Effects of Long-Term Home Exercise in Participants With Peripheral Artery Disease.

Background This randomized controlled trial compared long-term changes in peak walking time (PWT) and exercise time-to-minimum calf muscle oxygen saturation (StO2) in symptomatic participants with peripheral artery disease following a long-term home exercise program (HEP), a short-term supervised exercise therapy (SET) program that transitioned to a long-term HEP (SET/HEP), and a control intervention. Methods and Results For the first 3 months, HEP and SET/HEP groups performed intermittent walking to mild-to-moderate claudication pain, whereas the control group performed light resistance training. For the subsequent 15 months, the HEP group continued their exercise program, the SET/HEP group transitioned from SET to the HEP program, and the control group transitioned to only receive walking advice. PWT increased significantly from baseline to month 18 in the HEP group (408±279 meters to 814±393 meters, P<0.001) and in the SET/HEP group (457±288 meters to 818±313 meters, P<0.001). Exercise time-to-minimum calf muscle StO2 increased significantly from baseline to month 18 in the HEP group (238±241 seconds to 497±485 seconds, P<0.05) and in the SET/HEP group (296±289 seconds to 620±450 seconds, P<0.001). These changes in PWT and exercise time-to-minimum calf muscle StO2 were greater than in the control group (P<0.001 and P<0.01, respectively). Additionally, the change in exercise time-to-minimum calf muscle StO2 was correlated with the change in PWT in both exercise groups combined (r=0.601, P=0.0015). Conclusions Long-term HEP and SET/HEP were efficacious in improving PWT and exercise time-to-minimum calf muscle StO2 in symptomatic participants with peripheral artery disease, and these changes were correlated with each other. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT00618670.

Comparison of whole blood cytokine immunoassays for rapid, functional immune phenotyping in critically ill patients with sepsis.

BACKGROUND: Sepsis is characterized by highly heterogeneous immune responses associated with a spectrum of disease severity. Methods that rapidly and sensitively profile these immune responses can potentially personalize immune-adjuvant therapies for sepsis. We hypothesized that the ELLA microfluidic approach to measure cytokine production from the whole blood of septic and critically ill patients would deliver faster, more precise results than the existing optic-driven ELISpot quantification. We tested our hypothesis by measuring ex vivo-stimulated production of TNF and IFNγ in critically ill and septic patients (n = 22), critically ill and non-septic patients (n = 10), and healthy volunteers (n = 10) through both ELLA and ELISpot immunoassays. Blood samples were subjected to one of three stimulants for 4 h or 18 h durations during days 1, 7-10, and 14 of critical illness. Stimulants for lymphocytes included anti-CD3/anti-CD28 and phorbol 12-myristate 13-acetate (PMA), whereas LPS was used for monocytes. Stimulated TNF and IFNγ concentrations were then associated with 30-day mortality. RESULTS: Both ELISpot and ELLA immunoassays showed substantial agreement in TNF concentrations post 4 h and 18 h LPS stimulation, with concordance correlation coefficients at 0.62 and 0.60, respectively. ELLA had a broad dynamic measurement range and provided accurate TNF and IFNγ readings at both minimal and elevated cytokine concentrations (with mean coefficients of variation between triplicate readings at 2.1 ± 1.4% and 4.9 ± 7.2%, respectively). However, there was no association between the ELLA-determined cytokine concentrations on the first day of critical illness and 30-day mortality rate. In contrast, using the ELISpot for cytokine quantification revealed that non-survivors had reduced baseline TNF levels at 18 h, decreased LPS-induced TNF levels at 18 h, and diminished TNF levels post 4 h/18 h anti-CD3/28 stimulation. CONCLUSIONS: Our study affirms the feasibility of obtaining dependable immune phenotyping data within 6 h of blood collection from critically ill patients, both septic and non-septic, using the ELLA immunoassay. Both ELLA and ELISpot can offer valuable insights into prognosis, therapeutic strategies, and the underlying mechanisms of sepsis development.

Tackling dynamic prediction of death in patients with recurrent cardiovascular events.

