Sarcopenia and myosteatosis are associated with survival in patients receiving immunotherapy for advanced hepatocellular carcinoma.

OBJECTIVES: To investigate the association of sarcopenia, myosteatosis, and sarcopenic obesity with survival outcomes among patients who underwent immunotherapy for advanced hepatocellular carcinoma (HCC). METHODS: In this retrospective analysis, patients who initiated immunotherapy for advanced HCC were enrolled. Sarcopenia and myosteatosis were evaluated on pretreatment CT at L3 level by skeletal muscle index and mean muscle attenuation using predefined cutoff values. Sarcopenic obesity was defined as concurrent sarcopenia and body mass index > 25 kg/m2. The log-rank test and the Cox proportional hazards model were used to compare overall survival (OS) and progression-free survival (PFS). RESULTS: A total of 138 patients was included (discovery cohort n = 111, validation cohort n = 27). In the discovery cohort, patients with sarcopenia exhibited significantly poorer PFS (p = 0.048) and OS (p = 0.002) than patients without sarcopenia. Patients with myosteatosis exhibited significantly poorer PFS (p < 0.001) and OS (p < 0.001) than patients without myosteatosis. Patients with sarcopenic obesity compared to patients without sarcopenic obesity exhibited significantly poorer OS (p = 0.006) but not PFS (p = 0.31). In multivariate analysis adjusting for patient demographics, tumor extent, and liver function reserve, myosteatosis remained an independent predictor of poor PFS (p = 0.014) and OS (p = 0.007); sarcopenia remained an independent predictor for poor OS (p = 0.007). The prediction models for survival outcomes built by the discovery cohort showed similar performance in the validation cohort. CONCLUSIONS: Sarcopenia and myosteatosis are independent prognostic factors in patients who received immunotherapy for advanced HCC. KEY POINTS: • Sarcopenia and myosteatosis can be evaluated by CT at L3 level. • Sarcopenia, myosteatosis, and sarcopenic obesity were associated with poor survival outcomes in patients who underwent immunotherapy for advanced HCC. • Myosteatosis was an independent predictor of PFS and OS, and sarcopenia was independent for OS in these patients.

Kinematic magnetic resonance imaging for the evaluation of active motion of the mandibular condyle in patients with temporomandibular joint disorders.

PURPOSE: To explore the mandibular condylar movements in patients with temporomandibular joint (TMJ) disorders using kinematic magnetic resonance imaging (MRI). METHODS: We retrospectively recruited patients who were clinically diagnosed with internal derangement of the TMJ and referred to our center for MRI examination. The TMJ discs were categorized into normal disc (ND), anteriorly displaced disc (ADD), and disc with destruction (DD) groups using static images obtained in the closed-mouth view. The difference between the "open-mouth" and "closed-mouth" views on kinematic MRI was used to calculate the condylar translation and rotation. Two radiologists consensually performed the image readings and measurements. One-way analysis of variance and chi-squared test were used to compare the variables in the three groups. Pearson's correlation and general linear models were used to evaluate the correlation and differences between condylar translation and rotation in the three groups. RESULTS: This study included 98 TMJs from 54 patients. Twenty-six, 49, and 23 TMJs were classified as ND, ADD, and DD, respectively. Condylar rotation and translation demonstrated a significant correlation in all TMJs examined (r = 0.635, p < 0.001), with similar coefficients for all groups. The mean condylar translation in the ND group was greater than that in the ADD and DD groups (ND versus ADD: p = 0.003; ND versus DD: p = 0.002). However, the change in condylar rotation was not affected by the disc status (ND as reference; DD∗condylar translation: coefficient = 0.341, p = 0.332; ADD∗condylar translation: coefficient = -0.100, p = 0.696). CONCLUSION: Kinematic MRI studies revealed that TMJ condylar translation was correlated with its rotation for all disc statuses.

Computed tomography-based sarcopenia in patients receiving peritoneal dialysis: Correlation with lean soft tissue and survival.

