Palliative care in the cardiovascular intensive care unit: A systematic review of current literature.

BACKGROUND: There has been an evolution in the disease severity and complexity of patients presenting to the cardiac intensive care unit (CICU). There are limited data evaluating the role of palliative care in contemporary CICU practice. METHODS: PubMed Central, CINAHL, EMBASE, Medline, Cochrane Library, Scopus, and Web of Science databases were evaluated for studies on palliative care in adults (≥18 years) admitted with acute cardiovascular conditions - acute myocardial infarction, cardiogenic shock, cardiac arrest, advanced heart failure, post-cardiac surgery, spontaneous coronary artery dissection, Takotsubo cardiomyopathy, and pulmonary embolism - admitted to the CICU, coronary care unit or cardiovascular intensive care unit from 1/1/2000 to 8/8/2022. The primary outcome of interest was the utilization of palliative care services. Secondary outcomes of included studies were also addressed. Meta-analysis was not performed due to heterogeneity. RESULTS: Of 5711 citations, 30 studies were included. All studies were published in the last seven years and 90 % originated in the United States. Twenty-seven studies (90 %) were retrospective analyses, with a majority from the National Inpatient Sample database. Heart failure was the most frequent diagnosis (47 %), and in-hospital mortality was reported in 67 % of studies. There was heterogeneity in the timing, frequency, and background of the care team that determined palliative care consultation. In two randomized trials, there appeared to be improvement in quality of life without an impact on mortality. CONCLUSIONS: Despite the growing recognition of the role of palliative care, there are limited data on palliative care consultation in the CICU.

Urinary Plasminogen as a Marker of Disease Progression in Human Glomerular Disease.

RATIONALE & OBJECTIVE: Glomerular disorders have a highly variable clinical course, and biomarkers that reflect the molecular mechanisms underlying their progression are needed. Based on our previous work identifying plasminogen as a direct cause of podocyte injury, we designed this study to test the association between urine plasmin(ogen) (ie, plasmin and its precursor plasminogen) and end-stage kidney disease (ESKD). STUDY DESIGN: Multicenter cohort study. SETTING & PARTICIPANTS: 1,010 patients enrolled in the CureGN Cohort with biopsy-proven glomerular disease (focal segmental glomerulosclerosis, membranous nephropathy, and immunoglobulin A nephropathy). PREDICTORS: The main predictor was urine plasmin(ogen) at baseline. Levels were measured by an electrochemiluminescent immunoassay developed de novo. Traditional clinical and analytical characteristics were used for adjustment. The ratio of urine plasmin(ogen)/expected plasmin(ogen) was evaluated as a predictor in a separate model. OUTCOME: Progression to ESKD. ANALYTICAL APPROACH: Cox regression was used to examine the association between urinary plasmin(ogen) and time to ESKD. Urinary markers were log2 transformed to approximate normal distribution and normalized to urinary creatinine (Log2uPlasminogen/cr, Log2 urinary protein/cr [UPCR]). Expected plasmin(ogen) was calculated by multiple linear regression. RESULTS: Adjusted Log2uPlasminogen/cr was significantly associated with ESKD (HR per doubling Log2 uPlasminogen/cr 1.31 [95% CI, 1.22-1.40], P<0.001). Comparison of the predictive performance of the models including Log2 uPlasminogen/cr, Log2 UPCR, or both markers showed the plasmin(ogen) model superiority. The ratio of measured/expected urine plasmin(ogen) was independently associated with ESKD: HR, 0.41 (95% CI, 0.22-0.77) if ratio<0.8 and HR 2.42 (95% CI, 1.54-3.78) if ratio>1.1 (compared with ratio between 0.8 and 1.1). LIMITATIONS: Single plasmin(ogen) determination does not allow for the study of changes over time. The use of a cohort of mostly white patients and the restriction to patients with 3 glomerular disorders limits the external validity of our analysis. CONCLUSIONS: Urinary plasmin(ogen) and the ratio of measured/expected plasmin(ogen) are independently associated with ESKD in a cohort of patients with glomerular disease. Taken together with our previous experimental findings, urinary plasmin(ogen) could be a useful biomarker in prognostic decision making and a target for the development of novel therapies in patients with proteinuria and glomerular disease. PLAIN-LANGUAGE SUMMARY: Glomerular diseases are an important cause of morbidity and mortality in patients of all ages. Knowing the individual risk of progression to dialysis or transplantation would help to plan the follow-up and treatment of these patients. Our work studies the usefulness of urinary plasminogen as a marker of progression in this context, since previous studies indicate that plasminogen may be involved in the mechanisms responsible for the progression of these disorders. Our work in a sample of 1,010 patients with glomerular disease demonstrates that urinary plasminogen (as well as the ratio of measured to expected plasminogen) is associated with the risk of progression to end-stage kidney disease. Urine plasminogen exhibited good performance and, if further validated, could enable risk stratification for timely interventions in patients with proteinuria and glomerular disease.

