Transarterial Embolization of Renal Arteriovenous Malformations: Treatment Outcomes According to Angiographic Classification.

PURPOSE: To assess the different adjunctive catheter techniques required to achieve complete occlusion of renal arteriovenous malformations (rAVMs) of different angioarchitectural types. MATERIALS AND METHODS: Overall, data on 18 patients with rAVM (Type 1, n = 7; Type 2, n = 2; Type 3, n = 9; mean age, 53.8 years) who underwent 25 procedures between 2011 and 2022 were reviewed. The clinical presentations, endovascular techniques, arteriovenous malformation (AVM) occlusion rate, adverse events (including the incidence of renal infarction), and clinical symptoms and outcomes (including recurrence/increase of AVM) were analyzed according to the Cho-Do angioarchitectural classification. Posttreatment renal infarction was classified as no infarction, small infarction (<12.5%), medium infarction (12.5%-25%), and large infarction (>25%) using contrast-enhanced computed tomography or magnetic resonance imaging. RESULTS: Hematuria and heart failure were presenting symptoms in 10 and 2 patients, respectively. The embolic materials used were as follows: Type 1 rAVM, coils alone or with n-butyl-2-cyanoacrylate (nBCA); Type 2 rAVM, nBCA alone or with coils; and Type 3 rAVMs, nBCA alone. Fourteen patients underwent adjunctive catheter techniques, including flow control with a balloon catheter and multiple microcatheter placement, alone or in combination. Immediate postprocedural angiography revealed complete occlusion in 15 patients (83%) and marked regression of rAVM in 3 (17%). Small asymptomatic renal infarctions were observed in 6 patients with Type 3 rAVMs without any decrease in renal function. No major adverse events were observed. All symptomatic patients experienced symptom resolution. Recurrence/increase of rAVM was not observed during the mean 32-month follow-up period (range, 2-120 months). CONCLUSIONS: Transarterial embolization using adjunctive catheter techniques according to angioarchitectural types can be an effective treatment for rAVMs.

Association of metabolic dysfunction-associated steatotic liver disease with erosive esophagitis development: a longitudinal observational study.

BACKGROUND AND AIM: Although erosive esophagitis (EE) is associated with fatty liver and metabolic dysregulation, the association between EE and metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. Thus, this study aimed to investigate the longitudinal association between MASLD and EE. METHODS: We included 1578 patients without EE at baseline who underwent more than two health checkups over 2 years. Generalized estimation equations were used to analyze associations between MASLD and EE according to repeated measures at baseline and most recent stages. RESULTS: EE development rates in men and women were 14.5% and 7.2%, respectively. After adjusting for lifestyle habits, the odds ratios of MASLD for EE development in men and women were 1.907 (95% confidence interval [CI]: 1.289-2.832, P < 0.005) and 1.483 (95% CI: 0.783-2.811, P = 0.227), respectively. In the subgroup analysis, after adjusting for lifestyle habits, among men and women aged ≥50 years with more than three MASLD components, the odds ratios for EE development were 2.408 (95% CI: 1.505-3.855, P < 0.001) and 2.148 (95% CI: 1.093-4.221, P < 0.05), respectively. After adjusting for various factors, the significant risk factors for EE development were different between men and women. CONCLUSION: The influence of MASLD and other factors on EE development differed by sex and age. Particularly, patients aged ≥50 years with MASLD and with an increased number of MASLD components should be considered at increased risk for EE.

Histological Correlation between Tonsillar and Glomerular Lesions in Patients with IgA Nephropathy Justifying Tonsillectomy: A Retrospective Cohort Study.