BACKGROUND/PURPOSE: We evaluated whether the results of the computed tomography (CT)-based sarcopenia assessment were correlated with edema-free lean soft tissue (LST) and were associated with the prognosis of patients receiving peritoneal dialysis (PD). METHODS: We conducted a prospective cohort study and enrolled patients aged >20 years who started to undergo PD between February 2009 and February 2012. All patients underwent LST evaluation and non-contrast abdominal CT for assessing the total skeletal muscle (TSM) and psoas muscle (PM) indices at the level of the third lumbar vertebra. We analyzed the correlation between LST and CT assessment of muscle mass. Then we determined optimal sex-specific cutoff values for TSM-defined and PM-defined sarcopenia to predict mortality, aided by the maximally selected rank statistics. RESULTS: A total of 158 patients were enrolled, of whom 41 (25.9%) and 65 (41.1%) had sarcopenia based on the TSM and PM indices, respectively. LST was significantly strong correlated with TSM and PM indices (r = 0.517, p < 0.001 and r = 0.688, p < 0.001, respectively). In univariate and multivariate analyses after adjusting clinical and PD-related parameters, only patients with PM-defined sarcopenia had poorer survival than did those without (hazard ratio [HR]: 2.386, 95% confidence interval [CI]: 1.315-4.330), but patients with TSM-defined sarcopenia did not show a poorer survival (HR: 1.608, 95% CI: 0.860-3.006). CONCLUSION: Sarcopenia assessment based on CT was strongly correlated with LST and PM-defined sarcopenia indicated poor prognosis in patients receiving long-term PD.

Predictors of changes in preoperative tumor stage between dynamic computed tomography and gadoxetate disodium-enhanced magnetic resonance imaging for hepatocellular carcinoma.

BACKGROUND/PURPOSE: Gadoxetate disodium-enhanced magnetic resonance imaging (EOB-MRI) has a higher diagnostic accuracy for hepatocellular carcinoma (HCC) than computed tomography (CT). However, indications for performing EOB-MRI after dynamic CT are not well defined. Therefore, we investigated the clinical factors associated with changes in the preoperative tumor stage between dynamic CT and EOB-MRI. METHODS: A prospective cohort was conducted from January 2014 to December 2017. 156 adult patients with clinical suspicion of HCC before liver resection were enrolled and we retrospectively reviewed the images. The tumor staging was evaluated by dynamic CT and then EOB-MRI subsequently according to the TNM staging system. The changes in tumor stage between two modalities were identified, and the associated clinical factors were analyzed. RESULTS: A total of 99 patients were analyzed after excluding 57 patients. 20 patients (20.2%) had changes in tumor stage between dynamic CT and EOB-MRI. The change occurred only in early stage (T1 and T2 lesions) based on dynamic CT initially. Furthermore, in univariate and multivariate analyses, albumin-bilirubin (ALBI) grade 2 and log alpha-fetoprotein (AFP) levels were associated with changes in tumor staging by EOB-MRI than those without (50% vs. 9.9%, p < 0.001 and 2.04 ± 1.35 vs. 1.40 ± 1.16, p = 0.038, respectively). Patients with changes in tumor stage also exhibited higher 1-year recurrence rate and shorter recurrence-free survival. CONCLUSION: Changes in preoperative tumor stage between dynamic CT and EOB-MRI were associated with CT-defined early stage, ALBI grades, higher log AFP levels, and early recurrence.

An international expert opinion statement on the utility of PET/MR for imaging of skeletal metastases.

BACKGROUND: MR is an important imaging modality for evaluating musculoskeletal malignancies owing to its high soft tissue contrast and its ability to acquire multiparametric information. PET provides quantitative molecular and physiologic information and is a critical tool in the diagnosis and staging of several malignancies. PET/MR, which can take advantage of its constituent modalities, is uniquely suited for evaluating skeletal metastases. We reviewed the current evidence of PET/MR in assessing for skeletal metastases and provided recommendations for its use. METHODS: We searched for the peer reviewed literature related to the usage of PET/MR in the settings of osseous metastases. In addition, expert opinions, practices, and protocols of major research institutions performing research on PET/MR of skeletal metastases were considered. RESULTS: Peer-reviewed published literature was included. Nuclear medicine and radiology experts, including those from 13 major PET/MR centers, shared the gained expertise on PET/MR use for evaluating skeletal metastases and contributed to a consensus expert opinion statement. [18F]-FDG and non [18F]-FDG PET/MR may provide key advantages over PET/CT in the evaluation for osseous metastases in several primary malignancies. CONCLUSION: PET/MR should be considered for staging of malignancies where there is a high likelihood of osseous metastatic disease based on the characteristics of the primary malignancy, hight clinical suspicious and in case, where the presence of osseous metastases will have an impact on patient management. Appropriate choice of tumor-specific radiopharmaceuticals, as well as stringent adherence to PET and MR protocols, should be employed.

