Erratum: Toward standardization, harmonization, and integration of social determinants of health data: A Texas Clinical and Translational Science Award institutions collaboration - CORRIGENDUM.

[This corrects the article DOI: 10.1017/cts.2024.2.].

Increasing and sustaining discharges by noon - a multi-year process improvement project.

High hospital occupancy degrades emergency department performance by increasing wait times, decreasing patient satisfaction, and increasing patient morbidity and mortality. Late discharges contribute to high hospital occupancy by increasing emergency department (ED) patient length of stay (LOS). We share our experience with increasing and sustaining early discharges at a 650-bed academic medical center in the United States. Our process improvement project followed the Institute of Medicine Model for Improvement of successive Plan‒Do‒Study‒Act cycles. We implemented multiple iterative interventions over 41 months. As a result, the proportion of discharge orders before 10 am increased from 8.7% at baseline to 22.2% (p < 0.001), and the proportion of discharges by noon (DBN) increased from 9.5% to 26.8% (p < 0.001). There was no increase in balancing metrics because of our interventions. RA-LOS (Risk Adjusted Length Of Stay) decreased from 1.16 to 1.09 (p = 0.01), RA-Mortality decreased from 0.65 to 0.61 (p = 0.62) and RA-Readmissions decreased from 0.92 to 0.74 (p < 0.001). Our study provides a roadmap to large academic facilities to increase and sustain the proportion of patients discharged by noon without negatively impacting LOS, 30-day readmissions, and mortality. Continuous performance evaluation, adaptability to changing resources, multidisciplinary engagement, and institutional buy-in were crucial drivers of our success.

Facilitators of and barriers to gastric cancer and precursor diagnosis among South Texas residents: Social determinants of health.

BACKGROUND: Latinos/Hispanics are at higher risk for developing gastric cancer (GC) compared with non-Hispanic whites, and social determinants of health (SDoH) are thought to contribute. AIMS/MATERIALS AND METHODS: This study addressed SDoH and their interactions contributing to disparities in the testing and treatment of Helicobacter pylori (HP) infection and diagnosis of GC and its known precursors, among Latinos/Hispanics relative to non-Latinos at two affiliated but independent health systems in San Antonio, Texas, using a mixed methods approach. RESULTS: Secondary data abstraction and analysis showed that GCs represented 2.6% (n = 600) of our population. Men and older individuals were at higher GC risk. Individuals with military insurance were 2.7 times as likely to be diagnosed as private insurance. Latinos/Hispanics had significantly (24%) higher GC risk than Whites. Poverty and lack of insurance contributed to GC risk among the minorities classified as other (Asians, Native Americans, Multiracial; all p < 0.01). All SDoH were associated with H. pylori infection (p < 0.001). Qualitative analysis of patient and provider interviews showed providers reporting insurance as a major care barrier; patients reported appointment delays, and lack of clinic staff. Providers universally agreed treatment of H. pylori was necessary, but disagreed on its prevalence. Patients did not report discussing H. pylori or its cancer risk with providers. DISCUSSION/CONCLUSION: These data indicate the importance of considering SDoH in diagnosis and treatment of GC and its precursors, and educating providers and patients on H. pylori risks for GC.

Toward standardization, harmonization, and integration of social determinants of health data: A Texas Clinical and Translational Science Award institutions collaboration.

Introduction: The focus on social determinants of health (SDOH) and their impact on health outcomes is evident in U.S. federal actions by Centers for Medicare & Medicaid Services and Office of National Coordinator for Health Information Technology. The disproportionate impact of COVID-19 on minorities and communities of color heightened awareness of health inequities and the need for more robust SDOH data collection. Four Clinical and Translational Science Award (CTSA) hubs comprising the Texas Regional CTSA Consortium (TRCC) undertook an inventory to understand what contextual-level SDOH datasets are offered centrally and which individual-level SDOH are collected in structured fields in each electronic health record (EHR) system potentially for all patients. Methods: Hub teams identified American Community Survey (ACS) datasets available via their enterprise data warehouses for research. Each hub's EHR analyst team identified structured fields available in their EHR for SDOH using a collection instrument based on a 2021 PCORnet survey and conducted an SDOH field completion rate analysis. Results: One hub offered ACS datasets centrally. All hubs collected eleven SDOH elements in structured EHR fields. Two collected Homeless and Veteran statuses. Completeness at four hubs was 80%-98%: Ethnicity, Race; < 10%: Education, Financial Strain, Food Insecurity, Housing Security/Stability, Interpersonal Violence, Social Isolation, Stress, Transportation. Conclusion: Completeness levels for SDOH data in EHR at TRCC hubs varied and were low for most measures. Multiple system-level discussions may be necessary to increase standardized SDOH EHR-based data collection and harmonization to drive effective value-based care, health disparities research, translational interventions, and evidence-based policy.

