Association of Size Matching Using Predicted Heart Mass With Mortality in Heart Transplant Recipients With Obesity or High Pulmonary Vascular Resistance.

Importance: Pretransplant obesity and higher pulmonary vascular resistance (PVR) are risk factors for death after heart transplant. However, it remains unclear whether appropriate donor-to-recipient size matching using predicted heart mass (PHM) is associated with lower risk. Objective: To investigate the association of size matching using PHM with risk of death posttransplant among patients with obesity and/or higher PVR. Design, Setting, and Participants: All adult patients (>18 years) who underwent heart transplant between 2003 and 2022 with available information using the United Network for Organ Sharing cohort database. Multivariable Cox models and multivariable-adjusted spline curves were used to examine the risk of death posttransplant with PHM matching. Data were analyzed from October 2022 to March 2023. Exposure: Recipient's body mass index (BMI) in categories (<18.0 [underweight], 18.1-24.9 [normal weight, reference], 25.0-29.9 [overweight], 30.0-34.9 [obese 1], 35-39.9 [obese 2], and ≥40.0 [obese 3]) and recipient's pretransplant PVR in categories of less than 4 (29 061 participants), 4 to 6 (2842 participants), and more than 6 Wood units (968 participants); and less than 3 (24 950 participants), 3 to 5 (6115 participants), and 5 or more (1806 participants) Wood units. Main Outcome: All-cause death posttransplant on follow-up. Results: The mean (SD) age of the cohort of 37 712 was 52.8 (12.8) years, 27 976 (74%) were male, 25 342 were non-Hispanic White (68.0%), 7664 were Black (20.4%), and 3139 were Hispanic or Latino (8.5%). A total of 12 413 recipients (32.9%) had a normal BMI, 13 849 (36.7%) had overweight, and 10 814 (28.7%) had obesity. On follow-up (median [IQR] 5.05 [0-19.4] years), 12 785 recipients (3046 female) died. For patients with normal weight, overweight, or obese 2, receiving a PHM-undermatched heart was associated with an increased risk of death (normal weight hazard ratio [HR], 1.20; 95% CI, 1.07-1.34; overweight HR, 1.12; 95% CI, 1.02-1.23; and obese 2 HR, 1.07; 95% CI, 1.01-1.14). Moreover, patients with higher pretransplant PVR who received an undermatched heart had a higher risk of death posttransplant in multivariable-adjusted spline curves in graded fashion until appropriately matched. In contrast, risk of death among patients receiving a PHM-overmatched heart did not differ from the appropriately matched group, including in recipients with an elevated pretransplant PVR. Conclusion and Relevance: In this cohort study, undermatching donor-to-recipient size according to PHM was associated with higher posttransplant mortality, specifically in patients with normal weight, overweight, or class II obesity and in patients with elevated pretransplant PVR. Overmatching donor-to-recipient size was not associated with posttransplant survival.

Sex-Specific Differences in Ventricular Dimensions in Repaired Tetralogy of Fallot: A Retrospective Study.

The timing of pulmonary valve replacement (PVR) in asymptomatic patients with repaired tetralogy of Fallot (TOF) is typically based on cardiac magnetic resonance imaging-derived ventricular volume measurements. Current criteria do not account for sex-based differences in chamber size. The purpose of this study was to compare male and female ventricular volumes and function in TOF patients with a hypothesis that females are less likely to meet common-indexed right ventricular end-diastolic volume (RVEDVi) and right ventricular end-systolic volume (RVESVi) criteria for PVR. Cardiac magnetic resonance data from 17 females (age 31.7 ± 15.4 years) and 23 males (30.7 ± 15.4 years) with TOF were retrospectively analyzed. Demographic and imaging data were recorded. Differences in sex-based means and standard deviations were evaluated using the Wilcoxon rank-sum test with continuity correction. Age and pulmonary regurgitant fraction were similar in females and males. RVEDVi was lower in females than in males, but the difference was not statistically significant. Differences in RVESVi, LVEDVi, LVESVi, and left ventricular ejection fraction were statistically significant, while the difference in right ventricular ejection fraction was not. RVEDVi was greater than 150 mL/m2 in 3/17 (17.6%) females and 10/23 (43.5%) males (OR 3.6). RVESVi was greater than 82 mL/m2 in 2/17 females and 8/23 males (OR 4.0). Sex-specific differences in right ventricular and left ventricular volumes and function are present in patients with TOF despite similar pulmonary regurgitation. These differences may need to be considered when evaluating patients for PVR.

