The Identity of Human Tissue-Emigrant CD8+ T Cells.

Lymphocyte migration is essential for adaptive immune surveillance. However, our current understanding of this process is rudimentary, because most human studies have been restricted to immunological analyses of blood and various tissues. To address this knowledge gap, we used an integrated approach to characterize tissue-emigrant lineages in thoracic duct lymph (TDL). The most prevalent immune cells in human and non-human primate efferent lymph were T cells. Cytolytic CD8+ T cell subsets with effector-like epigenetic and transcriptional signatures were clonotypically skewed and selectively confined to the intravascular circulation, whereas non-cytolytic CD8+ T cell subsets with stem-like epigenetic and transcriptional signatures predominated in tissues and TDL. Moreover, these anatomically distinct gene expression profiles were recapitulated within individual clonotypes, suggesting parallel differentiation programs independent of the expressed antigen receptor. Our collective dataset provides an atlas of the migratory immune system and defines the nature of tissue-emigrant CD8+ T cells that recirculate via TDL.

The Transcription Factor T-bet Resolves Memory B Cell Subsets with Distinct Tissue Distributions and Antibody Specificities in Mice and Humans.

B cell subsets expressing the transcription factor T-bet are associated with humoral immune responses and autoimmunity. Here, we examined the anatomic distribution, clonal relationships, and functional properties of T-bet+ and T-bet- memory B cells (MBCs) in the context of the influenza-specific immune response. In mice, both T-bet- and T-bet+ hemagglutinin (HA)-specific B cells arose in germinal centers, acquired memory B cell markers, and persisted indefinitely. Lineage tracing and IgH repertoire analyses revealed minimal interconversion between T-bet- and T-bet+ MBCs, and parabionts showed differential tissue residency and recirculation properties. T-bet+ MBCs could be subdivided into recirculating T-betlo MBCs and spleen-resident T-bethi MBCs. Human MBCs displayed similar features. Conditional gene deletion studies revealed that T-bet expression in B cells was required for nearly all HA stalk-specific IgG2c antibodies and for durable neutralizing titers to influenza. Thus, T-bet expression distinguishes MBC subsets that have profoundly different homing, residency, and functional properties, and mediate distinct aspects of humoral immune memory.

Selective Lymphatic Duct Embolization for Treatment of Thoracic Lymphatic Flow Disorders in Children: Technical Aspects and Comparison with Thoracic Duct Embolization.

PURPOSE: To assess effectiveness of selective lymphatic duct embolization (SLDE) for treatment of thoracic lymphatic flow disorders, performed to maintain patency of the thoracic duct (TD), compared to thoracic duct embolization (TDE). MATERIALS AND METHODS: Records of 39 patients (mean age 7.6±7.1 years) with thoracic lymphatic flow disorders who underwent 43 SLDE procedures were analyzed and compared to a cohort of 104 patients (7.8±7.6 y) who underwent TDE. Relevant clinical and imaging data were collated. All patients presented with chylous effusion and/or plastic bronchitis. For the SLDE cohort, etiology of disorders included single-ventricle heart disease palliation in 28 patients (72%) and vascular malformation/aneuploidy in 8 (21%). For the TDE cohort, 92/104(88%) had single-ventricle heart disease palliation. RESULTS: SLDE was performed with glue via microcatheter in 35 procedures, and dextrose flood technique was used in 26. SLDE via direct needle access was performed in 11. After SLDE, presenting symptoms resolved in 33/39 patients (85%), improved in 5 (13%), and were unchanged in 1 (3%) (mean follow-up 693±523 days). The TD remained patent in all cases. There was a significant difference in outcomes (P=0.001) with the TDE cohort-symptoms resolved or improved in 75/104 patients (72%), were unchanged in 15 (14%); and new leak (e.g., ascites, protein-losing enteropathy) developed in 14 TDE patients (13%) (follow-up 1041±879 d). CONCLUSION: SLDE was effective for treatment of thoracic lymphatic flow disorders, and outcomes were comparable to TDE. Selective techniques preserve the patency of the TD and may have potential benefits that warrant further study.

