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1.
Front Med (Lausanne) ; 11: 1457611, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39391043

RESUMEN

Objective: Adenomyosis-related infertility is increasingly being diagnosed, and surgical intervention has been suggested to improve fertility. Elastography, a noninvasive ultrasound technique, is promising for diagnosing and guiding the resection of adenomyosis. This report presents the first case of successful delivery after twin pregnancies achieved with IVF following intraoperative elastography-guided laparoscopic adenomyomectomy. Case report: A 35-year-old Japanese woman with uterine adenomyosis received a gonadotropin analog before surgery. Preoperative MRI revealed a 5.0 × 7.0 cm adenomyoma, leading to scheduled laparoscopic adenomyomectomy with intraoperative elastography. During surgery, elastography ensured the complete resection of the adenomyotic tissue while preserving the endometrium. Postoperative MRI confirmed the absence of residual adenomyosis. The patient underwent in vitro fertilization and embryo transfer, leading to a successful twin pregnancy after double blastocyst transfer. Despite a stable perinatal course, she required hospitalization to prevent preterm labor. At 32 weeks, an elective cesarean section delivered healthy twins. The intra- and post-operation was uncomplicated, and the patient and infants had an optimal health. Conclusion: This is the first reported case of a twin pregnancy resulting from vitrified-warmed embryo transfer after elastography-guided laparoscopic adenomyomectomy, culminating in a successful delivery via cesarean section. This technique allows precise resection and mitigates the risks of uterine rupture and placenta accreta spectrum disorders. Although promising, further studies are required to validate the safety and efficacy of this innovative surgical approach.

2.
Int J Mol Sci ; 25(10)2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38791134

RESUMEN

We report the histological changes over time for a patient with infection-related glomerulonephritis (IRGN) that developed in a transplanted kidney. A 47-year-old man had undergone renal transplantation 3 years ago for end-stage kidney disease (ESKD). After several episodes of acute rejection, the patient was in a stable CKD condition. The abrupt development of severe microscopic hematuria and renal dysfunction was observed approximately 2 weeks after the onset of a phlegmon in his right leg. An allograft biopsy showed prominent glomerular endocapillary proliferation on light microscopy, granular C3 deposition on immunofluorescent microscopy, and subepithelial electron-dense deposits on electron microscopy, suggesting IRGN accompanied by moderate interstitial fibrosis and tubular atrophy (IFTA). Positive glomerular staining for nephritis-associated plasmin receptor (NAPlr) and plasmin activity, which are biomarkers of bacterial IRGN, supported the diagnosis. Although the infection was completely cured with antibiotic therapy, renal dysfunction persisted. A re-biopsy of the allograft 2 months later revealed resolution of the glomerular endocapillary proliferation and negative staining for NAPlr/plasmin activity, with worsening IFTA. We showed, for the first time, the chronological changes in infiltrating cells and histological markers of IRGN in transplanted kidneys. Glomerular changes, including NAPlr/plasmin activity staining, almost disappeared after the cessation of infection, while interstitial changes continuously progressed, contributing to ESKD progression.


Asunto(s)
Aloinjertos , Glomerulonefritis , Trasplante de Riñón , Humanos , Masculino , Trasplante de Riñón/efectos adversos , Persona de Mediana Edad , Glomerulonefritis/patología , Glomerulonefritis/etiología , Fallo Renal Crónico/patología , Fallo Renal Crónico/complicaciones , Fallo Renal Crónico/etiología , Fallo Renal Crónico/cirugía , Glomérulos Renales/patología , Glomérulos Renales/metabolismo , Biopsia , Riñón/patología
3.
Mol Ther Oncol ; 32(1): 200765, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38596294

RESUMEN

Gallbladder cancer incidence has been increasing globally, and it remains challenging to expect long prognosis with the current systemic chemotherapy. We identified a novel nucleic acid-mediated therapeutic target against gallbladder cancer by using innovative organoid-based gallbladder cancer models generated from KrasLSL-G12D/+; Trp53f/f mice. Using comprehensive microRNA expression analyses and a bioinformatics approach, we identified significant microRNA-34a-5p downregulation in both murine gallbladder cancer organoids and resected human gallbladder cancer specimens. In three different human gallbladder cancer cell lines, forced microRNA-34a-5p expression inhibited cell proliferation and induced cell-cycle arrest at the G1 phase by suppressing direct target (CDK6) expression. Furthermore, comprehensive RNA sequencing revealed the significant enrichment of gene sets related to the cell-cycle regulators after microRNA-34a-5p expression in gallbladder cancer cells. In a murine xenograft model, locally injected microRNA-34a-5p mimics significantly inhibited gallbladder cancer progression and downregulated CDK6 expression. These results provide a rationale for promising therapeutics against gallbladder cancer by microRNA-34a-5p injection, as well as a strategy to explore therapeutic targets against cancers using organoid-based models, especially for those lacking useful genetically engineered murine models, such as gallbladder cancer.

