Early Volume Research Articles

P53 Loss Mitigates Early Volume Deficits in the Brains of Irradiated Young Mice

Pediatric cranial radiation therapy results in lasting changes in brain structure. Though different facets of radiation response have been characterized, the relative contributions of each to altered development is unclear. We sought to determine the role of radiation-induced programmed cell death, as mediated by the Trp53 (p53) gene, on neuroanatomic development. Mice having a conditional knockout of p53 (p53KO) or wildtype p53 (WT) were irradiated with a whole-brain dose of 7Gy (IR; n=30) or 0Gy (sham; n=28) at 16days of age. Invivo magnetic resonance imaging was performed before irradiation and at 4 time points after irradiation, until 3months posttreatment, followed by exvivo magnetic resonance imaging and immunohistochemistry. The role of p53 in development was assessed at 6weeks of age in another group of untreated mice (n=37). Neuroanatomic development in p53KO mice was normal. After cranial irradiation, alterations in neuroanatomy were detectable in WT mice and emerged through 2 stages: an early volume loss within 1week and decreased growth through development. In many structures, the early volume loss was partially mitigated by p53KO. However, p53KO had a neutral or negative impact on growth; thus, p53KO did not widely improve volume at endpoint. Partial volume recovery was observed in the dentate gyrus and olfactory bulbs of p53KO-IR mice, with corresponding increases in neurogenesis compared with WT-IR mice. Although p53 is known to play an important role in mediating radiation-induced apoptosis, this is the first study to look at the cumulative effect of p53KO through development after cranial irradiation across the entire brain. It is clear that apoptosis plays an important role in volume loss early after radiation therapy. This early preservation alone was insufficient to normalize brain development on the whole, but regions reliant on neurogenesis exhibited a significant benefit.

Childhood maltreatment, pituitary volume and adolescent hypothalamic-pituitary-adrenal axis – Evidence for a maltreatment-related attenuation

BackgroundAlterations of the development of the hypothalamic-pituitary-adrenal axis (HPAA) have been suggested to be related to experiences of early maltreatment. It has been postulated that early stress (i.e., maltreatment) leads to initial hyperactivation of the HPAA, which subsequently may progress to hypoactivation during the course of adolescence, however empirical studies on this hypothesis are rare. In the current study, we aimed to examine the longitudinal relationships between childhood maltreatment, early adolescent pituitary gland volume (PGV) and mid-adolescent cortisol output in an existing data set to explore the utility of PGV as a measure of HPAA function, and as an indirect test of the attenuation hypothesis. MethodsThe sample comprised 69 adolescents (30 females), subsampled from a larger longitudinal, community-based study on adolescent development. PGV, as an estimate of chronic childhood HPAA activity, was measured by magnetic resonance imaging during early adolescence (mean age 12.62 ± 0.45 years). Cortisol output was assessed via multiple salivary cortisol measures in mid-adolescence (mean age 15.52 ± 0.39 years). The cortisol awakening response (CAR) was calculated as a measure of HPAA functioning. Retrospective assessment of childhood maltreatment was performed using the Childhood Trauma Questionnaire (CTQ). Regression analyses were conducted to examine whether childhood maltreatment, PGV, and their interaction, predicted mid-adolescent CAR. ResultsNo main effect of PGV or maltreatment was found on adolescent CAR. PGV did however significantly interact with childhood maltreatment in predicting the CAR (t = −2.26; p = 0.024). Larger PGV positively predicted lower CAR in the context of relatively high childhood maltreatment (t = 2.032; p = 0.046), but showed no relationship in the context of relatively low maltreatment (t = 0.723; p = 0.472). Maltreatment also interacted with sex, such that (only) in females, higher levels of maltreatment predicted a lower CAR (t = −2.04, p = 0.042). ConclusionsIn the presence of childhood maltreatment, larger PGV was associated with lower CAR in adolescence, providing support for the application of PGV in studies of HPA axis function. Our finding is consistent with a maltreatment-related attenuation of HPAA functioning that may derive from a stress induced chronic hyperactivation during childhood. Prospective longitudinal studies are now required to further explicate these findings and relationships with psychopathology.

Quantitative Lesion Water Uptake in Acute Stroke Computed Tomography Is a Predictor of Malignant Infarction.