Increased levels of eIF2A inhibit translation by sequestering 40S ribosomal subunits.

eIF2A was the first eukaryotic initiator tRNA carrier discovered but its exact function has remained enigmatic. Uncharacteristic of translation initiation factors, eIF2A is reported to be non-cytosolic in multiple human cancer cell lines. Attempts to study eIF2A mechanistically have been limited by the inability to achieve high yield of soluble recombinant protein. Here, we developed a purification paradigm that yields ∼360-fold and ∼6000-fold more recombinant human eIF2A from Escherichia coli and insect cells, respectively, than previous reports. Using a mammalian in vitro translation system, we found that increased levels of recombinant human eIF2A inhibit translation of multiple reporter mRNAs, including those that are translated by cognate and near-cognate start codons, and does so prior to start codon recognition. eIF2A also inhibited translation directed by all four types of cap-independent viral IRESs, including the CrPV IGR IRES that does not require initiation factors or initiator tRNA, suggesting excess eIF2A sequesters 40S subunits. Supplementation with additional 40S subunits prevented eIF2A-mediated inhibition and pull-down assays demonstrated direct binding between recombinant eIF2A and purified 40S subunits. These data support a model that eIF2A must be kept away from the translation machinery to avoid sequestering 40S ribosomal subunits.

Gastric bypass alters diurnal feeding behavior and reprograms the hepatic clock to regulate endogenous glucose flux.

The molecular clock machinery regulates several homeostatic rhythms, including glucose metabolism. We previously demonstrated that Roux-en-Y gastric bypass (RYGB) has a weight-independent effect on glucose homeostasis and transiently reduces food intake. In this study we investigate the effects of RYGB on diurnal eating behavior as well as on the molecular clock and this clock's requirement for the metabolic effects of this bariatric procedure in obese mice. We find that RYGB reversed the high-fat diet-induced disruption in diurnal eating pattern during the early postsurgery phase of food reduction. Dark-cycle pair-feeding experiments improved glucose tolerance to the level of bypass-operated animals during the physiologic fasting phase (Zeitgeber time 2, ZT2) but not the feeding phase (ZT14). Using a clock gene reporter mouse model (mPer2Luc), we reveal that RYGB induced a liver-specific phase shift in peripheral clock oscillation with no changes to the central clock activity within the suprachiasmatic nucleus. In addition, we show that weight loss effects were attenuated in obese ClockΔ19 mutant mice after RYGB that also failed to improve glucose metabolism after surgery, specifically hepatic glucose production. We conclude that RYGB reprograms the peripheral clock within the liver early after surgery to alter diurnal eating behavior and regulate hepatic glucose flux.

Interobserver variation in clinical target volume (CTV) delineation for stereotactic radiotherapy to non-spinal bone metastases in prostate cancer: CT, MRI and PET/CT fusion.

