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.     

Micropapillary bladder cancer: Current treatment patterns and review of the literature

ObjectivesNo guidelines exist for the management of micropapillary bladder cancer (MPBC) and most reports of this variant of urothelial carcinoma are case series comprising small numbers of patients. We sought to determine current practice patterns for MPBC using a survey sent to the Society of Urologic Oncology (SUO) and to present those results in the setting of a comprehensive review of the existing literature.Materials and methodsA survey developed by the Translational Science Working Group of the Bladder Cancer Advocacy Network–sponsored Think Tank meeting was distributed to members of the SUO. The results from 118 respondents were analyzed and presented with a literature review.ResultsMost survey respondents were urologists, with 80% considering bladder cancer their primary area of interest. Although 78% of the respondents reported a dedicated genitourinary pathologist at their institution, there were discrepant opinions on how a pathologic diagnosis of MPBC is determined as well as variability on the proportion of MPBC that is clinically significant. Among them, 78% treat MPBC differently than conventional urothelial carcinoma, with 81% reporting that they would treat cT1 MPBC with upfront radical cystectomy. However, the respondents had split opinions regarding the sensitivity of MPBC to cisplatin-based chemotherapy, which affected utilization of neoadjuvant chemotherapy in muscle-invasive disease.ConclusionsThe management of MPBC is diverse among members of the SUO. Although most favors early cystectomy for cT1 MPBC, there is no consensus on the use of neoadjuvant chemotherapy for muscle-invasive MPBC.     

Heel ultrasonography is not a good screening tool for bone loss after kidney and pancreas transplantation

BACKGROUND: Solid organ transplant recipients, particularly simultaneous pancreas kidney recipients, are at high fracture risk. We tested whether quantitative ultrasonography (QUS) of the heel predicts bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) in solid organ transplant recipients. METHODS: Thirty-eight transplant recipients (22 Female/16 Male) were studied. Spine and hip BMD was measured with a Hologic DXA scanner. 'Stiffness' of the heel was measured with a Lunar Ultrasound densitometer and compared with BMD by DXA. Contributing factors to bone loss were also assessed. RESULTS: Mean age was 43.1 +/- 1.3 yr. Simultaneous pancreas-kidney, kidney, and pancreas alone transplant recipients were assessed. Mean time post-transplantation was 3.0 +/- 0.6 yr. Mean DXA spine T-score was -1.15 +/- 0.22 (mean +/- SEM) and hip T-score was -1.22 +/- 0.20. There was no difference in mean T-score between women and men at the hip or spine. Mean right heel stiffness T-score was -0.97 +/- 0.25. There was no correlation between QUS and DXA at either the hip or spine in women or men. QUS had a false negative rate for identifying osteopenia or osteoporosis of 17% compared with DXA. The false positive rate for identifying osteopenia was 61%. CONCLUSIONS: The QUS is an unacceptable tool for identifying those at risk for bone loss after kidney or pancreas transplantation.     

The effectiveness of polyethylene versus titanium particles in inducing osteolysis in vivo.

Bearing surface wear and periprosthetic osteolysis due to wear particles are among the most common reasons for joint replacement failure. A murine calvarial model of wear particle-induced osteolysis has been used to identify different biologic factors associated with this problem and to test nonsurgical methods of modulating the host response to particulate debris. This model has utilized titanium particles, however, in clinical practice the most common source of particulate debris is polyethylene particles from bearing surface wear. We now report a calvarial model of wear particle-induced osteolysis based on commercially available polyethylene particles. We found that compared to sham surgery osteoclast recruitment and bone resorption can be induced by introduction of the titanium particles or polyethylene particles. However, bone resorption was significantly higher with polyethylene particles compared to titanium particles (p=0.02). We consider the polyethylene based murine calvarial model of wear particle-induced osteolysis a reliable and clinically relevant tool to understand the host factors and potential pharmacologic interventions that can influence wear debris generated osteolysis. This model might serve as an extension of the well-established titanium based bone resorption model.     

