General Anesthesia With Remimazolam During Minimally Invasive Cardiac Surgery for Atrial Septal Defect: A Pediatric Case Report.

Remimazolam is a new ultrashort-acting benzodiazepine sedative, the use of which has not been reported for pediatric cardiac surgery. This case report describes the use of remimazolam in a 6-year-old girl who underwent minimally invasive cardiac surgery with right-sided thoracotomy for an atrial septal defect. Under electroencephalographic monitoring, remimazolam (2-4 mg kg-1 h-1) and remifentanil (0.05 µg kg-1 min-1) were administered with an intercostal nerve block during the procedure. The patient awoke and was extubated promptly after surgery, without any serious adverse events, including intraoperative awareness. Remimazolam may be a viable option for general anesthesia during pediatric cardiac surgery.

Carboxyhemoglobin and Methemoglobin Levels and Hemolysis in Children Undergoing Cardiac Surgery With Cardiopulmonary Bypass.

Hemolysis is a complication of cardiopulmonary bypass (CPB). Carboxyhemoglobin (COHb) and methemoglobin (MetHb) were suggested as potential hemolysis biomarkers. This retrospective study was based on a prospective registry aimed to determine the association of COHb and MetHb levels with hemolysis in pediatric patients <4 years old who underwent cardiac surgery with CPB. Plasma-free hemoglobin (PFH), COHb, and MetHb levels were measured before CPB; every 30 minutes during CPB; and on postoperative days 1, 2, and 3. Patients were classified into hemolysis and nonhemolysis groups based on the maximum PFH levels during CPB. A total of 193 patients were included. No significant difference was observed in the maximum COHb levels during CPB (COHb CPB ) between the hemolysis and nonhemolysis groups (1.2% [interquartile range {IQR} 0.9-1.4%] vs. 1.1% [IQR: 0.9-1.4%]; p = 0.17). The maximum MetHb levels during CPB (MetHb CPB ) were significantly higher in the hemolysis group than in the nonhemolysis group (1.3% [IQR: 1.1-1.5%] vs. 1.2% [IQR: 1.0-1.4%]; p = 0.007). Areas under the receiver operating curves of COHb CPB and MetHb CPB were 0.557 (95% confidence interval: 0.475-0.640) and 0.615 (95% confidence interval: 0.535-0.695), respectively. Therefore, the predictive ability of both hemolysis biomarkers during CPB is limited.

Dasatinib attenuates airway inflammation of asthma exacerbation in mice induced by house dust mites and dsRNA.

Asthma exacerbation is a significant clinical problem that causes resistance to corticosteroid therapy and elevated hospitalization risk. Src family kinases (SFKs) contribute to various steps of the immune response, such as airway inflammation in viral or bacterial infections and allergic asthma. Therefore, we determined the effects of dasatinib (DAS), a typical Src inhibitor, on a murine asthma exacerbation model induced by house dust mites (HDM) and synthetic analog of double-stranded RNA, poly(I:C). A/J mice were sensitized to intrapreneurial HDM twice every seven days and challenged with intranasal HDM once every second day for a total of six exposures, and/or exposed to poly(I:C) twice daily for three consecutive days. Drug treatments were performed twice daily for three days, starting one day after the last HDM challenge or 2 h before each poly(I:C) exposure. DAS improved poly(I:C)-induced acute inflammation dose-dependently. Both DAS and fluticasone propionate (FP) attenuated HDM-induced allergic airway inflammation. However, in HDM and poly(I:C) induced-asthma exacerbated mice, DAS significantly improved inflammatory cells in bronchoalveolar lavage fluid and histological changes in the lungs, whereas FP did not. Therefore, SFKs are important targets for controlling severe asthma refractory to conventional therapies.

Next-Generation Sequencing for Non-Ampullary Duodenal Carcinoma Suggesting the Existence of an Adenoma-Carcinoma Sequence.

Duodenal tumors with a sporadic adenoma-carcinoma sequence are extremely rare. For such clinically suspected cases without a specific family history, performing a comprehensive gene search is important to understand the germline mutation background. We present a 68-year-old woman without a genetic or familial history of familial adenomatous polyposis (FAP), Peutz-Jeghers syndrome, or Lynch syndrome who presented to Kosei Hospital, Japan, with exertional dyspnea induced by abdominal pain lasting 3 weeks. A duodenal tumor was suspected by contrast-enhanced computed tomography. Esophagogastroduodenoscopy showed a lesion accompanied by a white microprotuberance on the descending part of the duodenum opposite the papilla, with a giant ulcerative lesion at the center of the white lesion. Biopsy revealed a low-grade adenoma, high-grade adenoma, and adenocarcinoma. Immunohistochemical analysis of the adenoma and adenocarcinoma showed Ki-67, p53, cytokeratin 20, caudal-type homeobox 2, and carcinoembryonic antigen positivity and cytokeratin 7 negativity. The findings suggested the presence of an adenoma-adenocarcinoma sequence in duodenal carcinoma. However, in the mutational analysis using next-generation sequencing, c.4348C>T (p.Arg1450Ter) mutation in APC was detected in all normal mucosal, adenoma, and carcinoma tissues. This mutation is common in FAP patients. Even if the presence of an adenoma-adenocarcinoma sequence in duodenal carcinoma is suggested in cases without a familial FAP history, as in this case, genetic analysis may reveal FAP. Thus, performing a comprehensive genetic analysis of duodenal carcinoma patients with a possible adenoma-carcinoma sequence is necessary to explore their genetic background.