BACKGROUND AND PURPOSE: The use of SBRT for the treatment of oligometastatic prostate cancer is increasing rapidly. While consensus guidelines are available for non-spinal bone metastases practice continues to vary widely. The aim of this study is to look at inter-observer variability in the contouring of prostate cancer non-spinal bone metastases with different imaging modalities. MATERIALS AND METHODS: 15 metastases from 13 patients treated at our centre were selected. 4 observers independently contoured clinical target volumes (CTV) on planning CT alone, planning CT with MRI fusion, planning CT with PET-CT fusion and planning CT with both MRI and PET-CT fusion combined. The mean inter-observer agreement on each modality was compared by measuring the delineated volume, generalized conformity index (CIgen), and the distance of the centre of mass (dCOM), calculated per metastasis and imaging modality. RESULTS: Mean CTV volume delineated on planning CT with MRI and PET-CT fusion combined was significantly larger compared to other imaging modalities (p = 0.0001). CIgen showed marked variation between modalities with the highest agreement between planning CT + PET-CT (mean CIgen 0.55, range 0.32-0.73) and planning CT + MRI + PET-CT (mean CIgen 0.59, range 0.34-0.73). dCOM showed small variations between imaging modalities but a significantly shorter distance found on planning CT + PET-CT when compared with planning CT + PET-CT + MRI combined (p = 0.03). CONCLUSIONS: Highest consistency in CTV delineation between observers was seen with planning CT + PET-CT and planning CT + PET-CT + MRI combined.

Oligoprogression in Metastatic, Castrate-Resistant Prostate Cancer-Prevalence and Current Clinical Practice.

Aims: Oligoprogression is poorly defined in current literature. Little is known about the natural history and significance of oligoprogression in patients with hormone-resistant prostate cancer on abiraterone or enzalutamide treatment [termed androgen receptor-targeted therapy (ARTT)]. The aim of this study was to determine the prevalence of oligoprogression, describe the characteristics of oligoprogression in a cohort of patients from a single center, and identify the number of patients potentially treatable with stereotactic body radiotherapy (SBRT). Methods: Castration-resistant prostate cancer (CRPC) patients who radiologically progressed while on ARTT were included. Patients with oligoprogressive disease (OPD) (≤3 lesions) on any imaging were identified in a retrospective analysis of electronic patient records. Kaplan-Meier method and log-rank test were used to calculate progression-free and overall survival. Results: A total of 102 patients with metastatic CRPC on ARTT were included. Thirty (29%) patients presented with oligoprogression (46 lesions in total); 21 (21% of total) patients had lesions suitable for SBRT. The majority of lesions were in the bone (21, 46%) or lymph nodes (15, 33%). Patients with oligoprogression while on ARTT had a significantly better prostate-specific antigen (PSA) response on commencing ARTT as compared to patients who later developed polyprogression. However, PSA doubling time immediately prior to progression did not predict OPD. Median progression-free survival to oligoprogression versus polyprogression was 16.8 vs. 11.7 months. Time to further progression after oligoprogression was 13.6 months in those treated with radiotherapy (RT) for oligoprogression vs. 5.7 months in those treated with the continuation of ARTT alone. Conclusions: In this study, nearly a third of patients on ARTT for CRPC were found to have OPD. OPD patients had a better PSA response on ART and a longer duration on ARTT before developing OPD as compared to those developing polyprogressive disease (Poly-PD). The majority of patients (70%) with OPD had lesions suitable for SBRT treatment. Prospective randomized control trials are needed to establish if there is a survival benefit of SBRT in oligoprogressive prostate cancer and to determine predictive indicators.

Bile Acid Malabsorption as a Consequence of Cancer Treatment: Prevalence and Management in the National Leading Centre.

The aim was to establish prevalence of bile acid malabsorption (BAM) and management in patients who underwent treatment for malignancy. Retrospective evaluation of data in patients seen within six months (August 2019-January 2020) was carried out. Demographic, nuclear medicine (Selenium Homocholic Acid Taurine (SeHCAT) scan result), clinical (previous malignancy, type of intervention (medication, diet), response to intervention) and laboratory (vitamin D, vitamin B12 serum levels) data were searched. In total, 265 consecutive patients were reviewed. Out of those, 87/265 (33%) patients (57 females, 66%) were diagnosed with BAM. Mean age was 59 +/- 12 years. The largest group were females with gynaecological cancer (35), followed by haematology group (15), colorectal/anal (13), prostate (9), upper gastrointestinal cancer (6), another previous malignancy (9). Severe BAM was most common in haematology (10/15; 67%) and gynaecological group (21/35; 60%). Medication and low-fat diet were commenced in 65/87 (75%), medication in 10/87 (11%), diet in 6/87 (7%). Colesevelam was used in 71/75 (95%). Symptoms improved in 74/87 (85%) patients. Vitamin D insufficiency/deficiency was diagnosed in 62/87 (71%), vitamin B12 deficiency in 39/87 (45%). BAM is a common condition in this cohort however treatments are highly effective.

