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.

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.

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.

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 .

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.

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.

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.

Effects of low dose metformin in adolescents with type I diabetes mellitus: a randomized, double-blinded placebo-controlled study.

BACKGROUND: Insulin resistance increases during adolescence in those with type 1 diabetes mellitus (T1DM), complicating glycemic control and potentially increasing cardiovascular disease (CVD) risk. Metformin, typically used in type 2 diabetes mellitus (T2DM), is a possible adjunct therapy in T1DM to help improve glycemic control and insulin sensitivity. OBJECTIVE: We hypothesized that metformin would improve metabolic parameters in adolescents with T1DM. DESIGN, SETTING, AND PARTICIPANTS: This randomized, double-blinded, placebo-controlled trial included 74 pubertal adolescents (ages: 13-20 yr) with T1DM. Participants were randomized to receive either metformin or placebo for 6 months. Glycated hemoglobin (HbA1c), insulin dose, waist circumference, body mass index (BMI), and blood pressure were measured at baseline, 3 and 6 months, with fasting lipids measured at baseline and 6 months. RESULTS: Total daily insulin dose, BMI z-score and waist circumference significantly decreased at 3 and 6 months compared to baseline within the metformin group, even among normal-weight participants. In the placebo group, total insulin dose and systolic blood pressure increased significantly at 3 months and total insulin dose increased significantly at 6 months. No significant change was observed in HbA1c at any time point between metformin and placebo groups or within either group. CONCLUSIONS: Low-dose metformin likely improves BMI as well as insulin sensitivity in T1DM adolescents, as indicated by a decrease in total daily insulin dose. The decrease in waist circumference indicates that fat distribution is also likely impacted by metformin in T1DM. Further studies with higher metformin doses and more detailed measurements are needed to confirm these results, their underlying mechanisms, and potential impact on CVD in T1DM youth.

Bioactive lipid mediators in polycystic kidney disease.

Inflammatory activity is evident in patients with chronic kidney disease with limited data available in autosomal dominant polycystic kidney disease (ADPKD). We hypothesized that inflammation is an upstream event in the pathogenesis of ADPKD and may be a contributing factor in the disease severity and progression. Serum samples from 61 HALT study A group patients were compared with samples from 49 patients from HALT study B group with moderately advanced disease. Targeted MS analysis of bioactive lipid mediators as markers of inflammation was performed and correlated with eGFR and total kidney volume (TKV) normalized to the body surface area (BSAR) to assess if these markers are predictive of ADPKD severity. ADPKD patients with eGFR >60 ml/min/1.73 m(2) showed higher levels of 5- and 12/15-lipoxygenase (LOX) and cyclooxygenase, and generated higher levels of hydroxy-octadecadienoic acids 9-HODE and 13-HODE and HETEs 8-HETE, 11-HETE, 12-HETE, and 15-HETE as compared with healthy subjects. Linear regression of 9-HODE and 13-HODE revealed a significant relationship with eGFR and TKV, while 15-HETE significantly correlated with TKV/BSAR. Production of 20-HETE, a P450-produced metabolite of arachidonic acid, was higher in ADPKD patients as compared with healthy subjects and significantly correlated with eGFR and TKV/BSAR. Perturbation in fatty acid metabolism is evident early in ADPKD patients, even in those with preserved kidney function. The identified LOX pathways may be potential therapeutic targets for slowing down ADPKD progression.

Endothelial dysfunction and oxidative stress in polycystic kidney disease.

Cardiovascular disease (CVD) is the leading cause of premature mortality in ADPKD patients. The aim was to identify potential serum biomarkers associated with the severity of ADPKD. Serum samples from a homogenous group of 61 HALT study A ADPKD patients [early disease group with estimated glomerular filtration rate (eGFR) >60 ml·min(-1)·1.73 m(-2)] were compared with samples from 49 patients from the HALT study B group with moderately advanced disease (eGFR 25-60 ml·min(-1)·1.73 m(-2)). Targeted tandem-mass spectrometry analysis of markers of endothelial dysfunction and oxidative stress was performed and correlated with eGFR and total kidney volume normalized to the body surface area (TKV/BSA). ADPKD patients with eGFR >60 ml·min(-1)·1.73 m(-2) showed higher levels of CVD risk markers asymmetric and symmetric dimethylarginine (ADMA and SDMA), homocysteine, and S-adenosylhomocysteine (SAH) compared with the healthy controls. Upon adjustments for age, sex, systolic blood pressure, and creatinine, SDMA, homocysteine, and SAH remained negatively correlated with eGFR. Resulting cellular methylation power [S-adenosylmethionine (SAM)/SAH ratio] correlated with the reduction of renal function and increase in TKV. Concentrations of prostaglandins (PGs), including oxidative stress marker 8-isoprostane, as well as PGF2α, PGD2, and PGE2, were markedly elevated in patients with ADPKD compared with healthy controls. Upon adjustments for age, sex, systolic blood pressure, and creatinine, increased PGD2 and PGF2α were associated with reduced eGFR, whereas 8-isoprostane and again PGF2α were associated with an increase in TKV/BSA. Endothelial dysfunction and oxidative stress are evident early in ADPKD patients, even in those with preserved kidney function. The identified pathways may provide potential therapeutic targets for slowing down the disease progression.

