptoms were vague and misleading in our case. CONCLUSIONS: A high level of suspicion, rapid diagnostic capability, and prompt surgical or endovascular intervention, as well as effective teamwork in the emergency department, are critical to avoid the devastating consequences of a ruptured visceral artery aneurysm.

Inflammatory stimuli induce inhibitory S-nitrosylation of the deacetylase SIRT1 to increase acetylation and activation of p53 and p65.

Inflammation increases the abundance of inducible nitric oxide synthase (iNOS), leading to enhanced production of nitric oxide (NO), which can modify proteins by S-nitrosylation. Enhanced NO production increases the activities of the transcription factors p53 and nuclear factor κB (NF-κB) in several models of disease-associated inflammation. S-nitrosylation inhibits the activity of the protein deacetylase SIRT1. SIRT1 limits apoptosis and inflammation by deacetylating p53 and p65 (also known as RelA), a subunit of NF-κB. We showed in multiple cultured mammalian cell lines that NO donors or inflammatory stimuli induced S-nitrosylation of SIRT1 within CXXC motifs, which inhibited SIRT1 by disrupting its ability to bind zinc. Inhibition of SIRT1 reduced deacetylation and promoted activation of p53 and p65, leading to apoptosis and increased expression of proinflammatory genes. In rodent models of systemic inflammation, Parkinson's disease, or aging-related muscular atrophy, S-nitrosylation of SIRT1 correlated with increased acetylation of p53 and p65 and activation of p53 and NF-κB target genes, suggesting that S-nitrosylation of SIRT1 may represent a proinflammatory switch common to many diseases and aging.

Malignant Hyperthermia during Thoracoscopic Pulmorrhaphy in a 70-Year-Old Man.

Malignant hyperthermia (MH) is a rare but potentially fatal complication that may develop under general anesthesia (GA) and is rarely reported in elderly patients. We encountered a case of mild-onset MH in a 70-year-old patient who was receiving an elective thoracoscopic pulmorrhaphy and had a history of several GA procedures. Anesthesia was induced with propofol, fentanyl, and rocuronium and maintained with sevoflurane and remifentanil. His body temperature (BT) was 37.9°C after induction. During the procedure, the end-tidal CO2 (ETCO2) increased steadily to 47-50 mmHg, presumably in response to the single lung ventilation. At the end, BT was 38.1°C and ETCO2 was 47 mmHg under spontaneous breathing. After extubation, the patient wheezed on inspiration and expiration, and his trachea was reintubated. Sixty minutes after surgery, BT increased to 40.5°C and the arterial blood gas analysis showed severe metabolic acidosis. Based on these findings, MH was suspected and a bolus dose of dantrolene was administered. He responded to the dantrolene, and no complications or recurrence of MH was observed postoperatively. In this patient, the initial signs of MH were so subtle that making the diagnosis of MH was difficult. A high degree of suspicion is necessary to prevent a fulminant MH crisis.

Reduction of cardiomyocyte S-nitrosylation by S-nitrosoglutathione reductase protects against sepsis-induced myocardial depression.

Myocardial depression is an important contributor to morbidity and mortality in septic patients. Nitric oxide (NO) plays an important role in the development of septic cardiomyopathy, but also has protective effects. Recent evidence has indicated that NO exerts many of its downstream effects on the cardiovascular system via protein S-nitrosylation, which is negatively regulated by S-nitrosoglutathione reductase (GSNOR), an enzyme promoting denitrosylation. We tested the hypothesis that reducing cardiomyocyte S-nitrosylation by increasing GSNOR activity can improve myocardial dysfunction during sepsis. Therefore, we generated mice with a cardiomyocyte-specific overexpression of GSNOR (GSNOR-CMTg mice) and subjected them to endotoxic shock. Measurements of cardiac function in vivo and ex vivo showed that GSNOR-CMTg mice had a significantly improved cardiac function after lipopolysaccharide challenge (LPS, 50 mg/kg) compared with wild-type (WT) mice. Cardiomyocytes isolated from septic GSNOR-CMTg mice showed a corresponding improvement in contractility compared with WT cells. However, systolic Ca(2+) release was similarly depressed in both genotypes after LPS, indicating that GSNOR-CMTg cardiomyocytes have increased Ca(2+) sensitivity during sepsis. Parameters of inflammation were equally increased in LPS-treated hearts of both genotypes, and no compensatory changes in NO synthase expression levels were found in GSNOR-overexpressing hearts before or after LPS challenge. GSNOR overexpression however significantly reduced total cardiac protein S-nitrosylation during sepsis. Taken together, our results indicate that increasing the denitrosylation capacity of cardiomyocytes protects against sepsis-induced myocardial depression. Our findings suggest that specifically reducing protein S-nitrosylation during sepsis improves cardiac function by increasing cardiac myofilament sensitivity to Ca(2+).

