Lymphoscintigraphy Findings are Associated with Outcome in Children with Chylothorax After Cardiac Surgery.

Postoperative chylothorax in patients with congenital heart diseases (CHD) results in poor outcomes if anatomical and functional abnormalities of the lymphatic system are present. While these abnormalities are typically diagnosed by intranodal lymphangiography and dynamic contrast magnetic resonance lymphangiography, the usefulness of lymphoscintigraphy in these patients has not been evaluated. Between January 2019 and December 2021, 28 lymphoscintigraphies were performed in our institution for investigating prolonged pleural effusion after cardiac surgery. The images were assessed by three board-certified pediatric cardiologists retrospectively to determine the likelihood of a central lymphatic flow disorder. The likelihood was scored (range 1-3) based on structural abnormalities and congestive flow in the lymphatic system. Those scores were summed and the likelihood was categorized as low to intermediate (< 8 points) or high (8 or 9 points). Median age at lymphoscintigraphy was 129 days (IQR, 41-412 days), it was performed at a median of 22 days (IQR, 17-43) after surgery, and median score was 6 points (IQR, 4-7.5). Kendall's coefficient of concordance (0.867; p < 0.05) indicated high inter-rater reliability. Overall survival at 6 months after surgery was 92.5% in the low-to-intermediate group but 68.6% in the high group (p < 0.05), and duration of postoperative thoracic drainage was 27 and 58 days, respectively (p < 0.05). Lymphatic abnormalities detected by lymphoscintigraphy were associated with poorer outcomes. Lymphoscintigraphy was thought to be useful in assessing anatomic and functional lymphatic abnormalities, despite its minimal invasiveness.

Simultaneous Visualization of the Thoracic Duct and Blood Vessels Using MRI: A Comparison Between Balanced Turbo-field-echo and Spin-echo.

OBJECTIVE: Magnetic resonance thoracic ductography (MRTD), concomitant with blood vessel imaging, provides useful anatomical information. The purpose of this study was to assess the visibility of the thoracic duct and blood vessels simultaneously by MRTD using balanced turbo-field-echo (bTFE) and turbo spin-echo (TSE). METHODS: MRTDs concomitant with blood vessel imaging on bTFE and TSE were obtained for 10 healthy volunteers with a 1.5T-magnetic resonance unit. Visibility of the thoracic duct, blood vessels in the thoracic region; motion artifacts; and overall image quality were scored by two radiologists using three-to-five-point scales; those were compared between bTFE and TSE. RESULTS: The thoracic duct was generally well-visualized on MRTD sequences. The upper part of the thoracic duct was better visualized on TSE than on bTFE (p < 0.05). The blood vessels were well visualized on bTFE and TSE; the bilateral subclavian arteries and the right subclavian veins were better visualized on TSE than on bTFE (all p < 0.05). Motion artifacts and overall image quality were better on TSE than on bTFE (p = 0.0039 and 0.0020, respectively). CONCLUSION: MRTD concomitant with blood vessel imaging on TSE has better visibility of the thoracic duct and blood vessels than bTFE.

Fusion imaging of single-photon emission computed tomography and magnetic resonance lymphangiography for post-Fontan chylothorax.

A preschool male patient with an extensive cardiac surgical history developed refractory chylothorax after a total cavopulmonary connection. Neither lymphoscintigraphy nor single-photon emission computed tomography (SPECT)/computed tomography could identify the lymphatic system leakage sites. Non-contrast heavy T2-weighted magnetic resonance lymphangiography (MRL) was performed to visualize the lymphatic system. Nevertheless, distinguishing lymphatic ducts from other watery structures of the patient remained difficult. Therefore, non-contrast MRL and SPECT images were fused. This hybrid diagnostic tool elucidated the pathophysiology of the prolonged chylothorax; pulmonary lymphatic perfusion syndrome and illustrated the anatomical connection of the thoracic duct and an abnormally dilated lymphatic network in the neck and left hilar regions. Subsequent intranodal lymphangiography with ethiodized oil confirmed these findings. SPECT/MRL may become an alternative modality for revealing the mechanism of prolonged chylothorax by visualizing the lymphatic system when dynamic contrast-enhanced magnetic resonance lymphangiography is unavailable.