Diabetic foot ulcer severity predicts mortality among veterans with type 2 diabetes.

AIM: Diabetic foot ulcers are associated with an increased risk of death. We evaluated whether ulcer severity at presentation predicts mortality. METHODS: Patients from a national, retrospective, cohort of veterans with type 2 diabetes who developed incident diabetic foot ulcers between January 1, 2006 and September 1, 2010, were followed until death or the end of the study period, January 1, 2012. Ulcers were characterized as early stage, osteomyelitis, or gangrene at presentation. Cox proportional hazard regression identified independent predictors of death, controlling for comorbidities, laboratory parameters, and healthcare utilization. RESULTS: 66,323 veterans were included in the cohort and followed for a mean of 27.7months: 1-, 2-, and 5-year survival rates were 80.80%, 69.01% and 28.64%, respectively. Compared to early stage ulcers, gangrene was associated with an increased risk of mortality (HR 1.70, 95% CI 1.57-1.83, p<0.001). The magnitude of this effect was greater than diagnosed vascular disease, i.e., coronary artery disease, peripheral arterial disease, or stroke. CONCLUSION: Initial diabetic foot ulcer severity is a more significant predictor of subsequent mortality than coronary artery disease, peripheral arterial disease, or stroke. Unrecognized or under-estimated vascular disease and/or sepsis secondary to gangrene should be explored as possible causal explanations.

Computerized Tailored Interventions to Enhance Prevention and Screening for Hepatitis C Virus Among People Who Inject Drugs: Protocol for a Randomized Pilot Study.

BACKGROUND: Hepatitis C virus (HCV) infection is a growing problem among people who inject drugs. Strategies to reduce disease transmission (eg, syringe exchange programs) and facilitate HCV screening and linkage are available but are under-utilized in many communities affected by injection drug use. Novel approaches to increasing the use of these strategies are needed. OBJECTIVE: The goals of this project are to (1) develop and pilot test a computerized tailored intervention for increasing HCV screening and decreasing risky drug use behavior among people who inject drugs and (2) determine the feasibility of disseminating such an intervention using peer-based referrals in the setting of a community-based syringe exchange program. METHODS: This 2-arm, randomized pilot study is being conducted in a large-volume, multisite syringe exchange program in southern Wisconsin. A social network-based strategy was used to recruit a total of 235 adults who reported past-month injection of opioids, cocaine, or methamphetamine. Network recruiters were identified among clients requesting services from the syringe exchange program and were enlisted to refer eligible peers to the study. All participants completed a computer-adapted questionnaire eliciting information about risk behaviors and their knowledge, attitudes, and prior experiences related to HCV screening. Subjects were then randomly assigned to receive usual care, consisting of standard counseling by syringe exchange staff, or the Hep-Net intervention, which provides algorithm-based, real-time tailored feedback and recommendations for behavior change in the style of motivational interviewing. Changes in drug use behaviors and attitudes will be assessed during a second session between 90 and 180 days after the baseline visit. Frequency of repeat HCV testing and HCV incidence will be assessed through a database search 1 year after study completion. RESULTS: Recruitment for this study was completed in April 2015. Follow-up of enrolled participants is expected to continue until March 2016. Network recruiters were enrolled who referred a total of 195 eligible peers (overall N=235). At baseline, the median age was 34 years; 41.3% (97/235) were non-white; and 86.4% (203/235) reported predominantly injecting heroin. Most participants (161/234, 68.8%) reported sharing injection equipment in the past and of these, 30.4% (49/161) had never been tested for HCV. CONCLUSIONS: This study will provide preliminary evidence to determine whether incorporating computerized behavioral interventions into existing prevention services at syringe exchange programs can lead to adoption of healthier behaviors. TRIAL REGISTRATION: ClinicalTrials.gov NCT02474043; https://clinicaltrials.gov/ct2/show/NCT02474043 (Archived by WebCite at http://www.webcitation.org/6dbjUQG7J).