New C-indices for assessing importance of longitudinal biomarkers in fitting competing risks survival data in the presence of partially masked causes.

Competing risks survival data in the presence of partially masked causes are frequently encountered in medical research or clinical trials. When longitudinal biomarkers are also available, it is of great clinical importance to examine associations between the longitudinal biomarkers and the cause-specific survival outcomes. In this article, we propose a cause-specific C-index for joint models of longitudinal and competing risks survival data accounting for masked causes. We also develop a posterior predictive algorithm for computing the out-of-sample cause-specific C-index using Markov chain Monte Carlo samples from the joint posterior of the in-sample longitudinal and competing risks survival data. We further construct the Δ $$ \Delta $$ C-index to quantify the strength of association between the longitudinal and cause-specific survival data, or between the out-of-sample longitudinal and survival data. Empirical performance of the proposed assessment criteria is examined through an extensive simulation study. An in-depth analysis of the real data from large cancer prevention trials is carried out to demonstrate the usefulness of the proposed methodology.

Outcome of pulpotomy in permanent teeth with irreversible pulpitis: a systematic review and meta-analysis.

Treatment planning is key to clinical success. Permanent teeth diagnosed with "irreversible pulpitis" have long been implied to have an irreversibly damaged dental pulp that is beyond repair and warranting root canal treatment. However, newer clinical approaches such as pulpotomy, a minimally invasive and biologically based procedure have re-emerged to manage teeth with pulpitis. The primary aim of the study was to conduct a meta-analysis to comprehensively estimate the overall success rate of pulpotomy in permanent teeth with irreversible pulpitis as a result of carious pulp exposure. The secondary aim of the study was to investigate the effect of predictors such as symptoms, root apex development (closed versus open), and type of pulp capping material on the success rate of pulpotomy. Articles were searched using PubMed, Scopus, CENTRAL, and Web of Science databases, until January 2021. Outcomes were calculated by pooling the success rates with a random effect model. Comparison between the different subgroups was conducted using the z statistic test for proportion with significance set at alpha = 0.05. A total of 1,116 records were retrieved and 11 studies were included in the quantitative analysis. The pooled success rate for pulpotomy in teeth with irreversible pulpitis was 86% [95% CI: 0.76-0.92; I2 = 81.9%]. Additionally, prognostic indicators of success were evaluated. Stratification of teeth based on (1) symptoms demonstrated that teeth with symptomatic and asymptomatic irreversible pulpitis demonstrated success rate of 84% and 91% respectively, with no significant difference (p = 0.18) using z-score analysis; (2) open apex teeth demonstrated a significantly greater success rate (96%) compared to teeth with closed apex (83%) (p = 0.02), and (3) pulp capping materials demonstrated that Biodentine yielded significantly better success rates compared to Mineral Trioxide Aggregate (MTA), calcium hydroxide, and Calcium Enriched Mixture (CEM.) Collectively, this is the first meta-analytical study to determine the clinical outcome of pulpotomy for carious teeth with irreversible pulpitis and it's predictors for success. Moreover, we identify the stage of root development and type of biomaterial as predictors for success of pulpotomy.

Nasal and Parotid Blood Pool Activity Is Significantly Correlated with Metabolic Syndrome Components and Sleep Apnea.

