Combined cardiomegaly and aortic arch calcification predict mortality in hemodialysis patients.

INTRODUCTION: This study aimed to investigate the relationship between cardiomegaly and aortic arch calcification (AAC) and overall/cardiovascular mortality in hemodialysis patients. METHODS: We conducted a retrospective cohort study and enrolled patients who underwent initial hemodialysis. Cardiomegaly and AAC were determined by chest radiography and classified into four groups according to cross-classification of cardiothoracic ratio (CTR) of 0.5 and lower/higher grade AAC (LGAAC/HGAAC). The relationship between these groups and mortality was then analyzed by Cox proportional hazards model. RESULTS: In multivariate Cox regression analysis, those in CTR ≤ 0.5 and HGAAC [hazard ratio (95% confidence interval): 2.07 (1.14-3.77)], CTR > 0.5 & LGAAC [3.60 (2.07-6.25)] and CTR > 0.5 & HGAAC [3.42 (2.03-5.77)] were significantly associated with overall mortality; while those in CTR > 0.5 & LGAAC [2.81 (1.28-6.19)] and CTR > 0.5 & HGAAC [2.32 (1.09-4.95)] were significantly related to cardiovascular mortality. CONCLUSION: Combined cardiomegaly and AAC predicted overall and cardiovascular mortality in hemodialysis patients.

Association of early failure of arteriovenous fistula with mortality in hemodialysis patients.

Arteriovenous fistula (AVF) is prone to early dysfunction and relates to poor outcome. However, little is known about the role of early AVF dysfunction as an independent risk factor for death in hemodialysis patients. A retrospective cohort study was performed using data of patients who underwent initial AVF surgery at a single institution. Demographic, clinical, biochemistry and AVF parameters were extracted from the electronic records, and the association between these variables and mortality was analyzed by Cox proportional hazards model. A total of 501 patients on hemodialysis (63.4 ± 12.7 years, 57.3% male) were included, and the median observation period was 3.66 years. In multivariate analysis, early failure of AVF (hazard ratio (95% confidence interval): 1.54 (1.06-2.24); p = 0.023) was associated with overall mortality but not cardiovascular mortality. Other identified predictors of overall mortality included older age, peripheral artery disease (PAD), cardiomegaly, higher white blood cell (WBC) count and corrected calcium level, and lower total cholesterol level, while predictors of cardiovascular mortality included older age, coronary artery disease (CAD), PAD and lower hemoglobin level. In conclusion, patients with early AVF failure were associated with increased risk of overall mortality.

Factors affecting patency of arteriovenous fistula following first percutaneous transluminal angioplasty.

BACKGROUND: Percutaneous transluminal angioplasty (PTA) has generally replaced surgical procedures to treat arteriovenous fistula (AVF) dysfunction, but the predictors of post-intervention patency are highly variable. This study aimed to determine predictors of primary patency following PTA of dysfunctional AVF. MATERIALS AND METHODS: Retrospective analysis of first-time PTA of 307 AVF in 307 patients (171 males, mean age 64.3 ± 12.4 years). Demographic, clinical, anatomical and medication variables were reviewed and subjected to univariate and multivariate Cox regression analysis. RESULTS: The post-intervention primary patency rates at 6, 12, 24, and 36 months were 76.3%, 58.3%, 43.2%, and 38.2%, respectively. The higher aortic arch calcification (AAC) grade patients were older, had higher incidence of comorbidities and cardiomegaly, and younger AVF age, but their dialysis vintage term was shorter and diastolic blood pressure was lower, and the maximum diameter of balloon angioplasty was mostly ≤ 6 mm, and had lower phosphorus level and less calcium-containing phosphate binder use. In multivariate Cox proportional hazard analysis, the presence of higher AAC grade [hazard ratio (95% confidence interval): (1.46 (1.02-2.09); p = 0.037)] and stenosis at upper arm [1.76 (1.16-2.67); p = 0.008] were associated with shorter post-intervention primary patency. CONCLUSION: In conclusion, higher AAC grade and anatomic factor related to the location of AVF (upper arm) were the important predictors of AVF dysfunction after PTA. These results could assist in tailoring surveillance programs and performing appropriate interventions for risky AVF.

