A Direct Assessment of Noninvasive Continuous Blood Pressure Monitoring in the Emergency Department and Intensive Care Unit.

INTRODUCTION: Noninvasive continuous blood pressure monitoring has the potential to improve patient treatment in the hospital setting. Such noninvasive devices can be applied earlier in the treatment process to empower nurses and clinicians to react more quickly to patient deterioration with the added benefit of eliminating the risks associated with invasive monitoring. However, emerging technologies must be capable of reproducing current clinical measures for medical decision making. METHODS: This study aimed to determine the usability and willingness of nurses to implement a noninvasive continuous blood pressure monitoring device. The secondary aim directly compared the systolic blood pressure, diastolic blood pressure, and mean arterial pressure values recorded by the device (VitalStream; CareTaker Medical LLC, Charlottesville, VA) with the "gold standard" brachial cuff and arterial line measures recorded in the emergency department and intensive care unit settings. RESULTS: VitalStream was similarly received by nurses in the emergency department and intensive care setting, but ultimately had greater promotion from emergency nurses. Despite some statistical similarity between measurement methodologies, all direct comparisons were found to not meet the Association for the Advancement of Medical Instrumentation 2008 and Association for the Advancement of Medical Instrumentation / European Society of Hypertension / International Organization for Standardization 2019 consensus statement criteria for acceptable blood pressure measure differences between the VitalStream and "gold standard" clinical measures. In all instances, the standard deviation of the Bland-Altman bias exceeded 8 mm Hg with less than 85% of paired differences falling within 10 mm Hg of the "gold standard." DISCUSSION: Taken together, the tested device requires additional postprocessing for medical decision making in trauma or emergent care.

Building capacity for ATLS trauma education: role of nurse practitioners and physician assistants.

Objectives: Advanced Trauma Life Support (ATLS) focuses on care of injured patients in the first hour of resuscitation. Expanded demand for courses has led to a concurrent need for new instructors. Nurse practitioners and physician assistants (NPs/PAs) work on trauma services and duties include patient, staff, and outreach education. The goal of this project was to assess NP/PA self-reported knowledge and skills pertinent to ATLS and identify potential barriers to becoming instructors. Materials: This was a voluntary 91-question survey emailed to NP/PA lists obtained from professional societies and online social media channels. NPs/PAs completed a survey reflecting self-reported knowledge, experience, comfort level, and barriers to teaching ATLS interactive discussions and skills. Responses were recorded using a Likert scale and results were documented as percentages. Number of years of experience versus perceived knowledge and comfort teaching were compared using a χ2 test of independence. Results: There were 1696 completed surveys. Most NPs/PAs thought they had adequate knowledge and experience to teach interactive discussions and skills. Those with more years of experience and those who completed more ATLS courses had higher percentages. The number 1 barrier to teaching was lack of formal teaching experience followed by perceived hierarchy concerns. Experience and comfort with skills that fell below 50% were pediatric airway (49.5%), needle and surgical cricothyrotomy (49.8% and 44.8%), diagnostic peritoneal lavage (21.6%), and venous cutdown (20.8%). Conclusion: NPs/PAs with experience in trauma reported having the knowledge and skill to teach ATLS. A majority are comfortable teaching interactive discussions and skills for which they are knowledgeable. The primary barrier to teaching was lack of formal teaching experience, which is covered in the ATLS Instructor course. Training NPs/PAs to become instructors would increase the instructor base and allow for increased promulgation of ATLS and trauma education. Level of evidence: IV.

Missed blunt cerebrovascular injuries using current screening criteria - The time for liberalized screening is now.

