Assessment of drainage vein of focal nodular hyperplasia using contrast-enhanced ultrasound.

PURPOSE: Identification of drainage vessels is useful for differential diagnosis of hepatic tumors. Direct drainage to the hepatic vein has been reported to occur in focal nodular hyperplasia (FNH), but studies evaluating the drainage veins of FNH are limited. We aimed to investigate the detection rate of the FNH drainage vein and the factors related to visualization of the drainage vein on contrast-enhanced ultrasound (CEUS). METHODS: Fifty consecutive patients with 50 FNH lesions were retrospectively evaluated in this study. We calculated and compared the detection rate of the FNH drainage vein on CEUS, contrast-enhanced magnetic resonance imaging (CEMRI), and contrast-enhanced computed tomography (CECT), and identified the factors correlated with visualization of the FNH drainage vein on CEUS by using multivariate logistic regression analyses. RESULTS: Visualization of the drainage vein was confirmed in 31 of 50 lesions (62%) using CEUS, three of 44 lesions (6.8%) using CEMRI, and one of 18 lesions (5.6%) using CECT. The detection rate of the FNH drainage vein on CEUS was significantly higher than that on CEMRI and CECT (p < 0.001). Multivariate analysis identified lesion size (≥ 25 mm) and detection of the spoke-wheel pattern on Doppler US as independent factors for drainage vein detection in FNH. CONCLUSION: Our study showed that rapid FNH drainage to the hepatic vein was observed at a relatively high rate on CEUS, suggesting that CEUS focusing on detection of drainage veins is important for diagnosing FNH.

Acute Flaccid Myelitis With Human Rhinovirus A19 Detection: Case Report and Literature Review.

Human rhinovirus (HRV) has been sporadically detected in patients with acute flaccid myelitis (AFM). We report a case of AFM in a 2-year-old boy with severe neurologic sequelae, whose nasopharyngeal and stool samples tested positive for HRV-A19. Clinical information related to AFM with HRV is limited. Further study of the association of AFM with HRV is warranted.

Effect of Water Absorption on Electric Properties of Temperature-Resistant Polymers.

The effects of water absorption on the electric resistivity and dielectric constant of polyimide (PI) and poly(ethylene terephthalate) (PET) were investigated, and the mechanism of deterioration in electrical insulation properties was discussed. The polyimides are poly(oxydianiline pyromellitimide) (PMDA-ODA) and poly(para-phenylene diamine biphenyltetracarboxydiimide) (BPDA-PDA). These polymer films were immersed in pure water for various immersion times at room temperature, and the water absorption ratio was evaluated. The electric resistance for these films was measured at room temperature using a high-resistance meter, and the dielectric constant at room temperature was measured using an LCR meter in a frequency range of 200 kHz to 2 MHz. The absorption ratios at equilibrium absorption for PMDA-ODA, BPDA-PDA, and PET were 2.7, 2.5, and 0.5%, respectively. The critical volume fraction of the percolation threshold of electric conductivity due to water absorption was 0.034 for both PMDA-ODA and BPDA-PDA. On the other hand, PET did not show a significant decrease in the resistivity. For both PIs and PET, the dielectric constant observed could be explained by a series model of the respective capacitances of pure water and polymer. Actually, the resistivity of samples cut from the edges of the film after water absorption was almost the same value as that in the dry state. These results suggest that the absorbed water molecules are not uniformly dispersed in the film but are localized at the edges of the film even after the absorption equilibrium has been reached.

Synthesis of the MN Ring of Caribbean Ciguatoxin C-CTX-1 via Desymmetrization by Acetal Formation.

The MN ring of Caribbean ciguatoxin C-CTX-1 was synthesized from a meso-syn-2,7-dimethyloxepane derivative corresponding to the M ring via desymmetrization by acetal formation with a camphor derivative, followed by construction of the N ring via the Horner-Wadsworth-Emmons reaction and acetal formation. The meso-syn-2,7-dimethyloxepane derivative was synthesized via photoinduced electrocyclization of a conjugated exo-diene under flow conditions, giving a cyclobutene derivative, followed by ring expansion via oxidative cleavage and diastereoselective reduction of a ß-hydroxy ketone.

Aorta and main pulmonary artery segmentation using stacked U-Net and localization on non-contrast-enhanced computed tomography images.

