Quality of Life and Outcomes in African Americans with CKD

Low health-related quality of life (HRQOL) has been associated with increased risk for hospitalization and death in ESRD. However, the relationship of HRQOL with outcomes in predialysis CKD is not well understood. We evaluated the association between HRQOL and renal and cardiovascular (CV) outcomes in 1091 African Americans with hypertensive CKD enrolled in the African American Study of Kidney Disease and Hypertension (AASK) trial and cohort studies. Outcomes included CKD progression (doubling of serum creatinine/ESRD), CV events/CV death, and a composite of CKD progression or death from any cause (CKD progression/death). We assessed HRQOL, including mental health composite (MHC) and physical health composite (PHC), using the Short Form-36 survey. Cox regression analyses were used to assess the relationship between outcomes and five-point decrements in MHC and PHC scores using measurements at baseline, at the most recent annual visit (time-varying), or averaged from baseline to the most recent visit (cumulative). During approximately 10 years of follow-up, lower mean PHC score was associated with increased risk of CV events/CV death and CKD progression/death across all analytic approaches, but only time-varying and cumulative decrements were associated with CKD progression. Similarly, lower mean MHC score was associated with increased risk of CV events/CV death regardless of analytic approach, while only time-varying and cumulative decrements in mean MHC score was associated with CKD progression and CKD progression or death. In conclusion, lower HRQOL is associated with a range of adverse outcomes in African Americans with hypertensive CKD.     

Diagnostic criteria for testing for BRCA1 and BRCA2: the experience of the Department of Defense Familial Breast/Ovarian Cancer Research Project

The Department of Defense Familial Breast/Ovarian Cancer Research Project has offered genetic counseling and testing for BRCA1 and BRCA2 on a research basis to patients meeting specific diagnostic criteria, with risk for BRCA1 and BRCA2 mutations calculated based on the Couch model. In 2.5 years, 250 patients were evaluated and 101 patients met criteria requirements, including 33 who met criteria in more than one category. Ninety patients elected to undergo DNA testing. In this group of 90 patients, 14 mutations (15.5%) and 16 unclassified variants (17.7%) were identified. The most common inclusion criteria were onset of breast/ovarian cancer before age 45 years (n = 32) and onset of breast/ovarian cancer before age 45 years with strong family history (n = 21). However, when number of mutations and unclassified variants found were compared separately across all diagnostic criteria (including those of more than one capacity) using the chi 2 statistic, no significant differences were seen among the categories to suggest that one criterion was more predictive of mutations or variants than another. Couch risk values for patients with mutations showed a mean of 14% and ranged from 3.2 to 43.5% (range for all patients, 1.2-69.7%). These findings emphasize the importance of using multiple diagnostic criteria and suggest that a Couch risk value of > 3% may be useful in selecting patients for testing. The data also underscore the necessity of genetic counseling in the testing process, particularly given the large number of unclassified variants diagnosed and their uncertain status for disease predisposition.     

Clinical experience of mycophenolate mofetil in the treatment of chronic allograft nephropathy in kidney transplantation: three-year follow-up

BACKGROUND: Mycophenolate mofetil (MMF) in conjunction with calcineura antagonists has been shown to prevent acute rejection in renal allograft recipients. Its role in treatment of chronic rejection or allograft nephropathy is still controversial. We initiated the study to investigate the effect of adding MMF to a cyclosporine plus prednisolone regimen in renal recipients with chronic allograft nephropathy. MATERIALS AND METHODS: We retrospectively studied 36 patients with chronic allograft nephropathy, defined clinically as increased of serum creatinine, proteinuria, and hypertension. Renal function, cyclosporine level, renal biopsy, and renal scan were regularly done as indicated. MMF was added to 20 recipients after initial treatment with cyclosporine and prednisolone. The other 16 recipients were managed without adding MMF. Serum creatinine was monitored for 3 years. RESULTS: The demographic characteristics of the patients in the two groups were comparable. The average dose of prednisolone was unchanged throughout the study and the trough level of cyclosporine was maintained in the range of 100 to 150 ng/mL. The serum creatinine decreased initially in the group on MMF, but renal function deteriorated progressively after 6 months. There was a difference in serum creatinine between the two groups but this did not reach statistical significance. CONCLUSION: MMF therapy tender to improve renal function initially but did not attenuate significantly the impairment in chronic allograft nephropathy.     

