Sleep-disordered breathing is associated with depletion of circulating endothelial progenitor cells and elevation in pulmonary arterial pressure in patients with decompensated systolic heart failure

Background Sleep-disordered breathing (SDB) is known to occur frequently in and may predict worsening progression of patients with congestive heart failure (CHF). SDB is also known to play an important role in the development of idiopathic pulmonary arterial hyperten?sion (PAH) via inducing endothelial dysfunction and vascular remodeling, a pathological process that can be significantly influenced by factors such as osteoprotegerin (OPG) and endothelial progenitor cells (EPCs). The objective of this study is to determine if CHF with SDB is associated with changes in OPG, EPCs, and PAH. Methods EPCs were isolated, cultured, and quantified from CHF patients with SDB (n = 52), or without SDB (n = 68). OPG and N-terminal pro-brain natriuretic peptide (NT-proBNP) from each group was analyzed and correlated with EPCs and the mean pulmonary artery pressure (mPAP) measured by right heart catheterization. Results A significant decrease in circulating EPCs (29.30 ± 9.01 vs. 45.17 ± 10.51 EPCs/× 200 field; P < 0.05) was found in CHF patients with SDB compared to those without SDB. Both OPG (789.83 ± 89.38 vs. 551.29 ± 42.12 pg/mL; P < 0.05) and NT-proBNP (5946.50 ± 1434.50 vs. 3028.60 ± 811.90 ng/mL; P < 0.05) were also significantly elevated in SDB CHF patients who also had significantly elevated mPAP (50.2 ± 9.5 vs. 36.4 ± 4.1 mm Hg; P < 0.05). EPC numbers correlated inversely with the episodes of apnea and hypopnea per hour (RDI, r = –0.45, P = 0.037) and blood level of OPG (r = –0.53, P = 0.011). Although NT-proBNP was also increased significantly in patients with SDB, it had no correlation with either EPCs or RDI. Conclusions SDB due to hypoxemia from decompensated CHF is associated with (1) OPG elevation, (2) EPC depletion, and (3) mPAP elevation. The inverse relationship of circulating OPG with EPCs suggests a likely mechanism for hypoxemia and OPG in the development of pulmonary vascular dysfunction via depleting EPCs, thus worsening prognosis of CHF.     

Determinants of the accuracy of continuous glucose monitoring in non-critically ill patients with heart failure or severe hyperglycemia

Background

The accuracy of continuous glucose monitoring (CGM) in non-critically ill hospitalized patients with heart failure or severe hyperglycemia (SH) is unknown.

Methods

Hospitalized patients with congestive heart failure (CHF) exacerbation (receiving IV or subcutaneous insulin) or SH requiring insulin infusion were compared to outpatients referred for retrospective CGM.

Results

Forty-three patients with CHF, 15 patients with SH, and 88 outpatients yielded 470, 164, and 2150 meter–sensor pairs, respectively. Admission glucose differed (188 versus 509 mg/dl in CHF and SH, p < .001) but not the first sensor glucose (p = .35). In continuous glucose error grid analysis, 67–78% of pairs during hypoglycemia were in zones A+B (p = .63), compared with 98–100% in euglycemia (p < .001) and 98%, 92%, and 99% (p = .001) during hyperglycemia for the CHF, SH, and outpatient groups, respectively. Mean absolute relative difference (MARD) was lower in the CHF versus the SH group in glucose strata above 100 mg/dl, but there was no difference between the CHF and outpatient groups. Linear regression models showed that CHF versus outpatient, SH versus CHF, and coefficient of variation were significant predictors of higher MARD. Among subjects with CHF, MARD was not associated with brain natriuretic peptide or change in plasma volume, but it was significantly higher in subjects randomized to IV insulin (p = .04).

Conclusions

The results suggest that SH and glycemic variability are more important determinants of CGM accuracy than known CHF status alone in hospitalized patients.     