4.
Tohoku J Exp Med ; 263(2): 97-104, 2024 Jun 28.
Artículo en Inglés | MEDLINE | ID: mdl-38355109

RESUMEN

The concept of infection-related glomerulonephritis (IRGN) has been introduced as adults diagnosed with glomerulonephritis often have coexisting active infections. Furthermore, IgA-dominant IRGN is associated with staphylococcal infections in adults with comorbidities, which often progress to end-stage renal disease. Little is known about IgA-dominant IRGN in children, and no consensus for a management strategy of this condition has been reached. We describe the case of a 9-year-old boy with IgA-dominant IRGN that was diagnosed using specific staining for nephritis-associated plasmin receptor (NAPlr)/plasmin activity and galactose-deficient IgA1 (Gd-IgA1), a marker of IgA nephropathy. The patient was successfully treated using a combination of prednisolone, mizoribine (an immunosuppressive drug), and lisinopril (an angiotensin-converting enzyme inhibitor) and three courses of methylprednisolone pulse therapy. The patient was admitted to our hospital with generalized edema, gross hematuria, proteinuria, hypertension, and renal dysfunction. Hypocomplementemia contributed to a diagnosis of IRGN, although the causative organism was unknown. A renal biopsy performed when the patient presented with nephrotic syndrome showed IgA deposition, positive staining for NAPlr, and negative staining for Gd-IgA1, in addition to findings consistent with IRGN, leading to a pathologic diagnosis of IgA-dominant IRGN. The histological staining for NAPlr/plasmin activity and Gd-IgA1, together with clinical symptoms, could be helpful for diagnosing IgA-dominant IRGN. Our findings indicate that otherwise healthy children can also develop IgA-dominant IRGN. Therefore, early diagnosis and aggressive treatment should be considered when IgA-dominant IRGN is suspected to avoid the possibility of incomplete recovery of renal function.


Asunto(s)
Inmunoglobulina A , Humanos , Masculino , Niño , Inmunoglobulina A/sangre , Glomerulonefritis por IGA/complicaciones , Glomerulonefritis/tratamiento farmacológico , Glomerulonefritis/complicaciones , Glomerulonefritis/diagnóstico
5.
Int J Mol Sci ; 25(4)2024 Feb 09.
Artículo en Inglés | MEDLINE | ID: mdl-38396790

RESUMEN

Platelet-activating factor (PAF) is a phospholipid-derived inflammatory mediator that triggers various inflammatory conditions, including eosinophil activation and recruitment. This study aimed to evaluate the expressions of PAF-metabolism-associated genes, namely genes coding the enzymes involved in PAF synthesis (LPCAT1, LPCAT2, LPCAT3, and LPCAT4), PAF degradation (PAFAH1B2, PAFAH1B3, and PAFAH2), and the gene for the PAF receptor (PTAFR) in subtypes of CRSwNP classified by clinical- or hierarchal-analysis-based classifications. Transcriptomic analysis using bulk RNA barcoding and sequencing (BRB-seq) was performed with CRSwNP, including eosinophilic CRS (ECRS) (n = 9), nonECRS (n = 8), ECRS with aspirin-exacerbated respiratory disease (Asp) (n = 3), and controls with a normal uncinate process mucosa (n = 6). PTAFR was only upregulated in ECRS and nonECRS. In the hierarchical cluster analysis with clusters 1 and 2 reflecting patients with low-to-moderate and high levels of type 2 inflammation, respectively, cluster 1 exhibited a significant downregulation of LPCAT2 and an upregulation of PTAFR expression, while cluster 2 showed an upregulation of LPCAT1, PAFAH1B2, and PTAFR and downregulation of PAFAH2 expression. Understanding this strong PAF-associated pathophysiology in the severe type 2 inflammation group could provide valuable insights into the treatment and management of CRSwNP.