Diagnostic Criteria Study BACKGROUND: The morbidity and mortality associated with ischemic stroke attributable to blunt cerebrovascular injury (BCVI) warrant aggressive screening. The Denver Criteria (DC) and Expanded Denver Criteria (eDC) have imprecise elements that can be difficult and subjective in application and can delay or prevent screening. We hypothesize these screening criteria lack adequate ability to consistently identify BCVI and that the use of a liberalized screening approach with CT angiography (CTA) is superior without increasing risk of acute kidney injury (AKI). METHODS: This was a multi-institutional retrospective cohort study of trauma patients who presented between 2015-2020 with radiographically confirmed BCVI diagnosed using each institutions' liberalized screening protocol, defined as automatic CTA of the head and neck for all patients undergoing head and neck CT. Outcomes of interest included AKI, stroke, and death due to BCVI. Outcomes were reported as frequency, percent, and 95% confidence interval as calculated by the Clopper-Pearson method. Incidence of medical follow-up within 1 year of first medical visit was quantified as the median and inter-quartile range of days to follow-up visit. RESULTS: We identified 433 BCVI patients with a mean age of 45.2 (standard deviation 18.9) years, 256 men and 177 women, 1.73 m (0.10) tall, and weighed 80.3 kg (20.3). Forty-one patients had strokes (9.5% [95% confidence interval 6.9, 12.6] and 12 patients (2.8% [1.4, 4.5]) had mortality attributable to BCVI. Of 433 total cases, 132 (30.5% [26.2, 35.1]) would have been missed by DC and 150 (34.6% [30.2, 39.3]) by eDC. Incidence of AKI in our BCVI population was 6 (1.4% [0.01, 3.0]). CONCLUSIONS: BCVI would be missed over 30% of the time using the DC and eDC compared to liberalized use of screening CTA. Risk of AKI due to CTA did not occur at a clinically meaningful level, supporting liberal CTA screening.

Persistent CD8+ T cell proliferation and activation in COVID-19 adult survivors with post-acute sequelae: a longitudinal, observational cohort study of persistent symptoms and T cell markers.

Introduction: Post-acute sequelae of COVID-19 affects the quality of life of many COVID-19 survivors, yet the etiology of post-acute sequelae of COVID-19 remains unknown. We aimed to determine if persistent inflammation and ongoing T-cell activation during convalescence were a contributing factor to the pathogenesis of post-acute sequelae of COVID-19. Methods: We evaluated 67 individuals diagnosed with COVID-19 by nasopharyngeal polymerase chain reaction for persistent symptoms during convalescence at separate time points occurring up to 180 days post-diagnosis. Fifty-two of these individuals were evaluated longitudinally. We obtained whole blood samples at each study visit, isolated peripheral blood mononuclear cells, and stained for multiple T cell activation markers for flow cytometry analysis. The activation states of participants' CD4+ and CD8+ T-cells were next analyzed for each of the persistent symptoms. Results: Overall, we found that participants with persistent symptoms had significantly higher levels of inflammation at multiple time points during convalescence when compared to those who fully recovered from COVID-19. Participants with persistent dyspnea, forgetfulness, confusion, and chest pain had significantly higher levels of proliferating effector T-cells (CD8+Ki67+), and those with chest pain, joint pain, difficulty concentrating, and forgetfulness had higher levels of regulatory T-cells (CD4+CD25+). Additionally, those with dyspnea had significantly higher levels of CD8+CD38+, CD8+ Granzyme B+, and CD8+IL10+ cells. A retrospective comparison of acute phase inflammatory markers in adults with and without post-acute sequelae of COVID-19 showed that CD8+Ki67+ cells were significantly higher at the time of acute illness (up to 14 days post-diagnosis) in those who developed persistent dyspnea. Discussion: These findings suggest continued CD8+ T-cell activation following SARS-CoV-2 infection in adults experiencing post-acute sequelae of COVID-19 and that the increase in T regulatory cells for a subset of these patients represents the ongoing attempt by the host to reduce inflammation.

Correlation between 25-hydroxyvitamin D/D3 Deficiency and COVID-19 Disease Severity in Adults from Northern Colorado.

Vitamin D deficiency is common in the United States and leads to altered immune function, including T cell and macrophage activity that may impact responses to SARS-CoV-2 infection. This study investigated 131 adults with a history of a positive SARS-CoV-2 nasopharyngeal PCR and 18 adults with no COVID-19 diagnosis that were recruited from the community or hospital into the Northern Colorado Coronavirus Biorepository (NoCo-COBIO). Participants consented to enrollment for a period of 6 months and provided biospecimens at multiple visits for longitudinal analysis. Plasma 25-hydroxyvitamin D levels were quantified by LC-MS/MS at the initial visit (n = 149) and after 4 months (n = 89). Adults were classified as deficient (<30 nM or <12 ng/mL), insufficient (<30−50 nM or 12−20 ng/mL), or optimal (50−75 nM or >20 ng/mL) for 25-hydroxyvitamin D status. Fisher's exact test demonstrated an association between disease severity, gender, and body mass index (BMI) at baseline. Mixed model analyses with Tukey-Kramer were used for longitudinal analysis according to BMI. Sixty-nine percent (n = 103) of the entire cohort had optimal levels of total 25(OH)D, 22% (n = 32) had insufficient levels, and 9% (n = 14) had deficent levels. Participants with severe disease (n = 37) had significantly lower 25-hydroxyvitamin D (total 25(OH)D) when compared to adults with mild disease (p = 0.006) or no COVID-19 diagnosis (p = 0.007). There was 44% of the cohort with post-acute sequalae of COVID-19 (PASC) as defined by experiencing at least one of the following symptoms after 60 days' post-infection: fatigue, dyspnea, joint pain, chest pain, forgetfulness or absent-mindedness, confusion, or difficulty breathing. While significant differences were detected in 25-hydroxyvitamin D status by sex and BMI, there were no correlations between 25-hydroxyvitamin D for those without and without PASC. This longitudinal study of COVID-19 survivors demonstrates an important association between sex, BMI, and disease severity for 25-hydroxyvitamin D deficiency during acute stages of infection, yet it is not clear whether supplementation efforts would influence long term outcomes such as developing PASC.

