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Introduction: We aimed to implement the enhanced recovery after surgery (ERAS) protocol for pediatric neuromuscular scoliosis (NMS) surgery and to examine the effectiveness of this program in this study. Methods: Subjects were children with NMS who underwent scoliosis surgery at our department by a surgeon using a single posterior approach. A series of 27 cases before the introduction of ERAS and 27 cases during program stabilization were included in the study. Patient backgrounds did not show significant differences before and after introducing ERAS. Perioperative data, complications, length of hospital stay (LOS), and readmission within 90 days were investigated and statistically analyzed. Results: When the pre- and post-ERAS induction groups were compared, no significant differences in anesthesia induction time (p=0.979), pelvic fixation (p=0.586), fusion levels (p=0.479), intraoperative hypothermia duration (p=0.154), end-of-surgery body temperature (p=0.197), operative time (p=0.18), postoperative main Cobb angle (p=0.959), main Cobb angle correction rate (p=0.91), postoperative spino-pelvic obliquity (SPO) (p=0.849), and SPO correction rate (p=0.267) were observed. However, significant differences in using V-flap technique (p=0.041), intraoperative blood loss (p=0.001), and LOS (p=0.001) were observed. Intraoperative blood loss was weakly correlated with LOS (p=0.432 and 0.001). No statistically significant difference existed between the V-flap method and LOS (p=0.265). Multiple regression analysis using LOS as the objective variable and ERAS protocols and intraoperative blood loss as explanatory variables revealed that the effect of ERAS on LOS was greater than that of intraoperative blood loss. No statistically significant differences in the readmission rates within 90 days were found. Conclusions: After the introduction of ERAS, LOS decreased without an increase in complications or readmissions within 90 days.

Abstract Background Transcatheter arterial embolization (TAE) has long been used for hemostasis of traumatic or postoperative hemorrhage and embolization of tumors. Previous retrospective studies of TAE for painful bone metastases showed 60%–80% pain reduction with a median time to response of 1–2 days. Compared with radiotherapy and bisphosphonates, time to response appeared earlier than that of radiotherapy or bone-modifying agents. However, few prospective studies have examined TAE for this indication. Here, we describe the protocol for a confirmatory study designed to clarify the efficacy and safety profile of TAE. Methods This study will be a multicenter, single-arm confirmatory study (phase 2–3 design). Patients with painful bone metastases from any primary tumor are eligible for enrollment. TAE will be the main intervention. Following puncture of the femoral artery under local anesthesia and insertion of an angiographic sheath, angiography will confirm that the injected region includes tumor vasculature. Catheter position will be adjusted so that the embolization range does not include non-target tissues. Spherical embolic material will then be slowly injected into the artery to embolize it. The primary endpoint (efficacy) is the proportion of subjects with pain relief at 72 h after TAE and the secondary endpoint (safety) is the incidence of all NCI Common Terminology Criteria for Adverse Events version 5.0 Grade 4 adverse events and Grade ≥ 3 necrosis of the central nervous system. Discussion If the primary and secondary endpoints are met, TAE can be a treatment choice for painful bone metastases. Trial registry number is UMIN-CTR ID: UMIN000040794. Trial registration The study is ongoing, and patients are currently being enrolled. Enrollment started in March 2021. A total of 36 patients have participated as of Aug 2022. Protocol Version: Ver1.4, 13/07/2022.

Abstract A 2-step approach, Fibrosis-4 index (FIB-4) followed by vibration-controlled transient elastography (VCTE), has been proposed to predict advanced fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). We aimed to develop a novel 3-step approach for predicting advanced fibrosis. We enrolled 284 biopsy-confirmed NAFLD patients from two tertiary care centers and developed subgroups (n = 190), including 3.7% of patients with advanced fibrosis, assuming a primary care setting. In the 3-step approach, patients with intermediate-to-high FIB-4 in the first step underwent an enhanced liver fibrosis test or measurement of type IV collagen 7S domain as the second step, and VCTE was performed if the second step value was higher than the cutoff. In 284 cases, a tertiary care cohort with 36.3% advanced fibrosis, the 3-step approach showed significantly higher specificity and positive predictive value than the 2-step approach. In the subgroup with 3.7% advanced fibrosis, the 3-step approach significantly reduced the referral rate to specialists, the number of high-risk patients (i.e., liver biopsy candidates), and healthcare costs by 12.5% to 15.8%. The 3-step approach may improve the diagnostic performance to predict advanced fibrosis in NAFLD, which could lower rates of referrals to specialists, liver biopsies, and medical costs.

