Publications by authors named "W Garrett Hunt"

676 Publications

Transition Planning for Chronic Illnesses in the Time of COVID-19.

J Patient Exp 2020 Dec 3;7(6):848-850. Epub 2020 Dec 3.

Children's Healthcare of Atlanta and Emory University Cystic Fibrosis Center, Emory University, Atlanta, GA, USA.

Transition from pediatric to adult care for those with chronic illnesses must have special considerations during the COVID-19 pandemic. The SARS-CoV-2 coronavirus has significantly disrupted social, economic, and health care practices globally. Young adults with special health care needs are at increased risk for poor outcomes during this unprecedented time. We have found that heightened anxiety, health care service disruption, and other logistical complications surrounding the new virus may further confound health care transitions. Increased communication and collaboration with young adults is necessary to provide patient-centered care and ensure they successfully cross the transition chasm.
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http://dx.doi.org/10.1177/2374373520978875DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7786738PMC
December 2020

Next generation swale design for stormwater runoff treatment: A comprehensive approach.

J Environ Manage 2021 Feb 23;279:111756. Epub 2020 Dec 23.

Department of Biological and Agricultural Engineering, North Carolina State University, Box 7625, Raleigh, NC, 27695, USA.

Swales are the oldest and most common stormwater control measure for conveying and treating roadway runoff worldwide. Swales are also gaining popularity as part of stormwater treatment trains and as crucial elements in green infrastructure to build more resilient cities. To achieve higher pollutant reductions, swale alternatives with engineered media (bioswales) and wetland conditions (wet swales) are being tested. However, the available swale design guidance is primarily focused on hydraulic conveyance, overlooking their function as an important water quality treatment tool. The objective of this article is to provide science-based swale design guidance for treating targeted pollutants in stormwater runoff. This guidance is underpinned by a literature review. The results of this review suggest that well-maintained grass swales with check dams or infiltration swales are the best options for runoff volume reduction and removal of sediment and heavy metals. For nitrogen removal, wet swales are the most effective swale alternative. Bioswales are best for phosphorus and bacteria removal; both wet swales and bioswales can also treat heavy metals. Selection of a swale type depends on the site constraints, local climate, and available funding for design, construction, and operation. Appropriate siting, pre-design site investigations, and consideration of future maintenance during design are critical to successful long-term swale performance. Swale design recommendations based on a synthesis of the available research are provided, but actual design standards should be developed using local empirical data. Future research is necessary to identify optimal design parameters for all swale types, especially for wet swales.
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http://dx.doi.org/10.1016/j.jenvman.2020.111756DOI Listing
February 2021

Severe SARS-CoV-2 disease in the context of a NF-κB2 loss-of-function pathogenic variant.

J Allergy Clin Immunol 2021 Feb 30;147(2):532-544.e1. Epub 2020 Sep 30.

Department of Pediatrics, Nationwide Children's Hospital and The Ohio State University College of Medicine, Columbus, Ohio; Center for Vaccines and Immunity, The Abigail Wexner Research Institute, Nationwide Children's Hospital, Columbus, Ohio; Division of Infectious Diseases, Nationwide Children's Hospital, Columbus, Ohio.

Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that emerged recently and has created a global pandemic. Symptomatic SARS-CoV-2 infection, termed coronavirus disease 2019 (COVID-19), has been associated with a host of symptoms affecting numerous organ systems, including the lungs, cardiovascular system, kidney, central nervous system, gastrointestinal tract, and skin, among others.

Objective: Although several risk factors have been identified as related to complications from and severity of COVID-19, much about the virus remains unknown. The host immune response appears to affect the outcome of disease. It is not surprising that patients with intrinsic or secondary immune compromise might be particularly susceptible to complications from SARS-CoV-2 infection. Pathogenic loss-of-function or gain-of-function heterozygous variants in nuclear factor-κB2 have been reported to be associated with either a combined immunodeficiency or common variable immunodeficiency phenotype.

Methods: We evaluated the functional consequence and immunologic phenotype of a novel NFKB2 loss of function variant in a 17-year-old male patient and describe the clinical management of SARS-CoV-2 infection in this context.

Results: This patient required a 2-week hospitalization for SARS-CoV-2 infection, including 7 days of mechanical ventilation. We used biologic therapies to avert potentially fatal acute respiratory distress syndrome and treat hyperinflammatory responses. The patient had an immunologic phenotype of B-cell dysregulation with decreased switched memory B cells. Despite the underlying immune dysfunction, he recovered from the infection with intense management.

Conclusions: This clinical case exemplifies some of the practical challenges in management of patients with SARS-CoV-2 infection, especially in the context of underlying immune dysregulation.
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http://dx.doi.org/10.1016/j.jaci.2020.09.020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525247PMC
February 2021

Scrofula associated with a patient receiving adalimumab therapy for Crohn disease.

Clin Exp Dermatol 2021 Jan 15;46(1):216-218. Epub 2020 Sep 15.