Background: Patients with metabolic syndrome components were frequently noted to have increased nasal and parotid activity on clinically referred scintigraphic whole-body blood pool scans. This increase in activity was not observed in patients without metabolic syndrome. Increased nasal blood pool activity in patients with elevated body mass indices (BMIs) has implications for (1) sleep apnea, (2) risk of nasal infection, and (3) possible impaired nasal lymphatic drainage of brain waste proteins. Methods: To follow-up this clinical observation, a retrospective study was performed on 200 patients having whole-body blood pool scans referred over a 3-year period. The whole-body blood pool scans were evaluated for an association between nose and parotid region of interest (ROI) to heart ROI maximum (max) pixel ratios as correlated with clinical conditions, including obesity, diabetes, hypertension, and sleep apnea. Continuous variables of BMI, hemoglobin A1c (HbA1c), blood glucose, and blood lipids were also correlated with these ratios. Results: A direct association of nose to heart max ratio (NHMR) with diabetes, sleep apnea, and hypertension was found with an increase in the ratio of +0.10 (P = 0.002), +0.13 (P = 0.0002), +0.08 (P = 0.0123), respectively. Correlation of NHMR with continuous variables had moderate correlation with BMI (r = 0.36, P < 0.0001), glucose (r = 0.27, P = 0.0001), HbA1c (r = 0.25, P = 0.0008) and less association with the number of diabetes medications (r = 0.22, P = 0.0021). Similar associations were found for parotid to heart max ratios but were weaker than the NHMR. Conclusions: Patients with metabolic syndrome components have significantly increased nasal and parotid activity on blood pool scans. These associations have implications for the treatment of sleep apnea, for nasal infections involving such agents as Covid-19, and for the risk of dementias related to decreased clearance of brain waste proteins through nasal turbinate lymphatics in patients with metabolic syndrome. If further studies support these findings, the nasal turbinates and the increased parasympathetic activity controlling their dilation could become a new therapeutic target.

Children's Afterschool Culinary Education Improves Eating Behaviors.

Objectives: Culinary education may be one way to improve children's eating behaviors. We formatively evaluated the effect of a hands-on afterschool 12-module, registered dietitian-led culinary education program on healthy eating behaviors in a predominately Hispanic/Latino, low-socioeconomic community. Methods: Of 234 children participating in the program, 77% completed both pre- and post-assessment surveys (n = 180; mean age 9.8 years; 63.3% female; 74.3% Hispanic/Latino, 88.4% receiving free/reduced lunch). In addition to program satisfaction, we assessed changes in children's self-reported fruit, vegetable, and whole-grain consumption, knowledge, and culinary skills using binary and continuous mixed effects models. We report false discovery rate adjusted p-values and effect sizes. Results: 95.5% of participants reported liking the program. Improved whole grain consumption had a medium effect size, while effect sizes for whole grain servings and vegetable consumption were small, but significant (all p < 0.05). Culinary skills increased between 15.1 to 43.4 percent points (all p < 0.01), with medium to large effect sizes. Conclusions: The program was well-received by participants. Participants reported improved eating behaviors and culinary skills after program completion. Therefore, this hands-on afterschool culinary education program can help improve healthy eating in a predominantly Hispanic/Latino, low-socioeconomic community.

Prediction of future risk of any and higher-grade prostate cancer based on the PLCO and SELECT trials.

BACKGROUND: A model was built that characterized effects of individual factors on five-year prostate cancer (PCa) risk in the Prostate, Lung, Colon, and Ovarian Cancer Screening Trial (PLCO) and the Selenium and Vitamin E Cancer Prevention Trial (SELECT). This model was validated in a third San Antonio Biomarkers of Risk (SABOR) screening cohort. METHODS: A prediction model for 1- to 5-year risk of developing PCa and Gleason > 7 PCa (HG PCa) was built on PLCO and SELECT using the Cox proportional hazards model adjusting for patient baseline characteristics. Random forests and neural networks were compared to Cox proportional hazard survival models, using the trial datasets for model building and the SABOR cohort for model evaluation. The most accurate prediction model is included in an online calculator. RESULTS: The respective rates of PCa were 8.9%, 7.2%, and 11.1% in PLCO (n = 31,495), SELECT (n = 35,507), and SABOR (n = 1790) over median follow-up of 11.7, 8.1 and 9.0 years. The Cox model showed higher prostate-specific antigen (PSA), BMI and age, and African American race to be associated with PCa and HGPCa. Five-year risk predictions from the combined SELECT and PLCO model effectively discriminated risk in the SABOR cohort with C-index 0.76 (95% CI [0.72, 0.79]) for PCa, and 0.74 (95% CI [0.65,0.83]) for HGPCa. CONCLUSIONS: A 1- to 5-year PCa risk prediction model developed from PLCO and SELECT was validated with SABOR and implemented online. This model can individualize and inform shared screening decisions.