Tonsillectomy with steroid pulse therapy (SPT) has been established as an effective treatment for immunoglobulin A nephropathy (IgAN) in Japan. However, the underlying mechanisms supporting tonsillectomy remain unclear. This study assessed palatine tonsils from 77 patients with IgAN, including 14 and 63 who received SPT before and after tonsillectomy, respectively. Tonsils from 21 patients with chronic tonsillitis were analyzed as controls. Specific tonsillar lesions were confirmed in patients with IgAN, correlating with active or chronic renal glomerular lesions and SPT. T-nodule and involution of lymphoepithelial symbiosis scores in tonsils correlated with the incidence of active crescents and segmental sclerosis in the glomeruli, respectively. The study revealed an essential role of the tonsil-glomerular axis in early active and late chronic phases. Moreover, the SPT-preceding group demonstrated no changes in the T-nodule score, which correlated with active crescent formation, but exhibited a considerable shrinkage of lymphatic follicles that produced aberrant IgA1. The study underscores the involvement of innate and cellular immunity in IgAN and advocates for tonsillectomy as a necessary treatment alongside SPT for IgAN, based on a stepwise process.

TIMP1 promotes cell proliferation and invasion capability of right-sided colon cancers via the FAK/Akt signaling pathway.

Although right-sided colorectal cancer (CRC) shows a worse prognosis than left-sided CRC, the underlying mechanism remains unclear. We established patient-derived organoids (PDOs) from left- and right-sided CRCs and directly compared cell proliferation and invasion capability between them. We then analyzed the expression of numerous genes in signal transduction pathways to clarify the mechanism of the differential prognosis. Cell proliferation activity and invasion capability in right-sided cancer PDOs were significantly higher than in left-sided cancer PDOs and normal PDOs, as revealed by Cell Titer Glo and transwell assays, respectively. We then used quantitative RT-PCR to compare 184 genes in 30 pathways among right-sided and left-sided cancer and normal PDOs and found that the TIMP1 mRNA level was highest in right-sided PDOs. TIMP1 protein levels were upregulated in right-sided PDOs compared with normal PDOs but was downregulated in left-sided PDOs. TIMP1 knockdown with shRNA significantly decreased cell proliferation activity and invasion capability in right-sided PDOs but not in left-sided PDOs. Moreover, TIMP1 knockdown significantly decreased pFAK and pAkt expression levels in right-sided PDOs but not in left-sided PDOs. A database analysis of The Cancer Genome Atlas revealed that TIMP1 expression in right-sided CRCs was significantly higher than in left-sided CRCs. Kaplan-Meier survival analysis showed significantly shorter overall survival in high-TIMP1 patients versus low-TIMP1 patients with right-sided CRCs but not left-sided CRCs. Our data suggest that TIMP1 is overexpressed in right-sided CRCs and promotes cell proliferation and invasion capability through the TIMP1/FAK/Akt pathway, leading to a poor prognosis. The TIMP1/FAK/Akt pathway can be a target for therapeutic agents in right-sided CRCs.

Multi-Redox Active Carbons and Hydrocarbons: Control of their Redox Properties and Potential Applications.

Precise control over redox properties is essential for high-performance organic electronic devices such as organic batteries, electrochromic devices, and information storage devices. In this context, multi-redox active carbons and hydrocarbons, represented as Cx Hy molecules (x≥1, y≥0), are highly sought after, because they can switch between multiple redox states. Herein, we outline the redox properties of Cx Hy molecules as solutes and adsorbed species. Furthermore, the limitations of evaluating their redox properties and the possible solutions are summarized. Additionally, the theoretical capacity (mAh/g) and gravimetric energy density (Wh/kg) of secondary batteries were estimated based on the redox properties of 185 Cx Hy molecules, which have primarily been reported in the last decade. Among them, seven Cx Hy molecules were found to have the potential to surpass the energy density of LiNi0.6 Mn0.2 Co0.2 O2 /graphite batteries. The use of Cx Hy molecules in multielectrochromic devices and multi-bit memory is also explained. We believe that this review will encourage further utilization of Cx Hy molecules thereby promoting its applications in organic electronic devices.

Encapsulating peritoneal sclerosis in a patient after allogeneic hematopoietic stem cell transplantation: a case report.