Understanding the next circulation: lymphatics and what the future holds.

PURPOSE OF REVIEW: The lymphatic system was previously considered the forgotten circulation because of an absence of adequate options for imaging and intervention. However, recent advances over the last decade have improved management strategies for patients with lymphatic disease, including chylothorax, plastic bronchitis, ascites, and protein-losing enteropathy. RECENT FINDINGS: New imaging modalities have enabled detailed visualization of lymphatic vessels to allow for a better understanding of the cause of lymphatic dysfunction in a variety of patient subsets. This sparked the development of multiple transcatheter and surgery-based techniques tailored to each patient based on imaging findings. In addition, the new field of precision lymphology has added medical management options for patients with genetic syndromes, who have global lymphatic dysfunction and typically do not respond as well to the more standard lymphatic interventions. SUMMARY: Recent developments in lymphatic imaging have given insight into disease processes and changed the way patients are managed. Medical management has been enhanced and new procedures have given patients more options, leading to better long-term results.

Characterization and treatment of thoracic duct obstruction in patients with lymphatic flow disorders.

PURPOSE: The contribution of thoracic duct obstruction to lymphatic flow disorders has not been well-characterized. We describe imaging findings, interventions, and outcomes in patients with suspected duct obstruction by imaging or a lympho-venous pressure gradient (LVPG). MATERIALS AND METHODS: Clinical, imaging, and interventional data, including the LVPG, of patients with flow disorders and imaging features of duct obstruction who underwent lymphatic intervention were retrospectively reviewed, collated, and analyzed with descriptive statistics. RESULTS: Eleven patients were found to have obstruction, median age 10.4 years (interquartile range: 8-14.9 years). Pleural effusions were seen in 8/11 (72%), ascites in 8/11 (72%), both in 5/11 (45%), and protein-losing enteropathy in 5 (45%). Eight patients (72%) had congenital heart disease. The most common site of obstruction was at the duct outlet in 7/11 patients (64%). Obstruction was secondary to extrinsic compression or ligation 4 patients (36%). Nine patients (82%) underwent interventions, with balloon dilation in 7/9 (78%), massive lymphatic malformation drainage and sclerotherapy in 1, and lympho-venous anastomosis in 1. There was resolution of symptoms in 7/9 (78% who underwent intervention, with worsening in 1 patient and no change in 1. In these patients, preprocedure mean LVPG was 7.9 ± 5.7 mmHg and postprocedure gradient was 1.6 ± 1.9 mmHg (p = 0.014). Five patients in this series underwent intervention solely to alleviate duct obstruction and in 4/5 (80%) this led to resolution of symptoms (p = 0.05). CONCLUSION: Duct obstruction may be seen in lymphatic flow disorders and can occur from intrinsic and extrinsic causes. Stenosis at the outlet was most common. Obstruction can be demonstrated by an elevated LVPG, and interventions to alleviate the obstruction can be beneficial.

Treatment of severe Kaposiform lymphangiomatosis positive for NRAS mutation by MEK inhibition.

BACKGROUND: Kaposiform lymphangiomatosis (KLA) is a complex lymphatic anomaly involving most commonly the mediastinum, lung, skin and bones with few effective treatments. In recent years, RAS-MAPK pathway mutations were shown to underlie the pathogenesis of several complex lymphatic anomalies. Specifically, an activating NRAS mutation (p.Q61R) was found in the majority of KLA patients. Recent reports demonstrated promising results of treatment with the MEK inhibitor, Trametinib, in patients with complex lymphatic anomalies harboring gain of function mutations in ARAF and SOS1, as well as loss of function mutation in the CBL gene, a negative regulator of the RAS-MAPK pathway. We present a 9-year-old child with a severe case of KLA harboring the typical NRAS (p.Q61R) mutation detected by plasma-derived cell free DNA, responsive to trametinib therapy. METHODS: The NRAS somatic mutation was detected from plasma cfDNA using droplet digital PCR. Concurrent in-vitro studies of trametinib activity on mutant NRAS affected lymphatic endothelial cells were performed using a three-dimensional spheroid sprouting assay. RESULTS: Trametinib treatment lead to resolution of lifelong thrombocytopenia, improvement of pulmonary function tests and wellbeing, as well as weaning from prolonged systemic steroid treatment. Concurrent studies of mutant NRAS-expressing cells showed enhanced lymphangiogenic capacity along with over activation of the RAS-MAPK and PI3K-AKT-mTOR pathways, both reversed by trametinib. CONCLUSIONS: Trametinib treatment can substantially change the prognosis of patients with RAS pathway associated lymphatic anomalies. IMPACT: This is the first description of successful trametinib treatment of a patient with KLA harboring the most characteristic NRAS p.Q61R mutation. Treatment can significantly change the prognosis of patients with RAS pathway-associated lymphatic anomalies. We devised an in vitro model of KLA enabling a reproducible method for the continued study of disease pathogenesis. Mutated NRAS p.Q61R cells demonstrated increased lymphangiogenic capacity.