This study concerns a method for detecting the structural anomaly of F type support information board from acceleration measurements. The evaluation of structural anomaly is performed by the autoencoder method．By the proposed method, training of the autoencoder is conducted from data of normal conditions, and diagnosis of the structure is conducted from reconstruction error of the autoencoder. To validate the effectiveness of the method, the method is applied to long-term measurement data from actual equipment. To evaluate the detection accuracy and reliability of the method, the method is applied to sites with fluctuating natural frequencies and sites with stable natural frequencies. As a result, the proposed method with the autoencoder is able to correctly evaluate anomalies of the structure with more than 80% detection and a low false positive rate of 5%, and is able to evaluate the normality of the structure stably over a long period of time.

Abstract Background The development of chemotherapy and treatment strategies for metastatic colorectal cancer (mCRC) have provided patients with significant survival benefits. Currently, molecular targeting agents and late‐line treatment with regorafenib and trifluridine/tipiracil (FTD/TPI) are available. However, the impact of this increase in drug availability on overall survival (OS) in mCRC remains a clinical question. Methods We retrospectively collected data on consecutive mCRC patients who were treated at three institutions in Japan. We divided the patients into three cohorts: patients who initiated first‐line treatment from Jan 2005 to Dec 2006 (cohort A: only cytotoxic drugs available), Jan 2007 to Dec 2011 (cohort B: molecular targeting drugs available), and Jan 2012 to Sep 2016 (cohort C: late‐line treatment available). Results A total of 1409 consecutive patients were analyzed. The median survival time (MST) in cohorts A, B, and C was 18.6, 25.4, and 26.4 months, respectively. The hazard ratio (HR) for cohort B versus A was 0.81 (95% CI 0.68–0.97), for cohort C versus A was 0.74 (95% CI 0.61–0.89), and for cohort C versus B was 0.92 (0.81–1.03). The median number of administered drugs (range) was 3 (1–5) in cohort A, 4 (1–7) in cohort B, and 4 (1–7) in cohort C. The increase in drug availability extended the MST from 15.5 months in patients treated with ≤3 drugs to 36.0–37.3 months in patients treated with six to seven drugs. Conclusion The development of chemotherapy including late‐line treatments could improve the prognosis of mCRC patients.

Abstract Aims There is a paucity of comparative data on the use of sorafenib and lenvatinib for unresectable hepatocellular carcinoma. We assessed the real‐world treatment outcomes between using sorafenib and lenvatinib for unresectable hepatocellular carcinoma in the multiple molecular‐targeted therapy era. Methods and Results We enrolled 386 patients treated with sorafenib or lenvatinib as the first‐line therapy for unresectable hepatocellular carcinoma at multiple centers. Propensity score matching was performed to adjust for differences in baseline and tumor characteristics between the two groups. Propensity score matching identified 110 patients in each treatment group. The median overall survival was similar between lenvatinib and sorafenib (14.8 and 13.0 months, respectively; P = 0.352). The median progression‐free survival was longer with lenvatinib than with sorafenib (7.6 and 3.9 months, respectively; P

Abstract Background Although childhood undervaccination among single mother families is a concern for child healthcare, their association is still under debate. This study aimed to investigate the association between maternal marital status and the risk of childhood undervaccination and determine the mediating effect of household income. Methods We utilised prospective birth cohort from the Japan Environment and Children’s Study (JECS). Of 104,062 foetal records (children) from 97,413 mothers, 82,462 that included mothers recruited between 2011 and 2014, were analysed. Childhood undervaccination was defined as not having been vaccinated with at least one routine vaccine. A log-binomial regression analysis was used to estimate the risk ratio (RR) for the association between maternal marital status and the risk of childhood undervaccination. A causal mediation analysis was further performed to investigate the proportion of the association mediated by household income. Results Among 82,462 children, 3188 and 79,274 had unmarried and married mothers, respectively. Childhood undervaccination was observed in 1053 (33.0%) and 16,901 (21.3%) children of unmarried and married mothers, respectively. Maternal marital status was associated with a higher risk of childhood undervaccination (adjusted risk ratio [aRR], 1.34; 95% confidence interval [CI], 1.27 to 1.41). Compared with married and older mothers, both unmarried and older (aRR, 1.54; 95% CI, 1.35 to 1.77) and unmarried and younger (aRR, 1.66; 95% CI, 1.54 to 1.79) mothers were associated with a higher risk of childhood undervaccination. The causal mediation analysis showed that the proportion mediated by household income was 10.5% (95% CI, 9.9 to 11.0%). Conclusions This nationwide, prospective, large-scale birth cohort study found that a household with a single mother was associated with an increased risk of childhood undervaccination, and 10% of this association was explained by household income. These findings underscore the importance of improving the social environment among single mother families, including not only poverty but also working conditions.