Older-age onset of Kimura's disease.

A 60-year-old man was admitted to our hospital with bilateral post auricular masses, first noticed 1 year earlier. Blood tests showed eosinophilia and high immunoglobulin E (IgE) levels, and cervical computed tomography showed 10-mm soft tissue masses with scattered lymphadenopathy. The tumors showed intermediate and high signal intensity on T1- and T2-weighted cervical magnetic resonance imaging, respectively. After mass resection, the tumors were diagnosed as Kimura's disease (KD). Generally, KD affects young men; however, even in older patients, KD should be included as a differential diagnosis for head and neck tumors in patients with eosinophilia and high IgE.

Utilization of a new technology of 3D biliary CT for ERCP-related procedures: a case report.

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is still performed using two-dimensional (2D) X-ray images. The success rate and risk of complications are considered operator-dependent. We explored performing an ERCP-related procedure with 3D-computed tomography (CT) biliary imaging for preoperative simulation and intraoperative reference in a patient with malignant biliary obstruction. CASE PRESENTATION: The patient was a 66-year-old man who underwent rectal resection and postoperative chemotherapy for rectal cancer. A liver metastasis caused obstructive jaundice and acute cholangitis, necessitating emergency hospitalization. A 3.5 cm mass in the hilar region of the biliary tree caused type IV biliary obstruction according to the Bismuth-Corlette classification of hilar cholangiocarcinoma. ERCP and biliary drainage were performed repeatedly, but had no effect. Given that selective bile duct drainage had proven extremely difficult with the conventional procedures, three-dimensional (3D) images were created from preoperative CT image data using a 3D image reconstruction system (SYNAPSE VINCENT version 5, FUJIFILM Corporation, Tokyo, Japan). Using the 3D images for preoperative planning and intraoperative reference, biliary drainage and stent placement were successfully performed without complications. Postoperatively, the patient had no further cholangitis or need for stent replacement up to his death. CONCLUSIONS: We report the first case of an ERCP-related procedure with 3D biliary imaging for preoperative simulation and intraoperative reference in a patient with malignant biliary obstruction. The 3D image reconstruction is useful for preoperative planning and could contribute to an increased success rate, decreased complications, a shorter operation time, and reduced radiation exposure to the operator.

Influence of a community-based approach to improve risk factors of lifestyle diseases by Japanese public health nurses: A case-control study.

BACKGROUND AND OBJECTIVES: It is important to examine the roles of specific health check-up and specific health guidance in individuals at high risk of common lifestyle diseases, but evaluation based on a stratified analysis of people undergoing a health check-up has not been adequately performed. In this study, we examined the effects of providing specific health guidance to individuals considered at high risk for a lifestyle disease after specific health check-ups. METHOD: Subjects who underwent a specific health check-up in 2012 were assigned to either a group that received health guidance from public health nurses over three years (n = 393) or a control group (n = 109). Clinical findings of both groups were analysed to evaluate the correlation between their changes and health guidance. RESULTS: A significant decrease was observed in blood pressure, and lipid and glucose levels only in the health guidance group. Multiple regression analysis revealed that health guidance was the explanatory variable of serum lipid improvement. DISCUSSION: Continued support by Japanese public health nurses through health guidance closely related to the subject's lifestyle over three years may lead to a comprehensive reduction in the risk of lifestyle diseases.

Pharmacokinetic-pharmacodynamic comparison of ceftriaxone regimens in acute cholangitis.

