Near-infrared light scattering and water diffusion in newborn brains.

OBJECTIVE: MRI provides useful information regarding brain maturation and injury in newborn infants. However, MRI studies are generally restricted during acute phase, resulting in uncertainty around upstream clinical events responsible for subtle cerebral injuries. Time-resolved near-infrared spectroscopy non-invasively provides the reduced scattering coefficient ( µ s ' ), which theoretically reflects tissue structural complexity. This study aimed to test whether µ s ' values of the newborn head reflected MRI findings. METHODS: Between June 2009 and January 2015, 77 hospitalised newborn infants (31.7 ± 3.8 weeks gestation) were assessed at 38.8 ± 1.3 weeks post-conceptional age. Associations of µ s ' values with MRI scores, mean diffusivity and fractional anisotropy were assessed. RESULTS: Univariable analysis showed that µ s ' values were associated with gestational week (p = 0.035; regression coefficient [B], 0.065; 95% confidence interval [CI], 0.005-0.125), fractional anisotropy in the cortical grey matter (p = 0.020; B, -5.994; 95%CI, -11.032 to -0.957), average diffusivity in the cortical grey matter (p < 0.001; B, -4.728; 95%CI, -7.063 to -2.394) and subcortical white matter (p = 0.001; B, -2.071; 95%CI, -3.311 to -0.832), subarachnoid space (p < 0.001; B, -0.289; 95%CI, -0.376 to -0.201) and absence of brain abnormality (p = 0.042; B, -0.422; 95%CI, -0.829 to -0.015). The multivariable model to explain µ s ' values comprised average diffusivity in the subcortical white matter (p < 0.001; B, -2.066; 95%CI, -3.200 to -0.932), subarachnoid space (p < 0.001; B, -0.314; 95%CI, -0.412 to -0.216) and absence of brain abnormality (p = 0.021; B, -0.400; 95%CI, -0.739 to -0.061). INTERPRETATION: Light scattering was associated with brain structure indicated by MRI-assessed brain abnormality and diffusion-tensor-imaging-assessed water diffusivity. When serially assessed in a larger population, µ s ' values might help identify covert clinical events responsible for subtle cerebral injury.

A New Quantitative Triage System for Hospitalized Neonates to Assist with Decisions of Hospital Evacuation Priorities.

INTRODUCTION: Hospitalized neonates are vulnerable to natural and man-made disasters because of their persistent requirement for medical resources and may need to be evacuated to safe locations when electricity and medical gas supply become unreliable. In Japan, a triage system for hospitalized neonates, or the Simple Triage and Rapid Treatment for Neonates, Revised (START-Neo-R), has been used to determine whether neonates are in suitable conditions for transportation. However, this scale is not useful to determine the evacuation order of neonates because a considerable number of evacuees are classified into the same categories. STUDY OBJECTIVE: To solve this problem, a novel triage system, Neonatal Extrication Triage (NEXT) was developed. This study tested the validity and reproducibility of both triages and compared them with a standardized prognostic scoring system for hospitalized neonates, the Neonatal Therapeutic Intervention Scoring System (NTISS). METHODS: In this retrospective observational study, physicians and nurses independently assessed each neonate hospitalized at a tertiary neonatal intensive care unit (NICU) twice weekly using NEXT and START-Neo-R. The NEXT system comprises six questionnaires regarding medical resources required during transition and transportation, providing composite scores on a 12-point scale. The START-Neo-R classified neonates into five levels based on the severity of disease and dependence on medical care. Inter-rater reliability of both systems was assessed using Cohen's kappa coefficient, whereas the criterion validity with NTISS was assessed using Spearman's correlation coefficient. RESULTS: Overall, 162 neonates were assessed for 49 days, resulting in triage data for 1,079 accumulated patients. Both NEXT scores and START-Neo-R ranks were well-dispersed across different levels without excessive accumulation in specific categories. Inter-rater reliability of NEXT (kappa coefficient, 0.973; 95% confidence interval, 0.969-0.976) and START-Neo-R (kappa coefficient, 0.952; 95% confidence interval, 0.946-0.957) between physicians and nurses was sufficiently high. The correlation coefficient of NEXT and START-Neo-R scores with NTISS scores were 0.889 (P <.001) and 0.850 (P <.001), respectively. CONCLUSIONS: Both START-Neo-R and NEXT had good reproducibility and correlation with the severity of neonates indicated by NTISS. With its well-dispersed scores across different levels, the NEXT system might be a powerful tool to determine the priority of evacuation objectively.