Abstract The COVID-19 pandemic is an unprecedented threat to humanity that has provoked global health concerns. Since the etiopathogenesis of this illness is not fully characterized, the prognostic factors enabling treatment decisions have not been well documented. Accurately predicting the progression of the disease would aid in appropriate patient categorization and thus help determine the best treatment option. Here, we have introduced a proteomic approach utilizing data-independent acquisition mass spectrometry (DIA-MS) to identify the serum proteins that are closely associated with COVID-19 prognosis. Twenty-seven proteins were differentially expressed between severely ill COVID-19 patients with an adverse or favorable prognosis. Ingenuity Pathway Analysis revealed that 15 of the 27 proteins might be regulated by cytokine signaling relevant to interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF), and their differential expression was implicated in the systemic inflammatory response and in cardiovascular disorders. We further evaluated practical predictors of the clinical prognosis of severe COVID-19 patients. Subsequent ELISA assays revealed that CHI3L1 and IGFALS may serve as highly sensitive prognostic markers. Our findings can help formulate a diagnostic approach for accurately identifying COVID-19 patients with severe disease and for providing appropriate treatment based on their predicted prognosis.

A 68-year-old male was found unconscious in a hot bathtub on a cold winter’s day and was brought to our hospital. On arrival, the patient’s systolic blood pressure was 65 mm hg, heart rate was 134 beats per min, and rectal temperature was 40.5°C. A large volume infusion of acetated Ringer’s solution and vasopressors were administered as an immediate treatment for circulatory failure due to heatstroke. Although the circulatory failure temporarily improved, the blood pressure dropped almost to the point of cardiac arrest. Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) was implemented and the hemodynamics were soon stabilized. Subsequently, VA-ECMO was withdrawn on the third hospital day. The patient recovered enough to feed normally on the 40th hospital day and was transferred to another hospital on the 116th hospital day. Based on this case study, we consider that VA-ECMO implementation before cardiac arrest might be a suitable strategy.

Introduction: Although data accumulated in clinical trials have higher accuracy compared with real-world data and are irreplaceably valuable, most previous clinical trial data have been left unused. Methods: The Japan Lung Cancer Society (JLCS) asked six clinical trial groups that conducted randomized clinical trials on curative chemoradiation for locally advanced NSCLC to provide data. After obtaining consent from all six groups, data were collected from August 2019 to June 2021. Results: A total of eight trials, JCOG9812, JCOG0301, NJLCG0601, OLCSG0007, WJTOG0105, WJOG5008L, SPECTRA, and TORG1018, were included. More than 3000 data items were integrated into 408 items by adjusting their definitions and units. The total number of collected cases was 1288: median age (range), 66 (30–93) years; sex (male/female) 1064/224; pathological type (squamous cell carcinoma, adenocarcinoma, other NSCLC, and unknown) 517, 629, 138, and 4; and stage IIIA and B, 536 and 752. The median overall survival was 26.0 months, with 2-, 5-, and 10-year survival rates of 53.7%, 24.8%, and 15.2%, respectively, in all enrollments. The median progression-free survival was 9.6 months, with 2-, 5-, and 10-year progression-free survival rates of 23.6%, 14.0%, and 9.4%, respectively. Part of the information in the database has been made available on the JLCS web page, and the JLCS members were provided the right to propose research using the database. Conclusions: The integration and sharing of clinical trial data for research purposes was made real by the nonprofit, academic organization, the JLCS. This database will lead to innovative researches and contribute to the improvement of lung cancer treatment and future research.

