Chronic hypoxia exacerbates diabetic glomerulosclerosis through mesangiolysis and podocyte injury in db/db mice.

BACKGROUND: Chronic hypoxia may play a pivotal role in the development of diabetic nephropathy (DN). However, the precise mechanisms underlying progressive hypoxia-induced glomerular injury remain unclear. METHODS: We housed db/db mice in a hypoxia chamber (12% O2) for up to 16 weeks beginning at 8 weeks of age. Various urine, serum and kidney abnormalities and glomerular messenger RNA (mRNA) expression were compared with those in age-matched db/db mice housed under normoxia. RESULTS: Levels of urinary albumin and podocalyxin (PCX) were significantly higher in hypoxic mice early during hypoxia. Ultracentrifugation of urine samples revealed that podocytes in the hypoxic mice shed PCX-positive microparticles into the urine. After 16 weeks of hypoxia, the mice also had higher hematocrits with lower serum glucose and various degrees of mesangiolytic glomerulosclerosis with microaneurysms and the infrequent occurrence of nodular lesions. Immunohistologically, hypoxic mice showed significantly decreased endothelial cell densities early during hypoxia and decreased podocyte densities later. In both hypoxic and normoxic mice, glomerular macrophage and transforming growth factor-ß1 (TGF-ß1) staining significantly increased with aging, without changes in vascular endothelial growth factor or endothelial nitric oxide synthase (eNOS). Glomerular mRNA expression of monocyte chemoattractant protein-1, eNOS and TGF-ß1 was significantly enhanced in the hypoxic mice. CONCLUSIONS: These results indicate that chronic hypoxia induces advanced glomerulosclerosis with accelerated albuminuria triggered by mesangiolysis and podocyte injury in a murine model of DN.

Pulmonary Artery Banding for Congenitally Corrected Transposition of the Great Arteries With Hydrops Fetalis: A Case Report.

At 32 weeks of gestation, a male fetus with congenitally corrected transposition of the great arteries developed hydrops fetalis caused by a combination of mitral valve regurgitation and tricuspid valve regurgitation (TR). We performed a pulmonary artery banding (PAB) at 108 days old for gradually progressing TR, after confirming that a balloon dilatation test in the main pulmonary artery reduced TR. As the patient grew, the PAB became tighter and systolic blood pressure in the morphological left ventricle increased. At present, the patient is waiting for a double switch operation.

Novel quantitative and objective structured assessment of technical skill for slip knotting.

OBJECTIVE: Currently, no quantitative and objective method has been established for evaluating competencies in basic surgical techniques. The aim of this study was to develop a structured assessment tool for slip knotting and verify how well current board certification system discriminates the level of basic surgical skill. METHODS: We examined 171 cardiovascular surgical fellows using a novel assessment method for slip knotting that was developed by the committee of the Under-Forty of the Japanese Society of Cardiovascular Surgery. We compared the scores and examinees' surgical experience for validation. We analyzed the relationship between board certification and the scores. RESULTS: The scores differentiated the general surgical board-certified surgeons from those without certification. Surgical experiences such as training years and number of operated cases and scores were correlated. Among the board-certified surgeons, the group with daily off-the-job training, or simulator-based skill training had a significantly higher mean score (67.4 ± 3.0 vs 55.4 ± 3.1, p = 0.008) and lower rate of poor scorers (7.1% vs 38.5%, p = 0.004). A multivariate analysis revealed that board certification did not predict high scores. Daily off-the-job training was the only independent predictor of high scores (odds ratio: 2.41, 95% confidence interval: 0.01-1.20, p = 0.014). CONCLUSIONS: This novel quantitative and objective assessment tool for technical skill in slip knotting was found to be valid to examine the skill for slip knotting. In this study, current board certification discriminated the level of basic surgical skill. However, it could not distinguish extremely low scorers perfectly. Some board-certified surgeons showed poor technical competency, especially those without off-the-job training.

Correction to: Novel quantitative and objective structured assessment of technical skill for slip knotting.

The article "Novel quantitative and objective structured assessment of technical skill for slip knotting", written by.