PET/MRI in Cervical Cancer: Associations Between Imaging Biomarkers and Tumor Stage, Disease Progression, and Overall Survival.

BACKGROUND: Positron emission tomography (PET)/MRI biomarkers have been shown to have prognostic significance in patients with cervical cancer. Their associations with progression-free survival (PFS) and overall survival (OS) merit further investigation. PURPOSE: To evaluate the association between PET/MRI biomarkers and tumor stage, PFS, and OS in patients with cervical cancer. STUDY TYPE: Prospective cohort study. POPULATION: In all, 54 patients with newly diagnosed cervical cancer and measurable tumors (>1 cm) were included in the image analysis. FIELD STRENGTH/SEQUENCE: 3.0T integrated PET/MRI including diffusion-weighted echo-planar imaging (b = 50 and 1000 s/mm2 ) and [18F]fluorodeoxyglucose PET. ASSESSMENT: Two radiologists measured the minimum and mean apparent diffusion coefficient (ADCmin and ADCmean ), maximum standardized uptake value (SUVmax ), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) of the primary tumors. STATISTICAL TESTS: A Mann-Whitney U-test was used to evaluate the association between the imaging biomarkers and tumor stage. A Cox proportional hazards model was used to assess the relationships between the imaging biomarkers and survival. RESULTS: In advanced tumors (T ≥ 1b2, M1, stage ≥ IB3), ADCmin was significantly lower and MTV, TLG, MTV/ADCmin , and TLG/ADCmin were significantly higher (P values between <0.001 and 0.036). In N1 tumors, ADCmin was significantly lower and MTV and MTV/ADCmin were significantly higher (P values between 0.005 and 0.016). In survival analysis, SUVmax was an independent predictor of PFS (hazard ratio [HR] = 4.57, P < 0.05), and ADCmin was an independent predictor of OS (HR = 0.02, P < 0.05). In subgroup analysis of patients with different stages, MTV/ADCmin was a predictor of PFS in stage I disease (P = 0.003), ADCmin (P = 0.038), and MTV (P = 0.020) in stage II, SUVmax (P = 0.006), and TLG (P = 0.006) in stage IV; and ADCmin was a predictor of OS in stage III disease (P = 0.008). DATA CONCLUSION: PET/MRI biomarkers of cervical cancer are associated with tumor stage and survival. SUVmax and ADCmin are independent predictors of PFS and OS, respectively. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY: 3.

Total skeletal, psoas and rectus abdominis muscle mass as prognostic factors for patients with advanced hepatocellular carcinoma.

PURPOSE: We investigated whether low skeletal muscle mass (LSMM) defined according to different muscle groups on computed tomography (CT) scans are predictive factors of survival for advanced hepatocellular carcinoma (HCC). METHODS: In this retrospective study, we analyzed patients who received sorafenib therapy for advanced HCC in a prospective patient cohort between 2007 and 2012. The total skeletal muscle (TSM), paraspinal muscle (PS), psoas muscle (PM), rectus abdominis (RA), and abdominal wall (AW) muscle areas were evaluated using a single CT slice at the third lumbar vertebra before treatment. LSMM was determined according to the TSM, PS, PM, RA and AW indices, which was calculated as the parameters divided by the square of the body height. RESULTS: We enrolled 137 patients. Women had significantly lower TSM index than men did (p < .001). Among men, the optimal cut points of the TSM, PM and RA indices for LSMM diagnosis were 39.1, 8.3 and 2.9 cm2/m2, respectively. Patients with LSMM defined by TSM (median 5.1 vs. 8.0 months, p = .007), PM (5.8 vs. 11.8 months, p < .001), and RA (7.2 vs. 8.1 months, p = .003) indices exhibited poorer overall survival than patients without LSMM. After adjusting for clinical variables, TSM (hazard ratio [HR]: 2.122, 95% confidence interval [CI]: 1.134-3.971) and PM (HR: 1.730, 95% CI: 1.058-2.828) indices-defined LSMM remained independent predictors for poor OS, but RA index-defined LSMM did not. CONCLUSION: LSMM defined by TSM and PM indices are independent predictors of poor prognosis for advanced HCC.