Foetal growth, birth transition, enteral nutrition and brain light scattering.

If the brain structure is assessed at neonatal intensive care units, covert clinical events related with subtle brain injury might be identified. The reduced scattering coefficient of near-infrared light (µS') obtained using time-resolved near-infrared spectroscopy from the forehead of infants is associated with gestational age, body weight and Apgar scores, presumably reflecting subtle changes of the brain related to foetal growth and birth transition. One hundred twenty-eight preterm and term infants were studied to test whether µS' obtained from the head at term-equivalent age is associated with foetal growth, birth transition and nutritional status after birth, which are key independent variables of developmental outcomes. As potential independent variables of µS', birth weight, Apgar scores, age at full enteral feeding and post-conceptional age at the study were assessed to represent foetal growth, birth transition and nutritional status after birth. Subsequently, higher µS' values were associated with higher Apgar scores (p = 0.003) and earlier establishment of enteral feeding (p < 0.001). The scattering property of near-infrared light within the neonatal brain might reflect changes associated with birth transition and nutritional status thereafter, which might be used as a non-invasive biomarker to identify covert independent variables of brain injury in preterm infants.

A retrospective review of 10-year trends in general anesthesia for cesarean delivery at a university hospital: the impact of a newly launched team on obstetric anesthesia practice.

BACKGROUND: The indications for general anesthesia (GA) in obstetric settings, which are determined in consideration of maternal and fetal outcome, could be affected by local patterns of clinical practice grounded in unique situations and circumstances that vary among medical institutions. Although the use of GA for cesarean delivery has become less common with more frequent adoption of neuraxial anesthesia, GA was previously chosen for pregnancy with placenta previa at our institution in case of unexpected massive hemorrhage. However, the situation has been gradually changing since formation of a team dedicated to obstetric anesthesia practice. Here, we report the results of a review of all cesarean deliveries performed under GA, and assess the impact of our newly launched team on trends in clinical obstetric anesthesia practice at our institution. METHODS: Our original database for obstetric GA during the period of 2010 to 2019 was analyzed. The medical records of all parturients who received GA for cesarean delivery were reviewed to collect detailed information. Interrupted time series analysis was used to evaluate the impact of the launch of our obstetric anesthesia team. RESULTS: As recently as 2014, more than 10% of cesarean deliveries were performed under GA, with placenta previa accounting for the main indication in elective and emergent cases. Our obstetric anesthesia team was formed in 2015 to serve as a communication bridge between the department of anesthesiology and the department of obstetrics. Since then, there has been a steady decline in the percentage of cesarean deliveries performed under GA, decreasing to a low of less than 5% in the latest 2 years. Interrupted time series analysis revealed a significant reduction in obstetric GA after 2015 (P = 0.04), which was associated with decreased use of GA for pregnancy with placenta previa. On the other hand, every year has seen a number of urgent cesarean deliveries requiring GA. CONCLUSIONS: There has been a trend towards fewer obstetric GA since 2015. The optimized use of GA for cesarean delivery was made possible mainly through strengthened partnerships between anesthesiologists and obstetricians with the support of our obstetric anesthesia team.

Association of Weight Fluctuation With Mortality in Japanese Adults.

