Search

Bronchopulmonary fistulae (BPFs) are a severe complication of lobectomy and pneumonectomy and are associated with high rates of morbidity and mortality. We have developed a novel, minimally invasive method of central BPF closure using Amplatzer devices (ADs) that were originally designed for the transcatheter closure of cardiac defects. Ten patients with 11 BPFs (eight men and two women, aged 66.3±10.1 years [mean±SD]) were treated under conscious sedation with bronchoscopic closure of the BPFs using ADs. A nitinol double-disk occluder device was delivered under direct bronchoscopic guidance over a guidewire into the fistula. By extruding a disk on either side of the BPF, the fistula was occluded. Bronchography was performed by injecting contrast medium through the delivery sheath following the procedure to ensure correct device positioning. In nine patients, the procedure was successful and symptoms related to the BPF disappeared following closure by the AD. The results were maintained over a median follow-up period of 9 months. Therefore, we state that endobronchial closure using an AD is a safe and effective method for treatment of a postoperative BPF. [ABSTRACT FROM AUTHOR]

The measurement of exhaled pulmonary nitric oxide concentrations requires that contamination from the upper respiratory tract and inhaled gases be eliminated. This can be achieved with no risk in the clinical setting of intubated patients of all ages in the operating room or intensive care unit. Further modifications of the anesthetic/ventilatory circuit allow for accurate determination of tidal volume and minute ventilation. [ABSTRACT FROM AUTHOR]

Background: To assess the safety and efficacy of bronchopleural fistulae closure with Amplatzer occluder devices (AGA Medical, Golden Valley, MN) through our experience of over 14 years., Methods: Retrospective data review of patients from Rabin Medical Center who underwent Amplatzer occluder device placement between March 2007 and September 2021 for bronchopleural fistulae closure., Results: In total, 72 patients had 83 Amplatzer occluder devices implanted for bronchopleural fistulae closure. The median age was 65.5 (interquartile range 56.0-72.3) years. The primary diseases were lung malignancy (48 [66.7%]) and thoracic infection (9 [12.5%]). Bronchopleural fistulae developed mainly following pneumonectomy (40.3%) and lobectomy (33.3%), with a median time from surgery to Amplatzer placement of 3.9 (interquartile range 1.4-16.4) months. We encountered no procedural or immediate postprocedural complications or deaths. Six months after Amplatzer insertion, there were 7 (8.4%) Amplatzer removals and 11 (15.3%) fistula-related deaths., Conclusions: Amplatzer occluders are a safe modality for nonsurgical bronchopleural fistulae management with ease of placement under moderate sedation and flexible bronchoscopy with good short- and long-term effectivity., (Copyright © 2024 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Competing Interests: Conflict of interest: None declared.