Long-term growth and bone development in children of HBV-infected mothers with and without fetal exposure to tenofovir disoproxil fumarate.

BACKGROUND & AIMS: Tenofovir disoproxil fumarate (TDF) is the preferred treatment to prevent maternal transmission of HBV, owing to its efficacy and safety. However, data are lacking on the long-term safety outcomes in children following fetal exposure to TDF. METHODS: Children participating in a prospective, multisite trial of maternal TDF treatment during late pregnancy were recruited for follow-up visits once a year. Growth parameters, serum biochemistry, HBV serology, and bone mineral density (BMD) by dual-energy x-ray absorptiometery scan were measured. RESULTS: One hundred and twenty-eight children, 71 in the TDF and 57 in the control group, completed 255 follow-up visits at the age of 2 to 7 (median, 4.08) years. No differences in z-scores for weight-for-age (0.26 ± 0.90 vs. 0.22 ± 0.99, p = 0.481), z-scores for height-for-age (0.20 ± 1.02 vs. 0.25 ± 0.98, p = 0.812), and estimated glomerular filtration rate (169.12 ± 50.48 vs. 169.06 ± 34.46 ml/min/1.73m2, p = 0.479) were detected. After adjustment for age, sex and HBV status by multiple linear regression, children in the TDF and control group had comparable levels of serum calcium, phosphorus, bone-specific alkaline phosphatase, calcidiol and BMD of lumbar spines (0.55 ± 0.01 vs. 0.57 ± 0.01 g/cm2, p = 0.159) and left hip (0.56 ± 0.01 vs. 0.56 ± 0.01 g/cm2, p = 0.926). CONCLUSIONS: Children of HBV-infected mothers who did or did not receive tenofovir disoproxil fumarate treatment during late pregnancy had comparable long-term growth, renal function, and bone development up to 6-7 years after delivery. CLINICAL TRIAL NUMBER: NCT01312012 (ClinicalTrials.gov) LAY SUMMARY: Currently there are insufficient long-term safety data in children born to mothers who took antiviral agents during pregnancy to prevent mother-to-infant transmission of hepatitis B virus (HBV). In this study, we found that children of HBV-infected mothers who did or did not receive tenofovir disoproxil fumarate treatment during late pregnancy had comparable long-term growth, renal function, and bone development up to 6-7 years after delivery.

Intravoxel Incoherent Motion Diffusion-weighted MRI of Infiltrated Marrow for Predicting Overall Survival in Newly Diagnosed Acute Myeloid Leukemia.

Background Acute myeloid leukemia (AML) features relatively low overall survival (OS). Intravoxel incoherent motion (IVIM) diffusion-weighted MRI separates tissue microcapillary perfusion and diffusivity and may have potential for helping to assess prognosis in infiltrated marrow disease apart from solid tumor. Thus, a study of overall survival would contribute to clarifying the value of IVIM for assessing long-term prognosis in AML. Purpose To determine whether the IVIM-derived parameters of infiltrated bone marrow may be associated with OS in newly diagnosed AML. Materials and Methods This prospective study enrolled participants with newly diagnosed AML between July 2014 to March 2016 consecutively. Participants underwent MRI of the lumbar spine by using an IVIM sequence. Participant clinical characteristics and OS were collected. The median of follow-up period was 20 months (range, 1-56 months). The IVIM parameters (pseudoperfusion fraction, f; diffusion coefficient, D; and pseudodiffusion coefficient, D*) were obtained. A nonparametric log-rank test was used to identify the threshold of IVIM parameters for OS. Univariable Kaplan-Meier and multivariable Cox proportional hazards regression analyses were performed to investigate prognostic significance of possible indicators. Results Fifty-three participants (mean age, 42 years ± 17; 30 men) were evaluated. Nonparametric log-rank test results showed that the thresholds of f and D values for OS were 31.0% and 0.2 × 10-3 mm2/sec, respectively. Univariable analyses indicated that high f value (>31.0%) and low D value (≤0.2 × 10-3 mm2/sec) were associated with shorter OS (P = .003 and .01, respectively). An f value greater than 31.0% (hazard ratio, 2.4; 95% confidence interval: 1.0, 5.6; P = .046) was associated with OS, independent of clinical confounders (age, karyotype, and white blood cell counts) in a multivariable analysis. Conclusion Pseudoperfusion fraction and diffusion coefficient from intravoxel incoherent motion diffusion-weighted MRI may be viable prognosis predictors of newly diagnosed acute myeloid leukemia. © RSNA, 2020.

