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Recurrent peritonitis is a serious complication of peritoneal dialysis (PD), which could result in PD withdrawal and mortality. However, cases of recurrent peritonitis occurring during ongoing antimicrobial therapy are rarely reported. Herein, we present a 71-year-old man who experienced initial peritonitis due to Enterococcus faecalis. Despite effective antimicrobial therapy, he developed recurrent peritonitis while on antimicrobial therapy. PD fluid culture analysis yielded Stenotrophomonas maltophilia (S. maltophilia). He was treated with multiple antimicrobials, and the peritoneal catheter was removed. To the best of our knowledge, this is the first case of recurrent peritonitis caused by S. maltophilia, which was developed during antimicrobial treatment. Our report findings suggest the importance of considering S. maltophilia infection in an atypical case of very early recurrent peritonitis.
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Introduction: Kidney disease of unknown etiology accounts for 1 in 10 adult end-stage renal disease (ESRD) cases worldwide. The aim of this study is to clarify the genetic background of patients with chronic kidney disease (CKD) of unknown etiology who initiated renal replacement therapy (RRT) in adulthood. Methods: This is a multicenter cross-sectional cohort study. Of the 1164 patients who attended 4 dialysis clinics in Japan, we first selected patients who started RRT between the ages of 20 and 49 years. After excluding patients with apparent causes of CKD (e.g., diabetic nephropathy, polycystic kidney disease (PKD) with family history, patients who underwent renal biopsy), 90 patients with CKD of unknown cause were included. The 298 genes associated with CKD were analyzed using capture-based targeted next-generation sequencing. Results: Of the 90 patients, 10 (11.1%) had pathogenic variants in CKD-causing genes and 17 (18.9%) had variant of unknown significance (VUS). Three patients had PKD1 pathogenic variants, and 1 patient had PKD1 and COL4A4 pathogenic variants. In addition, 2 patients were diagnosed with atypical hemolytic uremic syndrome (aHUS) due to C3 or CFHR5. One patient each was diagnosed with Alport syndrome due to COL4A4 and COL4A3 variants, nephronophthisis due to NPHP1 variants, Fabry disease due to GLA variants, and autosomal-dominant tubulointerstitial kidney disease due to UMOD variants. Genetic diagnoses were not concordant with clinical diagnoses, except for patients with PKD1 variant. Conclusion: This largest study on genetic analysis in hemodialysis-dependent adults revealed the presence of undiagnosed inherited kidney diseases.
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INTRODUCTION: Chronic kidney disease (CKD) causes a progressive loss of muscle and bone mass, which frequently overlap with and affect clinical outcomes. However, the impact of sarcopenia, low bone mineral density (BMD; osteopenia or osteoporosis), and osteosarcopenia (sarcopenia and low BMD) on CKD progression is yet to be determined. We aimed to address these issues in patients with CKD without kidney replacement therapy (KRT). METHODS: This prospective cohort study included 251 outpatients aged ≥65 years with CKD without KRT enrolled in our hospital between June 2016 and March 2017. Sarcopenia was defined according to the 2014 criteria of the Asian Working Group for Sarcopenia (AWGS), and low BMD was defined as a T-score of ≤-1.0. The patients were divided into four groups: normal (no sarcopenia/normal BMD), only low BMD (no sarcopenia/low BMD), only sarcopenia (sarcopenia/normal BMD), and osteosarcopenia (sarcopenia/low BMD). The primary outcome was a composite of all-cause deaths, initiating KRT, and admissions owing to major adverse cardiovascular and cerebrovascular events (MACEs). The secondary outcome was a kidney composite outcome that included a 30 % reduction in creatinine-based estimated glomerular filtration rate (eGFR) and initiating KRT. The outcome risk was determined using the Cox regression models adjusted for potential confounders. RESULTS: Median age (25th-75th percentile) and eGFR of the outpatients (35 % women) were 76 (69-81) years and 32.1 (20.8-41.7) ml/min/1.73 m2, respectively. During a median follow-up period of 5.2 years, there were 22 deaths, 117 30 % eGFR reductions, 48 KRTs, and 18 admissions owing to MACEs. The osteosarcopenia group rather than the only low BMD or only sarcopenia groups exhibited a higher risk of the primary (hazard ratio [HR]: 3.28, 95 % confidence interval [CI]: 1.52-7.08) and kidney composite (HR: 2.07, 95 % CI: 1.10-3.89) outcomes. Among the osteosarcopenia-related body compositions and physical functions, low handgrip strength (HGS) was strongly associated with a high risk of primary and kidney composite outcomes (HR: 2.44, 95 % CI: 1.46-4.08; HR: 1.48, 95 % CI: 0.97-2.24, respectively). The increase in HGS but not the body mass index, skeletal muscle mass index, or BMD was associated with lower risks of primary and kidney composite outcomes (HR: 0.93, 95 % CI: 0.89-0.98; HR: 0.96, 95 % CI: 0.92-0.99 per 1 kg, respectively). CONCLUSIONS: Osteosarcopenia was associated with poor survival and kidney outcomes in older patients with CKD. Low HGS, which is common in patients with osteosarcopenia and CKD, was associated with increased mortality risk and kidney function decline. These findings can help the risk prediction and pathogenesis of the kidney-bone-muscle axis and improving muscle strength can help mitigate CKD progression.