In the field of cardiovascular disease, recurrent events such as stroke or myocardial infarction (MI) are often encountered, leading to an increase in the risk of death. Accurately evaluating the prognosis of patients and dynamically predicting the risk of death by considering the historical recurrent events can improve medical decisions and lead to better health care outcomes. Recently proposed joint modeling approaches within the Bayesian framework have inspired the development of a dynamic prediction tool, which can be applied for subject-level prediction of death with implementation in software packages. The prediction model incorporates subject heterogeneity with subject-level random effects that account for unobserved time-invariant factors and an extra copula function capturing the part caused by unmeasured time-dependent factors. Thereafter, given the prespecified landmark time t ' $$ {t}^{\prime } $$ , the survival probability for a prediction horizon time of interest t $$ t $$ can be estimated for each individual. The prediction accuracy is assessed by time-dependent receiving operating characteristic curve and the area under the curve and the Brier score with calibration plots is compared to traditional joint frailty models. Finally, the tool is applied to patients with multiple attacks of stroke or MI in the Cardiovascular Health study and the Atherosclerosis Risk in Communities study for illustration.

First-time tethered cord release among adults with myelomeningocele: an analysis of people in the National Spina Bifida Patient Registry.

OBJECTIVE: The authors analyzed the National Spina Bifida Patient Registry (NSBPR), a national registry that tracks the outcomes for people with various forms of spinal dysraphism, to determine the ongoing longitudinal risk for tethered cord release (TCR) among adults with myelomeningocele who had not previously undergone TCR during childhood. The authors also sought to identify the impact of lesion level, ambulation status, and prior treatments for hydrocephalus or Chiari malformations on TCR rates. METHODS: Adults in the registry who had not previously undergone TCR during childhood were studied. This group was compared with the remaining adults in the registry. The frequency of first-time TCR and time to TCR (using Kaplan-Meier analysis) were determined independently for males and females. Cox proportional hazards analysis identified correlations between sex, best lesion level and ambulation status prior to TCR, and previous treatments for hydrocephalus and Chiari decompression. RESULTS: Among 967 adults in the NSBPR (422 [43.6%] males and 545 [56.4%] females) who had not undergone TCR during childhood, the authors identified 47 people (4.9%) who underwent their first TCR during adulthood. This study cohort had significantly better mean functional motor levels and ambulation compared with the remaining adult cohort (both p < 0.001). The study group included 35 females (74.5%) and 12 males (25.5%); this sex distribution was significantly different in comparison with the remaining adult cohort (p = 0.016). The Kaplan-Meier curves for first TCR for females and males were significantly different (p = 0.01, log-rank test). TCR rates were correlated with sex (males had decreased risk; OR 0.31, 95% CI 0.16-0.62, p < 0.001), prior treatment for hydrocephalus (those who underwent prior treatment had decreased risk; OR 0.21, 95% CI 0.20-0.42, p < 0.001), and prior treatment for Chiari malformation (those who underwent prior treatment had greater risk; OR 3.84, 95% CI 1.50-9.88, p = 0.005). CONCLUSIONS: Adults with myelomeningocele who escape childhood without undergoing TCR have an ongoing, albeit decreased, risk for spinal cord tethering requiring TCR. This risk is obviously not due to spinal column growth and therefore must reflect other factors such as dynamic changes in spinal cord health over time. Among people with MMC who underwent their first TCR as adults, females seemed to be overrepresented. Similar to the authors' prior childhood study, people who underwent previous Chiari decompression seemed to be overrepresented, whereas those who underwent previous treatment for hydrocephalus seem to be underrepresented. These novel findings deserve further study.

Unknown Causes of Death in Cancer Patients.

