Protein and energy depletion in chronic hemodialysis patients: clinical applicability of diagnostic tools.

Protein and energy depletion states are common and associated with increased morbidity and mortality in chronic hemodialysis (CHD) patients. Therefore, proper use of diagnostic tools to assess depleted states in CHD patients is critical. Assessment of protein and energy status can be done by an array of methodologies that include simple estimates of the visceral and somatic pools of protein to more refined techniques to measure protein and energy balance. The nutritional and metabolic derangements in the CHD population are highly complex and can be confounded by multiple comorbidities and fluid shifts between body compartments. Therefore, assessment of protein and energy status in CHD patients requires a wide range of methodologies that not only identify depleted states but also monitor nutrition therapy and predict clinical outcome. Most important, these methods require cautious and individualized interpretation in order to minimize the interference of comorbid conditions frequently observed in the CHD population. Currently, there is not a single method that can be considered the gold standard for assessment of protein and energy status in CHD patients. Therefore, a combination of methods is recommended. In this review, we describe available methods to assess protein and energy status, with special considerations pertaining to CHD patients.     

Who will need long-term care? Creation and validation of an instrument that identifies older people at risk.

The aim of this study was to create and measure the predictive validity of a screening instrument that identifies older people who are at risk for developing a need for long-term care within a year. This was an observational study, with participants allocated to either a derivation cohort or a validation cohort, in the United States. A nationally representative sample of older community-dwelling Medicare beneficiaries (n = 6,538) participated in the Medicare Current Beneficiary Survey. Questions addressed sociodemographic, functional, health-related, and utilization characteristics in 1991 and 1992, linked to records of Medicare payments for health services during 1991-1992. In the derivation cohort, 14 self-reported characteristics were significant predictors of developing a need for long-term care within 1 year. In the validation cohort, these 14 characteristics identified a high-risk subgroup (18%) that, during the following year, developed a need for long-term care at six times the rate of the low-risk majority. This brief survey instrument identifies a high-risk minority of older people that will, during the following year, develop a need for long-term care at six times the rate of the low-risk majority. This instrument may be useful for targeting at-risk subgroups of older populations to receive interventions designed to preserve functional independence and avert the need for long-term care.     

What do pediatric primary care providers think are important research questions? A perspective from PROS providers.

OBJECTIVE: To describe what pediatric primary care providers involved in the Pediatric Research in Office Settings (PROS) research network think are important yet inadequately addressed questions in pediatric primary care research. METHODS: A total of 1785 pediatric primary care providers in the PROS network were asked what they thought were important yet inadequately addressed areas of primary care research. We used a single, open-ended question in a mail survey. Written answers to this question were analyzed by qualitative methods to determine the main themes of interest to pediatric primary care providers. RESULTS: Overall survey response rate was 48.7%; the open-ended question yielded 1109 individual answers. Six lines of inquiry were identified as being important to these providers: (1) effective counseling techniques to use in anticipatory guidance; (2) strategies to prevent and treat obesity; (3) the effectiveness of well-child care; (4) ongoing management of patients with attention-deficit/hyperactivity disorder; (5) the role of the primary care provider in caring for children with mental health needs; and (6) optimal organization of office practices. CONCLUSIONS: The translation of research into practice may be improved by a better understanding of the needs and interests of those who see pediatric patients in the primary care setting.     

Phase I and pharmacologic study of the human DNA methyltransferase antisense oligodeoxynucleotide MG98 given as a 21-day continuous infusion every 4 weeks

