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Background The role of recurrence-free survival (RFS) as a valid surrogate endpoint for overall survival (OS) in patients who underwent upfront surgery for colorectal liver metastases remains uncertain. The aim of the study was to compare the two survival measures in a nationwide cohort of upfront resected colorectal liver metastasis. Methods Data from patients with colorectal liver metastases without extrahepatic metastases who underwent curative surgery for liver metastases were retrieved from the Japanese nationwide database (data collection 2005–2007 and 2013–2014). RFS, OS, and survival after recurrence were estimated using the Kaplan–Meier method. The correlation (ρ) between RFS and OS was assessed using the rank correlation method combined with iterative multiple imputation, to account for censoring. As a secondary analysis, the correlation was evaluated according to adjuvant chemotherapy regimen. In sensitivity analysis, the pairwise correlation between RFS and OS was calculated. Results A total of 2385 patients with colorectal liver metastases were included. In the primary analysis, there was a moderately strong correlation between RFS and OS (ρ = 0.73, 95 per cent c.i. 0.70 to 0.76). The strength of the correlation was similar regardless of the adjuvant treatment regimen (oxaliplatin plus 5-fluorouracil: ρ = 0.72, 0.67 to 0.77; 5-fluorouracil alone: ρ = 0.72, 0.66 to 0.76; observation: ρ = 0.74, 0.69 to 0.78). The mean(s.d.) pairwise correlation coefficient between 3-year RFS and 5-year OS was 0.87(0.06). Conclusion In surgically treated patients with colorectal liver metastases, there was a moderately strong correlation between RFS and OS, which was unaffected by the treatment regimen. Further validation using a trial-level analysis is required.

This study aimed to investigate and determine the best deep learning (DL) model to predict breast cancer (BC) with dedicated breast positron emission tomography (dbPET) images.Of the 1598 women who underwent dbPET examination between April 2015 and August 2020, a total of 618 breasts on 309 examinations for 284 women who were diagnosed with BC or non-BC were analyzed in this retrospective study. The Xception-based DL model was trained to predict BC or non-BC using dbPET images from 458 breasts of 109 BCs and 349 non-BCs, which consisted of mediallateral and craniocaudal maximum intensity projection images, respectively. It was tested using dbPET images from 160 breasts of 43 BC and 117 non-BC. Two expert radiologists and two radiology residents also interpreted them. Sensitivity, specificity, and area under the receiver operating characteristic curves (AUCs) were calculated.Our DL model had a sensitivity and specificity of 93% and 93%, respectively, while radiologists had a sensitivity and specificity of 77-89% and 79-100%, respectively. Diagnostic performance of our model (AUC = 0.937) tended to be superior to that of residents (AUC = 0.876 and 0.868, p = 0.073 and 0.073), although not significantly different. Moreover, no significant differences were found between the model and experts (AUC = 0.983 and 0.941, p = 0.095 and 0.907).Our DL model could be applied to dbPET and achieve the same diagnostic ability as that of experts.

The study group of the Japanese Society of Gastroenterology released evidence-based clinical practice guidelines for chronic constipation (CC) in 2017, and irritable bowel syndrome (IBS) was treated as one of the causes of CC. We examined the differences in characteristics between IBS and non-IBS subjects with CC who underwent a medical check-up in Japan. A total of 10,658 subjects participated in this study, and we focused on 467 subjects who fulfilled the diagnostic criteria of CC using a questionnaire survey. The number of IBS subjects was 21, and they had sleep disorders, were more symptomatic (e.g., abdominal pain, abdominal bloating/distension, feeling stressed, annoyance, lack of motivation, fatigue upon waking, and feeling depressed), and had more episodes of sensation of incomplete evacuation and anorectal obstruction/blockage during defecation than non-IBS subjects. Furthermore, stool frequency of IBS subjects was significantly different from non-IBS subjects. Multivariate ordinal logistic regression analysis revealed that the factors associated with a higher stool frequency were IBS [odds ratio (OR), 2.46; 95% confidence interval (CI), 1.00-6.05

A binary classification problem is common in medical field, and we often use sensitivity, specificity, accuracy, negative and positive predictive values as measures of performance of a binary predictor. In computer science, a classifier is usually evaluated with precision (positive predictive value) and recall (sensitivity). As a single summary measure of a classifier’s performance, F1 score, defined as the harmonic mean of precision and recall, is widely used in the context of information retrieval and information extraction evaluation since it possesses favorable characteristics, especially when the prevalence is low. Some statistical methods for inference have been developed for the F1 score in binary classification problems; however, they have not been extended to the problem of multi-class classification. There are three types of F1 scores, and statistical properties of these F1 scores have hardly ever been discussed. We propose methods based on the large sample multivariate central limit theorem for estimating F1 scores with confidence intervals.