BACKGROUND: Encapsulating peritoneal sclerosis (EPS) is a chronic clinical syndrome of acute or subacute gastrointestinal obstruction seen mainly in patients undergoing peritoneal dialysis. Although there are a few reports on EPS developing in non-peritoneal dialysis patients, it has not been reported in patients undergoing allogeneic haematopoietic stem cell transplantation (HSCT). Here, we report a case of EPS after a second HSCT. CASE PRESENTATION: A 46-year-old man with myelodysplastic syndrome showed relapse after HSCT and received a second HSCT. The patient was diagnosed with chronic graft-versus-host disease (cGVHD)-associated serositis because of persistent ascites. His ascites improved gradually and disappeared without immunosuppressive therapy. He presented with nausea, weight loss, and constipation 1 year after improvement of ascites. Computed tomography revealed no organic obstruction, but did reveal dilated, thickened, and adhered small bowel loops with a mass-like appearance. He was diagnosed with EPS on the basis of clinical symptoms and image findings. He received corticosteroid therapy (20 mg/body) without any improvement in symptoms. He developed recurrence of myelodysplastic syndrome at 1 month after initiation of corticosteroid therapy. This progressed into acute myeloid leukaemia after 3 months. He died 31 months after the second HSCT. At autopsy, the small and large intestines had formed extensive adhesions and showed signs of progressive fibrosis with peritoneal sclerosis, fibroblast swelling, fibrin deposition, and inflammatory cell infiltration, which confirmed the diagnosis of EPS. CONCLUSION: This case suggests that EPS may complicate patients with cGVHD-associated serositis. Although the mechanism of EPS development is not clear, clinicians should be aware of this eventuality.

Forced expression of vascular endothelial growth factor-A in podocytes decreases mesangial cell numbers and attenuates endothelial cell differentiation in the mouse glomerulus.

BACKGROUND: Glomerular podocyte-derived vascular endothelial growth factor (VEGF) is indispensable for the migration and proliferation of glomerular endothelial cells. In contrast, podocyte-specific Vegf overexpression leads to the collapse of glomerular tufts; however, the mechanisms underlying this outcome have not yet been reported. METHODS: To further clarify the effects of elevated levels of Vegf expression on glomerular cells, we established a dual transgenic mouse line in which Vegf was exclusively and inducibly expressed in podocytes under the control of the "Tet-on system" (Podocin-rtTA/TetO-Vegf164 mice). RESULTS: Macroscopic and microscopic examination of Podocin-rtTA/TetO-Vegf164 animals following Vegf induction identified the presence of prominent red bloody spots. In addition, the endothelial cell number was increased along with enlargement of the subendothelial spaces. We also observed impaired endothelial fenestrations and aberrant plasmalemmal vesicle-associated protein-1 (PV-1) expression. In contrast, the mesangial cell number markedly decreased, resulting in a glomerular tuft intussusceptive splitting defect. Furthermore, whereas platelet-derived growth factor-B (PDGF-B) expression in the glomerular cells of Podocin-rtTA/TetO-Vegf164 mice was not decreased, phospho-PDGF receptor immunoreactivity in the mesangial cells was significantly decreased when compared to wild-type animals. CONCLUSION: Taken together, the results of this study indicated that the upregulation of podocyte VEGF decreased the number of mesangial cells, likely owing to inhibition of PDGF-B-mediated signaling.

Maternally inherited diabetes and deafness complicated by mesangial galactose-deficient IgA1 deposits: a case report.