Role of Nrf2 in Methotrexate-Induced Epithelial-Mesenchymal Transition in Alveolar A549 Cells.

Methotrexate (MTX) is known to induce serious lung diseases, such as pulmonary fibrosis. Although we demonstrated that MTX is associated with epithelial-mesenchymal transition (EMT), the underlying mechanism remains unclear. Nuclear factor erythroid 2-related factor 2 (Nrf2), an oxidative stress response regulator, is related to EMT induction. In the present study, we examined the association of Nrf2 with the MTX-induced EMT in the alveolar epithelial cell line A549. MTX treatment decreased the mRNA expression of heme oxidase-1 (HO-1), a target of Nrf2, which was inhibited by co-treatment with diethyl maleate (DEM), an Nrf2 activator. Additionally, the MTX-induced increase in reactive oxygen species (ROS) production was significantly suppressed by DEM. Furthermore, DEM decreased mRNA/protein expression levels of α-smooth muscle actin (SMA), a representative EMT marker, which were upregulated by MTX. Nuclear expression and localization of Nrf2 were suppressed by MTX treatment, which led to a decrease in Nrf2 activity. Finally, in Nrf2 knockdown cells, the MTX-induced enhancement of α-SMA mRNA/protein expression was not observed, indicating that downregulation of Nrf2 may play a critical role in the MTX-induced EMT in A549 cells. These results suggest that Nrf2-regulated transcriptional activity would be associated with the MTX-induced EMT induction.

Planar or Biaxial Stretching of Poly(ethylene terephthalate) Fiber Webs Prepared by Laser-Electrospinning.

In this work, laser-heated electrospinning (LES) process using carbon dioxide laser was explored as an eco-friendly method for producing ultrafine fibers. To enhance the thinning of fibers and the formation of fiber structure, planar or equibiaxial stretching and subsequent annealing processes were applied to poly(ethylene terephthalate) (PET) fiber webs prepared by LES. The structure and properties of the obtained webs were investigated. Ultrafine fiber webs with an average diameter of approximately 1 µm and a coefficient of variation of 20-25% were obtained when the stretch ratios in the MD (machine direction) × TD (transverse direction) were 3 × 1 and 3 × 3 for the planar and equibiaxial stretching, respectively. In the wide-angle X-ray diffraction analysis of the web samples, preferential orientation of crystalline c-axis were confirmed along the MD for planar stretching and only along the web plane for equibiaxial stretching, which was in contrast to the stretching of film samples, where additional preferential orientation of benzene ring along the film plane proceeded. The results obtained suggest that PET fiber webs fabricated through LES and subsequent planar or biaxial stretching processes have potential for a wide variety of applications, such as packaging and battery separator materials.

Onset of pulmonary Epstein-Barr virus-positive diffuse large B-cell lymphoma in a patient with silicosis.

How Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) occasionally occurs following chronic inflammation remains to be elucidated. The case of a 57-year-old man who developed pulmonary EBV-positive DLBCL from underlying silicosis lesions is presented. Immunohistochemical examination of the resected silicosis lesions showed predominant helper T cells and M1/M2 macrophages, with a lack of B cells, regulatory T cells, and resident memory T cells. Two years later, EBV-positive DLBCL emerged unexpectedly from the silicosis. The imbalance of the immune cells in the microenvironment, at least in part, may help explain how chronic inflammation contributes to EBV-positive DLBCL.

Ultraselective transcatheter arterial embolization with small-sized microcoils for acute lower gastrointestinal bleeding.