BACKGROUND: The contact between the aorta, main pulmonary artery (MPA), main pulmonary vein, vena cava (VC), and esophagus affects segmentation of the aorta and MPA in non-contrast-enhanced computed tomography (NCE-CT) images. PURPOSE: A two-stage stacked U-Net and localization of the aorta and MPA were developed for the segmentation of the aorta and MPA in NCE-CT images. METHODS: Normal-dose NCE-CT images of 24 subjects with chronic thromboembolic pulmonary hypertension (CTEPH) and low-dose NCE-CT images of 100 subjects without CTEPH were used in this study. The aorta is in contact with the ascending aorta (AA) and MPA, the AA with the VC, the aortic arch (AR) with the VC and esophagus, and the descending aorta (DA) with the esophagus. These contact surfaces were manually annotated. The contact surfaces were quantified using the contact surface ratio (CSR). Segmentation of the aorta and MPA in NCE-CT images was performed by localization of the aorta and MPA and a two-stage stacked U-Net. Localization was performed by extracting and processing the trachea and main bronchus. The first stage of the stacked U-Net consisted of a 2D U-Net, 2D U-Net with a pre-trained VGG-16 encoder, and 2D attention U-Net. The second stage consisted of a 3D U-Net with four input channels: the CT volume and three segmentation results of the first stage. The model was trained and tested using 10-fold cross-validation. Segmentation of the entire volume was evaluated using the Dice similarity coefficient (DSC). Segmentation of the contact area was also assessed using the mean surface distance (MSD). The statistical analysis of the evaluation underwent a multi-comparison correction. CTEPH and non-CTEPH cases were classified based on the vessel diameters measured from the segmented MPA. RESULTS: For the noncontact surfaces of AA, the MSD of stacked U-Net was 0.31 ± 0.10 mm (p < 0.05) and 0.32 ± 0.13 mm (p < 0.05) for non-CTEPH and CTEPH cases, respectively. For contact surfaces with a CSR of 0.4 or greater in AA, the MSD was 0.52 ± 0.23 mm (p < 0.05), and 0.68 ± 0.29 mm (p > 0.05) for non-CTEPH and CTEPH cases, respectively. MSDs were lower than those of 2D and 3D U-Nets for contact and noncontact surfaces; moreover, MSDs increased slightly with larger CSRs. However, the stacked U-Net achieved MSDs of approximately 1 pixel for a wide contact surface. The area under the receiver operating characteristic curve for CTEPH and non-CTEPH classification using the right main pulmonary artery (RMPA) diameter was 0.97 (95% confidence interval [CI]: 0.94-1.00). CONCLUSIONS: Segmentation of the aorta and MPA on NCE-CT images were affected by vascular and esophageal contact. The application of stacked U-Net and localization techniques for non-CTEPH and CTEPH cases mitigated the impact of contact, suggesting its potential for diagnosing CTEPH.

Anomalous Magnetorheological Response for Carrageenan Magnetic Hydrogels Prepared by Natural Cooling.

The effect of the cooling rate on magnetorheological response was investigated for magnetic hydrogels consisting of carrageenan and carbonyl iron particles with a concentration of 50 wt.%. For magnetic gels prepared via natural cooling, the storage moduli at 0 and 50 mT were 3.7 × 104 Pa and 5.6 × 104 Pa, respectively, and the change in the modulus was 1.9 × 104 Pa. For magnetic gels prepared via rapid cooling, the storage moduli at 0 and 50 mT were 1.2 × 104 Pa and 1.8 × 104 Pa, respectively, and the change in the modulus was 6.2 × 103 Pa, which was 1/3 of that for the magnetic gel prepared by natural cooling. The critical strains, where G' is equal to G″ on the strain dependence of the storage modulus, for magnetic gels prepared by natural cooling and rapid cooling, were 0.023 and 0.034, respectively, indicating that the magnetic gel prepared by rapid cooling has a hard structure compared to that prepared by natural cooling. Opposite to this, the change in the storage modulus at 500 mT for the magnetic gel prepared by rapid cooling was 1.6 × 105 Pa, which was 2.5 times higher than that prepared by natural cooling. SEM images revealed that many small aggregations of the carrageenan network were found in the magnetic gel prepared by natural cooling, and continuous phases of carrageenan network with large sizes were found in the magnetic gel prepared by rapid cooling. It was revealed that magnetic particles in the magnetic gel prepared by rapid cooling can move and form a chain structure at high magnetic fields by breaking the restriction from the continuous phases of carrageenan.