Introduction: Outcomes of immune checkpoint inhibitor (ICI) rechallenge in NSCLC remain uncertain. This study estimated the safety and efficacy of ICI rechallenge and compared rechallenge benefit among different reasons of initial ICI discontinuation in NSCLC. Methods: PubMed, EMBASE, and Cochrane Library were searched for studies on NSCLC retreated with ICI. Immune-related adverse events (irAEs), overall response rate (ORR), disease control rate (DCR), and progression-free survival (PFS) at initial ICI and rechallenge were analyzed. Results: A total of 15 studies including 442 patients between 2018 and 2022 were eligible for meta-analysis. The incidence of grade 3 or 4 irAE was lower in rechallenge than initial ICI (8.6% versus 17.8%, p < 0.001). Patients rechallenged with ICI had lower ORR and DCR than initial ICI (13.2% versus 42.4%, p < 0.001; 51.1% versus 74.0%, p < 0.001). The ORR and DCR to ICI rechallenge were both higher in patients who experienced disease progression after stopping ICI or irAE than patients with disease progression during ICI treatment (ORR: 46.2% versus 20% versus 11.4%, p = 0.003; DCR: 84.6% versus 90.0% versus 55.0%, p = 0.002). In addition, 34.7% of 69 patients with individual response to ICI and PFS experienced the same or better response to ICI rechallenge in comparison with initial ICI, although PFS in initial ICI was longer than that in ICI rechallenge (median: 8.90 versus 3.67 mo, hazard ratio = 0.44, 95% confidence interval: 0.33–0.59). Conclusions: ICI rechallenge had less severe toxicity than initial ICI treatment. Patients undergoing disease progression after ICI cessation or ICI discontinuation owing to irAE are more likely to benefit from ICI rechallenge in NSCLC.

Transporting patients down stairs by carrying is associated with a particularly high fall risk for patients and the occurrence of back pain among emergency medical technicians. The present study aimed to verify the effectiveness of the Airstretcher device, which was developed to reduce rescuers' physical burden when transporting patients by dragging along the floor and down stairs. Forty-one paramedical students used three devices to transport a 65-kg manikin down stairs from the 3rd to the 1st floor. To verify the physical burden while carrying the stretchers, ratings of perceived exertion were measured using the Borg CR10 scale immediately after the task. Mean Borg CR10 scores (standard deviation) were 3.6 (1.7), 4.1 (1.8), 5.6 (2.4), and 4.2 (1.8) for the Airstretcher with dragging, Airstretcher with lifting, backboard with lifting, and tarpaulin with lifting conditions, respectively (p < 0.01). Multiple comparisons revealed that the Airstretcher with dragging condition was associated with significantly lower Borg CR10 scores compared with the backboard with lifting condition (p < 0.01). When the analysis was divided by handling position, estimated Borg CR10 values (standard error) for head position were 4.4 (1.3), 2.9 (0.9), 3.2 (0.8), and 4.0 (1.1) for the Airstretcher with dragging, Airstretcher with lifting, backboard with lifting, and tarpaulin with lifting conditions, respectively, after adjusting for participant and duration time (F = 1.4, p < 0.25). The estimated Borg CR10 value (standard error) for toe position in the Airstretcher with dragging condition was 2.0 (0.8), and the scores for the side position were 4.9 (0.4), 6.1 (0.3), and 4.7 (0.4) for the Airstretcher with lifting, backboard with lifting, and tarpaulin with lifting conditions, respectively, after adjusting for participant and duration time (F = 3.6, p = 0.02). Transferring a patient down stairs inside a house by dragging using the Airstretcher may reduce the physical burden for rescuers.

Clinical studies often collect longitudinal and time-to-event data for each subject. Joint modeling is a powerful methodology for evaluating the association between these data. The existing models, however, have not sufficiently addressed the problem of missing data, which are commonly encountered in longitudinal studies. In this paper, we introduce a novel joint model with shared random effects for incomplete longitudinal data and time-to-event data. Our proposed joint model consists of three submodels: a linear mixed model for the longitudinal data, a Cox proportional hazard model for the time-to-event data, and a Cox proportional hazard model for the time-to-dropout from the study. By simultaneously estimating the parameters included in these submodels, the biases of estimators are expected to decrease under two missing scenarios. We estimated the proposed model by Bayesian approach, and the performance of our method was evaluated through Monte Carlo simulation studies.