Management implications of fluorodeoxyglucose positron emission tomography/magnetic resonance in untreated intrahepatic cholangiocarcinoma.

PURPOSE: Intrahepatic cholangiocarcinoma (ICC) is associated with a poor prognosis with surgical resection offering the best chance for long-term survival and potential cure. However, in up to 36% of patients who undergo surgery, more extensive disease is found at time of operation requiring cancellation of surgery. PET/MR is a novel hybrid technology that might improve local and whole-body staging in ICC patients, potentially influencing clinical management. This study was aimed to investigate the possible management implications of PET/MR, relative to conventional imaging, in patients affected by untreated intrahepatic cholangiocarcinoma. METHODS: Retrospective review of the clinicopathologic features of 37 patients with iCCC, who underwent PET/MR between September 2015 and August 2018, was performed to investigate the management implications that PET/MR had exerted on the affected patients, relative to conventional imaging. RESULTS: Of the 37 patients enrolled, median age 63.5 years, 20 (54%) were female. The same day PET/CT was performed in 26 patients. All patients were iCCC-treatment-naïve. Conventional imaging obtained as part of routine clinical care demonstrated early-stage resectable disease for 15 patients and advanced stage disease beyond the scope of surgical resection for 22. PET/MR modified the clinical management of 11/37 (29.7%) patients: for 5 patients (13.5%), the operation was cancelled due to identification of additional disease, while 4 "inoperable" patients (10.8%) underwent an operation. An additional 2 patients (5.4%) had a significant change in their operative plan based on PET/MR. CONCLUSIONS: When compared with standard imaging, PET/MR significantly influenced the treatment plan in 29.7% of patients with iCCC. TRIAL REGISTRATION: 2018P001334.

The roles of lumbar load thresholds in cumulative lifting exposure to predict disk protrusion in an Asian population.

BACKGROUND: The purpose of this study was to determine whether a specific threshold per lifting movement, the accumulation above which best predicts lumbar disk protrusion, exists or the total lifting load should be considered. METHODS: This was a retrospective study. Subjects with various lifting exposures were recruited. Disk protrusion was assessed by magnetic resonance imaging. The cumulative lifting load was defined as the sum of the time-weighed lumbar load for each job and was calculated using a biomechanical software system. The effectiveness of accumulation above different thresholds in predicting disk protrusion were compared using four statistical methods. RESULTS: A total of 252 men and 301 women were included in the final analysis. For the men, 3000 Newtons for each lifting task was the optimal threshold for predicting L4-S1 disk protrusion, whereas for the women, 2800 Newtons was optimal. CONCLUSIONS: Our findings suggested that for cumulative lifting exposure, including the total lifting load without defining a minimal exposure limit might not be the optimal method for predicting disk protrusion. The NIOSH 3400 Newton recommended limits do not appear to be the optimal thresholds for preventing disk protrusion. Different lifting thresholds might be needed for men and women in the workplace for their safety.

Multiparametric PET/MR imaging biomarkers are associated with overall survival in patients with pancreatic cancer.