Long-Term Outcomes of Spontaneous Isolated Superior Mesenteric Artery Dissection.

Spontaneous isolated dissection of the superior mesenteric artery (SMAD) is not still well known. We retrospectively analyzed our 30 patients with SMAD to elucidate the treatment strategy and long-term follow-up outcomes. Due to severe abdominal symptom we performed a stents deployment and surgical reconstructive surgery for each one case. Anerysmectomy and bypass surgery was performed for a patient with aneurysmal change. Other 27 patients were managed conservatively. SMAD patients had only two vascular events (renal infarction and graft occlusion), and showed good prognosis for 6-146 (mean 69) months follow-up. We found that there is a few SMAD patients necessary of invasive management at acute phase and that most patients are safely conservatively treated with good prognosis. (This is a translation of J Jpn Coll Angiol 2018; 58: 195-199.).

Serum podocalyxin levels correlate with carotid intima media thickness, implicating its role as a novel biomarker for atherosclerosis.

Podocalyxin is a cell surface sialomucin, which is expressed in not only glomerular podocytes but also vascular endothelial cells. Urinary podocalyxin is used as a marker for glomerular disease. However, there are no reports describing serum podocalyxin (s-Podxl) levels. Therefore, the association between s-Podxl levels and clinical parameters were examined with 52 patients. s-Podxl level was evaluated using enzyme-linked immunosorbent assay. The median s-Podxl level was 14.2 ng/dL (interquartile range: 10.8-22.2 ng/dL). There were significant correlations (correlation coefficient: r > 0.2) of s-Podxl levels with carotid intima media thickness (IMT) (r = 0.30, p = 0.0307). Multiple logistic regression analysis showed that s-Podxl levels remained significantly associated with carotid IMT > 1 mm (OR: 1.15; 95% CI 1.02-1.31, p = 0.026) after adjustments for traditional cardiovascular risk factors such as age, sex, current smoking status, hypertension, dyslipidemias, and diabetes. In conclusion, s-Podxl is independently associated with carotid IMT and might be used as a novel biomarker for cardiovascular disease.

Urinary C-megalin for screening of renal scarring in children after febrile urinary tract infection.

BackgroundFebrile urinary tract infection (fUTI) in children may cause renal scarring. This study aimed to investigate the usefulness of urinary biomarkers for diagnosing renal scarring after fUTI.MethodsThirty-seven children (median age: 1.36 years, range: 0.52-12.17 years, 25 boys) with a history of fUTI, who underwent renal scintigraphy for 4 months or longer after the last episode of fUTI, were analyzed. A spot urine sample was obtained on the day of renal scintigraphy to measure levels of total protein, N-acetyl-ß-D-glucosaminidase (NAG), ß2-microglobulin (BMG), neutrophil gelatinase-associated lipocalin (NGAL), liver-type fatty acid binding protein (L-FABP), and C-megalin (full-length megalin). Results were corrected for urinary creatinine (Cr) and compared between the group with renal scarring (n=23) and that without scarring (n=14). Urinary levels of C-megalin were also measured in healthy control subjects.ResultsNo significant differences in total protein, NGAL, L-FABP, NAG, and BMG levels were found between the groups. However, C-megalin levels were significantly higher in the renal scarring group than in the non-renal scarring group and healthy controls (P<0.001). A cutoff value of 6.5 pmol/nmol of urinary C-megalin/Cr yielded 73.9% of specificity and 92.9% of sensitivity.ConclusionUrinary C-megalin is useful for diagnosing renal scarring caused by fUTI.

Decreased urinary excretion of the ectodomain form of megalin (A-megalin) in children with OCRL gene mutations.