MRG-binding protein contributes to colorectal cancer development.

MRGBP (MORF4-related gene-binding protein; also known as chromosome 20 open reading frame 20) encodes a subunit of the transformation/transcription domain-associated protein (TRRAP)/tat-interacting protein 60 (TIP60)-containing histone acetyltransferase complex. We previously showed that MRGBP was upregulated in the majority of colorectal tumors, and the enhanced expression was associated with cell proliferation. In this study, we investigated its role in colorectal carcinogenesis and searched for genes regulated by MRGBP. Immunohistochemical staining of 22 adenomas and 47 carcinomas in the colon and rectum showed that high levels of MRGBP expression were observed more frequently in carcinomas (45%) than adenomas (5%), linking its role to malignant properties of colorectal tumors. No clinicopathological factors were associated with the levels MRGBP expression in colorectal cancer. Copy number analysis revealed that gene amplification is involved in the elevated expression. A genome-wide expression analysis identified a total of 41 genes upregulated by MRGBP. These genes were implicated in biological processes, including DNA replication, minichromosome maintenance, and cell division. Theses results suggest that MRGBP contributes to colorectal carcinogenesis through rendering advantages in cell proliferation and/or division of cancer cells. Our findings might be helpful for the identification of a specific biomarker for colorectal cancer and the development of diagnostic and/or therapeutic approaches.

Intracellular polarity protein PAR-1 regulates extracellular laminin assembly by regulating the dystroglycan complex.

Cell polarity depends on extrinsic spatial cues and intrinsic polarity proteins including PAR-aPKC proteins. In mammalian epithelial cells, cell-cell contacts provide spatial cues that activate the aPKC-PAR-3-PAR-6 complex to establish the landmark of the initial cellular asymmetry. PAR-1, a downstream target of the aPKC-PAR-3-PAR-6 complex, mediates further development of the apical and basolateral membrane domains. However, the relationships between the PAR-aPKC proteins and other extrinsic spatial cues provided by the extracellular matrix (ECM) remain unclear. Here, we show that PAR-1 colocalizes with laminin receptors and is required for the assembly of extracellular laminin on the basal surface of epithelial cells. Furthermore, PAR-1 regulates the basolateral localization of the dystroglycan (DG) complex, one of the laminin receptors essential for basement membrane formation. We also show that PAR-1 interacts with the DG complex and is required for the formation of a functional DG complex. These results reveal the presence of a novel inside-out pathway in which an intracellular polarity protein regulates the ECM organization required for epithelial cell polarity and tissue morphogenesis.

Involvement of the FGF18 gene in colorectal carcinogenesis, as a novel downstream target of the beta-catenin/T-cell factor complex.

To search for potential molecular targets for development of novel anticancer drugs, we have been analyzing expression profiles of clinical samples from cancer patients, using a genome-wide cDNA microarray. In experiments with colon cancer cells, the gene encoding fibroblast growth factor 18 (FGF18) was among those that showed elevated expression. The promoter region of this gene was found to contain putative Tcf4-binding motifs; moreover a reporter-gene assay using luciferase activity as a marker and an electromobility shift assay indicated that FGF18 is a downstream transcription target in the beta-catenin/Tcf4 pathway. We showed that exogenous FGF18 promoted growth of NIH3T3 cells in an autocrine manner and that transfection of FGF18 short interfering RNAs suppressed growth of colon cancer cells in culture. Our results indicate that FGF18 is activated in colon cancers as a direct downstream target of the Wnt signaling pathway and that it might represent a marker for early diagnosis and a molecular target for treatment of this life-threatening tumor.