Prospective Evaluation of Whole-Body MRI versus FDG PET/CT for Lesion Detection in Participants with Myeloma.

Purpose To compare disease detection of myeloma using contemporary whole-body (WB) MRI and fluorine 18 (18F) fluorodeoxyglucose (FDG) PET/CT protocols and to correlate imaging with laboratory estimates of disease burden, including molecular characteristics. Materials and Methods In this observational, prospective study, participants were recruited from November 2015 to March 2018 who had a diagnosis of myeloma, who were planned to undergo chemotherapy and autologous stem cell transplantation, and who underwent baseline WB-MRI and FDG PET/CT (ClinicalTrials.gov identifier NCT02403102). Baseline clinical data, including genetics, were collected. Paired methods were used to compare burden and patterns of disease. Results Sixty participants (mean age, 60 years ± 9 [standard deviation]; 35 men) underwent baseline WB-MRI and FDG PET/CT. WB-MRI showed significantly higher detection for focal lesions at all anatomic sites (except ribs, scapulae, and clavicles) and for diffuse disease at all sites. Two participants presented with two or more focal lesions smaller than 5 mm only at WB-MRI but not FDG PET/CT. Participants with diffuse disease at MRI had higher plasma cell infiltration (percentage of nucleated cells: median, 60% [interquartile range {IQR}, 50%-61%] vs 15% [IQR, 4%-50%]; P = .03) and paraprotein levels (median, 32.0 g/L [IQR, 24.0-48.0 g/L] vs 20.0 g/L [IQR, 12.0-22.6 g/L]; P = .02) compared with those without diffuse disease. All genetically high-risk tumors showed diffuse infiltration at WB-MRI. Conclusion WB-MRI helped detect a higher number of myeloma lesions than FDG PET/CT, and diffuse disease detected at WB-MRI correlated with laboratory measures of disease burden and molecular markers of risk. Keywords: MR-Imaging, Skeletal-Appendicular, Skeletal-Axial, Bone Marrow, Hematologic Diseases, Oncology Clinical trial registration no. NCT02403102. Supplemental material is available for this article. © RSNA, 2021.

The Ground State Electronic Energy of Benzene.

We report on the findings of a blind challenge devoted to determining the frozen-core, full configuration interaction (FCI) ground-state energy of the benzene molecule in a standard correlation-consistent basis set of double-ζ quality. As a broad international endeavor, our suite of wave function-based correlation methods collectively represents a diverse view of the high-accuracy repertoire offered by modern electronic structure theory. In our assessment, the evaluated high-level methods are all found to qualitatively agree on a final correlation energy, with most methods yielding an estimate of the FCI value around -863 mEH. However, we find the root-mean-square deviation of the energies from the studied methods to be considerable (1.3 mEH), which in light of the acclaimed performance of each of the methods for smaller molecular systems clearly displays the challenges faced in extending reliable, near-exact correlation methods to larger systems. While the discrepancies exposed by our study thus emphasize the fact that the current state-of-the-art approaches leave room for improvement, we still expect the present assessment to provide a valuable community resource for benchmark and calibration purposes going forward.

Impact of Ga-68-PSMA PET/CT on management in prostate cancer patients with very early biochemical recurrence after radical prostatectomy.