Pathogenic variants in PIK3CA are associated with clinical phenotypes of kaposiform lymphangiomatosis, generalized lymphatic anomaly, and central conducting lymphatic anomaly.

Complex lymphatic anomalies are debilitating conditions characterized by aberrant development of the lymphatic vasculature (lymphangiogenesis). Diagnosis is typically made by history, examination, radiology, and histologic findings. However, there is significant overlap between conditions, making accurate diagnosis difficult. Recently, genetic analysis has been offered as an additional diagnostic modality. Here, we describe four cases of complex lymphatic anomalies, all with PIK3CA variants but with varying clinical phenotypes. Identification of PIK3CA resulted in transition to a targeted inhibitor, alpelisib. These cases highlight the genetic overlap between phenotypically diverse lymphatic anomalies.

State-of-the-art imaging for lymphatic evaluation in children.

The lymphatic system has been poorly understood and its importance neglected for decades. Growing understanding of lymphatic flow pathophysiology through peripheral and central lymphatic flow imaging has improved diagnosis and treatment options in children with lymphatic diseases. Flow dynamics can now be visualized by different means including dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL), the current standard technique to depict central lymphatics. Novel imaging modalities including intranodal, intrahepatic and intramesenteric DCMRL are quickly evolving and have shown important advances in the understanding and guidance of interventional procedures in children with intestinal lymphatic leaks. Lymphatic imaging is gaining importance in the radiologic and clinical fields and new techniques are emerging to overcome its limitations.

Surgical creation of lymphocutaneous fistulas for the management of infants with central lymphatic obstruction.

PURPOSE: Central lymphatic obstructions are associated with anasarca and high mortality. We hypothesized that opening dilated cutaneous lymphatic channels by creating a lymphocutaneous fistula (LCF) would decompress the lymphatic circulation and improve anasarca. METHODS: We reviewed all patients that had at least one LCF created between 9/2019 and 12/2022. LCF efficacy was determined by changes in weight, urine/diuresis, ventilation, and clinical status. RESULTS: We created eleven LCFs in four infants. LCFs initially drained 108 cc/kg/d (IQR68-265 cc/kg/d). Weights significantly decreased after LCF creation (6.9 [IQR6.1-8.1] kg vs. 6.1 [IQR 4.9-7.6] kg, P = 0.042). Ventilatory support decreased significantly in all patients after at least one LCF was created, and 3/4 patients (75%) had significantly lower peak inspiratory pressures (28 [IQR 25-31] cmH2O vs. 22 [IQR 22-24] cmH2O, P = 0.005; 36 [IQR36-38] cmH2O vs. 33 [IQR 33-35] cmH2O, P = 0.002; 36 [IQR 34-47] cmH2O vs. 28 [28-31] cmH2O, P = 0.002). LCFs remained patent for 29d (IQR 16-49d). LCFs contracted over time, and 6/11 (54.5%) were eventually revised. There were no complications. Two patients died from overwhelming disease, one died from unrelated causes, and one remains alive 29 months after their initial LCF. CONCLUSION: LCFs provide safe and effective temporary lymphatic decompression in patients with central lymphatic obstruction. While LCFs are not a cure, they can serve as a bridge to more definitive therapies or spontaneous lymphatic remodeling. LEVEL OF EVIDENCE: IV.