We present the cases of 2 children diagnosed with extrahepatic portosystemic shunts, a very rare vascular anomaly, on investigation of cardiac symptomatology. Poorly developed portal venous systems necessitated staged shunt occlusion. This was achieved using atrial flow regulator devices positioned in an inferior vena cava stent platform performed in the cardiac catheterization laboratory., Competing Interests: The Occlutech Atrial Flow Regulators (65AFR04M) used in this study were provided on a compassionate basis by Occlutech. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Introduction: Historically, neuroblastoma has been diagnosed by surgical open biopsy (SB). In recent decades, core needle biopsy (CNB) has replaced surgical biopsy due to its safe and adequate method of obtaining tissue diagnosis., Aim: Our study aimed to assess the effectiveness of CNB in obtaining tissue diagnosis for neuroblastoma and evaluate its safety profile in terms of post-operative complications, in comparison to SB., Methods: A retrospective cohort study, including all patients younger than 18 years who were diagnosed with neuroblastoma from 2012 until 2022 in a single tertiary medical center. Patients' demographics, tumor size and location, pathological results, and clinical outcomes were collected., Results: 79 patients were included in our study: 35 biopsies were obtained using image-guided CNB and 44 using SB. Patients' and tumor characteristics including age, gender, tumor volume, and stage were similar in both groups. The biopsy adequacy rate in the CNB group was 91% and 3 patients in this group underwent repeated biopsy. The safety profile in the CNB group was similar to the SB group., Conclusions: CNB is a safe method and should be considered the first choice for obtaining tissue diagnosis when feasible due to its high adequacy in terms of tumor histopathological features., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: MYC genes regulate ornithine decarboxylase (Odc) to increase intratumoral polyamines. We conducted a Phase I trial [NCT02030964] to determine the maximum tolerated dose (MTD) of DFMO, an Odc inhibitor, with celecoxib, cyclophosphamide and topotecan., Methods: Patients 2-30 years of age with relapsed/refractory high-risk neuroblastoma received oral DFMO at doses up to 9000 mg/m 2 /day, with celecoxib (500 mg/m 2 daily), cyclophosphamide (250 mg/m 2 /day) and topotecan (0.75 mg/m 2 /day) IV for 5 days, for up to one year with G-CSF support., Results: Twenty-four patients (median age, 6.8 years) received 136 courses. Slow platelet recovery with 21-day courses (dose-levels 1 and 2) led to subsequent dose-levels using 28-day courses (dose-levels 2a-4a). There were three course-1 dose-limiting toxicities (DLTs; hematologic; anorexia; transaminases), and 23 serious adverse events (78% fever-related). Five patients (21%) completed 1-year of therapy. Nine stopped for PD, 2 for DLT, 8 by choice. Best overall response included two PR and four MR. Median time-to-progression was 19.8 months, and 3 patients remained progression-free at >4 years without receiving additional therapy. The MTD of DFMO with this regimen was 6750 mg/m 2 /day., Conclusion: High-dose DFMO is tolerable when added to chemotherapy in heavily pre-treated patients. A randomized Phase 2 trial of DFMO added to chemoimmunotherapy is ongoing [NCT03794349]., (© 2024. The Author(s).)

Background: Some patients with pulmonary stenosis present with a complex multilevel disease that involves the valve, the leaflets, and the sinotubular junction (STJ) forming an hourglass appearance. We herein report the mid-term results of our experience with the reconstruction of the supravalvar narrowing using three pericardial patches., Material and Methods: Retrospective analysis of patient charts and echocardiography studies of patients who underwent three-patch reconstruction of the pulmonary valve (PV) from 2013 to 2022. After PV transection distal to STJ, vertical incisions into the sinuses were performed, and leaflets were trimmed and thinned. The three sinuses were augmented using three pericardial patches., Results: Nineteen patients underwent repair of hourglass supravalvar pulmonary stenosis. Mean weight at surgery was 9.4 kg (median 7.2, range 4.7-35); 16 patients underwent previous catheterization with unsuccessful balloon dilatation of the PV (13 pts.). Preoperative aortic/pulmonary annulus ratio was 1.02 (median 1, range 0.89-1.25). After surgery, gradients across the PV were significantly reduced (94 ± 26 vs 29 ± 9 mm Hg, P  = .02). Postoperatively, 14 patients had mild or no pulmonary insufficiency (PI) and five had mild to moderate PI. At a mean follow-up of 71 months (median 78 months, range 8-137), gradients continued to decrease (29 ± 9 vs 15 ± 5 mm Hg, P  < .001)., Conclusion: The three-patch technique for the repair of supravalvar pulmonary stenosis is simple, reproducible, and achieves excellent and long-standing relief of the right ventricular outflow tract gradient., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Purpose: Evaluate Piccolo and ADOII devices for transcatheter patent ductus arteriosus (PDA) closure. Piccolo has smaller retention discs reducing risk of flow disturbance but residual leak and embolization risk may increase., Methods: Retrospective review of all patients undergoing PDA closure with an Amplatzer device between January 2008 and April 2022 in our institution. Data from the procedure and 6 months follow-up were collected., Results: 762 patients, median age 2.6 years (range 0-46.7) years and median weight 13 kg (range 3.5-92) were referred for PDA closure. Overall, 758 (99.5%) had successful implantation: 296 (38.8%) with ADOII, 418 (54.8%) with Piccolo, and 44 (5.8%) with AVPII. The ADOII patients were smaller than the Piccolo patients (15.8 vs. 20.5 kg, p  < 0.001) and with larger PDA diameters (2.3 vs. 1.9 mm, p  < 0.001). Mean device diameter was similar for both groups. Closure rate at follow-up was similar for all devices ADOII 295/296 (99.6%), Piccolo 417/418 (99.7%), and AVPII 44/44 (100%). Four intraprocedural embolizations occurred during the study time period: two ADOII and two Piccolo. Following retrieval the PDA was closed with an AVPII in two cases, ADOI in one case and with surgery in the fourth case. Mild stenosis of the left pulmonary artery (LPA) occurred in three patients with ADOII devices (1%) and one patient with Piccolo device (0.2%). Severe LPA stenosis occurred in one patient with ADOII (0.3%) and one with AVPII device (2.2%)., Conclusions: ADOII and Piccolo are safe and effective for PDA closure with a tendency to less LPA stenosis with Piccolo. There were no cases of aortic coarctation related to a PDA device in this study., Competing Interests: EB is a proctor for Abbott Vascular. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Bruckheimer, Steiner, Barak-Corren, Slanovic, Levinzon, Lowenthal, Amir, Dagan and Birk.)