BACKGROUND: The oculocerebrorenal syndrome of Lowe gene (OCRL) is located on chromosome Xq25-26 and encodes an inositol polyphosphate-5-phosphatase (OCRL-1). Mutations in this gene cause Lowe syndrome (LS) or type 2 Dent disease, of which low-molecular-weight (LMW) proteinuria is a characteristic feature. Megalin is considered to play an important role in the development of renal tubular proteinuria. Two forms of megalin are excreted into the urine: full-length megalin (C-megalin) and megalin ectodomain (A-megalin). We have explored the role of megalin in the development of LMW proteinuria in patients with OCRL mutations by determining urinary megalin fractions. METHODS: We measured A- and C-megalin in spot urine samples from five male patients with OCRL mutations (median age 9 years), using sandwich enzyme-linked immunosorbent assays, and adjusted the obtained values for excreted creatinine. The results were compared with those of 50 control subjects and one patient with type 1 Dent disease (T1D). RESULTS: All patients demonstrated normal levels of urinary C-megalin. However, patients with OCRL mutations or T1D showed abnormally low levels of urinary A-megalin, with the exception of one 5-year-old boy with LS, who was the youngest patient enrolled in the study. CONCLUSIONS: Decreased excretion of urinary A-megalin in four out of five patients with OCRL mutations suggests that LMW proteinuria may be caused by impaired megalin recycling within the proximal tubular cells. Homologous enzymes, similar to inositol polyphosphate-5-phosphatase B in mice, may help to compensate for defective OCRL-1 function during early childhood.

Urinary Podocalyxin as a Biomarker to Diagnose Membranous Nephropathy.

BACKGROUND: A non-invasive diagnostic marker of membranous nephropathy (MN) is desirable. The urinary level of podocalyxin (PCX) is higher in various glomerular diseases, including MN. The aim of this study was to construct a diagnostic model of MN with the combination of urinary PCX and clinical parameters. METHODS: We performed this cross-sectional study to construct the diagnostic models for MN by using data and samples from the multicenter kidney biopsy registry of Nagoya University and its affiliated hospitals. Urinary (u-) PCX was measured by sandwich ELISA. We constructed 3 types of diagnostic models in 105 training samples: u-PCX univariate model, the combined model of clinical parameters other than u-PCX (clinical model), and the combined model of both u-PCX and clinical parameters (combined model). We assessed the clinical usefulness of the diagnostic models through the comparison of c-statistics and decision curve analysis (DCA) in 209 validation samples. RESULTS: The clinical model consisted of age, glomerular filtration rate, and diabetes mellitus. In the training cohort, the c-statistics were 0.868 [95% CI, 0.799-0.937] in the combined model. In the validation cohort, sensitivity was 80.5% and specificity was 73.5% on the cut-off value. The net benefit of the combined model was better between threshold probabilities of 40-80% in DCA. CONCLUSIONS: In this study, we demonstrated the utility of u-PCX as a diagnostic marker for MN and the clinical usefulness of the diagnostic models, through the combination of u-PCX and clinical parameters including age, glomerular filtration rate, and diabetes mellitus.

[Efficacy of Early Surgical Strategy for Active Infective Endocarditis].

UNLABELLED: The aim of study was to analyze the outcome of aggressive, early surgical intervention to active infective endocarditis (IE) complicated by acute congestive heart failure, uncontrollable infection and large, mobile vegetation and to evaluate the validity of current therapeutic strategy on it's long-term outcome. PATIENTS AND METHODS: We retrospectively investigated surgical outcome of 51 patients who underwent surgical intervention to eradicate intra-cardiac infection and to reconstruct subsequent structural destruction due to active IE performed between 2002 and 2013. Patient's mean age was 56 ± 17 (14~83) years and 36 males, 2 prior cardiac surgery-performed and 2 hemodialysis-dependent renal failure patients were included. All patients were followed on long-term basis. Mean follow up duration was 61 ± 46 (1~164) months. We classified patients into 2 groups according to urgency of surgical intervention:early surgical (ES) group who underwent surgery within 2 weeks from diagnosis of IE and conservative surgical (CS) group who underwent after 2 weeks more from the diagnosis. RESULTS: Two patients died during hospitalization due to low cardiac output syndrome (LOS) for ischemic myopathy after old myocardial infarction and postoperative ischemic colitis (preoperative hemodialysis-dependent patient). Two cerebral infarctions and 1 hemorrhagic transformation of cerebral infarction occurred postoperatively. There was no mediastinal infection and recurrent intracardiac infection postoperatively. On long-term follow up, cumulative survival was 90/79/68% in 1/5/10 years. on ES group and 100/89/79% in 1/5/10 years. on CS group, respectively. Freedom from cardiac death were 100/100/100% in 1/5/10 years. on ES group and 100/100/100% in 1/5/10 years. on CS group, respectively. There were 1 cardiac death(125 months after operation) and 8 non-cardiac deaths on long-term survival. CONCLUSION: Early surgical strategy for active infective endocarditis to prevent IE-related preoperative adverse complications seems to be acceptable.