Racial variations in Department of Veterans Affairs ambulatory care use and unmet health care needs

Our objective was to describe racial/ethnic variations in Department of Veterans Affairs (VA) ambulatory care use and its association with the presence of unmet health care needs. Using the 1992 National Survey of Veterans, we examined race/ethnicity and unmet health care need for ambulatory care users of VA and non-VA facilities. Black and Hispanic veterans were more likely to report any VA use. In unadjusted analyses, American Indian/Eskimo, Hispanic, and black veterans were 4.4, 2.5, and 1.9 times more likely, respectively, than white veterans to report an inability to get needed care. Adjusting for VA ambulatory care use diminished the disparity in inability to get needed care between American Indian/Eskimo or Hispanic veterans and white veterans and eliminated the disparity between black and white veterans. Our findings support the VA's role as a medical safety net provider and suggest that VA ambulatory care use is effective in mitigating health-related racial disparities for some veterans. Additional facilitators for reducing unmet need should be explored.     

Comparison of central venous and arterial pH and PCO2 during open-chest CPR in the canine model

Arterial blood gases are difficult to obtain during cardiopulmonary resuscitation (CPR) in human beings, and the possibility of venous sampling is raised frequently. The reliability of central venous gases as a substitute for arterial blood gases in assessing acid base status, however, has not been investigated adequately under conditions of CPR. Therefore, femoral arterial and central venous catheters were placed in 24 mongrel dogs, and ventricular fibrillation was electrically induced. After varying predetermined downtimes from five to 60 minutes, open-chest CPR was begun, and arterial and central venous blood gases were simultaneously drawn every five minutes during a 30-minute period. Arterial pH (pHa) was consistently higher than central venous pH (pHcv) by an average of .048 units. A significant correlation existed between the pHa and pHcv at all times during CPR, with an overall r = .9771 (P less than .0001). The difference between central venous PCO2 (PcvCO2) and arterial PCO2 (PaCO2) was 5.17 mm Hg prior to cardiac arrest, but it increased 300% to a mean of 15.51 mm Hg during CPR. Correction of pHcv using conventional methods to account for this respiratory component decreased the correlation between pHa and pHcv to r = .6905. The ability of pHcv to substitute for pHa was assessed, and showed a sensitivity of 100% when pHa of 7.2 was used as a criterion for treatment. In this model, pHcv is a sensitive indicator of pHa and it may be used to guide bicarbonate therapy. The increased PcvCO2 during CPR probably results from the marked tissue lactic acid production and subsequent shift of the bicarbonate buffer into free carbon dioxide.     

Parcellations and hemispheric asymmetries of human cerebral cortex analyzed on surface-based atlases

We report on surface-based analyses that enhance our understanding of human cortical organization, including its convolutions and its parcellation into many distinct areas. The surface area of human neocortex averages 973 cm(2) per hemisphere, based on cortical midthickness surfaces of 2 cohorts of subjects. We implemented a method to register individual subjects to a hybrid version of the FreeSurfer "fsaverage" atlas whose left and right hemispheres are in precise geographic correspondence. Cortical folding patterns in the resultant population-average "fs_LR" midthickness surfaces are remarkably similar in the left and right hemispheres, even in regions showing significant asymmetry in 3D position. Both hemispheres are equal in average surface area, but hotspots of surface area asymmetry are present in the Sylvian Fissure and elsewhere, together with a broad pattern of asymmetries that are significant though small in magnitude. Multiple cortical parcellation schemes registered to the human atlas provide valuable reference data sets for comparisons with other studies. Identified cortical areas vary in size by more than 2 orders of magnitude. The total number of human neocortical areas is estimated to be ～150 to 200 areas per hemisphere, which is modestly larger than a recent estimate for the macaque.     

Intervertebral cages for degenerative spinal diseases.

Interbody fusion techniques have been used for many years for the treatment of a variety of lumbar spine diagnoses. Part of the interest in increasing methods of interbody fusion has stemmed from concern that posterior fusion alone may allow micro-motion, which may generate pain in a ruptured or degenerated disc. Stabilization of the anterior segment led to the development of interbody fusion cages. These devices were designed to stabilize the spine while bony ingrowth from the vertebrae to the bone graft occurred. There are a variety of techniques for cage insertion, including open and laparoscopic techniques anteriorly, and open posterior approach. A lateral approach for cage placement has also been reported. The purpose of this paper is to present a review of the literature on lumbar intervertebral fusion performed using interbody cages. The reported results for these procedures vary, but in general the majority of patients have had favorable results. The complications are similar to those encountered with traditional interbody fusion procedures using bone grafts. There is a learning curve associated with the procedures, particularly with the laparoscopic techniques. Appropriate training for the spine surgeon as well as the access surgeon is important. There is a great deal of disparity in reports on using the cages as stand-alone devices as well as on laparoscopic approaches. Overall, the use of interbody cages for fusion appears to be a viable treatment, yielding good results. Fusion cages appear to have a role in spine care; however, as with any procedure, patient selection and proper training of the surgeon are critical.     