Departments of, Department of, Dermatology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.

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http://dx.doi.org/10.1111/ced.14434DOI Listing
January 2021

First detection of infectious spleen and kidney necrosis virus (ISKNV) associated with massive mortalities in farmed tilapia in Africa.

Transbound Emerg Dis 2020 Sep 13. Epub 2020 Sep 13.

Cefas Weymouth Laboratory, Weymouth, UK.

In late 2018, unusual patterns of very high mortality (>50% production) were reported in intensive tilapia cage culture systems across Lake Volta in Ghana. Samples of fish and fry were collected and analysed from two affected farms between October 2018 and February 2019. Affected fish showed darkening, erratic swimming and abdominal distension with associated ascites. Histopathological observations of tissues taken from moribund fish at different farms revealed lesions indicative of viral infection. These included haematopoietic cell nuclear and cytoplasmic pleomorphism with marginalization of chromatin and fine granulation. Transmission electron microscopy showed cells containing conspicuous virions with typical iridovirus morphology, that is enveloped, with icosahedral and/or polyhedral geometries and with a diameter c.160 nm. PCR confirmation and DNA sequencing identified the virions as infectious spleen and kidney necrosis virus (ISKNV). Samples of fry and older animals were all strongly positive for the presence of the virus by qPCR. All samples tested negative for TiLV and nodavirus by qPCR. All samples collected from farms prior to the mortality event were negative for ISKNV. Follow-up testing of fish and fry sampled from 5 additional sites in July 2019 showed all farms had fish that were PCR-positive for ISKNV, whether there was active disease on the farm or not, demonstrating the disease was endemic to farms all over Lake Volta by that point. The results suggest that ISKNV was the cause of disease on the investigated farms and likely had a primary role in the mortality events. A common observation of coinfections with Streptococcus agalactiae and other tilapia bacterial pathogens further suggests that these may interact to cause severe pathology, particularly in larger fish. Results demonstrate that there are a range of potential threats to the sustainability of tilapia aquaculture that need to be guarded against.
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http://dx.doi.org/10.1111/tbed.13825DOI Listing
September 2020

Relationship Between Estrogen Treatment and Skeletal Health in Women With Cystic Fibrosis.

Am J Med Sci 2020 11 6;360(5):581-590. Epub 2020 Jun 6.

Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine and the Atlanta VA Medical Center, Atlanta, GA. Electronic address:

Background: Patients with cystic fibrosis (CF) are at risk for CF-related bone disease. Women with CF may use estrogen supplementation for reasons other than skeletal health. It is unknown whether estrogen therapy has a beneficial impact on skeletal health in women with CF.

Methods: In this retrospective cohort study of women with CF followed at a single CF center, the lumbar spine bone mineral density (BMD) of women with CF exposed to supplemental and not exposed to supplemental estrogen were compared. Spline function models included the main effect of estrogen exposure and the interaction between age and estrogen supplementation.

Results: Of the 145 subjects analyzed, 44 subjects were exposed to supplemental estrogen. The baseline characteristics of estrogen exposed and unexposed subjects were similar except for use of CF transmembrane conductance regulator modulators and anti-osteoporosis medications. Women exposed to estrogen reached peak BMD around 21 years of age, but women not exposed to estrogen reached peak BMD around 25 years of age. A significant interaction of age and estrogen supplementation indicated that the lumbar spine BMD trajectories differed by exposure group.

Conclusions: Our study demonstrates that few women with CF of reproductive age are prescribed estrogen therapy. Furthermore, estrogen exposure up to age 21 is associated with improved BMD, but estrogen exposure after age 21 does not appear to be associated with improved BMD. Further studies are needed to understand the reasons for the low rates of estrogen use in young women with CF and the optimal timing, dose and formulation of estrogen prescription.
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http://dx.doi.org/10.1016/j.amjms.2020.06.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609599PMC
November 2020

Noodles Made from High Amylose Wheat Flour Attenuate Postprandial Glycaemia in Healthy Adults.

Nutrients 2020 Jul 22;12(8). Epub 2020 Jul 22.

School Public Health, Curtin University, Perth 6845, Western Australia, Australia.

Previous research has not considered the effect of high amylose wheat noodles on postprandial glycaemia. The aim of the study is to investigate the effect of consumption of high amylose noodles on postprandial glycaemia over 2-h periods by monitoring changes in blood glucose concentration and calculating the total area under the blood glucose concentration curve. Twelve healthy young adults were recruited to a repeated measure randomised, single-blinded crossover trial to compare the effect of consuming noodles (180 g) containing 15%, 20% and 45% amylose on postprandial glycaemia. Fasting blood glucose concentrations were taken via finger-prick blood samples. Postprandial blood glucose concentrations were taken at 15, 30, 45, 60, 90 and 120 min. Subjects consuming high amylose noodles made with flour containing 45% amylose had significantly lower blood glucose concentration at 15, 30 and 45 min (5.5 ± 0.11, 6.1 ± 0.11 and 5.6 ± 0.11 mmol/L; = 0.01) compared to subjects consuming low amylose noodles with 15% amylose (5.8 ± 0.12, 6.6 ± 0.12 and 5.9 ± 0.12 mmol/L). The total area under the blood glucose concentration curve after consumption of high amylose noodles with 45% amylose was 640.4 ± 9.49 mmol/L/min, 3.4% lower than consumption of low amylose noodles with 15% amylose (662.9 ± 9.49 mmol/L/min), = 0.021. Noodles made from high amylose wheat flour attenuate postprandial glycaemia in healthy young adults, as characterised by the significantly lower blood glucose concentration and a 3.4% reduction in glycaemic response.
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http://dx.doi.org/10.3390/nu12082171DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468775PMC
July 2020