Relationships between plasma fatty acids in adults with mild, moderate, or severe COVID-19 and the development of post-acute sequelae.

Background: SARS-CoV-2 has infected millions across the globe. Many individuals are left with persistent symptoms, termed post-acute sequelae of COVID-19 (PASC), for months after infection. Hyperinflammation in the acute and convalescent stages has emerged as a risk factor for poor disease outcomes, and this may be exacerbated by dietary inadequacies. Specifically, fatty acids are powerful inflammatory mediators and may have a significant role in COVID-19 disease modulation. Objective: The major objective of this project was to pilot an investigation of plasma fatty acid (PFA) levels in adults with COVID-19 and to evaluate associations with disease severity and PASC. Methods and procedures: Plasma from adults with (N = 41) and without (N = 9) COVID-19 was analyzed by gas chromatography-mass spectrometry (GC-MS) to assess differences between the concentrations of 18 PFA during acute infection (≤14 days post-PCR + diagnosis) in adults with varying disease severity. Participants were grouped based on mild, moderate, and severe disease, alongside the presence of PASC, a condition identified in patients who were followed beyond acute-stage infection (N = 23). Results: Significant differences in PFA profiles were observed between individuals who experienced moderate or severe disease compared to those with mild infection or no history of infection. Palmitic acid, a saturated fat, was elevated in adults with severe disease (p = 0.04), while behenic (p = 0.03) and lignoceric acid (p = 0.009) were lower in adults with moderate disease. Lower levels of the unsaturated fatty acids, γ-linolenic acid (GLA) (p = 0.03), linoleic (p = 0.03), and eicosapentaenoic acid (EPA) (p = 0.007), were observed in adults with moderate disease. Oleic acid distinguished adults with moderate disease from severe disease (p = 0.04), and this difference was independent of BMI. Early recovery-stage depletion of GLA (p = 0.02) and EPA (p = 0.0003) was associated with the development of PASC. Conclusion: Pilot findings from this study support the significance of PFA profile alterations during COVID-19 infection and are molecular targets for follow-up attention in larger cohorts. Fatty acids are practical, affordable nutritional targets and may be beneficial for modifying the course of disease after a COVID-19 diagnosis. Moreover, these findings can be particularly important for overweight and obese adults with altered PFA profiles and at higher risk for PASC. Clinical trial registration: [ClinicalTrials.gov], identifier [NCT04603677].

Validation of the Nelson Tool: A Scoring Tool for Nonsurgical Service Admission of Injured Patients.

BACKGROUND: Trauma performance improvement programs are required by the American College of Surgeons to review all nonsurgical admissions if the annual rate exceeds 10%. These reviews can have varying consistency between reviewers, are time consuming, and the consequent aggregate data are difficult to evaluate for trends. OBJECTIVE: This study set forth to standardize nonsurgical admission review through validation of the Nelson tool, which is a published objective scoring tool to determine the appropriateness of nonsurgical admissions. We hypothesized that implementation of this tool would facilitate earlier identification of events resulting in meaningful intervention and a reduction of inappropriate nonsurgical admissions. METHODS: The Nelson tool and scoring was integrated into the nonsurgical admission review process. A customized audit filter and report were built in the trauma registry. Data were reviewed with respect to scores and admitting service. Statistical analysis included using analysis of variance and t tests to examine differences between admitting services, χ2 test of independence or Fisher's exact to test the association of categorical variables, and ordinal logistic regression to test the ability of the total Nelson tool to predict appropriateness of admission. RESULTS: Using the Nelson tool, scores resulted in appropriate admission service in over 90% of cases. Implementation of the tool resulted in a decreased performance improvement workload with a 78% reduction in nonsurgical admission cases required to go to secondary level of review. CONCLUSIONS: Utilization of a validated scoring tool decreases performance improvement workload without compromising patient safety.

