Are multiple projections necessary when assessing umbilical venous catheter placement in neonates? A retrospective study.

INTRODUCTION: There is variability in clinical practice regarding the number of radiographic views required to accurately determine umbilical venous catheter (UVC) tip position. Some units prefer performing a single anteroposterior (AP) view and others do both AP and lateral views. The aim of this study was to compare the need for one versus two radiographical views to accurately determine UVC tip position. METHODS: Radiographs of 382 infants (all gestations) from two level six neonatal units were included in the study. Patients with congenital anomalies and those who had adjustment of UVC position between AP and lateral films being performed were excluded. Six clinicians reviewed anonymized AP only images and documented UVC tip position. Subsequently, they reviewed both AP and lateral views and again documented the UVC tip position. Results were compared to the expert consensus which was taken from the consensus of two paediatric radiologists. RESULTS: The study population had a mean gestational age of 32.8 weeks and birth weight of 2190 g, with 58% males. The UVC tip positions were accurately determined 76% times by the AP view alone and 82% times by using both the AP and lateral views (P < 0.001). The low placed UVC tip position which is the most inappropriate for use was more accurately determined by two images (78% times) rather than single image (70% times) (P < 0.001). CONCLUSIONS: Utilising both AP and lateral views was superior in accurately determining UVC tip position to AP view alone.

Fostering research in pediatric interventional radiology: needs assessment and suggestions for support.

BACKGROUND: Due to the rarity of pediatric diseases, collaborative research is the key to maximizing the impact of research studies. A research needs assessment survey was created to support initiatives to foster pediatric interventional radiology research. OBJECTIVE: To assess the status of pediatric interventional radiology research, identify perceived barriers, obtain community input on areas of research/education/support, and create metrics for evaluating changes/responses to programmatic initiatives. MATERIALS AND METHODS: A survey link was sent to approximately 275 members of the Society for Pediatric Interventional Radiology (SPIR) between May and October 2020. Data was collected using a web-based interface. Data collected included practice setting, clinical role, research experience, research barriers, and suggestions for future initiatives. RESULTS: Fifty-nine surveys were analyzed with a staff physician survey response rate of 28% (56/198). A wide range of practice sizes from 15 countries were represented. Respondents were predominantly staff physicians (95%; 56/59) with an average of 11 years (range: 1-25 years) of clinical experience working at academic or freestanding children's hospitals. A total of 100% (59/59) had research experience, and 70% (41/58) had published research with a mean of 30 peer-reviewed publications (range: 1-200). For job security, 56% (33/59) of respondents were expected or required to publish, but only 19% (11/58) had research support staff, and 42% (25/59) had protected research time, but of those, 36% (9/25) got the time "sometimes or never." Lack of support staff, established collaborative processes, and education were identified as top barriers to performing research. CONCLUSIONS: The needs assessment survey demonstrated active research output despite several identified barriers. There is a widespread interest within the pediatric interventional radiology community for collaborative research.

Traumatic pseudoaneurysm of the internal iliac artery following bone marrow aspiration in a child: An extremely rare complication of a very common procedure.

Presented here is a very rare and potentially life-threatening complication of a very common procedure. Vascular injury with traumatic pseudoaneurysm following BMAT in a paediatric patient has only been reported once in the literature to the best of our knowledge. Presented here is a second case, with pathognomonic imaging findings on CT that underwent successful coil embolisation.

Use of Tissue Plasminogen Activator in Abdominal Abscesses in Children-A Single-Center Randomized Control Trial.