Hepatitis in children with tuberculosis: a case report and review of the literature.

BMC Pulm Med 2020 Jun 16;20(1):173. Epub 2020 Jun 16.

Division of Pediatric Infectious Diseases, Nationwide Children's Hospital, Columbus, OH, USA.

Background: Hepatitis in young children with tuberculosis (TB) outside miliary TB is not well described and represents a challenge because of the hepatotoxicity associated with first-line anti-TB treatment.

Case Presentation: We report an antibiotic naïve 13-month-old male from Nepal with pulmonary TB and hepatitis, who improved after TB treatment. We also performed a literature review for TB-associated hepatitis in children.

Conclusions: Liver function tests should be considered, when feasible, in infants and young children with pulmonary TB. Testing could help to identify and manage patients with TB-associated hepatic abnormalities, and also to establish a baseline for detection and management of liver injury associated with anti-TB therapy.
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http://dx.doi.org/10.1186/s12890-020-01215-6DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7298953PMC
June 2020

Oral ethinyl estradiol treatment in women with cystic fibrosis is associated with lower bone mineral density.

J Clin Transl Endocrinol 2020 Jun 19;20:100223. Epub 2020 Mar 19.

Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine and the Atlanta VA Medical Center, Atlanta, GA, USA.

Objective: The purpose of this study was to determine whether estrogen supplementation primarily from oral contraceptive pills compared to no estrogen supplementation is associated with differences in mean bone mineral density (BMD) measured by DXA in a cross-sectional study of women with cystic fibrosis (CF).

Methods: In this cross-sectional study of women with CF followed at a single center, we analyzed 49 women with CF ages 18-50 years with a documented DXA. BMD of women with CF taking estrogen supplementation was compared to BMD of women with CF not taking estrogen supplementation.

Results: Twelve women with CF were taking estrogen supplementation with mean dose of 23.3 mcg/day (SD 6.9 mcg/day) of ethinyl estradiol. There were no statistically significant differences between demographics of the 12 women with CF taking estrogen supplementation compared to the 37 women with CF not taking estrogen supplementation. Women taking estrogen had lower mean lumbar spine Z-score: -0.7 ± 0.7, compared to women not taking estrogen, Z-score: -0.04 ± 1.0 (p-value 0.046). Women taking estrogen had lower mean BMD at the lumbar spine: 0.952 ± 0.086 g/cm, compared to women not taking estrogen: 1.023 ± 0.105 g/cm (p-value 0.038). Similar trends were seen at the total hip and femoral neck.

Conclusion: Low-dose estrogen supplementation in premenopausal women with CF was associated with lower BMD compared to no estrogen supplementation in a similar group of premenopausal young women with CF. Future studies are needed to investigate the optimal formulation, route of administration, and dose to accrue and preserve bone mass in premenopausal women with CF.
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http://dx.doi.org/10.1016/j.jcte.2020.100223DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7109452PMC
June 2020

Accuracy of Two Point-of-Care Tests for Rapid Diagnosis of Bovine Tuberculosis at Animal Level using Non-Invasive Specimens.

Sci Rep 2020 03 25;10(1):5441. Epub 2020 Mar 25.

Texas Biomedical Research Institute, San Antonio, TX, United States.

Bovine tuberculosis (BTB) testing in cattle requires a significant investment of time, equipment, and labor. Novel, rapid, cheaper and accurate methods are needed. The Alere Determine TB lipoarabinomannan antigen (LAM-test) is a World Health Organization-endorsed point-of-care urine test designed to detect active TB disease in humans. The Lionex Animal TB Rapid Test (Lionex-test) is a novel animal specific TB diagnostic blood test. An animal level analysis was performed using urine (n = 141) and milk (n = 63) samples from depopulated BTB-suspected cattle to test the accuracy of the LAM-test when compared to results of positive TB detection by any routine BTB tests (BOVIGAM, necropsy, histology, culture, PCR) that are regularly performed by the United States Department of Agriculture (USDA). The agreement between the urine LAM-test and USDA standard tests were poor at varying testing time points. The same milk samples did not elicit statistically significant agreement with the Lionex-test, although positive trends were present. Hence, we cannot recommend the LAM-test as a valid BTB diagnostic test in cattle using either urine or milk. The Lionex-test's production of positive trends using milk samples suggests larger sample sizes may validate the Lionex-test in accurately diagnosing BTB in cattle using milk samples, potentially providing a quick and reliable field test for BTB.
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http://dx.doi.org/10.1038/s41598-020-62314-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096388PMC
March 2020

Glucose ingestion in cystic fibrosis induces severe redox imbalance: A potential role in diabetes.