OBJECTIVES: Deaths from an unknown cause are difficult to adjudicate and oncologic studies of comparative effectiveness often demonstrate inconsistencies in incorporating these deaths and competing events (eg, heart disease and stroke) in their analyses. In this study, we identify cancer patients most at risk for death of an unknown cause. METHODS: This retrospective, population-based study used cancer registry data from the Surveillance, Epidemiology, and End Results database (1992-2015). The absolute rate of unknown causes of death (COD) cases stratified by sex, marital status, race, treatment, and cancer site were calculated and a multivariable logistic regression model was applied to obtain adjusted odds ratios with 95% CIs. RESULTS: Out of 7,154,779 cancer patients across 22 cancer subtypes extracted from Surveillance, Epidemiology, and End Results, 3,448,927 died during follow-up and 276,068 (7.4%) of these deaths were from unknown causes. Patients with an unknown COD had a shorter mean survival time compared with patients with known COD (36.3 vs 65.7 mo, P < 0.001). The contribution of unknown COD to total mortality was highest in patients with more indolent cancers (eg, prostate [12.7%], thyroid [12.3%], breast [10.7%]) and longer follow-up (eg, >5 to 10 y). One, 3, and 5-year cancer-specific survival (CSS) calculations including unknown COD were significantly decreased compared with CSS estimates excluding cancer patients with unknown COD. CONCLUSION: Of the patients, 7.4% died of unknown causes during follow-up and the proportion of death was higher with longer follow-up and among more indolent cancers. The attribution of high percentages of unknown COD to cancer or non-cancer causes could impact population-based cancer registry studies or clinical trial outcomes with respect to measures involving CSS and mortality.

Diabetes Is Negatively Associated With Meeting Physical Activity Time-Intensity Guidelines in Patients With Claudication.

PURPOSES: We determined the percentage of patients with peripheral artery disease (PAD) and claudication who meet the 2018 physical activity (PA) time-intensity guidelines, and we identified the clinical characteristics associated with the status of meeting the guidelines. METHODS: Five hundred seventy-two patients were assessed on their daily ambulatory activity for 1 wk with a step activity monitor, and were evaluated on whether or not they achieved 150 min/wk of moderate-intensity PA. RESULTS: Thirty-one percent (n = 175) of the patients with PAD met the PA time-intensity guidelines and 69% (n = 397) did not. In a final multivariable logistic regression model identifying the independent predictors of meeting the PA time-intensity guidelines from clinical characteristics, diabetes was the only significant variable entered (OR = 0.310: 95% CI, 0.175-0.538; P < .001) and was associated with a 69% lower chance of meeting the guidelines. Patients with diabetes spent less daily time in moderate-intensity ambulatory PA than patients without diabetes (15 ± 13 vs 23 ± 20 min/d; P < .001). CONCLUSIONS: Thirty-one percent of patients with PAD and claudication met the PA time-intensity guidelines. Furthermore, patients with diabetes were least likely to meet the PA time-intensity guidelines, as they had a 69% lower chance than patients without diabetes. The clinical significance is that PAD patients who have diabetes are particularly susceptible to being physically sedentary, and are therefore prime patients who should be encouraged to increase their daily PA.

Maximal calf conductance is associated with 6-minute walk distance in participants with and without peripheral artery disease.

INTRODUCTION: The aims were (a) to compare the maximal calf conductance and 6-minute walk distance of participants with and without peripheral artery disease (PAD) and claudication, (b) to determine whether maximal calf conductance was more strongly associated with 6-minute walk distance in participants with PAD than in the controls, and (c) to determine whether this association was significant in participants with PAD after adjusting for ABI, as well as for demographic, anthropometric, and comorbid variables. METHODS: Participants with PAD (n = 633) and without PAD (n = 327) were assessed on maximal calf conductance using venous occlusion plethysmography, and on 6-minute walk distance. Participants were further characterized on ABI, and on demographic, anthropometric, and comorbid variables. RESULTS: The PAD group had lower maximal calf conductance than the control group (0.136 ± 0.071 vs 0.201 ± 0.113 mL/100 mL/min/mmHg, p < 0.001). Additionally, the PAD group had a lower 6-minute walk distance (375 ± 98 m vs 480 ± 107 m, p < 0.001). Maximal calf conductance was positively associated with 6-minute walk distance in both groups (p < 0.001) and was more strongly associated in the PAD group (p < 0.001). In adjusted analyses, maximal calf conductance remained positively associated with 6-minute walk distance in the PAD group (p < 0.001) and in the control group (p < 0.001). CONCLUSIONS: Participants with PAD and claudication had impaired maximal calf conductance and a lower 6-minute walk distance than those without PAD, and maximal calf conductance was positively and independently associated with 6-minute walk distance within each group before and after adjusting for ABI, and for demographic, anthropometric, and comorbid variables.