Desmoid fibromatoses (DFs) are locally aggressive tumors composed of monoclonal fibroblasts within an abundant extracellular matrix. Systemic doxorubicin treatment is effective, but toxic. We investigated arterial doxorubicin eluting embolization (DEE), an approach characterized by high drug concentrations in the tumor alongside limited systemic drug exposure. The primary and secondary endpoints were radiological response using MRI and RECIST 1.1, respectively. The study included 24 patients (median age, 24; interquartile range, 16-34 years). Data were collected prospectively for 9 patients and retrospectively for 15 patients. The most frequent tumor locations were chest/abdomen wall and neck/shoulder/axilla (29% each). Of 24 patients, 7 (24%) were treatment naïve, and 17 (71%) had received one or two prior treatments. Patients underwent a median of two treatments (range, 1-4), with a median of 49 mg (range, 8-75) doxorubicin/treatment. Efficacy outcomes were available for 23 patients. With a median follow-up of 8 months (interquartile range, 3-13), median tumor volumes decreased by 59% (interquartile range, 40-71%) and T2 signal intensity decreased by 36% (interquartile range, 19-55%). Of 23 patients, 9 (39%), 12 (52%), and 2 (9%) had a partial response, stable disease, and progressive disease, respectively. DEE was safe and well tolerated, with one reported grade 3-4 adverse event (cord injury). In conclusion, DEE was safe and achieved rapid clinical/volumetric responses in DFs.

Objective: Routine use of central venous access is needed in children undergoing open heart surgery for pressure monitoring and inotrope infusion. We sought to evaluate the efficiency and safety of routine use of transthoracic intracardiac lines (ICLs) in patients undergoing cardiac surgery and to compare them to patients who have been previously treated with traditional central venous lines (non-ICLs)., Methods: Retrospective review of charts of all patients who underwent cardiac surgery and had an ICL inserted in the operating room. Case control matching was done with similar patient in which ICL was not inserted. Patients characteristics, diagnosis, operative, and intensive care data were collected for each patient and analyzed., Results: A total number of 376 patient records were reviewed (198 ICL patients and 178 non-ICL patients). Umbilical line and non-ICL durations were longer in the non-ICL group. ICL duration was the longest of all lines, averaging 12.87 ± 10.82 days. The necessity for multiple line insertions (˃2 insertions) was significantly higher in the non-ICL group, with a relative risk ratio of 3.24 (95% confidence interval: 1.617-6.428). There was no statistical difference of infections rate and line complications between the two groups., Conclusion: ICLs are safe in infants undergoing cardiac surgery and can be kept in place for a long period of time with a low rate of line complications and infection. Routine use of ICLs reduces the number of central venous catheter placement in this complex patient population., (© 2022 Wiley Periodicals LLC.)