PURPOSE: To establish the efficacy of once-per-day intracavitary tissue plasminogen activator (tPA) in the treatment of pediatric intra-abdominal abscesses. METHODS: A single-center prospective, double-blinded, randomized controlled trial of the use of intracavitary tPA in abdominal abscesses in children. Patients were randomized to either tPA-treatment or saline-treatment groups. Primary outcome was drainage catheter dwell (hours). Secondary outcomes were length of hospital stay, times to discharge, clinical and sonographic resolution, and adverse events (AEs). RESULTS: Twenty-eight children were randomized to either group (n = 14 each). Demographics between groups were not significantly different (age P = .28; weight P = .40; gender P = .44). There were significantly more abscesses in the tPA-treated group (P = .03). Abscesses were secondary to perforated appendicitis (n = 25) or postappendectomy (n = 3). Thirty-four abscesses were drained, 4 aspirated, 3 neither drained/aspirated. There was no significant difference in number of drains (P = .14), drain size (P = .19), primary outcome (P = .077), or secondary outcomes found. No procedural or intervention drug-related AEs occurred. No patient in the saline-treated group required to be switched/treated with tPA. CONCLUSION: No significant difference in the length of catheter dwell time, procedure time to discharge, or time to resolution was found. Intracavitary tPA was not associated with morbidity or mortality. The results neither support nor negate routine use of tPA in the drainage of intra-abdominal abscess in children. It is possible that a multicentre study with a larger number of patients may answer this question more definitively.

Vascular anomalies: special considerations in children.

The diagnosis and treatment of vascular anomalies are a large part of the caseload for paediatric interventional radiologists. Although many of the principles of sclerotherapy and embolisation are the same in adult and paediatric practice, there are some key differences in the approach for children, including some longer term thinking about managing these chronic diseases and their impact on a growing child. Vascular tumours are not often seen in adult IR practice and the rarest can be life threatening; knowledge of the commonest types and the role IR can play in their management can be instrumental in ensuring that children get appropriate treatment in a timely manner. Vascular anomalies also encompass some conditions associated with complex overgrowth, a subject that often causes confusion and uncertainty for interventional radiologists. This paper presents a simplified and practical approach to this spectrum of disease.

Pancreatic pseudocyst drainage in children by image-guided cystogastrostomy and stent insertion.

BACKGROUND: Endoscopic ultrasound is seldom available at paediatric centres; therefore drainage of pancreatic pseudocysts in children has traditionally been achieved by surgery. OBJECTIVE: This study assessed the feasibility and safety of performing image-guided internal drainage of pancreatic pseudocysts with a flanged self-expanding covered nitinol pancreatic pseudocyst drainage stent. MATERIALS AND METHODS: We conducted a retrospective case note review of children undergoing image-guided cystogastrostomy at two paediatric hospitals. Percutaneous access to the stomach was achieved via an existing gastrostomy tract or image-guided formation of a new tract. Under combined ultrasound, fluoroscopic or cone-beam CT guidance the pancreatic pseudocysts were punctured through the posterior wall of the stomach. A self-expanding covered nitinol stent was deployed to create a cystogastrostomy opening. RESULTS: Image-guided cystogastrostomy was performed in 6 children (4 male; median age 6 years, range 46 months to 15 years; median weight 18 kg, range 13.8-47 kg). Two children had prior failed attempts at surgical or endoscopic drainage. Median maximum cyst diameter was 11.5 cm (range 4.7-15.5 cm) pre-procedure. Technical success was 100%. There were no complications. There was complete pseudocyst resolution in five children and a small (2.1-cm) residual pseudocyst in one. Pseudocyst-related symptoms resolved in all children. CONCLUSION: Pancreatic pseudocyst drainage can be successfully performed in children by image-guided placement of a cystogastrostomy stent. In this cohort of six children there were no complications.

Impact of post-transplantation maintenance therapy on health-related quality of life in patients with multiple myeloma: data from the Connect® MM Registry.