Importance: Weight cycling is associated with the risk of mortality from heart disease, but many studies have not distinguished between simple nonlinear (monotone) weight changes and more complex changes that reflect fluctuations. Objective: To assess whether extreme body weight variation is associated with mortality after controlling for nonlinear weight changes. Design, Setting, and Participants: In this prospective clinical cohort study, 4796 Japanese atomic bomb survivors were examined in the clinic as part of a biennial health examination and research program. The study consisted of a 20-year longitudinal baseline period (July 1, 1958, to June 30, 1978) and subsequent mortality follow-up of 27 years (July 1, 1978, to June 30, 2005) Participants were initially between the ages of 20 and 49 years during the baseline period and, throughout the baseline period, had no diagnoses of cardiovascular disease (CVD) or cancer and attended at least 7 of 10 scheduled examinations. Data analysis was performed from October 16, 2015, to May 13, 2016. Exposures: Residual variability in body mass index (BMI) during the baseline period. Main Outcomes and Measures: Outcomes were mortality from ischemic heart disease, cerebrovascular disease, other CVDs combined, other causes (except cancer), and cancer. Root mean squared error was calculated to capture individual residual variation in BMI after adjustment for baseline BMI trends, and the association of magnitude of residual variation with mortality was calculated as relative risk. Results: In total, 4796 persons (mean [SD] age, 35.0 [7.3] years at first baseline examination; 3252 [67.8%] female; mean [SD] BMI, 21.2 [2.8] at first baseline visit [20.6 (2.4) among men and 21.5 (2.9) among women]) participated in the study. During follow-up, 1550 participants died: 82 (5.3% of all deaths) of ischemic heart disease, 181 (11.7%) of cerebrovascular disease, 186 (12.0%) of other CVDs, 615 (39.7%) of cancer, and 486 (31.3%) of other causes. Magnitude of residual variation in weight was associated with all-cause mortality (relative risk, 1.25 for 1 U of additional variation; 95% CI, 1.06-1.47) and ischemic heart disease mortality (relative risk, 2.49; 95% CI, 1.41-4.38). Conclusions and Relevance: The findings suggest that an association exists between weight variation and heart disease mortality and that weight loss interventions, if deemed to be necessary, should be considered carefully.

Parity As a Protective Biomarker Against Silent Brain Infarction in Community-Dwelling Older Adults: The Sefuri Study.

BACKGROUND: Although several studies have reported an association between parity and increased risk of stroke, this relationship remains controversial. AIMS: The present study aimed to determine whether parity is associated with silent brain infarction (SBI), independent of other confounders. METHODS: We analyzed the brain magnetic resonance imaging findings in 576 of community-dwelling older adults with a mean age of 72.1 years. All female participants were asked to provide information regarding the total number of live births, their age at the last parity, and their age at menopause. RESULTS: The prevalence of SBI and the number of infarcts per participant were higher in men than in women. Although all women who had given birth (0, 1-2, 3-4, or 5+ times) exhibited lower age-adjusted odds ratios (ORs) for SBI than men, a significant difference was observed between women with ≧5 births and men after adjustment for common vascular risk factors (OR: .348, 95% confidence interval [95% CI]: .123-.986). Among women who had given birth, the relationship between fertility and SBI was attenuated, but was enhanced after adjustment for age at the last parity (OR: .300, 95% CI: .102-.886). CONCLUSIONS: Our findings indicate that fertile women may be protected against SBI or cerebral small vessel disease via the biological effects associated with reproductive activity, and that high fertility may be a marker of protection against SBI. However, late childbearing may blunt protective effects of fertility against SBI.

Prediction of colorectal tumor grade and invasion depth through narrow-band imaging scoring.

AIM: To determine the usefulness of assigning narrow-band imaging (NBI) scores for predicting tumor grade and invasion depth in colorectal tumors. METHODS: A total of 161 colorectal lesions were analyzed from 138 patients who underwent endoscopic or surgical resection after conventional colonoscopy and magnifying endoscopy with NBI. The relationships between the surface and vascular patterns of the lesions, as visualized with NBI, and the tumor grade and depth of submucosa (SM) invasion were determined histopathologically. Scores were assigned to distinct features of the surface microstructures of tubular and papillary-type lesions. Using a multivariate analysis, a model was developed for predicting the tumor grade and depth of invasion based on NBI-finding scores. RESULTS: NBI findings that correlated with a high tumor grade were associated with the "regular/irregular" (P < 0.0001) surface patterns and the "avascular area" pattern (P = 0.0600). The vascular patterns of "disrupted vessels" (P = 0.0714) and "thick vessels" (P = 0.0133) but none of the surface patterns were associated with a depth of invasion of ≥ 1000 µm. In our model, a total NBI-finding score ≥ 1 was indicative of a high tumor grade (sensitivity: 0.97; specificity: 0.24), and a total NBI-finding score ≥ 9 (sensitivity: 0.56; specificity: 1.0) was predictive of a SM invasion depth ≥ 1000 µm. Scores less than these cutoff values signified adenomas and a SM invasion depth < 1000 µm, respectively. Associations were also noted between selected NBI findings and tumor tissue architecture and histopathology. CONCLUSION: Our multivariate statistical model for predicting tumor grades and invasion depths from NBI-finding scores may help standardize the diagnosis of colorectal lesions and inform therapeutic strategies.

Japanese clinical practice guidelines for allied disorders of Hirschsprung's disease, 2017.