Asunto(s)
Pólipos Nasales , Rinitis , Rinosinusitis , Sinusitis , Humanos , Rinitis/patología , Factor de Activación Plaquetaria/genética , Factor de Activación Plaquetaria/metabolismo , Mucosa Nasal/metabolismo , ARN/metabolismo , Pólipos Nasales/patología , Sinusitis/metabolismo , Inflamación/metabolismo , Enfermedad Crónica , Análisis por Conglomerados , Eosinófilos/metabolismo
6.
Int J Mol Sci ; 25(2)2024 Jan 06.
Artículo en Inglés | MEDLINE | ID: mdl-38255818

RESUMEN

Renal biopsy is the gold standard for making the final diagnosis and for predicting the progression of renal disease, but monitoring disease status by performing biopsies repeatedly is impossible because it is an invasive procedure. Urine tests are non-invasive and may reflect the general condition of the whole kidney better than renal biopsy results. We therefore investigated the diagnostic value of extensive urinary sediment analysis by immunofluorescence staining for markers expressed on kidney-derived cells (cytokeratin: marker for tubular epithelial cells, synaptopodin: marker for podocytes, claudin1: marker for parietal epithelial cells, CD68: marker for macrophages (MΦ), neutrophil elastase: marker for neutrophils). We further examined the expression levels of the mRNAs for these markers by real-time reverse transcription polymerase chain reaction. We also examined the levels of mRNAs associated with the M1 (iNOS, IL-6) and M2 (CD163, CD204, CD206, IL-10) MΦ phenotypes. Evaluated markers were compared with clinical and histological findings for the assessment of renal diseases. Claudin1- and CD68-positive cell counts in urinary sediments were higher in patients with glomerular crescents (especially cellular crescents) than in patients without crescents. The relative levels of mRNA for CD68 and the M2 MΦ markers (CD163, CD204, CD206, and IL-10) in urinary sediments were also higher in patients with glomerular crescents. These data suggest that immunofluorescence staining for claudin1 and CD68 in urinary sediments and the relative levels of mRNA for CD68 and M2 MΦ markers in urinary sediments are useful for evaluating the state of glomerular diseases.


Asunto(s)
Enfermedades Renales , Sistema Urinario , Humanos , Interleucina-10 , Riñón , Técnica del Anticuerpo Fluorescente
7.
CEN Case Rep ; 13(2): 110-116, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37452997

RESUMEN

Poststreptococcal acute kidney glomerulonephritis (PSAGN) has been seen in adults in recent years, especially in patients with type 2 diabetes mellitus, and the renal prognosis has not always been good. There have been cases of PSAGN in which complete remission was not achieved and hematuria and proteinuria persisted, leading to end-stage renal disease. Previous reports showed that the patients subjected to PSAGN have an underlying defect in regulating the alternative pathway of complement, and they identified that antibodies to the C3 convertase, C3 nephritic factors (C3NeF), are involved. C3NeF stabilizes C3 convertase, sustains C3 activation, and causes C3 glomerulonephritis (C3GN). On the other hand, factor H is a glycoprotein that suppresses the overactivation of the alternative pathway by decaying the C3 convertase. Anti-factor H (aFH) antibodies interfere with factor H and cause the same activation of the alternative pathway as C3NeF. However, a limited number of reports describe the clinical course of C3GN with aFH antibodies. We encountered a 49-year-old Japanese man with type 2 diabetes mellitus. He was referred to our hospital because of his elevated serum creatinine, proteinuria, hematuria, and developed edema on both legs. He was diagnosed as PSAGN at the first kidney biopsy, and his renal function improved and edema and hematuria disappeared, but proteinuria persisted after 5 months. He was diagnosed as C3GN at the second kidney biopsy. In our case, no C3NeF was detected. However, a high titer of aFH antibodies was detected in stored serum from the initial presentation, providing a unified diagnosis of aFH antibody-positive C3GN secondary to PSAGN. He progressed to end-stage renal disease (ESRD) and hemodialysis was started. The persistence of high levels of aFH autoantibodies may have caused C3GN secondary to PSAGN due to activating the alternative complement pathway, which eventually worsened the nephropathy and led to ESRD.


Asunto(s)
Diabetes Mellitus Tipo 2 , Nefropatías Diabéticas , Glomerulonefritis , Fallo Renal Crónico , Masculino , Adulto , Humanos , Persona de Mediana Edad , Factor H de Complemento , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/diagnóstico , Hematuria/complicaciones , Diabetes Mellitus Tipo 2/complicaciones , Factor Nefrítico del Complemento 3 , Fallo Renal Crónico/complicaciones , Proteinuria/complicaciones , Enfermedad Aguda , Convertasas de Complemento C3-C5 , Edema
8.
Mol Ther Nucleic Acids ; 34: 102054, 2023 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-38111913