The association of subcortical brain injury and abusive head trauma.

BACKGROUND: Abusive head trauma (AHT) remains a major pediatric problem with diagnostic challenges. A small pilot study previously associated subcortical brain injury with AHT. OBJECTIVES: To investigate the association of subcortical injury on neuroimaging with the diagnosis of AHT. PARTICIPANTS AND SETTING: Children <3 years with acute TBI admitted to 18 PICUs between 2011 and 2021. METHODS: Secondary analysis of existing, combined, de-identified, cross-sectional dataset. RESULTS: Deepest location of visible injury was characterized as scalp/skull/epidural (n = 170), subarachnoid/subdural (n = 386), cortical brain (n = 170), or subcortical brain (n = 247) (total n = 973). Subcortical injury was significantly associated with AHT using both physicians' diagnostic impression (OR: 8.41 [95 % CI: 5.82-12.44]) and a priori definitional criteria (OR: 5.99 [95 % CI: 4.31-8.43]). Caregiver reports consistent with the child's gross motor skills and historically consistent with repetition decreased as deepest location of injury increased, p < 0.001. Patients with subcortical injuries were significantly more likely to have traumatic extracranial injuries such as rib fractures (OR 3.36, 95 % CI 2.30-4.92) or retinal hemorrhages (OR 5.97, 95 % CI 4.35-8.24), respiratory compromise (OR 12.12, 95 % CI 8.49-17.62), circulatory compromise (OR 6.71, 95 % CI 4.87-9.29), seizures (OR 3.18, 95 % CI 2.35-4.29), and acute encephalopathy (OR 12.44, 95 % CI 8.16-19.68). CONCLUSIONS: Subcortical injury is associated with a diagnosis of AHT, historical inaccuracies concerning for abuse, traumatic extracranial injuries, and increased severity of illness including respiratory and circulatory compromise, seizures, and prolonged loss of consciousness. Presence of subcortical injury should be considered as one component of the complex AHT diagnostic process.

Increased pulse wave velocity is related to impaired working memory and executive function in older adults with metabolic syndrome.

Age-related vascular alterations promote the pathogenesis of vascular cognitive impairment (VCI). Cardiovascular risk factors that accelerate vascular aging exacerbate VCI. Metabolic syndrome (MetS) constitutes a cluster of critical cardiovascular risk factors (abdominal obesity, hypertension, elevated triglycerides, elevated fasting glucose, reduced HDL cholesterol), which affects nearly 37% of the adult US population. The present study was designed to test the hypotheses that MetS exacerbates cognitive impairment and that arterial stiffening moderates the association between cognitive dysfunction and MetS in older adults. MetS was defined by the NCEP ATP III guidelines. Cognitive function (digit span and trail-making tests) and brachial-ankle pulse wave velocity (baPWV; a non-invasive clinical measurement of arterial stiffness) were assessed in older adults with MetS and age- and sex-matched controls. Multiple linear regression models were applied to test for the main effects of MetS, baPWV, and their interaction on cognitive performance. Fifty-three participants with MetS (age: 68 ± 8 years) and 39 age-matched individuals without MetS (age: 66 ± 9 years) were enrolled into the study. In adjusted multivariable regression analyses of the digit span backward length score, both MetS (ß = 1.97, p = 0.048) and MetS by baPWV interaction (ß = - 0.001, p = 0.026) were significant predictors. In participants with MetS, higher baPWV was associated with poorer performance on digit span backward length score, a test of working memory (R = - 0.44, p = 0.0012), but there was no association in those without MetS (R = 0.035, p = 0.83). MetS was negatively associated with performance on the digit span backward length score, baPWV was negatively associated with multiple neuropsychological outcomes, and baPWV moderated the association between digit span backward length score and MetS, as individuals with both MetS and higher baPWV had the most impaired cognitive function. Our findings add to the growing body of evidence that individuals with MetS and higher baPWV may be prone to VCI.

