Galactose-deficient IgA1 (Gd-IgA1) plays a crucial role in the development of IgA nephropathy (IgAN). However, the pathogenic mechanisms driving Gd-IgA1 production have not been fully elucidated. ...Innate-immune activation via Toll-like receptor 9 (TLR9) is known to be involved in Gd-IgA1 production. A proliferation inducing ligand (APRIL) and IL-6 are also known to enhance Gd-IgA1 synthesis in IgAN. With this as background, we investigated how TLR9 activation in IgA secreting cells results in overproduction of nephritogenic IgA in the IgAN-prone ddY mouse and in human IgA1-secreting cells. Injection of the TLR9 ligand CpG-oligonucleotides increased production of aberrantly glycosylated IgA and IgG-IgA immune complexes in ddY mice that, in turn, exacerbated kidney injury. CpG-oligonucleotide-stimulated mice had elevated serum levels of APRIL that correlated with those of aberrantly glycosylated IgA and IgG-IgA immune complexes. In vitro, TLR9 activation enhanced production of the nephritogenic IgA as well as APRIL and IL-6 in splenocytes of ddY mice and in human IgA1-secreting cells. However, siRNA knock-down of APRIL completely suppressed overproduction of Gd-IgA1 induced by IL-6. Neutralization of IL-6 decreased CpG-oligonucleotide-induced overproduction of Gd-IgA1. Furthermore, APRIL and IL-6 pathways each independently mediated TLR9-induced overproduction of Gd-IgA1. Thus, TLR9 activation enhanced synthesis of aberrantly glycosylated IgA that, in a mouse model of IgAN, further enhanced kidney injury. Hence, APRIL and IL-6 synergistically, as well as independently, enhance synthesis of Gd-IgA1.
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Acute kidney injury (AKI) is associated with prolonged hospitalization and high mortality, and it predisposes individuals to chronic kidney disease. To date, no effective AKI treatments have been ...established. Here we show that the apoptosis inhibitor of macrophage (AIM) protein on intraluminal debris interacts with kidney injury molecule (KIM)-1 and promotes recovery from AKI. During AKI, the concentration of AIM increases in the urine, and AIM accumulates on necrotic cell debris within the kidney proximal tubules. The AIM present in this cellular debris binds to KIM-1, which is expressed on injured tubular epithelial cells, and enhances the phagocytic removal of the debris by the epithelial cells, thus contributing to kidney tissue repair. When subjected to ischemia-reperfusion (IR)-induced AKI, AIM-deficient mice exhibited abrogated debris clearance and persistent renal inflammation, resulting in higher mortality than wild-type (WT) mice due to progressive renal dysfunction. Treatment of mice with IR-induced AKI using recombinant AIM resulted in the removal of the debris, thereby ameliorating renal pathology. We observed this effect in both AIM-deficient and WT mice, but not in KIM-1-deficient mice. Our findings provide a basis for the development of potentially novel therapies for AKI.
•Dynamic signal changes are seen on MRI after focal cryotherapy for prostate cancer.•Most lesions show hyperintensity at 3 months post-treatment on T2WI, T1WI, and DWI.•All lesions show hypointensity ...after 17 months on T2WI, T1WI, and DWI.•Peripheral enhancement is often observed and disappears after 23 months on DCE-MRI.•Transient internal enhancement may be observed in the early post-treatment period.
To evaluate the time-course changes of multiparametric MRI findings following focal cryotherapy for localized prostate cancer.
Sixteen patients who underwent focal cryotherapy as an initial curative treatment for localized prostate cancer during March 2017–April 2021 were included. Before the treatment, the patients underwent targeted prostate biopsy using MRI–transrectal ultrasound fusion. Overall, 64 MRIs were conducted after focal cryotherapy and the temporal post-treatment MR signal changes of the ablated area in T2WI, T1WI, DWI, and DCE-MRI were analyzed.
Technical success was achieved in all patients. The median follow-up period was 22 months. The initial post-treatment MRI revealed significant signal changes in the target lesions for all patients, including the disappearance of findings suggestive of cancer. At 3 months post-treatment, most lesions were hyperintense with a hypointense rim on T2WI, T1WI, and DWI (83.3 %). After 6 months, hyperintensity reduced, and after 17 months, all lesions showed hypointensity in these sequences. DCE-MRI of most patients showed loss of internal enhancement; however, one patient exhibited residual nodular enhancement in the ablated area at 3 months, which disappeared after 6 months. Peripheral enhancement was common at 3 months, disappearing after 23 months. Two patients showed biopsy-evidenced local recurrence. The recurrent lesions showed hypointensity on T2WI with diffusion restriction and early contrast enhancement in the ventral transition zone.
MRI findings of the ablated sites following focal cryotherapy for localized prostate cancer show dynamic signal changes, especially within the first 6 months.