Background and Purpose- Early selection of patients with acute middle cerebral artery infarction at risk for malignant edema is critical to initiate timely decompressive surgery. Net water uptake (NWU) per brain volume is a quantitative imaging biomarker of space-occupying ischemic edema which can be measured in computed tomography. We hypothesize that NWU in early infarct lesions can predict development of malignant edema. The aim was to compare NWU in acute brain infarct against other common predictors of malignant edema. Methods- After consecutive screening of single-center registry data, 153 patients with acute proximal middle cerebral artery occlusion fulfilled the inclusion criteria. A total of 29 (18.2%) patients developed malignant edema defined as end point in follow-up imaging leading to decompressive surgery and death as a direct implication of mass effect. Early infarct lesion volume and NWU were quantified in multimodal admission computed tomography; time from symptom onset to admission imaging was recorded. Results- Mean time from onset to admission imaging was equivalent between patients with and without malignant infarcts (mean±SD: 3.3±1.4 hours and 3.3±1.7 hours, respectively). Edematous tissue expansion by NWU within infarct lesions occurred across all patients in this cohort (NWU: 9.1%±6.8%; median, 7.9%; interquartile range, 8.8%; range, 0.1%-35.6%); 7.0% (±5.2) in nonmalignant and 18.0% (±5.7) in malignant infarcts. Based on univariate receiver operating characteristic curve analysis, NWU >12.7% or an edema rate >3.7% NWU/h identified malignant infarcts with high discriminative power (area under curve, 0.93±0.02). In multivariate binary logistic regression, the probability of malignant infarct was significantly associated with early infarct volume and NWU. Conclusions- Computed tomography-based quantitative NWU in early infarct lesions is an important surrogate marker for developing malignant edema. Besides volume of early infarct, the measurements of lesion water uptake may further support identifying patients at risk for malignant infarction.

Fluctuant Mass on an Infant’s Scalp

A term infant has the following scalp examination [click on the video]. Of the options shown in Fig 1A (A, B, C, or D) of the top of an infant’s head, what is the most likely location of the involved area in this infant? Video. Click here to view the video. Figure 1A. Locations for potential collections that are exterior and interior to an infant’s skull. The video of this newborn shows a moderate-to-large fluctuant mass gathered in the dependent portion of the neonate’s scalp. Upon gentle tapping of the boggy collection, there is a clearly visible fluid wave. This finding is most consistent with a subgaleal hemorrhage. Subgaleal hemorrhage is a serious, potentially fatal event in a newborn. It is caused by the rupture of large, bridging, emissary veins that connect the scalp veins to the intracranial dural sinuses. When these veins rupture, blood accumulates between the periosteum and the galeal aponeurotica, a large potential space composed of loose connective tissue. This space extends without restriction across the cranium and can hold as much as 260 mL of blood. (1) (Note: The average total blood volume in a term infant is 80–90 mL/kg.) A hemorrhage of …

Subacute Infarct Volume With Edema Correction in Computed Tomography Is Equivalent to Final Infarct Volume After Ischemic Stroke: Improving the Comparability of Infarct Imaging Endpoints in Clinical Trials.

Final infarct volume is regularly used as an end point of tissue outcome in stroke trials; however, the reported volumes are most commonly derived from early follow-up imaging. Those volumes are significantly impaired by ischemic edema, which causes an overestimation of the true final lesion volume. As net water uptake within ischemic brain can be quantified densitometrically in computed tomography (CT) as recently described, we hypothesized that the final lesion volume can be better estimated by correcting the lesion volume in early follow-up for the corresponding proportion of edema. After retrospective consecutive screening of the local registry, 20 patients with acute middle cerebral artery large vessel occlusion met the inclusion criteria with early and late follow-up CT; the latter acquired at least 4 weeks after admission. In early follow-up imaging 24 hours after onset, the proportion of edema contributing to the infarct lesion was calculated by quantifying the total volume of ischemic net water uptake. Edema volume was then subtracted from the total lesion volume to obtain edema-corrected lesion volumes. Finally, these corrected lesion volumes were compared with the final lesion volume on late follow-up serving as ground truth. The median lesion volume in the early follow-up was 115.1 mL (range, 21.9-539.9 mL) and significantly exceeded the median final lesion volume in the late follow-up CT, which was 86.6 mL (range, 11.2-399.0 mL; p < 0.001). The calculated mean proportion of edema within the early lesion volume was 25.8% (±5.9%; range, 11.1%-35.9%. The median edema-corrected lesion volume measured after 24 hours was 87.1 mL (range, 18.2-376.3 mL). The estimation of final lesion volume in the early follow-up CT was therefore improved by a mean of 31.4% (±2.1%) when correcting for the proportion of edema and did not differ significantly from the true final infarct volume (p = 0.2). Edema-corrected volumes of early follow-up infarct lesion in CT were in close agreement with the actual final infarct volumes. Computed tomography-based edema correction of subacute infarct lesions improves the estimation of final tissue outcome. This could especially improve the comparability of imaging end points and facilitate patient recruitment in clinical trials.

Ventriculoscopic Surgery for Cystic Retrochiasmatic Craniopharyngiomas: Indications, Surgical Technique, and Short-Term Patient Outcomes.