Maintenance therapy after autologous stem cell transplantation (ASCT) is recommended for use in multiple myeloma (MM); however, more data are needed on its impact on health-related quality of life (HRQoL). Presented here is an analysis of HRQoL in a Connect MM registry cohort of patients who received ASCT ± maintenance therapy. The Connect MM Registry is one of the earliest and largest, active, observational, prospective US registry of patients with symptomatic newly diagnosed MM. Patients completed the Functional Assessment of Cancer Therapy-MM (FACT-MM) version 4, EuroQol-5D (EQ-5D) questionnaire, and Brief Pain Inventory (BPI) at study entry and quarterly thereafter until death or study discontinuation. Patients in three groups were analyzed: any maintenance therapy (n = 244), lenalidomide-only maintenance therapy (n = 169), and no maintenance therapy (n = 137); any maintenance and lenalidomide-only maintenance groups were not mutually exclusive. There were no significant differences in change from pre-ASCT baseline between any maintenance (P = 0.60) and lenalidomide-only maintenance (P = 0.72) versus no maintenance for the FACT-MM total score. There were also no significant differences in change from pre-ASCT baseline between any maintenance and lenalidomide-only maintenance versus no maintenance for EQ-5D overall index, BPI, FACT-MM Trial Outcomes Index, and myeloma subscale scores. In all three groups, FACT-MM, EQ-5D Index, and BPI scores improved after ASCT; FACT-MM and BPI scores deteriorated at disease progression. These data suggest that post-ASCT any maintenance or lenalidomide-only maintenance does not negatively impact patients' HRQoL. Additional research is needed to verify these findings.

Long-term health-related quality of life in transplant-ineligible patients with newly diagnosed multiple myeloma receiving lenalidomide and dexamethasone.

The FIRST trial demonstrated that continuous therapy with lenalidomide and dexamethasone (Rd) prolongs overall survival (OS) and improves health-related quality of life (HRQoL) during the first 18 months of therapy in newly diagnosed multiple myeloma (NDMM) patients. However, patient-reported HRQoL data were not collected after 18 months. We therefore estimated HRQoL scores based on time-varying data collected during progression-free follow-up after 18 months. During the initial 18 months of Rd, observed changes from baseline were within the 95% confidence interval of the predictive models at 33 of 35 time points across 7 HRQoL scores. Predicted scores after 18 months of therapy showed that observed HRQoL improvements during therapy were maintained or improved. Therefore, the survival gain observed with Rd does not come at a cost of declining HRQoL during continuous therapy beyond 18 months, supporting long-term Rd as a standard of care for initial myeloma therapy.

The Cost Impact of Lenalidomide for Newly Diagnosed Multiple Myeloma in the EU5.

INTRODUCTION: Lenalidomide is an active agent that was approved for use in the EU in 2015 as a first-line therapy for previously untreated, non-transplant eligible multiple myeloma patients. Our objective was to assess the cost impact of lenalidomide when selected as a first-line treatment for transplant-ineligible patients in France, Germany, Italy, Spain, and the United Kingdom (EU5). METHODS: We developed a cost-impact model of the total costs associated with newly diagnosed multiple myeloma over 5 years in the EU5 based on treatment duration and time to progression (TTP) (taken from trial data). We compared a baseline scenario (of current lenalidomide uptake) with two alternative future scenarios. Future Scenario A used an increased uptake of first-line lenalidomide: up to 50% in Year 5. Future Scenario B was similar to the baseline, but included a 20% increased uptake of the triple therapy regimen, carfilzomib, lenalidomide, and dexamethasone (KRd) at second line. RESULTS: Compared to alternative first-line care pathways, lenalidomide provides a time to progression advantage of up to 5.1 months. In the baseline scenario, the costs per patient were €40,692 in Year 1. Future Scenario A showed an additional expenditure of €867 per patient in Year 1, increasing to €3358 per patient by Year 5, a 2.1% and 8.2% increase from baseline, respectively. However, lenalidomide use was associated with a lower monthly hospitalisation per-patient cost (€813) compared with bortezomib (€1173) and thalidomide (€1532). Future Scenario B was associated with a 29% increase in cost. CONCLUSIONS: Compared to other first line therapies, lenalidomide delays time to progression resulting in associated savings across a patient's treatment pathway and overall is likely to result in a limited impact on budget. Lenalidomide should, therefore, be considered as a first treatment option for multiple myeloma patients ineligible for transplant. FUNDING: Celgene Ltd.