Sulbactam-enhanced cytotoxicity of doxorubicin in breast cancer cells.

BACKGROUND: Multidrug resistance (MDR) is a major obstacle in breast cancer treatment. The predominant mechanism underlying MDR is an increase in the activity of adenosine triphosphate (ATP)-dependent drug efflux transporters. Sulbactam, a ß-lactamase inhibitor, is generally combined with ß-lactam antibiotics for treating bacterial infections. However, sulbactam alone can be used to treat Acinetobacter baumannii infections because it inhibits the expression of ATP-binding cassette (ABC) transporter proteins. This is the first study to report the effects of sulbactam on mammalian cells. METHODS: We used the breast cancer cell lines as a model system to determine whether sulbactam affects cancer cells. The cell viabilities in the present of doxorubicin with or without sulbactam were measured by MTT assay. Protein identities and the changes in protein expression levels in the cells after sulbactam and doxorubicin treatment were determined using LC-MS/MS. Real-time reverse transcription polymerase chain reaction (real-time RT-PCR) was used to analyze the change in mRNA expression levels of ABC transporters after treatment of doxorubicin with or without sulbactam. The efflux of doxorubicin was measures by the doxorubicin efflux assay. RESULTS: MTT assay revealed that sulbactam enhanced the cytotoxicity of doxorubicin in breast cancer cells. The results of proteomics showed that ABC transporter proteins and proteins associated with the process of transcription and initiation of translation were reduced. The mRNA expression levels of ABC transporters were also decreased when treated with doxorubicin and sulbactam. The doxorubicin efflux assay showed that sulbactam treatment inhibited doxorubicin efflux. CONCLUSIONS: The combination of sulbactam and doxorubicin enhances the cytotoxicity of doxorubicin in the breast cancer cells by inhibiting the expression of ABC transporter proteins and proteins associated with the process of transcription and initiation of translation, and blocking the efflux of doxorubicin. Co-treatment of doxorubicin and sulbactam can be used in breast cancer treatment to decrease the prescribed dose of doxorubicin to avoid the adverse effects of doxorubicin.

Aortic Arch Calcification as a Predictor of Repeated Arteriovenous Fistula Failure within 1-Year in Hemodialysis Patients.

OBJECTIVES: The aim of the study was to identify the factors associated with repeated arteriovenous fistula (AVF) failure within 1-year, especially the impact of aortic arch calcification (AAC) on patency of AVF. MATERIALS AND METHODS: We retrospectively assessed chest radiography in hemodialysis patients who had undergone initial AVF. The extent of AAC was categorized into four grades (0-3). The association between AAC grade, other clinical variables, and repeated failure of AVF was then analyzed by binary logistic regression analysis. RESULTS: This study included 284 patients (158 males, mean age 61.7 ± 13.1 years). Patients with higher AAC grade were older, had more frequently diabetes mellitus and cardiovascular disease, had lower diastolic blood pressure, and had higher corrected calcium and lower intact parathyroid hormone levels. In multivariate analysis, the presence of higher AAC grade (odds ratio (95% confidence interval): 2.98 (1.43-6.23); p = 0.004), lower mean corrected calcium (p = 0.017), and mean serum albumin level (p = 0.008) were associated with repeated failure of AVF. CONCLUSIONS: The presence of higher AAC grade, lower mean corrected calcium and mean serum albumin level were independently associated with repeated AVF failure within 1 year in hemodialysis patients.

Label-free, ultrahigh-speed, 3D observation of bidirectional and correlated intracellular cargo transport by coherent brightfield microscopy.

The investigation of intracellular transport at the molecular scale requires measurements at high spatial and temporal resolutions. We demonstrate the label-free, direct imaging and tracking of native cell vesicles in live cells at an ultrahigh spatiotemporal resolution. Using coherent brightfield (COBRI) microscopy, we monitor individual cell vesicles traveling inside the cell with nanometer spatial precision in 3D at 30 000 frames per second. The stepwise directional motion of the vesicle on the cytoskeletal track is clearly resolved. We also observe the repeated switching of the transport direction of the vesicle in a continuous trajectory. Our high-resolution measurement unveils the transient pausing and subtle bidirectional motion of the vesicle, taking place over tens of nanometers in tens of milliseconds. By tracking multiple particles simultaneously, we found strong correlations between the motions of two neighboring vesicles. Our label-free ultrahigh-speed optical imaging provides the opportunity to visualize intracellular cargo transport at the nanoscale in the microsecond timescale with minimal perturbation.