Attempted gross-total resection for the management of cystic retrochiasmatic craniopharyngiomas can cause severe hypothalamic dysfunction and decrease overall survival. Ventriculoscopic surgery is a minimally invasive alternative; however, potential indications and technique have not been well defined. To present our indications and technique for the ventriculoscopic treatment of cystic retrochiasmatic craniopharyngiomas. We evaluated all patients with retrochiasmatic craniopharyngiomas for ventriculoscopic surgery. Indications and operative technique were developed to minimize operative morbidity, relieve mass effect, and optimize functional outcome. Cyst size and functional outcomes were statistically evaluated to determine radiographic and short-term clinical outcome. Indications for ventriculoscopic surgery included (1) radiographic evidence of hypothalamic involvement and (2) major cystic component. Ten patients met indications, and mean follow-up was 2.5 ± 1.6 yr. The surgical technique included wide cyst fenestration at the foramen of Monro, and fenestration of inferior cyst wall/third ventriculostomy ("through-and-through" technique). Preoperative Karnofsky performance status was 70 ± 15 and was inversely correlated with preoperative cyst size (13 ± 13 cm3). A statistically significant reduction in cyst size was found on early postoperative imaging (2.1 ± 4.3 cm3). Seven patients received postoperative radiotherapy. Postoperative performance scores (81 ± 8.3) had improved; no patient suffered functional decline. Pre- and postoperative body mass indices were similar. No patient had short-term hypothalamic obesity. Ventriculoscopic surgery, with or without adjuvant treatments, can reduce early postoperative tumor volume and improve short-term functional status in cystic retrochiasmatic craniopharyngiomas with hypothalamic involvement; it should be considered a minimally invasive option in the multimodal treatment of craniopharyngiomas. Further studies are needed to determine long-term efficacy.

The Incidence and Risk Factors of Acute Kidney Disease after Total Knee Arthroplasty with Early Postoperative Volume Supplement.

Background Etiology of acute kidney disease (AKD) after total knee arthroplasty (TKA) was considered as multifactorial. However, the role of early postoperative volume supplement in AKD rate has not been investigated. The purpose of this study was to evaluate the incidence and risk factors of AKD in patients with early volume supplement following TKA. Methods This was a retrospective study with 458 patients who underwent unilateral TKA. All the patients received 6% tetrastarch, 7.5ml/kg, early in the postoperative period. Postoperative AKD was defined as the postoperative creatinine level ≥ 1.5 times compared with preoperative data. Potential variables associated with AKD were analyzed by multivariate logistic regression model to identify the AKD risk factors in TKA patients after early postoperative volume supplement. Results The AKD rate was 3.3% (15 patients) in all patients. Age (OR = 1.09; P = .031) and coronary artery disease (CAD) (OR = 3.63; P = .034) were associated with increased risk of development of postoperative AKD. Other comorbidities as hypertension, diabetes, and CKD were not statistically significant risk factors. Conclusion Our study demonstrated that age and CAD were independent risk factors of AKD in TKA patients. However, the common risk factors as hypertension, diabetes, and CKD were not significantly associated with AKD after TKA if early postoperative supplement of tetrastarch is administered.

Extended Release Liposomal Bupivacaine Injection (Exparel) for Early Postoperative Pain Control Following Palatoplasty.

Liposomal bupivacaine (LB) is a long-acting local anesthetic reported to decrease postoperative pain in adults. The authors demonstrate the safe use of LB in pediatric patients with improved pain control following palatoplasty. Retrospective patient series of all single-surgeon palatoplasty patients treated at a tertiary craniofacial center from August 2014 to December 2015 were included. All patients received 1.3% LB intraoperatively as greater palatal nerve and surgical field blocks in 2-flap V-Y pushback palatoplasty. Postoperative oral intake, opioids administered, duration of hospitalization, and FLACC (face, legs, activity, cry, consolability) pain scores were measured. Twenty-seven patients (16 males and 11 females, average age of 10.8 months, weight 8.8 kg) received 2.9 ± 0.9 mL (2.6 ± 1.9 mg/kg) 1.3% LB. Average FLACC scores were 2.4 ± 2.2/10 in the postanesthesia care unit and 3.8 ± 1.8/10 while inpatients. Oral intake was first tolerated 10.3 ± 11.5 hours postoperatively and tolerated 496.4 ± 354.2 mL orally in the first 24 hours postoperatively. Patients received 8.5 ± 8.4 mg hydrocodone equivalents (0.46 ± 0.45 mg/kg per d hydrocodone equivalents) and were discharged 2.1 ± 1.3 days postoperatively. Opioid-related adverse events included emesis in 7.4% and pruritis in 3.7% of patients. The LB may be used safely in pediatric patients. Intraoperative injection of LB during palatoplasty can yield low postoperative opioid use and an early and adequate volume of oral intake over an average hospital stay. Further cost-efficacy studies of LB are needed to assess its value in pediatric plastic surgery.