γδ T Cells Support Antigen-Specific αß T cell-Mediated Antitumor Responses during BCG Treatment for Bladder Cancer.

Bacillus Calmette-Guérin (BCG) is the most effective intravesical agent at reducing recurrence for patients with high-grade, non-muscle-invasive bladder cancer. Nevertheless, response to BCG is variable and strategies to boost BCG efficacy have not materialized. Prior work demonstrated a requirement for either conventional αß or nonconventional γδ T cells in mediating BCG treatment efficacy, yet the importance of T-cell antigen specificity for BCG's treatment effect is unclear. Here, we provide direct evidence to show that BCG increases the number of tumor antigen-specific αß T cells in patients with bladder cancer and protects mice from subsequent same-tumor challenge, supporting BCG induction of tumor-specific memory and protection. Adoptive T-cell transfers of antigen-specific αß T cells into immunodeficient mice challenged with syngeneic MB49 bladder tumors showed that both tumor and BCG antigen-specific αß T cells contributed to BCG efficacy. BCG-specific antitumor immunity, however, also required nonconventional γδ T cells. Prior work shows that the mTOR inhibitor rapamycin induces the proliferation and effector function of γδ T cells. Here, rapamycin increased BCG efficacy against both mouse and human bladder cancer in vivo in a γδ T cell-dependent manner. Thus, γδ T cells augment antitumor adaptive immune effects of BCG and support rapamycin as a promising approach to boost BCG efficacy in the treatment of non-muscle-invasive bladder cancer.

San Antonio Nathan Shock Center: your one-stop shop for aging research.

With evolving cores, enrichment and training programs, and supported research projects, the San Antonio (SA) Nathan Shock Center has for 26 years provided critical support to investigators locally, nationally, and abroad. With its existing and growing intellectual capital, the SA Nathan Shock Center provides to local and external investigators an enhanced platform to conduct horizontally integrated (lifespan, healthspan, pathology, pharmacology) transformative research in the biology of aging, and serves as a springboard for advanced educational and training activities in aging research. The SA Nathan Shock Center consists of six cores: Administrative/Program Enrichment Core, Research Development Core, Aging Animal Models and Longevity Assessment Core, Pathology Core, Analytical Pharmacology and Drug Evaluation Core, and Integrated Physiology of Aging Core. The overarching goal of the SA Nathan Shock Center is to advance knowledge in the basic biology of aging and to identify molecular and cellular mechanisms that will facilitate the development of pharmacologic interventions and other strategies to extend healthy lifespan. In pursuit of this goal, we provide an innovative "one-stop shop" venue to accelerate transformative research in the biology of aging through our integrated research cores. Moreover, we aim to foster and promote career development of early-stage investigators in aging biology through our research development programs, to serve as a resource and partner to investigators from other Shock Centers, and to disseminate scientific knowledge and enhanced awareness about aging research. Overall, the SA Nathan Shock Center aims to be a leader in research that advances our understanding of the biology of aging and development of approaches to improve longevity and healthy aging.

Joint modelling of longitudinal and survival data in the presence of competing risks with applications to prostate cancer data.

This research is motivated from the data from a large Selenium and Vitamin E Cancer Prevention Trial (SELECT). The prostate specific antigens (PSAs) were collected longitudinally, and the survival endpoint was the time to low-grade cancer or the time to high-grade cancer (competing risks). In this article, the goal is to model the longitudinal PSA data and the time-to-prostate cancer (PC) due to low- or high-grade. We consider the low-grade and high-grade as two competing causes of developing PC. A joint model for simultaneously analysing longitudinal and time-to-event data in the presence of multiple causes of failure (or competing risk) is proposed within the Bayesian framework. The proposed model allows for handling the missing causes of failure in the SELECT data and implementing an efficient Markov chain Monte Carlo sampling algorithm to sample from the posterior distribution via a novel reparameterization technique. Bayesian criteria, ΔDICSurv, and ΔWAICSurv, are introduced to quantify the gain in fit in the survival sub-model due to the inclusion of longitudinal data. A simulation study is conducted to examine the empirical performance of the posterior estimates as well as ΔDICSurv and ΔWAICSurv and a detailed analysis of the SELECT data is also carried out to further demonstrate the proposed methodology.