Relationship of response and survival in patients with relapsed and refractory multiple myeloma treated with pomalidomide plus low-dose dexamethasone in the MM-003 trial randomized phase III trial (NIMBUS).

Relapsed/refractory multiple myeloma (RRMM) patients have poor overall survival (OS). Pomalidomide plus low-dose dexamethasone (POM + LoDEX) significantly extends OS in RRMM vs. high-dose dexamethasone. Survival of patients with stable disease (SD) was compared to patients with progressive disease (PD) or ≥ partial response (≥PR) at cycles (C) 3, 5, and 7. Among 302 patients randomized to POM + LoDEX, at C3 19.2% achieved ≥ PR, 38.4% SD, and 14.6% PD. Patients with SD at C3 (17.4%) and C5 (13.6%) showed improved responses at C7. Median OS from randomization by response at C3 was 22.4 months for ≥ PR (n = 58, HR 0.66; 95% CI 0.40-1.08, p = 0.0976 vs. SD), 16.2 months for SD (n = 116), and 6.3 months for PD (n = 44, HR 3.43; 95% CI 2.23-5.27, p < 0.0001 vs. SD). Similar patterns were observed for C5 and C7. Results show that POM + LoDEX should be a standard treatment after lenalidomide and bortezomib, including in SD patients.

Pomalidomide and Low-Dose Dexamethasone Improves Health-Related Quality of Life and Prolongs Time to Worsening in Relapsed/Refractory Patients With Multiple Myeloma Enrolled in the MM-003 Randomized Phase III Trial.

BACKGROUND: Health-related quality of life (HRQoL) is an important element for consideration in treatment decisions in patients with relapsed/refractory multiple myeloma (RRMM). The pivotal MM-003 (A Phase 3, Multicenter, Randomized, Open-Label Study to Compare the Efficacy and Safety of Pomalidomide in Combination With Low-Dose Dexamethasone vs. High-Dose Dexamethasone in Patients With Refractory Multiple Myeloma or Relapsed and Refractory Multiple Myeloma and Companion Study [NIMBUS]) randomized, open-label, multicenter, phase III trial demonstrated improved progression-free survival (PFS) and prolonged overall survival (OS) with pomalidomide (POM) plus low-dose dexamethasone (POM + LoDEX) versus high-dose dexamethasone (HiDEX) in patients with RRMM in whom lenalidomide (LEN) and bortezomib (BORT) had failed. MM-003 also investigated HRQoL as a predefined secondary end point. PATIENTS AND METHODS: Recruited patients (n = 455) were refractory to their last treatment and had failed LEN and BORT after ≥ 2 consecutive cycles of each (alone or in combination). Eight clinically relevant and validated HRQoL domains from the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-MY20, and EQ-5D questionnaires were selected for analysis. Time to symptom worsening based on minimally important differences (MIDs) was calculated. RESULTS: Clinically meaningful improvements in HRQoL as determined by MIDs, regression analyses, and best response analyses were observed more frequently in patients receiving POM + LoDEX than in those receiving HiDEX. POM + LoDEX significantly extended median time to clinically meaningful worsening in HRQoL versus HiDEX in 4 HRQoL domains and demonstrated a trend in an additional 3 domains. Patients in the HiDEX arm experienced earlier HRQoL deterioration compared with those in the POM + LoDEX arm in each domain analyzed. CONCLUSION: POM + LoDEX offer good clinical outcomes that lead to improved and prolonged HRQoL compared with HiDEX in patients with RRMM and end-stage disease.

Patterns of total cost and economic consequences of progression for patients with newly diagnosed multiple myeloma.