In square contingency table analysis, we consider a partial measure that represents the degree of departure from symmetry for each of several pairs. It may be useful to pool the values of the measure into a single summary measure of partial asymmetry. We show that the estimator of partial measures is asymptotically mutually independent for a large sample size. The present paper proposes a symmetry measure in the class of weighted averages that is different from previous studies. The proposed measure is an approximation of the measure in the class of weighted averages that has the smallest variance.

Abstract Aim To investigate the frequency and risk factors of perioperative, symptomatic venous thromboembolism (VTE) after gastroenterological surgery. Methods We assessed the frequency of and risk factors for VTE after eight gastroenterological procedures (total 516 217 cases including, gastrectomy, total gastrectomy, hepatectomy, esophagectomy, right hemicolectomy, low anterior resection, pancreaticoduodenectomy, and acute pan‐peritonitis surgery) based on data from the National Clinical Database. Data collected between 2011 and 2013 (382 124 cases) were used as a test set, and data from 2014 (134 093 cases) were used as a validation set. Results The frequency of deep vein thrombosis (DVT) was 0.3% (382 124 cases), and the incidence of pulmonary embolism (PE) was 0.2% (382 124 cases) ranging from 0.1% to 0.7% for DVT and from 0.1% and 0.3% for PE among eight surgeries, respectively. Analyses using pre‐and intra‐operative factors identified the top three risk factors for VTE as esophagectomy, pancreaticoduodenectomy, and hepatectomy. Using pre‐, intra‐, and postoperative factors, the second through fourth risk factors were sepsis, prolonged ventilation >48 hours and readmission within 30 days. The highest risks factor for PE using pre‐, intra‐, and postoperative factors were any cardiac events. Unplanned intubation was the fourth risk factor. Conclusion The risk for DVT and PE differed for each surgical procedure. VTE and PE risk factors changed after considering postoperative factors. It may be necessary to reconsider the prophylaxis depending on whether the complication occurs after surgery, particularly breathing and cardiac complications.

Abstract Background We examined whether inferior thyroid artery peak systolic velocity (ITA-PSV) predicts an increase in levothyroxine (LT4) dosage in pregnant women with Hashimoto’s thyroiditis. Methods Twenty-two women with Hashimoto’s thyroiditis who were planning and later achieved pregnancy or confirmed as pregnant were enrolled in this retrospective longitudinal observational study. ITA-PSV and thyroid volume were measured using ultrasonography. Serum concentrations of free thyroxine (F-T4), free triiodothyronine (F-T3), and thyroid stimulating hormone (TSH) were simultaneously determined. We adjusted LT4 dosage to maintain serum TSH at

Abstract Background Active surveillance has the potential to prevent nosocomial transmission of carbapenem-resistant Acinetobacter baumannii (CRAB). We assessed whether rapid diagnosis using clinical specimen-direct loop-mediated isothermal amplification (LAMP), a rapid molecular diagnostic assay, and subsequent intervention, could reduce CRAB nosocomial transmission in intensive care units (ICUs). Methods A before and after (quasi-experimental) study was conducted in two ICUs at the Mahidol University Faculty of Medicine Ramathibodi Hospital with 3 months of observational period followed by 9 months of interventional period. All patients were screened for CRAB using both the culture and LAMP method from rectal swab and/or bronchial aspirates (intubated patients only) upon admission, weekly thereafter, and upon discharge. During the pre-intervention period, we performed contact precautions based on culture results. In contrast, during the intervention period, we initiated contact precautions within a few hours after sample collection on the basis of LAMP results. Results A total of 1335 patients were admitted to the ICUs, of which 866 patients (pre-intervention period: 187; intervention period: 679) were eligible for this study. Incidence rate of CRAB infection decreased to 20.9 per 1000 patient-days in the intervention period from 35.2 in the pre-intervention period (P

We present the case of a 79-year-old woman who presented at our center with a periprosthetic tibial fracture with a popliteal artery injury after total knee arthroplasty. Anastomosis of the popliteal artery was performed on the day of injury, and was later treated by open reduction and internal fixation. The patient was able to walk 3 months after injury.The present case was difficult to treat because of the arterial injury associated with periprosthetic fracture. Although revision of the implant was considered, open reduction and internal fixation was selected because of the severity of soft-tissue damage. The mechanism of injury is not uncommon, and it is expected that similar fractures will become more prevalent in the future as the number of knee replacement surgeries increases.