"Oops! I forgot HIV": resident physician self-audits and universal HIV screening.

BACKGROUND: Innovations are needed to increase universal HIV screening by primary care providers. One potential intervention is self-audit feedback, which describes the process of a clinician reviewing their own patient charts and reflecting on their performance. METHODS: The effectiveness of self-audit feedback was investigated using a mixed methods approach. A total of 2111 patient charts were analyzed in a quantitative pre-post intervention study design, where the intervention was providing self-audit feedback to all internal medicine residents at one institution through an annual chart review. Qualitative data generated from the subsequent resident focus group discussions explored the motivation and mechanism for change using a knowledge-attitude-behavior framework. RESULTS: The proportion of primary care patients screened for HIV increased from 17.9% (190/1060) to 40.3% (423/1051). The adjusted odds ratio of a patient being screened following resident self-audited feedback was 3.17 (95% CI 2.11, 4.76, p<0.001). Focus group participants attributed the improved performance to the self-audit feedback. CONCLUSIONS: Self-audit feedback is a potentially effective intervention for increasing universal HIV screening in primary care. This strategy may be most useful in settings where (1) baseline performance is low, (2) behavioral change is provider-driven, and (3) resident trainees are targeted.

Outcomes of Clostridium difficile infection in recipients of solid abdominal organ transplants.

Knowledge of outcomes of Clostridium difficile infection (CDI) in solid organ transplant (SOT) recipients is limited. To evaluate this population, we undertook a retrospective cohort study of all recipients of kidney and liver transplants diagnosed with CDI at a single center over 14 yr. Data pertaining to all episodes of CDI were collected. Multivariate analysis using logistic regression was performed to determine independent predictors of clinical cure. Overall, 170 patients developed 215 episodes of CDI. Among these patients, 162 episodes (75%) were cured, and in 103 episodes (48%), patients were cured within 14 d. In a multivariate analysis, lack of clinical cure at 14 d was predicted by recurrent episode (0.21, 95% CI 0.06-0.72, p = 0.0128), treatment with vancomycin (OR 0.27, 95% CI 0.1-0.74, p = 0.011), vasopressor support (OR 0.23, 95% CI 0.07-0.76, p = 0.0161), and CDI before the year 2004 (OR 0.44, 95% CI 0.2-0.98, p = 0.0446). The latter three factors are likely markers for severity of illness. In this cohort, 13 patients (8%) died during hospitalization, and 49 patients (29%) died within one yr. No deaths were attributed to CDI. Recurrent episode was a major predictor of treatment failure, suggesting that research into development of therapeutic options for recurrent disease is needed.

Low HDL Cholesterol is Associated with Lower Gray Matter Volume in Cognitively Healthy Adults.

Dyslipidemia is common in adults and contributes to high rates of cardiovascular disease and may be linked to subsequent neurodegenerative and neurovascular diseases. This study examined whether lower brain volumes and cognition associated with dyslipidemia could be observed in cognitively healthy adults, and whether apolipoprotein E (APOE) genotype or family history of Alzheimer's disease (FHAD) alters this effect. T1-weighted magnetic resonance imaging was used to examine regional brain gray matter (GM) and white matter (WM) in 183 individuals (58.4 +/- 8.0 years) using voxel-based morphometry. A non-parametric multiple linear regression model was used to assess the effect of high-density lipoprotein (HDL) and non-HDL cholesterol, APOE, and FHAD on regional GM and WM volume. A post hoc analysis was used to assess whether any significant correlations found within the volumetric analysis had an effect on cognition. HDL was positively correlated with GM volume in the bilateral temporal poles, middle temporal gyri, temporo-occipital gyri, and left superior temporal gyrus and parahippocampal region. This effect was independent of APOE and FHAD. A significant association between HDL and the Brief Visuospatial Memory Test was found. Additionally, GM volume within the right middle temporal gyrus, the region most affected by HDL, was significantly associated with the Controlled Oral Word Association Test and the Center for Epidemiological Studies Depression Scale. These findings suggest that adults with decreased levels of HDL cholesterol may be experiencing cognitive changes and GM reductions in regions associated with neurodegenerative disease and therefore, may be at greater risk for future cognitive decline.

