Citations

Background. The study investigates the occurrence, severity, and outcomes of acute kidney injury (AKI) in octogenarians following heart valve surgery.Methods. All patients, age>80 years, not on dialysis and without kidney transplant, undergoing heart valve replacement at Mayo Clinic, Rochester, in the years 2002-2003 were enrolled. AKI was diagnosed based on AKIN criteria.Results. 209 octogenarians (88.0% aortic valve, 6.2% mitral valve, 1.0% tricuspid valve, and 4.8% multivalve) with (58.4%) and without CABG were studied. 34 (16.3%) had preexisting CKD. After surgery, 98 (46.8%) developed AKI. 76.5% of the AKI were in Stage 1, 9.2% in Stage 2, and 14.3% in Stage 3. 76.5% CKD patients developed AKI. Length of hospital stay was longer for AKI patients. More AKI patients were discharged to care facilities. Patient survival at 30 days and 1 year for AKI versus non-AKI was 88.8 versus 98.7%,p=0.003, and 76.5 versus 88.3%,p=0.025, respectively. With follow-up of3.94±0.28years, Kaplan-Meier analysis showed a reduced survival for AKI octogenarians. Preexisting CKD and large volume intraoperative fluid administration were independent AKI predictors.Conclusions. Nearly half of the octogenarians developed AKI after valve replacement surgery. AKI was associated with significant functional impairment and reduced survival.

AbstractBackgroundThe reported risk of depression in patients with hypomagnesaemia is controversial.AimThe objective of this meta‐analysis was to assess the association between depression and hypomagnesaemia.MethodsA literature search was performed using MEDLINE, EMBASE, Cochrane Database and clinicaltrials.gov from inception through October 2014. Studies that reported odds ratios, relative risks or hazard ratios comparing the risk of depression in patients with hypomagnesaemia were included. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random‐effect, generic inverse variance method.ResultsSix observational studies (three cohort studies, two cross‐sectional studies and a case–control study) with a total of 19 137 patients were identified and included in the data analysis. The pooled RR of depression in patients with hypomagnesaemia was 1.34 (95% CI, 1.01–1.79, I2 = 33%). The association between depression and hypomagnesaemia was marginally insignificant after the sensitivity analysis including only cohort and case–control studies, with a pooled RR of 1.38 (95% CI, 0.92–2.07, I2 = 24%).ConclusionOur study demonstrates a potential association between hypomagnesaemia and depression. Further studies assessing the benefits of treatment of hypomagnesaemia in patients with depression are needed.

AbstractAimData on clinicopathological features, treatment and outcomes of IgA nephropathy (IgAN) in elderly patients are limited.MethodsNative kidney biopsies with a pathological diagnosis of IgAN (n = 1084) from Mayo Clinic Rochester in the years 1994–2013 were examined. After exclusion of the secondary IgAN, 45 elderly IgAN patients (age ≥65 years) were identified. One hundred sixty‐two younger adults (age 18–64 years) with IgAN were randomly selected for comparison.ResultsCompared with younger adults, elderly patients showed a higher rate of chronic hypertension (62.2 vs 27.2%), higher pulse pressures (65 ± 17 vs 51 ± 15 mmHg), requiring greater number of antihypertensive medications (2.5 ± 1.2 vs 1.7 ± 0.7) and lower blood haemoglobin (11.1 ± 2.3 vs 12.7 ± 2.1 g/dL) at time of kidney biopsy, all P < 0.001. Pathologically, elderly kidneys showed a higher degree of tubulointerstitial fibrosis (P = 0.04) and vascular sclerosis (P < 0.001). Treatments (including the use of angiotensin‐converting enzyme inhibitor (ACEI) inhibitor, angiotensin II receptor blocker (ARB) and immunosuppressants) were similar in the two cohorts. Elderly patients had more end‐stage renal disease at 6 months (HR 5.51; 95% CI 1.46–22.3, P = 0.01) and higher 6‐month and 5‐year mortality (HR 2.31; 95% CI 1.04–5.17, P = 0.04) after adjusting the age and comorbidities.ConclusionIgAN diagnosed at age >65 years tends to have a faster renal disease progression and higher patient mortality.

Cell transplantation is a potential treatment for the many liver disorders that are currently only curable by organ transplantation. However, one of the major limitations of hepatocyte (HC) transplantation is an inability to monitor cells longitudinally after injection. We hypothesized that the thyroidal sodium iodide symporter (NIS) gene could be used to visualize transplanted HCs in a rodent model of inherited liver disease: hereditary tyrosinemia type 1. Wild‐type C57Bl/6J mouse HCs were transduced ex vivo with a lentiviral vector containing the mouse Slc5a5 (NIS) gene controlled by the thyroxine‐binding globulin promoter. NIS‐transduced cells could robustly concentrate radiolabeled iodine in vitro, with lentiviral transduction efficiencies greater than 80% achieved in the presence of dexamethasone. Next, NIS‐transduced HCs were transplanted into congenic fumarylacetoacetate hydrolase knockout mice, and this resulted in the prevention of liver failure. NIS‐transduced HCs were readily imaged in vivo by single‐photon emission computed tomography, and this demonstrated for the first time noninvasive 3‐dimensional imaging of regenerating tissue in individual animals over time. We also tested the efficacy of primary HC spheroids engrafted in the liver. With the NIS reporter, robust spheroid engraftment and survival could be detected longitudinally after direct parenchymal injection, and this thereby demonstrated a novel strategy for HC transplantation. This work is the first to demonstrate the efficacy of NIS imaging in the field of HC transplantation. We anticipate that NIS labeling will allow noninvasive and longitudinal identification of HCs and stem cells in future studies related to liver regeneration in small and large preclinical animal models. Liver Transpl 21:442–453, 2015. © 2015 AASLD.