Early postoperative echocardiographic studies of atrial septal defects

Fifteen consecutive adult patients with uncomplicated atrial septal defects (ASD) underwent echocardiographic examinations both before and 3-8 days (mean 7 days) after surgery to study the early postoperative changes in cardiac dimensions and interventricular septal motion. Echocardiographic analyses included patterns of interventricular septal motion, right and left ventricular dimensions at end-diastole (RVDd & LVDd), aortic root dimension at end-diastole (ARDd) and left atrial dimension at end-systole (LADs). The results showed that the septal motion was abnormal in 87% (13/15) before and 40% (6/15) after operation. RVDd decreased from 36 +/- 7 mm to 27 +/- 7 mm (p less than 0.01) while LVDd increased from 33 +/- 6 mm to 39 +/- 4 mm (p less than 0.01). There were no significant changes in LADs and ARDd after surgery. These observations suggest that in patients with ASD the ventricular dimensions and patterns of interventricular septal motion are changed significantly shortly after surgical repair.     

N-acetylcysteine attenuates ventilator-induced lung injury in an isolated and perfused rat lung model

N-acetylcysteine (NAC) suppresses the generation of reactive oxygen species (ROS) that are implicated in ventilator-induced lung injury (VILI). We thus hypothesised that NAC attenuates VILI. VILI was induced by mechanical ventilation with a tidal volume (Vt) of 15mlkg(-1) in isolated and perfused rat lung. NAC was administered in the perfusate prior to the onset of mechanical ventilation. A group ventilated with low Vt of 5mlkg(-1) served as control. Haemodynamics, lung injury indices, inflammatory responses and activation of apoptotic pathways were determined upon completion of the mechanical ventilation. There was an increase in lung permeability and lung weight gain after mechanical ventilation with high Vt, compared to low Vt. The levels of inflammatory cytokines including interleukin-1β (IL-1β), tumour necrosis factor-α (TNF-α) and macrophage inflammatory protein-2 (MIP-2) increased in lung lavage fluids; the concentrations of H(2)O(2) were higher in lung lavage fluids, and the expression of myeloperoxidase (MPO), JNK, P38, pAKT and caspase-3 in lung tissue was greater in the high Vt than in the low Vt group. The concentrations of glutathione (GSH) in lung tissue were higher in low Vt than those in high Vt. The administration of NAC increased GSH, attenuated ROS, cytokines, MPO, JNK, pAKT and caspase-3 and lung permeability associated with decreased activation of nuclear factor-κB. VILI is associated with inflammatory responses including the generation of ROS, cytokines and the activation of mitogen-activated protein kinase cascade. The administration of NAC attenuates the inflammatory responses, apoptosis and VILI in the isolated, perfused rat lung model.     

Scale‐up of MSC under hypoxic conditions for allogeneic transplantation and enhancing bony regeneration in a rabbit calvarial defect model

To realize the therapeutic potential of mesenchymal stem cells (MSCs), we aimed to develop a method for isolating and expanding New Zealand rabbit MSCs in a great scale. Rabbit MSCs expanded under hypoxic and normoxic conditions were compared in terms of replication capacity, differentiation potential, and the capacity for allogeneic transplantation in a calvarial defect model. The cells from all tested rabbits were expanded more rapidly when plated at low‐density under hypoxic conditions compared to under normoxic conditions. Moreover, cells expanded under hypoxic conditions increased in the potential of osteoblastic, adipocytic, and chondrocytic differentiation. More importantly, radiographic analysis and micro‐CT measurement of bone volume revealed the hypoxic cells when transplanted in the calvarial defects of another rabbit increased in the ability to repair bone defect compared to the normoxic cells. Six weeks after allogeneic transplantation of hypoxic MSCs, histological analysis revealed a callus spanned the length of the defect, and several bone tissues spotted in the implant. At 12 weeks, new bone had formed throughout the implant. Using BrdU labeling to track the transplanted cells, the hypoxic cells were more detected in the newly formed bone compared to the normoxic cells. For defects treated with allogeneic MSCs, no adverse host response could be detected at any time‐point. In conclusion, we have developed a robust method for isolation and expansion of rabbit MSCs by combining low‐density with hypoxic culture, which can be applied for the design of clinical trials in allogeneic transplantation of MSCs for bone healing. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1213–1220, 2012     

Association of metabolic syndrome, atherosclerosis risk factors, sex hormones in ED in aboriginal Taiwanese