PURPOSE: With the availability of ultra-sensitive PSA assays, early biochemical relapse (eBCR) of prostate cancer is increasingly being detected at values much lower than the conventional threshold of 0.2 ng/ml. Accurate localisation of disease in this setting may allow treatment modification and improved outcomes, especially in patients with pelvis-confined or extra-pelvic oligometastasis (defined as up to three pelvic nodal or distant sites). We aimed to measure the detection rate of [68]Ga-PSMA-HBNED-CC (PSMA)-PET/CT and its influence on patient management in eBCR of prostate cancer following radical prostatectomy (RP). METHODS: We retrospectively identified 28 patients who underwent PSMA-PET/CT for post-RP eBCR (PSA < 0.5 ng/ml) at our tertiary care cancer centre. Two nuclear medicine physicians independently recorded the sites of PSMA-PET/CT positivity. Multidisciplinary meeting records were accessed to determine changes in management decisions following PSMA-PET/CT scans. RESULTS: The mean age of patients was 65.6 years (range: 50-76.2 years); median PSA was 0.22 ng/ml (interquartile range: 0.15 ng/ml to 0.34 ng/ml). Thirteen patients (46.4%) had received radiotherapy in the past. PSMA-PET/CT was positive in 17 patients (60.7%). Only one patient had polymetastasis (> 3 sites); the remainder either had prostatectomy bed recurrence (n = 2), pelvic oligometastasis (n = 10), or extra-pelvic oligometastasis (n = 4). PSMA-PET/CT resulted in management change in 12 patients (42.8%), involving stereotactic body radiotherapy (n = 6), salvage radiotherapy (n = 4), and systemic treatment (n = 2). CONCLUSIONS: Our findings show that PSMA-PET/CT has a high detection rate in the eBCR setting following RP, with a large proportion of patients found to have fewer than three lesions. PSMA-PET/CT may be of value in patients with early PSA failure, and impact on the choice of potentially curative salvage treatments.

Comparative Quantitative Lymph Node Assessment in Localized Esophageal Cancer Patients After R0 Resection With and Without Neoadjuvant Chemoradiation Therapy.

INTRODUCTION: The effects of neoadjuvant chemoradiation therapy on lymph node retrieval during esophagectomy for patients with esophageal cancer are unclear. The aim of this study was to quantify lymph node retrieval after R0 esophagectomy and to assess its impact on overall survival in induction therapy patients. METHODS: One hundred seventy-four consecutive patients underwent esophagectomy with or without induction therapy from 2008 to 2015 for esophageal cancer. Total lymph nodes, positive lymph nodes, and lymph node ratios were compared between two groups of patients: those treated with either upfront surgery or those treated with neoadjuvant chemoradiation therapy followed by surgery. Comparisons were made using Student's t test. Overall survival was obtained and compared using Kaplan Meier survival curves. RESULTS: Total lymph node counts were less in the induction therapy group (p = 0.027), while positive lymph node counts and lymph node ratios did not differ between groups (p = 0.262 and p = 0.310, respectively). In the neoadjuvant chemoradiation followed by surgery group, overall survival was significantly shorter for patients who had any positive lymph nodes in the pathologic specimen (p = 0.0065). CONCLUSIONS: Total lymph node counts were significantly lower in the induction therapy group, while positive lymph node counts and lymph node ratios did not differ from the upfront surgery group. Although overall survival was not different between groups, it was decreased within the induction therapy cohort among those who had any positive lymph nodes retrieved at surgery. This study confirms that unstratified gross lymph node counts do not substantially relate to prognosis in the heterogeneous population of locally advanced esophageal cancer patients who may or may not have had neoadjuvant chemoradiation.

Preliminary experience on the use of PET/CT in the management of pediatric post-transplant lymphoproliferative disorder.

INTRODUCTION: Post-transplant lymphoproliferative disorder (PTLD) is a well-known complication following prolonged immunosuppression. Contrary to other lymphomas, there is no standardized imaging approach to assess PTLD either at staging or for response to therapy. Positron emission tomography/computed tomography (PET/CT) is an imaging modality that has proven to be useful in lymphoma. However, there is still limited data concerning its use in pediatric PTLD. Our study evaluates the use of PET/CT in pediatric PTLD at our institution. METHODS: To assess the role of PET/CT in pediatric PTLD, we reviewed the pediatric patients with PTLD who had undergone PET/CT at our institution between 2000 and 2016. RESULTS: Nine patients were identified. Six had PET/CT at diagnosis. All lesions seen on CT were identified with PET/CT. Fourteen PET/CTs were done during treatment. Eight PET/CTs were negative, including three where CT showed areas of uncertain significance. In these cases, PET/CT helped us to stop treatment and the patients remain in remission after a long follow-up (mean 74.3 months; range 12.4-180.9 months). PET/CT revealed additional disease in two cases, therefore treatment was intensified. Six biopsies and close follow-up was done to confirm PET/CT results. In one case, PET/CT did not identify central nervous system involvement demonstrated on magnetic resonance imaging. CONCLUSION: PET/CT may have an important role in the staging and follow-up of pediatric PTLD. In our cohort, PET/CT was helpful in staging and assessing treatment response and in clarifying equivocal findings on other imaging modalities.