Protective effect of carbon monoxide inhalation for cold-preserved small intestinal grafts

BACKGROUND: Heme oxygenase (HO)-1 system has been shown to provide protection against oxidative stress through the degradation of heme to biliverdin, free iron, and carbon monoxide (CO). This study investigated cytoprotective efficacy of CO at a low concentration on cold ischemia/reperfusion (I/R) injury of transplanted intestine. METHODS: Lewis rat recipients of syngenic orthotopic small intestinal transplantation with 6 hours UW cold preservation were either kept in room air (air-treated control) or exposed to CO (250 ppm) for 1 hour before and 24 hours after surgery. RESULTS: In air-treated grafts, mRNA levels for interleukin-6, intracellular adhesion molecule-1, cyclooxygenase-2, and inducible nitric oxide synthase promptly increased. Sequential histopathologic analysis of untreated grafts revealed initial rapid epithelial loss, subsequent recruitment of inflammatory infiltrates, and local hemorrhage in the lamina propria, which extended downward to the epithelial crypt and muscle layer with time. CO effectively blocked proinflammatory cascade during I/R injury, inhibited upregulation of inflammatory molecules and ameliorated intestinal tissue injuries. Beneficial effects of CO were associated with improved graft blood flow without inhibiting endogenous HO-1 activity. Recipient animal survival was significantly improved with CO to 100% versus 58% in air-treated controls. CONCLUSIONS: These results indicate a significant role for CO in protecting the intestine from cold I/R injury associating with small intestinal transplantation.     

Estrogen blunts neuroendocrine and metabolic responses to hypoglycemia

This study tested the hypothesis that estrogen is the mechanism responsible for the sexual dimorphism present in the neuroendocrine and metabolic responses to hypoglycemia. Postmenopausal women receiving (E2; n = 8) or not receiving (NO E2; n = 9) estrogen replacement were compared with age- and BMI-matched male subjects (n = 8) during a single-step 2-h hyperinsulinemic-hypoglycemic clamp. Plasma insulin (599 +/- 28 pmol/l) and glucose (2.9 +/- 0.03 mmol/l) levels were similar among all groups during the glucose clamp. In response to hypoglycemia, epinephrine (2.8 +/- 0.6 vs. 5.8 +/- 0.8 and 4.4 +/- 0.5 nmol/l), glucagon (57 +/- 8 vs. 77 +/- 8 and 126 +/- 18 ng/l), and endogenous glucose production (2 +/- 2 vs. 10 +/- 2 and 6 +/- 3 micro mol x kg(-1) x min(-1)) were significantly lower in E2 vs. both NO E2 and male subjects (P < 0.05). These reduced counterregulatory responses resulted in significantly greater glucose infusion rates (16 +/- 2 vs. 6 +/- 2 and 6 +/- 3 micro mol x kg(-1) x min(-1); P < 0.01) in E2 vs. both NO E2 and male subjects. Pancreatic polypeptide was significantly lower (P < 0.05) in both the E2 and NO E2 groups compared with the male subjects (136 +/- 20 and 136 +/- 23 vs. 194 +/- 16 pmol/l). Last, glycerol (36 +/- 3 vs. 47 +/- 5 micro mol/l; P < 0.05), lactate (1.4 +/- 0.1 vs. 1.8 +/- 0.2 mmol/l; P < 0.05), and muscle sympathetic nerve activity (19 +/- 4 to 27 +/- 4 vs. 27 +/- 5 to 42 +/- 6 bursts/min; P < 0.05) responses to hypoglycemia were all significantly lower in E2 vs. NO E2 subjects. We conclude that estrogen appears to play a major role in the sexual dimorphism present in counterregulatory responses to hypoglycemia in healthy humans.