J Cyst Fibros 2020 05 27;19(3):476-482. Epub 2020 Feb 27.

Emory+Children's Center for Cystic Fibrosis and Airways Disease Research, Emory University, Atlanta, GA, USA; Division of Pulmonary, Allergy/Immunology, Cystic Fibrosis and Sleep, Department of Pediatrics, Atlanta, GA, USA.

Background: Cystic fibrosis related diabetes (CFRD) is the most common co-morbidity associated with cystic fibrosis (CF). Individuals with CF demonstrate airway and systemic oxidation compared to people without CF. Furthermore, systemic oxidation precipitated by hyperglycemia in non-CF diabetes has been shown to lead to enhanced inflammation. We hypothesized that the presence of both CF and diabetes in an individual would result in hyperglycemia-induced redox imbalance to an oxidative state. This in turn would result in enhanced production of pro-inflammatory cytokines.

Methods: Systemic redox balance and pro-inflammatory cytokines were measured before and following a standard oral glucose tolerance test in healthy controls (HC) and in CF individuals with a spectrum of glucose homeostasis (i.e. normal glucose tolerant - NGT, prediabetes or frank CFRD).

Results: There were no significant differences between groups in terms of basal or glucose-induced levels of inflammatory markers. However, baseline systemic redox potential was significantly more oxidized in CF subjects with prediabetes and CFRD compared to both CF with NGT and HC. Systemic oxidation was significantly worsened, and to a profound degree, two hours following ingestion of glucose in all CF groups (NGT, prediabetes, and CFRD). The level of redox imbalance at the two hour point was the same in all three CF groups and was not associated with the degree of hyperglycemia. There was a significant correlation between worse systemic oxidation and reduced insulin secretion.

Conclusions: This supports a newly identified abnormality of metabolism in CF - glucose induced redox imbalance to the oxidative state.
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http://dx.doi.org/10.1016/j.jcf.2020.02.010DOI Listing
May 2020

Cutaneous leishmaniasis in a globetrotting explorer.

BMJ Case Rep 2019 Dec 29;12(12). Epub 2019 Dec 29.

Dermatology, Royal Devon and Exeter NHS Foundation Trust, Exeter, Devon, UK.

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http://dx.doi.org/10.1136/bcr-2019-233056DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6936374PMC
December 2019

Seismic surveys reduce cetacean sightings across a large marine ecosystem.

Sci Rep 2019 12 16;9(1):19164. Epub 2019 Dec 16.

MaREI Centre, Environmental Research Institute, University College Cork, Beaufort Building, Ringaskiddy, Co. Cork, P43C573, Ireland.

Noise pollution is increasing globally, and as oceans are excellent conductors of sound, this is a major concern for marine species reliant on sound for key life functions. Loud, impulsive sounds from seismic surveys have been associated with impacts on many marine taxa including mammals, crustaceans, cephalopods, and fish. However, impacts across large spatial scales or multiple species are rarely considered. We modelled over 8,000 hours of cetacean survey data across a large marine ecosystem covering > 880,000 km to investigate the effect of seismic surveys on baleen and toothed whales. We found a significant effect of seismic activity across multiple species and habitats, with an 88% (82-92%) decrease in sightings of baleen whales, and a 53% (41-63%) decrease in sightings of toothed whales during active seismic surveys when compared to control surveys. Significantly fewer sightings of toothed whales also occurred during active versus inactive airgun periods of seismic surveys, although some species-specific response to noise was observed. This study provides strong evidence of multi-species impacts from seismic survey noise on cetaceans. Given the global proliferation of seismic surveys and large propagation distances of airgun noise, our results highlight the large-scale impacts that marine species are currently facing.
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http://dx.doi.org/10.1038/s41598-019-55500-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6915703PMC
December 2019

Incidentally Detected Malignancies in Lung Transplant Explants.

Transplant Direct 2019 Nov 8;5(11):e503. Epub 2019 Oct 8.

Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Emory University, Atlanta, GA.

Active malignancy diagnosed within 5 years is an absolute contraindication for lung transplantation. In this study, we evaluated the rate of incidental malignancies detected in explanted lungs at our institution and assessed the posttransplant survival in patients with nonsmall cell lung cancer (NSCLC).

Methods: A retrospective chart review of lung transplant recipients at our institution from February 1999 to June 2017 was conducted. A literature review was performed to evaluate the prevalence and survival outcomes in patients with unexpected malignancies.