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Maladies osseuses métaboliques , Ostéoporose , Insuffisance rénale chronique , Sarcopénie , Humains , Femelle , Sujet âgé , Sujet âgé de 80 ans ou plus , Mâle , Sarcopénie/complications , Force de la main , Études prospectives , Ostéoporose/complications , Maladies osseuses métaboliques/complications , Densité osseuse/physiologie , Insuffisance rénale chronique/complicationsRÉSUMÉ
In chromatography, the use of extreme conditions can often lead to unique separation selectivity. In this study, a highly basic mobile phase (pH > 11), which is not typically employed for reversed-phase liquid chromatography (RPLC), was utilized in RPLC-tandem mass spectrometry (MS/MS) to achieve effective separation between electrically neutral bases of aminoglycosides (AGs). A mixture of AGs was simultaneously analyzed using 500 mmol L-1 ammonia aqueous solution (pH 11.8) as the mobile phase. A total of 11 AGs, including 2 stereoisomers of neomycin (B and C) and 5 structurally similar components of gentamicin (C1, C1a, C2, C2a, and C2b), were completely separated for the first time. The high separation performance for AGs was mainly due to two factors: First, slight differences in hydrophobicity among the AGs were significantly enhanced at a high pH by the complete acid dissociation of amines. Second, the high pH of the mobile phase minimized any electrostatic interactions between the AGs and residual silanol groups in the stationary phase, resulting in extremely sharp peaks for the AGs. The sensitivity of spectinomycin decreased by more than 20% when using the highly basic mobile phase (pH 11.8) due to its degradation, therefore, a mixture of 10 AGs was analyzed with 250 mmol L-1 ammonia aqueous solution (pH 11.5) with less degradation as the optimum condition. The developed analytical method could be used to determine the concentrations of trace AGs in milk with high accuracy and precision. Thus, RPLC-MS/MS using a high-pH mobile phase has great potential for the efficient separation of basic compounds containing amino sugars such as AGs.
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Aminosides , Chromatographie en phase inverse , Chromatographie en phase inverse/méthodes , Aminosides/analyse , Spectrométrie de masse en tandem/méthodes , Ammoniac , Antibactériens/composition chimique , Concentration en ions d'hydrogène , Chromatographie en phase liquide à haute performance/méthodesRÉSUMÉ
BACKGROUND Down syndrome (DS) is the most common genetic disorder, and individuals with DS are known to have a low risk for solid tumors, including breast cancer. In contrast, Breast Cancer Susceptibility Gene (BRCA) pathogenic variant can cause breast cancer. We report a case of primary breast cancer harboring a BRCA2 pathogenic variant in a 35-year-old woman with DS. CASE REPORT A 35-year-old woman with DS presented with a palpable 2-cm mass in the upper-inner quadrant of the left breast. A biopsy confirmed an invasive ductal carcinoma of the breast. Her clinical diagnosis was cT2, N0, M0, cStageIIA. A left modified radical mastectomy with axillary node dissection was performed. Her final pathological diagnosis was invasive ductal carcinoma (T2, pN1, M0, stageIIB), positive estrogen receptors, negative progesterone receptors, negative human epidermal receptor-2 status. She was started on adjuvant hormonal therapy. Unfortunately, 23 months after the operation, multiple metastases were detected. Testing for a BRCA pathogenic variant was performed, and a BRCA2 pathogenic variant was detected. Olaparib was orally administered, and the levels of tumor markers rapidly declined; however, the levels of the tumor markers started to increase again 5 months after the initiation of olaparib. Subsequently, she developed bilateral carcinomatous lymphangiomatosis and died 59 months after the operation. CONCLUSIONS This report highlights a rare case of primary breast cancer harboring a germline BRCA2 pathogenic variant in an individual with DS. Our study highlights the importance of genetic testing as part of breast cancer management in these patients.