Background and Purpose: The antisense oligonucleotide nusinersen (Spinraza) regulates splicing of the survival motor neuron 2 (SMN2) messenger RNA to increase SMN protein expression. Nusinersen has improved ventilator-free survival and motor function outcomes in infantile onset forms of spinal muscular atrophy (SMA), treated early in the course of the disease. However, the response in later onset forms of SMA is highly variable and dependent on symptom severity and disease duration at treatment initiation. Therefore, we aimed to identify novel noninvasive biomarkers that could predict the response to nusinersen in type II and III SMA patients., Methods: Thirty-four SMA patients were included. We applied next generation sequencing to identify microRNAs in the cerebrospinal fluid (CSF) as candidate biomarkers predicting response to nusinersen. Hammersmith Functional Motor Scale Expanded (HFMSE) was conducted at baseline and 6 months after initiation of nusinersen therapy to assess motor function. Patients changing by ≥3 or ≤0 points in the HFMSE total score were considered to be responders or nonresponders, respectively., Results: Lower baseline levels of two muscle microRNAs (miR-206 and miR-133a-3p), alone or in combination, predicted the clinical response to nusinersen after 6 months of therapy. Moreover, miR-206 levels were inversely correlated with the HFMSE score., Conclusions: Lower miR-206 and miR-133a-3p in the CSF predict more robust clinical response to nusinersen treatment in later onset SMA patients. These novel findings have high clinical relevance for identifying early treatment response to nusinersen in later onset SMA patients and call for testing the ability of miRNAs to predict more sustained long-term benefit., (© 2022 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: Covered stent implantation for treatment of coarctation of the aorta (CoA) is effective and can prevent aortic wall injury. Prospective studies with long-term follow-up, including imaging, are lacking. We report the acute and long-term outcomes for use of the Large Diameter Advanta V12 covered stent for treatment of native and recurrent CoA., Methods: A prospective, multicenter, nonrandomized study was performed including 70 patients (43 male), median age 17 years, median weight 57.4 kg with CoA who underwent implantation of the Large Diameter Advanta V12 covered stent. Annual follow-up for 5 years included Doppler echocardiography to calculate diastolic velocity: systolic velocity ratio., Results: CoA diameter increased from 5.6±3.6 to 14.9±3.9 mm ( P <0.0001) and the pressure gradient decreased from 35.8±16.2 to 5.6±7.9 mm Hg ( P <0.0001). Preimplantation diastolic velocity:systolic velocity of 0.6±0.16 dropped to 0.34±0.13 ( P <0.0001) and was maintained at 5 years. Computed tomography angiograms at 12 months postimplantation demonstrated the stent:transverse arch diameter to be similar, 0.91±0.09 to postprocedure 0.86±0.14. Major adverse vascular events at 30 days and 12 months were 1.4% and 4.3%, respectively. Significant adverse events included three patients who required stent implantation to treat infolding. There were no mortalities., Conclusions: The Large Diameter Advanta V12 covered stent is safe and effective for the treatment of CoA with an immediate and sustained reduction of the pressure gradient over 12 months and 5 years as assessed by preimplantation and postimplantation Doppler echocardiography and 12-month computed tomography angiography. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT00978952. URL: http://www.anzctr.org.au; Unique identifier: ACTRN12612000013864.