PURPOSE: To evaluate the clinical outcome of ultraselective transcatheter arterial embolization (TAE) with small-sized microcoils for acute lower gastrointestinal bleeding (LGIB). MATERIALS AND METHODS: The subjects were 17 consecutive patients (mean age, 69 years) with LGIB who were treated with ultraselective TAE using small-sized microcoils between December 2013 and December 2019. Ultraselective TAE was defined as embolization of one or both of the long or short branches of the vasa recta. The etiologies of bleeding were colonic diverticulosis in 16 patients (94%) and malignancy in one patient (6%). The bleeding foci were in the ascending colon in 11 patients (65%), transverse colon in 2 patients (12%), and sigmoid colon in 4 patients (23%). A total of 18 branches (diameter: range 0.5-1.5 mm, mean 1.1 mm) of the vasa recta in 17 patients were embolized with small-sized microcoils (size range 1-3 mm, mean combined lengths of all microcoils 7.6 cm). The mean follow-up period was 19 months (range 1-80 months). The technical and clinical success rate, recurrent bleeding rate, major complications and long-term clinical outcomes were retrospectively evaluated. RESULTS: Technical and clinical success was achieved in all patients (17/17). The rates of early recurrent bleeding (within 30 days of TAE) and major complications were 0% (0/17). Recurrent bleeding occurred in one patient at 2 months after TAE, but was stopped with conservative treatment. There were no other bleeding episodes or complications in the follow-up period. CONCLUSION: Ultraselective TAE with small-sized microcoils is a highly effective and safe treatment modality for LGIB.

Intranodal Embolization for Groin Lymphocele.

Purpose: Intranodal embolization using n-butyl cyanoacrylate glue is an emerging treatment option for persistent lymphatic leakage. This report describes the procedure details of intranodal embolization for groin lymphocele and evaluates the efficacy of intranodal embolization at our institution via retrospective chart review. Material and Methods: Nine consecutive patients (six men and three women; median age, 77.4 years; range, 43-95 years) who underwent intranodal embolization for groin lymphocele between January 2017 and December 2019 were included as study subjects. Intranodal lymphangiography with iodinated contrast was performed to confirm lymphatic leakage, followed by intranodal embolization using n-butyl cyanoacrylate glue mixed with iodized oil for all nine patients. The etiologies of lymphocele, technical and clinical success rates of intranodal embolization, duration of treatment, follow-up period, and acute and chronic complications were retrospectively investigated. Results: The etiologies of groin lymphoceles were the cutdown access of inguinal vessels (n = 7), lymph node biopsy (n = 1), and trauma (n = 1). The technical and clinical success rates of both lymphangiography and subsequent intranodal embolization were 100%. For intranodal embolization, 16.7%-33.3% n-butyl cyanoacrylate glue was used. The median duration of treatment was 2 days (range, 1-13 days). The follow-up period lasted 0-895 days (median, 9 days). No acute or chronic complications were observed. Conclusions: In this study, intranodal embolization showed promising results for groin lymphocele with a short duration of treatment with a median of 2 days. Intranodal embolization using n-butyl cyanoacrylate glue could be a treatment option for persistent groin lymphocele. However, further research is warranted to further evaluate the efficacy of intranodal embolization.

Structure and Properties of Poly(ethylene terephthalate) Fiber Webs Prepared via Laser-Electrospinning and Subsequent Annealing Processes.

Melt-electrospinning is an eco-friendly method for producing ultra-fine fibers without using any solvent. We prepared webs of poly(ethylene terephthalate) (PET) through melt-electrospinning using CO2 laser irradiation for heating. The PET webs comprised ultra-fine fibers of uniform diameter (average fiber diameter = 1.66 µm, coefficient of variation = 19%). The co-existence of fibers with high and low molecular orientation was confirmed through birefringence measurements. Although the level of high orientation corresponded to that of commercial highly oriented yarn, crystalline diffraction was not observed in the wide-angle X-ray diffraction (WAXD) analysis of the webs. The crystallinity of the webs was estimated using differential scanning calorimetry (DSC). The fibers with higher birefringence did not exhibit any cold crystallization peak. After annealing the web at 116 °C for 5 min, a further increase in the birefringence of the fibers with higher orientation was observed. The WAXD results revealed that the annealed webs showed crystalline diffraction peaks with the orientation of the c-axis along the fiber axis. In summary, the formation of fibers with a unique non-crystalline structure with extremely high orientation was confirmed.