Impact of a physician-supervised exercise-nutrition program with testosterone substitution in partial androgen-deficient middle-aged obese men

Background Partial androgen deficiency syndrome in the aging male is associated with signs of aging such as a development of abdominal obesity, sexual dysfunction, increase body fat, weight gain and the development of cardiac disease. Objective We assessed the outcome of a commercially available physician supervised nutrition and exercise program with concomitant testosterone replacement therapy in middle age obese men with partial androgen deficiency in order to reduce cardiac risks factors. Methods Fifty-six self referred men without diabetes mellitus, hypertension, or cardiovascular disease (ages 52.3 ± 7.8 years) were randomly selected from a large cohort. Baseline weight, body fat composition, fasting glucose, hemoglobin A1c and fasting lipid levels, as well as free and total testosterone levels were assessed. All patients were assessed and followed 6–18 months after initiation of the program. The program consisted of a low glycemic load balanced nutrition diet, a recommended structured daily exercise program of 30–60 minutes, as well as once to twice weekly intramuscular testosterone injections (113.0 ± 27.8 mg). Results At follow up, weight was reduced from 233.9 ± 30.0 pounds (lbs) to 221.3 ± 25.1 lbs (P < 0.001), BMI was reduced from 33.2 ± 3.3 kg/m² to 31.3 ± 2.8 kg/m² (P < 0.0001). Total body fat was 27.1% ± 5.2% vs. 34.3% ± 5.7% at baseline (P < 0.0001). Fasting glucose was reduced from 95.3 ± 14.4 mg/dL to 87.5 ± 12.6 mg/dL (P < 0.0001). Total cholesterol was reduced from 195.4 ± 33.0 mg/dL to 172.7 ± 35.0 mg/dL (P < 0.005). No clinically significant adverse events were recorded. Conclusions Testosterone replacement therapy in middle aged obese men with partial androgen deficiency appeared safe and might have promoted the effects of a weight reduction diet and daily exercise program as long as an adequate physician supervision and follow up was granted. The combination therapy significantly reduced coronary risk factors such as glucose intolerance and hyperlipidemia.     

Nutritional status, hospitalization and mortality among patients with sickle cell anemia in Tanzania

Background

Reduced growth is common in children with sickle cell anemia, but few data exist on associations with long-term clinical course. Our objective was to determine the prevalence of malnutrition at enrolment into a hospital-based cohort and whether poor nutritional status predicted morbidity and mortality within an urban cohort of Tanzanian sickle cell anemia patients.

Design and Methods

Anthropometry was conducted at enrolment into the sickle cell anemia cohort (n=1,618; ages 0.5–48 years) and in controls who attended screening (siblings, walk-ins and referrals) but who were found not to have sickle cell anemia (n=717; ages 0.5–64 years). Prospective surveillance recorded hospitalization at Muhimbili National Hospital and mortality between March 2004 and September 2009.

Results

Sickle cell anemia was associated with stunting (OR=1.92, P<0.001, 36.2%) and wasting (OR=1.66, P=0.002, 18.4%). The greatest growth deficits were observed in adolescents and in boys. Independent of age and sex, lower hemoglobin concentration was associated with increased odds of malnutrition in sickle cell patients. Of the 1,041 sickle cell anemia patients with a body mass index z-score at enrolment, 92% were followed up until September 2009 (n=908) or death (n=50). Body mass index and weight-for-age z-score predicted hospitalization (hazard ratio [HZR]=0.90, P=0.04 and HZR=0.88, P=0.02) but height-for-age z-score did not (HZR=0.93, NS). The mortality rate of 2.5 per 100 person-years was not associated with any of the anthropometric measures.

Conclusions

In this non-birth-cohort of sickle cell anemia with significant associated undernutrition, wasting predicted an increased risk of hospital admission. Targeted nutritional interventions should prioritize treatment and prevention of wasting.     

Predictors of Atrasentan-Associated Fluid Retention and Change in Albuminuria in Patients with Diabetic Nephropathy

Background and objectives

Endothelin A receptor antagonists (ERAs) decrease residual albuminuria in patients with diabetic kidney disease; however, their clinical utility may be limited by fluid retention. Consequently, the primary objective of this study was to identify predictors for ERA-induced fluid retention among patients with type 2 diabetes and CKD. A secondary objective was to determine if the degree of fluid retention necessarily correlated with the magnitude of albuminuria reduction in those patients receiving ERAs.

Design, setting, participants, & measurements

A post hoc analysis was conducted of the phase IIb atrasentan trials assessing albuminuria reduction in 211 patients with type 2 diabetes, urine albumin/creatinine ratios of 300–3500 mg/g, and eGFRs of 30–75 ml/min per 1.73 m² who were randomly assigned to receive placebo (n=50) or atrasentan 0.75 mg/d (n=78) or 1.25 mg/d (n=83) for 12 weeks. Changes in body weight and hemoglobin (Hb) after 2 weeks of treatment were used as surrogate markers of fluid retention.