For square contingency tables with ordered categories, there would be some situations that one would like to analyze them by using collapsed 3×3 tables combining some adjacent categories in the original table. This paper considers the marginal homogeneity for collapsed tables and proposes a measure which represents the degree of departure from the marginal homogeneity. The proposed measure lies between 0 and 1, and it takes zero when the marginal homogeneity holds. Examples are given.

Background. Higher levels of uric acid production have been reported in individuals with visceral fat obesity, and obesity is known to enhance xanthine oxidoreductase (XOR) activity, although the precise mechanism remains unclear. We investigated the associations of visceral fat area (VFA), serum adiponectin level, and insulin resistance with plasma XOR activity using our novel highly sensitive assay based on [13C2,15N2] xanthine and liquid chromatography/triple quadrupole mass spectrometry. Methods. This cross-sectional study included 193 subjects (92 males and 101 females) registered in the MedCity21 health examination registry. Plasma XOR activity, serum adiponectin level, and VFA obtained by computed tomography were measured, and insulin resistance was determined based on the homeostasis model assessment (HOMA-IR) index. Results. The mean values for VFA, log HOMA-IR, and log plasma XOR activity were 76.8 ± 45.8 cm2, 0.14 ± 0.30, and 1.50 ± 0.44 pmol/h/mL, respectively. Multiple regression analysis showed that HOMA-IR was significantly (p=0.020) associated with plasma XOR activity independent of other factors, including VFA and adiponectin level, as well as age, sex, alcohol drinking habit, smoking habit, alanine transaminase, HbA1c, and eGFR. The “sex∗HOMA−IR” interaction was not significant (p=0.89), indicating that sex difference does not have an effect on the relationship between HOMA-IR and plasma XOR activity. Conclusions. Our results indicate that insulin resistance is associated with plasma XOR activity and that relationship is independent of visceral adiposity and adiponectin level, suggesting that the development of insulin resistance resulting from increased visceral adiposity and/or reduced serum adiponectin contributes to increased uric acid production by stimulating XOR activity.

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

Phenylketonuria (PKU) and hyperphenylalaninemia (HPA), both identified in newborn screening, are attributable to variants in PAH. Reportedly, the p.R53H(c.158G>A) variant is common in patients with HPA in East Asia. Here, we aimed to define the association between p.R53H and HPA phenotype, and study the long-term outcome of patients with HPA carrying p.R53H. We retrospectively reviewed the genotype in 370 patients detected by newborn screening, and identified the phenotype in 280 (117, HPA; 163, PKU). p.R413P(c.1238G>C) was the most frequently found (n = 117, 31.6%) variant, followed by p.R53H (n = 89, 24.1%). The odds ratio for heterozygous p.R53H to cause HPA was 48.3 (95% CI 19.410–120.004). Furthermore, we assessed the non-linear association between the phenylalanine (Phe) value and elapsed time using the follow-up data of the blood Phe levels of 73 patients with HPA carrying p.R53H. The predicted levels peaked at 161.9 μmol (95% CI 152.088–172.343) at 50–60 months of age and did not exceed 360 μmol/L during the 210-month long observation period. The findings suggest that patients with HPA, carrying p.R53H, do not need frequent Phe monitoring as against those with PKU. Our study provides convincing evidence to determine clinical management of patients detected through newborn screening in Japan.

For two-way contingency tables, Tomizawa (1985) considered the point-symmetry and marginal point-symmetry models, and Tomizawa, Yamamoto and Tahata (2007) proposed a measure to represent the degree of departure from point-symmetry. The present paper proposes a measure to represent the degree of departure from marginal pointsymmetry for two-way tables. The proposed measure is expressed by using Cressie-Read power-divergence or Patil-Taillie diversity index. This measure would be useful for comparing the degrees of departure from marginal point-symmetry in several tables. The relationship between the degree of departure from marginal point-symmetry and the measure is shown when it is reasonable to assume underlying bivariate normal distribution. Examples are shown.