Comprehensive Immune Profiling Reveals CD56+ Monocytes and CD31+ Endothelial Cells Are Increased in Severe COVID-19 Disease.

Immune response dysregulation plays a key role in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogenesis. In this study, we evaluated immune and endothelial blood cell profiles of patients with coronavirus disease 2019 (COVID-19) to determine critical differences between those with mild, moderate, or severe COVID-19 using spectral flow cytometry. We examined a suite of immune phenotypes, including monocytes, T cells, NK cells, B cells, endothelial cells, and neutrophils, alongside surface and intracellular markers of activation. Our results showed progressive lymphopenia and depletion of T cell subsets (CD3+, CD4+, and CD8+) in patients with severe disease and a significant increase in the CD56+CD14+Ki67+IFN-γ+ monocyte population in patients with moderate and severe COVID-19 that has not been previously described. Enhanced circulating endothelial cells (CD45-CD31+CD34+CD146+), circulating endothelial progenitors (CD45-CD31+CD34+/-CD146-), and neutrophils (CD11b+CD66b+) were coevaluated for COVID-19 severity. Spearman correlation analysis demonstrated the synergism among age, obesity, and hypertension with upregulated CD56+ monocytes, endothelial cells, and decreased T cells that lead to severe outcomes of SARS-CoV-2 infection. Circulating monocytes and endothelial cells may represent important cellular markers for monitoring postacute sequelae and impacts of SARS-CoV-2 infection during convalescence and for their role in immune host defense in high-risk adults after vaccination.

Quality of Life (QoL) Is Reduced in Those with Severe COVID-19 Disease, Post-Acute Sequelae of COVID-19, and Hospitalization in United States Adults from Northern Colorado.

The longitudinal quality of life (QoL) of COVID-19 survivors, especially those with post-acute sequelae (PASC) is not well described. We evaluated QoL in our COVID-19 survivor cohort over 6 months using the RAND SF-36 survey. From July 2020-March 2021 we enrolled 110 adults from the United States with a positive SARS-CoV-2 nasopharyngeal polymerase chain reaction (PCR) into the Northern Colorado Coronavirus Biobank (NoCo-COBIO). Demographic data and symptom surveillance were collected from 62 adults. In total, 42% were hospitalized, and 58% were non-hospitalized. The Rand SF-36 consists of 36 questions and 8 scales, and questions are scored 0-100. A lower-scale score indicates a lower QoL. In conclusion, hospitalization, PASC, and disease severity were associated with significantly lower scores on the RAND SF-36 in Physical Functioning, Role Limitation due to Physical Health, Energy/Fatigue, Social Functioning, and General Health. Long-term monitoring of COVID-19 survivors is needed to fully understand the impact of the disease on QoL and could have implications for interventions to alleviate suffering during recovery.

A longitudinal SARS-CoV-2 biorepository for COVID-19 survivors with and without post-acute sequelae.