Charting the course from abstract to published article.

OBJECTIVE: Abstracts act as short, efficient sources of new information. This intentional brevity potentially diminishes scientific reliability of described findings. The authors' objective was to 1) determine the proportion of abstracts submitted to the American Association of Neurological Surgeons (AANS) annual meeting that subsequently are published in peer-reviewed journals, 2) assess AANS abstract publications for publication bias, and 3) assess AANS abstract publications for differing results. METHODS: The authors screened all abstracts from the annual 2012 AANS meeting and identified their corresponding full-text publication, if applicable, by searching PubMed/MEDLINE. The abstract and subsequent publication were analyzed for result type (positive or negative) and differences in results. RESULTS: Overall, 49.3% of abstracts were published as papers. Many (18.1%) of these published papers differed in message from their original abstract. Publication bias exists, with positive abstracts being 40% more likely to be published than negative abstracts. The top journals in which the full-text articles were published were Journal of Neurosurgery (13.1%), Neurosurgery (7.3%), and World Neurosurgery (5.4%). CONCLUSIONS: Here, the authors demonstrate that alone, abstracts are not reliable sources of information. Many abstracts ultimately remain unpublished; therefore, they do not attain a level of scientific scrutiny that merits alteration of clinical care. Furthermore, many that are published have differing results or conclusions. In addition, positive publication bias exists, as positive abstracts are more likely to be published than negative abstracts.

County-level characteristics associated with incidence, late-stage incidence, and mortality from screenable cancers.

BACKGROUND: Cancer screening differs by rurality and racial residential segregation, but the relationship between these county-level characteristics is understudied. Understanding this relationship and its implications for cancer outcomes could inform interventions to decrease cancer disparities. METHODS: We linked county-level information from national data sources: 2008-2012 cancer incidence, late-stage incidence, and mortality rates (for breast, cervical, and colorectal cancer) from U.S. Cancer Statistics and the National Death Index; metropolitan status from U.S. Department of Agriculture; residential segregation derived from American Community Survey; and prevalence of cancer screening from National Cancer Institute's Small Area Estimates. We used multivariable, sparse Poisson generalized linear mixed models to assess cancer incidence, late-stage incidence, and mortality rates by county-level characteristics, controlling for density of physicians and median household income. RESULTS: Cancer incidence, late-stage incidence, and mortality rates were 6-18% lower in metropolitan counties for breast and colorectal cancer, and 2-4% lower in more segregated counties for breast and colorectal cancer. Generally, reductions in cancer associated with residential segregation were limited to non-metropolitan counties. Cancer incidence, late-stage incidence, and mortality rates were associated with screening, with rates for corresponding cancers that were 2-9% higher in areas with more breast and colorectal screening, but 2-15% lower in areas with more cervical screening. DISCUSSION: Lower cancer burden was observed in counties that were metropolitan and more segregated. Effect modification was observed by metropolitan status and county-level residential segregation, indicating that residential segregation may impact healthcare access differently in different county types. Additional studies are needed to inform interventions to reduce county-level disparities in cancer incidence, late-stage incidence, and mortality.

Survival after palliative radiation therapy for cancer: The METSSS model.