BACKGROUND: Despite the presence of ganglion cells in the rectum, some patients have symptoms similar to those of Hirschsprung's disease. A consensus has yet to be established regarding the terminology for these diseases. We defined this group of diseases as "allied disorders of Hirschsprung's disease" and compiled these guidelines to facilitate accurate clinician diagnosis and provide appropriate treatment strategies for each disease. METHODS: These guidelines were developed using the methodologies in the Medical Information Network Distribution System (MINDS). Of seven allied disorders, isolated hypoganglionosis; megacystis-microcolon-intestinal hypoperistalsis syndrome; and chronic idiopathic intestinal pseudo-obstruction were selected as targets of clinical questions (CQ). In a comprehensive search of the Japanese- and English-language articles in PubMed and Ichu-Shi Web, 836 pieces of evidence related to the CQ were extracted from 288 articles; these pieces of evidence were summarized in an evidence table. RESULTS: We herein outline the newly established Japanese clinical practice guidelines for allied disorders of Hirschsprung's disease. Given that the target diseases are rare and intractable, most evidence was drawn from case reports and case series. In the CQ, the diagnosis, medication, nutritional support, surgical therapy, and prognosis for each disease are given. We emphasize the importance of full-thickness intestinal biopsy specimens for the histopathological evaluation of enteric ganglia. Considering the practicality of the guidelines, the recommendations for each CQ were created with protracted discussions among specialists. CONCLUSIONS: Clinical practice recommendations for allied disorders of Hirschprung's disease are given for each CQ, along with an assessment of the current evidence. We hope that the information will be helpful in daily practice and future studies.

Identification of highly selective and potent orexin receptor 1 antagonists derived from a dual orexin receptor 1/2 antagonist based on the structural framework of pyrazoylethylbenzamide.

The design, synthesis, and structure activity relationships of the novel class of pyrazolylethylbenzamide orexin receptor 1-selective antagonists are described. Further derivatization of the prototype dual orexin receptor 1/2 antagonist lead (1) by installing a (S)-methyl group into the ethyl linker moiety between the pyrazole ring and benzamide resulted in an increase of the antagonist potency against orexin receptor 1/2 receptors. Optimization of the benzamide and pyrazole parts of compounds 2 and 9b led to the identification of N-ethyl-5-fluoro-N-{(2S)-1-[5-(4-fluorophenyl)-2H-tetrazol-2-yl]propan-2-yl}-2-(pyrimidin-2-yl)benzamide (24), which exhibited excellent antagonistic activity against orexin receptor 1 with an IC50 of 2.01nM and a 265-fold selectivity for orexin receptor 1 over orexin receptor 2.

Chronic Kidney Disease and Subclinical Brain Infarction Increase the Risk of Vascular Cognitive Impairment: The Sefuri Study.

BACKGROUND AND PURPOSE: The purpose of this study was to determine the complex associations among chronic kidney disease (CKD), subclinical brain infarction (SBI), and cognitive impairment. METHODS: We used structural equation modeling (SEM) to examine the complex relationships among CKD, SBI, and cognitive function with Mini-Mental State Examination (MMSE; global function) and modified Stroop test (executive function) in a population-based cohort of 560 non-demented elderly subjects. RESULTS: Path analysis based on SEM revealed that the direct paths from estimated glomerular filtration rate (eGFR) to SBI and from SBI to executive function were significant (ß = -.10, P = .027, and ß = .16, P < .001, respectively). Furthermore, the direct path from eGFR to executive function was also significant (ß = -.12, P = .006), indicating that the effects of CKD on executive function are independent of SBI. The direct paths from age and education to global cognitive function were highly significant (ß = -.17 and .22, respectively, P < .001), whereas the direct path from eGFR to MMSE was not significant. CONCLUSIONS: Our findings indicate that CKD confers a risk of vascular cognitive impairment or executive dysfunction through mechanisms dependent and independent of SBI. Treating CKD may be a potential strategy to protect against vascular cognitive impairment or executive dysfunction in healthy elderly subjects.

Hippocampal atrophy and memory dysfunction associated with physical inactivity in community-dwelling elderly subjects: The Sefuri study.