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Tumeurs du sein , Carcinome canalaire , Syndrome de Down , Femelle , Humains , Adulte , Tumeurs du sein/anatomopathologie , Mastectomie , Syndrome de Down/complications , Syndrome de Down/chirurgie , Marqueurs biologiques tumoraux , Carcinome canalaire/chirurgie , Cellules germinales/anatomopathologie , Protéine BRCA2/génétiqueRÉSUMÉ
PURPOSE: To examine the characteristics of drug-loaded superabsorbent polymer microspheres (SAP-MS) such as drug absorption, drug release, diameter, and visibility. MATERIALS AND METHODS: SAP-MS (HepaSphere150-200 µm; Merit Medical, South Jordan, UT, USA) were suspended in drug solutions: (a) cefazolin, (b) lidocaine, (c) iopamidol and cefazolin, (d) iopamidol and lidocaine, and (e) iopamidol, cefazolin, and lidocaine. The concentrations of drugs were measured, and the amount of each drug absorbed was calculated. Filtered drug-loaded SAP-MS were mixed with saline, and the drug release rates were calculated. The diameter changes of SAP-MS during absorption were observed. Radiography of drug-loaded SAP-MS was evaluated as radiopacity by contrast-to-noise ratio (CNR). RESULTS: The drug concentration did not change during absorption. The release rates increased for 10 min and then came to an equilibrium. The mean amounts of drug absorbed at 180 min and mean release rates at 24 h were (a) cefazolin: 265.4 mg, 64.2%; (b) lidocaine: 19.6 mg, 75.6%; (c) iopamidol: 830.2 mg, 22.5%; cefazolin: 137.6 mg, 21.2%; (d) iopamidol: 1620.6 mg, 78.5%; lidocaine: 13.5 mg, 81.4%; and (e) iopamidol: 643.7 mg, 52.9%; cefazolin: 194.0 mg, 51.6%; lidocaine: 5.3 mg, 58.4%. The diameter of SAP-MS increased for approximately 15 min. Finally, the diameters of SAP-MS were (a) 3.9 times, (b) 5.0 times, (c) 2.2 times, (d) 5.5 times, and (e) 3.6 times larger than the original size. Drug-loaded SAP-MS containing iopamidol were visible under X-ray imaging, with CNRs of (c) 3.0, (d) 9.0, and (e) 4.5. CONCLUSION: SAP-MS can absorb and release iopamidol, cefazolin, and lidocaine.
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Antibactériens , Produits de contraste , Humains , Iopamidol , Céfazoline , Microsphères , Polymères , Lidocaïne , AnalgésiquesRÉSUMÉ
Amyloid light chain (AL) amyloidosis is a rare disorder caused by the deposit of misfolded light chain proteins. AL amyloidosis causes multiple organ involvement and rarely causes fatal liver failure. We present a 68-year-old man who showed cholestatic liver injury and was diagnosed with AL amyloidosis. Due to rapidly progressing cholestatic liver involvement, the patient died five days after the renal biopsy. Preclinically, there was hypercholesterolemia, and levels of gamma-glutamyltransferase (GGT) were elevated. Previous studies have suggested hypercholesterolemia and elevated GGT levels in patients with AL amyloidosis and liver involvement; however, its clinical relevance remains unknown. Our report suggests that in addition to serum kappa/lambda, the combination of new-onset GGT level elevation and hypercholesterolemia could be preclinical characteristics of cholestatic liver involvement in AL amyloidosis.