BACKGROUND: Maternally inherited diabetes and deafness (MIDD), a mitochondrial genetic disorder, typically affects the kidneys and results in end-stage renal disease. Early diagnosis of MIDD is challenging when renal manifestations precede other key clinical features such as diabetes and deafness and/or when the disease is complicated by other renal pathologies. CASE PRESENTATION: Here, we present the case of a 33-year-old Japanese woman who had initially been diagnosed with IgA nephropathy but was found to have MIDD 6 years later. Two renal biopsies were conducted six years apart. While assessment of the first biopsy specimen with the monoclonal antibody (KM55) revealed mesangial IgA deposits (containing the galactose-deficient IgA1 variant [Gd-IgA1]), examination of the second specimen showed no mesangial IgA deposits and newly-developed glomerular global scleroses and tubular damage. Granular swollen epithelial cells (GSECs), characterised by abnormal mitochondria, were observed among the tubules and collecting ducts in both biopsy specimens. Mitochondrial DNA analysis revealed an m.3243A > G mutation. CONCLUSIONS: We rediscovered the usefulness of GSECs as a pathologically distinctive feature of mitochondrial nephropathy and reviewed the literature regarding MIDD complicated by mesangial IgA deposition. Furthermore, we demonstrate that the mesangial IgA deposits in this patient consisted of the galactose-deficient IgA1 variant. The monoclonal antibody (KM55) might be a useful tool to distinguish IgAN from latent IgA deposits.

TTX-Bearing Planocerid Flatworm (Platyhelminthes: Acotylea) in the Ryukyu Islands, Japan.

Polyclad flatworms comprise a highly diverse and cosmopolitan group of marine turbellarians. Although some species of the genera Planocera and Stylochoplana are known to be tetrodotoxin (TTX)-bearing, there are few new reports. In this study, planocerid-like flatworm specimens were found in the sea bottom off the waters around the Ryukyu Islands, Japan. The bodies were translucent with brown reticulate mottle, contained two conical tentacles with eye spots clustered at the base, and had a slightly frilled-body margin. Each specimen was subjected to TTX extraction followed by liquid chromatography with tandem mass spectrometry analysis. Mass chromatograms were found to be identical to those of the TTX standards. The TTX amounts in the two flatworm specimens were calculated to be 468 and 3634 µg. Their external morphology was found to be identical to that of Planocera heda. Phylogenetic analysis based on the sequences of the 28S rRNA gene and cytochrome-c oxidase subunit I gene also showed that both specimens clustered with the flatworms of the genus Planocera (Planocera multitentaculata and Planocera reticulata). This fact suggests that there might be other Planocera species that also possess highly concentrated TTX, contributing to the toxification of TTX-bearing organisms, including fish.

Dependence of the Electrochemical Redox Properties of Fullerenes on Ionic Liquids.

Control of the electrochemical properties of fullerenes via the chemical modification approach has attracted considerable attention. However, surface modification of fullerene cages with various functional groups can lead to the destruction of their original structures. Herein, we report a simple approach for controlling the electrochemical properties of fullerene thin films formed on Au(111) electrodes in various ionic liquids (ILs). A total of eight reversible redox couples for six reductive and two oxidative processes were observed for fullerenes in ammonium- and pyrrolidinium-based ILs. The redox potentials, the differences between two successive redox potentials, the average values of these potential differences for fullerene reduction, and the electrochemical band gaps of fullerene films in various ILs were found to depend on the cation and its alkyl chain length, the anion, and the chemical structure of the fullerene. Highly charged C70 anions were reduced more easily than C60 anions. An increase in the alkyl chain length of the cation led to an increase in the average potential difference between two successive redox potentials for fullerene reduction. The results indicate that the electrochemical band gaps of fullerenes can be manipulated using ILs with appropriate anions, which can be determined based on the size of the anion and the charge distribution.

Maximum rate of sweat ions reabsorption during exercise with regional differences, sex, and exercise training.