BACKGROUND: We propose a predictive model that identifies patients at greatest risk of death after palliative radiotherapy, and subsequently, can help medical professionals choose treatments that better align with patient choice and prognosis. METHODS: The National Cancer Database was queried for recipients of palliative radiotherapy during first course of treatment. Cox regression models and adjusted hazard ratios with 95% confidence intervals were used to evaluate survival predictors. The mortality risk index was calculated using predictors from the estimated Cox regression model, with higher values indicating higher mortality risk. Based on tertile cutpoints, patients were divided into low, medium, and high risk groups. RESULTS: A total of 68,505 patients were included from 2010-2014, median age 65.7 years. Several risk factors were found to predict survival: (1) location of metastases (liver, bone, lung, and brain); (2) age; (3) tumor primary (prostate, breast, lung, other); (4) gender; (5) Charlson-Deyo comorbidity score; and (6) radiotherapy site. The median survival times were 11.66 months, 5.09 months, and 3.28 months in the low (n=22,621), medium (n=22,638), and high risk groups (n=22,611), respectively. A nomogram was created and validated to predict survival, available online, https://tinyurl.com/METSSSmodel. Harrel's C-index was 0.71 and receiver operator characteristic area under the curve was 0.76 at 4 years. CONCLUSION: We created a predictive nomogram for survival of patients receiving palliative radiotherapy during their first course of treatment (named METSSS), based on Metastases location, Elderly (age), Tumor primary, Sex, Sickness/comorbidity, and Site of radiotherapy.

Bayesian Network Meta-analysis of Multiple Outcomes in Dental Research.

OBJECTIVES: Dental research typically targets multiple outcomes. Interdental cleaning devices such as interdental brushes (IB) and water jet devices (WJ) share a sizable portion of the medical device market. However, recommendations for device selection are limited by the conflicting evidence from multiple outcomes in available studies and the lack of an appropriate synthesis approach to summarize evidences taken from multiple outcomes. In particular, both pairwise meta-analyses and single-outcome network meta-analyses can give discordant results. The purpose of this multioutcome, Bayesian network meta-analysis is to introduce this innovative method to the dental research community using data from interdental cleaning device studies for illustrative purposes. METHODS: We reanalyzed a network meta-analysis of interproximal oral hygiene methods in the reduction of clinical indices of inflammation, which included 22 trials assessing 10 interproximal oral hygiene aids. We focused on the primary outcome of gingival inflammation, which was measured by 2 correlated outcome variables, the Gingival Index (GI) and bleeding on probing (BOP). RESULTS: In our previous single-outcome analysis, we concluded that IB and WJ rank high for reducing gingival inflammation while toothpick and flossing rank last. In this multioutcome Bayesian network meta-analysis with equal weight on GI and BOP, the surface under the cumulative ranking curve was 0.87 for WJ and 0.85 for IB. WJ and IB remained ranked as the 2 best devices across different sets of weightings for the GI and BOP. CONCLUSION: In conclusion, multioutcome Bayesian network meta-analysis naturally takes the correlations among multiple outcomes into account, which in turn can provide more comprehensive evidence.

Association of Head Injury with Brain Amyloid Deposition: The ARIC-PET Study.

Our objective was to examine associations of head injury with total and regional brain amyloid deposition. We performed cross-sectional analyses of 329 non-demented participants (81 with prior head injury) in the Atherosclerosis Risk in Communities-Positron Emission Tomography (ARIC-PET) Study who underwent 18-florbetapir PET imaging in 2012-2014. A history of head injury was defined by self-report or emergency department/hospitalization International Classification of Diseases, Ninth Revision codes. Generalized linear regression models adjusted for demographic, socioeconomic, and dementia/cardiovascular risk factors were used to estimate prevalence ratios (PRs; 95% confidence intervals [CIs]) for elevated (> 1.2) global and regional standard uptake value ratios (SUVRs). Mean age of participants was 76 years, 57% were women, and 43% were black. Head injury was associated with increased prevalence of elevated SUVR >1.2 globally (PR: 1.31; 95% CI: 1.19-1.57), as well as in the orbitofrontal cortex (PR: 1.23); (95% CI: 1.04-1.46), prefrontal cortex (PR: 1.18; 95% CI: 1.00-1.39), superior frontal cortex (PR: 1.24; 95% CI: 1.05-1.48), and posterior cingulate (PR: 1.26; 95% CI: 1.04-1.52). There also was evidence for a dose-response relationship, whereby a history of ≥1 head injury was associated with elevated SUVR >1.2 in the prefrontal cortex and superior frontal cortex compared with persons with a history of one head injury (all, p < 0.05). In conclusion, head injury was associated with increased amyloid deposition globally and in the frontal cortex and posterior cingulate, with suggestion of a dose-response association of head injuries with beta-amyloid deposition. Further work is needed to determine if increased amyloid deposition contributes to dementia in this population.