Effects of early diuretic response to carperitide in acute decompensated heart failure treatment: A single-center retrospective study.

BackgroundDiuretic response is a strong predictor of outcome for admitted patients of acute decompensated heart failure (ADHF). However, little is known about the effects of early diuretic response to carperitide.MethodsWe retrospectively analyzed records of 85 patients hospitalized for ADHF who received carperitide as initial treatment and <40 mg furosemide during the early period. The eligible patients were divided into good diuretic responder (GR) group and poor diuretic responder (PR) group on the basis of median urinary volume.ResultsThe PR group demonstrated older age, lower body mass index (BMI), lower estimated glomerular filtration rate, and higher blood urea nitrogen (BUN) level, left ventricular ejection fraction, and β-blockers prescribed at baseline than the GR group. The incidence of worsening renal function (WRF) was significantly higher in the PR group than in the GR group. There was no correlation between early intravenous furosemide dose and urinary volume (Spearman correlation, ρ = 0.111, p = 0.312). Multivariate analysis showed that the statistically significant independent factors associated with poor diuretic response to carperitide were BMI (Odds ratio (OR) = 0.82, 95% confidence interval (CI) 0.68–0.94, p = 0.004) and BUN (OR = 1.07, 95%CI 1.01–1.15, p = 0.018). Kaplan–Meier analysis indicated a lower event-free rate in the PR group than in the GR group (log-rank, p = 0.007).ConclusionsBMI and BUN levels on admission were significant determinants of early poor diuretic response to carperitide. Early poor diuretic response to carperitide was associated with future poor outcomes.

Shock subtypes by left ventricular ejection fraction following out-of-hospital cardiac arrest

BackgroundPost-resuscitation hemodynamic instability following out-of-hospital cardiac arrest (OHCA) may occur from myocardial dysfunction underlying cardiogenic shock and/or inflammation-mediated distributive shock. Distinguishing the predominant shock subtype with widely available clinical metrics may have prognostic and therapeutic value.MethodsA two-hospital cohort was assembled of patients in shock following OHCA. Left ventricular ejection fraction (LVEF) was assessed via echocardiography or cardiac ventriculography within 1 day post arrest and used to delineate shock physiology. The study evaluated whether higher LVEF, indicating distributive-predominant shock physiology, was associated with neurocognitive outcome (primary endpoint), survival, and duration of multiple organ failures. The study also investigated whether volume resuscitation exhibited a subtype-specific association with outcome.ResultsOf 162 patients with post-resuscitation shock, 48% had normal LVEF (> 40%), consistent with distributive shock physiology. Higher LVEF was associated with less favorable neurocognitive outcome (OR 0.74, 95% CI 0.58–0.94 per 10% increase in LVEF; p = 0.01). Higher LVEF also was associated with worse survival (OR 0.81, 95% CI 0.67–0.97; p = 0.02) and fewer organ failure-free days (β = – 0.67, 95% CI – 1.28 to − 0.06; p = 0.03). Only 51% of patients received a volume challenge of at least 30 ml/kg body weight in the first 6 h post arrest, and the volume received did not differ by LVEF. Greater volume resuscitation in the first 6 h post arrest was associated with favorable neurocognitive outcome (OR 1.59, 95% CI 0.99–2.55 per liter; p = 0.03) and survival (OR 1.44, 95% CI 1.02–2.04; p = 0.02) among patients with normal LVEF but not low LVEF.ConclusionsIn post-resuscitation shock, higher LVEF—indicating distributive shock physiology—was associated with less favorable neurocognitive outcome, fewer days without organ failure, and higher mortality. Greater early volume resuscitation was associated with more favorable neurocognitive outcome and survival in patients with this shock subtype. Additional studies with repeated measures of complementary hemodynamic parameters are warranted to validate the clinical utility for subtyping post-resuscitation shock.

Serum levels of omentin-1 association with early diagnosis, lesion volume and severity of acute ischemic stroke