Purpose: MG98 is a second generation phosphorothioate antisense oligodeoxynucleotide which is a highly specific inhibitor of translation of the mRNA for human DNA MeTase I (DNMT 1). This phase I study examined the toxicity and pharmacologic profile of MG98 administered as a continuous 21-day intravenous infusion every 4 weeks. Patients and methods: Fourteen patients with solid cancers received a total of 25 cycles of MG98 at doses ranging from 40 to 240 mg/m²/day. Steady-state concentrations of MG98 were measured as were several pharmacodynamic assessments including mRNA of the target gene, DNMT1, in PBMC. In addition, other potential surrogate markers of drug effects were explored, including hemoglobin F, Vimentin and GADD45. Results: Dose limiting effects were drug-related reversible transaminase elevation and fatigue seen at doses of 240, 200 and 160 mg/m²/day. The dose level of 80 mg/m²/day was felt to be safe and tolerable when delivered on this schedule. No evidence of antitumor activity was observed. Although pharmacokinetic analysis revealed that at the higher dose levels, mean Css values of MG98 were approximately 10-fold times the IC₅₀ values associated with target inhibition in vitro, the extent of MG98 penetration into target tumors in this trial was not determined. No consistent, dose-related changes in correlative markers including DNMT1 mRNA, hemoglobin F, Vimentin and GADD45, were observed. Conclusions: This schedule of MG98 given as a 21-day continuous intravenous infusion every 4 weeks was poorly tolerated in the highest doses; therefore, further disease-site specific evaluation of the efficacy of this agent will utilize a more favorable, intermittent dosing schedule. Pharmacodynamic evaluations undertaken in an attempt to explore and validate the biological mechanisms of MG98 did not show dose-related effects.     

Angiotensin-converting enzyme genotype and outcome in pediatric IgA nephropathy

Angiotensin-converting enzyme (ACE) I/D polymorphism has been implicated as a genetic marker for progression of glomerular disease. Studies of ACE genotypes in adults with IgA nephropathy (IgAN) have yielded conflicting results. We performed ACE genotyping on 79 patients with IgAN diagnosed prior to age 18 years who had either progressed to end-stage renal disease (ESRD) or are now more than 5 years post biopsy. Mean follow-up was 14.8 years for those with normal renal function. Forty-three (54.4%) subjects had normal renal function and a normal urinalysis at last evaluation. Sixteen (20%) progressed to ESRD and 1 has chronic renal insufficiency. Kaplan-Meier survival curves for progression to ESRD did not differ significantly for the ACE DD, ID, and II genotype groups (P=0.095, log-rank test). By univariate analysis, presence of hypertension and degree of proteinuria at diagnosis, and unfavorable histology but not ACE genotype, was significantly associated with progression to ESRD. In the Cox proportional hazards model that included grade of proteinuria, the ACE D allele was a significant independent predictor of outcome with a hazard ratio of 2.37 (P=0.031). Our data, while inconclusive, suggest that the ACE D allele may associate with poor outcome in pediatric IgAN.     

Autologous breast reconstruction: the Vanderbilt experience (1998 to 2005) of independent predictors of displeasing outcomes

BACKGROUND: Optimal surgical outcomes are dependent on an appreciation of comorbid conditions that may handicap results. The purpose of this retrospective analysis was to delineate risk factors for complications after autologous breast reconstruction. STUDY DESIGN: An institutional database was constructed of patients who underwent autologous breast reconstruction from 1998 to 2005. Variables captured included age, diabetes and smoking status, prereconstruction radiation therapy, concomitant breast resection, preoperative albumin, flap type, and body mass index (BMI; based on World Health Organization classifications: BMI>25, overweight; >30, obese). The primary outcome was noninfectious wound complications (NIWC), a novel classification based on the extent of tissue derangement and need for operative intervention. Secondary outcomes were wound infection, hematoma, hernia, and fat necrosis. Statistical analysis was performed using chi-square tests and multiple logistic regression. RESULTS: The analysis included 200 flaps (transverse rectus abdominis myocutaneous [TRAM]=171; latissimus dorsi=29) in 180 patients. There were 19 infections (9.5%), 3 total flap losses (1.5%), 14 hematomas (7%), and 11 donor-site hernias (6%). The incidences of fat necrosis and any NIWC were 18% and 36%, respectively. Mean followup was 13.1 months (range 1.1 to 51.7 months). Multiple logistic regression demonstrated that obesity (BMI>30) is a statistically significant independent risk factor for any NIWC (hazards ratio=6.58; 95% CI, 2.85 to 15.18; p < 0.01) and for NIWC requiring operative treatment (NIWC>or=3; hazard ratio=6.23; 95% CI 2.15 to 18.05; p < 0.01). Increased BMI predicts NIWC, NIWC requiring operative intervention, and wound infection (p < 0.01). CONCLUSIONS: These data suggest that obesity is a strong predictor of simple and complex NIWC and of wound infection after autologous breast reconstruction. Obese patients should be counseled about their significantly increased risk of experiencing these unwanted outcomes.     