The most important factors determining the prognosis of patients with acute cholangitis (AC) are prompt biliary drainage and appropriate choice of antibiotics. This study was performed to evaluate whether dividing the number of doses based on the PK-PD theory contributes to better clinical outcome in the management of acute cholangitis. We measured ceftriaxone levels in blood and bile in 21 cases diagnosed with moderate-to-severe AC. Eleven cases were administered 2 g of ceftriaxone once-daily (group A) and 10 cases were given 1 g of ceftriaxone twice-daily (group B). The theoretical effect of ceftriaxone was evaluated by pharmacokinetic-pharmacodynamic (PK-PD) parameters. Clinical efficacy was evaluated by body temperature, white blood cell count and serum levels of C-reactive protein. Minimum level of ceftriaxone in serum (in mg/L) in groups A and B at 24 h after the first dose was 9.1 and 9.2, whereas that in bile was 2.9 and 2.5, respectively. The minimum inhibitory concentration (MIC) of ceftriaxone for all isolated bacteria was below the minimum serum and biliary concentration of ceftriaxone 24 h after the first administration (except for Enterococcus species). The MIC for isolated bacterial strains was <16 mg/L, which is the PK-PD breakpoint for ceftriaxone at 2 g/day. Both regimens showed clinical efficacy and did not contradict the effect predicted based on PK-PD.

Prolonged Tachycardia with Higher Heart Rate Is Associated with Higher ICU and In-hospital Mortality.

Tachycardia is common in intensive care units (ICUs). It is unknown whether tachycardia or prolonged tachycardia affects patient outcomes. We investigated the association between tachycardia and mortality in critically ill patients. This retrospective cohort study's primary outcome was patient mortality in the ICU and the hospital. We stratified the patients (n=476) by heart rate (HR) as LowHR, MediumHR, and HighHR groups. We also stratified them by their durations of HR >100 (prolonged HR; tachycardia): MildT, ModerateT, and SevereT groups. We determined the six groups' mortality. The ICU mortality rates of the LowHR, MediumHR, and HighHR groups were 1.0%, 1.5%, and 7.9%, respectively; significantly higher in the HighHR vs. LowHR group. The in-hospital mortality rates of these groups were 1%, 4.5%, and 14.6%, respectively; significantly higher in the HighHR vs. LowHR group. The ICU mortality rates of the MildT, ModerateT, and SevereT groups were 0.9%, 5.6%, and 57.1%, respectively. The mortality of the HRT=0 (i.e., all HR ≤ 100) patients was 0%. The in-hospital mortality rates of the MildT, ModerateT, and SevereT groups were 1.8%, 16.7%, and 85.7%, respectively; that of the HRT=0 patients was 0.5%. Both higher HR and prolonged tachycardia were associated with poor outcomes.

Perioperative Management of a Child With Glucose Transporter Type 1 Deficiency Syndrome: A Case Report.

Glucose transporter type 1 deficiency syndrome (GLUT1DS) causes central nervous system dysfunction including intractable epilepsy caused by impaired glucose transport to the brain. To prevent convulsions and maintain an energy source for the brain in patients with GLUT1DS, the maintenance of adequate ketone body concentrations, compensation of metabolic acidosis, and reduction of surgical stress are essential. We here report the perioperative management of a child with GLUT1DS.

Novel Pretreatment Scoring Incorporating C-reactive Protein to Predict Overall Survival in Advanced Hepatocellular Carcinoma with Sorafenib Treatment.

OBJECTIVES: This study aimed to build a prediction score of prognosis for patients with advanced hepatocellular carcinoma (HCC) after sorafenib treatment. METHODS: A total of 165 patients with advanced HCC who were treated with sorafenib were analyzed. Readily available baseline factors were used to establish a scoring system for the prediction of survival. RESULTS: The median survival time (MST) was 14.2 months. The independent prognostic factors were C-reactive protein (CRP) <1.0 mg/dL [hazard ratio (HR) =0.51], albumin >3.5 g/dL (HR =0.55), alpha-fetoprotein <200 ng/mL (HR =0.45), and a lack of major vascular invasion (HR =0.39). Each of these factors had a score of 1, and after classifying the patients into five groups, the total scores ranged from 0 to 4. Higher scores were linked to significantly longer survival (p<0.0001). Twenty-nine patients (17.6%) with a score of 4 had a MST as long as 36.5 months, whereas MST was as short as 2.4 and 3.7 months for seven (4.2%) and 22 (13.3%) patients with scores of 0 and 1, respectively. CONCLUSIONS: A novel prognostic scoring system, which includes the CRP level, has the ability to stratify the prognosis of patients with advanced stage HCC after treatment with sorafenib.

Correction: Elastin Fiber Accumulation in Liver Correlates with the Development of Hepatocellular Carcinoma.

[This corrects the article DOI: 10.1371/journal.pone.0154558.].

Elastin Fiber Accumulation in Liver Correlates with the Development of Hepatocellular Carcinoma.