Results

Baseline predictors of weight gain after 2 weeks of atrasentan treatment were higher atrasentan dose, lower eGFR, higher glycated hemoglobin, higher systolic BP, and lower homeostatic metabolic assessment product. Higher atrasentan dose and lower eGFR also predicted decreases in Hb. There were no changes in B-type natriuretic peptide. There was no correlation between reduction in albuminuria after 2 weeks of atrasentan treatment and changes in body weight or Hb.

Conclusions

In the Reducing Residual Albuminuria in Subjects With Diabetes and Nephropathy With Atrasentan/JAPAN trials, atrasentan-associated fluid retention was more likely in patients with diabetes and nephropathy who had lower eGFR or received a higher dose of atrasentan. Finding that albuminuria reduction was not associated with changes in body weight and Hb suggests that the albuminuria-reducing efficacy of atrasentan is not impaired by fluid retention.     

Correlations between histopathological diagnosis of chemotherapy-induced hepatic injury, clinical features, and perioperative morbidity

Background

Chemotherapy has in some series been linked with increased morbidity after a hepatectomy. Hepatic injuries may result from the treatment with chemotherapy, but can also be secondary to co-morbid diseases. The aim of the present study was to draw correlations between clinical features, treatment with chemotherapy and injury phenotypes and assess the impact of each upon perioperative morbidity.

Patients and methods

Retrospective samples (n = 232) were scored grading steatosis, steatohepatitis and sinusoidal injury (SI). Clinical data were retrieved from medical records. Correlations were drawn between injury, clinical features and perioperative morbidity.

Results

Injury rates were 18%, 4% and 19% for steatosis, steatohepatitis and SI, respectively. High-grade steatosis was more common in patients with diabetes [odds ratio (OR) = 3.33, P = 0.01] and patients with a higher weight (OR/kg = 1.04, P = 0.02). Steatohepatitis was increased with metabolic syndrome (OR = 5.88, P = 0.02). Chemotherapy overall demonstrated a trend towards an approximately doubled risk of high-grade steatosis and steatohepatitis although not affecting SI. However, pre-operative chemotherapy was associated with an increased SI (OR = 2.18, P = 0.05). Operative morbidity was not increased with chemotherapy, but was increased with steatosis (OR = 2.38, P = 0.02).

Conclusions

Diabetes and higher weight significantly increased the risk of steatosis, whereas metabolic syndrome significantly increased risk of steatohepatitis. The presence of high-grade steatosis increases perioperative morbidity, not administration of chemotherapy per se.     

Survival Trends of US Dialysis Patients with Heart Failure: 1995 to 2005

Summary

Background and objectives

Congestive heart failure (CHF) is a major risk factor for death in end-stage kidney disease; however, data on prevalence and survival trends are limited. The objective of this study was to determine the prevalence and mortality effect of CHF in successive incident dialysis cohorts.

Design, setting, participants, & measurements

This was a population-based cohort of incident US dialysis patients (n = 926,298) from 1995 to 2005. Age- and gender-specific prevalence of CHF was determined by incident year, whereas temporal trends in mortality were compared using multivariable Cox regression.

Results

The prevalence of CHF was significantly higher in women than men and in older than younger patients, but it did not change over time in men (range 28% to 33%) or women (range 33% to 36%). From 1995 to 2005, incident death rates decreased for younger men (≤70 years) and increased for older men (>70 years). For women, the pattern was similar but less impressive. During this period, the adjusted mortality risks (relative risk [RR]) from CHF decreased in men (from RR = 1.06 95% Confidence intervals (CI) 1.02–1.11 in 1995 to 0.91 95% CI 0.87–0.96 in 2005) and women (from RR = 1.06 95% CI 1.01–1.10 in 1995 to 0.90 95% CI 0.85–0.95 in 2005 compared with referent year 2000; RR = 1.00). The reduction in mortality over time was greater for younger than older patients (20% to 30% versus 5% to 10% decrease per decade).

Conclusions

Although CHF remains a common condition at dialysis initiation, mortality risks in US patients have declined from 1995 to 2005.     