Magnetic resonance-based visualization of thermal ablative margins around hepatic tumors by means of systemic ferucarbotran administration before radiofrequency ablation: animal study to reveal the connection between excess iron deposition and T2*-weighted hypointensity in ablative margins.

OBJECTIVE: The objective of this study was to demonstrate experimentally that radiofrequency ablation (RFA) of ferucarbotran-accumulated healthy liver tissues causes excess iron deposition in the ablated liver tissues on postablation days and produces sustained T2*-weighted low signals indicative of ablative margins surrounding hepatic tumors. MATERIALS AND METHODS: We conducted 3 experiments using 30 rats. In experiment 1, we administered either ferucarbotran (n = 6) or saline (n = 4), acquired T2*-weighted images (T2*-WIs) of the liver by using a 3-T magnetic resonance scanner, and subsequently performed RFA of healthy liver lobes. We acquired follow-up T2*-WIs up to day 7 and histologically analyzed the liver specimens. In another 4 rats, we performed sham operation, instead of RFA, in ferucarbotran-accumulated liver lobes, followed by the same image acquisition and histological analysis. In experiment 2, we administered 59Fe-labeled ferucarbotran, subsequently performed either RFA (n = 4) or sham operation (n = 4) in the liver, and acquired autoradiograms of the liver specimens on day 7. In experiment 3, we conducted RFA treatment for 8 rats bearing orthotopic hepatic tumors after ferucarbotran administration and monitored tumor growth by using serial T2*-WIs. RESULTS: On days 4 and 7 of the experiment 1, T2*-WIs of 6 rats with systemic ferucarbotran administration and subsequent hepatic RFA showed low-signal regions indicative of ablated liver tissues, whereas high-signal areas were seen in 4 saline-administered rats. Neither high nor low signal areas were detected in 4 sham-operated rats. Histologically, larger amounts of iron were observed in the RFA-induced necrotic liver tissues in the ferucarbotran-administered rats than in the saline-administered-rats. The 59Fe autoradiography of the rats in experiment 2 revealed accumulation of ferucarbotran-derived iron in necrotic liver tissues. Among 6 hepatic tumors grown in 6 rats of the experiment 3, a total of 4 tumors were stable in size, but the other 2 increased markedly on day 7. Retrospectively, T2*-WIs showed the former tumor sites surrounded completely by low-signal areas on day 4. CONCLUSIONS: The RFA of ferucarbotran-accumulated healthy liver tissues in the rats caused excess iron deposition in the ablated liver tissues and produced sustained T2*-weighted hypointense regions. Similar hypointense regions surrounding hepatic tumors were indicative of ablative margins.

A heterozygous female with Fabry disease due to a novel α-galactosidase A mutation exhibits a unique synaptopodin distribution in vacuolated podocytes.

We report the case of a 42-yearold woman diagnosed with heterozygous Fabry disease (FD) due to a novel α-galactosidase A Pro210Ser mutation and exhibiting a unique distribution of synaptopodin within podocytes. The patient was referred to our hospital with moderate proteinuria, and a renal biopsy was performed. Light microscopic examination of the specimen revealed diffuse global enlargement of podocytes, which also showed foamy changes. Electron microscopy revealed abundant myeloid bodies in podocytes and focal mitochondrial abnormalities within the tubules. The patient exhibited none of the characteristic symptoms of FD except hypohidrosis and had no obvious family history. Genetic analysis revealed a novel missense mutation (Pro210Ser) in the α-galactosidase A gene. She was ultimately diagnosed with FD based on immunohistochemical staining indicating large amounts of accumulated globotriaosylceramide in her podocytes, detection of urinary globotriaosylceramide secretion using high-performance thin-layer chromatography/ immunostaining, and structural modeling of the mutated α-galactosidase A (Pro210Ser). Immunostaining of the swollen and foamy podocytes using podocyte-associated antibodies (against podocalyxin, Wilms tumor-1, vimentin, and synaptopodin) revealed a unique distribution of synaptopodin surrounding globotriaosylceramide. To our knowledge, this is the first report of immunohistologically detected synaptopodin upregulation in foamy podocytes in a patient with FD.