Effects of simvastatin on cerebrospinal fluid biomarkers and cognition in middle-aged adults at risk for Alzheimer's disease.

BACKGROUND: Statins reduce amyloid-beta (Abeta) levels in the brain and cerebrospinal fluid (CSF) in animals and may thereby favorably alter the pathobiology of AD. It is unclear if statins modify Abeta metabolism or improve cognition in asymptomatic middle-aged adults at increased risk for AD. METHODS: In a 4-month randomized, double-blind, controlled study, we evaluated the effects of simvastatin 40 mg daily vs. placebo on CSF Abeta42 levels and cognition in 57 asymptomatic middle-aged adult children of persons with AD. RESULTS: Compared to placebo, individuals randomized to simvastatin for 4 months had similar changes in CSF Abeta42 (p=0.344) and total tau levels (p=0.226), yet greater improvements in some measures of verbal fluency (p=0.024) and working memory (p=0.015). APOE4 genotype, gender, and vascular risk factors were associated with CSF biomarker levels, but did not modify treatment effects. CONCLUSION: In asymptomatic middle-aged adults at increased risk for AD, simvastatin use improved selected measures of cognitive function without significantly changing CSF Abeta42 or total tau levels. Further studies are needed to clarify the impact of higher dose and/or longer duration statin therapy on not only Abeta metabolism, but also other preclinical processes related to the development of AD.

fMRI activation during episodic encoding and metacognitive appraisal across the lifespan: risk factors for Alzheimer's disease.

In the present study, we used fMRI to examine the influence of age on two other known risk factors for Alzheimer's disease (AD), APOE genotype and parental history of AD (FH status), during episodic encoding (ENC) and metacognitive self-appraisal (SA) paradigms. These paradigms have previously been shown to evoke activity from brain regions that are implicated in AD. First we examined the effect of age across the adult lifespan (age 18-84 years) on cerebral activity in a large sample (n=231) of cognitively healthy individuals. Next we examined a subset (n=155) on whom APOE status and FH status were known. For ENC, we found that increasing age was associated with reduced activity in the ventral temporal lobes and hippocampus. Our analysis of risk factors suggested that FH and age exerted independent effects, but APOE interacted with age such that APOE e4 carriers exhibit age-related increases in activity in the hippocampus. For the metacognitive SA task, increasing age was found to be associated with reduced activity in the medial prefrontal cortex, and increased activity in the mesial temporal lobe, posterior orbital cortex and striatum. Neither AD risk factor significantly modified age-related changes in brain activity during SA. These results suggest that FH and aging are exerting independent effects in both tasks while APOE affected the relationship with age in the hippocampus in one of the two tasks given.

Effect of Alzheimer disease risk on brain function during self-appraisal in healthy middle-aged adults.

CONTEXT: Asymptomatic middle-aged adult children of patients with Alzheimer disease (AD) recently were found to exhibit functional magnetic resonance imaging (fMRI) deficits in the mesial temporal lobe during an encoding task. Whether this effect will be observed on other fMRI tasks is yet unknown. This study examines the neural substrates of self-appraisal (SA) in persons at risk for AD. Accurate appraisal of deficits is a problem for many patients with AD, and prior fMRI studies of healthy young adults indicate that brain areas vulnerable to AD such as the anterior mesial temporal lobe and posterior cingulate are involved during SA tasks. OBJECTIVE: To determine whether parental family history of AD (hereafter referred to as FH) or presence of the epsilon4 allele of the apolipoprotein E gene (APOE4) exerts independent effects on brain function during SA. DESIGN: Cross-sectional factorial design in which APOE4 status (present vs absent) was one factor and FH was the other. All participants received cognitive testing, genotyping, and an fMRI task that required subjective SA decisions regarding trait adjective words in comparison with semantic decisions about the same words. SETTING: An academic medical center with a research-dedicated 3.0-T MR imaging facility. PARTICIPANTS: Cognitively normal middle-aged adults (n = 110), 51 with an FH and 59 without an FH. MAIN OUTCOME MEASURE: Blood oxygen-dependent contrast measured using T2*-weighted echo-planar imaging. RESULTS: Parental family history of AD and APOE4 status interacted in the posterior cingulate and left superior and medial frontal regions. There were main effects of FH (FH negative > FH positive) in the left hippocampus and ventral posterior cingulate. There were no main effects of APOE genotype. CONCLUSIONS: Our results suggest that FH may affect brain function during subjective SA in regions commonly affected by AD. Although the participants in this study were asymptomatic and middle-aged, the findings suggest that there may be subtle alterations in brain function attributable to AD risk factors.