ObjectiveThis study was aimed to explore whether the omentin-1, a novel adipokine marker, could be a biomarker for stroke, as well as its association with stroke severity. MethodsThis study included 239 patients with ischemic stroke. The serum omentin-1 level was determined and the stroke was evaluated when the patients were hospitalized. The control groups consisted of 108 patients with matched age, gender and prior vascular risk factors and 120 health control with matched age and gender. The stroke severity was assessed with National Institutes of Health Stroke Scale (NIHSS) when the patients were hospitalized, and NIHSS score > 6 was evaluated as moderate-to-severe stroke. ResultsOmentin-1 level in serum samples of 239 stroke patients was determined, with the median value of 109.5 ng/ml [Inter Quartile Range (IQR), 78.4–142.9 ng/ml]. There was a negative relation between omentin-1 level and the infarct volume (r = −0.289, P = 0.001). The level of omentin-1 was significantly reduced in stroke patients than that of in control group 1 [125.3 (IQR, 95.8–158.7); P = 0.002] and control group 2 [146.5 (IQR, 116.2–177.3); P < 0.001]. With the analysis of multivariate model, omentin-1 as a continuous variable was related to lowered stroke risk (odds ratios [OR] 0.994, 95% confidence interval (CI): 0.990–0.998; P = 0.006). In addition, omentin-1 was an independent indicator for stroke severity (OR 0.992, 95% CI: 0.989–0.996). Levels of omentin-1 in the Q1 showed a relative risk of 2.66 (95% CI: 1.52–4.18) for moderate-to-severe stroke after adjusting for above possible confounders compared to reference category [Quartile (Q): 2–4]. ConclusionThe data indicated a negative relation between omentin-1 level and risk of ischemic stroke. The omentin-1 could be promising indicator of stroke and its severity.

‘MILK VOLUME, MILK FAT AND CHILDHOOD FRACTURE RISK

Abstract BACKGROUND Children who do not consume cow’s milk have been associated with an increased risk of fracture. Cow’s milk is consumed by most North American children yet the relationships between the volume of cow’s milk consumed, the fat content of cow’s milk and childhood fracture risk are unclear. OBJECTIVES The primary objective was to evaluate whether volume of cow’s milk consumed between ages 1 - 3 was associated with fracture between ages 3 - 10. Secondary objectives explored whether milk-fat consumed between ages 1 - 3 was associated with fracture between ages 3 - 10 and whether milk-fat content modified the relationship between milk volume and fracture. DESIGN/METHODS This was a prospective analysis of 2466 healthy urban children with exposure between 1 and 3 years of age and outcome between 3 and 10 years of age enrolled in the TARGet Kids! -Applied Research Group for Kids cohort. The primary exposure was the volume of cow’s milk consumed and the secondary exposure was the average percentage of milk-fat consumed by each child. The outcome was one or more fractures experienced, measured as yes or no. A modified Poisson regression was used to evaluate the relationship between volume of cow’s milk at exposure, and one or more fractures at outcome. The same analysis was used to explore the relationship between cow’s milk-fat and fracture. Effect modification by milk-fat consumed on the relationship between milk volume and fracture risk was explored by adding an interaction term to the statistical model. RESULTS In the primary adjusted analysis, a statistically significant association between the volume of cow’s milk consumed at exposure and risk of one or more fractures at outcome was not observed (aRR= 1.04; 95% CI: 0.87 to 1.26). In the secondary analysis, a statistically significant association between cow’s milk-fat consumed at exposure and fracture risk at outcome was also not observed (aRR= 1.05; 95% CI: 0.84 to 1.31). Cow’s milk-fat did not modify the relationship between milk volume and risk of fracture. (p= 0.24). CONCLUSION In this prospective cohort study of young children, we did not identify a protective effect of early childhood volume of cow’s milk or milk-fat consumption on fracture risk in later childhood. Future research in young children is needed to evaluate specific low impact fracture mechanisms, which may be more sensitive to nutritional factors.

Heart volume reduction during radiotherapy involving the thoracic region in children: An unexplained phenomenon

Background and purposeRadiotherapy involving the thoracic region is associated with cardiotoxicity in long-term childhood cancer survivors. We quantified heart volume changes during radiotherapy in children (<18 years) and investigated correlations with patient and treatment related characteristics. Material and methodsBetween 2010 and 2016, 34 children received radiotherapy involving the thoracic region. We delineated heart contours and measured heart volumes on 114 CBCTs. Relative volume changes were quantified with respect to the volume on the first CBCT (i.e., 100%). Cardiac radiation dose parameters expressed as 2 Gy/fraction equivalent doses were calculated from DVHs. Chemotherapy was categorized as treatment with anthracyclines, alkylating agents, vinca-alkaloids, and other. ResultsThe overall median heart volume reduction from the first to the last CBCT was 5.5% (interquartile range1.6–9.7%; p < 0.001). Heart volumes decreased significantly between the baseline measurement and the first week (Bonferroni’s adjusted p = 0.002); volume changes were not significant during the following weeks. Univariate analysis showed a significant correlation between heart volume reduction and alkylating agents; however, no multivariate analyses could be done to further confirm this. ConclusionsWe found a significant heart volume reduction in children during radiotherapy. Elucidation of underlying mechanisms, clinical relevance, and possible long-term consequences of early heart volume reduction require a prospective follow-up study.

