A Patient with Mitochondrial Disease on Dialysis with Long-term Follow-up of Cardiomyopathy: An Autopsy Case Report.

A 59-year-old man developed diabetes at 24 years old and underwent hemodialysis at 42 years old. At 54 years old, cardiac dysfunction with left ventricular hypertrophy was detected, followed by complete atrioventricular block at 57 years old. The patient was diagnosed with mitochondrial disease based on a myocardial biopsy and the presence of a mitochondrial DNA mutation (3243A>G). He died of septic shock at 59 years old, and an autopsy confirmed mitochondrial cardiomyopathy. If progressive cardiac hypertrophy and conduction disturbances are observed in patients with diabetes mellitus on long-term hemodialysis, mitochondrial disease needs to be considered.

Dural arteriovenous fistula following cerebral venous sinus thrombosis in a patient with minimal change disease: A case report.

A 78-year-old man presented with nephrotic syndrome and new-onset disorientation. Plasma D-dimer level was increased, and a lower leg deep vein thrombosis was identified on ultrasound. Histopathologic analysis of percutaneous renal biopsy samples confirmed the diagnosis of minimal change disease. Treatment with prednisone (20 mg/day), cyclosporine (50 mg/day), and anticoagulant therapy with edoxaban tosylate hydrate led to the complete resolution of nephrotic syndrome after 4 weeks. Despite this, his disorientation persisted. Head CT and MRI have revealed cerebral venous sinus thrombosis and dural arteriovenous fistula, which was considered a possible complication of nephrotic syndrome. Embolization dramatically improved his disorientation. This paper highlights that cerebral venous sinus thrombosis and dural arteriovenous fistula should always be considered in patients with nephrotic syndrome and new-onset disorientation.

Detection of Treponema pallidum by immunocytochemistry of cervical smear: A case report.

Syphilis is an infectious disease caused by Treponema pallidum (T. pallidum). A cervical smear is useful when screening for sexually transmitted diseases; however, T. pallidum is not detected in the usual Papanicolaou smear. We report the detection of T. pallidum by immunocytological examination of a cervical smear. A 22-year-old woman presented with nephrotic syndrome. On admission, we performed screening tests for infections, and her serology was positive for syphilis. A Papanicolaou cervical smear (Thin-Prep) showed slight nuclear enlargement, nuclear irregularity, and mild hyperchromasia in the superficial cells, but no organism was detected. T. pallidum was detected in the remaining specimen using immunocytochemistry. We also detected the T. pallidum DNA in a cervical biopsy specimen by polymerase chain reaction (PCR). Our findings suggest that immunocytological examination and PCR assay examination are useful tests for syphilis diagnosis.

A case of lupus vasculopathy presenting favorable renal outcome.

Noninflammatory necrotizing vasculopathy, also referred to as lupus vasculopathy, is not infrequently observed in the pathology of lupus nephritis. It affects vessels causing them to become severely narrowed and occluded by a mechanism involving immune complexes. We experienced a 51-year-old woman with lupus nephritis class IV + V, which was accompanied by lupus vasculopathy. Renal biopsy and light microscopy showed eosinophilic hyaline-like material in the afferent and/or efferent arterioles, which narrowed the lumen, and which were positive for IgG by immunofluorescent analysis. Electron microscopy indicated that amorphous material and endothelial detachment occluded the arterioles. These findings were consistent with those of lupus vasculopathy. We treated the patient with steroids and cyclophosphamide. By the day of discharge, her levels of creatinine and proteinuria had undergone partial remission. Although lupus vasculopathy was implied as a lesion with unfavorable renal prognosis, some recent reports suggest its true renal prognosis is not unfavorable necessarily. Nevertheless, lupus vasculopathy is an important finding in diagnosis in contradiction to other vascular legions in systemic lupus erythematosus. In addition, a standard therapy has also not been established. Therefore, it is important to accumulate cases of lupus vasculopathy to determine its prognosis and develop standard treatments.

Dasatinib-induced nephrotic syndrome in a patient with chronic myelogenous leukemia: a case report.