ObjectivesDelirium commonly occurs during hospitalisation and is associated with increased mortality, especially in elderly patients. This study aimed to determine the demographic and clinical characteristics of patients with delirium in the Japanese real-world clinical setting using a nationwide database comprising claims and discharge abstract data.DesignThis was an observational, cross-sectional, retrospective study in hospitalised patients with an incident delirium identified by a diagnosis based on International Classification of Diseases, 10th Revision codes or initiating antipsychotics recommended for delirium treatment in Japan during their hospitalisation.SettingPatients from the Medical Data Vision database including more than 400 acute care hospitals in Japan were evaluated from admission to discharge.ParticipantsOf the 32 910 227 patients who were included in the database between April 2012 and September 2020, a total of 145 219 patients met the criteria for delirium.Primary and secondary outcome measuresDemographic and baseline characteristics, comorbidities, clinical profiles and pharmacological treatments were evaluated in patients with delirium.ResultsThe mean (SD) patient age was 76.5 (13.8) years. More than half of the patients (n=82 159; 56.6%) were male. The most frequent comorbidities were circulatory system diseases, observed in 81 954 (56.4%) patients. Potentially inappropriate medications (PIMs) with risk of delirium including benzodiazepines and opioids were prescribed to 76 798 (52.9%) patients. Approximately three-fourths of these patients (56 949; 74.2%) were prescribed ≥4 PIMs. The most prescribed treatment for delirium was injectable haloperidol (n=82 490; 56.8%). Mean (SD) length of hospitalisation was 16.0 (12.1) days.ConclusionsThe study results provide comprehensive details of the clinical characteristics of patients with delirium and treatment patterns with antipsychotics in the Japanese acute care setting. In this patient population, the prescription rate of injectable haloperidol and PIMs was high, suggesting the need for improved understanding among healthcare providers about the appropriate management of delirium, which may benefit patients.

Background Extrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection are indicative of poor prognoses. We aimed to develop nomograms to predict extrahepatic recurrence and early intrahepatic recurrence after hepatic resection. Methods The participants of this study were 1,206 patients who underwent initial and curative hepatic resection for hepatocellular carcinoma. Multivariate logistic regression analyses using the Akaike information criterion were used to construct nomograms to predict extrahepatic recurrence and early intrahepatic recurrence (within 1 year of surgery) at the first recurrence sites after hepatic resection. Performance of each nomogram was evaluated by calibration plots with bootstrapping. Results Extrahepatic recurrence was identified in 95 patients (7.9%) and early intrahepatic recurrence in 296 patients (24.5%). Three predictive factors, α-fetoprotein >200 ng/mL, tumor size (3–5 cm or >5 cm vs ≤3 cm), and image-diagnosed venous invasion by computed tomography, were adopted in the final model of the extrahepatic recurrence nomogram with a concordance index of 0.75. Tumor size and 2 additional predictors (ie, multiple tumors and image-diagnosed portal invasion) were adopted in the final model of the early intrahepatic recurrence nomogram with a concordance index of 0.67. The calibration plots showed good agreement between the nomogram predictions of extrahepatic recurrence and early intrahepatic recurrence and the actual observations of extrahepatic recurrence and early intrahepatic recurrence, respectively. Conclusion We have developed reliable nomograms to predict extrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection. These are useful for the diagnostic prediction of extrahepatic recurrence and early intrahepatic recurrence and could guide the surgeon’s selection of treatment strategies for hepatocellular carcinoma patients.