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The long non-coding RNA (lncRNA) LINC00460 is involved in tumor growth, metastasis and drug resistance. The present study investigated the clinical significance of LINC00460 expression in patients with epidermal growth factor receptor (EGFR) mutation-positive lung cancer treated with osimertinib. Osimertinib-resistant cells we derived from EGFR-mutant non-small-cell lung cancer (NSCLC) cell lines, after which, small interfering RNA (siRNA)-mediated silencing and in vitro-transcribed (IVT), synthetic LINC00460 RNA transfection were used to investigate the effects of LINC00460 expression on acquired resistance to osimertinib. Reverse transcription-quantitative polymerase chain reaction was performed to evaluate LINC00460 expression in 54 samples (RNA extracted from the tumor tissues of 30 cases and cell-free RNA from 24 cases) obtained from patients with EGFR mutation-positive lung cancer who had received osimertinib as the initial treatment. The acquisition of osimertinib resistance increased the expression of LINC00460 in the EGFR-mutant NSCLC cell lines. By contrast, knockdown of LINC00460 in osimertinib-resistant cell lines increased their sensitivity to osimertinib, whereas treatment of NSCLC cells with IVT LINC00460 RNA decreased their sensitivity to osimertinib. The present study examined LINC00460 expression at the primary tumor site and demonstrated that compared with in the low-expression group (n=24), the high-expression group (n=6) had a significantly lower best overall response rate to osimertinib (16.6% vs. 60.0%; P=0.044), significantly shorter median progression-free survival (PFS; 224 days vs. 669 days; P=0.001) and significantly shorter median overall survival (724 days vs. not reached; P=0.011). Moreover, following osimertinib therapy, PFS was significantly shorter for patients with high LINC00460 expression in plasma cell-free RNA (n=12) than for those with low LINC00460 expression (n=12) (median PFS: 655 days vs. 210 days; P=0.020). In conclusion, the upregulation of LINC00460, the expression of which is implicated in osimertinib resistance, in the primary site and plasma of patients with EGFR mutation-positive lung cancer may be associated with a poor prognosis in those treated with osimertinib.
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Introduction: Sensory dysfunctions and cognitive impairments are related to each other. Although a relationship between tinnitus and subjective olfactory dysfunction has been reported, there have been no reports investigating the relationship between tinnitus and olfactory test results. Methods: To investigate the relationship between tinnitus and olfactory test results, we conducted sensory tests, including hearing and visual examinations. The subjects included 510 community-dwelling individuals (295 women and 215 men) who attended a health checkup in Yakumo, Japan. The age of the subjects ranged from 40 to 91 years (mean ± standard deviation, 63.8 ± 9.9 years). The participants completed a self-reported questionnaire on subjective tinnitus, olfactory function, and hearing function, as well as their lifestyle. The health checkup included smell, hearing, vision, and blood examinations. Results: After adjusting for age and sex, the presence of tinnitus was significantly associated with subjective olfactory dysfunction, poor olfactory test results, hearing deterioration, vertigo, and headache. Additionally, high serum calcium levels and a low albumin/globulin ratio were significantly associated with low physical activity and nutrition. Women scored higher than men in olfactory and hearing examinations, but there was no gender difference in vision examinations. Conclusion: Subjective smell dysfunction and poor smell test results were significantly associated with tinnitus complaints. Hearing and vision were associated even after adjusting for age and sex. These findings suggest that evaluating the mutual relationships among sensory organs is important when evaluating the influence of sensory dysfunctions on cognitive function.
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Troubles de l'olfaction , Acouphène , Mâle , Humains , Femelle , Adulte , Adulte d'âge moyen , Sujet âgé , Sujet âgé de 80 ans ou plus , Odorat , Ouïe , Troubles de l'olfaction/épidémiologie , Enquêtes et questionnairesRÉSUMÉ
We present venous valve stenosis, which is an uncommon cause of arteriovenous fistula (AVF) dysfunction. Owing to the thin structure in echography, venous valves are challenging to observe; however, we have found that the aliasing phenomenon is useful for diagnosing venous valve stenosis.