BACKGROUND: Physical inactivity is one of the modifiable risk factors for hippocampal atrophy and Alzheimer's disease. We investigated the relationship between physical activity, hippocampal atrophy, and memory using structural equation modeling (SEM). MATERIALS AND METHODS: We examined 213 community-dwelling elderly subjects (99 men and 114 women with a mean age of 68.9 years) without dementia or clinically apparent depression. All participants underwent Mini-Mental State Examination (MMSE) and Rivermead Behavioral Memory Test (RBMT). Physical activities were assessed with a structured questionnaire. We evaluated the degree of hippocampal atrophy (z-score-referred to as ZAdvance hereafter), using a free software program-the voxel-based specific regional analysis system for Alzheimer's disease (VSRAD) based on statistical parametric mapping 8 plus Diffeomorphic Anatomical Registration Through an Exponentiated Lie algebra. RESULTS: Routine magnetic resonance imaging findings were as follows: silent brain infarction, n = 24 (11.3%); deep white matter lesions, n = 72 (33.8%); periventricular hyperintensities, n = 35 (16.4%); and cerebral microbleeds, n = 14 (6.6%). Path analysis based on SEM indicated that the direct paths from leisure-time activity to hippocampal atrophy (ß = -.18, p < .01) and from hippocampal atrophy to memory dysfunction (RBMT) (ß = -.20, p < .01) were significant. Direct paths from "hippocampus" gray matter volume to RBMT and MMSE were highly significant, while direct paths from "whole brain" gray matter volume to RBMT and MMSE were not significant. The presented SEM model fit the data reasonably well. CONCLUSION: Based on the present SEM analysis, we found that hippocampal atrophy was associated with age and leisure-time physical inactivity, and hippocampal atrophy appeared to cause memory dysfunction, although we are unable to infer a causal or temporal association between hippocampal atrophy and memory dysfunction from the present observational study.

[Work-Related Issues of Adolescent and Young Adult(AYA)Cancer Survivors - Tips for Supporting Them in and out of Hospitals].

Recent advances in cancer treatment have steadily improved the overall survival rate, and enhancing the quality of life of cancer survivors is the challenge faced at present. One of the major topics in studies on cancer survivors is work-related issues, and the government has been focusing on improving the circumstances of the working population and children. In 2015, the Cancer Control Accelerating Plan set adolescent and young adult(AYA)cancer survivors as the top priority for this plan. Work-related issues of AYA cancer survivors are highly individualized and complicated, mainly because of three characteristics: 1 ) Cancer treatments and/or outpatient follow-ups are accompanied by major life-stage transitions, 2 ) Treatments are prone to be nonstandardized in "rare cancers" or "advanced-stage cancers" and 3 ) Achieving economic independence is difficult because of high medical costs. This article provides some tips for medical professionals working in hospitals on how to support AYA cancer survivors along with their main responsibilities. It also provides an overview of online and offline resources available for supporting this population.

Therapeutic hypothermia for neonatal encephalopathy: a report from the first 3 years of the Baby Cooling Registry of Japan.

Therapeutic hypothermia is recommended for moderate and severe neonatal encephalopathy, but is being applied to a wider range of neonates than originally envisaged. To examine the clinical use of therapeutic hypothermia, data collected during the first 3 years (2012-2014) of the Baby Cooling Registry of Japan were analysed. Of 485 cooled neonates, 96.5% were ≥36 weeks gestation and 99.4% weighed ≥1,800 g. Severe acidosis (pH < 7 or base deficit ≥16 mmol/L) was present in 68.9%, and 96.7% required resuscitation for >10 min. Stage II/III encephalopathy was evident in 88.3%; hypotonia, seizures and abnormal amplitude-integrated electroencephalogram were observed in the majority of the remainder. In-hospital mortality was 2.7%; 90.7% were discharged home. Apgar scores and severity of acidosis/encephalopathy did not change over time. The time to reach the target temperature was shorter in 2014 than in 2012. The proportion undergoing whole-body cooling rose from 45.4% to 81.6%, while selective head cooling fell over time. Mortality, duration of mechanical ventilation and requirement for tube feeding at discharge remained unchanged. Adherence to standard cooling protocols was high throughout, with a consistent trend towards cooling being achieved more promptly. The mortality rate of cooled neonates was considerably lower than that reported in previous studies.

Paradoxical diurnal cortisol changes in neonates suggesting preservation of foetal adrenal rhythms.