The overall prevalence of metabolic syndrome (MS) in aboriginal male Taiwanese is very high. Many studies have found that those with cardiovascular disease and MS have a significantly higher risk of ED. In this study, we attempted to find the correlation among MS risk factor, atherosclerosis risk factors and low serum testosterone in relation to the development of ED. This was a cross-sectional study of 238 cases, and collected data included demographic data, lifestyle questionnaires, sexual desire scale, sexual satisfaction scale and International Index of Erectile Function (IIEF) questionnaire. Among our 238 subjects, 146 had MS (61.3%) and 114 subjects with MS had ED (85.7%). Using age-adjusted multivariate logistic regressive analysis, this study showed that aboriginal males with ED had a significantly higher prevalence of MS (OR=12.02, 95% confidence intervals (CI): 6.33-22.83, P<0.001). Among the MS components, abnormal fasting blood sugar was the most significantly independent factor for ED in aboriginal males (OR=8.94, 95% CI: 4.71-16.97, P<0.001). The presence of MS had a significant correlation with lower IIEF-5 scores, lower sexual desire scores, lower testosterone serum level (P<0.01) and abnormal interleukin-6 (IL-6) and high sensitivity C-reactive protein (HsCRP). The results of this study support the idea that MS, low serum testosterone and HsCRP may predict ED in aboriginal Taiwanese males. Further studies with population-based and longitudinal design should be conducted to confirm this finding and design to compare rates of ED in aboriginal men with MS.     

Robot-Assisted Transaxillary Thyroid Surgery in the United States: Is it Comparable to Open Thyroid Lobectomy?

Background  

The purpose of this study was to compare the outcome of robot-assisted transaxillary thyroid surgery (RATS) to the standard open technique for thyroid lobectomy in the U.S. population.     

Improvement of Nonalcoholic Fatty Liver Disease After Bariatric Surgery in Morbidly Obese Chinese Patients

Background

Obesity is a risk factor for nonalcoholic fatty liver disease (NAFLD), which appears to improve after weight loss induced by bariatric surgery in Western countries. The present study aims to determine the alterations of clinical measurements and liver histology of NAFLD after bariatric surgery in morbidly obese Chinese patients.

Methods

Between November 2006 and December 2007, 21 morbidly obese patients receiving intra-operative liver biopsy and follow-up liver biopsy 1?year after laparoscopic Roux-en-Y gastric bypass were enrolled. NAFLD activity score (NAS) and fibrosis stage were histologically evaluated.

Results

The mean body mass index fell from 43.8?±?7.5 to 28.3?±?4.6?kg/m² (P?P?P?<?0.01), but not aspartate aminotransferase (P?=?0.66). Histological improvement was noted in NAS (P?P?P?P?=?0.02). Pre-operatively, 4 (19.0%), 11 (52.4%), and 6 (28.6%) patients were found to have NAS ?R5, 3 or 4, and ?Q2, respectively. All patients had NAS ?Q2 after surgery. Fibrosis stage also showed significant improvement (P?Conclusions Bariatric surgery can achieve a dramatic improvement of NAFLD both biochemically and histologically in morbidly obese Chinese patients.     

Genetic testing for hereditary nonpolyposis colorectal cancer

Approximately 80 per cent of patients with colorectal cancer have sporadic disease whereas the remaining 20 per cent seem to have a genetic component. Hereditary nonpolyposis colorectal cancer (HNPCC) is the most common autosomal dominant hereditary syndrome predisposing to colorectal cancer. Various methods have been described to screen for HNPCC and to directly test for mismatch repair gene mutations. This study evaluates the initial results of 1) microsatellite instability (MSI) and immunohistochemistry (IHC) staining of tumors and 2) genetic sequencing for mismatch repair gene mutations in patients suspected to have HNPCC. Appropriate patients for HNPCC testing were identified through a high-risk colorectal cancer clinic. Of those patients screened only those who met Amsterdam criteria (AC) for HNPCC or were young age onset (YAO) (<40 years of age) were eligible for testing. The tumors underwent testing for MSI and had IHC performed in those patients with available tumor specimens. MSI was performed on the five markers approved by the NIH consensus conference. MSI-High (MSI-H) was defined as two or more markers being unstable. IHC was done with commercially available stains for MLH1 and MSH2. All patients had sequencing of the MLH1 and MSH2 genes performed to search for mutations by a commercial laboratory. Genetic counseling was provided and written informed consent was obtained. Fourteen patients were part of kindreds that met the AC. An additional 10 patients were <40 years of age at diagnosis of colorectal cancer but lacked any family history. Testing for MSI and IHC was performed on those available tissue blocks. Of the AC patients five had MSH2 mutations and two had MLH1 variants. Of the five with MSH2 mutations three of four had MSI-H tumors and all four had loss of expression of MSH2 on IHC. Of the MLH1 variants only one had MSI-H tumor and lacked expression of MLH-1 on IHC. Of those patients with no mutation identified three of six had MSI-H tumors. For those patients YAO no genetic mutations were identified. Two of the seven had MSI-H tumors. Genetic testing for HNPCC even in those patients fulfilling the rigid AC yielded mutations in only five of 14 patients with variants of unknown significance being found in an additional two patients. Only one MSH2 variant of unknown significance was identified in the 10 YAO patients, which would suggest that screening in this group of patients with MSI and/or IHC would be appropriate.