Plasma galectin-3 levels are associated with the risk of incident chronic kidney disease.

Galectin-3 has been proposed as a novel biomarker of heart failure and cardiac fibrosis, and may also be associated with fibrosis of other organs such as the kidney. To determine this, we prospectively analyzed data from 9,148 Atherosclerosis Risk in Communities (ARIC) Study participants with measured plasma galectin-3 levels (baseline, visit 4, 1996-98) and without prevalent chronic kidney disease (CKD) or heart failure. We identified 1,983 incident CKD cases through December 31, 2013 over a median follow-up of 16 years. At baseline, galectin-3 was cross-sectionally associated with estimated glomerular filtration rate and urine albumin-to-creatinine ratio; both significant. The results were adjusted for age, sex, race-center, education, physical activity, smoking status, body mass index, systolic blood pressure, anti-hypertensive medication use, history of cardiovascular disease, diabetes, fasting blood glucose, and rs4644 (a single nucleotide polymorphism of galactin-3). There was a significant, graded, and positive association between galectin-3 and incident CKD (quartile 4 vs. 1 hazard ratio: 2.22 [95% confidence interval: 1.89, 2.60]). The association was attenuated but remained significant after adjustment for estimated glomerular filtration rate, urine albumin-to-creatinine ratio, troponin T, and N-terminal pro-brain natriuretic peptide (quartile 4 vs. 1 hazard ratio: 1.75 [95% confidence interval: 1.49, 2.06]), and was stronger among those with hypertension at baseline (significant interaction). Thus, in this community-based population, higher plasma galectin-3 levels were associated with an elevated risk of developing incident CKD, particularly among those with hypertension.

Risk of ESRD and Mortality Associated With Change in Filtration Markers.

BACKGROUND: Using change in estimated glomerular filtration rate (eGFR) based on creatinine concentration as a surrogate outcome in clinical trials of chronic kidney disease has been proposed. Risk for end-stage renal disease (ESRD) and all-cause mortality associated with change in concentrations of other filtration markers has not been studied in chronic kidney disease populations. STUDY DESIGN: Observational analysis of 2 clinical trials. SETTING & PARTICIPANTS: Participants in the MDRD (Modification of Diet in Renal Disease; n=317) Study and AASK (African American Study of Kidney Disease and Hypertension; n=373). PREDICTORS: Creatinine, cystatin C, ß-trace protein (BTP), and ß2-microglobulin (B2M) were measured in serum samples collected at the 12- and 24-month follow-up visits, along with measured GFR (mGFR) at these time points. OUTCOMES: ESRD and all-cause mortality. MEASUREMENTS: Poisson regression was used to estimate incidence rate ratios and 95% CIs for ESRD and all-cause mortality during long-term follow-up (10-16 years) per 30% decline in mGFR or eGFR for each filtration marker and the average of all 4 markers. RESULTS: 1-year decline in mGFR, eGFRcr, eGFRBTP, and the average of the 4 filtration markers was significantly associated with increased risk for incident ESRD in both studies (all P≤0.02). Compared to mGFR, only decline in eGFRBTP was statistically significantly more strongly associated with ESRD risk in both studies (both P≤0.03). Decline in eGFRcr, but not mGFR or the other filtration markers, was significantly associated with risk for all-cause mortality in AASK only (incidence rate ratio per 30% decline, 4.17; 95% CI, 1.78-9.74; P<0.001), but this association was not significantly different from decline in mGFR (P=0.2). LIMITATIONS: Small sample size. CONCLUSIONS: Declines in mGFR, eGFRcr, eGFRBTP, and the average of 4 filtration markers (creatinine, cystatin C, BTP, and B2M) were consistently associated with progression to ESRD.