BACKGROUND: SARS-CoV-2 has swept across the globe, causing millions of deaths worldwide. Though most survive, many experience symptoms of COVID-19 for months after acute infection. Successful prevention and treatment of acute COVID-19 infection and its associated sequelae is dependent on in-depth knowledge of viral pathology across the spectrum of patient phenotypes and physiologic responses. Longitudinal biobanking provides a valuable resource of clinically integrated, easily accessed, and quality-controlled samples for researchers to study differential multi-organ system responses to SARS-CoV-2 infection, post-acute sequelae of COVID-19 (PASC), and vaccination. METHODS: Adults with a history of a positive SARS-CoV-2 nasopharyngeal PCR are actively recruited from the community or hospital settings to enroll in the Northern Colorado SARS-CoV-2 Biorepository (NoCo-COBIO). Blood, saliva, stool, nasopharyngeal specimens, and extensive clinical and demographic data are collected at 4 time points over 6 months. Patients are assessed for PASC during longitudinal follow-up by physician led symptom questionnaires and physical exams. This clinical trial registration is NCT04603677 . RESULTS: We have enrolled and collected samples from 119 adults since July 2020, with 66% follow-up rate. Forty-nine percent of participants assessed with a symptom surveillance questionnaire (N = 37 of 75) had PASC at any time during follow-up (up to 8 months post infection). Ninety-three percent of hospitalized participants developed PASC, while 23% of those not requiring hospitalization developed PASC. At 90-174 days post SARS-CoV-2 diagnosis, 67% of all participants had persistent symptoms (N = 37 of 55), and 85% percent of participants who required hospitalization during initial infection (N = 20) still had symptoms. The most common symptoms reported after 15 days of infection were fatigue, loss of smell, loss of taste, exercise intolerance, and cognitive dysfunction. CONCLUSIONS: Patients who were hospitalized for COVID-19 were significantly more likely to have PASC than those not requiring hospitalization, however 23% of patients who were not hospitalized also developed PASC. This patient-matched, multi-matrix, longitudinal biorepository from COVID-19 survivors with and without PASC will allow for current and future research to better understand the pathophysiology of disease and to identify targeted interventions to reduce risk for PASC. Registered 27 October 2020 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04603677 .

Optimal Duration of Antibiotics Following Appendectomy for Patients With Complicated Appendicitis.

BACKGROUND: Complicated appendicitis patients typically undergo appendectomy followed by antibiotics. The optimal course of antibiotics for complicated appendicitis is poorly defined. METHODS: Data were collected from patients presenting with acute appendicitis and underwent appendectomy at the index hospitalization (2015-2017). Primary outcomes were readmission rate, superficial surgical site infection (SSI), deep space infection (DSI), which includes abscess. Length of post-operative antibiotic use was recorded and an average intent-to-treat (ITT) by operative grade was calculated. RESULTS: Two hundred seventy-two patients (23%) were diagnosed with complicated appendicitis. SSI occurred in 4% of patients (n = 11); SSI rates ranged from 0% to 14.6% by ITT group with 3-4 days being the lowest (0%) and <3 days the highest (14.6%) (P = .008). DSI including abscesses occurred in 27 (9.9%) patients; least frequently in the 5-6 day ITT group (7.4%). Length of stay (LOS) was significantly related to longer antibiotic use (P < .001) and increasing operative grade (P < .01). CONCLUSIONS: Given the lower incidence of postoperative complications between 3 and 6 days and no added benefit for ITT >6 days, we recommend limiting antibiotic treatment to 3-6 days for all complicated appendicitis cases with additional workup warranted if infectious symptoms persist.

Effect of the National Diabetes Prevention Program on Weight Loss for English- and Spanish-Speaking Latinos.

PURPOSE: To study the effect of the National Diabetes Prevention Program (NDPP) on weight loss in Latinos. DESIGN: No-control, cohort study comparing Latino and non-Hispanic white (NHW) participants. SETTING: A health-care system. PARTICIPANTS: Five hundred sixty-seven Latino and 175 NHW patients who enrolled in the NDPP. A total of 45.2% of Latinos selected the Spanish-language NDPP. INTERVENTION: The NDPP is a nationwide translation of a clinical trial and seeks to prevent diabetes through weight loss in a yearlong group program. MEASURES: Independent variables included ethnicity, class language, and number of sessions attended. Main outcomes were initial attendance, number of sessions attended, and weight loss. ANALYSIS: Multivariate logistic regression and analysis of covariance were used to determine differences in NDPP outcomes by ethnicity, language, and number of sessions attended. RESULTS: Mean attendance was 8.60 of 22 sessions. Each session was associated with 0.30% (±0.02; P < .001) body weight loss. Latinos were half as likely to attend as NHWs, odds ratio 0.52 ( P < .001). Latino attendees came to 2.67 ± 0.63 ( P < .001) fewer sessions than NHWs. There were no weight loss differences by ethnicity after controlling for attendance. Outcomes did not differ among Latinos in the English- and Spanish-language NDPP. CONCLUSION: Latinos appeared to benefit less from the NDPP compared to NHWs, likely due to lower attendance rates. Further efforts are needed to support their participation.

Effect of Volume of Fluid Resuscitation on Metabolic Normalization in Children Presenting in Diabetic Ketoacidosis: A Randomized Controlled Trial.