RESUMEN

Gemcitabine is an effective chemotherapeutic agent for biliary tract cancers (BTCs), including gallbladder cancer (GBC) and cholangiocarcinoma (CCA). However, few other effective agents are currently available, particularly for GEM-refractory BTCs. We previously identified microRNA-451a (miR-451a) as a potential therapeutic target in GBC. To elucidate the antineoplastic effects of miR-451a and its underlying mechanisms, we transfected miR-451a into GBC, gemcitabine-resistant GBC (GR-GBC), and gemcitabine-resistant CCA (GR-CCA) cell lines. Furthermore, mimicking in vivo conditions, tumorigenic GBC organoids and three-dimensional (3D) cell culture systems were employed to investigate the anti-proliferative effects of miR-451a on BTCs, and its effect on stem cell properties. We found that miR-451a significantly inhibited cell proliferation, induced apoptosis, and reduced chemoresistant phenotypes, such as epithelial-mesenchymal transition, in both GBC and GR-GBC. The principal mechanism is probably the negative regulation of the phosphatidylinositol 3-kinase/AKT pathway, partially accomplished by directly downregulating macrophage migration inhibitory factor. The Gene Expression Omnibus database revealed that miR-451a was the most significantly downregulated microRNA in CCA tissues. The introduction of miR-451a resulted in similar antineoplastic effects in GR-CCA. Furthermore, miR-451a reduced cell viability in 3D spheroid models and tumorigenic GBC organoids. These findings suggest that the supplementation of miR-451a is a potential treatment strategy for GEM-refractory BTCs.

9.
Pancreatology ; 23(8): 988-995, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37951728

RESUMEN

BACKGROUND: EUS-FNA/B for pancreatic ductal adenocarcinoma (PDAC) is generally considered to be safe; however, while the incidence is low, there are occurrences of complications. Among these complications, there are serious ones like needle tract seeding (NTS), and it is not known than which types of tumors have the risks of EUS-FNA/B complications. This study aimed to evaluate the risk of EUS-FNA/B complications in patients with PDAC, focusing on morphological features. METHODS: Overall, 442 patients who underwent EUS-FNA/B for solid pancreatic masses between January 2018 and May 2022 in four institutions were retrospectively surveyed. Finally, 361 patients histopathologically diagnosed with PDAC were analyzed. Among these patients, 79 tumors with cysts or necrotic components were compared with 282 tumors without cysts or necrotic components. The incidence and risk of EUS-FNA/B complications including NTS were evaluated. RESULTS: There were 9 (2.4 %) of total EUS-FNA/B complications and 3 (0.8 %) of NTS. The incidence of total complication rate and NTS in tumors with cysts or necrotic components were significantly higher than in those without cysts or necrotic components (total complication 6.3 % vs. 1.4 %, p = 0.026, NTS 3.7 % vs. 0 %, p = 0.01). The transgastric route of puncture (OR: 93.3, 95 % CI: 3.81-2284.23) and the existence of cysts or necrotic components (OR: 7.3, 95 % CI: 1.47-36.19) were risk factors for EUS-FNA/B complications identified by the multivariate analysis. CONCLUSIONS: We should pay attention to the risks of EUS-FNA/B complications, including NTS, when the tumor has cysts or necrotic components.


Asunto(s)
Carcinoma Ductal Pancreático , Quistes , Neoplasias Pancreáticas , Humanos , Biopsia por Aspiración con Aguja Fina Guiada por Ultrasonido Endoscópico/efectos adversos , Estudios Retrospectivos , Neoplasias Pancreáticas/patología , Carcinoma Ductal Pancreático/patología
10.
Medicine (Baltimore) ; 102(46): e36091, 2023 Nov 17.
Artículo en Inglés | MEDLINE | ID: mdl-37986327

RESUMEN

RATIONALE: Reports have suggested a relationship between coronavirus disease 2019 (COVID-19) vaccination and new-onset or recurring renal diseases, of which immunoglobulin A (IgA) nephropathy is a representative disease. Alveolar hemorrhage in patients with IgA nephropathy is rare but reportedly has a high mortality and morbidity. To our knowledge, there have been no reports regarding the development of IgA nephropathy with alveolar hemorrhage following COVID-19 vaccination. PATIENTS CONCERN: A 23-year-old Japanese man presented with hemoptysis and peripheral edema a few days after receiving a second dose of a COVID-19 mRNA vaccine. Severe renal failure and alveolar hemorrhage were noted thereafter, and renal biopsy showed crescentic glomerulonephritis with mesangial proliferation accompanied by mesangial electron-dense deposits containing IgA. Renal biopsy tissue also showed chronic histological changes suggestive of acute exacerbation of preexisting IgA nephropathy. DIAGNOSIS: The diagnosis of IgA nephropathy complicated by alveolar hemorrhage was made. INTERVENTIONS AND OUTCOMES: Renal function did not recover despite treatment with high-dose steroids; the patient was maintained on hemodialysis and eventually underwent successful renal transplantation. LESSONS: The present case suggested that although extremely rare, severe renal failure requiring renal replacement therapy could occur in patients with IgA nephropathy after COVID-19 vaccination. Future accumulation of similar cases is needed to predict the risk of renal injury following vaccination.