Longitudinal changes in global brain volume between 79 and 409 days after traumatic brain injury: relationship with duration of coma.

Neuropathological and experimental animal studies indicate that traumatic brain injury (TBI) results in long-term, neurodegenerative changes. Structural image evaluation using normalization of atrophy (SIENA) offers an automated analysis of the subtle changes in percent brain volume change (%BVC) associated with TBI. In the present study, SIENA was used to evaluate %BVC in individuals who had sustained a mild to severe TBI. We obtained three-dimensional (3D) T1-weighted anatomical magnetic resonance imaging (MRI) scans approximately 79 days and again 409 days post-injury. TBI patients (n = 37) displayed significantly greater decline in %BVC (-1.43%) relative to a normal comparison group (+0.1%, n = 30). Greater %BVC was associated with longer duration of post-injury coma. These results confirm previous findings from cross-sectional studies and argue that the brain undergoes continued structural change for several months post-injury.

Celecoxib for the prevention of sporadic colorectal adenomas.

BACKGROUND: Studies showing that drugs that inhibit cyclooxygenase-2 (COX-2) reduce the number of colorectal adenomas in animals and patients with familial adenomatous polyposis suggest that COX-2 inhibitors may also prevent sporadic colorectal neoplasia. METHODS: We randomly assigned patients who had adenomas removed before study entry to receive placebo (679 patients) or 200 mg (685 patients) or 400 mg (671 patients) of celecoxib twice daily. Randomization was stratified for the use of low-dose aspirin. Follow-up colonoscopies were performed at one and three years after randomization. The occurrence of newly detected colorectal adenomas was compared among the groups with the life-table extension of the Mantel-Haenszel test. RESULTS: Follow-up colonoscopies were completed at year 1 in 89.5 percent of randomized patients, and at year 3 in 75.7 percent. The estimated cumulative incidence of the detection of one or more adenomas by year 3 was 60.7 percent for patients receiving placebo, as compared with 43.2 percent for those receiving 200 mg of celecoxib twice a day (risk ratio, 0.67; 95 percent confidence interval, 0.59 to 0.77; P<0.001) and 37.5 percent for those receiving 400 mg of celecoxib twice a day (risk ratio, 0.55; 95 percent confidence interval, 0.48 to 0.64; P<0.001). Serious adverse events occurred in 18.8 percent of patients in the placebo group, as compared with 20.4 percent of those in the low-dose celecoxib group (risk ratio, 1.1; 95 percent confidence interval, 0.9 to 1.3; P=0.5) and 23.0 percent of those in the high-dose group (risk ratio, 1.2; 95 percent confidence interval, 1.0 to 1.5; P=0.06). As compared with placebo, celecoxib was associated with an increased risk of cardiovascular events (risk ratio for the low dose, 2.6; 95 percent confidence interval, 1.1 to 6.1; and risk ratio for the high dose, 3.4; 95 percent confidence interval, 1.5 to 7.9). CONCLUSIONS: These findings indicate that celecoxib is an effective agent for the prevention of colorectal adenomas but, because of potential cardiovascular events, cannot be routinely recommended for this indication. (ClinicalTrials.gov number, NCT00005094 [ClinicalTrials.gov].).