Background and aim Functional constipation (FC) is one of the functional bowel disorders with symptoms of constipation in the Rome IV criteria. This study aimed to examine the epidemiology of FC in a large-scale survey of individuals undergoing a medical check-up in Japan. Methods A total of 13 729 subjects who underwent a medical check-up at MedCity21 between April 2018 and March 2019 were given a questionnaire that inquired about bowel habits. Among them, 10 658 subjects participated in this study, and FC was diagnosed based on the Rome IV criteria. Results The number of subjects who fulfilled diagnostic criteria of FC was 220, and the prevalence of FC was 2.1%. Compared with subjects with non-FC, those with FC were more complaining of abdominal bloating and distension, feeling stressed, getting annoyed, lack of motivation, fatigue upon waking, and feeling depressed. The risk of FC was significantly lower among subjects who drank alcohol more than 5 days a week, exercised for more than 30 min at least twice a week for more than 1 year, and were getting enough rest by sleeping, whereas it was significantly higher among women and subjects who were eating faster than other people. Conclusions The prevalence of FC in Japanese subjects during a medical check-up was relatively low compared with that in Western countries. Subjects with FC had troublesome symptoms, and it might be suggested that female sex, lack of regular exercise with moderate activity, insufficient rest by sleeping, and eating faster were a risk of FC.

The SNAr reaction of 1-fluoroxanthone derivatives with alkoxide of 1,1-dimethylallyl alcohol cleanly afforded the corresponding ethers, which have thus far been unavailable. The obtained ethers underwent the Claisen rearrangement at room temperature by treatment with silica gel in toluene. This two-step protocol provides expeditious and high-yield access to xanthones possessing isoprenyl or the related allylic side chain at the C2 position.

An efficient installation of a 3,7-dimethylocta-2,6-dien-1-yl (geranyl or neryl) side chain at the C(1) position of a xanthone core by utilizing an anion-accelerated aromatic oxy-Cope rearrangement is described. Experiments revealed that this uncommon rearrangement takes place in a stereospecific manner through a chair-like transition-state structure. An application to the syntheses of the natural xanthone fuscaxanthone F, possessing a geranyl side chain, and its neryl analogue is also described.

Positive and negative predictive values describe the clinical performance of the diagnostic test when it is applied to a cohort of individuals. Testing non-inferiority of predictive values may be a...

Error grid analysis was recently proposed to compare blood pressure obtained by 2 measurement methods. This study aimed to compare continuous noninvasive blood pressure (CNBP) with invasive blood pressure (IBP) using the error grid analysis and investigate the confounding risk factors attributable to the differences between CNBP and IBP.Sixty adult patients undergoing general anesthesia were prospectively enrolled. Simultaneous comparative data regarding CNBP and IBP were collected. The Bland-Altman analysis was conducted to compare CNBP and IBP for systolic blood pressure (SBP) and mean blood pressure (MBP; acceptable accuracy: mean bias5 mm Hg; standard deviation8 mm Hg). The clinical relevance of the discrepancies between CNBP and IBP was evaluated by the error grid analysis, which classifies the differences into 5 zones from "no risk" (A) to "dangerous risk" (E). Additionally, an ordinal logistic regression analysis was performed to evaluate the relationship between the risk zones for MBP, classified by the error grid analysis and covariates of interest.A total of 10,663 pairs of CNBP/IBP were finally analyzed. The Bland-Altman analysis showed an acceptable accuracy with a bias of -3.3 ± 5.6 mm Hg for MBP but a poor accuracy with a bias of 5.4 ± 10.5 mm Hg for SBP. The error grid analysis showed the proportions of zones A to E as 96.7%, 3.2%, 0.1%, 0%, and 0% for SBP, respectively, and 72.0%, 27.9%, 0.1%, 0%, and 0% for MBP, respectively. The finger cuff missed 23.9% of epochs when SBP90 mm Hg and 55.3% of epochs when MBP65 mm Hg. The ordinal logistic regression analysis revealed that older age (adjusted odds ratio for decade: 1.54, 95% confidence interval [CI], 1.15-2.08; P = .004) and length of time from the initiation of finger cuff inflation (adjusted odds ratio for 60 minutes: 1.40, 95% CI, 1.13-1.73; P = .002) were significant factors of being in a more dangerous zone of the error grid.The error grid analysis revealed the larger clinical discrepancy between CNBP and IBP in MBP compared with that in SBP. Old age and longer finger cuff inflation time were significant factors of being in a more dangerous zone of the error grid, which could affect the hemodynamic management during surgery.