Background: Vascular rings cause respiratory symptoms in children. Treatment consists of surgical division; however, data regarding mid-term results are scarce. The purpose of this study was to evaluate clinical results of vascular ring surgery., Methods: Retrospective chart review of consecutive patients who underwent vascular ring surgery. Mid-term follow-up consisted of clinic visits and telephone questionnaire over a 1-year period sampling at five points in time., Results: Follow-up of 85 patients who underwent vascular rings surgery revealed significant symptomatic improvement within 6 months. In total, 50% were symptomatic to some degree at their last documented clinic visit complaining of stridor (36.8%), cough (34.2%), wheezing (10.5%), dyspnoea on exertion (10.5%), or recurrent respiratory infections (23.7%). By telephone questionnaires, 83% described a significant improvement in respiratory symptoms, 63.4% had some residual symptoms, 36.6% stridor, 38.8% chronic cough, 32.4% bronchodilator use,18.3% had at least one episode of pneumonia per year, 31% of children had dyspnoea or respiratory limitation, and 12.7% while doing physical activities. We found no association between the age at surgery or anatomic variant to the presence of symptoms at mid-term follow-up., Conclusions: Surgical division of vascular rings results in significant clinical improvement within 1 year; nevertheless, some patients remain symptomatic to some degree. We found no association between the age at surgery or anatomic variant to the presence of symptoms at mid-term follow-up. Further evaluation is warranted to assess the nature of residual symptoms and explore whether anatomical causes can be identified leading to surgical modifications.

Objectives: Congenital portosystemic shunt (CPSS) in a growth-restricted fetus may lead to cardiac overload and ultimately hemodynamic imbalance. The aim of the study was to describe the application of tricuspid annular plane systolic excursion (TAPSE) for surveillance of cardiac function in growth-restricted fetuses diagnosed with CPSS., Methods: The study group consisted of 7 fetuses with growth restriction diagnosed with CPSS between 2018 and 2020. Patients were followed longitudinally every 2 weeks. Sonographic fetal-TAPSE (f-TAPSE) was performed every 2 weeks. At each visit, the following parameters were recorded: estimated fetal weight, biophysical profile, nonstress test, Doppler flow indices, and fetal cardiothoracic index. Postnatal laboratory and imaging tests were retrieved from the medical files., Results: Mean gestational age at diagnosis of CPSS was 32 + 1 weeks. Cardiomegaly was observed in all cases. All portosystemic shunts were classified as intrahepatic. Values of f-TAPSE were above the 95th percentile in 6/7 fetuses at presentation and throughout follow-up. Gestational age at delivery ranged between 36 + 5 and 38 + 5 weeks. Postnatally, spontaneous closure of the shunt was noted in 2 infants. Transient hyperammonemia was diagnosed in 2 neonates, with no signs of the characteristic complication., Conclusions: In growth-restricted fetuses diagnosed concomitantly with CPSS, f-TAPSE offers a practical sonographic tool for assessment of cardiac function and may serve as an additional clinical marker for follow-up. The appearance of cardiomegaly in growth-restricted fetuses should prompt a dedicated sonographic evaluation of the fetal portal system., (© 2021 American Institute of Ultrasound in Medicine.)

This is the first published case, as far as we know, of a term neonate with refractory chylothorax secondary to diastolic dysfunction in the cardiac postoperative period, where extracorporeal membrane oxygenation (ECMO) was used to improve the physiologic derangements, thus allowing resolution of the chylous effusion. The infant was prenatally diagnosed with d-transposition of the great arteries. He was started on prostaglandin infusion and underwent balloon atrial septostomy followed by arterial switch operation. After surgery, he developed anasarca and high-volume chylothorax that did not respond to medical management and fasting. Cardiac catheterization demonstrated severe diastolic dysfunction and pulmonary hypertension. On postoperative day 19, he was placed on veno-arterial (VA) ECMO and had gradual regression of the chylothorax and edema. After 13 days on ECMO support, he was decannulated with small, self-limiting, reaccumulation of chylous effusion. He was discharged home on postoperative day 57, and has since been thriving with no evidence of reaccumulation of the chylous effusion. In summary, VA ECMO support could be considered as a rescue modality for patients with uncontrollable refractory high-volume chylous effusion, after other treatment options have been pursued., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © 2021 by the ASAIO.)

Kingella spp. have emerged as an important cause of invasive pediatric diseases. Data on Kingella infective endocarditis (KIE) in children are scarce. We compared the clinical features of pediatric KIE cases with those of Streptococcus species IE (StIE) and Staphylococcus aureus IE (SaIE). A total of 60 patients were included in the study. Throughout the study period, a rise in incidence of KIE was noted. KIE patients were significantly younger than those with StIE and SaIE, were predominately boys, and had higher temperature at admission, history of oral aphthae before IE diagnosis, and higher lymphocyte count (p<0.05). Pediatric KIE exhibits unique features compared with StIE and SaIE. Therefore, in young healthy children <36 months of age, especially boys, with or without a congenital heart defect, with a recent history of oral aphthae, and experiencing signs and symptoms compatible with endocarditis, Kingella should be suspected as the causative pathogen.