IgA nephropathy (IgAN) begins with aberrant IgA deposition in glomeruli, progresses to IgM/IgG/complement codeposition, and results in chronic inflammation and glomerular damage. However, the ...mechanism that drives such phlogogenic cascade has been unclear. Recently, apoptosis inhibitor of macrophage (AIM) protein was shown to modulate macrophages' function in various pathologic conditions, thereby profoundly affecting the progression of renal disorders, including AKI. A spontaneous IgAN model, grouped ddY (gddY) mouse, revealed the requirement of AIM for the overall inflammatory glomerular injury following IgA deposition.
We established an AIM-deficient IgAN model (
gddY) using CRISPR/Cas9 and compared its phenotype with that of wild-type gddY with or without recombinant AIM administration. An IgA-deficient IgAN model (
gddY) was also generated to further determine the role of AIM.
In both human and murine IgAN, AIM colocalized with IgA/IgM/IgG in glomeruli, whereas control kidneys did not exhibit AIM deposition. Although
gddY showed IgA deposition at levels comparable with those of wild-type gddY, they did not exhibit glomerular accumulation of IgM/IgG complements, CD45
leukocyte infiltration, and upregulation of inflammatory/fibrogenic genes, indicating protection from glomerular lesions and proteinuria/hematuria. Recombinant AIM administration reconstituted the IgAN phenotype, resulting in IgM/IgG/complement IgA codeposition. Neither spontaneous IgM/IgG codeposition nor disease was observed in
gddY mice.
AIM may contribute to stable immune complex formation in glomeruli, thereby facilitating IgAN progression. Therefore, AIM deposition blockage or disassociation from IgM/IgG may present a new therapeutic target on the basis of its role in IgAN inflammation initiation.
Purpose: This study aimed to examine MRI features and staging of neuroendocrine carcinoma (NEC) of the endometrium and evaluate survival.Methods: Clinical data, pathological, and preoperative pelvic ...MRI findings in 22 patients with histologically surgery-proven endometrial NEC were retrospectively reviewed. Tumors were pure NEC (n = 10) or mixed histotype (n = 12), with 13 large and nine small cell type.Results: International Federation of Gynecology and Obstetrics (FIGO) staging was I, II, III, and IV in 6, 2, 12, and 2 patients, respectively. In 13 (76.4%) of 17 patients with pathological deep myometrial invasion, MRI showed abnormal diffusely infiltrative high T2 signal intensity throughout the myometrium with loss of normal uterine architecture. All tumors had restricted diffusion (apparent diffusion coefficient map low signal intensity, diffusion weighted imaging high signal intensity). Accuracy of T staging by MRI for all cases was 81.8%, with reference to pathology staging, while patient-based sensitivity, specificity, and accuracy for detecting metastatic pelvic lymph nodes was 60.0%, 100%, and 77.8%, respectively. Two intrapelvic peritoneal dissemination cases were detected by MRI. During follow-up (mean 30.4, range 3.3–138.4 months), 16 patients (72.7%) experienced recurrence and 12 (54.5%) died of disease. Two-year disease-free and overall survival rates for FIGO I, II, III, and IV were 66.7% and 83.3%, 50% and 100%, 10% and 33.3%, and 0% and 0%, respectively.Conclusion: Abnormal diffusely infiltrative high T2 signal intensity throughout the myometrium with normal uterine architecture loss and obvious restricted diffusion throughout the tumor are suggestive features of endometrial NEC. Pelvic MRI is reliable for intrapelvic staging of affected patients.
To evaluate whether susceptibility-weighted MR imaging (SWI) findings are associated with tumor infarction on contrast-enhanced MRI (CE-MRI) after uterine artery embolization (UAE) for leiomyoma.
...This was a single institution, retrospective study. Between February 2016 and April 2017, 27 consecutive patients underwent UAE and completed SWI and CE-MRI before and 1 week after UAE. Two blinded readers independently reviewed the MRI of 261 tumors ≥1 cm in all patients. We evaluated the relationship between the hypointense peripheral rim observed on the tumor surface on post-procedural SWI and the infarction rates (≥90%, <90%) of each tumor based on post-procedural CE-MRI. Inter-reader correlation coefficients (ICC) and the sensitivity and specificity of the rim were measured.
Substantial inter-reader agreement was noted in post-procedural SWI interpretations (ICC = 0.681, 95% CI; 0.547, 0.771). The rim was observed in 66.7% (174/261) of tumors by reader 1 and 55.9% (146/261) of tumors by reader 2 on post-procedural SWI. Correlations were observed between the rim and ≥90% tumor infarction by readers 1 and 2 (Spearman's coefficient = 0.474 and 0.438, p < 0.001 and p < 0.001, respectively). The sensitivity and specificity of the rim to tumor infarction were 77.2 and 82.6% (reader 1), and 65.8 and 100% (reader 2), respectively.
The present study demonstrated that the hypointense peripheral rim was observed on some leiomyomas on SWI immediately after UAE. The rim correlated with tumor infarction on post-procedural CE-MRI. This SWI finding was helpful for evaluating embolic effects on leiomyomas in the acute phase after UAE.