Mobilization-based transplantation of young-donor hematopoietic stem cells extends lifespan in mice.

Mammalian aging is associated with reduced tissue regeneration and loss of physiological integrity. With age, stem cells diminish in their ability to regenerate adult tissues, likely contributing to age-related morbidity. Thus, we replaced aged hematopoietic stem cells (HSCs) with young-donor HSCs using a novel mobilization-enabled hematopoietic stem cell transplantation (HSCT) technology as an alternative to the highly toxic conditioning regimens used in conventional HSCT. Using this approach, we are the first to report an increase in median lifespan (12%) and a decrease in overall mortality hazard (HR: 0.42, CI: 0.273-0.638) in aged mice following transplantation of young-donor HSCs. The increase in longevity was accompanied by reductions of frailty measures and increases in food intake and body weight of aged recipients. Young-donor HSCs not only preserved youthful function within the aged bone marrow stroma, but also at least partially ameliorated dysfunctional hematopoietic phenotypes of aged recipients. This compelling evidence that mammalian health and lifespan can be extended through stem cell therapy adds a new category to the very limited list of successful anti-aging/life-extending interventions. Our findings have implications for further development of stem cell therapies for increasing health and lifespan.

Growth recovery lines: a specific indicator of child abuse and neglect?

BACKGROUND: Growth recovery lines are radiodense lines in long bones reported to be indicators of stress. OBJECTIVE: The purpose of this study was to understand the distribution, quantity and associations of growth recovery lines in children ages 0-24 months with high and low risk for child maltreatment. MATERIALS AND METHODS: We conducted a retrospective cohort study of children ages 0-24 months who had skeletal surveys and an assessment for maltreatment. Growth recovery lines, fractures and osteopenia were assessed independently by two pediatric radiologists blinded to the abuse likelihood. RESULTS: Of the 135 children in this study, 58 were in the low-risk group, 26 were in the neglect group, and 51 were in the physical abuse group. Children in the neglected and physically abused groups had 1.73 times (95% confidence interval [CI] of 1.16, 2.59), P=0.007) and 1.84 times (95% CI 1.28, 2.63, P<0.001) more growth recovery lines than the low-risk group, respectively. Growth recovery lines occurred at an earlier age in the neglect group (age interaction P=0.03) and abuse group (age interaction P=0.01) compared to the low-risk group. The specificity for maltreatment in children with at least 10 growth recovery lines in the long bones was greater than 84%, while sensitivity was less than 35%. The most common locations for growth recovery lines were distal radius, proximal tibia and distal tibia. CONCLUSION: In the absence of a known major stressor, physical abuse and neglect should be considered in children younger than 24 months with at least 10 growth recovery lines.

Joint analysis of single-cell and bulk tissue sequencing data to infer intratumor heterogeneity.

Many computational methods have been developed to discern intratumor heterogeneity (ITH) using DNA sequence data from bulk tumor samples. These methods share an assumption that two mutations arise from the same subclone if they have similar mutant allele-frequencies (MAFs), and thus it is difficult or impossible to distinguish two subclones with similar MAFs. Single-cell DNA sequencing (scDNA-seq) data can be very informative for ITH inference. However, due to the difficulty of DNA amplification, scDNA-seq data are often very noisy. A promising new study design is to collect both bulk and single-cell DNA-seq data and jointly analyze them to mitigate the limitations of each data type. To address the analytic challenges of this new study design, we propose a computational method named BaSiC (Bulk tumor and Single Cell), to discern ITH by jointly analyzing DNA-seq data from bulk tumor and single cells. We demonstrate that BaSiC has comparable or better performance than the methods using either data type. We further evaluate BaSiC using bulk tumor and single-cell DNA-seq data from a breast cancer patient and several leukemia patients.

Does assisted hatching affect live birth in fresh, first cycle in vitro fertilization in good and poor prognosis patients?