Significance of urinary full-length megalin in patients with IgA nephropathy.

BACKGROUND AND OBJECTIVES: Megalin is highly expressed at the apical membranes of proximal tubular epithelial cells. A urinary full-length megalin (C-megalin) assay is linked to the severity of diabetic nephropathy in type 2 diabetes. This study examined the relationship between levels of urinary C-megalin and histological findings in adult patients with IgA nephropathy (IgAN). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Urine samples voided in the morning on the day of renal biopsy were obtained from 73 patients with IgAN (29 men and 44 women; mean age, 33 years) and 5 patients with membranous nephropathy (MN). Renal pathologic variables were analyzed using the Oxford classification of IgAN, the Shigematsu classification and the Clinical Guidelines of IgAN in Japan. The levels of urinary C-megalin were measured by sandwich ELISA. RESULTS: Histological analysis based on the Oxford classification revealed that the levels of urinary C-megalin were correlated with mesangial hypercellularity in IgAN patients (OR = 1.76, 95% CI: 1.04-3.27, P<0.05). There was a significant correlation between the levels of urinary C-megalin and the severity of chronic extracapillary abnormalities according to the Shigematsu classification in IgAN patients (ß = 0.33, P = 0.008). The levels of urinary C-megalin were significantly higher in all risk levels of IgAN patients requiring dialysis using the Clinical Guidelines of IgAN in Japan than in the control group. The levels of urinary C-megalin were significantly higher in the high risk and very high risk grades than in the low risk grade (P<0.05). The levels of urinary C-megalin were significantly higher in MN patients compared to the control group. CONCLUSIONS: The levels of urinary C-megalin are associated with histological abnormalities in adult IgAN patients. There is a possibility that urinary C-megalin is an independent predictor of disease progression of IgAN. In addition, our results suggest that urinary C-megalin is a marker of glomerular abnormalities in various glomerular diseases as well as IgAN.

Comparison of radioactive iodide uptake in the rat thyroid between oral and intravenous bolus administration.

OBJECTIVE: Radioiodide is commonly used to diagnose and treat hyperthyroidism and thyroid carcinoma. However, we could not find any experimental data that strictly compared the biodistribution and thyroid uptake of radioactive iodide between the oral and intravenous (iv) routes with time. This prompted us to compare (123)I biodistribution and thyroid uptake to clarify the differences between oral and iv bolus administration in rats. METHODS: The rats were divided into two groups, A and B (n = 5, each). In the first imaging experiment, Na(123)I solution (35 MBq/200 µL) was administered as a bolus to the rats orally in group A and intravenously in group B. Two weeks later, the second imaging experiment was performed as a crossover experiment. (123)I biodistribution was evaluated visually and quantitatively with a gamma camera at 10 min, 3, 6, 12, 24, and 48 h after (123)I administration. Thyroid uptake was compared between oral and iv groups. Correlation of (123)I thyroid uptake and whole-body excretion was evaluated. The area under the curve (AUC) of thyroid uptake was also calculated. RESULTS: (123)I biodistribution differed visually during 6 h between the two groups. (123)I thyroid uptake was significantly higher in the iv group at 10 min (P < 0.05) and in the oral group at 6 or more hour time points (P < 0.005-P < 0.0001) and peaked at 12 h in both groups (oral: 24.4 ± 2.8 %ID, iv: 15.2 ± 2.8 %ID). (123)I thyroid uptake showed significant inverse correlations with whole-body excretion from 6 h (r = -0.799, P < 0.0001), and thereafter [12 h (r = -0.957, P < 0.0001), 24 h (r = -0.905, P < 0.0001) and 48 h (r = -0.893, P < 0.0001)], respectively. (123)I whole-body excretion was significantly higher in the iv group at each time point (P < 0.0001). The AUC of (123)I thyroid uptake was 1.6 times higher in the oral group than the iv group. CONCLUSIONS: These results suggest that radioiodide accumulates in the rat thyroid more effectively by oral than iv administration probably due to slower and lower (123)I clearance from the body in the oral administration when administered in a bolus fashion.