Electrical Stimulation of the Gut for the Treatment of Type 2 Diabetes: The Role of Automatic Eating Detection

Background

Automatic eating detection (AED) can potentially support treatments that need to be synchronized with food intake. This article analyzes an implantable AED device working in conjunction with gastric stimulation intended to treat type 2 diabetes (T2DM). The device continuously senses for changes in tissue impedance and electrical activity induced by food intake and initiates treatment sessions upon detection. This article reviews AED performance as well as its relevance to treatment outcomes.

Methods

Obese T2DM (n = 12) were implanted with gastric leads and the TANTALUS^® device. An AED algorithm was embedded in the device and was used to initiate periods of electrical stimulation during food intake. AED performance was assessed using patients'' food diaries. The treatment outcome at 37 weeks postimplants was correlated with the rates of stimulation during large meals vs stimulation during periods of no caloric intake.

Results

The algorithm was able to detect 73% of meals consumed while sensing. The rate of false stimulations was 28%. Stimulation during meals was significantly correlated (R² = 0.45, p < 0.05) with hemoglobin A1c change (average drop in hemoglobin A1c was −1 ± 0.4%) but not with changes in body weight (average drop −4.7 ± 2.8 kg). Stimulation during periods with no caloric intake was negatively correlated with hemoglobin A1c reduction (R² = 0.27, p < 0.05).

Conclusions

Sensing of gastric activity can be used for detection of food intake. The synchronization of gastric stimulation to periods of food intake is correlated with metabolic outcomes. AED may also benefit other applications such as drug delivery and control of food restriction devices.     

Serum S-adenosylmethionine,but not methionine,increases in response to overfeeding in humans

Background:

Plasma concentration of the methyl donor S-adenosylmethionine (SAM) is linearly associated with body mass index (BMI) and fat mass. As SAM is a high-energy compound and a sensor of cellular nutrient status, we hypothesized that SAM would increase with overfeeding.

Methods:

Forty normal to overweight men and women were overfed by 1250 kcal per day for 28 days.

Results:

Serum SAM increased from 106 to 130 nmol/l (P=0.006). In stratified analysis, only those with weight gain above the median (high-weight gainers; average weight gain 3.9±0.3 kg) had increased SAM (+42%, P=0.001), whereas low-weight gainers (weight gain 1.5±0.2 kg) did not (P_interaction=0.018). Overfeeding did not alter serum concentrations of the SAM precursor, methionine or the products, S-adenosyl-homocysteine and homocysteine. The SAM/SAH (S-adenosylhomocysteine) ratio was unchanged in the total population, but increased in high-weight gainers (+52%, P=0.006, P_interaction =0.005). Change in SAM correlated positively with change in weight (r=0.33, P=0.041) and fat mass (r=0.44, P=0.009), but not with change in protein intake or plasma methionine, glucose, insulin or low-density lipoprotein (LDL)-cholesterol.

Conclusion:

Overfeeding raised serum SAM in proportion to the fat mass gained. The increase in SAM may help stabilize methionine levels, and denotes a responsiveness of SAM to nutrient state in humans. The role of SAM in human energy metabolism deserves further attention.     

Consultation with cardiologists for persons with new-onset chronic heart failure: A population-based study

BACKGROUND:

It is recommended that persons recently diagnosed with heart failure consult with a specialist in heart failure.

OBJECTIVES:

To determine whether patients who were diagnosed with new-onset chronic heart failure (CHF) by a noncardiologist consulted with a cardiologist, and identify the factors associated with delayed consultation.

METHODS:

Physician reimbursement administrative data were obtained for all adults with suspected new-onset CHF in the year 2000 in Quebec, defined operationally as a physician visit for CHF (based on the International Classification of Diseases, 9th Revision diagnostic codes), with no previous physician visit code for CHF in the preceding three years. Among those first diagnosed by a noncardiologist, Cox regression modelling was used to identify patient and physician characteristics associated with time to cardiology consultation.

RESULTS:

Of the 13,523 persons coded as having incident CHF, 54.9% consulted a cardiologist within the next 2.5 to 3.5 years, and 67.4% were seen by an internist or cardiologist. Older patients, women, and those with lower comorbidity and socioeconomic status had significantly longer times to cardiology consultation.

CONCLUSION:

The data suggest that many patients with suspected new-onset CHF do not receive prompt cardiology care, as stipulated by current recommendations. Equity of access for women and those with lower socioeconomic status appears to be problematic.     

Using an alternate reality game to increase physical activity and decrease obesity risk of college students

Background

This quasi-experimental study investigated a game intervention—specifically, an alternate reality game (ARG)—as a means to influence college students’ physical activity (PA). An ARG is an interactive narrative that takes place in the real world and uses multiple media to reveal a story.