Dynamic contrast-enhanced MR lymphangiography: feasibility of using ferumoxytol in patients with chronic kidney disease.

PURPOSE: To assess the feasibility of direct intra-lymphatic administration of diluted ferumoxytol as a T1-positive contrast agent for dynamic contrast-enhanced MR lymphangiography (DCMRL) imaging of the central lymphatics in children with renal disease. METHODS: In vitro scan of dilute ferumoxytol was initially performed using time-resolved and high-resolution 3D gradient echo (GRE) sequences with short TE values (1 to 1.5 ms). A ferumoxytol concentration of 0.25 to 0.40 mg/mL was found to retain high signal in the T1-weighted sequences. DCMRL was then performed in 4 children with renal disease with the same 3D GRE sequences administrating diluted ferumoxytol via intra-mesenteric (IM), intra-hepatic (IH), and intra-nodal (IN) routes (6 to 9 mL to each site; average total dose of 0.75 mg/kg) by slow hand injection (0.5 to 1.0 mL/min). The signal-to-noise ratio (SNR) of the lymphatics was measured for quantitative evaluation. RESULTS: Ferumoxytol-enhanced DCMRL was technically successful in all patients. Contrast conspicuity within the lymphatics was sufficient without subtraction. The mean SNR was significantly higher than the muscle (50.1 ± 12.2 vs 13.2 ± 2.8; t = 15.9; p < .001). There were no short-term complications attributed to the administration of ferumoxytol in any of the four patients. CONCLUSION: Magnetic resonance lymphangiography using ferumoxytol via IN, IH, and IM access is a new method to directly visualize the central lymphatic system and can be applied safely in patients with renal failure based on our preliminary report of four cases. Ferumoxytol-enhanced DCMRL shows diagnostic image quality by using 3D GRE sequences with short TE values and appropriate dilution of ferumoxytol. KEY POINTS: • MR lymphangiography using ferumoxytol via intra-nodal, intra-hepatic, and intra-mesenteric access is a new method to directly visualize the central lymphatic system from the groin to the venous angle. • FDCMRL can be applied safely in patients with renal failure based on our preliminary report of four cases. • FDCMRL shows diagnostic image quality by using 3D GRE sequences with short TE values and appropriate dilution of the ferumoxytol.

Liver lymphatic anatomy and role in systemic lymphatic disease.

OBJECTIVES: To characterize hepatic to systemic lymphatic connections in patients with systemic lymphatic disease using intra-hepatic lymphangiography and to compare outcomes after lymphatic intervention. METHODS: In this retrospective study, patients with intra-hepatic lymphangiography from May 2014 - April 2019 at our institution were included. Imaging review was performed and hepatic lymphatic connections and flow patterns were characterized. Clinical data were reviewed and comparisons between patients undergoing lymphatic intervention with or without abnormal hepatic lymphatics were performed. RESULTS: During the study period, 105 patients underwent intra-hepatic lymphangiography. Primary clinical presentation included ascites (19/105), chylothorax (27/105), plastic bronchitis (PB) (17/105), and protein losing enteropathy (PLE) (42/105). Five categories of hepatic lymphatic connections and flow patterns were identified (%): normal (25%, 26/105), hepatoperitoneal (12%, 13/105), hepatopulmonary (10.5%, 11/105), hepatomesenteric (7.5%, 8/105), and hepatoduodenal (41%, 43/105) with four patients having more than one abnormal pattern. A comparison between clinical presentation and imaging category revealed an increased likelihood of having ascites with hepatoperitoneal (p < .0001), chylothorax/PB with hepatopulmonary (p = .01), and PLE with hepatoduodenal (p < .001) connections. Seventy-six patients had a lymphatic intervention, 24% with normal, and 76% with abnormal liver lymphatics. There was no difference in length of hospital stay or mortality between the two groups, but there was a prolonged time to symptom resolution (p = .006) and persistent symptoms after 6 months (5% vs 44%, p = .002) in the group with abnormal liver lymphatics. CONCLUSION: We identified five liver lymphatic imaging categories with a substantial correlation to presenting lymphatic disease. Abnormal imaging patterns correlated with increased morbidity. Evaluation of liver lymphatics should be considered in patients with a systemic lymphatic disease if central lymphatic imaging is normal. KEY POINTS: • We identified five liver lymphatic imaging patterns: normal, hepatoperitoneal, hepatomesenteric, hepatopulmonary, and hepatoduodenal. • Imaging patterns were correlated with disease presentation (normal - chylothorax/PB, hepatoperitoneal - ascites/chylothorax, hepatopulmonary - chylothorax/PB, hepatoduodenal - PLE). • Abnormal imaging patterns correlated with increased morbidity.