Early life predictors of brain development at term-equivalent age in infants born across the gestational age spectrum

BackgroundIt is well established that preterm infants have altered brain development compared with full-term (FT; ≥37 weeks' gestational age [GA]) infants, however the perinatal factors associated with brain development in preterm infants have not been fully elucidated. In particular, perinatal predictors of brain development may differ between very preterm infants (VP; <32 weeks' GA) and infants born moderate (MP; 32–33 weeks' GA) and late (LP; 34–36 weeks' GA) preterm, but this has not been studied. This study aimed to investigate the effects of early life predictors on brain volume and microstructure at term-equivalent age (TEA; 38–44 weeks), and whether these effects differ for GA groups (VP, MP, LP or FT). MethodsStructural images from 328 infants (91 VP, 63 MP, 104 LP and 70 FT) were segmented into white matter, cortical grey matter, cerebrospinal fluid, subcortical grey matter, brainstem and cerebellum. Cortical grey matter and white matter images were analysed using voxel-based morphometry. Fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD) and radial diffusivity (RD) images from 361 infants (92 VP, 69 MP, 120 LP and 80 FT) were analysed using Tract-Based Spatial Statistics. Relationships between early life predictors (birthweight standard deviation score [BWSDS], multiple birth, sex, postnatal growth and social risk) and global brain volumes were analysed using linear regressions. Relationships between early life predictors and regional brain volumes and diffusion measures were analysed using voxelwise non-parametric permutation testing. ResultsMale sex was associated with higher global volumes of all tissues and higher regional volumes throughout much of the cortical grey matter and white matter, particularly in the FT group. Male sex was also associated with lower FA and higher AD, RD and MD in the optic radiation, external and internal capsules and corona radiata, and these associations were generally similar between GA groups. Higher BWSDS was associated with higher global volumes of all tissues and higher regional volumes in much of the cortical grey matter and white matter in all GA groups, as well as higher FA and lower RD and MD in many major tracts (corpus callosum, optic radiation, internal and external capsules and corona radiata), particularly in the MP and LP groups. Multiple birth and social risk also showed associations with global and regional volumes and regional diffusion values which varied by GA group, but these associations were not independent of the other early life predictors. Postnatal growth was not associated with brain volumes or diffusion values. ConclusionEarly life predictors of brain volumes and microstructure at TEA include sex, BWSDS, multiple birth and social risk, which have different effects based on GA group at birth. This study improves knowledge of the perinatal factors associated with brain abnormalities in infants born across the prematurity spectrum.

Nutrient- and Climate-Induced Shifts in the Phenology of Linked Biogeochemical Cycles in a Temperate Estuary

The response of estuarine ecosystems to long-term changes in external forcing is strongly mediated by interactions between the biogeochemical cycling of carbon, oxygen, and inorganic nutrients. Although long-term changes in estuaries are often assessed at the annual scale, phytoplankton biomass, dissolved oxygen concentrations, and biogeochemical rate processes have strong seasonal cycles at temperate latitudes. Thus, changes in the seasonal timing, or phenology, of these key processes can reveal important features of long-term change and help clarify the nature of coupling between carbon, oxygen, and nutrient cycles. Changes in the phenology of estuarine processes may be difficult to assess, however, because many organisms are mobile and migratory, key primary and secondary producers have relatively rapid physiological turnover rates, sampling in time and space is often limited, and physical processes may dominate variability. To overcome these challenges, we have analyzed a 32-year record (1985-2016) of relatively frequent and consistent measurements of chlorophyll-a, dissolved oxygen, nitrogen, and physical drivers to understand long-term change in Chesapeake Bay. Using a suite of metrics that directly test for altered phenology, we quantified changes in the seasonal timing of key biogeochemical events, which allowed us to illustrate spatially- and seasonally-dependent shifts in the magnitude of linked biogeochemical parameters. Specifically, we found that a modest reduction in nitrate input was linked to a suppression of spring phytoplankton biomass in seaward Bay regions. This was, in turn, associated with an earlier breakup in hypoxia and decline in late-summer NH4+ accumulation in seaward waters. In contrast, we observed an increase in winter phytoplankton biomass in landward regions, which was associated with elevated early summer hypoxic volumes and NH4+ accumulation. Seasonal shifts in oxygen depletion and NH4+ accumulation are consistent with reduced nitrogen inputs, spatial patterns of chlorophyll-a, and increases in temperature. In addition, these increases have likely elevated rates of organic matter degradation, thus “speeding-up” the typical seasonal cycle. The causes for the recent landward shift in phytoplankton biomass and NH4+ accumulation are less clear; however, these altered patterns are analyzed here and discussed in terms of numerous physical, climatic, and biological changes in the estuary.