Method

Three sections of a college health course (n = 115 freshman students) were assigned either to a game group that played the ARG or to a comparison group that learned how to use exercise equipment in weekly laboratory sessions. Pre- and post-intervention measures included weight, waist circumference, body mass index (BMI), percentage body fat (PBF), and self-reported moderate physical activity (MPA) and vigorous physical activity (VPA), and PA (steps/week).

Results

A significant group x time interaction (p = .001) was detected for PA, with a significant increase in PA for the game (p < .001) versus a significant decrease (p = .001) for the comparison group. Significant within-group increases for weight (p = .001), BMI (p = .001), and PBF (p = .001) were detected. A significant group x time interaction (p = .001) was detected when analyzing self-reported VPA, with both groups reporting decreases in VPA over time; however, the decrease was only significant for the comparison group (p < .001). No significant group differences were found for MPA.

Conclusions

It is important that any intervention meet the needs and interests of its target population. Here, the ARG was designed in light of the learning preferences of today’s college students—collaborative and social, experiential and media-rich. Our results provide preliminary evidence that a game intervention can positively influence PA within the college student population.     

Preoperative body composition is influenced by the stage of operable pancreatic adenocarcinoma but does not predict survival after Whipple's procedure

Objectives:

Cachexia is common in pancreatic cancer and may have an influence on longterm survival but few studies have investigated this in patients with operable tumours. Therefore, this study was carried out to document body composition status in patients with pancreatic adenocarcinoma (PCa) presenting for a Whipple''s procedure (WP) and to relate the findings to histopathology and longterm survival.

Methods:

Body composition was measured 1 day before a WP for ductal PCa in 36 patients (15 men, 21 women) aged 41–81 years. Results for total body nitrogen (TBN), nitrogen index (NI), total body water (TBW), fat mass (FM) and total body potassium (TBK) were compared with results in 73 age- and sex-matched controls. Patients'' survival and details from histopathology synoptic reports were documented.

Results:

Patients undergoing WPs had low TBK values (P < 0.001) and females had lower body fat (P= 0.007) compared with controls. Five of 36 presented with significant protein deficiency, but this was not associated with a prolonged length of stay or reduced survival. The 12 patients who had involved surgical margins had larger tumours and reduced weight (P= 0.015), FM (P= 0.001), TBN (P= 0.045), TBK (P= 0.014) and survival (P= 0.036). However, multivariate Cox''s regression analysis only included FM along with vascular invasion and margin status as independent predictors of survival.

Conclusions:

PCa patients undergoing a WP have reduced body fat and TBK compared with community controls while those with stage III tumours had greater deficits of fat, TBK and protein stores. However, preoperative body composition was a poor predictor of postoperative survival after pathological data were considered.     

Effects of Weight Loss in Outpatients With Mild Chronic Heart Failure: Findings From the J-MELODIC Study

Background

Weight loss is a strong prognostic factor in chronic heart failure (CHF); however, little is known about its effects in patients with mild CHF. Therefore, we investigated the effects of weight loss in patients with mild CHF.

A Cause-and-Effect-Based Mathematical Curvilinear Model That Predicts the Effects of Self-Monitoring of Blood Glucose Frequency on Hemoglobin A1c and Is Suitable for Statistical Correlations

Background

Previous studies have shown an association between the frequency of self-monitored blood glucose (SMBG) and hemoglobin A1c. Randomized controlled trials (RCTs) have shown this to be a causal correlation for insulin-using patients. Several studies have used linear regression, but a straight line will descend into negative hemoglobin A1c values (an impossibility). This study developed a cause-and-effect-based nonlinear model to predict the outcome of RCTs on this subject, tested this model with clinical data, and offered this model in place of linear regression, especially for the still-debated case of noninsulin-using patients.

Methods

The model was developed from cause-and-effect principles. The clinical study utilized retrospective data from patient histories of a large endocrine practice. Data sets were obtained for five treatment regimens: continuous subcutaneous insulin infusion (CSII), subcutaneous insulin (SC), no insulin (NI), oral medication (OM), and no medication (NM). OM and NM are subgroups of NI. The model was fitted to each group using nonlinear leastsquares methods. Each group was ordered by SMBG tests per day (BGpd) and was divided in half; t tests were run between the A1C''s of the two halves.