BACKGROUND: The optimal rate of fluid administration in pediatric diabetic ketoacidosis (DKA) is unknown. OBJECTIVE: Our aim was to determine whether the volume of fluid administration in children with DKA influences the rate of metabolic normalization. METHODS: We performed a randomized controlled trial conducted in a tertiary pediatric emergency department from December 2007 until June 2010. The primary outcome was time to metabolic normalization; secondary outcomes were time to bicarbonate normalization, pH normalization, overall length of hospital treatment, and adverse outcomes. Children between 0 and 18 years of age were eligible if they had type 1 diabetes mellitus and DKA. Patients were randomized to receive intravenous (IV) fluid at low volume (10 mL/kg bolus + 1.25 × maintenance rate) or high volume (20 mL/kg bolus + 1.5 × maintenance rate) (n = 25 in each). RESULTS: After adjusting for initial differences in bicarbonate levels, time to metabolic normalization was significantly faster in the higher-volume infusion group compared to the low-volume infusion group (hazard ratio [HR] = 2.0; 95% confidence interval [CI] 1.0-3.9; p = 0.04). Higher-volume IV fluid infusion appeared to hasten, to a greater extent, normalization of pH (HR = 2.5; 95% CI 1.2-5.0; p = 0.01) than normalization of serum bicarbonate (HR = 1.2; 95% CI 0.6-2.3; p = 0.6). The length of hospital treatment HR (0.8; 95% CI 0.4-1.5; p = 0.5) and time to discharge HR (0.8; 95% CI 0.4-1.5; p = 0.5) did not differ between treatment groups. CONCLUSIONS: Higher-volume fluid infusion in the treatment of pediatric DKA patients significantly shortened metabolic normalization time, but did not change overall length of hospital treatment. ClinicalTrials.gov ID NCT01701557.

Reduced Bone Mineral Density Is Associated with Celiac Disease Autoimmunity in Children with Type 1 Diabetes.

OBJECTIVE: To evaluate the association between bone mineral density (BMD), glycemic control (hemoglobin A1c [HbA1c]), and celiac autoimmunity in children with type 1 diabetes mellitus (T1D) and in an appropriate control population. STUDY DESIGN: BMD was assessed cross-sectionally in 252 children with T1D (123 positive for anti-tissue transglutaminase antibody [tTGA] and 129 matched children who were negative for tTGA). In addition, BMD was assessed in 141 children without diabetes who carried T1D-associated HLD-DR, DQ genotypes (71 positive for tTGA and 70 negative). RESULTS: Children with T1D who were positive for tTGA had significantly worse BMD L1-L4 z-score compared with children with T1D who were negative for tTGA (-0.45 ± 1.22 vs 0.09 ± 1.10, P = .0003). No differences in growth measures, urine N-telopeptides, 25-hydroxyvitamin D, ferritin, thyroid stimulating hormone, or HbA1c were found. However, both higher HbA1c (ß = -1.25 ± 0.85, P = .0016) and tTGA (ß = -0.13 ± 0.05, P = .0056) were significant and independent predictors of lower BMD in multivariate analyses. No differences in BMD or other variables measured were found between children without diabetes who were positive vs negative for tTGA. CONCLUSIONS: The results suggest a synergistic effect of hyperglycemia and celiac autoimmunity on low BMD.

Genetic Mutations in Pediatric Pancreatitis.

OBJECTIVES: The aim of our study was to describe the prevalence, characteristics, and outcomes of children with acute recurrent (ARP) or chronic (CP) pancreatitis with or without mutations in PRSS1, CFTR or SPINK1. METHODS: Retrospective chart review of children with ARP or CP with and without testing for PRSS1, CFTR, and SPINK1. Demographics, clinical features, management, and outcome were collected. Analysis of variance was used to compare continuous variables and χ or Fisher exact test for categorical variables. RESULTS: Ninety-one subjects with ARP (n = 77) or CP (n = 14) were identified and included in this study. Of these, 37 (41%) were male, 44 were white, and 30 were Hispanic. Thirty-three (36%) had at least 1 mutation identified (Pan-Mut): PRSS1 (7), CFTR (21), SPINK1 (3), SPINK/CFTR (2). Thirty-six were tested but had no mutation, and 22 were not tested. The Pan-Mut subjects were more likely to have a family history of pancreatitis but there were no differences in the clinical features, imaging or outcome. CONCLUSIONS: Mutations in CFTR, SPINK1 or PRSS1 are present in one third of pediatric ARP and CP with no other cause. No clinical features or outcomes differentiated between the Pan-Mut group and the no-mutation group. The Pan-Mut subjects were more likely to have a family history of pancreatitis. Pediatric ARP and CP without identified cause should undergo genetic testing.