How does prosthesis head size affect vibration transmission in ossiculoplasty?

OBJECTIVES: The transmission of vibrations from the tympanic membrane to the stapes footplate by an ossicular reconstruction prosthesis is affected by the size of the prosthesis head. We sought to determine if augmenting or reducing the head size of prosthesis had a systematic effect on transmission of vibrations to the stapes. STUDY DESIGN: We conducted a fresh cadaveric temporal bone middle ear study. METHODS: The incus was replaced with a prosthesis using a tympanic membrane to stapes head (TASH)-type hydroxyapatite prosthesis in nine fresh cadaveric temporal bones. Three prosthesis head sizes were created: unaltered, reduced, and augmented. Stapes vibrations were measured with a laser Doppler vibrometer in response to acoustic frequency chirps at 90 dB SPL. RESULTS: All three head size prostheses resulted in smaller stapes vibrations than the intact ear. There was no difference in the vibration transmission between the three different head sizes. All prostheses showed a vibration loss of 10 to 15 dB compared to the intact ear. CONCLUSIONS AND SIGNIFICANCE: Within the range of sizes tested, prosthesis head size had little impact on vibration transmission to the stapes footplate.     

High prevalence of low bone mineral density in pre-dialysis chronic kidney disease patients: bone histomorphometric analysis

Chronic kidney disease (CKD) leads to reduced bone mineral density (BMD) in pre-dialysis and dialysis patients. A few studies have used dual-energy x-ray absorptiometry (DEXA) to assess BMD in pre-dialysis CKD patients and have shown low BMD to be highly prevalent. Until now there have been no studies reporting the histological features of low BMD in pre-dialysis CKD patients. AIM: To determine the prevalence and histological features of low BMD in pre-dialysis CKD patients. METHOD: Pre-dialysis CKD patients (n = 103, 46 females/57 males), median creatinine clearance of 29 (10 - 78) ml/min/ 1.73 m2, were evaluated using biochemical analysis and DEXA. Bone biopsies were obtained from those with low BMD. RESULTS: Fifty (48.5%) out of the 103 patients had low BMD (LBD group) and 53 (51.5%) had normal BMD (NBD group). The risk for low BMD was increased in those patients with alkaline phosphatase levels above 190 U/l and intact-PTH (iPTH) below 70 pg/ml (p < 0.05). Demographic and biochemical parameters from both groups were comparable, except for lower body mass index (BMI) in LBD subjects (p = 0.04). Women who had been post-menopausal for at least 1 year comprised 65% (13/20) and 50% (13/26) of the LBD and NBD groups, respectively (p = NS). In 40 LBD patients, bone histomorphometry revealed adynamic bone disease (ABD, 52.5%), osteomalacia (OM, 42.5%) and mixed bone disease (MBD, 5%). Trabecular bone volume (BV/TV) was lower in ABD and OM patients. A nearly significant association was found between ABD and iPTH < or = 150 pg/ml (p = 0.056), whereas higher values of iPTH were associated with OM. Total alkaline phosphatase < or = 190 U/l was significantly associated with ABD, whereas higher values were associated with OM. No correlation was observed between BV/TV and BMD. CONCLUSION: Low BMD is frequent in pre-dialysis CKD patients, and low turnover bone disease, manifesting as ABD and OM, was the hallmark of this bone loss.