Anomalous retro-psoas iliac artery in a patient with right renal cancer: A case report.

Anomalous retro-psoas artery is an extremely rare congenital anomaly of the iliac arteries reported in the English-language literature. Using contrast-enhanced computed tomography, we incidentally diagnosed an anomalous retro-psoas artery in a 60-year-old male patient with right renal cancer. Although anomalous retro-psoas artery is extremely rare and mostly asymptomatic, knowledge of it is needed to avoid severe vascular complications in the event of vascular intervention and surgery.

Detection of the oil-producing microalga Botryococcus braunii in natural freshwater environments by targeting the hydrocarbon biosynthesis gene SSL-3.

The green microalga Botryococcus braunii produces hydrocarbon oils at 25-75% of its dry weight and is a promising source of biofuel feedstock. Few studies have examined this species' ecology in natural habitats, and few wild genetic resources have been collected due to difficulties caused by its low abundance in nature. This study aimed to develop a real-time PCR assay for specific detection and quantification of this alga in natural environments and to quantify spatiotemporal variations of wild B. braunii populations in a tropical pond. We designed PCR primers toward the hydrocarbon biosynthesis gene SSL-3 and examined amplification specificity and PCR efficiency with 70 wild strains newly isolated from various environments. The results demonstrated that this PCR assay specifically amplified B. braunii DNA, especially that of B-race strains, and can be widely used to detect wild B. braunii strains in temperate and tropical habitats. Field-testing in a tropical pond suggested a diurnal change in the abundance of B. braunii in surface water and found B. braunii not only in surface water, but also at 1-1.5 m deep and in bottom sediments. This method can contribute to efficient genetic resource exploitations and may also help elucidate the unknown ecology of B. braunii.

Investigation on inhibitory effect of folic acid on methotrexate-induced epithelial-mesenchymal transition focusing on dihydrofolate reductase.

Use of methotrexate (MTX) can induce serious adverse lung reactions, such as pulmonary fibrosis. Recently, we demonstrated that the epithelial-mesenchymal transition (EMT), which triggers pulmonary fibrosis, was induced by MTX, and folic acid (FA) suppressed MTX-induced EMT in A549 cells. In this study, the role of dihydrofolate reductase (DHFR), a target of MTX, in FA-mediated inhibition of MTX-induced EMT was evaluated. The inhibitory effects of FA and tetrahydrofolate (THF), a metabolite of FA produced by DHFR, on MTX-induced increases in mRNA expression of α-SMA, an EMT marker, were compared. The IC50 values of FA and THF for DHFR were 103.3 and 19.4 µM, respectively. In contrast, DHFR knockdown did not alter the mRNA expression of α-SMA. Notably, the inhibitory effect of FA, but not THF, on MTX-induced EMT was blunted in DHFR knockdown cells. These results suggested that DHFR may not directly contribute to MTX-induced EMT, but may contribute to suppression of MTX-induced EMT via production of THF in A549 cells.

Endovascular Catheter Biopsy for the Diagnosis of Pulmonary Artery Sarcoma.

The diagnosis of pulmonary artery sarcoma (PAS) is challenging, and its definitive diagnosis is mainly confirmed using specimens obtained during surgery or autopsy. Endovascular catheter biopsy was performed in five patients with suspected PAS to establish a definitive diagnosis. Aspiration biopsy was performed in all patients, and forceps biopsy was performed in one patient. Three patients were diagnosed with PAS, and no definitive diagnosis was obtained in two patients with squamous cell lung carcinoma with pulmonary artery infiltration. Endovascular catheter biopsy is helpful in the diagnosis of PAS and should be performed when a tumor is suspected.