Studies suggested the presence of foetal adrenal rhythms of cortisol, which are entrained in antiphase to maternal rhythms. In contrast, neonates are thought to have no adrenal rhythm until 2-3 months after birth. To test the hypothesis that a foetal-type adrenal rhythm is preserved after birth, saliva samples were collected from 65 preterm/term infants during hospital stay (30-40 weeks corrected age) at 10:00 and 19:00 h. Cortisol levels were assessed for their diurnal difference and dependence on antenatal/postnatal clinical variables. Cortisol levels were lower during periods 15-28 days and >28 days than ≤5 days of life. Lower cortisol was associated with pregnancy-induced hypertension (PIH), gestational age <28 weeks, and mechanical ventilation after birth. Higher cortisol was associated with vaginal delivery and non-invasive ventilation support at saliva collection. PIH and non-invasive mechanical ventilation at saliva collection were associated with cortisol levels even after adjustment for postnatal age. Cortisol levels were higher in the evening than in the morning, which was unassociated with gestational and postnatal age. Higher cortisol levels in the evening suggest the preservation of a foetal-type diurnal rhythm. Cortisol levels are associated with intrinsic and extrinsic variables, such as PIH, delivery mode, gestational age, and respiratory conditions.

Region-specific growth restriction of brain following preterm birth.

Regional brain sizes of very-preterm infants at term-equivalent age differ from those of term-born peers, which have been linked with later cognitive impairments. However, dependence of regional brain volume loss on gestational age has not been studied in detail. To investigate the spatial pattern of brain growth in neonates without destructive brain lesions, head MRI of 189 neonates with a wide range of gestational age (24-42 weeks gestation) was assessed using simple metrics measurements. Dependence of MRI findings on gestational age at birth (Agebirth) and the corrected age at MRI scan (AgeMRI) were assessed. The head circumference was positively correlated with AgeMRI, but not Agebirth. The bi-parietal width, deep grey matter area and the trans-cerebellar diameter were positively correlated with both Agebirth and AgeMRI. The callosal thickness (positive), atrial width of lateral ventricle (negative) and the inter-hemispheric distance (negative) were exclusively correlated with Agebirth. The callosal thickness and cerebral/cerebellar transverse diameters showed predominant dependence on Agebirth over AgeMRI, suggesting that brain growth after preterm-birth was considerably restricted or even became negligible compared with that in utero. Such growth restriction after preterm birth may extensively affect relatively more matured infants, considering the linear relationships observed between brain sizes and Agebirth.

Physiological and pathological clinical conditions and light scattering in brain.

MRI of preterm infants at term commonly reveals subtle brain lesions such as diffuse white matter injury, which are linked with later cognitive impairments. The timing and mechanism of such injury remains unclear. The reduced scattering coefficient of near-infrared light (µs') has been shown to correlate linearly with gestational age in neonates. To identify clinical variables associated with brain µs', 60 preterm and full-term infants were studied within 7 days of birth. Dependence of µs' obtained from the frontal head on clinical variables was assessed. In the univariate analysis, smaller µs' was associated with antenatal glucocorticoid, emergency Caesarean section, requirement for mechanical ventilation, smaller gestational age, smaller body sizes, low 1- and 5-minute Apgar scores, higher cord blood pH and PO2, and higher blood HCO3(-) at the time of study. Multivariate analysis revealed that smaller gestational age, requirement for mechanical ventilation, and higher HCO3(-) at the time of study were correlated with smaller µs'. Brain µs' depended on variables associated with physiological maturation and pathological conditions of the brain. Further longitudinal studies may help identify pathological events and clinical conditions responsible for subtle brain injury and subsequent cognitive impairments following preterm birth.

Use of Normothermic Default Humidifier Settings Causes Excessive Humidification of Respiratory Gases During Therapeutic Hypothermia.