PURPOSE: To correlate the overall survival (OS) with the imaging biomarkers of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI), diffusion-weighted imaging (DWI), magnetic resonance spectroscopy, and glucose metabolic activity derived from integrated fluorine 18 fluorodeoxyglucose positron emission tomography (18F-FDG PET)/MRI in patients with pancreatic cancer. METHODS: This prospective study was approved by the institutional review board and informed consent was obtained from all participants. Sixty-three consecutive patients (mean age, 62.7 ± 12 y; men/women, 40/23) with pancreatic cancer underwent PET/MRI before treatment. The imaging biomarkers were comprised of DCE-MRI parameters (peak, IAUC 60 , K trans , k ep , v e ), the minimum apparent diffusion coefficient (ADCmin), choline level, standardized uptake values, metabolic tumor volume, and total lesion glycolysis (TLG) of the tumors. The relationships between these imaging biomarkers with OS were evaluated with the Kaplan-Meier and Cox proportional hazard models. RESULTS: Seventeen (27%) patients received curative surgery, with the median follow-up duration being 638 days. Univariate analysis showed that patients at a low TNM stage (≦3, P = 0.041), high peak (P = 0.006), high ADCmin (P = 0.002) and low TLG (P = 0.01) had better OS. Moreover, high TLG/peak ratio was associated with poor OS (P = 0.016). Multivariate analysis indicated that ADCmin (P = 0.011) and TLG/peak ratio (P = 0.006) were independent predictors of OS after adjustment for age, gender, tumor size, and TNM stage. The TLG/peak ratio was an independent predictor of OS in a subgroup of patients who did not receive curative surgery (P = 0.013). CONCLUSION: The flow-metabolism mismatch reflected by the TLG/peak ratio may better predict OS than other imaging biomarkers from PET/MRI in pancreatic cancer patients.

Imaging biomarkers from multiparametric magnetic resonance imaging are associated with survival outcomes in patients with brain metastases from breast cancer.

OBJECTIVES: The aim of this study is to investigate the correlation of survival outcomes with imaging biomarkers from multiparametric magnetic resonance imaging (MRI) in patients with brain metastases from breast cancer (BMBC). METHODS: This study was approved by the institutional review board. Twenty-two patients with BMBC who underwent treatment involving bevacizumab on day 1, etoposide on days 2-4, and cisplatin on day 2 in 21-day cycles were prospectively enrolled for a phase II study. Three brain MRIs were performed: before the treatment, on day 1, and on day 21. Eight imaging biomarkers were derived from dynamic contrast-enhanced MRI (Peak, IAUC60, Ktrans, kep, ve), diffusion-weighted imaging [apparent diffusion coefficient (ADC)], and MR spectroscopy (choline/N-acetylaspartate and choline/creatine ratios). The relative changes (Δ) in these biomarkers were correlated with the central nervous system (CNS)-specific progression-free survival (PFS) and overall survival (OS) using the Kaplan-Meier and Cox proportional hazard models. RESULTS: There were no significant differences in the survival outcomes as per the changes in the biomarkers on day 1. On day 21, those with a low ΔKtrans (p = 0.024) or ΔADC (p = 0.053) reduction had shorter CNS-specific PFS; further, those with a low ΔPeak (p = 0.012) or ΔIAUC60 (p = 0.04) reduction had shorter OS compared with those with high reductions. In multivariate analyses, ΔKtrans and ΔPeak were independent prognostic factors for CNS-specific PFS and OS, respectively, after controlling for age, size, hormone receptors, and performance status. CONCLUSIONS: Multiparametric MRI may help predict the survival outcomes in patients with BMBC. KEY POINTS: • Decreased angiogenesis after chemotherapy on day 21 indicated good survival outcome. • ΔK trans was an independent prognostic factors for CNS-specific PFS. • ΔPeak was an independent prognostic factors for OS. • Multiparametric MRI helps clinicians to assess patients with BMBC. • High-risk patients may benefit from more intensive follow-up or treatment strategies.

Short-term costs of preeclampsia to the United States health care system.

BACKGROUND: Preeclampsia is a leading cause of maternal morbidity and mortality and adverse neonatal outcomes. Little is known about the extent of the health and cost burden of preeclampsia in the United States. OBJECTIVE: This study sought to quantify the annual epidemiological and health care cost burden of preeclampsia to both mothers and infants in the United States in 2012. STUDY DESIGN: We used epidemiological and econometric methods to assess the annual cost of preeclampsia in the United States using a combination of population-based and administrative data sets: the National Center for Health Statistics Vital Statistics on Births, the California Perinatal Quality Care Collaborative Databases, the US Health Care Cost and Utilization Project database, and a commercial claims data set. RESULTS: Preeclampsia increased the probability of an adverse event from 4.6% to 10.1% for mothers and from 7.8% to 15.4% for infants while lowering gestational age by 1.7 weeks (P < .001). Overall, the total cost burden of preeclampsia during the first 12 months after birth was $1.03 billion for mothers and $1.15 billion for infants. The cost burden per infant is dependent on gestational age, ranging from $150,000 at 26 weeks gestational age to $1311 at 36 weeks gestational age. CONCLUSION: In 2012, the cost of preeclampsia within the first 12 months of delivery was $2.18 billion in the United States ($1.03 billion for mothers and $1.15 billion for infants), and was disproportionately borne by births of low gestational age.