Dietary Protein Sources and Risk for Incident Chronic Kidney Disease: Results From the Atherosclerosis Risk in Communities (ARIC) Study.

OBJECTIVE: Dietary protein restriction is recommended for patients with moderate to severe renal insufficiency. Long-term data on the relationship between dietary protein sources and risk for incident kidney disease in individuals with normal kidney function are largely missing. This study aimed to assess the association between dietary protein sources and incident chronic kidney disease (CKD). DESIGN: Prospective cohort. SETTING: Atherosclerosis Risk in Communities study participants from 4 US communities. SUBJECTS: A total of 11,952 adults aged 44-66 years in 1987-1989 who were free of diabetes mellitus, cardiovascular disease, and had an estimated glomerular filtration rate (eGFR) ≥ 60 mL/minute/1.73 m2. MAIN OUTCOME MEASURE: A 66-item food frequency questionnaire was used to assess food intake. CKD stage 3 was defined as a decrease in eGFR of ≥25% from baseline resulting in an eGFR of less than 60 mL/minute/1.73 m2; CKD-related hospitalization; CKD-related death; or end-stage renal disease. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazards regression. RESULTS: During a median follow-up of 23 years, there were 2,632 incident CKD cases. Red and processed meat consumption was associated with increased CKD risk (HRQ5 vs. Q1: 1.23, 95% CI: 1.06-1.42, ptrend = 0.01). In contrast, higher dietary intake of nuts, legumes, and low-fat dairy products was associated with lower CKD risk (nuts: HRQ5 vs. Q1: 0.81, 95% CI: 0.72-0.92, ptrend <0.001; low-fat dairy products: HRQ5 vs. Q1: 0.75, 95% CI: 0.65-0.85, ptrend <0.001; legumes: HRQ5 vs. Q1: 0.83, 95% CI: 0.72-0.95, ptrend = 0.03). CONCLUSION: There were varied associations of specific dietary protein sources with risk of incident CKD; with red and processed meat being adversely associated with CKD risk; and nuts, low-fat dairy products, and legumes being protective against the development of CKD.

Association of a Biomarker of Glucose Peaks, 1,5-Anhydroglucitol, With Subclinical Cardiovascular Disease.

OBJECTIVE: 1,5-Anhydroglucitol (1,5-AG) is a biomarker of glucose peaks and has been associated with clinical cardiovascular disease. However, the association between 1,5-AG and subclinical cardiovascular disease is unknown. We investigated the association of 1,5-AG with subclinical myocardial damage (assessed by high-sensitivity cardiac troponin T [hs-cTnT]) and atherosclerosis (assessed by carotid intima-media thickness [CIMT] and carotid plaque). RESEARCH DESIGN AND METHODS: We measured 1,5-AG, hs-cTnT, CIMT, and carotid plaque among 10,072 people without diabetes and 681 with diabetes who attended the second examination of the Atherosclerosis Risk in Communities (ARIC) Study (baseline, 1990-1992). We used Poisson regression to characterize the associations between 1,5-AG and prevalent elevated hs-cTnT, thick CIMT, or carotid plaque. Among 9,145 people with a second hs-cTnT measurement 6 years later, we used multinomial logistic regression to assess associations with incident elevation in hs-cTnT. RESULTS: We found that in people with diabetes, lower 1,5-AG (<6 µg/mL) was cross-sectionally associated with elevated hs-cTnT (prevalence ratio 2.06, 95% CI 1.23-3.46) compared with higher 1,5-AG (≥10 µg/mL). Associations in people without diabetes and with thick CIMT or the presence of carotid plaque were less robust. Low 1,5-AG was prospectively associated with the 6-year incident elevation in hs-cTnT (relative risk 2.90, 95% CI 1.23-6.85) in people with diabetes. All associations were strongly attenuated with further adjustment for HbA1c. CONCLUSIONS: In people with diabetes, 1,5-AG was associated with subclinical cardiovascular disease, particularly chronic subclinical myocardial damage. Nonetheless, whether observed associations are truly independent of average glycemia is unclear.