Effects of phenylephrine and noradrenaline on coronary artery motion in an open-chest porcine beating heart model.

PURPOSE: During off-pump coronary artery bypass (OPCAB), surgeons are required to perform a precise anastomosis on the beating heart. The hypotension caused by vertical displacement of the heart during OPCAB is usually treated with vasopressors, such as noradrenaline and phenylephrine. However, the effects of these agents on coronary artery motion are unknown. The present study analyzed the motion of the target coronary arteries during noradrenaline or phenylephrine infusion using three-dimensional motion capture and reconstruction technology. METHODS: The left anterior descending (LAD) artery, left circumflex (LCX) artery and right coronary artery (RCA) of 12 female landrace pigs (weight 50 ± 1 kg) were stabilized using a tissue stabilizer. The motions in the regions were captured before and during noradrenaline (n = 5) and phenylephrine (n = 7) infusion. RESULTS: Noradrenaline (0.15 µg/kg/min) and phenylephrine (1.1 µg/kg/min) significantly increased the blood pressure. Noradrenaline significantly increased the motion parameters, such as the distance moved, maximum velocity, acceleration and deceleration at the LAD (4.2 vs. 7.9 mm, P = 0.025; 95.7 vs. 215.5 mm/s, P = 0.0074; 35.3 vs. 83.6 m/s(2), P = 0.0096 and -35.6 vs. -83.6 m/s(2), P = 0.005, respectively). The values during phenylephrine infusion did not change except for the distance moved at the LAD (3.8 vs. 7.7 mm, P = 0.042). The motion parameters at the LCX and RCA during noradrenaline and phenylephrine infusion did not change significantly. CONCLUSIONS: The effect of phenylephrine on the coronary artery motion was less dramatic than that of noradrenaline.

Left ventricular noncompaction complicated by mitral valve prolapse: report of a case.

A 31-year-old male was diagnosed with congestive heart failure due to left ventricular noncompaction and coarctation of the aorta by echocardiography and computed tomography. He also developed mitral valve prolapse of the posteromedial commissural leaflet due to rupture of chordae tendineae. Segmental leaflet resection was performed with ring annuloplasty. Aorto-bifemoral bypass was carried out simultaneously to attenuate the ventricular afterload. His postoperative course was uneventful.

Open-stent grafting with a GORE TAG thoracic endoprosthesis for an extended severely atheromatous thoracic aortic aneurysm: report of a case.

An 82-year-old man with asthma and chronic obstructive pulmonary disease experienced sudden back pain. Chest computed tomography (CT) showed a thoracic aortic aneurysm (TAA) 63 mm in maximum diameter, with severe atheromas, representing "shaggy aorta", extending down to the level of the ninth thoracic vertebra. Emergency surgery was necessitated by the impending rupture of the aneurysm. The patient underwent successful total arch replacement with open-stent grafting using a GORE(®) TAG(®) thoracic endoprosthesis. His postoperative course was uneventful and there were no neurological complications. We discuss the advantages and disadvantages of using the GORE TAG system for an open-stent graft.

Relationships between levels of urinary podocalyxin, number of urinary podocytes, and histologic injury in adult patients with IgA nephropathy.