Asunto(s)
Vacunas contra la COVID-19 , Glomerulonefritis por IGA , Humanos , Masculino , Adulto Joven , COVID-19/prevención & control , Vacunas contra la COVID-19/efectos adversos , Glomerulonefritis por IGA/patología , Hemorragia/complicaciones , Inmunoglobulina A/efectos adversos , Insuficiencia Renal/complicaciones
11.
BMC Nephrol ; 24(1): 329, 2023 11 07.
Artículo en Inglés | MEDLINE | ID: mdl-37936128

RESUMEN

BACKGROUND: Glomerular lipidosis is a rare histological feature presenting the extensive glomerular accumulation of lipids with or without histiocytic infiltration, which develops under various conditions. Among its various etiologies, macrophage activation syndrome (MAS) is a condition reported to be associated with histiocytic glomerular lipidosis. Here we describe the first case of glomerular lipidosis observed in a renal allograft that histologically mimicked histiocytic glomerulopathy owing to MAS. CASE PRESENTATION: A 42-year-old man underwent successful living-donor kidney transplantation. However, middle-grade proteinuria and increased serum triglyceride levels indicative of type V hyperlipidemia developed rapidly thereafter. An allograft biopsy performed 6 months after the transplantation showed extensive glomerular infiltration of CD68+ foam cells (histiocytes) intermingled with many CD3+ T-cells (predominantly CD8+ cells). Furthermore, frequent contact between glomerular T-cells and histiocytes, and the existence of activated CD8+ cells (CD8+, HLA-DR+ cells) were observed by double immunostaining. There was no clinicopathological data suggesting lipoprotein glomerulopathy or lecithin cholesterol acyltransferase deficiency, both of which are well-known causes of glomerular lipidosis. The histological findings were relatively similar to those of histiocytic glomerulopathy caused by MAS. As systemic manifestations of MAS, such as fever, pancytopenia, coagulation abnormalities, hyperferritinemia, increased liver enzyme levels, hepatosplenomegaly, and lymphadenopathy were minimal, this patient was clinicopathologically diagnosed as having renal-limited MAS. Although optimal treatment strategies for MAS in kidney transplant patients remains unclear, we strengthened lipid-lowering therapy using pemafibrate, without modifying the amount of immunosuppressants. Serum triglyceride levels were normalized with this treatment; however, the patient's extensive proteinuria and renal dysfunction did not improve. Biopsy analysis at 1 year after the transplantation demonstrated the disappearance of glomerular foamy changes, but the number of glomerular infiltrating cells remained similar. CONCLUSION: To our knowledge, this is the first reported case of glomerular lipidosis in a transplanted kidney. Increased interaction-activation of histiocytes (macrophages) and CD8+ T-cells, the key pathogenic feature of MAS, was observed in the glomeruli of this patient, who did not demonstrate overt systemic manifestations, suggesting a pathological condition of renal-limited MAS. The clinical effects of triglyceride-lowering therapy were limited, suggesting that hypertriglyceridemia was not the cause of but rather may be a consequence of renal-limited MAS.


Asunto(s)
Enfermedades Renales , Trasplante de Riñón , Lipidosis , Síndrome de Activación Macrofágica , Masculino , Humanos , Adulto , Síndrome de Activación Macrofágica/etiología , Síndrome de Activación Macrofágica/complicaciones , Trasplante de Riñón/efectos adversos , Linfocitos T CD8-positivos , Riñón/patología , Enfermedades Renales/patología , Proteinuria/complicaciones , Triglicéridos
12.
Therap Adv Gastroenterol ; 16: 17562848231206980, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37900006

RESUMEN

Background: Drainage exceeding 50% of total liver volume is a beneficial prognostic factor in patients with unresectable malignant hilar biliary obstruction (UMHBO). However, it is unclear what threshold percentage of total liver volume drained ('liver drainage rate') significantly improves survival in patients with UMHBO who received systemic chemotherapy. Objectives: We aimed to assess the optimal liver drainage rate that improves survival in patients with UMHBO receiving chemotherapy using a three-dimensional (3D)-image volume analyzer. Design: This study was a single-center retrospective cohort study. Methods: Data from 90 patients with UMHBO who received chemotherapy after endoscopic biliary drainage using metal stents at Okayama University Hospital from January 2003 to December 2020 were reviewed. The liver drainage rate was calculated by dividing the drained liver volume by the total liver volume using a 3D-image volume analyzer. The primary endpoint was overall survival by liver drainage rate. The secondary endpoints were time to recurrent biliary obstruction (TRBO) and prognostic factors. Results: The median total liver volume was 1172 (range: 673-2032) mL, and the median liver drainage rate was 83% (range: 50-100). Overall survival was 376 (95% CI: 271-450) days, and patients with >80% drainage (n = 67) had significantly longer survival than those with <80% drainage (n = 23) (450 days versus 224 days, p = 0.0033, log-rank test). TRBO was 201 (95% CI: 155-327) days and did not differ significantly by liver drainage rate. Multivariate Cox proportional hazards regression analysis revealed >80% liver drainage [hazard ratio (HR): 0.35, 95% CI: 0.20-0.62, p = 0.0003] and hilar cholangiocarcinoma (HR: 0.30, 95% CI: 0.17-0.50, p < 0.0001) as significant prognostic factors. Conclusion: In patients with UMHBO scheduled for chemotherapy, >80% drainage is associated with improved survival. Further prospective multicenter studies are needed to verify the results of this study. Trail registration: Okayama University Hospital, IRB number: 2108-011.