Early perfusion changes within 1 week of systemic treatment measured by dynamic contrast-enhanced MRI may predict survival in patients with advanced hepatocellular carcinoma.

OBJECTIVES: To correlate early changes in the parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) within 1 week of systemic therapy with overall survival (OS) in patients with advanced hepatocellular carcinoma (HCC). METHODS: Eighty-nine patients with advanced HCC underwent DCE-MRI before and within 1 week following systemic therapy. The relative changes of six DCE-MRI parameters (Peak, Slope, AUC, Ktrans, Kep and Ve) of the tumours were correlated with OS using the Kaplan-Meier model and the double-sided log-rank test. RESULTS: All patients died and the median survival was 174 days. Among the six DCE-MRI parameters, reductions in Peak, AUC, and Ktrans, were significantly correlated with one another. In addition, patients with a high Peak reduction following treatment had longer OS (P = 0.023) compared with those with a low Peak reduction. In multivariate analysis, a high Peak reduction was an independent favourable prognostic factor in all patients [hazard ratio (HR), 0.622; P = 0.038] after controlling for age, sex, treatment methods, tumour size and stage, and Eastern Cooperative Oncology Group performance status. CONCLUSIONS: Early perfusion changes within 1 week following systemic therapy measured by DCE-MRI may aid in the prediction of the clinical outcome in patients with advanced HCC. KEY POINTS: • DCE-MRI is helpful to evaluate perfusion changes of HCC after systemic treatment. • Early perfusion changes within 1 week after treatment may predict overall survival. • High Peak reduction was an independent favourable prognostic factor after systemic treatment.

Safety of gadobutrol in over 23,000 patients: the GARDIAN study, a global multicentre, prospective, non-interventional study.

OBJECTIVES: To investigate the safety and tolerability of gadobutrol at the recommended dose in patients requiring contrast-enhanced magnetic resonance imaging/angiography (MRI/MRA) in the routine setting. METHODS: GARDIAN prospectively enrolled 23,708 patients undergoing routine gadobutrol-enhanced MRI/MRA for approved indications at 272 study centres in Europe, Asia, North America, and Africa and monitored for adverse events. RESULTS: Median gadobutrol dose was 0.11 mmol/kg body weight. The overall incidence of adverse drug reactions (ADRs) was 0.7 % (n = 170 patients), with similar incidences in patients with renal impairment or cardiac disease, from different geographic regions and in different gadobutrol dose groups. Patients at risk for contrast media reaction had an ADR incidence of 2.5 %. Five patients (0.02 %) experienced serious adverse events, four were drug-related. One patient experienced a fatal anaphylactoid shock, assessed to be related to injection of gadobutrol. The contrast quality of gadobutrol-enhanced images was rated by treating physicians as good or excellent in 97 % cases, with similar ratings in all patient subgroups and indications. CONCLUSIONS: The GARDIAN study shows that gadobutrol at the recommended dose is well tolerated across a large, diverse patient population. KEY POINTS: • Gadobutrol at recommended dose shows low rates of adverse drug reactions • Gadobutrol demonstrates a uniform safety profile across diverse patient groups • Gadobutrol provides excellent contrast quality in routine practice.

Transcellular degradation of axonal mitochondria.

It is generally accepted that healthy cells degrade their own mitochondria. Here, we report that retinal ganglion cell axons of WT mice shed mitochondria at the optic nerve head (ONH), and that these mitochondria are internalized and degraded by adjacent astrocytes. EM demonstrates that mitochondria are shed through formation of large protrusions that originate from otherwise healthy axons. A virally introduced tandem fluorophore protein reporter of acidified mitochondria reveals that acidified axonal mitochondria originating from the retinal ganglion cell are associated with lysosomes within columns of astrocytes in the ONH. According to this reporter, a greater proportion of retinal ganglion cell mitochondria are degraded at the ONH than in the ganglion cell soma. Consistently, analyses of degrading DNA reveal extensive mtDNA degradation within the optic nerve astrocytes, some of which comes from retinal ganglion cell axons. Together, these results demonstrate that surprisingly large proportions of retinal ganglion cell axonal mitochondria are normally degraded by the astrocytes of the ONH. This transcellular degradation of mitochondria, or transmitophagy, likely occurs elsewhere in the CNS, because structurally similar accumulations of degrading mitochondria are also found along neurites in superficial layers of the cerebral cortex. Thus, the general assumption that neurons or other cells necessarily degrade their own mitochondria should be reconsidered.