Testosterone concentration and insulin sensitivity in young men with type 1 and type 2 diabetes.

OBJECTIVE: Reduced testosterone, a recognized comorbidity of reduced insulin sensitivity (IS) and type 2 diabetes (T2D), has also been reported in adult males with type 1 diabetes (T1D). However, there are limited data on how early reduced testosterone occurs, and whether it is related to the reduced IS in T1D. Leptin, a modulator of the HPG-axis, may also influence testosterone in T1D. We hypothesized that IS and leptin would be associated with total testosterone (TT), and free androgen index (FAI) in adolescent males with T1D. METHODS: T1D (n = 35), T2D (n = 13), lean (n = 13) and obese (n = 9) adolescent males had IS measured by hyperinsulinemic-euglycemic clamps (glucose infusion rate [GIR]), in addition to leptin, sex hormone binding globulin (SHBG), TT, and FAI. The cohort was stratified into those with T1D (n = 35) and those without (n = 35). RESULTS: TT and SHBG were lower in T2D boys vs. lean controls, and GIR and leptin correlated with FAI and TT in non-T1D participants. However, despite being insulin resistant, adolescent males with T1D had normal TT and FAI, unrelated to GIR. In T1D, leptin was inversely associated with TT (p = 0.005) and FAI (p = 0.01), independent of puberty, hemoglobin A1c (HbA1c), diabetes duration, body mass index (BMI) z-score and GIR. CONCLUSION: Leptin accounted for a significant proportion of the variability of testosterone in T1D. However, despite reduced IS, there was no association between IS and testosterone in T1D adolescents. These observations suggest that the mechanisms affecting testosterone may differ between adolescent males with and without T1D.

Use of Telemedicine to Improve Adherence to American Diabetes Association Standards in Pediatric Type 1 Diabetes.

BACKGROUND: The American Diabetes Association (ADA) recommends that children with type 1 diabetes (T1D) see a multidisciplinary team and have hemoglobin A1c (A1C) levels measured every 3 months. Patients in rural areas may not follow guidelines because of limited specialty care access. We hypothesized that videoconferencing would result in equivalent A1C compared with in-person visits and increased compliance with ADA recommendations. MATERIALS AND METHODS: The Barbara Davis Center (BDC) (Aurora, CO) telemedicine program provides diabetes care to pediatric patients in Casper and Cheyenne, WY, via remote consultation with annual in-person visits. Over 27 months, 70 patients were consented, and 54 patients completed 1 year in the study. RESULTS: Patients were 70% male, with a mean age of 12.1 ± 4.1 years and T1D duration of 5.4 ± 4.1 years. There was no significant change between baseline and 1-year A1C levels for patients with data at both time points. Patients saw diabetes specialists an average of 2.0 ± 1.3 times per year in the year prior to starting telemedicine and 2.9 ± 1.3 times (P < 0.0001) in the year after starting telemedicine. Patients and families missed significantly less school and work time to attend appointments. CONCLUSIONS: Our study suggests telemedicine is equivalent to in-person visits to maintain A1C, whereas families increase the number of visits in line with ADA recommendations. Patients and families miss less school and work. Decreased financial burden and increased access may improve overall diabetes care and compliance for rural patients. Further study is needed to detect long-term differences in complications screenings and the financial impact of telemedicine on pediatric diabetes care.

Parathyroid Imaging with Simultaneous Acquisition of 99mTc-Sestamibi and 123I: The Relative Merits of Pinhole Collimation and SPECT/CT.