13.
Medicine (Baltimore) ; 102(41): e35470, 2023 Oct 13.
Artículo en Inglés | MEDLINE | ID: mdl-37832087

RESUMEN

RATIONALE: A predominant Th2 immune response is suggested in the pathogenesis of both minimal change disease (MCD) and membranous nephropathy (MN); however, consecutive development of the 2 diseases in a patient is extremely rare. PATIENT CONCERN: A Japanese man, who developed nephrotic syndrome in his 50s and was diagnosed with MCD by renal biopsy, experienced a relapse of proteinuria approximately 3 years later during long-term steroid treatment. Since the proteinuria was resistant to increase in steroid dosage, repeat renal biopsy was performed, which revealed a small amount of glomerular subepithelial immune deposits containing immunoglobulin (Ig)G (dominantly IgG4). Immunostaining for thrombospondin-type-1-domain-containing-7A (THSD7A) was positive on the glomerular capillary walls, whereas that for other causative antigens of MN, such as phospholipase A2 receptor or neural epidermal growth factor-like 1 protein, was negative. Detailed examination found no associated condition, including malignancies and allergic diseases. DIAGNOSIS: The diagnosis of THSD7A-associated idiopathic MN was made. INTERVENTIONS AND OUTCOMES: He received further increased dose of steroids. Thereafter he maintained clinical improvement because his urinary protein level was decreased. LESSONS: The present case suggested that histological transition from MCD to MN is possible and repeat biopsy would be crucial for accurate diagnosis.


Asunto(s)
Glomerulonefritis Membranosa , Nefrosis Lipoidea , Masculino , Humanos , Nefrosis Lipoidea/inducido químicamente , Nefrosis Lipoidea/tratamiento farmacológico , Nefrosis Lipoidea/patología , Glomérulos Renales/patología , Proteinuria/patología , Inmunoglobulina G , Esteroides , Autoanticuerpos , Receptores de Fosfolipasa A2
14.
Int J Mol Sci ; 24(11)2023 May 27.
Artículo en Inglés | MEDLINE | ID: mdl-37298319

RESUMEN

In this rare case of infection-related cryoglobulinemic glomerulonephritis with infective endocarditis, a 78-year-old male presented with an acute onset of fever and rapidly progressive glomerulonephritis. His blood culture results were positive for Cutibacterium modestum, and transesophageal echocardiography showed vegetation. He was diagnosed with endocarditis. His serum immunoglobulin M, IgM-cryoglobulin, and proteinase-3-anti-neutrophil cytoplasmic antibody levels were elevated, and his serum complement 3 (C3) and C4 levels were decreased. Renal biopsy results showed endocapillary proliferation, mesangial cell proliferation, and no necrotizing lesions on light microscopy, with strong positive staining for IgM, C3, and C1q in the capillary wall. Electron microscopy showed deposits in the mesangial area in the form of fibrous structures without any humps. Histological examination confirmed a diagnosis of cryoglobulinemic glomerulonephritis. Further examination showed the presence of serum anti-factor B antibodies and positive staining for nephritis-associated plasmin receptor and plasmin activity in the glomeruli, suggesting infective endocarditis-induced cryoglobulinemic glomerulonephritis.


Asunto(s)
Endocarditis , Glomerulonefritis , Nefritis , Masculino , Humanos , Anciano , Fibrinolisina , Glomerulonefritis/complicaciones , Glomerulonefritis/diagnóstico , Glomérulos Renales/patología , Nefritis/patología , Endocarditis/complicaciones , Endocarditis/diagnóstico , Endocarditis/patología , Coloración y Etiquetado
15.
Kidney Med ; 5(5): 100625, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-37122392