Coherent Brightfield Microscopy Provides the Spatiotemporal Resolution To Study Early Stage Viral Infection in Live Cells.

Viral infection starts with a virus particle landing on a cell surface followed by penetration of the plasma membrane. Due to the difficulty of measuring the rapid motion of small-sized virus particles on the membrane, little is known about how a virus particle reaches an endocytic site after landing at a random location. Here, we use coherent brightfield (COBRI) microscopy to investigate early stage viral infection with ultrahigh spatiotemporal resolution. By detecting intrinsic scattered light via imaging-based interferometry, COBRI microscopy allows us to track the motion of a single vaccinia virus particle with nanometer spatial precision (<3 nm) in 3D and microsecond temporal resolution (up to 100,000 frames per second). We explore the possibility of differentiating the virus signal from cell background based on their distinct spatial and temporal behaviors via digital image processing. Through image postprocessing, relatively stationary background scattering of cellular structures is effectively removed, generating a background-free image of the diffusive virus particle for precise localization. Using our method, we unveil single virus particles exploring cell plasma membranes after attachment. We found that immediately after attaching to the membrane (within a second), the virus particle is locally confined within hundreds of nanometers where the virus particle diffuses laterally with a very high diffusion coefficient (∼1 µm2/s) at microsecond time scales. Ultrahigh-speed scattering-based optical imaging may provide opportunities for resolving rapid virus-receptor interactions with nanometer clarity.

Aortic Arch Calcification Predicts Patency Loss of Arteriovenous Fistula in End-Stage Renal Disease Patients.

Aortic arch calcification (AAC) is recognized as an important cardiovascular risk factor in patients with end-stage renal disease (ESRD). The aim of the study was to evaluate the impact of AAC grade on patency rates of arteriovenous fistula (AVF) in this specific population. The data of 286 ESRD patients who had an initial AVF placed were reviewed. The extent of AAC identified on chest radiography was divided into four grades (0-3). The association between AAC grade, other clinical factors, and primary patency of AVF was then analyzed by Cox proportional hazard analysis. The multivariate analysis demonstrated that the presence of AAC grade 2 (hazard ratio (95% confidence interval): 1.80 (1.15-2.84); p = 0.011) and grade 3 (3.03 (1.88-4.91); p < 0.001), and higher level of intact-parathyroid hormone (p = 0.047) were associated with primary patency loss of AVF. In subgroup analysis, which included AVF created by a surgeon assisted with preoperative vascular mapping, only AAC grade 3 (2.41 (1.45-4.00); p = 0.001), and higher intact-parathyroid hormone (p = 0.025) level were correlated with AVF patency loss. In conclusion, higher AAC grade and intact-parathyroid hormone level predicted primary patency loss of AVF in an ESRD population.

Risk Factors for Early Failure of Arteriovenous Vascular Access Among Patients With Type 2 Diabetes Mellitus.

The aim of the study was to identify the potential risk factors for early arteriovenous access failure in a diabetic population. The data of 223 end-stage renal disease (ESRD) patients with type 2 diabetes who had an arteriovenous fistula (AVF) or arteriovenous graft (AVG) placed as their initial vascular accesses were retrospectively reviewed. The association between clinical factors and risk for early failure was then analyzed. In multivariate analysis, the predictors associated with early failure were female gender (odds ratio (95% confidence interval): 2.52 (1.32-4.81); P = 0.005), AVF with prior peritoneal dialysis (3.26 (1.05-10.11); P = 0.039), and lower hemoglobin level (P = 0.015). The results of significant predictors in the AVF group remained similar to the entire study population. In conclusion, there was an association of female gender, AVF with prior peritoneal dialysis and lower hemoglobin level with early arteriovenous access failure in a diabetic ESRD population.

Preoperative and Intraoperative Factors for Early Failure of Native Arteriovenous Fistulas.