Results: From 407 patients who underwent lung transplantation, 9 (2.2%) were discovered to have malignant neoplasms. There were 3 cases of adenocarcinoma, 3 cases of adenocarcinoma in situ, 2 cases of squamous cell carcinoma, and 1 case of metastatic renal cell carcinoma. An extensive literature review found 12 case reports or case series reporting malignancy discovered at the time of lung transplantation. The overall prevalence of incidental neoplasms among 6746 recipients is around 1.5% (n = 103). The most common neoplasms discovered included adenocarcinoma (n = 56, 54%) and squamous cell carcinoma (n = 29, 28%). The overall 3-year survival was 54.4% for patients with localized NSCLC compared to 5.7% for those with nonlocalized disease.

Conclusions: Unidentified malignancies occur despite aggressive radiographic surveillance with poor posttransplant outcomes in patients with advanced malignancy. Malignancy-related radiographic findings may be missed pretransplant secondary to architectural distortion of lung parenchyma related to end-stage lung disease or because of the critical timing of surgery when donor lungs are available.
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http://dx.doi.org/10.1097/TXD.0000000000000947DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6831122PMC
November 2019

Hydrologic and water quality performance of two aging and unmaintained dry detention basins receiving highway stormwater runoff.

J Environ Manage 2020 Feb 21;255:109853. Epub 2019 Nov 21.

Department of Crop and Soil Science, North Carolina State University, Raleigh, NC, USA. Electronic address:

Dry detention basins (DDBs) are a type of stormwater control measure (SCM) designed to provide flood storage, peak discharge reduction, and some water quality improvement through sedimentation. DDBs are ubiquitous in the urban environment, but are expensive to maintain. In this study, two overgrown DDBs near Raleigh, NC, receiving highway runoff were monitored for up to one year to quantify their water quality and hydrologic performance. Both basins, B1 and B2, have not received vegetation maintenance since construction in 2007. Flow-weighted composite samples were collected during storm events and analyzed for nutrients (Total Phosphorus (TP), Ortho-phosphorus (OP), Ammonia-N (NH), NO-N (NO), and Total Kjeldahl Nitrogen (TKN)), total suspended solids (TSS), and total Cd, Cu, Pb, and Zn. An annual water balance was also conducted to quantify runoff volume reduction. Despite low influent concentrations from the highway, significant removal efficiencies were found for all constituents except NH in B1. TP, OP, NO, TSS, and Zn were reduced in B2. Both basins achieved greater than 41% volume reduction through soil infiltration and evapotranspiration, resulting in significant pollutant load reductions for all detected constituents, between 59% and 79% in B1 and 35% and 81% in B2. This study provides evidence that overgrown and unmaintained DDBs can reduce pollutant concentrations comparable to those reported for maintained DDBs, while reducing more volume than standard DDBs. Moreover, carbon sequestration likely increases while maintenance costs decrease.
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http://dx.doi.org/10.1016/j.jenvman.2019.109853DOI Listing
February 2020

Relationships of p16 Immunohistochemistry and Other Biomarkers With Diagnoses of Cervical Abnormalities: Implications for LAST Terminology.

Arch Pathol Lab Med 2020 06 13;144(6):725-734. Epub 2019 Nov 13.

From Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York (Dr Castle); Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, United Kingdom (Ms Adcock and Dr Cuzick); Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland (Drs Wentzensen and Schiffman); the Department of Pathology, University of New Mexico Cancer Center, Albuquerque (Ms Torrez-Martinez, Dr Torres, Dr Joste, Dr Gravitt, Mr Hunt, and Dr Wheeler); the Department of Pathology, University of Virginia Health System, Charlottesville (Dr Stoler); the Department of Pathology, Johns Hopkins University, Baltimore, Maryland (Dr Ronnett); the Department of Pathology, University of California, San Francisco (Dr Darragh); and Sacramento, California (Dr Kinney).

Context.—: Lower Anogenital Squamous Terminology (LAST) standardization recommended p16 immunohistochemistry (p16 IHC) for biopsies diagnosed morphologically as cervical intraepithelial neoplasia (CIN) grade 2 (CIN2) to classify them as low-grade or high-grade squamous intraepithelial lesions (HSILs).

Objective.—: To describe the relationships of p16 IHC and other biomarkers associated with cervical cancer risk with biopsy diagnoses.

Design.—: A statewide, stratified sample of cervical biopsies diagnosed by community pathologists (CPs), including 1512 CIN2, underwent a consensus, expert pathologist panel (EP) review (without p16 IHC results), p16 IHC interpretation by a third pathology group, and human papillomavirus (HPV) genotyping, results of which were grouped hierarchically according to cancer risk. Antecedent cytologic interpretations were also available.