UNLABELLED: The objective of this study was to determine the relative utility of 3 state-of-the-art parathyroid imaging protocols: single-time-point simultaneous acquisition of (99m)Tc-sestamibi and (123)I images with pinhole collimation in the anterior and bilateral anterior oblique projections, single-time-point simultaneous acquisition of (99m)Tc-sestamibi and (123)I images with SPECT/CT, and the combination of the first and second protocols. METHODS: Fifty-nine patients with surgical proof of parathyroid adenomas were evaluated retrospectively. All 3 protocols included perfectly coregistered subtraction images created by subtracting the (123)I images from the (99m)Tc-sestamibi images, plus an anterior parallel-hole collimator image of the neck and upper chest. The pinhole protocol was performed first, followed by the SPECT/CT protocol. Three image sets were derived from each study in each patient according to the above protocols. Two experienced observers recorded the size, location, and degree of certainty of any identified lesion. RESULTS: The 59 patients had 61 adenomas. For the 2 observers combined, the localization success rate was 88% for the pinhole protocol, 69% for the SPECT/CT protocol, and 81% for the combined protocol. The pinhole protocol detected more adenomas than the SPECT/CT protocol and missed fewer adenomas than either the SPECT/CT protocol or the combined pinhole and SPECT/CT protocol (P < 0.01). The 2 protocols that included SPECT/CT provided superior anatomic information relative to the location and size of the parathyroid adenomas. CONCLUSION: The pinhole protocol localized significantly more adenomas than the SPECT/CT protocol. However, the protocols that included SPECT/CT provided more anatomic information than pinhole imaging alone.

Pravastatin Therapy and Biomarker Changes in Children and Young Adults with Autosomal Dominant Polycystic Kidney Disease.

BACKGROUND AND OBJECTIVES: Disease-specific treatment options for autosomal dominant polycystic kidney disease are limited. Clinical intervention early in life is likely to have the greatest effect. In a 3-year randomized double-blind placebo-controlled phase 3 clinical trial, the authors recently showed that pravastatin decreased height-corrected total kidney volume (HtTKV) progression of structural kidney disease over a 3-year period. However, the underlying mechanisms have not been elucidated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Participants were recruited nationally from July 2007 through October 2009. Plasma and urine samples collected at baseline, 18 months, and 36 months from 91 pediatric patients enrolled in the above-mentioned clinical trial were subjected to mass spectrometry-based biomarker analysis. Changes in biomarkers over 3 years were compared between placebo and pravastatin-treated groups. Linear regression was used to evaluate the changes in biomarkers with the percent change in HtTKV over 3 years. RESULTS: Changes in plasma concentrations of proinflammatory and oxidative stress markers (9- hydroxyoctadecadienoic acid, 13-hydroxyoctadecadienoic acid, and 15-hydroxyeicosatetraenoic acid [HETE]) over 3 years were significantly different between the placebo and pravastatin-treated groups, with the pravastatin group showing a lower rate of biomarker increase. Urinary 8-HETE, 9-HETE, and 11-HETE were positively associated with the changes in HtTKV in the pravastatin group. CONCLUSIONS: Pravastatin therapy diminished the increase of cyclooxygenase- and lipoxygenase-derived plasma lipid mediators. The identified biomarkers and related molecular pathways of inflammation and endothelial dysfunction may present potential targets for monitoring of disease severity and therapeutic intervention of autosomal dominant polycystic kidney disease.

Association of Uric Acid With Vascular Stiffness in the Framingham Heart Study.

BACKGROUND: Uric acid is associated with increased risk of cardiovascular disease and arterial stiffness in patients with hypertension or stroke. It remains unknown if uric acid is associated with arterial stiffness in the general population. METHODS: We analyzed the association between serum uric acid levels and measures of arterial stiffness such as carotid-femoral pulse wave velocity (CF PWV), carotid-radial pulse wave velocity (CR PWV) and augmentation index (AI) in 4,140 participants from the Generation 3 Framingham cohort using linear regression. RESULTS: Mean (SD) age was 40.0 (8.8) years and mean (SD) serum uric acid levels were 5.3 (1.5) mg/dl. Mean (SD) CF PWV was 7.0 (1.4) m/s. Individuals in the highest quartile of uric acid were more likely to be male, have a higher prevalence of hypertension, higher BMI, fasting glucose and insulin, and lower estimated glomerular filtration rate (eGFR). Multivariate adjusted means of CF PWV were 6.90, 6.94, 7.06, and 7.15 m/s for uric acid quartile 1, 2, 3, and 4 respectively. In unadjusted analysis each 1mg/dl increase in uric acid was associated with higher CF-PWV (ß = 0.27; 95% CI = 0.25, 0.29; P < 0.0001). This was attenuated but remained significant after adjusting for age, sex, smoking, hypertension, BMI, fasting glucose, insulin, animal protein intake, and eGFR (ß= 0.06; 95% CI = 0.02, 0.09; P < 0.0007). There was no association between serum uric acid levels and AI upon adjustment for cardiovascular risk factors. CONCLUSIONS: Serum uric acid levels are significantly associated with CF PWV and CR PWV in a younger Caucasian population.