Objective comparison of lesion detectability in low and medium-energy collimator iodine-123 mIBG images using a channelized Hotelling observer.

Iodine-123 mIBG imaging is widely regarded as a gold standard for diagnostic studies of neuroblastoma and adult neuroendocrine cancer although the optimal collimator for tumour imaging remains undetermined. Low-energy (LE) high-resolution (HR) collimators provide superior spatial resolution. However due to septal penetration of high-energy photons these provide poorer contrast than medium-energy (ME) general-purpose (GP) collimators. LEGP collimators improve count sensitivity. The aim of this study was to objectively compare the lesion detection efficiency of each collimator to determine the optimal collimator for diagnostic imaging. The septal penetration and sensitivity of each collimator was assessed. Planar images of the patient abdomen were simulated with static scans of a Liqui-Phil™ anthropomorphic phantom with lesion-shaped inserts, acquired with LE and ME collimators on 3 different manufacturers' gamma camera systems (Skylight (Philips), Intevo (Siemens) and Discovery (GE)). Two-hundred normal and 200 single-lesion abnormal images were created for each collimator. A channelized Hotelling observer (CHO) was developed and validated to score the images for the likelihood of an abnormality. The areas under receiver-operator characteristic (ROC) curves, Az, created from the scores were used to quantify lesion detectability. The CHO ROC curves for the LEHR collimators were inferior to the GP curves for all cameras. The LEHR collimators resulted in statistically significantly smaller Azs (p < 0.05), of on average 0.891 ± 0.004, than for the MEGP collimators, 0.933 ± 0.004. In conclusion, the reduced background provided by MEGP collimators improved 123I mIBG image lesion detectability over LEHR collimators that provided better spatial resolution.

First-in-Human Phase 1 Trial of Agarose Beads Containing Murine RENCA Cells in Advanced Solid Tumors.

PURPOSE: Agarose macrobeads containing mouse renal adenocarcinoma cells (RMBs) release factors, suppressing the growth of cancer cells and prolonging survival in spontaneous or induced tumor animals, mediated, in part, by increased levels of myocyte-enhancing factor (MEF2D) via EGFR-and AKT-signaling pathways. The primary objective of this study was to determine the safety of RMBs in advanced, treatment-resistant metastatic cancers, and then its efficacy (survival), which is the secondary objective. METHODS: Thirty-one patients underwent up to four intraperitoneal implantations of RMBs (8 or 16 macrobeads/kg) via laparoscopy in this single-arm trial (FDA BB-IND 10091; NCT 00283075). Serial physical examinations, laboratory testing, and PET-CT imaging were performed before and three months after each implant. RESULTS: RMBs were well tolerated at both dose levels (mean 660.9 per implant). AEs were (Grade 1/2) with no treatment-related SAEs. CONCLUSION: The data support the safety of RMB therapy in advanced-malignancy patients, and the preliminary evidence for their potential efficacy is encouraging. A Phase 2 efficacy trial is ongoing.

Effects of Liver Transplantation on Lipids and Cardiovascular Disease in Children With Homozygous Familial Hypercholesterolemia.

Homozygous familial hypercholesterolemia (HoFH) is a rare, inherited, life-threatening, metabolic disorder of low-density lipoprotein (LDL) receptor function characterized by elevated serum LDL cholesterol (LDL-C) and rapidly progressive atherosclerotic cardiovascular disease (ACVD). Since LDL receptors are predominantly found on hepatocytes, orthotopic liver transplantation (OLT) has emerged as a viable intervention for HoFH because LDL receptor activity is restored. This study assessed the effects of OLT on ACVD and ACVD risk factors in pediatric patients with HoFH. We analyzed lipids, lipoproteins, body mass index, glucose, blood pressure, and cardiovascular imaging in 8 pediatric patients who underwent OLT for HoFH. Total serum cholesterol, LDL-C, lipoprotein (a), and apolipoprotein B/apolipoprotein A1 ratio decreased to normal values in all subjects (p values <0.001) at 1 month after OLT and were maintained for the length of follow-up (2 to 6 years). There were few complications related to surgery or immunosuppressive therapy. Two patients developed mild hypertension. In the first 4 subjects monitored for 4 to 6 years after OLT, coronary artery disease did not develop or progress except in 1 minor artery in 1 subject and actually regressed in 2 subjects with >50% stenosis. However, aortic valve stenosis progressed in 2 of 4 subjects. In conclusion, OLT is an effective therapeutic option for patients with HoFH with coronary artery disease and persistently elevated serum LDL-C despite maximum medical therapy. Aortic valvular disease may progress. Long-term data are needed to evaluate the true risk-benefit ratio of this surgical approach.