Results.—: Biopsies were more likely to test p16 IHC positive with increasing severity of CP diagnoses, overall ( ≤ .001) and within each HPV risk group ( ≤ .001 except for low-risk HPV [ < .010]). All abnormal grades of CP-diagnosed biopsies were more likely to test p16 IHC positive with a higher HPV risk group ( < .001), and testing p16 IHC positive was associated with higher HPV risk group than testing p16 IHC negative for each grade of CP-diagnosed biopsies ( < .001). p16 IHC-positive, CP-diagnosed CIN2 biopsies were less likely than CP-diagnosed CIN3 biopsies to test HPV16 positive, have an antecedent HSIL cytology, or to be diagnosed as CIN3 by the EP ( .001 for all). p16 IHC-positive, CP-diagnosed CIN1 biopsies had lower HPV risk groups than p16 IHC-negative, CP-diagnosed CIN2 biopsies ( < .001).

Conclusions.—: p16 IHC-positive, CP-diagnosed CIN2 appears to be lower cancer risk than CP-diagnosed CIN3. LAST classification of "HSIL" diagnosis, which includes p16 IHC-positive CIN2, should annotate the morphologic diagnosis (CIN2 or CIN3) to inform all management decisions, which is especially important for young (<30 years) women diagnosed with CIN2 for whom surveillance rather than treatment is recommended.
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http://dx.doi.org/10.5858/arpa.2019-0241-OADOI Listing
June 2020

A service evaluation between 2-week wait (2WW) skin cancer referrals via teledermatology and the standard face-to-face pathway at a teaching hospital.

Clin Exp Dermatol 2020 Jun 12;45(4):473-476. Epub 2019 Dec 12.

Bristol Dermatology Centre, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.

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http://dx.doi.org/10.1111/ced.14137DOI Listing
June 2020

Determining the clinical significance of the Chest Wall Injury Society taxonomy for multiple rib fractures.

J Trauma Acute Care Surg 2019 12;87(6):1282-1288

From the Department of Cardiothoracic Surgery, Sheffield Teaching Hospitals NHS Foundation Trust, Northern General Hospital, Sheffield, United Kingdom.

Background: The Chest Wall Injury Society (CWIS) proposals for standardized nomenclature for multiple rib fracture (MRF) classifications were derived by international expert Delphi consensus. This study aimed to validate the CWIS taxonomy using a single-instituion clinical database.

Methods: Computed tomography (CT) scans, of 539 consecutive patients with MRFs admitted to a regional major trauma center over a 33-month period, were reviewed (blinded for clinical outcomes). Every rib fracture in every patient was assessed according to each of the CWIS criteria (the degree of displacement, characterization of the fracture line, location of each fracture, and the relationship to neighboring fractures). The clinical significance of the proposed CWIS definitions were determined from independently coded, routinely collected Hospital Episodes Statistics data.

Results: The radiologic aspects of 3,944 individual rib fractures were assessed. Indicators of injury severity (severe displacement greater series length, and flail segment) were positively associated with other fractures (p < 0.001), hemopneumothorax (p < 0.001), pulmonary complications (p = 0.002), adverse outcomes (p = 0.006), mechanical ventilation (p < 0.001) and prolonged hospital and intensive therapy unit length of stay (p = 0.006, p = 0.007 respectively). Four of the CWIS-proposed definitions were correlated with pulmonary complications and adverse outcomes: the categories of displacement, the definition of individual fracture characterization, the presence of a flail segment. Two definitions for which there was CWIS consensus were not correlated with clinical outcomes: the definition of a series to describe associated fractures on neighboring ribs, the inclusion of a paravertebral sector for fracture localization.

Conclusion: The CWIS rib fracture taxonomy demonstrates clinical relevance. There were associations between the severity of category groups within three of the proposed definitions, based on the clinical outcomes observed. Clinical outcome assessment proved inconclusive for four agreed definitions. Comprehensive, multiinstitutional data collection would be required to provide validation for all the CWIS-proposed definitions.

Levels Of Evidence: Level IV.
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http://dx.doi.org/10.1097/TA.0000000000002519DOI Listing
December 2019

Evaluation of Mycobacterium tuberculosis lipoarabinomannan antigen assay and rapid serology blood test for the diagnosis of bovine tuberculosis in Ethiopia.

BMC Vet Res 2019 Oct 22;15(1):359. Epub 2019 Oct 22.

Aklilu Lemma Institute of Pathobiology, Addis Ababa University, Addis Ababa, Ethiopia.

Background: Bovine tuberculosis (bTB) is prevalent in dairy cattle in Ethiopia. Currently used diagnostic tools such as the single intradermal comparative tuberculin test (SICTT) are time consuming and labor intensive. A rapid, easy-to-use and cost-effective diagnostic test would greatly contribute to the control of bTB in developing countries like Ethiopia. In the present study, two point-of-care diagnostic tests were evaluated for the detection of bTB: LIONEX® Animal TB Rapid test, a membrane-based test for the detection of antibodies to Mycobacterium bovis in blood and ALERE® Determine TB Lipoarabinomannan (LAM) Ag, an immunoassay for the detection of lipoarabinomannan (LAM) antigen (Ag) of mycobacteria in urine. A combination of the SICTT and gamma interferon (IFN-γ) test was used as the gold standard for the validation of these point-of-care tests, as it was not feasible to slaughter the study animals to carry out the historical gold standard of mycobacterial culture. A total of 175 heads of cattle having three different bTB infection categories (positive SICTT, negative SICTT, and unknown SICTT status) were used for this study.