Epistaxis is a common debilitating manifestation in hereditary hemorrhagic telangiectasia (HHT), due to mucocutaneous telangiectases. The epistaxis can be difficult to control despite available treatments. Dysregulated angiogenesis has been shown to be associated with telangiectases formation. Topical propranolol has demonstrated antiangiogenic properties. We performed a two-phase study, i.e., a double-blind placebo-controlled phase, followed by an open-label phase. The aim of the study was assessment of safety and efficacy of nasal propranolol gel in HHT-related epistaxis. Twenty participants with moderate-severe HHT-related epistaxis were randomized to eight weeks of propranolol gel 1.5%, or placebo 0.5 cc, applied to each nostril twice daily; and continued propranolol for eight weeks in an open-label study. For the propranolol group, the epistaxis severity score (ESS) improved significantly (-2.03 ± 1.7 as compared with -0.35 ± 0.68 for the placebo group, p = 0.009); hemoglobin levels improved significantly (10.5 ± 2.6 to 11.4 ± 2.02 g/dL, p = 0.009); and intravenous iron and blood transfusion requirement decreased. The change in nasal endoscopy findings was not significant. During the open-label period, the ESS score improved significantly in the former placebo group (-1.99 ± 1.41, p = 0.005). The most common adverse event was nasal mucosa burning sensation. No cardiovascular events were reported. Our results suggest that topical propranolol gel is safe and effective in HHT-related epistaxis.

Background: Accessory pathways (APs) are a common reason for supraventricular tachycardia in small children. Trans-septal puncture (TSP) approach is commonly used for the ablation of left-sided APs, however it may be challenging in small children. The aim of this study was to assess the efficacy and safety of trans-septal approach radiofrequency (RF) ablation of left-sided APs in children weighing up to 30 kg., Methods: Of the 658 children who underwent catheter ablation of APs since 06/2002, 86 children had left-sided AP and weighed less than 30 kg. TSP approach guided with TEE and fluoroscopy was used for left atrium access., Results: The mean age, height, and body weight were 7.6 ± 1.9 years, 122.4 ± 9.3 cm and 24.0 ± 4.2 kg, respectively. Forty-three children (50%) were male, 46 of 86 (53%) had manifest AP, 17 of 86 (20%) weighed less than 20 kg and in 24 of 86 children (28%) a three-dimensional system (3DS) was used to reduce fluoroscopy time. The acute success rate was 98.8% (85/86), with a recurrence rate of 2.4% (2/85) in a mean follow-up of 66.2 ± 42.7 (9.1-184.2) months. The mean procedure time and fluoroscopy time were significantly lower for the 3DS group compared to the standard fluoroscopy group 131 ± 41 (55-262) and 2.4 ± 1.5 (1-6) minutes vs 164 ± 51 (62-249) and 27 ± 13 (8-77) minutes, P  < 0.01 and P  < 0.0001, respectively. There were no ablation-related complications., Conclusions: RF ablation of left-sided APs using TSP approach in small children had an excellent efficacy and safety profile. The use of 3DS significantly reduces the procedure and fluoroscopy time., Competing Interests: Authors declare no conflict of interests for this article., (© 2019 The Authors. Journal of Arrhythmia published by John Wiley & Sons Australia, Ltd on behalf of the Japanese Heart Rhythm Society.)