Transplantable cell-encapsulation device using a semipermeable ethylene-vinyl alcohol copolymer membrane in a mouse diabetic model.

Cell-based therapy is an attractive approach, and encapsulation of therapeutic cells is a promising strategy because it prevents immune responses and allows transplanted cells to be retrieved in case of dysfunction. Bioartificial pancreas, in which insulin-secreting cells are encapsulated in a semipermeable membrane bag, is a new class of medical device for treating type-I diabetes. In this study, we developed a macroencapsulation device in which the pancreatic beta cell line MIN6 was encapsulated in a semipermeable bag made of an ethylene-vinyl alcohol copolymer membrane. In vitro evaluation of ATP and insulin levels revealed that MIN6 cells grown in Matrigel within the device secreted insulin in response to glucose levels. Transplantation of the device lowered blood glucose levels for 30 days in diabetic mice. Histological observation revealed that MIN6 cells formed spheroids in Matrigel, and no host cells were detected within the device. Blood levels of inflammatory cytokines in the transplanted mice were similar to those in non-transplanted mice, and antibody levels in the device were lower than those in the intraperitoneal fluid. These results suggest that the semipermeable ethylene-vinyl alcohol copolymer membrane developed in this study is useful for cell encapsulation in cell-based therapies, including beta-cell macroencapsulation for type-1 diabetes.

Expansion of human mesenchymal stem cells on poly(vinyl alcohol) microcarriers.

Microcarriers provide a high surface-area-to-volume ratio that can realize high yields of cell products, including human mesenchymal stem cells (hMSCs). Here, we report a novel poly(vinyl alcohol) (PVA)-based microcarrier for hMSC expansion in suspension culture. PVA microcarriers were prepared as collagen-coated PVA hydrogels 181 µm in size and a high surface-area-to-weight ratio of 2945 cm2/g. The PVA microcarriers supported a 2.6-fold expansion of hMSCs in a 30-mL single-use stirred bioreactor after a 7 d culture period, comparable to that of commercially available microcarriers. Interestingly, we observed that hMSCs on PVA microcarriers adhered to adjacent microcarriers, resulting in the aggregation of hMSC-PVA microcarriers. Therefore, we conducted a long-term expansion culture using a bead-to-bead cell transfer method with PVA microcarriers. Fresh microcarriers were added to the cell-populated microcarriers in the bioreactor on days 7 and 14. hMSCs on PVA microcarriers continued to grow for 21 d using the bead-to-bead cell transfer method. Furthermore, magnetic PVA (PVA-mag) microcarriers were developed by loading magnetic nanoparticles into PVA microcarriers, and we demonstrated that these PVA-mag microcarriers enabled cell recovery by magnetic separation. These results suggest that these PVA microcarriers can contribute to the large-scale culture of hMSCs for regenerative medicine and cell therapy.

Effective magnetic hyperthermia induced by mitochondria-targeted nanoparticles modified with triphenylphosphonium-containing phospholipid polymers.

Magnetic hyperthermia (MHT) is a promising cancer treatment because tumor tissue can be specifically damaged by utilizing the heat generated by nano-heaters such as magnetite nanoparticles (MNPs) under an alternating magnetic field. MNPs are taken up by cancer cells, enabling intracellular MHT. Subcellular localization of MNPs can affect the efficiency of intracellular MHT. In this study, we attempted to improve the therapeutic efficacy of MHT by using mitochondria-targeting MNPs. Mitochondria-targeting MNPs were prepared by the modification of carboxyl phospholipid polymers containing triphenylphosphonium (TPP) moieties that accumulate in mitochondria. The mitochondrial localization of polymer-modified MNPs was supported by transmission electron microscopy observations of murine colon cancer CT26 cells treated with polymer-modified MNPs. In vitro and in vivo MHT using polymer-modified MNPs revealed that the therapeutic effects were enhanced by introducing TPP. Our results indicate the validity of mitochondria targeting in enhancing the therapeutic outcome of MHT. These findings will pave the way for developing a new strategy for the surface design of MNPs and therapeutic strategies for MHT.

Nanowarming of vitrified pancreatic islets as a cryopreservation technology for transplantation.