Uric acid level and erectile dysfunction in patients with coronary artery disease.

INTRODUCTION: Erectile dysfunction (ED) is a frequent complaint of elderly subjects and is closely associated with endothelial dysfunction and cardiovascular disease (CVD). Uric acid is also associated with endothelial dysfunction, oxidative stress, and CVD, raising the hypothesis that an increased serum uric acid might predict ED in patients who are at risk for coronary artery disease (CAD). AIM: This study aims to evaluate the association of serum uric acid levels with presence and severity of ED in patients presenting with chest pain of presumed cardiac origin. METHODS: This is a cross-sectional study of 312 adult male patients with suspected CAD who underwent exercise stress test (EST) for workup of chest pain and completed a sexual health inventory for men survey form to determine the presence and severity of ED. Routine serum biochemistry (and uric acid levels) were measured. Logistic regression analysis was used to assess risk factors for ED. MAIN OUTCOME MEASURES: The short version of the International Index of Erectile Function questionnaire diagnosed ED (cutoff score ≤ 21). Serum uric acid levels were determined. Patients with chest pain of suspected cardiac origin underwent an EST. RESULTS: One hundred forty-nine of 312 (47.7%) male subjects had ED by survey criteria. Patients with ED were older and had more frequent CAD, hypertension, diabetes and impaired renal function, and also had significantly higher levels of uric acid, fibrinogen, glucose, C-reactive protein, triglycerides compared with patients without ED. Uric acid levels were associated with ED by univariate analysis (odds ratio = 1.36, P = 0.002); however, this association was not observed in multivariate analysis adjusted for estimated glomerular filtration rate. CONCLUSION: Subjects presenting with chest pain of presumed cardiac origin are more likely to have ED if they have elevated uric acid levels.

Hemoglobin A1c assay variations and implications for diabetes screening in obese youth.

BACKGROUND: Standardization of the hemoglobin A1c (A1c) assay has led to its increasing utilization as a screening tool for the diagnosis of prediabetes and type 2 diabetes in youth. However, significant A1c assay variability remains and has implications for clinical management. OBJECTIVE: To describe our center's experiences with A1c results in youth and to evaluate inter-method differences and their clinical implications. SUBJECTS: Seventy-five youth (aged 10-18 yr old), body mass index (BMI) ≥85th‰ participated. METHODS: Seventy-two participants had two A1c values performed on the same sample, one via immunoassay (DCA Vantage Analyzer, A1c1 ) and the other via high performance liquid chromatography (Bio-Rad Variant II, A1c2 ). Nineteen had A1c run on two immunoassay devices (A1c1 and Dimensions Vista, A1c3 ). RESULTS: Mean age of participants was 13.9 years, BMI% 97.89%, 33% male, 16% white, 21% black, and 61% Hispanic (H). Mean A1c1 was 5.68% ± 0.38 vs. a mean A1c2 of 5.73% ± 0.39, p = 0.049. Concordance in diabetes status between methods was achieved in 79% of subjects. Nineteen subjects with A1c3 results had testing performed an average of 22 ± 9 days prior to A1c1 . Mean A1c3 was 6.24% ± 0.4, compared to a mean A1c1 of 5.74% ± 0.31, (p < 0.0001). A1c1 was on average systematically -0.5 ± 0.28 lower compared to A1c3 . There was poor agreement in diabetes classification between A1c1 and A1c3 , with a concordance in classification between methods of only 36.8%. CONCLUSIONS: Clinically significant inter-method A1c variability exists that impacts patient classification and treatment recommendations. In the screening of obese youth for diabetes, A1c results should be interpreted with caution.

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.

Congenital adrenal hyperplasia and the second newborn screen.