Longitudinal development of hippocampal subregions from childhood to adulthood

Detailed descriptions of the development of the hippocampus promise to shed light on the neural foundation of development of memory and other cognitive functions, as well as the emergence of major mental disorders. Hippocampus is a heterogeneous structure with a well characterized internal complexity, but development of its distinct subregions in humans has remained poorly described. We analyzed magnetic resonance imaging (MRI) data from a large longitudinal sample (270 participants, 678 scans) using an automated segmentation tool and mixed models to delineate the development of hippocampal subregion volumes from childhood to adulthood. We also examined sex differences in subregion volumes and their development, and associations between hippocampal subregions and general cognitive ability. Nonlinear developmental trajectories with early volume increases were observed for subiculum, cornu ammonis (CA) 1, molecular layer (ML) and fimbria. In contrast, parasubiculum, presubiculum, CA2/3, CA4 and the granule cell layer of the dentate gyrus (GC-DG) showed linear volume decreases. No sex differences were found in hippocampal subregion development. Finally, general cognitive ability was positively associated with CA2/3 and CA4 volumes, as well as with ML development. In conclusion, hippocampal subregions appear to develop in diversified ways across adolescence, and specific subregions may link to general cognitive level.

Could early tumour volume changes assessed on morphological MRI predict the response to chemoradiation therapy in locally-advanced rectal cancer?

To investigate the potential role of an additional magnetic resonance imaging (MRI) examination performed during neoadjuvant chemoradiation therapy (CRT) in the prediction of pathological response in locally advanced rectal cancer (LARC). Forty-eight consecutive patients with LARC underwent neoadjuvant CRT. MRI studies at 1.5 T, including high-resolution T2-weighted sequences that were acquired parallel and perpendicular to the main axis of the tumour were performed before (preMRI), during (midMRI), and 6-8 weeks after the end of CRT (postMRI). Cancer volumes (Vpre, Vmid, Vpost) were drawn manually and the reduction rate calculated (ΔVmid, ΔVpost). According to Rödel's pathological tumour regression grade (TRG), patients were considered non-responders (NR; TRG0-2), partial responders (PR; TRG3), and complete responders (CR; TRG4). Multivariate regression analysis was performed to identify the best MRI predictors of NR, PR, and CR. Twenty-five patients were considered PR (52%), 13 CR (27%), and 10 NR (22%). Tumour shrinkage mainly occurred shortly after CRT (ΔVmid: CR: 80±10% versus PR: 56±19% versus NR: 28±22%, p=2.2×10-16). Vmid, Vpost, ΔVmid, and ΔVpost correlated with TRG (p<0.001). At multivariate analysis, the combined assessment of Vmid and ΔVmid was selected as the best predictor of response to CRT, in that it distinguishes CR, PR, and NR early and accurately (81.5%). MidMRI allows final response assessment to neoadjuvant CRT earlier and better than the MRI performed after the end of CRT. MRI findings at midMRI may be useful to tailor patient treatment.

Visual–motor integration and fine motor skills at 6½ years of age and associations with neonatal brain volumes in children born extremely preterm in Sweden: a population-based cohort study

ObjectivesThis exploratory study aimed to investigate associations between neonatal brain volumes and visual–motor integration (VMI) and fine motor skills in children born extremely preterm (EPT) when they reached 6½ years...

Effects of application of pulse contour cardiac output monitoring technology in early treatment of patients with large area burns