Biobanking of pancreatic islets for transplantation could solve the shortage of donors, and cryopreservation of vitrified islets is a possible approach. However, a technological barrier is rewarming of large volumes both uniformly and rapidly to prevent ice formation due to devitrification. Here, we describe successful recovery of islets from the vitrified state using a volumetric rewarming technology called "nanowarming," which is inductive heating of magnetic nanoparticles under an alternating magnetic field. Convective warming using a 37°C water bath as the gold standard for rewarming of vitrified samples resulted in a decrease in the viability of mouse islets in large volumes (>1 ml) owing to devitrification caused by slow warming. Nanowarming showed uniform and rapid rewarming of vitrified islets in large volumes. The viability of nanowarmed islets was significantly improved and islets transplanted into streptozotocin-induced diabetic mice successfully lowered serum glucose. The results suggest that nanowarming will lead to a breakthrough in biobanking of islets for transplantation.

Treatment planning comparison of high-dose-rate brachytherapy vs. robotic and conventional stereotactic body radiotherapy for ultrahypofractionated treatment of prostate cancer.

Background and purpose: Ultrahypofractionated radiation therapy is increasingly used in the treatment of prostate cancer. High-dose-rate brachytherapy (HDR-BT) and stereotactic body radiotherapy (SBRT) are representative methods of ultrahypofractionation. This study was performed to compare clinically applied treatment plans for patients who had been treated using HDR-BT vs. conventional or robotic SBRT. Materials and methods: Calculated dose-volume indices between HDR-BT without a perirectal spacer (n = 20), robotic SBRT without a spacer (n = 40), and conventional (non-robotic) SBRT with a spacer (n = 40) were compared. Percentages against the prescription dose regarding the planning target volume (PTV), bladder, rectum, and urethra were statistically compared. Results: The D50% of the PTV with HDR-BT (140.5% ± 4.9%) was significantly higher than that with robotic or conventional SBRT (116.2% ± 1.6%, 101.0% ± 0.4%, p < 0.01). The D2cm3 of the bladder with HDR-BT (65.6% ± 6.4%) was significantly lower than those with SBRT (105.3% ± 2.9%, 98.0% ± 1.3%, p < 0.01). The D2cm3 of the rectum with HDR-BT (60.6% ± 6.2%) was also significantly lower than those with SBRT (85.1% ± 8.8%, 70.4% ± 9.6%, p < 0.01). By contrast, the D0.1cm3 of the urethra with HDR-BT (117.1% ± 3.6%) was significantly higher than those with SBRT (100.2% ± 0.7%, 104.5% ± 0.6%, p < 0.01). Conclusions: HDR-BT could administer a higher dose to the PTV and a lower dose to the bladder and rectum, at the cost of a slightly higher dose to the urethra compared with SBRT.

Management of autoimmune factor XIII deficiency in a frail, elderly patient.

Autoimmune factor XIII/13 deficiency (aFXIII deficiency) is a rare hemorrhagic disorder, for which typical guideline-directed treatment is aggressive immunosuppressive therapy. Approximately 20% of patients are over 80 years old; however, and optimum management of such patients has not reached consensus. Our elderly patient had massive intramuscular hematoma, and aFXIII deficiency was diagnosed. The patient opted against aggressive immunosuppressive therapy, so he was managed with conservative treatment only. Thorough survey of other correctable causes of bleeding and anemia is also required in similar cases. Our patient's serotonin-norepinephrine reuptake inhibitor use and multivitamin deficiency (vitamin C, B 12 and folic acid) were revealed to be aggravating factors. Fall prevention and muscular stress prevention are also important in elderly patients. Our patient had two relapses of bleeding within 6 months, which were improved spontaneously by bed rest without factor XIII replacement therapy or blood transfusion. Conservative management may be preferred for frail and elderly patients with aFXIII deficiency when they opt against standard therapy.

Development of a Method for Peeling Off Paper from Celluloid Pictures for Animation Films.