Results

Self-monitored blood glucose readings from 1255 subjects were analyzed (CSII, N = 417; SC, N = 286; NI, N = 552; OM, N = 505; NM, N = 47). The CSII, SC, NI, and OM groups showed the expected declining statistically fitted curve and a significant association of BGpd with hemoglobin A1c (P < 0.004). The NM group showed insignificant results.

Conclusions

The nonlinear model is based on cause-and-effect principles and mathematics. It yields a prediction that RCTs will be able to reveal that higher SMBG frequency causes lower hemoglobin A1c.     

Association of Sarcopenia with eGFR and Misclassification of Obesity in Adults with CKD in the United States

Background and objectives

Muscle wasting is common among patients with ESRD, but little is known about differences in muscle mass in persons with CKD before the initiation of dialysis. If sarcopenia was common, it might affect the use of body mass index for diagnosing obesity in people with CKD. Because obesity may be protective in patients with CKD and ESRD, an accurate understanding of how sarcopenia affects its measurement is crucial.

Design, setting, participants, & measurements

Differences in body composition across eGFR categories in adult participants of the National Health and Nutrition Examination Survey 1999–2004 who underwent dual-energy x-ray absorptiometry were examined. Obesity defined by dual-energy x-ray absorptiometry versus body mass index and sarcopenia as a contributor to misclassification by body mass index were examined.

Results

Sarcopenia and sarcopenic obesity were more prevalent among persons with lower eGFR (P trend <0.01 and P trend <0.001, respectively). After multivariable adjustment, the association of sarcopenia with eGFR was U-shaped. Stage 4 CKD was independently associated with sarcopenia among participants ≥60 years old (adjusted odds ratio, 2.58; 95% confidence interval, 1.02 to 6.51 for eGFR=15–29 compared with 60–89 ml/min per 1.73 m²; P for interaction by age=0.02). Underestimation of obesity by body mass index compared with dual-energy x-ray absorptiometry increased with lower eGFR (P trend <0.001), was greatest among participants with eGFR=15–29 ml/min per 1.73 m² (71% obese by dual-energy x-ray absorptiometry versus 41% obese by body mass index), and was highly likely among obese participants with sarcopenia (97.7% misclassified as not obese by body mass index).

Conclusions

Sarcopenia and sarcopenic obesity are highly prevalent among persons with CKD and contribute to poor classification of obesity by body mass index. Measurements of body composition beyond body mass index should be used whenever possible in the CKD population given this clear limitation.     

Serum cystatin C concentration as an independent marker for hypertensive left ventricular hypertrophy

Background Serum cystatin C levels can be used to predict morbidity and mortality in patients with cardiovascular disease. However, the clinical relevance of serum cystatin C levels in patients with hypertensive left ventricular hypertrophy (LVH) has rarely been investigated. We designed the present study to investigate whether serum cystatin C levels are associated with cardiac structural and functional alterations in hypertensive patients. Methods We enrolled 823 hypertensive patients and classified them into two groups: those with LVH (n = 287) and those without LVH (n = 536). All patients underwent echocardiography and serum cystatin C testing. We analyzed the relationship between serum cystatin C levels and LVH. Results Serum cystatin C levels were higher in hypertensive patients with LVH than in those without LVH (P < 0.05). Using linear correlation analysis, we found a positive correlation between serum cystatin C levels and interventricular septal thickness (r = 0.247, P < 0.01), posterior wall thickness (r = 0.216, P < 0.01), and left ventricular weight index (r = 0.347, P < 0.01). When analyzed by multiple linear regression, the positive correlations remained between serum cystatin C and interventricular septal thickness (β = 0.167, P < 0.05), posterior wall thickness (β = 0.187, P < 0.05), and left ventricular weight index (β = 0.245, P < 0.01). Conclusion Serum cystatin C concentration is an independent marker for hypertensive LVH.     

Interaction of time-varying albumin and phosphorus on mortality in incident dialysis patients

Summary

Background and objectives

Hypoalbuminemia and hyperphosphatemia have been shown to be strong predictors of mortality in dialysis patients that might not be independent from each other. We prospectively investigated the relationship and interaction between serum albumin and phosphorus with all-cause mortality in an inception cohort of incident dialysis patients.

Design, setting, participants, & measurements

We followed 235 incident dialysis patients in a prospective single-center cohort study (INVOR study) applying a time-dependent Cox proportional hazards model using all measured laboratory values (2887 albumin and 10306 phosphorus values).