Dynamic Contrast-enhanced MR Imaging of Advanced Hepatocellular Carcinoma: Comparison with the Liver Parenchyma and Correlation with the Survival of Patients Receiving Systemic Therapy.

Purpose To retrospectively compare the perfusion parameters of advanced hepatocellular carcinoma (HCC) measured with dynamic contrast material-enhanced (DCE) magnetic resonance (MR) imaging with surrounding liver parenchyma to determine the relationship between these parameters and uncensored overall survival (OS). Materials and Methods This retrospective study had institutional review board approval, and informed consent was waived. DCE MR imaging was performed in 92 patients with advanced HCC before systemic treatment was administered (19 patients received a placebo). Three semiquantitative (peak, slope, and area under the gadolinium concentration-time curve [AUC]) and six quantitative (arterial fraction, arterial flow, portal flow, total blood flow, distribution volume, and mean transit time) parameters were calculated by placing regions of interest in the largest area of the tumor and background liver parenchyma. The DCE MR imaging parameters between the tumor and normal liver were compared with paired Wilcoxon test. By using the Cox proportional hazards model for univariate and multivariate analyses, the association of DCE MR imaging parameters and OS was investigated. Results HCC demonstrated significantly higher peak, slope, AUC, arterial fraction, and arterial flow but lower portal flow, distribution volume, and mean transit time than did the background liver (all P < .05). Patients with high peak in the tumor had longer OS (P = .005) than did those with low peak. Cox multivariate analysis identified peak as an independent predictor of OS (P = .032) after adjusting for age, sex, treatment, tumor size, and portal vein thrombosis. Conclusion DCE MR imaging parameters can be used to differentiate advanced HCC from the background liver, and peak, a semiquantitative parameter, is associated with outcome in patients with advanced HCC before systemic therapy. © RSNA, 2016 An earlier incorrect version of this article appeared online. This article was corrected on July 22, 2016.

PET/MRI in pancreatic and periampullary cancer: correlating diffusion-weighted imaging, MR spectroscopy and glucose metabolic activity with clinical stage and prognosis.

PURPOSE: To correlate the clinical stage and prognosis of pancreatic or periampullary cancer with the imaging biomarkers on diffusion-weighted imaging, magnetic resonance spectroscopy and glucose metabolic activity derived from integrated PET/MRI. METHODS: This prospective study was approved by the institutional review board and informed consent was obtained. The study group comprised 60 consecutive patients with pancreatic or periampullary cancer who underwent PET/MRI before treatment. The imaging biomarkers were the minimal apparent diffusion coefficient (ADCmin), choline levels, standardized uptake values, metabolic tumour volume (MTV), and total lesion glycolysis (TLG) of the tumours. The relationships between these biomarkers and clinical TNM stage were evaluated using the Pearson test and the Mann-Whitney U test. The area under the receiver operating characteristic curve (AUROC) was used to evaluate accuracy. The correlation between the imaging biomarker and progression-free survival (PFS) was investigated using the Cox proportional hazards model. RESULTS: ADCmin was significantly lower in N1 and TNM stage 3+ tumours. Choline levels significantly higher in T4 tumours. TLG was significantly higher in T4, N1 and TNM stage 3+ tumours. MTV was significantly higher in T4, N1, M1, and TNM stage 3+ tumours (all P < 0.05). The MTV/ADCmin ratio exhibited the highest AUROC for predicting T4, N1, M1, and advanced TNM stages tumours, and was an independent predictor of PFS (P = 0.018) after adjustment for age, sex, tumour size and stage. CONCLUSION: The imaging biomarkers from integrated PET/MRI may predict clinical stage and PFS in patients with pancreatic or periampullary cancer.