Additional Therapies to Improve Metastatic Response to Induction Therapy in Children With High-risk Neuroblastoma.

Children with high-risk neuroblastoma who fail to achieve adequate metastatic response after induction chemotherapy have dismal outcome and new therapeutic strategies are needed. However, timing of introduction of novel agents still remains under discussion. Given an increase in number of phase I-II studies of molecularly targeted drugs in neuroblastoma, it is crucial to determine, as early as possible, which patients may be suitable candidates for new therapeutic strategies. This single-center retrospective analysis of patients with high-risk neuroblastoma showed that the addition of conventional chemotherapy improved the quality of metastatic response only for the group of patients with partial response. It is therefore proposed to develop stratification criteria for those patients very unlikely to benefit from a plethora of additional lines of treatment, but might benefit from introduction of novel agents.

An emerging evidence base for PET-CT in the management of childhood rhabdomyosarcoma: systematic review.

INTRODUCTION: Rhabdomyosarcoma (RMS) management depends on risk stratification at diagnosis and treatment response. Assessment methods include CT, MRI, bone scintigraphy, histological analysis and bone marrow biopsy. Advanced functional imaging (FI) has potential to improve staging accuracy and management strategies. METHODS AND ANALYSIS: We conducted a systematic review (PROSPERO 2013:CRD42013006128) of diagnostic accuracy and clinical effectiveness of FI in histologically proven paediatric RMS. PRISMA guidance was followed. We searched 10 databases to November 2013. Studies with ≥10 patients with RMS which compared positron emission tomography (PET), PET-CT or diffusion-weighted imaging (DWI) MRI to conventional imaging at any treatment stage were included. Study quality was assessed. Limited, heterogeneous effectiveness data required narrative synthesis, illustrated by plotting sensitivity and specificity in receiver operating curve (ROC) space. RESULTS: Eight studies (six PET-CT, two PET) with 272 RMS patients in total were included. No DWI-MRI studies met inclusion criteria. Pooled estimates were not calculated due to sparseness of data. Limited evidence indicated initial PET-CT results were predictive of survival. PET-CT changed management of 7/40 patients. Nodal involvement PET-CT: sensitivity ranged from 80% to 100%; specificity from 89% to 100%. Distant metastatic involvement: PET-CT sensitivity ranged from 95% to 100%; specificity from 80% to100%. Data on metastases in different sites were sparse. Limited data were found on outcome prediction by PET-CT response. DISSEMINATION AND ETHICS: PET/PET-CT may increase initial staging accuracy in paediatric RMS, specifically in the detection of nodal involvement and distant metastatic spread. There is a need to further assess PET-CT for this population, ideally in a representative, unbiased and transparently selected cohort of patients.

Evaluation of the eZono 4000 with eZGuide for ultrasound-guided procedures.

Ultrasound-guided procedures are increasingly common in a variety of acute care settings, such as the operating room, critical care unit and emergency room. However, accurate judgment of needle tip position using traditional ultrasound technology is frequently difficult, and serious injury can result from inadvertently advancing beyond or through the target. Needle navigation is a recent innovation that allows the clinician to visualize the needle position and trajectory in real time as it approaches the target. A novel ultrasound machine has recently been introduced that is portable and designed for procedural guidance. The eZono 4000™ features an innovative needle navigation technology that is simple to use and permits the use of a wide range of commercially available needles, avoiding the inconvenience and cost of proprietary equipment. This article discusses this new ultrasound machine in the context of other currently available ultrasound machines featuring needle navigation.