PURPOSE: It is recently reported that determining sweat rate (SR) threshold for increasing galvanic skin conductance (GSC) would represent a maximum rate of sweat ion reabsorption in sweat glands. We evaluate the maximum rate of sweat ion reabsorption over skin regions, sex, and long-term exercise training by using the threshold analysis in the present study. METHODS: Ten males (2 untrained, 4 sprinters, and 4 distance runners) and 12 females (5 untrained, 4 sprinters, and 3 distance runners) conducted graded cycling exercise for 45 min at low, middle, and high exercise intensities (heart rate 100-110, 120-130, and 140-150 beats/min, respectively) for 10, 15, and 20 min, respectively, at 30 °C and 50% relative humidity. Comparisons were made between males and females and among untrained individuals, distance runners, and sprinters on the back and forearm. RESULTS: SR threshold for increasing GSC on back was significantly higher than that of forearm (P < 0.05) without any sex differences (back 0.70 ± 0.08 and 0.61 ± 0.04, forearm 0.40 ± 0.05 and 0.45 ± 0.06 mg/cm2/min for males and females, respectively). Distance runners and sprinters showed higher SR threshold for increasing GSC than that of untrained subjects on back (P < 0.05) but not on forearm (back 0.45 ± 0.06, 0.83 ± 0.06, and 0.70 ± 0.04, forearm 0.33 ± 0.04, 0.49 ± 0.02, and 0.39 ± 0.07 mg/cm2/min for untrained subjects, distance runners, and sprinters, respectively). CONCLUSION: These results suggest that the maximum sweat ion reabsorption rate on the back is higher than that of forearm without sex differences. Furthermore, exercise training in distance runners and sprinters improves the maximum sweat ion reabsorption rate on the back.

Seasonal Changes in the Tetrodotoxin Content of the Flatworm Planocera multitentaculata.

Tetrodotoxin (TTX) is a potent neurotoxin that acts specifically on voltage-gated sodium channels on excitable membranes of muscle and nerve tissues. The biosynthetic process for TTX is unclear, although marine bacteria are generally thought to be the primary producers. The marine flatworm Planocera multitentaculata is a known TTX-bearing organism, and is suspected to be a TTX supplier to pufferfish. In this study, flatworm specimens were collected from an intertidal zone in Hayama, Kanagawa, Japan, the TTX content of the flatworm was measured using liquid chromatography with tandem mass spectrometry (LC-MS/MS), and seasonal changes in TTX content were investigated. No significant difference in TTX concentration of the flatworm body was found between the spawning period and other periods. However, the TTX content in individual flatworms was significantly higher in the spawning period than at other times. The TTX content rose in association with an increase in the body weight of the flatworm.

Dependence of cobaltocenium diffusion in ionic liquids on the alkyl chain length of 1-alkyl-3-methylimidazolium cations.

The electrochemical behavior of cobaltocenium (Cc(+)) on a Au(111) electrode was investigated in five 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amide ([Cnmim][Tf2N], n = 2, 4, 6, 8, or 10) ionic liquids (ILs) in the temperature range from 293.15 to 343.15 K by cyclic voltammetry and chronoamperometry. The redox couple of Cc(+) exhibited a clear reversible one-electron reaction in all the [Cnmim][Tf2N] ILs. The diffusion coefficients of Cc(+) increased with an increase in the alkyl chain length of [Cnmim](+) and a decrease in the viscosity of the IL upon elevating the temperature. The viscosity of the IL plays an important role in determining the activation energy for the diffusion of Cc(+). The obtained results suggested that the alkyl chain length of [Cnmim](+) affects the strength of the interaction between Cc(+) and the surrounding ion species. The results also clarified that the equation proposed by Sutherland adequately describes the diffusion of Cc(+) in ILs when the effect of the type of IL and the temperature on the product of the Stokes radius of Cc(+) and the Sutherland coefficient is considered.

Clinicopathological characteristics of patients with immunoglobulin A nephropathy showing acute exacerbations after favorable long-term clinical courses.