During the storage of celluloid pictures for animation films over half a century, an interleave paper adhered to acrylic paint. The purpose of this study is to establish a methodology to cleanly remove the paper from the paint. A layered film, a replica of the celluloid pictures, adhered with paper was prepared and immersed in water or ethanol. The effect of these solvents on the peeling behavior was investigated using a peel test. The maximum peel force for the dry layered film in was distributed at ~0.5 N, independently of the peel speed. The peel force was significantly reduced after the layered film was immersed in pure water or ethanol. A morphological observation revealed that the dry paper was peeled off via the cohesive failure of the paper. After the layered film was immersed in pure water, the paper was also peeled off via cohesive failure. The layered film immersed in ethanol was peeled off at the paper/paint interface. To clear the effect of the volume change in the paint on peel behavior, the relative volume was determined via image analysis. The relative volume of paint was 1.56 in pure water and 1.37 in ethanol. It can be considered that the large difference in the volume of paint induces a large shear stress at the paint/paper interface.

Skin-to-Renal Pelvis Distance Predicts Costovertebral Angle Tenderness in Adult Patients with Acute Focal Bacterial Nephritis.

OBJECTIVES: The aim of this study was to examine whether the distance between the skin and the renal pelvis affects the detection of costovertebral angle (CVA) tenderness in patients with acute focal bacterial nephritis (AFBN). METHODS: We retrospectively reviewed the charts of our patients between April 2013 and June 2019 who were diagnosed as having AFBN. Diagnosis was based on ultrasound or computed tomography with contrast, revealing at least one wedge-shaped area of decreased vascularity and confirmation of fever not attributable to another condition. RESULTS: We extracted 23 cases, all Japanese (mean age 60.0 years old [range 45-81 years], 7 males, 16 females). CVA tenderness was present in 8 of these 23 patients. Receiver operating characteristic curves were drawn to evaluate the ability to differentiate skin-to-renal pelvis distance (SPD), body mass index, and age. Only SPD was a useful predictor of CVA tenderness, and 66 mm was determined as the optimal cutoff point (area under the receiver operating characteristic curve 0.858, 95% confidence interval 0.70-1.00). Logistic regression analysis was performed with CVA tenderness as a dependent variable, and SPD, body mass index, and age as explanatory variables. SPD was an independent predictive variable of CVA tenderness (P = 0.038, odds ratio 0.76, 95% confidence interval 0.590-0.986). CONCLUSIONS: CVA tenderness showed low yield in the diagnosis of AFBN in patients with longer SPD. Its use for diagnosis in obese patients may therefore be limited.

Combination of magnetic hyperthermia and immunomodulators to drive complete tumor regression of poorly immunogenic melanoma.

Hyperthermia using magnetic nanoparticles enables tumor-specific heating and can destroy tumor tissues. This approach works as in situ vaccination with tumor antigens released from dying tumor cells. However, in situ vaccination caused by magnetic hyperthermia is often insufficient to induce complete regression of poorly immunogenic tumors surrounded by an immunosuppressive microenvironment. In this study, we explored a novel strategy for immunotherapy using magnetic hyperthermia to regress poorly immunogenic melanoma. Magnetic hyperthermia induced tumor cell death in a B16-F10 melanoma mouse model. After hyperthermia treatment, we found elevated levels of HMGB1, which is known to be released from dying cells to promote inflammation, and the proinflammatory cytokine TNF-α was increased in serum of the mice. Systemic administration of glycyrrhizin, an HMGB1 inhibitor, reduced the levels of TNF-α in serum and successfully delayed the regrowth of tumors after magnetic hyperthermia. To achieve complete tumor regression, TLR9 activation by intratumor injection of CpG was combined with systemic administration of anti-PD-1 antibody and anti-CTLA-4 antibody. The combination therapy of magnetic hyperthermia at 46°C with the immunomodulators (glycyrrhizin+CpG+anti-PD-1+anti-CTLA-4) achieved complete tumor regression in 80% of growing 5-mm B16-F10 tumors. These findings have important implications for the development of novel cancer immunotherapy using magnetic hyperthermia for poorly immunogenic tumors.

Mizoribine halts kidney fibrosis in childhood IgA nephropathy: association with modulation of M2-type macrophages.