To investigate the ability of deep learning (DL) using convolutional neural networks (CNNs) for distinguishing between normal and metastatic axillary lymph nodes on ultrasound images by comparing the diagnostic performance of radiologists.We retrospectively gathered 300 images of normal and 328 images of axillary lymph nodes with breast cancer metastases for training. A DL model using the CNN architecture Xception was developed to analyze test data of 50 normal and 50 metastatic lymph nodes. A board-certified radiologist with 12 years' experience. (Reader 1) and two residents with 3- and 1-year experience (Readers 2, 3), respectively, scored these test data with and without the assistance of the DL system for the possibility of metastasis. The sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) were calculated.Our DL model had a sensitivity of 94%, a specificity of 88%, and an AUC of 0.966. The AUC of the DL model was not significantly different from that of Reader 1 (0.969; p = 0.881) and higher than that of Reader 2 (0.913; p = 0.101) and Reader 3 (0.810; p 0.001). With the DL support, the AUCs of Readers 2 and 3 increased to 0.960 and 0.937, respectively, which were comparable to those of Reader 1 (p = 0.138 and 0.700, respectively).Our DL model demonstrated great diagnostic performance for differentiating benign from malignant axillary lymph nodes on breast ultrasound and for potentially providing effective diagnostic support to residents.

Pain during cannulation for vascular access is a considerable problem for patients with kidney disease who are undergoing hemodialysis. We examined whether listening to music can reduce cannulation pain in these patients.We conducted a multicenter, single-blind, crossover, randomized trial of 121 patients who reported pain during cannulation for hemodialysis. We compared participants listening to "Sonata for Two Pianos in D Major, K.448" or white noise as control while undergoing the cannulation procedure. The cannulation operator was blinded to the intervention, and the hypothesized superiority of music over white noise was concealed during explanations to the participants. The primary end point was the visual analog scale score for cannulation pain independently evaluated by participants.The primary analysis was on the basis of the modified intention-to-treat principle. The median baseline visual analog scale pain score was 24.7 mm (interquartile range, 16.5-42.3). Median change of the visual analog scale pain score from the "no sound" to the music period was -2.7 mm (interquartile range, -9.2 to 3.6), whereas it was -0.3 mm (interquartile range, -5.8 to 4.5) from "no sound" to white noise. The visual analog scale pain score decreased when listening to music compared with white noise. (Adjusted difference of visual analog scale pain score: -12%; 95% confidence interval, -21 to -2;Listening to music reduced cannulation pain in patients on hemodialysis, although there was no significant effect on anxiety, BP, or stress markers.

ObjectivesDelirium is a neuropsychiatric disorder that commonly occurs in elderly patients with cognitive impairment. The economic burden of delirium in Japan has not been well characterised. In this study, we assessed incremental medical costs of delirium in hospitalised elderly Japanese patients with cognitive impairment.DesignRetrospective, cross-sectional, observational study.SettingAdministrative data collected from acute care hospitals in Japan between April 2012 and September 2020.ParticipantsHospitalised patients ≥65 years old with cognitive impairment were categorised into groups—with and without delirium. Delirium was identified using a delirium identification algorithm based on the International Classification of Diseases 10thRevision codes or antipsychotic prescriptions.Outcome measuresTotal medical costs during hospitalisation were compared between the groups using a generalised linear model.ResultsThe study identified 297 600 hospitalised patients ≥65 years of age with cognitive impairment: 39 836 had delirium and 257 764 did not. Patient characteristics such as age, sex, inpatient department and comorbidities were similar between groups. Mean (SD) unadjusted total medical cost during hospitalisation was 979 907.7 (871 366.4) yen for patients with delirium and 816 137.0 (794 745.9) yen for patients without delirium. Adjusted total medical cost was significantly greater for patients with delirium compared with those without delirium (cost ratio=1.09, 95% CI: 1.09 to 1.10; pConclusionsMedical costs during hospitalisation were significantly higher for patients with delirium compared with those without delirium in elderly Japanese patients with cognitive impairment, regardless of patient subgroups such as age, sex, intensive care unit admission and most comorbidities. These findings suggest that delirium prevention strategies are critical to reducing the economic burden as well as psychological/physiological burden in cognitively impaired elderly patients in Japan.