The aim of the study was to assess the potential predictive factors for early arteriovenous fistula (AVF) failure following the fistula first initiative. We retrospectively reviewed the data of 159 end-stage renal disease (ESRD) patients who underwent AVF creation. The preoperative factors such as demographic, comorbidity condition, laboratory parameters and medication, and intraoperative or surgical-related factors were assessed. In multivariate logistic regression analysis, significant predictive factors of early AVF failure were female gender (odds ratio (95% confidence interval): 2.63 (1.19-5.81); P = 0.017), higher body mass index (P = 0.038), and lower hemoglobin level (P = 0.048), while adjusting for preoperative factors or all factors. For adjusting of intraoperative factors, reduced venous diameter (P = 0.056) tended to be associated with early AVF failure. In conclusion, female gender, higher body mass index and lower hemoglobin level predicted the occurrence of early AVF failure in ESRD patients.

Studying antibiotic-membrane interactions via X-ray diffraction and fluorescence microscopy.

Antibiotic drug resistance is a serious issue for the treatment of bacterial infection. Understanding the resistance to antibiotics is a key issue for developing new drugs. We used penicillin and sulbactam as model antibiotics to study their interaction with model membranes. Cholesterol was used to target the membrane for comparison with the well-known insertion model. Lamellar X-ray diffraction (LXD) was used to determine membrane thickness using successive drug-to-lipid molar ratios. The aspiration method for a single giant unilamellar vesicle (GUV) was used to monitor the kinetic binding process of antibiotic-membrane interactions in an aqueous solution. Both penicillin and sulbactam are found positioned outside the model membrane, while cholesterol inserts perpendicularly into the hydrophobic region of the membrane in aqueous solution. This result provides structural insights for understanding the antibiotic-membrane interaction and the mechanism of antibiotics.

Bactericidal effect of sulbactam against Acinetobacter baumannii ATCC 19606 studied by 2D-DIGE and mass spectrometry.

Acinetobacter baumannii has been associated with several severe hospital-acquired infections such as ventilator-associated pneumonia and meningitis. Sulbactam, a ß-lactamase inhibitor, is usually combined with ß-lactam antibiotics to treat infections. It has been found that sulbactam alone may be used to treat infections caused by A. baumannii, although the mechanism of the bactericidal effect remains unknown. In this study, proteomics was used to analyse protein intensity changes and to identify the proteins of A. baumannii following sulbactam treatment. In total, 54 proteins were found to exhibit significant changes in intensity. Proteins with reduced intensity included ATP-binding cassette (ABC) transporters as well as 30S and 50S ribosomal subunit proteins. These proteins are essential for nutrient import and protein synthesis and are vital for bacterial survival. The amplified proteins included glutamine synthetase, malic enzyme, RNA polymerase subunit α, and the molecular chaperones DnaK and GroEL, which function in metabolism, DNA and protein synthesis, and repair machinery. These amplified proteins were increased to rescue bacteria, however they could not overcome the effects of the reduced proteins and the bacteria were killed. This is the first report that the reduction of ABC transporters and 30S and 50S ribosomal subunit proteins plays an important role in the bactericidal effect of sulbactam against A. baumannii.

Factors related to nephrotic-range proteinuria in late-stage chronic kidney disease patients with diabetes mellitus.

PURPOSE: Diabetic nephropathy and proteinuria are important risk factors for both end-stage renal disease and cardiovascular events. The present study aimed to identify the factors associated with nephrotic-range proteinuria in patients with advanced diabetic nephropathy. METHODS: This cross-sectional study enrolled 386 diabetic patients with chronic kidney disease (CKD) stages 3-5, from our outpatient Department of Nephrology. Urinary protein-to-creatinine ratio was recorded. Additionally, other laboratory parameters, body mass index, blood pressure, comorbidities, and medications were also reviewed. RESULTS: The mean age of the patients was 65.1 ± 11.6 years. Among patients with CKD stage 3 and 4, the odds ratio (OR) for nephrotic-range proteinuria in relation with systolic blood pressure significantly increased starting from 121 mmHg (OR 7.04 and 11.79 for systolic blood pressure of 121-140 and ≥141 mmHg, respectively, in comparison with systolic blood pressure below 121 mmHg). In addition, serum phosphorus ≥4.7 mg/dl was associated with significantly higher risk (OR 15.45) for severe proteinuria, compared with a phosphorus level ≤2.6 mg/dl. Finally, hypertriglyceridemia ≥241 mg/dl was also associated with higher OR for severe proteinuria, compared with a triglyceride level ≤200 mg/dl. Similar associations were found in patients with CKD stage 5. CONCLUSIONS: Higher systolic blood pressure, serum phosphorus, and triglyceride levels are associated with nephrotic-range proteinuria in patients with diabetic nephropathy and CKD stage 3-5. Further studies should clarify whether a reduction in serum phosphorus would lead to a decrease in proteinuria in these patients.