Adult patients frequently suffer from serious respiratory complications during therapeutic hypothermia. During therapeutic hypothermia, respiratory gases are humidified close to saturated vapor at 37°C (44 mg/L) despite that saturated vapor reduces considerably depending on temperature reduction. Condensation may cause serious adverse events, such as bronchial edema, mucosal dysfunction, and ventilator-associated pneumonia during cooling. To determine clinical variables associated with inadequate humidification of respiratory gases during cooling, humidity of inspiratory gases was measured in 42 cumulative newborn infants who underwent therapeutic hypothermia. Three humidifier settings of 37-default (chamber outlet, 37°C; distal circuit, 40°C), 33.5-theoretical (chamber outlet, 33.5°C; distal circuit, 36.5°C), and 33.5-adjusted (optimized setting to achieve 36.6 mg/L using feedback from a hygrometer) were tested to identify independent variables of excessively high humidity >40.7 mg/L and low humidity <32.9 mg/L. The mean (SD) humidity at the Y-piece was 39.2 (5.2), 33.3 (4.1), and 36.7 (1.2) mg/L for 37-default, 33.5-theoretical, and 33.5-adjusted, respectively. The incidence of excessive high humidity was 10.3% (37-default, 31.0%; 33.5-theoretical, 0.0%; 33.5-adjusted, 0.0%), which was positively associated with the use of a counter-flow humidifier (p < 0.001), 37-default (compared with 33.5-theoretical and 33.5-adjusted, both p < 0.001) and higher fraction of inspired oxygen (p = 0.003). The incidence of excessively low humidity was 17.5% (37-default, 7.1%; 33.5-theoretical, 45.2%; 33.5-adjusted, 0.0%), which was positively associated with the use of a pass-over humidifier and 33.5-theoretical (both p < 0.001). All patients who used a counter-flow humidifier achieved the target gas humidity at the Y-piece (36.6 ± 0.5 mg/L) required for 33.5-adjusted with 33.5-theoretical. During cooling, 37-default is associated with excessively high humidity, whereas 33.5-theoretical leads to excessively low humidity. Future studies are needed to assess whether a new regimen with optimized Y-piece temperature and humidity control reduces serious respiratory adverse events during cooling.

Marriage and fertility in long-term survivors of childhood, adolescent and young adult (AYA) high-grade sarcoma.

PURPOSE: We investigated the marital status and the presence or absence of children in survivors of childhood, adolescent and young adult (AYA) high-grade sarcoma and examined the influence of these factors on the quality of life (QOL) of these survivors. METHODS: Thirty-eight survivors of childhood and AYA high-grade sarcoma (18 males, 20 females) participated in a questionnaire survey on marital status and presence or absence of children, as well as on the health-related QOL (HR-QOL), using the Short Form 36 Health Survey. Diagnoses among these survivors were osteosarcoma (28 participants), Ewing's sarcoma (4 participants), synovial sarcoma (4 participants) and others (2 participants). RESULTS: Of the 18 males who participated in the survey, eight (44.4 %) were married, of whom five (62.5 %) had children. Fifteen (75.0 %) of the 20 females were married, of whom 14 (93.3 %) had children. The proportions of surviving male patients who were married and who had children, respectively, were lower than those of surviving female patients. The proportion of ifosfamide-treated men with children was significantly lower than that of non-ifosfamide-treated men (p = 0.018). With respect to the relationship between marital status and HR-QOL, the scores for the vitality and mental health domains of the SF-36 of survivors who were married were significantly higher than those of unmarried survivors. CONCLUSIONS: The results of our questionnaire survey reveal that among the male survivors of high-grade sarcoma, the proportions of those who were married and of those with children were lower than those of female survivors, suggesting that strategies providing support for marriage and child-rearing may be necessary for the male survivor group. In the married group, mental QOL was high.

[A Case of an EXIT (Ex-utero Intrapartum Treatment) Procedure for a Fetal Giant Oronasopharyngeal Tumor.]

We report successful anesthetic management of an EXIT (ex-utero intrapartum treatment) procedure for fetal giant oronasopharyngeal tumor. A 34-year-old nul- liparous woman was diagnosed as having a fetus with giant oronasopharyngeal tumor and scheduled for an EXIT procedure at 34 weeks of pregnancy. After induction of general anesthesia and tracheal intubation, 6% desflurane and a moderate dose of remifentanil infusion were started to provide anesthesia for both the mother and the fetus. To achieve sufficient uterine relaxation during an EXIT procedure, desflurane was gradually increased up to 10% and nitroglycerin infu- sion was added just before uterine incision. Maternal blood pressure was maintained with continuous infu- sion of phenylephrine. Fetal monitoring during an EXIT procedure was performed with an electrocar- diogram using needle electrodes in addition to trans- thoracic echocardiography. No additional anesthetics were necessary for fetal immobilization. After the completion of tracheostomy followed by the separation of the fetus, nitroglycerin and desflurane were discon- tinued and adequate uterine tone was soon obtained. Maintenance of anesthesia was achieved with propofol and remifentanil for the remaining of the operation. The postoperative course was uneventful. The impor- tance of preoperative detailed simulation and discussion about the procedure among multidisciplinary team members was reconfirmed.