BACKGROUND & AIMS: The fibrosis stage, which is evaluated by the distribution pattern of collagen fibers, is a major predictor for the development of hepatocellular carcinoma (HCC) for patients with hepatitis C. Meanwhile, the role of elastin fibers has not yet been elucidated. The present study was conducted to determine the significance of quantifying both collagen and elastin fibers. METHODS: We enrolled 189 consecutive patients with hepatitis C and advanced fibrosis. Using Elastica van Gieson-stained whole-slide images of pretreatment liver biopsies, collagen and elastin fibers were evaluated pixel by pixel (0.46 µm/pixel) using an automated computational method. Consequently, fiber amount and cumulative incidences of HCC within 3 years were analyzed. RESULTS: There was a significant correlation between collagen and elastin fibers, whereas variation in elastin fiber was greater than in collagen fiber. Both collagen fiber (p = 0.008) and elastin fiber (p < 0.001) were significantly correlated with F stage. In total, 30 patients developed HCC during follow-up. Patients who have higher elastin fiber (p = 0.002) in addition to higher collagen fiber (p = 0.05) showed significantly higher incidences of HCC. With regard to elastin fiber, this difference remained significant in F3 patients. Furthermore, for patients with a higher collagen fiber amount, higher elastin was a significant predictor for HCC development (p = 0.02). CONCLUSIONS: Computational analysis is a novel technique for quantification of fibers with the added value of conventional staging. Elastin fiber is a predictor for the development of HCC independently of collagen fiber and F stage.

Pretreatment Gastric Lavage Reduces Postoperative Bleeding after Endoscopic Submucosal Dissection for Gastric Neoplasms.

AIM: For patients receiving endoscopic submucosal dissection (ESD), there is urgent need pertaining to the prevention of postoperative bleeding. We conducted a retrospective propensity score-matched study that evaluated whether pre-ESD gastric lavage prevents postoperative bleeding after ESD for gastric neoplasms. METHODS: From September 2002 to October 2015, the 760 consecutive patients receiving ESD for gastric neoplasm were enrolled and data regarding them were retrospectively analyzed. All patients received conventional preventive treatment against delayed bleeding after ESD, including the administration of proton pump inhibitor and preventive coagulation of visible vessels, at the end of the ESD procedure. RESULTS: Pre-ESD risk factors for postoperative bleeding included tumor size and no gastric lavage. Using multivariate analysis tumor size >2.0 cm (HR 2.90, 95% CI 1.65-5.10, p = 0.0002) and no gastric lavage (HR 3.20, 95% CI 1.13-9.11, p = 0.029) were found to be independent risk factors. Next, we evaluated the effect of gastric lavage on the prevention of post-ESD bleeding using a propensity score-matching method. A total of 284 subjects (142 per group) were selected. Adjusted odds ratio of gastric lavage for post-ESD bleeding was 0.25 (95% CI 0.071-0.886, p = 0.032). CONCLUSION: Pretreatment gastric lavage reduced postoperative bleeding in patients receiving ESD for gastric neoplasm.

Urinary excretion of the water channel aquaporin 2 correlated with the pharmacological effect of tolvaptan in cirrhotic patients with ascites.

BACKGROUND: The water channel aquaporin 2 (AQP2) at the apical membrane of renal collecting duct cells mediates water reabsorption. The expression of AQP2 at the apical membrane is tightly regulated by vasopressin and was quantitated by measurement of the urinary form by a recently developed ELISA. Tolvaptan, an antagonist of vasopressin type 2 receptor, inhibits water reabsorption in cirrhosis. The aim of this study was to determine the correlation between the pharmacological effect of tolvaptan and the dynamics of urinary AQP2 levels. METHODS: Tolvaptan was administered to 41 cirrhotic patients with ascites unresponsive to standard diuretic therapy. Urinary excretion of AQP2 and urinary osmolarity were measured at the baseline and at 4, 8, and 24 h after administration of tolvaptan. RESULTS: At the baseline, urinary AQP2/creatinine ratios were significantly higher in cirrhotic patients with ascites than in healthy controls (P < 0.0001). After administration of tolvaptan, urinary AQP2/creatinine ratios decreased by 45.0 % at 4 h and 77.0 % at 8 h. Similarly, urinary osmolarity decreased by 42.0 % at 4 h and 41.5 % at 8 h. Urinary AQP2 levels and urinary osmolarity significantly correlated at the baseline and at all time points after tolvaptan administration. The degree of the decrease in urinary AQP2 levels and degree of the decrease in urinary osmolarity correlated significantly at 4 h (r = 0.452, P = 0.009) and 8 h (r = 0.384, P = 0.030) after tolvaptan administration. CONCLUSIONS: These results indicate that the vasopressin-AQP2 system plays a major role in fluid retention in cirrhosis and that the pharmacological effect of tolvaptan to inhibit water reabsorption can be monitored by measurement of the dynamics of urinary AQP2 levels.