Presence of few PD-1-expressing tumor-infiltrating immune cells is a potential predictor of improved response to salvage chemotherapy following nivolumab for non-small cell lung cancer: An exploratory case series.

BACKGROUND: The combination of PD-1 inhibitors and cytotoxic drugs is reported to enhance anti-tumor activity in non-small cell lung cancer; however, the underlying synergistic mechanisms remain uncertain. This retrospective case series was designed to investigate objective response and survival rates of salvage chemotherapy following nivolumab and explore the immunohistochemical profiles of tumor-infiltrating immune cells. METHODS: The medical records of 37 patients administered nivolumab were retrospectively reviewed. Overall response rate and progression-free survival were compared among three groups: salvage chemotherapy following nivolumab, nivolumab therapy alone, and chemotherapy preceding nivolumab. RESULTS: Eight cases met the study criteria. Salvage chemotherapy following nivolumab improved the overall response rate to 62.5% (95% confidence interval [CI] 34.4-90.6%; P = 0.004) and median progression-free survival to six months (95% CI 4.6-7.4; P = 0.016), compared to nivolumab alone and preceding chemotherapy. The response to salvage chemotherapy was not associated with tumor PD-L1 expression. A partial response was achieved in four cases with ≤ 5% and ≤ 2.9 cells/mm2 of PD-1+ immune cells, whereas stable disease and progressive disease were observed in three cases with ≥ 30% and ≥ 12.7 cells/mm2 . Responders had fewer PD-1+ immune cells than non-responders (percentage P = 0.028; density P = 0.034). CONCLUSION: Salvage chemotherapy following nivolumab improved anti-tumor activity regardless of tumor PD-L1 status, but nivolumab following chemotherapy did not. The presence of few PD-1+ tumor-infiltrating immune cells may serve as a potential predictor of response to salvage chemotherapy. Further studies involving a large cohort are needed to clarify how nivolumab re-sensitizes the tumor immune microenvironment to chemotherapy.

Utility of a 3D Roadmap During Balloon-occluded Retrograde Transvenous Obliteration for Gastric Varices.

OBJECTIVE: We describe our initial clinical experience regarding the use of a 3D roadmap during balloon-occluded retrograde transvenous obliteration (BRTO) in three patients. METHODS: Between June 2016 and July 2016, three BRTO procedures were performed in three patients with gastric varices. Preprocedural intravenous dynamic CT was performed, and portal venous phase CT images were postprocessed to obtain volume rendering (VR) images. A 3D roadmap was developed by overlaying the VR images onto the real-time X-ray fluoroscopy images. This 3D roadmap was used for interventional guidance during the BRTO procedure. RESULTS: Using a 3D roadmap, the catheterization of the gastrorenal shunt was successfully accomplished. In addition, in all three patients, the sclerosant could reach the gastric varices without the administration of iodinated contrast medium. Fluoroscopy time and the iodinated contrast dose administered in the present cohort were also substantially lower than in our previous cohorts that did not use a 3D roadmap. CONCLUSION: Using a 3D roadmap during BRTO enables easier and faster catheter manipulation, thereby helping to reduce both radiation exposure and the need to administer iodinated contrast medium.

Successful treatment with nivolumab for lung cancer with low expression of PD-L1 and prominent tumor-infiltrating B cells and immunoglobulin G.

Little is known about the anti-tumor activity of humoral immunity in lung cancer patients treated with nivolumab, an immune checkpoint inhibitor. Herein, we report a case of lung cancer with 5% expression of PD-L1, in which a partial response to nivolumab was sustained for > 7 months. Immunohistochemical analysis of the metastatic lymph node biopsy specimen showed prominent accumulation of plasma cells and immunoglobulin G. These findings suggest that pre-existing humoral immunity may be worth considering as a candidate therapeutic biomarker of nivolumab in some lung cancer patients.