BACKGROUND: Few studies have addressed the cost patterns of patients with multiple myeloma (MM) before and after first relapse. This US claims analysis evaluated, from a US health plan perspective, patterns of total direct costs of care from treatment initiation to progression for patients with MM treated with novel agents, using time to next therapy (TTNT) as a proxy measure for progression. METHODS: A retrospective study was conducted using a large US claims database, evaluating patients with claims for MM between 2006 and 2013. Patients with claims for stem cell transplant (SCT) were excluded. The analysis focused on patients receiving lenalidomide (LEN) or bortezomib (BORT) based treatment, for whom complete claim history was available through initiation of subsequent treatment. Average patient monthly direct costs were determined, including medical and pharmacy costs, and total cost patterns over quarterly time periods were calculated. RESULTS: The study population comprised 2843 patients with newly diagnosed MM (NDMM) and 1361 with relapsed MM. Total monthly cost for patients with NDMM declined steadily, from $15,734 initially to $5082 at 18+ months after therapy. Upon initiation of second-line therapy, total monthly costs rose to $13,876 and declined to $6446 18 months later. Although NDMM cost levels for individual ordinal months were similar between the LEN and BORT groups, TTNT was longer for LEN-based treatments (37 months). The BORT-treated cohort had higher average monthly total costs for NDMM and for the common time period through 37 months after initiation of therapy ($7534 vs $10,763 for LEN and BORT, respectively). Key limitations of this study, in addition to the lack of mortality and staging information available from claims data, include the definition of TTNT based on change in treatment or a defined gap in therapy prior to retreatment, which may differ from actual time of progression in some patients. CONCLUSIONS: For patients with NDMM receiving either LEN- or BORT-based treatment without SCT, followed until TTNT, total direct monthly costs (drug + medical) declined steadily over time. Monthly costs returned to near initial levels when patients began second-line therapy and then followed a similar pattern of decline. Due to the longer TTNT for patients initiated on LEN and the associated longer period of below-average costs, patients initiated with LEN-based treatments had mean monthly total costs >$3200 lower than total costs for patients initiated on BORT during the first 3 years after starting treatment, cumulating to nearly $120,000 in lower costs for patients initiated on LEN.

Peripherally inserted central catheters: use at a tertiary care pediatric center.

PURPOSE: To examine the use of peripherally inserted central catheters (PICCs) in a tertiary care pediatric setting. MATERIALS AND METHODS: An observational study of use and referral practices for PICCs in a tertiary care pediatric setting was performed with three distinct approaches: (i) in an institutional overview of trends, data from 2001 to 2012 were initially analyzed to identify high-level trends; (ii) an in-depth analysis of PICC referrals during 1 year was performed to determine details of referral patterns and clinical practices; and (iii) an electronic survey of the perception and understanding of referring clinical staff was conducted. RESULTS: During the past decade, there has been a steady increase in the number of PICC insertions and a decrease in median PICC dwell times. Discrepancies were identified between the anticipated versus actual dwell times. A large proportion of patients was found to have multiple PICC insertions, short dwell times, and premature PICC removals, potentially resulting in increasing risks of short- and long-term complications. Large percentages of the staff respondents valued the role of PICCs and had a good understanding of short-term complications, but underestimated the scale of the PICC service (numbers placed, resources involved) and several long-term complications associated with PICCs. CONCLUSIONS: The number of PICCs inserted in children is increasing while PICC dwell times are decreasing. Better postprocedure care is important to minimize premature removals and avoid repeat insertions. Associated complications are not fully appreciated by the referring pediatricians. Further education and guidelines are needed.

Doctors in ancient Greek and Roman rhetorical education.

This article collects and examines all references to doctors in rhetorical exercises used in ancient Greek and Roman schools in the Roman Empire. While doctors are sometimes portrayed positively as philanthropic, expert practitioners of their divinely sanctioned art, they are more often depicted as facing charges for poisoning their patients.