Objective Therapeutic predictors derived from the venous pressure before therapy have not been identified for Budd-Chiari syndrome (BCS). The aim of this study was to determine whether or not measuring the distal pressure or pressure gradient was useful for predicting treatment efficacy in BCS. Methods We retrospectively analyzed seven consecutive patients diagnosed with symptomatic BCS at our hospital between 2008 and 2017. Distal and proximal venous pressures at occlusion sites of BCS were measured before treatment in all cases. The pressure gradient was defined as the difference between distal and proximal venous pressures. A receiver operating characteristics (ROC) analysis was performed for venous pressures. Results Percutaneous old balloon angioplasty (POBA) was performed in seven cases, with technical success achieved in all cases (100%). No complications were encountered. The median primary patency was 574 (interquartile range, 439.5-1,056.5) days. The 1-year primary patency rate was 71.73%. Six cases (85.7%) showed resolution of symptoms, representing clinical success. The ROC analysis revealed a high distal pressure (area under the ROC curve = 0.83, cut-off=12 mmHg) as a predictor of treatment efficacy of POBA for symptomatic BCS. In addition, the pressure gradient was considered significant from a clinical perspective, because the 6 successful cases with resolution of symptoms showed a large pressure gradient (range, 8-21 mmHg) before treatment, whereas the failed case showed a relatively small pressure gradient (7 mmHg). Conclusion High distal pressure and a large pressure gradient might predict the treatment efficacy of balloon angioplasty for symptomatic BCS.

Dirhodium(II)-catalyzed oxonium ylide formation–[2,3]-sigmatropic rearrangement of 6-allyloxy-2-diazo-3-ketoesters possessing a C-6 substituent is described. The reaction of 6-alkyl- or 6-aryl-substituted 6-allyloxy-2-diazo-3-ketoesters with a catalytic amount of Rh2(S-PTTL)4 proceeded in a chemoselective and stereoselective manner to provide 6-substituted 2-allyl-3-oxotetrahydropyran-2-carboxylates in good yields and with high diastereoselectivities. To demonstrate the utility of this sequential reaction, we conducted the total synthesis of (+)-tanikolide, in which the construction of the δ-lactone skeleton was achieved by employing a 2-iodobenzamide-catalyzed oxidative cleavage of tetrahydropyran-2-methanol.

We previously found an association of insulin resistance (IR) with plasma xanthine oxidoreductase (XOR) activity in a cross-sectional study. However, whether IR induces increased XOR activity has not been elucidated. This retrospective longitudinal observational study included 347 participants (173 males, 174 females) who underwent annual health examinations and were medication naïve. Homeostasis model assessment of IR (HOMA-IR) index, and physical and laboratory measurements were determined at the baseline. At baseline and 12-month follow-up examinations, plasma XOR activity was determined using our novel assay based on [13C2,15N2] xanthine and liquid chromatography/triple quadrupole mass spectrometry. Subjects with IR, defined as HOMA-IR index ≥ 1.7 (n = 92), exhibited significantly (p p = 0.033) and increased plasma XOR activity over the 12-month period (odds ratio, 1.986; 95% confidence interval, 1.048–3.761;p = 0.035), after adjustments for various clinical parameters, including plasma XOR activity at baseline. These results suggest that IR induces increased plasma XOR activity in a manner independent of adiposity.

Background Febrile urinary tract infection (fUTI) is the most common serious bacterial infection in children. Despite this, there have been no studies examining the clinical features of pediatric fUTI in Japan. The purpose of this study was to describe the clinical characteristics of fUTI in Japanese children. Methods A multicenter, retrospective, observational study was conducted at 21 hospitals in Japan. Children under the age of 15 years who were diagnosed with fUTI between 2008 and 2017 were included. The diagnostic criteria were a temperature over 38 °C and the presence of a single bacterial pathogen in urine culture. Patient characteristics were obtained from medical records. Results In total, 2,049 children were included in the study. The median age was 5 months, and 59.3% were male. It was found that 87.0% of the males and 53.2% of the females were under 1 year of age. The main causative pathogens identified were Escherichia coli and Enterococcus spp., accounting for 76.6% and 9.8% of infections, respectively. Conclusions There was a male predominance of fUTI in Japanese children, particularly in infants. Enterococcus spp. were the second most frequent causative pathogen; therefore, Gram staining of urine samples is strongly recommended before initiating antibiotic therapy.

Intravascular fasciitis (IF), a variant of nodular fasciitis (NF), is a reactive intravascular proliferation of myofibroblasts. IF is an indolent subcutaneous or intramuscular nodule that is most commonly found on the extremities, head and neck.1, 2 This article is protected by copyright. All rights reserved.