Infective endocarditis (IE) in the pediatric population can present as a life-threatening condition. Optimal timing for surgical intervention should consider surgical risks versus the risk of neurologic complications. We herein report our experience with this group of critically ill children. Retrospective analysis of patient charts of all patients who underwent urgent surgical treatment of aortic IE from 1994 to 2014 was performed. Nine patients with acute storming IE of the aortic valve or the ascending aorta were urgently operated (eight normal heart, one congenital aortic stenosis), age ranged from 8 weeks to 4.2 years. Causative organisms were Staphylococcus aureus (2), Staphylococcus coagulase negative (1), Kingella kingae (2), Streptococcus pneumoniae (2), or culture negative (2). Presenting symptoms other than hemodynamic instability were neurologic decompensation (5) coronary embolization (1) and cardiogenic shock due to scalded skin syndrome (1). CT and MRI demonstrated significant brain infarcts in four patients. Operations performed were the Ross operation (7) and ascending aortic reconstruction (2). There were no operative deaths. At a median follow-up of 6 years (range 2-196 months), all patients are alive and well. Re-intervention included homograft replacement (2) and transcatheter Melody valve implantation (1). At their last follow-up, the neo-aortic valve was functional in all patients with minimal regurgitation and all had full resolution of the neurological deficits. Urgent surgical treatment for aortic valve IE in infants is challenging. Although surgery is complex and pre-disposing conditions such as sepsis, neurologic and cardiac decompensations are prevalent, operative results are excellent and gradual and significant neurologic improvement was noted over time.

Cancer is a set of diseases characterized by uncontrolled cell growth. In certain cancers of the gastrointestinal tract, the adenomatous polyposis coli (APC) tumor suppressor gene is altered in either germline or somatic cells and causes formation of risk factors, such as benign colonic or intestinal neoplasia, which can progress to invasive cancer. APC is a key component of the WNT pathway, contributing to normal GI tract development, and APC alteration results in dysregulation of the pathway for production of polyamines, which are ubiquitous cations essential for cell growth. Studies with mice have identified nonsteroidal anti-inflammatory drugs (NSAIDs) and difluoromethylornithine (DFMO), an inhibitor of polyamine synthesis, as potent inhibitors of colon carcinogenesis. Moreover, gene expression profiling has uncovered that NSAIDs activate polyamine catabolism and export. Several DFMO-NSAID combination strategies are effective and safe methods for reducing risk factors in clinical trials with patients having genetic or sporadic risk of colon cancer. These strategies affect cancer stem cells, inflammation, immune surveillance, and the microbiome. Pharmacotherapies consisting of drug combinations targeting the polyamine pathway provide a complementary approach to surgery and cytotoxic cancer treatments for treating patients with cancer risk factors. In this Minireview, we discuss the role of polyamines in colon cancer and highlight the mechanisms of select pharmacoprevention agents to delay or prevent carcinogenesis in humans., (© 2018 Gerner et al.)

Systemic doxorubicin is effective for desmoid fibromatosis (DF), but its use is limited by dose-dependent cardiotoxicity. A protocol of selective intra-arterial doxorubicin drug-eluting embolization (DEE) was designed to maximize target tissue efficacy of doxorubicin, while minimizing systemic exposure. Four children with recurrent or refractory DF were treated between 2014 and 2017. Tumor volumes were reduced by 54%-97% over a follow-up interval of 6-32 months. A single patient experienced transient lower extremity paresthesia (Common Terminology Criteria for Adverse Events grade I). Further investigation is needed to better establish these promising results for doxorubicin DEE in DF treatment., (Copyright © 2018 SIR. Published by Elsevier Inc. All rights reserved.)