How we approach pediatric congenital chylous effusions and ascites.

Congenital lymphatic leak may develop in patients with maldeveloped lymphatics and result in life-threatening fluid and electrolyte imbalance, protein deficiency, and immunodeficiency. Rapid diagnosis and therapy are necessary to prevent these complications; however, the field lacks clinical trials to support standardized diagnostic treatment guidelines. We present our current multidisciplinary approach to the diagnosis and management of congenital lymphatic leak including chylous pleural effusions and ascites. Depending on the rate of lymphatic leak, therapy can range from observation with nutritional modifications to surgical and interventional procedures aimed to reduce lymphatic drainage. Modalities to image central and peripheral lymphatics have advanced considerably. Genetic variants and subsequent targets that drive lymphatic maldevelopment have expanded the repertoire of possible pharmacotherapeutic options.

Dynamic Contrast Magnetic Resonance Lymphangiography Localizes Lymphatic Leak to the Duodenum in Protein-Losing Enteropathy.

OBJECTIVES: Protein-losing enteropathy (PLE) is a disorder of intestinal lymphatic flow resulting in leakage of protein-rich lymph into the gut lumen. Our primary aim was to report the imaging findings of dynamic contrast magnetic resonance lymphangiography (DCMRL) in patients with PLE. Our secondary objective was to use these imaging findings to characterize lymphatic phenotypes. METHODS: Single-center retrospective cohort study of patients with PLE unrelated to single-ventricle circulation who underwent DCMRL. We report imaging findings of intranodal (IN), intrahepatic (IH), and intramesenteric (IM) access points for DCMRL. RESULTS: Nineteen patients 0.3-58 years of age (median 1.2 years) underwent 29 DCMRL studies. Primary intestinal lymphangiectasia (PIL) was the most common referring diagnosis (42%). Other etiologies included constrictive pericarditis, thoracic insufficiency syndrome, and genetic disorders. IN-DCMRL demonstrated a normal central lymphatic system in all patients with an intact thoracic duct and localized duodenal leak in one patient (1/19, 5%). IH-DCMRL detected a duodenal leak in 12 of 17 (71%), and IM-DCMRL detected duodenal leak in 5 of 6 (83%). Independent of etiology, lymphatic leak was only visualized in the duodenum. CONCLUSIONS: In patients with PLE, imaging via DCMRL reveals that leak is localized to the duodenum regardless of etiology. Comprehensive imaging evaluation with three access points can provide detailed information about the site of duodenal leak.

Lymphatic anomalies in congenital heart disease.

Congenital heart disease can lead to various lymphatic complications including traumatic leaks, lymphatic overproduction, conduction abnormalities or lymphedema. Advancements in the imaging of central lymphatics and guided interventions have improved outcomes in these children. Dynamic contrast-enhanced magnetic resonance (MR) lymphangiography allows for the assessment of abnormal lymphatic drainage. This technique is preferred for evaluating lymphatic conditions such as plastic bronchitis, chylothorax, chyloptysis, chylopericardium, protein-losing enteropathy and chylous ascites, among other lymphatic disorders. In this review, we discuss lymphatic abnormalities encountered on MRI in children with congenital heart disease. We also briefly review treatment options.

Dynamic contrast-enhanced magnetic resonance lymphangiography.