For the analysis of square contingency tables with ordered categories, Tomizawa et al. (2003) considered a measure to represent the degree of departure from marginal homogeneity (MH). Tomizawa (1993) considered an extended marginal homogeneity (EMH) model. This paper (i) proposes a measure to represent the degree of departure from EMH, (ii) proposes a measure from equality of marginal means (E), and (iii) gives a theorem that the value of measure for MH is equal to the sum of the value of measure for EMH and that for E.

For the analysis of square contingency tables, Tomizawa (1994), Tomizawa, Seo, and Yamamoto (1998), and Tomizawa, Miyamoto, and Hatanaka (2001) considered measures to represent the degree of departure from symmetry. However, the maximum value of these measures cannot distinguish two kinds of complete asymmetry (say, complete-upper-asymmetry and complete-lower-asymmetry). The present paper proposes a measure which can distinguish two kinds of complete asymmetry for square tables with ordered categories. Especially the proposed measure is useful for representing the degree of departure from symmetry when the conditional symmetry model holds. Examples are given.

For 2 x 2 x K contingency tables, Tomizawa considered a Shannon entropy type measure to represent the degree of departure from a log-linear model of no three-factor interaction (the NOTFI model). This paper proposes a generalization of Tomizawa's measure for 2 x 2 x K tables. The measure proposed is expressed by using Patil-Taillie diversity index or Cressie-Read power-divergence. A special case of the proposed measure includes Tomizawa's measure. The proposed measure would be useful for comparing the degrees of departure from the NOTFI model in several tables.

ObjectivesIn the brain, the mechanisms of attention to the left and the right are known to be different. It is possible that brain activity when driving also differs with different horizontal road alignments (left or right curves), but little is known about this. We found driver brain activity to be different when driving on left and right curves, in an experiment using a large-scale driving simulator and functional near-infrared spectroscopy (fNIRS).Research design and methodsThe participants were fifteen healthy adults. We created a course simulating an expressway, comprising straight line driving and gentle left and right curves, and monitored the participants under driving conditions, in which they drove at a constant speed of 100 km/h, and under non-driving conditions, in which they simply watched the screen (visual task). Changes in hemoglobin concentrations were monitored at 48 channels including the prefrontal cortex, the premotor cortex, the primary motor cortex and the parietal cortex. From orthogonal vectors of changes in deoxyhemoglobin and changes in oxyhemoglobin, we calculated changes in cerebral oxygen exchange, reflecting neural activity, and statistically compared the resulting values from the right and left curve sections.ResultsUnder driving conditions, there were no sites where cerebral oxygen exchange increased significantly more during right curves than during left curves (p > 0.05), but cerebral oxygen exchange increased significantly more during left curves (p < 0.05) in the right premotor cortex, the right frontal eye field and the bilateral prefrontal cortex. Under non-driving conditions, increases were significantly greater during left curves (p < 0.05) only in the right frontal eye field.ConclusionsLeft curve driving was thus found to require more brain activity at multiple sites, suggesting that left curve driving may require more visual attention than right curve driving. The right frontal eye field was activated under both driving and non-driving conditions.

Recently, it has been reported that circulating free DNA (cf-DNA) in the blood is increased in various infectious diseases, including sepsis. Moreover, a relationship between cf-DNA and neutrophil extracellular traps (NETs) has been suggested. However, it is still unclear what the source and physiological role of cf-DNA in sepsis are. In this study, we examined the source of cf-DNA by detecting citrullinated histone H3, a characteristic feature of NET formation, in cecal ligation and puncture- (CLP-)operated mice. In addition, neutrophil depletion using anti-Ly6G antibodies was performed to assess the association between neutrophils and cf-DNA. Increased cf-DNA levels were observed only in CLP mice and not in the control groups; the qPCR findings revealed that the cf-DNA was mainly host-derived, even in bacteremic conditions. Citrullinated histone H3 was not increased in the neutrophils upon CLP, and the depletion of neutrophils showed limited effects on decreasing the amount of cf-DNA. Taken together, these results suggested that elevated cf-DNA levels during early-phase sepsis may represent a candidate biomarker for the severity of sepsis and that, contrary to previous findings, cf-DNA is not derived from neutrophils or NETs.