A novel approach to endovascular treatment of severe hepatic vein stenoses following liver transplant in children.

Hepatic vein stenoses are a rare but serious complication of liver transplants in children. Restoration of flow by radiological methods often provides a viable treatment option. This technique relies on the interventional radiologist's ability to advance a guide wire across the obstruction, thus allowing for balloon dilatation and other necessary interventions. Failure to cross the stenosis reduces graft survival and increases patient morbidity. We report two cases with tight hepatic vein stenosis where the guide wire could not be advanced in a conventional approach across the upper end of the stenosis. Utilizing prominent intrahepatic collateral vessels, the stenoses were able to be crossed, facilitating successful PTA with good clinical outcome.

Isoform-specific regulation of the inositol 1,4,5-trisphosphate receptor by O-linked glycosylation.

The inositol 1,4,5-trisphosphate receptor (InsP(3)R), an intracellular calcium channel, has three isoforms with >65% sequence homology, yet the isoforms differ in their function and regulation by post-translational modifications. We showed previously that InsP(3)R-1 is functionally modified by O-linked ß-N-acetylglucosamine glycosylation (O-GlcNAcylation) (Rengifo, J., Gibson, C. J., Winkler, E., Collin, T., and Ehrlich, B. E. (2007) J. Neurosci. 27, 13813-13821). We now report the effect of O-GlcNAcylation on InsP(3)R-2 and InsP(3)R-3. Analysis of AR4-2J cells, a rat pancreatoma cell line expressing predominantly InsP(3)R-2, showed no detectable O-GlcNAcylation of InsP(3)R-2 and no significant functional changes despite the presence of the enzymes for addition (O-ß-N-acetylglucosaminyltransferase) and removal (O-ß-N-acetylglucosaminidase) of the monosaccharide. In contrast, InsP(3)R-3 in Mz-ChA-1 cells, a human cholangiocarcinoma cell line expressing predominantly InsP(3)R-3, was functionally modified by O-GlcNAcylation. Interestingly, the functional impact of O-GlcNAcylation on the InsP(3)R-3 channel was opposite the effect measured with InsP(3)R-1. Addition of O-GlcNAc by O-ß-N-acetylglucosaminyltransferase increased InsP(3)R-3 single channel open probability. Incubation of Mz-ChA-1 cells in hyperglycemic medium caused an increase in the InsP(3)-dependent calcium release from the endoplasmic reticulum. The dynamic and inducible nature of O-GlcNAcylation and the InsP(3)R isoform specificity suggest that this form of modification of InsP(3)R and subsequent changes in intracellular calcium transients are important in physiological and pathophysiological processes.

Inositol 1,4,5-trisphosphate receptor movement is restricted by addition of elevated levels of O-linked sugar.

The inositol 1,4,5-trisphosphate receptor (InsP3R) is a versatile, ubiquitous intracellular calcium channel. Traditionally, visualizing the InsP3R in live cells involves attaching a fluorescent marker to either terminal of the protein, but the termini themselves contain binding sites for accessory molecules and proteins. Using random transposition, constructs have been developed that express the type I InsP3R with green fluorescent protein (GFP) inserted at various points within its sequence. We have used two of these constructs, one in the ligand-binding domain, and another in the regulatory domain, to investigate InsP3R dynamics within the endoplasmic reticulum. We present evidence that endogenous calcium signaling is maintained when these constructs are expressed. In addition, by measuring the fluorescent recovery after photobleaching of a subcellular region, we demonstrate that treatment with 8mM N-acetylglucosamine (GlcNAc), known to lead to increased O-linked GlcNAcylation of proteins, leads to a reduction in the ability of the InsP3R to travel laterally within the endoplasmic reticulum. Each construct serves as the control for the other one, suggesting that this decrease in mobility is not specific to the insertion site of GFP within the InsP3R. These constructs represent a new tool that will allow us to follow receptor turnover and translocation events.