Lymphatic flow disorders include a broad spectrum of abnormalities that can originate in the lymphatic or the venous system. The development of these disorders is multifactorial and is most commonly associated with congenital heart diseases and palliative surgeries that these patients undergo. Central lymphatic disorders might be secondary to traumatic leaks, lymphatic overproduction, conduction abnormalities or lymphedema, and they can progress to perfusion anomalies. Several imaging modalities have been used to visualize the lymphatic system. However, the imaging of central lymphatic flow has always been challenging. Dynamic contrast-enhanced magnetic resonance lymphangiography (DCMRL) allows for visualization of central lymphatic flow disorders and has been recently applied for the assessment of plastic bronchitis, protein-losing enteropathy, chylothorax and chylopericardium, among other lymphatic disorders. The hepatic and mesenteric accesses are innovative and promising techniques for better identification and understanding of these abnormalities. The main objectives of this review are to discuss the physiology and anatomy of the lymphatic system and review the current uses of DCMRL in the diagnosis and management of lymphatic flow disorders.

Post-operative Chylothorax in Patients with Repaired Transposition of the Great Arteries.

Patients with dextro-transposition of the great arteries (d-TGA) require surgical repair as neonates. These patients are at risk for post-operative chylothorax. We sought to describe the presentation, imaging, and outcomes after intervention for patients with d-TGA with post-operative chylothorax. A retrospective chart review was performed in patients with repaired d-TGA who were referred from 1/1/2013 to 4/1/2020 for evaluation of chylothorax. Patient history, lymphatic imaging, and interventional data were collected. Impact of intervention on lymphatic drainage was evaluated with a student's t-test. Eight patients met inclusion criteria for this study. Five patients had a history of central venous thrombus leading to thoracic duct outlet occlusion. Five patients underwent intervention, two were managed conservatively, and one was not a candidate for intervention. Chylothorax resolved in six patients. There was a significant difference in output from 7 days prior to first intervention (114 mL/kg/day) compared to 28 days following final intervention (27 mL/kg/day, p = 0.034). There were no procedural complications. Chylothorax in patients with repaired transposition of the great arteries is often amenable to intervention. Early surveillance and management of central venous thrombosis may reduce the burden of lymphatic disease in these patients.

Pathogenic variant in EPHB4 results in central conducting lymphatic anomaly.

Central conducting lymphatic anomaly (CCLA) is one of the complex lymphatic anomalies characterized by dilated lymphatic channels, lymphatic channel dysmotility and distal obstruction affecting lymphatic drainage. We performed whole exome sequencing (WES) of DNA from a four-generation pedigree and examined the consequences of the variant by transfection of mammalian cells and morpholino and rescue studies in zebrafish. WES revealed a heterozygous mutation in EPHB4 (RefSeq NM_004444.4; c.2334 + 1G>C) and RNA-Seq demonstrated that the EPHB4 mutation destroys the normal donor site, which leads to the use of a cryptic splice donor that results in retention of the intervening 12-bp intron sequence. Transient co-expression of the wild-type and mutant EPHB4 proteins showed reduced phosphorylation of tyrosine, consistent with a loss-of-function effect. Zebrafish ephb4a morpholino resulted in vessel misbranching and deformities in the lymphatic vessel development, indicative of possible differentiation defects in lymphatic vessels, mimicking the lymphatic presentations of the patients. Immunoblot analysis using zebrafish lysates demonstrated over-activation of mTORC1 as a consequence of reduced EPHB4 signaling. Strikingly, drugs that inhibit mTOR signaling or RAS-MAPK signaling effectively rescued the misbranching phenotype in a comparable manner. Moreover, knock-in of EPHB4 mutation in HEK293T cells also induced mTORC1 activity. Our data demonstrate the pathogenicity of the identified EPHB4 mutation as a novel cause of CCLA and suggesting that ERK inhibitors may have therapeutic benefits in such patients with complex lymphatic anomalies.

Thoracic duct lymphatic fluid harbors phenotypically naive T cells for use in adoptive T-cell therapy.