BACKGROUND: Dasatinib is a second-generation tyrosine kinase inhibitor that is indicated for the treatment of patients with chronic myeloid leukemia. Here, we report the case of a man with nephrotic syndrome that was caused by dasatinib. CASE PRESENTATION: A 40-year-old man with chronic myeloid leukemia was referred to our hospital because of proteinuria 1 month after dasatinib therapy was introduced. A percutaneous kidney biopsy was performed, diffuse glomerular endothelial injury and effacement of the foot process were noted, and the patient was diagnosed with dasatinib-induced nephrotic syndrome. Additionally, in an electron microscopy study, randomly arranged fibrils were observed in the mesangial and subendothelial regions. Switching from dasatinib to nilotinib led to a decrease in the proteinuria level, from 12 to 0.6 g/g creatinine, within 2 weeks. The patient was discharged from our department on the 25th day after hospitalization, without any drug aftereffects. CONCLUSIONS: Drug-related nephrotic syndrome should be considered when nephrotic syndrome develops during treatment with dasatinib.

Emergence of Haemophilus influenzae with low susceptibility to quinolones and persistence in tosufloxacin treatment.

BACKGROUND: The use of non-ß-lactam agents has increased in Japan due to the prevalence of ß-lactam-resistant pathogens. This study aimed to clarify the recent trend of antimicrobial susceptibility and molecular epidemiological features in Haemophilus influenzae. METHODS: Fifty-seven Haemophilus influenzae isolated from a Japanese teaching hospital in 2017 were characterised, and the data were compared with those of a previous study. The MICs were determined using the broth dilution method. Genetic backgrounds were compared by multilocus sequence typing. The bactericidal activity of tosufloxacin at, or near, the therapeutic Cmax was determined in vitro, with susceptible isolates and quinolone low-susceptible isolates by time-kill assay. RESULTS: The results of the susceptibility tests showed that >90% of isolates were susceptible to cephalosporins and carbapenems, whereas ampicillin-susceptible and clarithromycin-susceptible isolates decreased. Regarding quinolones, low-susceptible isolates were noted in 2017, although all isolates were judged as susceptible. All low-susceptible isolates had an amino acid substitution in GyrA, and two isolates had an additional substitution in ParC. These isolates had different genetic backgrounds. Furthermore, the time-kill kinetic assay using the Cmax of tosufloxacin indicated that the low-susceptible isolates could persist for at least 8hours. CONCLUSIONS: This study revealed that Haemophilus influenzae has demonstrated multidrug low-susceptibility in recent years. The low-susceptible isolates had genetic diversity, meaning that resistance occurred independently.

Prognostic significance of inflammatory parameters and nutritional index in clinical stage IVB endometrial carcinomas.

Recently, neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) or prognostic nutritional index (PNI) have been investigated as prognostic parameters in various malignancies. Herein, we detail how we have investigated the prognostic significance of NLR, PLR and PNI together with the other clinicopathological factors for International Federation of Gynaecology and Obstetrics stage IVB endometrial carcinoma. Thirty-two patients with clinical stage IVB disease were enrolled. The relationship between clinicopathological factors, NLR, PLR or PNI and overall survival (OS) rates was investigated. The 5-year OS rate was 9.7%, and the median survival time was 9 months. In univariate analysis, PS 0-1, G1-2 endometrioid carcinoma, occurrence of surgery, NLR (below median) and PNI (≥median) were identified as favourable prognostic factors. In multivariate analysis, only a histology (G1-2 endometrioid carcinoma) was identified as an independent favourable prognostic factor. Additional large-scale studies are required to confirm the prognostic significance of NLR, PLR and PNI in clinical stage IVB endometrial carcinoma. Impact Statement What is already known on this subject? Several parameters representing the systemic inflammatory response (e.g. neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR)) or the nutritional condition (e.g. prognostic nutritional index (PNI)) have been investigated as prognostic parameters in various malignancies, whereas they have not been thoroughly investigated in endometrial carcinoma. What the results of this study add? In univariate analysis of various factors for overall survival, the performance status (PS) 0-1, grade 1-2 endometrioid carcinoma, occurrence of surgery, NLR (below median) and PNI (≥median) were identified as favourable prognostic factors. However, in a multivariate analysis, only the histology (grade 1-2 endometrioid carcinoma) was identified as an independent favourable prognostic factor. What the implications are of these findings for clinical practice and/or further research? This retrospective study identified that neither inflammatory parameters nor the nutritional index were revealed to be independent prognostic factors by multivariate analyses. Additional large-scale studies are required to confirm the prognostic significance of NLR, PLR and PNI in clinical stage IVB endometrial carcinoma to improve the poor prognosis of this disease.

Liposarcoma of the uterine corpus: A case report and literature review.