BACKGROUND AND OBJECTIVES: Podocalyxin (PCX) is present on the apical cell membrane of podocytes and is shed in urine from injured podocytes. Urinary podocalyxin (u-PCX) is associated with severity of active glomerular injury in patients with glomerular diseases. This study examined the relationship between number of urinary podocytes, levels of u-PCX, and glomerular injury in adults with IgA nephropathy (IgAN). DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Urine samples voided in the morning on the day of biopsy were obtained from 51 patients with IgAN (18 men and 33 women; mean age, 31 years). All renal biopsy specimens were analyzed histologically. Pathologic variables of IgAN were analyzed per Shigematsu classification, the Oxford classification of IgAN, and the Clinical Guidelines of IgAN in Japan. Levels of u-PCX were measured by sandwich ELISA. RESULTS: Histologic analysis based on Shigematsu classification revealed a significant correlation between levels of u-PCX and severity of acute extracapillary abnormalities (r=0.72; P<0.001), but levels of urinary protein excretion did not correlate with acute glomerular abnormalities. Levels of urinary protein excretion in patients with segmental sclerosis (n=19) were higher than in patients without (n=22) (0.49 [interquartile range (IQR), 0.20-0.88] g/g creatinine versus 0.20 [IQR, 0.10-0.33] g/g creatinine; P<0.01). The number of urinary podocytes in patients with segmental sclerosis was higher than in patients without (1.05 [IQR, 0.41-1.67] per mg creatinine versus 0.28 [IQR, 0.10-0.66] per mg creatinine; P<0.01). CONCLUSIONS: Levels of u-PCX and the number of urinary podocytes are associated with histologic abnormalities in adults with IgAN.

Severe intraglomerular detachment of podocytes in a Gitelman syndrome patient.

We report the case of a 38-year-old woman diagnosed with Gitelman syndrome. A kidney biopsy showed abundant floating cells in the Bowman's space of the mildly cystic glomeruli, moderate tubulointerstitial changes and apparent intimal thickening of small arteries. These floating cells were immunohistologically identified as podocytes, by the expression of podocalyxin, vimentin, Wilms' tumor 1, synaptopodin and nephrin with positivities of 100%, 88.4%, 80.4%, 74.7% and 22.6%, respectively. In these phenotypes, nephrin expression was notably decreased in both detached and capillary-attached podocytes in comparison with normal control podocytes. Immunostaining of both detached and capillary-attached podocytes for Bax, Bcl-2, desmin, fibroblast-specific protein-1, α-smooth muscle actin and Ki-67 was negative, as were TUNEL assays. These results suggest that apoptosis and epithelial-mesenchymal transition were not the main cause of podocyte detachment in this patient. In addition, levels of urinary podocalyxin were not elevated, suggesting the detached podocytes were not excreted in the urine. To the best of our knowledge, this is the first report of severe intraglomerular non-apoptotic detachment of podocytes in Gitelman syndrome. This podocyte detachment may be associated with nephron obstruction and reduced nephrin expression.

Short-term and long-term outcomes of octogenarians after off-pump coronary artery bypass surgery.

PURPOSE: Off-pump coronary artery bypass has been reported to be associated with reduced morbidity and mortality after surgical coronary revascularization, especially in high-risk patients. The aim of this study was to clarify the efficacy of off-pump coronary artery bypass for the very elderly patients. METHODS: We compared the outcomes of octogenarians (n = 28, 82 ± 2 years) undergoing off-pump coronary artery bypass and those of the patients <80 years of age (n = 315, 67 ± 9 years) during short- and long-term periods. RESULTS: There was no difference in hospital mortality between octogenarians and the younger cohort (3.8% vs. 0.6%; P = 0.11). A high rate of postoperative complications (e.g., pneumonia, transient renal dysfunction, ventricular arrhythmia) were observed in the octogenarians. The long-term survival (81% at 5 years) and the rate of freedom from cardiac death (92% at 5 years) and from cardiac events (85% at 5 years) were excellent in the octogenarians; they appeared less favorable, however, when compared with the younger group (95%, 98%, and 94% at 5 years, respectively). Most of the cardiac adverse events, including unexplained sudden death, occurred 6 months after the surgery in octogenarians. CONCLUSION: Off-pump coronary artery bypass can be performed safely in octogenarians, with excellent early and late outcomes. Careful postoperative follow-up is required to reduce postoperative long-term adverse events. Off-pump coronary artery bypass is a feasible modality of coronary revascularization for octogenarians.