BACKGROUND AIMS: Manufacturing of potent chimeric antigen receptor (CAR) T cells requires phenotypically naive and early memory T cells. We hypothesized lymphatic fluid collected from the thoracic duct of children would serve as a unique reservoir for early T cells, which could then be used for CAR T-cell therapy. METHODS: We evaluated lymphatic fluid collected from 25 pediatric patients undergoing thoracic duct cannulation for other clinical indications. RESULTS: Lymphatic fluid in the thoracic duct was rich in T cells, with higher percentage of naive and stem central memory T-cell subsets compared with paired blood samples. T cells from lymphatic fluid showed decreased negative checkpoint regulators on the surface and increased rapid expansion with bead activation. Creation of CD19-directed CAR T cells from blood and lymphatic T cells showed similar lentiviral transduction properties, but CAR T cells generated from lymphatic fluid produced superior cytotoxicity in a murine leukemia model because they were able to achieve equivalent tumor eradication at lower doses. CONCLUSIONS: These results are the first characterization of T cells from the thoracic duct of pediatric patients and suggest an alternative approach for manufacturing of cellular therapy that will improve both expansion and cytotoxic effect.

Decompression of the thoracic duct: A novel transcatheter approach.

In patients with total cavopulmonary connections, elevated central venous pressures (CVP) have detrimental effects on the lymphatic system causing an imbalance in fluid production and drainage of the interstitium. This combination may result in life-threatening lymphatic complications including plastic bronchitis (PB), protein losing enteropathy (PLE), chylothorax, and ascites. While embolization of the abnormal lymphatics has greatly improved outcomes from these complications, alternative treatment strategies have been proposed that would result in improved lymphatic drainage while leaving the lymphatic system intact. We report two novel transcatheter approaches for thoracic duct (TD) decompression in two patients who developed PLE after completion of the Fontan procedure as part of staged palliation for congenital heart disease. In addition, one patient had severe concurrent PB. In both patients, a connection was created between a left superior vena cava (LSVC) to the left atrium allowing for a nonsurgical method to decompress the TD. This procedure resulted in significant clinical and laboratory improvement of both patients' PLE and other symptoms of lymphatic dysfunction.

Incidence and fate of device-related left pulmonary artery stenosis and aortic coarctation in small infants undergoing transcatheter patent ductus arteriosus closure.

OBJECTIVES: To evaluate short- and middle-term outcomes after transcatheter patent ductus arteriosus (TC-PDA) closure in small infants, specifically device-related left pulmonary artery (LPA) stenosis and aortic coarctation, risk factors, and changes over time. BACKGROUND: Recent studies have demonstrated successful transcatheter PDA (TC-PDA) closure in small infants. LPA stenosis and aortic coarctation have been seen after TC-PDA, but it is not clear whether device-related LPA/aortic obstruction persists. METHODS: A single-center retrospective study of infants ≤4 kg who underwent TC-PDA closure from February 1, 2007 to September 1, 2018 was performed, evaluating the incidence and risk factors for LPA stenosis and coarctation. RESULTS: Forty-four patients underwent successful TC-PDA with Amplatzer Vascular Plug II (AVPII; n = 30), Amplatzer Duct Occluder II-Additional Sizes (n = 10), Amplatzer Duct Occluder I (n = 3), and coil-filled AVPI (n = 1) devices, all via an antegrade approach. Median birthweight and procedural weight were 890 g (range: 490-3,250) and 2.8 kg (range: 1.2-4.0), respectively. Median follow-up was 0.7 years (range: 2 days-7 years). Thirty-eight patients had post-procedure echocardiograms assessing LPA/aortic obstruction. Of those, 17 had LPA flow acceleration/stenosis (≥1.5 m/s), which improved or resolved in all patients with available follow-up; 3 developed mild coarctation (>2 m/s), which improved in the two with more than short-term follow-up; 4 developed mild flow acceleration (1.5-2 m/s) in the descending aorta, which resolved in three and increased in one (2.4 m/s). Flow acceleration in the LPA was associated with younger procedural age, larger PDA minimal diameter, and placement of a device other than the AVPII. There was no device-related mortality or need for reintervention. CONCLUSION: TC-PDA in small infants is effective, without significant complications. Device-related LPA/aortic obstruction can improve with time/growth.