Neutrophil extracellular traps (NETs), a newly identified immune mechanism, are induced by inflammatory stimuli. Modification by citrullination of histone H3 is thought to be involved in the in vitro formation of NETs. The purposes of this study were to evaluate whether NETs and citrullinated histone H3 (Cit-H3) are present in the bloodstream of critically ill patients and to identify correlations with clinical and biological parameters. Blood samples were collected from intubated patients at the time of ICU admission from April to June 2011. To identify NETs, DNA and histone H3 were visualized simultaneously by immunofluorescence in blood smears. Cit-H3 was detected using a specific antibody. We assessed relationships of the presence of NETs and Cit-H3 with the existence of bacteria in tracheal aspirate, SIRS, diagnosis, WBC count, and concentrations of IL-8, TNF-α, cf-DNA, lactate, and HMGB1. Forty-nine patients were included. The median of age was 66.0 (IQR: 52.5-76.0) years. The diagnoses included trauma (7, 14.3%), infection (14, 28.6%), resuscitation from cardiopulmonary arrest (8, 16.3%), acute poisoning (4, 8.1%), heart disease (4, 8.1%), brain stroke (8, 16.3%), heat stroke (2, 4.1%), and others (2, 4.1%). We identified NETs in 5 patients and Cit-H3 in 11 patients. NETs and/or Cit-H3 were observed more frequently in "the presence of bacteria in tracheal aspirate" group (11/22, 50.0%) than in "the absence of bacteria in tracheal aspirate" group (4/27, 14.8%) (p

For the analysis of square contingency tables, Tomizawa, Miyamoto and Ashihara (2003) considered a measure to represent the degree of departure from marginal homogeneity. However, the maximum value of this measure cannot distinguish two kinds of marginal inhomogeneity. This paper proposes a measure which can distinguish two kinds of marginal inhomogeneity for square tables with ordered categories. The measure is constructed using the arc-cosine function of symmetric cumulative probabilities. Especially the proposed measure is useful for representing the degree of departure from marginal homogeneity when the extended marginal homogeneity model holds. Examples are given.

For the analysis of square contingency tables, Tomizawa and Makii (2001), and Tomizawa, Miyamoto and Ashihara (2003) considered the measures to represent the degree of departure from marginal homogeneity (MH). Tomizawa (1984) considered an extended marginal homogeneity (EMH) model for square tables with ordered categories. This paper proposes a measure to represent the degree of departure from EMH. The measure proposed is expressed by using the Cressie and Read’s (1984) power-divergence or Patil and Taillie’s (1982) diversity index. The measure would be useful for comparing the degree of departure from EMH in several tables. Examples are given.

Objective: In Japan, perioperative prophylaxis of pulmonary embolism (PE) in gynecologic cancer patients with preoperative asymptomatic venous thromboembolism (VTE) has not been well established yet. The GOTIC-VTE trial was a prospective, multi-center, single-arm clinical trial to investigate the prevention of postoperative symptomatic PE onset by seamless anticoagulant therapy from the preoperative period to 4 weeks after surgery instead of using intermittent pneumatic compression. Methods: Anticoagulant therapy was started immediately after asymptomatic VTE diagnosis and stopped preoperatively according to the rules of each institution. Unfractionated heparin administration was resumed within 12 hours postoperatively, and this was followed by the switch to low-molecular-weight heparin and subsequently, edoxaban; this cycle was continued for 28 days. Primary outcome was the occurrence of symptomatic PE in 28 days postoperatively. Secondary outcomes were the incidence of VTE-related events in 28 days and 6 months postoperatively and protocol-related adverse events. Results: Between February 2018 and September 2020, 99 patients were enrolled; of these, 82 patients were assessed as the full analysis set, including 58 for ovarian cancer, fallopian tube, or peritoneal cancer; 21 for endometrial cancer; and 3 for cervical cancer. No symptomatic PE was observed within 28 days postoperatively; two patients had bleeding events (major bleeding and clinically relevant nonmajor bleeding) and three had grade 3 adverse events (increased alanine transaminase, aspartate aminotransferase, or gamma-glutamyl transferase). Conclusion: The multifaceted perioperative management for gynecologic malignancies with asymptomatic VTE effectively prevented postoperative symptomatic PE. [ABSTRACT FROM AUTHOR]