Sepsis remains a major cause of death. Cytokines interact closely with each other and play a crucial role in the progression of sepsis. We focussed on the associations of a cytokine network with prognosis and disease severities in sepsis. This retrospective study included 31 patients with sepsis and 13 healthy controls. Blood samples were collected from patients on days 1, 2, 4, 6, 8, 11 and 15 and from healthy controls. Levels of PAI-1, IFN-α, IFN-γ, IL-1β, IL-6, IL-8, IL-12/IL-23p40, IL-17A, TNF-α, MCP-1, IL-4 and IL-10 were measured. SOFA, JAAM DIC and ISTH DIC scores were evaluated at the same times blood samples were taken. Network analysis revealed a network formed by PAI-1, IL-6, IL-8, MCP-1 and IL-10 on days 1, 2 and 4 throughout the acute phase of sepsis. There were positive correlations of each cytokine and the combined score (IL-6 + IL-8 + IL-10 + MCP-1) with the SOFA, JAAM DIC and ISTH DIC scores throughout the acute phase. A Cox proportional hazards model focussed on the acute phase showed that the above combined score was significantly related with patient prognosis, suggesting that the cytokine network of IL-6, IL-8, MCP-1 and IL-10 could play a pivotal role in the acute phase of sepsis.

Positive and negative predictive values describe the performance of a diagnostic test. There are several methods to test the equality of predictive values in paired designs. However, these methods were premised on large sample theory, and they may not be suitable for small-size clinical trials because of inflation of the type 1 error rate. In this study, we propose an exact test to control the type 1 error rate strictly for conducting a small-size clinical trial that investigates the equality of predictive values in paired designs. In addition, we execute simulation studies to evaluate the performance of the proposed exact test and existing methods in small-size clinical trials. The proposed test can calculate the exact P value, and as a result of simulations, the empirical type 1 error rate for the proposed test did not exceed the significance level regardless of the setting, and the empirical power for the proposed test is not much different from the other methods based on large-sample theory. Therefore, it is considered that the proposed exact test is useful when the type 1 error rate needs to be controlled strictly.

Background and study aims An increasing number of patients have been using anticoagulants including anti-vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs); however, in patients using anticoagulants, limited data are available with regard to the risks of gastrointestinal bleeding and thromboembolic events during the peri-endoscopic period. We aimed to evaluate the peri-endoscopic bleeding and thrombotic risks in patients administered VKAs or DOACs. Patients and methods Consecutive patients using anticoagulants who underwent endoscopic biopsy, mucosal resection, or submucosal dissection were prospectively enrolled across 11 hospitals. The primary outcome assessed was difference in incidence of post-procedural gastrointestinal bleeding in patients using VKAs and DOACs. Duration of hospitalization and peri-procedural thromboembolic events were also compared. Results We enrolled 174 patients using VKAs and 37 using DOACs. In total, 16 patients using VKA were excluded from the analysis because of cancellation of endoscopic procedures and contraindications to the use of DOACs; 128 (81 %) patients using VKAs and 17 (46 %) using DOACs received heparin-bridging therapy (HB). The rate of post-procedural gastrointestinal bleeding in DOAC users was similar to that in VKA users (16.2 % vs. 16.4 %, P = 1.000). Duration of hospitalization was significantly longer in patients using VKAs than in those using DOACs (median 15 vs. 7 days, P Conclusion DOAC administration showed similar post-procedural gastrointestinal bleeding risk to VKA administration in patients undergoing endoscopic procedures, but it shortened the hospital stay.

Delirium after cardiac surgery is a serious complication, increasing morbidity and mortality. Despite its high expectations, off-pump coronary artery bypass grafting (OPCAB) has largely failed to reduce the incidence of postoperative neurological complications. To further investigate the reasons for this failure, we used perioperative brain magnetic resonance imaging (MRI) to determine the relation between MRI findings and postoperative delirium. Altogether, 98 patients undergoing elective OPCAB were enrolled in this prospective observational study. Patients underwent brain MRI and magnetic resonance angiography (MRA) before and after surgery to identify cerebral infarction, white matter lesions, and intracranial artery stenosis. Postoperative delirium in the intensive care unit was measured using the delirium rating scale. The relation between postoperative delirium and MRI findings was examined using logistic regression. Magnetic resonance imaging and MRA was completed in 88 (90%) of the patients. New ischemic lesions were present in seven (7.9%) patients. Delirium rating scale scores of 0, 1-7, and ≥ 8 were found in 25 (31%), 48 (60%), and seven (9%) patients, respectively. Multivariate logistic regression analysis revealed that new ischemic lesions (odds ratio [OR] 11.07, 95% confidence interval [CI]: 1.53 to 80.03; P = 0.017), carotid artery stenosis (OR 7.06, 95% CI: 1.59 to 31.13; P = 0.010), history of myocardial infarction (OR 3.78, 95% CI: 1.05 to 13.65; P = 0.043), and deep subcortical white matter hyperintensity (OR 3.04, 95% CI: 1.14 to 8.12; P = 0.027) were significantly associated with postoperative delirium. Magnetic resonance imaging findings of new cerebral ischemic lesions, carotid stenosis, and deep subcortical white matter hyperintensity correlated significantly with postoperative delirium in patients who had undergone OPCAB surgery.