BACKGROUND: Sometimes, acute and progressive proteinuria increases occur in patients with IgA nephropathy (IgAN) after favorable long-term clinical courses of >10 years, but their clinical and histological characteristics are not well understood. METHODS: We retrospectively selected 20 IgAN patients who had been followed for >10 years after their initial biopsies ((1st)Bx) and underwent second biopsies ((2nd)Bx), because their proteinuria increased to >1 g/day. Eight patients with acute exacerbations (Group A) showed acute proteinuria increases after long periods of mild proteinuria. Their clinicopathological characteristics were analyzed as a case series and were compared with those in Group B that comprised 12 patients with persistent proteinuria. RESULTS: Group A experienced acute proteinuria increases and significant hematuria increases compared with the -1-year (P = 0.006) and -3-year (P = 0.010) time points before the (2nd)Bx, which contrasted to the clinical course in Group B. In Group A, glomerulosclerosis (GS) and the arteriosclerosis score did not differ between the (2nd)Bx and the (1st)Bx, and most patients (88 %) showed cellular and/or fibrocellular crescents within the (2nd)Bx. Compared with Group B, the (2nd)Bx revealed that the percentage of cellular and/or fibrocellular crescents (P = 0.001) was significantly higher, whereas the percentage of GS (P = 0.012) and the arteriosclerosis score (P = 0.020) were significantly lower in Group A. CONCLUSION: Rapid proteinuria and hematuria increases, and acute histological lesions characterize acute exacerbations in IgAN after favorable long-term clinical courses.

A multicenter randomized controlled trial of tonsillectomy combined with steroid pulse therapy in patients with immunoglobulin A nephropathy.

BACKGROUND: The study aim was, for the first time, to conduct a multicenter randomized controlled trial to evaluate the effect of tonsillectomy in patients with IgA nephropathy (IgAN). METHODS: Patients with biopsy-proven IgAN, proteinuria and low serum creatinine were randomly allocated to receive tonsillectomy combined with steroid pulses (Group A; n = 33) or steroid pulses alone (Group B; n = 39). The primary end points were urinary protein excretion and the disappearance of proteinuria and/or hematuria. RESULTS: During 12 months from baseline, the percentage decrease in urinary protein excretion was significantly larger in Group A than that in Group B (P < 0.05). However, the frequency of the disappearance of proteinuria, hematuria, or both (clinical remission) at 12 months was not statistically different between the groups. Logistic regression analyses revealed the assigned treatment was a significant, independent factor contributing to the disappearance of proteinuria (odds ratio 2.98, 95% CI 1.01-8.83, P = 0.049), but did not identify an independent factor in achieving the disappearance of hematuria or clinical remission. CONCLUSIONS: The results indicate tonsillectomy combined with steroid pulse therapy has no beneficial effect over steroid pulses alone to attenuate hematuria and to increase the incidence of clinical remission. Although the antiproteinuric effect was significantly greater in combined therapy, the difference was marginal, and its impact on the renal functional outcome remains to be clarified.

[A case report of hepatocellular carcinoma with metastases to the lip, stomach, and colorectum].

A 79-year-old man was diagnosed with hepatocellular carcinoma in 2000 and treated with partial hepatectomy. Intrahepatic carcinoma recurred with lung metastases 7 years later. Several transcatheter arterial chemoembolizations were performed to treat the recurrence, and a right lower lobectomy was performed for lung metastasis. Twelve years after the original carcinoma diagnosis, lip and lung metastases were detected, and he was hospitalized for radiotherapy of the lung metastasis; an oral molecular-targeting drug was initiated. During the therapy, hematochezia was observed, and a colonoscopy was performed. A submucosal lesion with a blood clot measuring approximately 4mm in diameter was found in the sigmoid colon, and endoscopic mucosal resection was performed. Furthermore, an elevated lesion with a 5-mm diameter recess was observed on upper gastrointestinal endoscopy. Both lesions were diagnosed histopathologically as hepatocellular carcinoma metastases.

A 20-year follow-up study of identical twin sisters with immunoglobulin A nephropathy.

Immunoglobulin A nephropathy (IgAN) is characterized by diverse clinicopathological phenotypes. Herein we present a follow-up study of previously reported identical twin sisters with IgAN. The older sister exhibited more severe kidney histopathology and proteinuria and a lower birthweight than did her younger sister, and only the older sister experienced two childbirths. These raised concerns regarding her kidney outcomes. However, with timely multidisciplinary treatments, the older sister's kidney function remained preserved after 20 years of IgAN history. Our findings indicate the significant contribution of environmental/epigenetic factors to IgAN progression and the need for tailored medical care corresponding to life events.