BACKGROUND: The immunosuppressant mizoribine (Miz) can reduce progression of childhood IgA nephropathy (IgAN). This study examined whether Miz affects CD163+ M2-type macrophages which are associated with kidney fibrosis in childhood IgAN. METHODS: A retrospective cohort of 90 children with IgAN were divided into groups treated with prednisolone (PSL) alone (P group; n = 42) or PSL plus Miz (PM group; n = 48) for a 2-year period. Normal human monocyte-derived macrophages were stimulated with dexamethasone (Dex), or Dex plus Miz, and analyzed by DNA microarray. RESULTS: Clinical and histological findings at first biopsy were equivalent between patients entering the P and PM groups. Both treatments improved proteinuria and haematuria, and maintained normal kidney function over the 2-year course. The P group exhibited increased mesangial matrix expansion, increased glomerular segmental or global sclerosis, and increased interstitial fibrosis at 2-year biopsy; however, the PM group showed no progression of kidney fibrosis. These protective effects were associated with reduced numbers of glomerular and interstitial CD163+ macrophages in the PM versus P group. In cultured human macrophages, Dex induced upregulation of cytokines and growth factors, which was prevented by Miz. Miz also inhibited Dex-induced expression of CD300E, an activating receptor which can prevent monocyte apoptosis. CD300e expression by CD163+ macrophages was evident in the P group, which was reduced by Miz treatment. CONCLUSION: Miz halted the progression of kidney fibrosis in PSL-treated pediatric IgAN. This was associated with reduced CD163+ and CD163+CD300e+ macrophage populations, plus in vitro findings that Miz can suppress steroid-induced macrophage expression of pro-fibrotic molecules. A higher resolution version of the Graphical abstract is available as Supplementary information.

Mechanical Properties and Reinforcement of Paper Sheets Composited with Carboxymethyl Cellulose.

The mechanical properties for paper sheets composited with glucose (Glc), methyl cellulose (MC), and carboxymethyl cellulose (CMC) were investigated. The paper composites were prepared by immersing paper sheets in aqueous solutions of these materials and drying at 100 °C for 30 min. The stress-strain curves for these paper composites were measured by a uniaxial tensile apparatus with a stretching speed of 2 mm/min. The breaking stress and strain for untreated paper were 24 MPa and 0.016, respectively. The paper composites demonstrated stress-strain curves similar to the untreated paper; however, the breaking point largely differed for these composites. The breaking strain and breaking stress for the Glc composite slightly decreased and those for the MC composite gradually increased with the concentration of materials composited. Significant increases in the mechanical properties were observed for the CMC composite. The breaking stress, breaking strain, and breaking energy for the 3 wt.% CMC composite were 2.0-, 3.9-, and 8.0-fold higher than those for untreated paper, respectively. SEM photographs indicated that the CMC penetrated into the inner part of the paper. These results strongly suggest that the mechanical improvement for CMC composites can be understood as an enhancement of the bond strength between the paper fibrils by CMC, which acts as a bonding agent. It was also revealed that the breaking strain, breaking stress, and breaking energy for the CMC composites were at maximum at the first cycle and decreased gradually as the immersion cycles increased.

Long-term outcomes of hypoplastic left heart syndrome with analysis of the Norwood procedure in infants following bilateral pulmonary artery banding.

Objective: To investigate the early and long-term outcomes of the deferred Norwood procedure by bilateral pulmonary artery banding (BPAB) versus the neonatal Norwood procedure. Methods: This retrospective study examined 46 patients with hypoplastic left heart syndrome and its variants undergoing the Norwood procedure for single ventricle physiology between 2004 and 2022 at 3 institutions. The patients were divided into 2 groups: neonatal Norwood procedure (group N; n = 23) and staged Norwood procedure in infants following BPAB (group I; n = 23). Preoperative risk factors, surgical results, survival rates, Fontan candidacy, and long-term complications were compared. Results: Early survival rates after the Norwood procedure were 91.3% (21 of 23) in both groups. Late survival rates after the Norwood procedure were similar at the 10-year follow-up (group N, 76.3%; group I, 68.7%; P = .63). Fontan completion rates also were comparable in the 2 groups (group N, 77.8%; group I, 85.7%; P = .67). Group N showed a higher median pulmonary artery (PA) index before bidirectional cavopulmonary connection (group N, 177 [interquartile range (IQR), 147-243] mm2/m2; group I, 152 [IQR, 146-163] mm2/m2; P = .03); this trend continued until 5 years after Fontan completion (P = .01). Group N also had a lower rate of freedom from protein-losing enteropathy (PLE) at 9.0 years after the Fontan operation (90.0% vs 52.5% for group I; P = .04), although the incidences of other Fontan-associated events were not significantly different. Conclusions: Fontan candidacy and survival rates were similar regardless of the timing of the Norwood procedure. Early performance of the Norwood procedure may lead to lower rates of late Fontan-associated events, such as PLE.