Objective: To analyze the changes and relationship of early hemodynamic indexes of patients with large area burns monitored by pulse contour cardiac output (PiCCO) monitoring technology, so as to assess the guiding value of this technology in the treatment of patients with large area burns during shock period. Methods: Eighteen patients with large area burns, confirming to the study criteria, were admitted to our unit from May 2016 to May 2017. Pulse contour cardiac output index (PCCI), systemic vascular resistance index (SVRI), global end-diastolic volume index (GEDVI), and extravascular lung water index (EVLWI) of patients were monitored by PiCCO instrument from admission to post injury day (PID) 7, and they were calibrated and recorded once every four hours. The fluid infusion coefficients of patients at the first and second 24 hours post injury were calculated. The blood lactic acid values of patients from PID 1 to 7 were also recorded. The correlations among PCCI, SVRI, and GEDVI as well as the correlation between SVRI and blood lactic acid of these 18 patients were analyzed. Prognosis of patients were recorded. Data were processed with one-way analysis of variance, single sample ttest and Bonferroni correction, Pearson correlation analysis, and Spearman rank correlation analysis. Results: (1) There was statistically significant difference in PCCI value of patients from post injury hour (PIH) 4 to 168 (F=7.428, P<0.01). The PCCI values of patients at PIH 4, 8, 12, 16, 20, and 24 were (2.4±0.9), (2.6±1.2), (2.2±0.6), (2.6±0.7), (2.8±0.6), and (2.7±0.7) L·min(-1)·m(-2,) respectively, and they were significantly lower than the normal value 4 L·min(-1)·m(-2)(t=-3.143, -3.251, -11.511, -8.889, -6.735, -6.976, P<0.05 or P<0.01). At PIH 76, 80, 84, 88, 92, and 96, the PCCI values of patients were (4.9±1.5), (5.7±2.0), (5.9±1.7), (5.5±1.3), (5.3±1.1), and (4.9±1.4) L·min(-1)·m(-2,) respectively, and they were significantly higher than the normal value (t=2.277, 3.142, 4.050, 4.111, 4.128, 2.423, P<0.05 or P<0.01). The PCCI values of patients at other time points were close to normal value (P>0.05). (2) There was statistically significant difference in SVRI value of patients from PIH 4 to 168 (F=7.863, P<0.01). The SVRI values of patients at PIH 12, 16, 20, 24, and 28 were (2 298±747), (2 581±498), (2 705±780), (2 773±669), and (3 109±1 215) dyn·s·cm(-5)·m(2,) respectively, and they were significantly higher than the normal value 2 050 dyn·s·cm(-5)·m(2)(t=0.878, 3.370, 2.519, 3.747, 3.144, P<0.05 or P<0.01). At PIH 4, 8, 72, 76, 80, 84, 88, 92, and 96, the SVRI values of patients were (1 632±129), (2 012±896), (1 381±503), (1 180±378), (1 259±400), (1 376±483), (1 329±385), (1 410±370), and (1 346±346) dyn·s·cm(-5)·m(2,) respectively, and they were significantly lower than the normal value (t=-4.593, -0.112, -5.157, -8.905, -7.914, -5.226, -6.756, -6.233, -7.038, P<0.01). The SVRI values of patients at other time points were close to normal value (P>0.05). (3) There was no statistically significant difference in the GEDVI values of patients from PIH 4 to 168 (F=0.704, P>0.05). The GEDVI values of patients at PIH 8, 12, 16, 20, and 24 were significantly lower than normal value (t=-3.112, -3.554, -2.969, -2.450, -2.476, P<0.05). The GEDVI values of patients at other time points were close to normal value (P>0.05). (4) There was statistically significant difference in EVLWI value of patients from PIH 4 to 168 (F=1.859, P<0.01). The EVLWI values of patients at PIH 16, 20, 24, 28, 32, 36, and 40 were significantly higher than normal value (t=4.386, 3.335, 6.363, 4.391, 7.513, 5.392, 5.642, P<0.01). The EVLWI values of patients at other time points were close to normal value (P>0.05). (5) The fluid infusion coefficients of patients at the first and second 24 hours post injury were 1.90 and 1.39, respectively. The blood lactic acid values of patients from PID 1 to 7 were 7.99, 5.21, 4.57, 4.26, 2.54, 3.13, and 3.20 mmol/L, respectively, showing a declined tendency. (6) There was obvious negative correlation between PCCI and SVRI (r=-0.528, P<0.01). There was obvious positive correlation between GEDVI and PCCI (r=0.577, P<0.01). There was no obvious correlation between GEDVI and SVRI (r=0.081, P>0.05). There was obvious positive correlation between blood lactic acid and SVRI (r=0.878, P<0.01). (7) All patients were cured except the one who abandoned treatment. Conclusions: PiCCO monitoring technology can monitor the changes of early hemodynamic indexes and volume of burn patients dynamically, continuously, and conveniently, and provide valuable reference for early-stage comprehensive treatment like anti-shock of patients with large area burns.

Monitoring early changes in rectal tumor morphology and volume during 5 weeks of preoperative chemoradiotherapy – An evaluation with sequential MRIs

PurposeTo assess early changes in rectal tumor volume and morphology on sequential MRIs performed during 5 weeks of chemoradiotherapy. Materials and methodsThirteen patients underwent weekly T2W-MRI during 5 weeks of preoperative radiotherapy (total 50 Gy), starting after the first week of radiation. Two radiologists visually evaluated tumor volume and morphology and one reader manually segmented tumors for each time point to quantitatively calculate tumor volumes. Evolution in tumor volume/morphology was assessed over time and compared between good responders (tumor regression grade (TRG) 1–2) and poor responders (TRG 3–5). ResultsTumor volumes decreased significantly during radiation. Early signs of response were also visually apparent: in the majority of good responders an early fibrotic transformation (week 2–3) as well as a visually estimated early volume reduction of >1/3 (week 1–2), was observed while these early changes only occurred in a minority of poor responders. ConclusionResults of this exploratory pilot study suggest that changes in rectal tumor morphology (fibrosis) and volume can already be observed early during radiation, both when measured quantitatively and when assessed visually. These changes appear to be indicative of the final treatment outcome.