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Fistule artérioveineuse , Valves veineuses , Humains , Sténose pathologique , Dialyse rénale , Fistule artérioveineuse/complications , Fistule artérioveineuse/imagerie diagnostique , ÉchographieRÉSUMÉ
AMP-activated protein kinase (AMPK) inactivation in chronic kidney disease (CKD) leads to energy status deterioration in the kidney, constituting the vicious cycle of CKD exacerbation. Unc-51-like kinase 1 (ULK1) is considered a downstream molecule of AMPK; however, it was recently reported that the activity of AMPK could be regulated by ULK1 conversely. We demonstrated that AMPK and ULK1 activities were decreased in the kidneys of CKD mice. However, whether and how ULK1 is involved in the underlying mechanism of CKD exacerbation remains unknown. In this study, we investigated the ULK1 involvement in CKD, using ULK1 knockout mice. The CKD model of Ulk1-/- mice exhibited significantly exacerbated renal function and worsening renal fibrosis. In the kidneys of the CKD model of Ulk1-/- mice, reduced AMPK and its downstream ß-oxidation could be observed, leading to an energy deficit of increased AMP/ATP ratio. In addition, AMPK signaling in the kidney was reduced in control Ulk1-/- mice with normal renal function compared to control wild-type mice, suggesting that ULK1 deficiency suppressed AMPK activity in the kidney. This study is the first to present ULK1 as a novel therapeutic target for CKD treatment, which regulates AMPK activity in the kidney.
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AMP-Activated Protein Kinases , Insuffisance rénale chronique , Souris , Animaux , Homologue de la protéine-1 associée à l'autophagie/génétique , Homologue de la protéine-1 associée à l'autophagie/métabolisme , AMP-Activated Protein Kinases/génétique , AMP-Activated Protein Kinases/métabolisme , Rein/métabolisme , Insuffisance rénale chronique/métabolisme , Phosphorylation , AutophagieRÉSUMÉ
Recent applications of decellularized tissues include the ectopic use of sheets and powders for three-dimensional (3D) tissue reconstruction. Decellularized tissues are modified (or fabricated) with the desired functions for application to the target (transplanted or used) tissue, including soft-hard interregional tissues, such as ligaments, tendons, and periodontal ligaments. This study aimed to prepare a mineralized decellularized pericardium to construct a soft-hard interregional tissue by 3D fabrication of decellularized pericardium, for example, rolling up to a cylindrical form. The decellularized pericardial tissue was prepared using the high hydrostatic pressurization (HHP) and surfactants method. The pericardium consisted of bundles of aligned fibers, and the bundles were slightly disordered when prepared with the surfactant decellularization method compared with that prepared using the HHP decellularization method. Mineralization of the decellularized pericardium was performed using an alternate soaking process with various cycles. The surface of the decellularized pericardium was covered with calcium phosphate precipitates, which accumulated on the surface with an increasing number of soaking cycles. The inside of the HHP decellularized pericardium was mineralized uniformly, whereas the mineralization of the decellularized pericardium decreased toward the interior. These findings suggest that the decellularization method strongly affects the structure and mineralized parts of the decellularized pericardium. The mineralized decellularized pericardium could be a candidate material for reconstructing alternative interregional tissues, such as ligaments and tendons.
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BACKGROUND: Chronic kidney disease is associated with perioperative mortality. However, outcomes of patients who perioperatively received acute dialysis have not been clarified. We aimed to determine risks for in-hospital death and functional decline following various surgeries with an acute dialysis requirement versus maintenance dialysis and non-dialysis. MATERIALS AND METHODS: We analyzed 22,857 patients who underwent major surgeries during hospitalization in Japan from 2018 until 2019 using an inpatient administrative claims database. Risks of overall death and functional decline assessed by Barthel index scores were determined with logistic regression models. RESULTS: Among the propensity score-matched groups, mortality rates were 8.54% [95% confidence interval (CI) 7.92-9.17], 5.97% (95% CI 5.44-6.50), and 1.12% (95% CI 0.88-1.35) with an acute dialysis requirement, maintenance dialysis, and non-dialysis, respectively. The survivor rates with ≥20%-decline in Barthel index scores were 7.67% (95% CI 7.07-8.26), 8.56% (95% CI 7.93-9.19), and 3.48% (95% CI 3.07-3.89), respectively. Lower preoperative Barthel index scores were strongly associated with mortality independent of surgeries. Cardiac surgery, colorectal resection, esophagectomy, and gastrectomy led to higher mortality, while cardiac surgery, and orthopedic surgery were associated with higher risk of functional decline. In addition, mortality rates after hepatic lobectomy/cholecystectomy/pancreatectomy [odds ratio (OR) 3.09, 95% CI 1.61-5.91] and esophagectomy/gastrectomy (OR 2.65, 95% CI 1.68-4.38) were markedly higher with an acute dialysis requirement when compared with maintenance dialysis. CONCLUSION: Perioperative acute dialysis requirements were associated with substantial risks for mortality and functional decline. Several types of surgeries led to even higher mortality rates for acute dialysis than maintenance dialysis.