A high extracellular calcium level inhibits the formation of osteoclast-like cells and stimulates osteoblastic proliferation, indicating that extracellular calcium plays an important role in the process of bone remodeling. The present study examined the effects of a high extracellular calcium level on mRNA levels of bone morphogenetic protein (BMP)-2 and -4, which are well-documented osteoinductive proteins, and the differentiation of normal human mandible-derived bone cells in vitro. High extracellular calcium significantly increased cell proliferation at an optimal dose of 0.4 mM CaCl2 added to control medium containing 1.8 mM CaCl2. The addition of 0.1–0.4 mM CaCl2 markedly increased the mRNA levels of BMP-2 and -4 following incubation for 0.5 and 24 h as evaluated by reverse transcription–polymerase chain reaction. While an increased extracellular calcium level (addition of 0.1–1.2 mM CaCl2) failed to increase alkaline phosphatase activity and osteocalcin secretion, it did significantly increase type I collagen synthesis, monitored by the production of procollagen type I carboxy-terminal peptide. These results indicate that the extracellular calcium level regulates BMPs and type I collagen synthesis in osteoblastic cells.

□ The effects of absorpti on enhancers on the pulmonary absorption of (Asu1,7)-eel calcitonin (ECT) and their pulmonary toxicity were examined by means of in situ pulmonary experiments. The absorption of ECT from the lungs was estimated by its hypocalcemic effect. The pulmonary membrane toxicity of absorption enhancers was evaluated by the leakage of Evans Blue from the plasma into the lungs. in the absence of absorption enhancers, a slight hypocalcemic effect was obtained following intrapulmonary administration of ECT. However, we found significant hypocalcemic effects after the ECT administration with 10 mM n-lauryl β-D-maltopyranoside (LM), 10 mM sodium glyco- cholate (NaGC), and 10 mM linoleic acid-HCO60 (hydrogenated caster oil) mixed micelle (MM). The plasma calcium levels decreased as the amount of LM coadministered with ECT increased. In contrast, 10 mM EDTA did not improve the pulmonary absorption of ECT. Overall, a correlation between the pulmonary absorption of ECT and local toxicity was observed in the presence of these additives. However, 1 mM LM, 10 mM NaGC, and 10 mM MM improve the pulmonary absorption of ECT with low pulmonary toxicity. These findings suggest that the use of these adjuvants would be a useful approach for improving the pulmonary absorption of ECT.

The antigenecity and nutritional adequacy of N-253 formula, a partly hydrolyzed formula, were evaluated in high risk infants with a family history of atopy, on immunological and hematological parameters, weight gain, clinical conditions and stool characteristics; during the first four months of life. Its effects were compared with those observed in infants taking a conventional infant formula and breast-fed infants, There were no changes in serum IgE, cow's milk specific IgG, cow's milk-specific IgG4 concentrations and the number of eosinophils in the N-253 formula-fed infants during the study period. Whereas, those parameters were increased in infants fed with the conventional infant formula and in breast-fed infants. Positive RAST against cow's milk was not detected in the N-253 formula-fed infants (0/33), while it was detected in conventional infant formula-fed infants (2/13). Green and watery stools were observed more frequently in the N-253 formula-fed infants than in the conventional infant formula-fed infants. Weight gain and hematological values were within normal ranges in all three groups during the study period. These results suggest that the antigenecity of cow's milk is reduced in N-253 formula and that N-253 formula has nutritional efficacy for infants.

Purpose. The permeability of drugs across the Xenopus pulmonary membrane and the effects of various absorption enhancers on their absorption were examined using an in vitro Ussing chamber technique.