Result: The sensitivity and specificity of TB LAM Ag were 72.2% (95% CI = 62.2, 80.4) and 98.8% (95% CI = 93.6, 99.7), respectively, while the sensitivity and specificity of the LIONEX Animal TB rapid test assay were 54% (95% CI = 44.1 64.3) and 98.8% (95% CI = 93.6, 99.7) respectively. The agreement between TB LAM Ag and SICTT was higher (κ = 0.85; 95% CI = 0.65-0.94) than between TB LAM Ag and IFN-γ (κ = 0.67; 95% CI = 0.52-0.81). The agreement between LIONEX Animals TB Rapid blood test and SICTT was substantial, (κ = 0.63; 95% CI = 0.49-0.77) while the agreement between LIONEX Animal TB rapid blood test and IFN-γ test was moderate (κ = 0.53; 95% CI = 0.40-0.67). Analysis of receiver operating curve (ROC) indicated that the area under the ROC curve (AUC) for TB LAM Ag was 0.85 (95% CI = 0.79-0.91) while it was 0.76 (95% CI; =0.69-0.83) for LIONEX Animal TB rapid test assay.

Conclusion: This study showed that TB LAM Ag had a better diagnostic performance and could potentially be used as ancillary either to SICTT or IFN-γ test for diagnosis of bTB.
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http://dx.doi.org/10.1186/s12917-019-2114-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6805383PMC
October 2019

Insights from using in-situ ultraviolet-visible spectroscopy to assess nitrogen treatment and subsurface dynamics in a regenerative stormwater conveyance (RSC) system.

J Environ Manage 2019 Dec 12;252:109656. Epub 2019 Oct 12.

Department of Crop and Soil Sciences, Campus Box 7620, North Carolina State University, Raleigh, NC, 27695, USA. Electronic address:

Regenerative stormwater conveyance (RSC) is a recently developed stormwater control measure that marries the concepts of bioretention and stream restoration. RSC mitigates stormwater runoff by converting surface flow to subsurface seepage using a series of pools and riffles built over a sand media bed. Subsurface seepage flows through media and exits the RSC beneath the outlet weir. Previous studies on RSC pollutant mitigation have focused on surface flow discharges from the RSC. To date, no known research has been conducted on the potential pollutant contributions of RSC seepage, despite the fact that this water also enters receiving waters. This research used Multi-Point Sampling coupled with in-situ ultraviolet-visual spectroscopy to measure nitrogen in seepage during simulated storm events (n = 9) at a field-scale RSC in Raleigh, North Carolina. Calibrations between light absorbance and concentrations were acceptable (Nash-Sutcliffe coefficient > 0.65) for nitrate and total ammoniacal nitrogen (TAN) and very good (Nash-Sutcliffe coefficient > 0.90) for total Kjehdahl nitrogen (TKN). Early storm simulations revealed some initial nutrient flushing from the substrate, which subsided by the third simulation. Overall, subsurface seepage nitrate, TAN, and TKN concentrations were lower by 29%, 57%, and 4% relative to storm inflow concentrations, respectively. Computed subsurface nitrogen concentrations demonstrated temporal variability, highlighting dynamic transport and biogeochemical transformations in saturated and unsaturated conditions. Nitrogen concentrations were lower in seepage than in surface flow; however, due to the high volume of runoff converted to seepage, nitrogen loads discharged in seepage can be larger than those of surface flow. Further research is needed to examine subsurface pollutant reductions under varying hydrologic and seasonal conditions.
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http://dx.doi.org/10.1016/j.jenvman.2019.109656DOI Listing
December 2019

Axillary web syndrome induced by physical exertion.

Clin Exp Dermatol 2020 Apr 19;45(3):382-384. Epub 2019 Sep 19.

Department of Dermatology, Royal Devon and Exeter NHS Foundation Trust, Exeter, UK.

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http://dx.doi.org/10.1111/ced.14089DOI Listing
April 2020

Endothelial Glycocalyx Shedding Occurs during Ex Vivo Lung Perfusion: A Pilot Study.

J Transplant 2019 25;2019:6748242. Epub 2019 Aug 25.

Queensland Lung Transplant Service, The Prince Charles Hospital, Brisbane 4032, Australia.

Background: Damage to the endothelium has been established as a key pathological process in lung transplantation and ex vivo lung perfusion (EVLP), a new technology that provides a platform for the assessment of injured donor lungs. Damage to the lung endothelial glycocalyx, a structure that lines the endothelium and is integral to vascular barrier function, has been associated with lung dysfunction. We hypothesised that endothelial glycocalyx shedding occurs during EVLP and aimed to establish a porcine model to investigate the mechanism underlying glycocalyx breakdown during EVLP.