PURPOSE: To assess the effect of assisted hatching (AH) on live birth rate (LBR) in first cycle, fresh in vitro fertilization (IVF) in good and poor prognosis patients. METHODS: Retrospective cohort using cycles reported to the Society for Assisted Reproductive Technology Clinic Outcomes Reporting System. Live birth rate was compared in women who underwent first cycle, autologous, fresh IVF cycles with (n = 48,858) and without (n = 103,413) AH from 2007 to 2015. RESULTS: The propensity-weighted LBR was 39.2% with AH versus 43.9% without AH in all patients. The rate difference (RD) with AH was - 4.7% ([CI - 0.053, - 0.040], P < 0.001) with the calculated number needed to harm being 22. AH affected live birth in both good prognosis and poor prognosis patients. The propensity-weighted monozygotic twinning (MZT) rate was 2.3% in patients treated with AH as compared to 1.2% patients that did not receive AH. The RD with AH on MZT in fresh, first IVF cycles was 1.1% ([0.008, 0.014], P < 0.001). CONCLUSION: AH may affect LBR across all patients and in poor prognosis patients in fresh IVF cycles. Caution should be exercised when applying this technology. More prospective research is needed.

Genetically heterogeneous mice exhibit a female survival advantage that is age- and site-specific: Results from a large multi-site study.

The female survival advantage is a robust characteristic of human longevity. However, underlying mechanisms are not understood, and rodent models exhibiting a female advantage are lacking. Here, we report that the genetically heterogeneous (UM-HET3) mice used by the National Institute on Aging Interventions Testing Program (ITP) are such a model. Analysis of age-specific survival of 3,690 control ITP mice revealed a female survival advantage paralleling that of humans. As in humans, the female advantage in mice was greatest in early adulthood, peaking around 350 days of age and diminishing progressively thereafter. This persistent finding was observed at three geographically distinct sites and in six separate cohorts over a 10-year period. Because males weigh more than females and bodyweight is often inversely related to lifespan, we examined sex differences in the relationship between bodyweight and survival. Although present in both sexes, the inverse relationship between bodyweight and longevity was much stronger in males, indicating that male mortality is more influenced by bodyweight than is female mortality. In addition, male survival varied more across site and cohort than female survival, suggesting greater resistance of females to environmental modulators of survival. Notably, at 24 months the relationship between bodyweight and longevity shifted from negative to positive in both sexes, similar to the human condition in advanced age. These results indicate that the UM-HET3 mouse models the human female survival advantage and provide evidence for greater resilience of females to modulators of survival.

Acarbose improves health and lifespan in aging HET3 mice.

To follow-up on our previous report that acarbose (ACA), a drug that blocks postprandial glucose spikes, increases mouse lifespan, we studied ACA at three doses: 400, 1,000 (the original dose), and 2,500 ppm, using genetically heterogeneous mice at three sites. Each dose led to a significant change (by log-rank test) in both sexes, with larger effects in males, consistent with the original report. There were no significant differences among the three doses. The two higher doses produced 16% or 17% increases in median longevity of males, but only 4% or 5% increases in females. Age at the 90th percentile was increased significantly (8%-11%) in males at each dose, but was significantly increased (3%) in females only at 1,000 ppm. The sex effect on longevity is not explained simply by weight or fat mass, which were reduced by ACA more in females than in males. ACA at 1,000 ppm reduced lung tumors in males, diminished liver degeneration in both sexes and glomerulosclerosis in females, reduced blood glucose responses to refeeding in males, and improved rotarod performance in aging females, but not males. Three other interventions were also tested: ursolic acid, 2-(2-hydroxyphenyl) benzothiazole (HBX), and INT-767; none of these affected lifespan at the doses tested. The acarbose results confirm and extend our original report, prompt further attention to the effects of transient periods of high blood glucose on aging and the diseases of aging, including cancer, and should motivate studies of acarbose and other glucose-control drugs in humans.

A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort: Immunological, physical performance, and cognitive effects.