RESUMEN

A Japanese man in his early 70s was referred to our hospital because of massive proteinuria. Analysis of his kidney biopsy demonstrated glomerular subepithelial immune deposits containing immunoglobulin (Ig)G, which was dominant for the IgG1 subclass. Immunoperoxidase staining for neural epidermal growth factor-like 1 protein (NELL1) was positive on the glomerular capillary walls, whereas neither serum anti-phospholipase A2 receptor (PLA2R) antibodies nor immunofluorescence staining for PLA2R was positive. Detailed investigation revealed no associated conditions, including underlying malignancies, and thus he was diagnosed as having NELL1-associated idiopathic membranous nephropathy (MN). The patient was treated with steroids, which substantially improved his nephrotic syndrome. Interestingly, serum anti-NELL1 as well as anti-PLA2R antibodies became positive during his clinical course. Serology-based approaches are currently proposed for the treatment of patients suspected of having MN; however, an accurate diagnosis of the present patient would have been difficult if such an approach was performed only at a later phase of the disease. Several target antigens for the glomerular immune deposits observed in patients with MN have recently been identified, and dual positivity of antibodies to these antigens reportedly occurs in some patients. Further accumulation and analyses of such patients are needed to establish more appropriate diagnostic approaches for MN.

16.
Intern Med ; 62(2): 269-273, 2023 Jan 15.
Artículo en Inglés | MEDLINE | ID: mdl-35732451

RESUMEN

A 67-year-old woman who had undergone bone marrow transplantation 2 years previously for acute myeloid leukemia (AML) developed complications of chronic graft-versus-host disease (cGVHD). She thereafter also developed nephrotic syndrome, and membranous nephropathy (MN) was diagnosed by a renal biopsy. Although the causative antigens of the MN were not detected, immunofluorescence staining showed codominant deposition of immunoglobulins G2 and G3, a finding indicating secondary MN, thereby suggesting an association between MN and cGVHD. Rituximab treatment was initiated, and her nephrotic syndrome gradually improved without relapse of AML. Our present case suggests that rituximab is a safe and effective therapeutic option for cGVHD-associated MN.


Asunto(s)
Síndrome de Bronquiolitis Obliterante , Glomerulonefritis Membranosa , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Síndrome Nefrótico , Femenino , Humanos , Anciano , Trasplante de Médula Ósea/efectos adversos , Rituximab/uso terapéutico , Glomerulonefritis Membranosa/tratamiento farmacológico , Glomerulonefritis Membranosa/etiología , Glomerulonefritis Membranosa/diagnóstico , Síndrome Nefrótico/etiología , Síndrome Nefrótico/complicaciones , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Enfermedad Injerto contra Huésped/complicaciones , Enfermedad Injerto contra Huésped/tratamiento farmacológico , Leucemia Mieloide Aguda/complicaciones , Leucemia Mieloide Aguda/tratamiento farmacológico
17.
CEN Case Rep ; 12(2): 152-158, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-36180718

RESUMEN

Afatinib is a second-generation, oral, epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI). One of the most common adverse effects of affatinib is diarrhea, which may lead to acute kidney injury (AKI) due to severe plasma volume loss; however, no case of glomerular injury directly induced by afatinib has been reported to date. Here, we describe the case of a 53-year-old Japanese male patient with advanced lung adenocarcinoma who twice developed AKI requiring dialysis, once after starting and once after increasing the dose of afatinib. Although serum anti-neutrophil cytoplasmic antibodies were negative, crescentic glomerulonephritis with no immune deposits was confirmed on kidney biopsy. No vasculitis-like signs were observed in other organs, such as lung, skin, or peripheral nerves. Afatinib was considered the cause of glomerular damage and was immediately discontinued; corticosteroids were administered. Renal function gradually recovered thereafter, with serum creatinine levels at ~ 2.3 mg/dL after second-line therapy with bevacizumab and atezolizumab. Several cases of cutaneous leukocytoclastic vasculitis have been reported in patients treated with other EGFR-TKIs; therefore, afatinib-induced vasculitis may lead to crescentic glomerulonephritis. Although afatinib-induced glomerular injury is extremely rare and has an unclear mechanism, renal function and urinary findings need to be closely monitored.


Asunto(s)
Adenocarcinoma del Pulmón , Adenocarcinoma , Glomerulonefritis , Neoplasias Pulmonares , Humanos , Masculino , Persona de Mediana Edad , Afatinib/uso terapéutico , Neoplasias Pulmonares/patología , Adenocarcinoma/tratamiento farmacológico , Quinazolinas/farmacología , Quinazolinas/uso terapéutico , Receptores ErbB/metabolismo , Diálisis Renal , Adenocarcinoma del Pulmón/tratamiento farmacológico , Glomerulonefritis/tratamiento farmacológico
18.
Int J Mol Sci ; 23(21)2022 Oct 26.
Artículo en Inglés | MEDLINE | ID: mdl-36361742