OBJECTIVE: To evaluate the effectiveness of a second newborn screen for congenital adrenal hyperplasia (CAH) in the state of Colorado and report characteristics associated with cases identified on the first versus second screen. STUDY DESIGN: Colorado implemented newborn screening for CAH with 17-hydroxyprogesterone beginning August 2000. The first screening is performed within 72 hours of life and the second between 8 and 14 days of life. We compared infants diagnosed on the basis of the first versus second newborn screen. RESULTS: The first screen identified 29 cases of which 28 represented classical CAH. The incidence of classical CAH on the first screen was 1:24,766. The second screen identified 17 additional cases, of which 11 represented classical CAH. Combined, the incidence of classical CAH was 1:17,789. The sensitivity of the first screen was 71.79%. The false negative rate of the first screen was 28.2%. In the absence of a second screen, 1:47,824 infants would have been missed. Infants diagnosed on the first screen had higher 17-hydroxyprogesterone values compared with those diagnosed on the second screen (P = .0008). CONCLUSIONS: The use of a single newborn screen for CAH missed nearly 30% of classical CAH cases in Colorado. Addition of a second screen, therefore, can improve the operating characteristics of the newborn screening program.

The association of prevalent kidney stone disease with mortality in US adults: the National Health and Nutrition Examination Survey III, 1988-1994.

BACKGROUND: Kidney stone disease is associated with hypertension, diabetes, metabolic syndrome, kidney function decline, and increased cardiovascular (CV) events. However, its association with all-cause and CV mortality is unclear. METHODS: We used the Third National Health and Nutrition Examination Survey, a large US population-based study with mortality data through 2006 determined via linkage to the National Death Index to examine kidney stone disease in relation to all-cause and CV mortality risks. RESULTS: Among 14,879 men and women over 18 years of age who were eligible for analysis, 683 participants reported a history of kidney stones. There was a total of 3,590 all-cause and 1,608 CV deaths during a median follow-up of 14.9 years. Stone formers had a significantly higher risk for all-cause mortality [hazard ratio (HR): 1.95, 95% CI: 1.64-2.33, p < 0.0001) and CV mortality (HR: 2.05, 95% CI: 1.60-2.62, p < 0.0001) in unadjusted analyses. However, after multivariate adjustment for age, gender, race, and poverty, stone formers no longer had increased risk for all-cause mortality (HR: 1.08, 95% CI: 0.93-1.26, p = 0.3) and CV mortality (HR: 1.07, 95% CI: 0.84-1.36, p = 0.6). Results remain unchanged after further adjustment for other clinical variables including history of hypertension, diabetes, and CV disease. CONCLUSION: The increased risk of all-cause and CV mortality in kidney stone formers is likely a reflection of unique demographics and associated comorbidities. There is no independent association of prevalent kidney stone disease with all-cause and CV mortality.

Association between dietary sodium and potassium intake with chronic kidney disease in US adults: a cross-sectional study.

BACKGROUND/AIMS: Clinical guidelines recommend a diet low in sodium and high in potassium to reduce blood pressure and cardiovascular events. Little is known about the relationship between dietary sodium and potassium intake and chronic kidney disease (CKD). METHODS: 13,917 participants from the National Health and Nutrition Examination Survey (2001-2006) were examined. Sodium and potassium intake were calculated from 24-hour recall and evaluated in quartiles. CKD was defined as estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m(2) or eGFR ≥60 ml/min/1.73 m(2) with albuminuria (>30 mg/g creatinine). RESULTS: The mean (SE) age and eGFR of participants were 45.0 ± 0.4 years and 88.0 ± 0.60 ml/min/1.73 m(2), respectively. 2,333 (14.2%) had CKD: 1,146 (7.3%) had an eGFR <60 ml/min/1.73 m(2) and 1,514 (8.4%) had an eGFR ≥60 ml/min/1.73 m(2) and albuminuria. After adjustment for age, sex, race, BMI, diabetes, hypertension, cardiovascular disease and congestive heart failure, subjects in the highest quartile of sodium intake had lower odds of CKD compared to subjects in the lowest quartile (adjusted OR: 0.79; 95% CI: 0.66-0.96; p < 0.016). Compared to the highest quartile, the odds of CKD increased 44% for participants in the lowest quartile of potassium intake (adjusted OR: 1.44; 95% CI: 1.16-1.79; p = 0.0011). CONCLUSIONS: Higher intake of sodium and potassium is associated with lower odds of CKD among US adults. These results should be corroborated through longitudinal studies and clinical trials designed specifically to examine the effects of dietary sodium and potassium intake on kidney disease and its progression.

Serum uric acid, kidney volume and progression in autosomal-dominant polycystic kidney disease.