Hyperphosphatemia is associated with overt proteinuria in non-diabetic patients with late-stage chronic kidney disease: a cross-sectional study.

PURPOSE: Proteinuria plays an important role in the progression of chronic kidney disease (CKD), as well as a powerful predictor of cardiovascular morbidity and mortality. The aim of our study was to investigate the potential determinants associated with overt proteinuria in non-diabetic patients with late-stage CKD. METHODS: Between January 2006 and September 2011, a total of 418 non-diabetic patients with CKD stage 3-5 were enrolled from the outpatient department of nephrology. Urinary protein-to-creatinine ratio and serum phosphorus were determined. Other laboratory parameters, associated comorbidities, medication use, body mass index, and blood pressure were also assessed. RESULTS: The mean age of the patients was 66.7 ± 14.0 years. In multiple logistic regression analysis and adjusting for established risk factors, the odds ratios for overt proteinuria were 3.96 (95 % confidence interval, 1.80-8.76; p = 0.001) for higher serum phosphorus level (≥4.3 mg/dl) and 3.56 (95 % confidence interval, 1.47-8.63; p = 0.005) for hypercholesterolemia (≥217 mg/dl), compared to subjects with serum phosphorus <3.3 mg/dl and cholesterol level 158-184 mg/dl. The similar significant findings remained robust in individuals not receiving phosphate binder. CONCLUSIONS: Hyperphosphatemia and high serum cholesterol are associated with overt proteinuria in non-diabetic patients with late-stage CKD. Further studies should clarify whether this relation is causal and whether serum phosphorus level should be a new therapeutic target for proteinuria reduction.

The usefulness of fast-spin-echo T2-weighted MR imaging in Nutcracker syndrome: a case report.

Nutcracker syndrome occurs when the left renal vein (LRV) is compressed between the superior mesenteric artery and the aorta, and this syndrome is often characterized by venous hypertension and related pathologies. However, invasive studies such as phlebography and measuring the reno-caval pressure gradient should be performed to identify venous hypertension. Here we present a case of Nutcracker syndrome where the LRV and intra-renal varicosities appeared homogeneously hyperintense on magnetic resonance (MR) fast-spin-echo T2-weighted imaging, which suggested markedly stagnant intravenous blood flow and the presence of venous hypertension. The patient was diagnosed and treated without obtaining the reno-caval pressure gradient. The discomfort of the patient lessened after treatment. Furthermore, on follow-up evaluation, the LRV displayed a signal void, and this was suggestive of a restoration of the normal LRV flow and a decrease in LRV pressure.

Renal cell carcinoma complicated by emphysematous pyelonephritis in a non-diabetic patient with renal failure.

A 72-year-old non-diabetic uremic woman underwent right nephrectomy for urolithiasis at the age of 50. Because pyuria, fever, chilliness and left flank pain developed during preparing for arteriovenous fistula, she was admitted to National Cheng Kung University Hospital. Renal cell carcinoma (RCC) complicated with emphysematous pyelonephritis (EPN) was diagnosed and immediately treated with antibiotics and CT-guided percutaneous catheter drainage. Cultures of pus and blood yielded Escherichia coli. She received left radical nephrectomy later for the control of persistent sepsis and removal of left renal tumor. The pathology of the tumor was composed of a glandular arrangement of granular cells with the occasional atypism, and renal parenchyma had been totally replaced by RCC. The non-tumor part of the kidney showed chronic pyelonephritis. Five months later, multiple metastases developed. We reported this first uremic case with EPN and RCC, but without diabetes mellitus and urinary tract obstruction. The gas formation may be due to large RCC, which caused impaired tissue perfusion and E. coli infection.