Background: Severe epistaxis is often difficult to control in patients with hereditary hemorrhagic telangiectasia (HHT). Propranolol has been shown to have antiangiogenic properties in vitro and in vivo and is commonly used to treat hemangiomas. We present our experience with topical nasal propranolol for the treatment of moderate to severe epistaxis in patients with HHT., Methods: Retrospective case series. Six patients with HHT were treated with 0.5 cm 3 of 1.5% propranolol gel, applied to each nostril twice daily for at least 12 weeks. Outcome measures were epistaxis severity score (ESS), hemoglobin level, and number of blood transfusions prior to and while on treatment. Local and systemic side effects were recorded., Results: The mean duration of treatment was 30 ± 5.6 weeks. A significant improvement in the ESS was found in all patients, with a mean decrease from 6.4 ± 2.1 at treatment onset to 3.5 ± 1.7 at 12 weeks (p = 0.028). Hemoglobin level increased significantly from 8.4 ± 3.1 to 11.0 ± 1.8 g/dL at 12 weeks (p = 0.043). The mean number of blood transfusions decreased from 4.5 ± 4.9 before treatment to 2.5 ± 2.9 at 12 weeks and 0.3 ± 0.8 at 24 weeks, but the difference did not reach statistical significance (p = 0.109 for both). No significant side effects of treatment were recorded., Conclusions: These preliminary results suggest that topical propranolol may be effective for the treatment of epistaxis in patients with HHT. A prospective controlled trial is required to confirm our findings.

Background: Limited fluoroscopy ablation using 3D electro-anatomical system (3DS) has been used for arrhythmias in children, however it is not a common practice. We aimed to facilitate a fluoroscopy limited approach for ablation of accessory pathways (AP) in children., Methods: Following electrophysiologic (EP) catheter placement a single dual-plane fluoroscopic image (right anterior oblique-30° and left anterior oblique-60° views) was acquired and the 3DS views were rotated to be a perfect match to the fluoroscopy. Ninety-four consecutive pediatric patients [mean age 11.8±4.1 (4.2-18) years, 61.7% males] with Wolf-Parkinson-White syndrome underwent ablation of an AP. Fifty-seven had manifest AP, 54 had left-sided AP (LSAP) and 40 had right-sided AP (RSAP)., Results: The acute success rate was 95.7% (90/94), with a recurrence rate of 1.1% (1/90) at a mean follow-up of 13±5.5 (4.4-22.9) months. Mean procedure and fluoroscopy times were 144±45 (55-262)min and 1.8±1.4 (0.1-5.6)min, respectively. Comparison of the first 20 procedures to the next 74 procedures demonstrated an extended procedure time (171±53min vs 135±38min, p<0.005), however the fluoroscopy time, the number of long applications, the time to effect, and the acute success rate were similar. There were no permanent ablation-related complications., Conclusions: A limited fluoroscopy approach for ablation of AP in children using 3DS is easily acquired, adapted, reduces the fluoroscopy time, and has an excellent efficacy and safety profile., (Copyright © 2017 Japanese College of Cardiology. Published by Elsevier Ltd. All rights reserved.)

RRx-001 is an anticancer agent that subjects cancer cells to reactive oxygen/nitrogen species (ROS/RNS) and acts as an epigenetic modifier. We have used a thiol-bearing MRI contrast agent, Gd-LC7-SH, to investigate the pharmacodynamics of RRx-001 in CHP-100 Ewing's Sarcoma, HT-29 colorectal carcinoma, and PANC-1 pancreatic carcinoma xenografts in SCID mice. Binding of Gd-LC7-SH to the Cys 34 residue on plasma albumin prolongs retention in the tumor microenvironment and increases tumor enhancement on MRI. Mice were imaged by MRI and in vivo T1 maps acquired 50 min (T1 50 min ) after injection of 0.05 mmol/kg Gd-LC7-SH (i.v.) at baseline and 1, 24, and 72 h post-treatment with 10 mg/kg RRx-001 (i.v.). Consistent with an indirect thiol-modifying activity of RRx-001, tumor T1 50 min at 1 h post-drug was significantly longer than pre-drug tumor T1 50 min in all three tumor models, with the T1 50 min remaining significantly longer than baseline through 72 h post-drug in the HT-29 and PANC-1 tumors. The T1 50 min of CHP-100 tumors recovered to baseline by 24 h post-drug, suggesting a robust anti-oxidant response to the RRx-001 challenge that was presaged by a marked increase in perfusion at 1 h post-drug measured by DCE-MRI. MRI enhanced with Gd-LC7-SH provides a mechanistically rational biomarker of RRx-001 pharmacodynamics., Competing Interests: CONFLICTS OF INTEREST JS and BO are employees of EpicentRx.