Results

Eighty-two patients (35%) died during a median follow-up of 35.1 months. Albumin was inversely associated with mortality (hazard ratio [95% confidence interval]: 0.23 [0.14 to 0.36]; P < 0.001), whereas higher phosphorus concentrations showed a trend to an increasing risk for mortality (hazard ratio 1.57 [95% confidence interval 0.97 to 2.54]; P = 0.07). Importantly, we observed a significant interaction between albumin and phosphorus (P = 0.01). The lowest risk was found with concurrent low phosphorus and high albumin values, whereas risk was increased with either concurrent low phosphorus and low albumin values or high phosphorus and high albumin values.

Conclusions

In incident dialysis patients the associations of serum phosphorus and albumin concentrations with mortality are modified by each other over time. Phosphorus-lowering interventions that concomitantly can cause a fall in serum albumin level may be harmful and warrant additional studies. If confirmed, epidemiologic studies and therapeutic guidelines aiming for target values should consider this interplay.     

Similar effects on cognitive performance during high- and low-carbohydrate obesity treatment

Objective:

Low-carbohydrate (L-CHO) diets are often used for weight loss but their effects on cognitive function are not well understood. The present study compared the effects of a L-CHO and high-carbohydrate (H-CHO) weight-loss diet on cognitive function adults.

Design:

Participants were randomized to either a L-CHO (n=22) or H-CHO (n=25) weight-loss diet. Cognitive function was evaluated by four computerized cognitive tasks (Stroop Task, Continuous Performance Task, Word Recall and Wisconsin Card Sorting Task) presented in random order before and at 1, 4, 12 and 24 weeks after the initiation of the L-CHO or H-CHO diet.

Participants:

Forty-seven adults (25 males) with a mean±s.d. age of 47.4±8.7 years and body mass index of 35.3±3.4 kg m⁻².

Results:

There were no significant differences in weight loss between groups at any time point. There were significant improvements on color Stroop task accuracy over time in both diet groups (P<0.05), but there were no differences in performance between groups on this or any other cognitive task at any time period.

Conclusion:

These findings suggest that weight loss has neither a positive nor a negative effect on cognitive function and that L-CHO and H-CHO weight-loss diets have similar effects on cognitive performance.     

International Consensus Guidelines parameters for the prediction of malignancy in intraductal papillary mucinous neoplasm are not properly weighted and are not cumulative

Background

The International Consensus Guidelines (ICG) stratify risk for malignancy in patients with intraductal papillary mucinous neoplasm (IPMN) into three progressive categories according to whether patients show ‘no criteria’, ‘worrisome features’ (WFs) or ‘high-risk stigmata’ (HRS).

Objectives

This study was conducted to test the hypothesis that type (clinical versus radiological) and quantity of ICG WFs and HRS carry unequal weight and are not cumulative in the prediction of risk for malignancy or invasiveness in IPMN.

Methods

A retrospective review of a prospectively maintained database of patients who underwent surgical resection for IPMN at a single, university-based medical centre during 1992–2012 was performed. Differences that achieved a P-value of <0.05 were considered significant.

Results

Of 362 patients, 340 were eligible for entry into the study and were categorized as demonstrating no criteria (n = 70), WFs (n = 185) or HRS (n = 85). Patients in the WFs group had higher rates of malignant and invasive IPMN than those in the no-criteria group [26.5% versus 4.3% (P < 0.0001) and 15.7% versus 4.3% (P = 0.02), respectively]. Patients in the HRS group had higher rates of malignant and invasive IPMN than those in the WFs group [56.5% versus 26.5% (P = 0.0001) and 42.4% versus 15.7% (P = 0.0001), respectively]. When radiological parameters only were considered for WFs versus HRS, no difference was found in rates of malignant or invasive IPMN. By contrast, when clinical parameters only were considered, patients in the HRS group had higher rates of malignant or invasive IPMN [66.7% versus 8.1% (P = 0.04) and 66.7% versus 2.7% (P = 0.01), respectively]. There was no stepwise increase in rates of malignant or invasive IPMN with the number of WFs. However, patients with only one WF had a lower risk for malignancy than patients with two or more WFs.

Conclusions

The type and quantity of ICG WFs and HRS carry unequal weight and are not cumulative in the prediction of risk for malignancy or invasiveness in IPMN.