Encephalopathy is a rare side effect of third and fourth generation cephalosporins. Renal failure and preexisting neurological disease are notable risk factors. Recognition is important as discontinuing the offending agent usually resolves symptoms. We present a case of acute encephalopathy in a patient with end stage renal disease (ESRD) treated with peritoneal dialysis (PD) who received intravenous ceftriaxone for peritonitis. This case illustrates the potential severe neurologic effects of cephalosporins, which are recommended by international guidelines as first-line antimicrobial therapy for spontaneous bacterial peritonitis.

Endovascular coiling is the most common treatment for cerebral aneurysms. The treatment consists of deploying coils of different shapes and sizes into the aneurysm with the intent of reducing blood flow therein. While the treatment has been shown to be more effective than conventional surgical methods, it is successful in only 50–80% of cases, depending on the type of aneurysm [1]. Treatment success has been correlated with favorable post-treatment hemodynamics [2]. Understanding of the effects of coils on post-treatment hemodynamics is limited, however, due to limited in-vivo and in-vitro flow measurement techniques. Previous computational studies have also suffered from drastic assumptions about coil geometry.

Cell-based therapies for liver disease rely on a high-quality supply of hepatocytes and a means for storage during transportation from site of isolation to site of usage. Unfortunately, frozen cryopreservation is associated with unacceptable loss of hepatocyte viability after thawing. The purpose of this study was to optimize conditions for cold storage of rat hepatocyte spheroids without freezing. Rat hepatocytes were isolated by a two-step perfusion method; hepatocyte spheroids were formed during 48 h of rocked culture in serum-free medium (SFM). Spheroids were then maintained in rocked culture at 37°C (control condition) or cold stored at 4°C for 24 or 48 h in six different cold storage solutions: SFM alone; SFM + 1 mM deferoxamine (Def); SFM + 1 μM cyclosporin A (CsA); SFM + 1 mM Def + 1 μM CsA, University of Wisconsin (UW) solution alone, UW + 1 mM Def. Performance metrics after cold storage included viability, gene expression, albumin production, and functional activity of cytochrome P450 enzymes and urea cycle proteins. We observed that cold-induced injury was reduced significantly by the addition of the iron chelator (Def) to both SFM and UW solution. Performance metrics (ammonia detoxification, albumin production) of rat hepatocyte spheroids stored in SFM + Def for 24 h were significantly increased from SFM alone and approached those in control conditions, while performance metrics after cold storage in SFM alone or cold storage for 48 h were both significantly reduced. A serum-free medium supplemented with Def allowed hepatocyte spheroids to tolerate 24 h of cold storage with less than 10% loss in viability and functionality. Further research is warranted to optimize a solution for extended cold storage of hepatocyte spheroids.

Abstract Purpose: Glioblastoma multiforme (GBM) is a devastating disease. Recent studies suggest that the stem cell properties of GBM contribute to the development of therapy resistance. Experimental Design: The expression of Survivin and Ran was evaluated by immunohistochemistry with GBM tissues, and quantitative reverse transcriptase (qRT)-PCR and immunocytochemistry with patient-derived GBM sphere cultures. With a computational structure-based drug design, 11 small-molecule compounds were designed, synthesized, and evaluated as inhibitor candidates for the molecular interaction of Survivin protein. The molecular mechanism of the lead compound, LLP-3, was determined by Western blot, ELISA, in situ proximity ligation assay, and immunocytochemistry. The effects of LLP-3 treatment on GSCs were evaluated both in vitro and in vivo. Quantitative immunohistochemistry was carried out to compare Survivin expression in tissues from 44 newly diagnosed and 31 recurrent post-chemoradiation GBM patients. Lastly, the sensitivities of temozolomide-resistant GBM spheres to LLP-3 were evaluated in vitro. Results: Survivin and Ran were strongly expressed in GBM tissues, particularly in the perivasculature, and also in patient-derived GSC cultures. LLP-3 treatment disrupted the Survivin–Ran protein complex in cancer cells and abolished the growth of patient-derived GBM spheres in vitro and in vivo. This inhibition was dependent on caspase activity and associated with p53 status of cells. Immunohistochemistry showed that Survivin expression is significantly increased in recurrent GBM compared with newly diagnosed tumors, and temozolomide-resistant GBM spheres exhibited high sensitivities to LLP-3 treatment. Conclusions: Disruption of the Survivin–Ran complex by LLP-3 abolishes survival and growth of GSCs both in vitro and in vivo, indicating an attractive novel therapeutic approach for GBM. Clin Cancer Res; 19(3); 631–42. ©2012 AACR.