Aim
The aim of this study was to elucidate whether the presence of an ovarian endometrioma is associated with impaired vascular flow. We investigated changes in vascular flow on the ipsilateral and ...contralateral side of the endometrioma, before and after surgery.
Methods
This prospective case–control study included 144 women (ovarian endometrioma n = 40, endometriosis without ovarian endometrioma n = 33, non‐endometriotic ovarian cyst n = 17, and normal pelvis n = 54). The uterine artery (UtA) vascular resistance indices (pulsatility index PI and resistance index RI) were measured using transvaginal Doppler sonography, and UtA diameters were measured using magnetic resonance imaging.
Results
The UtA PI and RI were significantly higher on the ipsilateral side of the endometrioma than on the contralateral unaffected side in the endometrioma group (P < 0.01), as well as in the non‐endometriotic ovarian cyst group (P < 0.05), and normal pelvis group (P < 0.01). The UtA PI and RI on the ipsilateral side of the endometrioma were significantly lower after cystectomy than before cystectomy (P < 0.01). The UtA diameters were significantly larger (P < 0.01) on the ipsilateral side of the endometrioma than on the contralateral side.
Conclusion
The UtA‐vascular resistance might be higher on the ipsilateral side of the endometrioma than on the contralateral unaffected side, indicating a risk of subclinical atherosclerosis in women with endometriosis.
Aim
To assess and compare the uterine volume and endometrium length between women with and without endometriosis, using pelvic magnetic resonance imaging scans.
Methods
In this case–control study, a ...total of 75 nulligravid women (aged 20–45 years) with regular menstrual cycles whose uterus were free of any surgically confirmed lesions were enrolled. The endometriosis group underwent surgery for endometrioma (n = 39), and the control group underwent surgery for non‐endometrioma ovarian cysts (n = 36). The primary outcome was uterine corpus volume, which was assessed using three‐dimensional reconstructions of preoperative pelvic magnetic resonance imaging scans.
Results
The mean uterine volume was significantly larger in the endometriosis group than in the control group (mean ± standard deviation, 50.9 ± 14.4 cm3 vs 41.7 ± 14.3 cm3; P < 0.01). The longitudinal length and transverse diameter of the corpus and the longitudinal length of the endometrium were also significantly greater in the endometriosis group (all, P < 0.01).
Conclusions
An increase in uterine volume and endometrium length was observed in women with endometriosis.
Abstract Among diseases causing acute lower abdominal pain in women, isolated fallopian tube torsion is very rare with an annual prevalence of 1 in 1.5 million. Because it has fewer findings on ...imaging compared to adnexal torsion, the correct diagnosis can rarely be made before an operation. We present a case of isolated fallopian tube torsion that was suspected preoperatively by its clinical course and findings on computed tomography. A 24-year-old woman repeatedly experienced acute colicky pain in the right lower back. Transvaginal ultrasonography and magnetic resonance imaging showed a right pelvic cystic lesion with intact ovaries; these findings led us to schedule a laparoscopic examination. However, the patient presented to the emergency room with acute severe right back pain. The preoperative diagnosis considering the computed tomography findings and clinical course was consistent with fallopian tube torsion. An earlier diagnosis may have help to preserve the fallopian tube and future fertility.
Objectives
To investigate whether the number and size of endometrial–leiomyoma fistulas (ELFs) change following uterine artery embolization (UAE) for leiomyoma and the correlation between ELFs and ...vaginal discharge (VD).
Materials & Methods
This study was a retrospective analysis of 100 patients who underwent UAE at a single institution between May 2016 and March 2021. They all underwent MRI at baseline, 4 months, and 1 year after UAE. The number and size of the ELFs were compared with the MRI images each time. The ELF tumor characteristics and the correlation between the ELFs and VD were assessed. Additional gynecologic interventions due to VD associated with ELFs were evaluated.
Results
No ELF was observed at baseline. Ten ELFs were noted in nine patients at 4 months, and 35 ELFs were noted in 32 patients 1 year after UAE. The ELFs significantly increased over time (
p
= 0.004, baseline vs. 4 months;
p
< 0.001, 4 months vs. 1 year). The ELF size did not significantly change over time (
p
= 0.941). The tumors developing ELFs after UAE were mainly located at the submucosal or intramural area contacting the endometrium at baseline, with a mean size of 7.1 (2.6) cm. Nineteen patients (19%) had VD 1 year after UAE. There was no significant correlation between VD and the number of ELFs (
p
= 0.80). No patients underwent additional gynecologic interventions due to VD associated with ELFs.
Conclusion
ELFs increased in number and did not disappear over time after UAE in most tumors.
Clinical relevance statement
Despite the MR imaging findings, within the limited data of this study, ELFs were not seemingly associated with clinical symptoms, including VD.
Key Points
• Endometrial–leiomyoma fistula (ELF) is a complication of uterine artery embolization (UAE).
• ELFs increased in number over time after UAE and did not disappear in most tumors.
• Most tumors developing ELFs after UAE were located near/contacted the endometrium and were larger.
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