RESUMEN

Transglutaminase (TGM) isoform catalyze the cross-linking reaction of identical or different substrate proteins. Eosinophil has been recognized in chronic rhinosinusitis with nasal polyps (CRSwNP) forming tissue eosinophil in nasal polyp (NP), and TGM isoforms are suggested to be associated with a critical role in asthma and other allergic conditions. The aim of this study was to reveal the association of specific TGM isoform with both the tissue eosinophil infiltration deeply concerning with the intractable severity of CRSwNP and the fibrin polymerization ability of TGM isoform associated with the tissue eosinophil infiltration, which lead to NP formation and/or maintenance in CRSwNP. NP tissues (CRSwNP group) and uncinate process (UP) (control group) were collected from patients with CRSwNP and control subjects. We examined: (1) the expression level of TGM isoforms by using a real-time polymerase chain reaction (PCR) and the comparison to the issue eosinophil count in the CRSwNP group, (2) the location of specific TGM isoform in the mucosal tissue using immunohistochemistry, (3) the inflammatory cell showing the colocalization of specific TGM isoform in Laser Scanning Confocal Microscopy (LSCM) imaging, and (4) the fibrin polymerase activity of specific TGM isoform using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). A certain level of TGM 1, 2, 3, 5 expression was present in both the CRSwNP group and the control group. Only TGM 1 expression showed a positive significant correlation with the tissue eosinophil count in the CRSwNP group. The localization of TGM 1 in NP (CRSwNP) laid mainly in a submucosal layer as inflammatory cells and was at the cytoplasm in the tissue eosinophil. Fibrin polymerase activity of TGM 1 showed the same polymerase ability of factor XIIIA. TGM 1 might influence the NP formation and/or maintenance in CRSwNP related to the tissue eosinophil infiltration, which formed fibrin mesh composing NP stroma.


Asunto(s)
Pólipos Nasales , Rinitis , Sinusitis , Humanos , Pólipos Nasales/patología , Eosinófilos/metabolismo , Rinitis/patología , Fibrina/metabolismo , Polimerizacion , Sinusitis/metabolismo , Transglutaminasas/genética , Transglutaminasas/metabolismo , Enfermedad Crónica
19.
Int J Mol Sci ; 23(10)2022 May 18.
Artículo en Inglés | MEDLINE | ID: mdl-35628459

RESUMEN

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a chronic inflammatory disease with a high symptom burden, including nasal congestion and smell disorders. This study performed a detailed transcriptomic analysis in CRSwNP classified as eosinophilic CRS (ECRS), nonECRS according to the Japanese Epidemiological Survey of Refractory Eosinophilic Chronic Rhinosinusitis (JESREC) criteria, and a group of ECRS with comorbid aspirin intolerant asthma (Asp). Gene expression profiles of nasal polyps and the uncinate process in CRSwNP patients and normal subjects (controls) were generated by bulk RNA barcoding and sequencing (BRB-seq). A differentially expressed genes (DEGs) analysis was performed using DESeq2 software in iDEP to clarify any relationship between gene expression and disease backgrounds. A total of 3004 genes were identified by DEGs analysis to be associated with ECRS vs control, nonECRS vs control, and Asp vs control. A pathway analysis showed distinct profiles between the groups. A Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) showed distinct phenotype-specific pathways of expressed genes. In the specific pathway of "cytokine-cytokine receptor interaction", the differentially expressed genes were widely distributed. This study indicates that transcriptome analysis using BRB-seq may be a valuable tool to explore the pathogenesis of type 2 inflammation in CRSwNP.


Asunto(s)
Pólipos Nasales , Rinitis , Sinusitis , Enfermedad Crónica , Humanos , Pólipos Nasales/complicaciones , Pólipos Nasales/genética , Pólipos Nasales/metabolismo , ARN , Rinitis/complicaciones , Rinitis/genética , Sinusitis/complicaciones , Sinusitis/genética
20.
DEN Open ; 2(1): e32, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35310742

RESUMEN

Endoscopic migrated stent removal using a balloon-assisted enteroscope is technically difficult in patients with bowel reconstruction. We report the treatment outcomes and endoscopic removal methods for migrated stents using a double-balloon enteroscope (DBE). We retrospectively studied 12 patients with stent migration into the main pancreatic duct (MPD) or bile duct who underwent bowel reconstruction between January 2012 and June 2020. The successful removal rates in the MPD (n = 3) and the bile duct (n = 9) were 66.7% (2/3) and 88.9% (8/9), respectively. The removal techniques included the indirect method (n = 3), the direct method (n = 4), and a combination of indirect and direct methods (n = 3). The removal devices included an extraction balloon catheter (n = 7), basket catheter (n = 5), biopsy forceps (n = 3), and snare (n = 2). Stent removal using a DBE was feasible and useful as the first treatment for patients with bowel reconstruction. The choice of the direct and/or indirect method according to the situation of the migrated stent is important.

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