BACKGROUND: Hyperuricemia has been implicated in the development and progression of chronic kidney disease, both in animal experiments and in clinical studies. As a potentially modifiable risk factor, we examined whether serum uric acid levels correlate with early hypertension, kidney volume and progression to end-stage renal disease (ESRD) in autosomal-dominant polycystic kidney disease (ADPKD). METHODS: Retrospective analysis of a prospective observational study of the natural history of ADPKD, conducted at the University of Colorado between 1985 and 2005. Included are 680 ADPKD adults who provided data on blood pressure, renal volume, renal function, uric acid, age at the onset of ESRD or last known age without ESRD. Serum uric acid levels were examined as a continuous variable and as gender-specific quartiles. The main outcome of interest was age at the onset of ESRD; secondary outcomes were hypertension onset before age 30 years and total kidney volume (TKV) at the study visit. RESULTS: Subjects with early-onset hypertension had higher age-adjusted serum uric acid levels than those with no or late-onset hypertension despite similar creatinine clearance. After adjusting for age, gender and creatinine clearance, there was a 5.8% increase in TKV and 4.1% increase in TKV/body surface area for every 1 mg/dL increase in uric acid (P = 0.007). The multivariate-adjusted Cox regression demonstrated a greater hazard ratio for ESRD for subjects in the 4th and 3rd quartiles of uric acid compared with the 1st [4.8 (2.6-8.9; P < 0.001) and 2.9 (1.6-5.3; P < 0.001)]. CONCLUSIONS: Higher serum uric acid levels are associated with earlier onset of hypertension, larger kidney volume and increased hazard for ESRD in ADPKD independent of gender, body mass index and renal function at the study visit. Randomized interventional studies will be necessary to examine whether treating hyperuricemia has a protective role in ADPKD.

Age- and sex-specific normal values for shock index in National Health and Nutrition Examination Survey 1999-2008 for ages 8 years and older.

PURPOSE: Shock index (SI), the ratio of heart rate to systolic blood pressure, has found to outperform conventional vital signs as a predictor of shock. Although age-specific vital sign norms are recommended in screening for shock, there are no reported age- or sex-specific norms for SI. Our primary goal was to report age- and sex-specific SI normal values for a nationally representative population 10 years and older by 5-year age groups. A secondary goal was to report SI normal values for children ages 8 to 19 years by 1-year age groups. BASIC PROCEDURES: Weighted data from the National Health and Nutrition Examination Survey 1999-2008 data sets were used to generate age- and sex-specific percentile curves of SI for subjects 8 years and older. MAIN FINDINGS: The primary analysis included 33906 subjects (101837 weighted) 10 years and older. The secondary analysis included 13393 subjects (37983 weighted) 8 to 19 years old. Normalized SI values for each percentile decreased with increasing age and were higher for females across all ages. The most commonly cited SI threshold of 0.9 exceeded the 97th percentile for males younger than 25 years and for females younger than 40 years. CONCLUSIONS: This first report of age- and sex-specific normal values for SI indicates that SI norms vary by age and sex. Just as age-specific vital sign norms are recommended in screening for shock, our findings suggest that age- and sex-specific SI norms may be more effective in screening for shock than a single-value threshold.

Urine IL-18, NGAL, IL-8 and serum IL-8 are biomarkers of acute kidney injury following liver transplantation.

BACKGROUND: AKI is common following liver transplantation and is associated with significant morbidity and mortality. Biomarkers of AKI have not been well established in this setting but are needed to help guide patient care and facilitate development of novel therapeutics. METHODS: Serum creatinine, cystatin C, IL-6, and IL-8 and urine IL-18, NGAL, IL-6, and IL-8 were measured before and within 24 hours after liver transplantation in 40 patients. AKI was defined as a ≥50% sustained increase in creatinine above pre-operative values occurring within 24 hours of transplantation and persisting for at least 24 hours. RESULTS: Seven patients met criteria for AKI (17.5%), with mean creatinines of 0.81 mg/dL pre-operatively and 1.75 mg/dL post-operatively. While pre-operative biomarker levels in patients with AKI were similar to those in patients without AKI, differences were seen between the groups with regard to median post-operative serum IL-8 (pg/mL) (242.48 vs. 82.37, p = 0.0463) and urine NGAL (ng/mL) (386.86 vs. 24.31, p = 0.0039), IL-6 (pg/mL) (52 vs. 7.29, p=0.0532), IL-8 (pg/mL) (14.3 vs. 0, p = 0.0224), and IL-18 (pg/mL) (883.09 vs. 0, p = 0.0449). The areas under receiver operating characteristic (ROC) curves were 0.749 for urine IL-18, 0.833 for urine NGAL, 0.745 for urine IL-6, 0.682 for serum IL-6, 0.773 for urine IL-8, and 0.742 for serum IL-8. Post-operative cystatin C was not significantly different between AKI and no AKI groups. CONCLUSION: Serum IL-8 and urine IL-18, NGAL, IL-6, and IL-8 are elevated in AKI within the first 24 hours following liver transplantation.

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.