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Dialyse rénale , Insuffisance rénale chronique , Mortalité hospitalière , Humains , Score de propension , Études rétrospectives , Facteurs de risqueRÉSUMÉ
Although salvage therapy with rituximab is effective in some cases of immune-mediated thrombotic thrombocytopenic purpura (iTTP) refractory to standard plasma exchange (PEX) and glucocorticoid treatment or relapsed after treatment, protocols to address the subsequent high recurrence rate have not been established. We describe the use of cyclosporine (CSA) to prevent recurrence in a patient with iTTP relapse after rituximab therapy, and present a literature review. A 24-year-old woman was diagnosed with iTTP and initially received PEX and high-dose methylprednisolone therapy. However, weekly rituximab therapy was also needed for inhibitor boosting to achieve additional immunosuppression during the initial treatment. Although the patient achieved clinical remission after weekly rituximab therapy, iTTP relapsed twice when glucocorticoids were tapered, and was treated with a triplet regimen consisting of PEX, high-dose methylprednisolone, and weekly rituximab. CSA was administered along with glucocorticoids as prophylaxis against iTTP relapse. The additional CSA therapy successfully maintained iTTP remission and allowed reduction of the corticosteroid dose. Our findings demonstrate that prophylactic CSA can potentially prevent iTTP recurrence in patients with a history of multiple relapses. Data from more cases must be accumulated to establish a useful prophylactic therapy for iTTP that is refractory even to rituximab.
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Ciclosporine , Immunosuppresseurs , Purpura thrombotique thrombocytopénique , Protéine ADAMTS13 , Adulte , Ciclosporine/usage thérapeutique , Femelle , Humains , Immunosuppresseurs/usage thérapeutique , Méthylprednisolone/usage thérapeutique , Échange plasmatique , Purpura thrombotique thrombocytopénique/traitement médicamenteux , Récidive , Rituximab/usage thérapeutique , Jeune adulteRÉSUMÉ
CRISPR/Cas9 genome editing underwent remarkable progress and significantly contributed to the development of life sciences. Induced pluripotent stem cells (iPSCs) have also made a relevant contribution to regenerative medicine, pharmacological research, and genetic disease analysis. However, knockout iPSC generation with CRISPR/Cas9 in general has been difficult to achieve using approaches such as frameshift mutations to reproduce genetic diseases with full-length or nearly full-length gene deletions. Moreover, splicing and illegitimate translation could make complete knockouts difficult. Full-length gene deletion methods in iPSCs might solve these problems, although no such approach has been reported yet. In this study, we present a practical two-step gene-editing strategy leading to the precise, biallelic, and complete deletion of the full-length NPHP1 gene in iPSCs, which is the first report of biallelic (compound heterozygous) full-gene deletion in iPSCs using CRISPR/Cas9 and single-stranded oligodeoxynucleotides mainly via single-strand template repair (SSTR). Our strategy requires no selection or substances to enhance SSTR and can be used for the analysis of genetic disorders that are difficult to reproduce by conventional knockout methods.
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Systèmes CRISPR-Cas , Cellules souches pluripotentes induites , Protéines adaptatrices de la transduction du signal/génétique , Animaux , Systèmes CRISPR-Cas/génétique , Protéines du cytosquelette/génétique , Délétion de gène , Édition de gène/méthodes , Hétérozygote , HumainsRÉSUMÉ
Introduction: Minimal change disease (MCD), a common cause of primary nephrotic syndrome that accounts for 10%-15% of all primary nephrotic syndrome cases in adults, is frequently associated with malignant lymphoma. However, studies on MCD associated with prostate cancer are scarce. Case Presentation: A 73-year-old male with prostate cancer was referred to our department with hypoalbuminemia and severe proteinuria while waiting for prostatectomy. We diagnosed the patient with nephrotic syndrome and performed a renal biopsy. Renal pathological findings were consistent with those of MCD. The clinical course suggested an association between prostate cancer and MCD as our patient achieved complete remission of MCD after receiving androgen deprivation and radiation therapy for prostate cancer without the use of glucocorticoids or other immunosuppressants. Discussion: Although MCD can be associated with solid tumors, MCD associated with prostate cancer is very rare. The current case is the first to directly raise the possibility that secondary MCD may develop due to prostate cancer in some patients.