Liposarcoma of the uterine corpus is extremely rare. We performed a laparotomy on a 55-year-old woman with the complaints of abdominal distension and genital bleeding who was found to have a uterine tumor, 17 × 16 cm in diameter. The preoperative diagnosis was a lipoma or lipoleiomyoma of the uterine corpus. However, pathological examination revealed proliferation of mature adipocytes and lipoblast-like atypical cells with small, weakly pleomorphic nuclei and foamy or vacuolated cytoplasm present within a fibrous septum. Immunohistochemistry showed that the tumor cells were focally positive for mouse double minute 2 homolog (MDM2). The final pathological diagnosis was a well-differentiated liposarcoma of International Federation of Gynecology and Obstetrics (FIGO) stage IB (pT1bNxM0). On magnetic resonance imaging (MRI), T1 -weighted and fat-saturated images showed high and low intensity in the tumor, respectively, suggesting that this tumor contained a fat component. The septum inside the tumor had a contrast enhancement on T1-weighted, gadolinium-enhanced imaging. The septum was nonuniformly thickened and partially nodular. In hindsight, these findings may have suggested a well-differentiated liposarcoma in the uterine corpus rather than a lipoma or lipoleiomyoma. Clinicians should be aware of the possibility of a liposarcoma of the uterine corpus when a neoplasm contains adipose tissue and a nonuniformly thickened or partially nodular septum on MRI.

Proposed selection strategy of surrogate matrix to quantify endogenous substances by Japan Bioanalysis Forum DG2015-15.

It is important to select an appropriate surrogate matrix for preparing calibration standards and quality control samples while quantitatively assaying for endogenous substances, because a blank matrix that does not contain the endogenous substance cannot be derived from the species from which the target study samples are collected. This is because the assay results might be affected, depending on the characteristics of the analyte in the surrogate matrix. Our discussion group that participated in the Japan Bioanalysis Forum discussed the recommended selection strategies, focusing on large and small molecules in ligand binding assays and LC-MS, respectively. We established an efficient selection strategy for a surrogate matrix, with simple compositions as the first candidates stated in this article.

Cytological Findings of Ascitic Fluid with a Malignant Ovarian Steroid Cell Tumor: A Case Report and Literature Review.

BACKGROUND: Ovarian steroid cell tumors (SCTs) are rare and usually benign, although 25-43% are reportedly malignant. The cytologic findings of these rare ovarian tumors have almost never been reported. CASE: We report a rare case of a malignant ovarian SCT with peritoneal dissemination and malignant ascites in a 40-year-old woman. Her tumor was classified as stage IIB (pT2bNoM0) according to the FIGO (International Federation of Gynecology and Obstetrics) classification system, and she was treated with adjuvant chemotherapy following staging laparotomy. Cytology of the ascitic fluid revealed large, polygonal-to-round cells and multinucleated cells with atypia, appearing in clusters with slight overlapping or as isolated tumor cells. Numerous tumor cells had small central round or eccentric nuclei with conspicuous nucleoli, and a moderate-to-abundant amount of cytoplasm, varying from granular and eosinophilic to pale and multivacuolated (foamy), with cannibalism formations. The nuclear chromatin was fine and granular, with irregular distribution and nuclear-membrane thickening. CONCLUSION: These may be the first reported cytology results for ascites with a malignant SCT. Our patient's cytological ascitic findings, rather than the histopathologic features of the original and disseminated tumors, represent the malignant features of the tumor.

Comparison of potential risks of lactic acidosis induction by biguanides in rats.

Lactic acidosis has been considered to be a side effect of some biguanides, after phenformin was withdrawn from the market because of its association with lactic acidosis. The potential of lactic acidosis induced by biguanides at human therapeutic exposure levels, however, has not been examined. Then, we compared the risk of lactic acid at doses providing exposure levels comparable to human therapeutic doses. Metformin and phenformin were orally administered to rats for up to 28 days, and plasma drug concentrations and blood lactic acid levels were examined. Metformin did not elevate lactic acid levels at the dose corresponding to higher systemic drug exposure than human therapeutic level, even for repeated doses. In contrast, phenformin elevated lactic acid levels at the dose corresponding to lower exposure than human therapeutic level, and sustained high levels were observed up to 24h post-dose; furthermore, these changes were enhanced by repeated doses. Direct comparison at each rat equivalent dose clearly indicated that lactic acid levels of phenformin were higher than those of metformin. These non-clinical findings suggest that metformin dose not increase lactic acid levels like phenformin does, and therefore may not increase the risk for lactic acidosis at human therapeutic exposure level.