Changes in HepG2 spheroid behavior induced by differences in the gap distance between spheroids in a micropatterned culture system.

Micropatterning is a promising technique for modulating culture environments. In this study, we investigated the effect of spheroid separation distance on their properties in a micropatterned chip of HepG2 spheroids. The basic chip design consisted of 37 collagen spots (300 µm in diameter) in a hexagonal arrangement on a glass substrate; the region without collagen-spots was modified by polyethylene glycol to create the non-adhesive surface. Three similar chips were fabricated with gap distances between collagen-spots of 500, 1000, and 1500 µm. HepG2 cells adhered on the collagen spots and then formed spheroids via cell proliferation. Although the albumin secretion activities of HepG2 spheroids were almost the same in all chips, inhibition of spheroid growth and anaerobic metabolism were intensified when the gap distance was less than 1000 µm. Additionally, such phenomena which are induced by interference effects between spheroids, were more pronounced at the inside region of the chip than at the outside region. However, the interference effect between spheroids was nearly avoided when the gap distance was at least 1500 µm. Furthermore, the concentration of dissolved oxygen between neighboring spheroids decreased as the gap distance decreased, indicating that the spheroids competed for oxygen and became hypoxic in a way that depended on the spheroid separation distance. These results indicate that the spheroid separation distance is an important factor that can modulate the spheroid properties.

PARP9 and PARP14 cross-regulate macrophage activation via STAT1 ADP-ribosylation.

Despite the global impact of macrophage activation in vascular disease, the underlying mechanisms remain obscure. Here we show, with global proteomic analysis of macrophage cell lines treated with either IFNγ or IL-4, that PARP9 and PARP14 regulate macrophage activation. In primary macrophages, PARP9 and PARP14 have opposing roles in macrophage activation. PARP14 silencing induces pro-inflammatory genes and STAT1 phosphorylation in M(IFNγ) cells, whereas it suppresses anti-inflammatory gene expression and STAT6 phosphorylation in M(IL-4) cells. PARP9 silencing suppresses pro-inflammatory genes and STAT1 phosphorylation in M(IFNγ) cells. PARP14 induces ADP-ribosylation of STAT1, which is suppressed by PARP9. Mutations at these ADP-ribosylation sites lead to increased phosphorylation. Network analysis links PARP9-PARP14 with human coronary artery disease. PARP14 deficiency in haematopoietic cells accelerates the development and inflammatory burden of acute and chronic arterial lesions in mice. These findings suggest that PARP9 and PARP14 cross-regulate macrophage activation.

Construction of a linkage map based on retrotransposon insertion polymorphisms in sweetpotato via high-throughput sequencing.

Sweetpotato (Ipomoea batatas L.) is an outcrossing hexaploid species with a large number of chromosomes (2n = 6x = 90). Although sweetpotato is one of the world's most important crops, genetic analysis of the species has been hindered by its genetic complexity combined with the lack of a whole genome sequence. In the present study, we constructed a genetic linkage map based on retrotransposon insertion polymorphisms using a mapping population derived from a cross between 'Purple Sweet Lord' (PSL) and '90IDN-47' cultivars. High-throughput sequencing and subsequent data analyses identified many Rtsp-1 retrotransposon insertion sites, and their allele dosages (simplex, duplex, triplex, or double-simplex) were determined based on segregation ratios in the mapping population. Using a pseudo-testcross strategy, 43 and 47 linkage groups were generated for PSL and 90IDN-47, respectively. Interestingly, most of these insertions (~90%) were present in a simplex manner, indicating their utility for linkage map construction in polyploid species. Additionally, our approach led to savings of time and labor for genotyping. Although the number of markers herein was insufficient for map-based cloning, our trial analysis exhibited the utility of retrotransposon-based markers for linkage map construction in sweetpotato.