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Ramucirumab-induced renal dysfunction is rarely reported. The pathology of ramucirumab-associated nephropathy in past reports primarily shows thrombotic microangiopathy (TMA) lesions but podocytopathy is not yet known. We report a case of kidney injury induced by ramucirumab in a 71-year-old man with cecal cancer. He was referred to our department for increasing serum creatinine (Cr) levels from 1.08 mg/dL to 2.56 mg/dL after changing anticancer drugs from bevacizumab to ramucirumab. He showed nephrotic-range proteinuria (12.1 g/gCr). A renal biopsy revealed endothelial cell injuries, such as TMA and podocytopathy with epithelial cell hyperplasia, which looked like a crescent. After discontinuing ramucirumab, his renal function and proteinuria improved, as seen by his Cr levels and proteinuria which decreased to 1.74 mg/dL and 1.21 g/gCr, respectively, in 3 months. Unlike previous reports, we found that ramucirumab caused podocyte injuries.
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Insuffisance rénale , Microangiopathies thrombotiques , Sujet âgé , Anticorps monoclonaux humanisés/effets indésirables , Humains , Mâle , Protéinurie/induit chimiquement , Microangiopathies thrombotiques/induit chimiquement ,RÉSUMÉ
OBJECTIVES: Reticulated platelets circulating in the blood reflect megakaryopoietic activity and platelet turnover and can be automatically and low-invasively measured as the immature platelet fraction (IPF) using a Sysmex XN hematocytometer. The present study retrospectively investigated whether or not the IPF can predict the treatment response to corticosteroids in adult patients with primary immune thrombocytopenia (ITP). METHODS: Forty-six patients who had been newly diagnosed with primary treatment-naïve ITP and started treatment with corticosteroids were analyzed. RESULTS: Among the 46 primary ITP patients, 33 (72%) responded to the treatment and 13 (28%) did not. The percentage of IPF (IPF%) among the nonresponders was significantly lower than that of the responders (6.6 vs. 16.0%; p < 0.001). In the receiver operating characteristics analysis, the optimum IPF% cut-off value for predicting the treatment response was 12%, with a specificity of 85% and a sensitivity of 76%. CONCLUSIONS: Our findings thus suggest that measuring the IPF% as a surrogate of reticulated platelets is useful to identify patients likely to respond to corticosteroids.
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Hormones corticosurrénaliennes/usage thérapeutique , Plaquettes/cytologie , Transfusion de plaquettes , Purpura thrombopénique idiopathique/diagnostic , Adulte , Sujet âgé , Sujet âgé de 80 ans ou plus , Aire sous la courbe , Femelle , Humains , Mâle , Adulte d'âge moyen , Purpura thrombopénique idiopathique/traitement médicamenteux , Courbe ROC , Études rétrospectives , Résultat thérapeutique , Jeune adulteRÉSUMÉ
Introduction: Due to an increased incidence of copper deficiency, we investigated adult patients who had low serum levels of copper with cytopenia at our hospital from March 2014 to March 2021. Methods: We retrospectively reviewed the clinical data of patients who had been diagnosed with cytopenia due to copper deficiency at the Aichi Medical University Hospital from March 2014 to March 2021. Results: In the 15 patients with cytopenia secondary to low serum copper level, 11 had cytopenia of two to three lineages; three (27%) had pancytopenia, and eight (73%) had bicytopenia. Of the 15 patients, nine (60%) underwent bone marrow examinations; three (30%) showed typical morphologic features associated with copper deficiency, such as multiple clear cytoplasmic vacuoles in erythroblasts and myeloid cells, and three (30%) showed dysplastic features as observed in myelodysplastic syndrome. Among the 14 (93%) patients who were treated with copper supplements, had cessation of zinc supplements, or both, 11 (73%) and eight (53%) showed normal copper levels and hematological improvement, respectively. Conclusion: Copper deficiency is more common than expected and should be considered in patients with unexplained cytopenia.