Inhibition of the mechanistic target of rapamycin (mTOR) pathway by rapamycin (RAPA), an FDA-approved immunosuppressive drug used as a clinical therapy to prevent solid organ allograft rejection, enhances longevity in mice. Importantly, RAPA was efficacious even when initiated in relatively old animals, suggesting that mTOR inhibition could potentially slow the progression of aging-associated pathologies in older humans (Harrison et al., 2009; Miller et al., 2011). However, the safety and tolerability of RAPA in older human subjects have not yet been demonstrated. Towards this end, we undertook a placebo-controlled pilot study in 25 generally healthy older adults (aged 70-95 years); subjects were randomized to receive either 1 mg RAPA or placebo daily. Although three subjects withdrew, 11 RAPA and 14 controls completed at least 8 weeks of treatment and were included in the analysis. We monitored for changes that would indicate detrimental effects of RAPA treatment on metabolism, including both standard clinical laboratory assays (CBC, CMP, HbA1c) and oral glucose tolerance tests (OGTTs). We also monitored parameters typically associated with aging that could potentially be modified by RAPA; these included cognitive function which was assessed by three different tools: Executive Interview-25 (EXIT25); Saint Louis University Mental Status Exam (SLUMS); and Texas Assessment of Processing Speed (TAPS). In addition, physical performance was measured by handgrip strength and 40-foot timed walks. Lastly, changes in general parameters of healthy immune aging, including serum pro-inflammatory cytokine levels and blood cell subsets, were assessed. Five subjects reported potential adverse side effects; in the RAPA group, these were limited to facial rash (1 subject), stomatitis (1 subject) and gastrointestinal issues (2 subjects) whereas placebo treated subjects only reported stomatitis (1 subject). Although no other adverse events were reported, statistically significant decrements in several erythrocyte parameters including hemoglobin (HgB) and hematocrit (Hct) as well as in red blood cell count (RBC), red blood cell distribution width (RDW), mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH) were observed in the RAPA-treatment group. None of these changes manifested clinically significant effects during the short duration of this study. Similarly, no changes were noted in any other clinical laboratory, cognitive, physical performance, or self-perceived health status measure over the study period. Immune parameters were largely unchanged as well, possibly due to the advanced ages of the cohort (70-93 years; mean age 80.5). RAPA-associated increases in a myeloid cell subset and in TREGS were detected, but changes in most other PBMC cell subsets were not statistically significant. Importantly, the OGTTs revealed no RAPA-induced change in blood glucose concentration, insulin secretion, and insulin sensitivity. Thus, based on the results of our pilot study, it appears that short-term RAPA treatment can be used safely in older persons who are otherwise healthy; a trial with a larger sample size and longer treatment duration is warranted.

Limitations of multidetector computed tomography angiography for the diagnosis of blunt cerebrovascular injury.

OBJECTIVE Blunt cerebrovascular injuries (BCVIs) following trauma carry risk for morbidity and mortality. Since patients with BCVI are often asymptomatic at presentation and neurological sequelae often occur within 72 hours, timely diagnosis is essential. Multidetector CT angiography (CTA) has been shown to be a noninvasive, cost-effective, reliable means of screening; however, the false-positive rate of CTA in diagnosing patients with BCVI represents a key drawback. Therefore, the authors assessed the role of DSA in the screening of BCVI when utilizing CTA as the initial screening modality. METHODS The authors performed a retrospective analysis of patients who experienced BCVI between 2013 and 2015 at 2 Level I trauma centers. All patients underwent CTA screening for BCVI according to the updated Denver Screening Criteria. Patients who were diagnosed with BCVI on CTA underwent confirmatory digital subtraction angiography (DSA). Patient demographics, screening indication, BCVI grade on CTA and DSA, and laboratory values were collected. Comparison of false-positive rates stratified by BCVI grade on CTA was performed using the chi-square test. RESULTS A total of 140 patients (64% males, mean age 50 years) with 156 cerebrovascular blunt injuries to the carotid and/or vertebral arteries were identified. After comparison with DSA findings, CTA findings were incorrect in 61.5% of vessels studied, and the overall CTA false-positive rates were 47.4% of vessels studied and 47.9% of patients screened. The positive predictive value (PPV) for CTA was higher among worse BCVI subtypes on initial imaging (PPV 76% and 97%, for BCVI Grades II and IV, respectively) compared with Grade I injuries (PPV 30%, p < 0.001). CONCLUSIONS In the current series, multidetector CTA as a screening test for blunt cerebrovascular injury had a high-false positive rate, especially in patients with Grade I BCVI. Given a false-positive rate of 47.9% with an estimated average of 132 patients per year screening positive for BCVI with CTA, approximately 63 patients per year would potentially be treated unnecessarily with antithrombotic therapy at a busy United States Level I trauma center. The authors' data support the use of DSA after positive findings on CTA in patients with suspected BCVI. DSA as an adjunctive test in patients with positive CTA findings allows for increased diagnostic accuracy in correctly diagnosing BCVI while minimizing risk from unnecessary antithrombotic therapy in polytrauma patients.