Methods: Concentrations of endothelial glycocalyx breakdown products, syndecan-1, hyaluronan, heparan sulphate, and CD44, were measured using the ELISA and matrix metalloproteinase (MMP) activity by zymography in the perfusate of both human ( = 9) and porcine ( = 4) lungs undergoing EVLP. Porcine lungs underwent prolonged EVLP (up to 12 hours) with perfusion and ventilation parameters recorded hourly.

Results: During human EVLP, endothelial glycocalyx breakdown products in the perfusate increased over time. Increasing MMP-2 activity over time was positively correlated with levels of syndecan-1 ( = 0.886; =0.03) and hyaluronan ( = 0.943; =0.02). In the porcine EVLP model, hyaluronan was the only glycocalyx product detectable during EVLP (1 hr: 19 (13-84) vs 12 hr: 143 (109-264) ng/ml; =0.13). Porcine hyaluronan was associated with MMP-9 activity ( = 0.83; =0.02) and also with dynamic compliance ( = 0.57; =0.03).

Conclusion: Endothelial glycocalyx products accumulate during both porcine and human EVLP, and this accumulation parallels an accumulation of matrix-degrading enzyme activity. Preliminary evidence in our porcine EVLP model suggests that shedding may be related to organ function, thus warranting additional study.
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http://dx.doi.org/10.1155/2019/6748242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6732651PMC
August 2019

Role of HPV Genotype, Multiple Infections, and Viral Load on the Risk of High-Grade Cervical Neoplasia.

Cancer Epidemiol Biomarkers Prev 2019 11 5;28(11):1816-1824. Epub 2019 Sep 5.

Center for HPV Prevention, University of New Mexico Health Sciences Center, Albuquerque, New Mexico.

Background: Human papillomavirus (HPV) testing provides a much more sensitive method of detection for high-grade lesions than cytology, but specificity is low. Here, we explore the extent to which full HPV genotyping, viral load, and multiplicity of types can be used to improve specificity.

Methods: A population-based sample of 47,120 women undergoing cervical screening was tested for 13 high-risk HPV genotypes. Positive predictive values (PPV) for cervical intraepithelial neoplasia (CIN) grade 2 or worse (CIN2+; = 3,449) and CIN3 or worse (CIN3+; = 1,475) over 3 years of follow-up were estimated for HPV genotype and viral load. Weighted multivariate logistic regression models were used to estimate the odds of CIN2+ or CIN3+ according to genotype, multiplicity of types, and viral load.

Results: High-risk HPV was detected in 15.4% of women. A hierarchy of HPV genotypes based on sequentially maximizing PPVs for CIN3+ found HPV16>33>31 to be the most predictive, followed sequentially by HPV18>35>58>45>52>59>51>39>56>68. After adjusting for higher ranked genotypes, the inclusion of multiple HPV infections added little to risk prediction. High viral loads for HPV18, 35, 52, and 58 carried more risk than low viral loads for HPV16, 31, and 33. High viral load for HPV16 was significantly more associated with CIN3+ than low viral load.

Conclusions: HPV genotype and viral load, but not multiplicity of HPV infections, are important predictors of CIN2+ and CIN3+.

Impact: The ability to identify women at higher risk of CIN2+ and CIN3+ based on both HPV genotype and viral load could be important for individualizing triage plans, particularly as HPV becomes the primary screening test.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-0239DOI Listing
November 2019

Sofa dermatitis again? A case report of allergic contact dermatitis to octylisothiazolinone from a leather reclining chair.

Contact Dermatitis 2020 Mar 28;82(3):161-162. Epub 2019 Aug 28.

Bristol Dermatology Centre, University Hospitals Bristol NHS Foundation Trust, Bristol, UK.

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http://dx.doi.org/10.1111/cod.13380DOI Listing
March 2020

Evaluation of the tuberculosis culture color plate test for rapid detection of drug susceptible and drug-resistant Mycobacterium tuberculosis in a resource-limited setting, Addis Ababa, Ethiopia.

PLoS One 2019 28;14(5):e0215679. Epub 2019 May 28.

Department of Microbiology, Immunology and Parasitology, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.

Timely diagnosis of tuberculosis (TB) is limited in Ethiopia. We evaluated the performance of a low technology, thin layer agar, Mycobacterium tuberculosis (M.tb) culture color plate (TB-CX) test with concurrent drug susceptibility testing (DST) to isoniazid (INH), rifampin (RIF), and pyrazinamide (PZA) directly from sputum specimens. Patients undergoing examination for TB and multidrug-resistant (MDR)-TB were enrolled in Addis Ababa, Ethiopia from March 2016 to February 2017. All subjects received a GeneXpert MTB/RIF PCR test. TB-CX test results were compared to reference Löwenstein-Jensen (LJ) culture for M.tb detection and DST for susceptibility to INH and RIF. Kappa statistic was applied to test agreement between results for TB-CX test and the reference methods, a cut-off Kappa value of 0.75 was considered as high level of agreements. A total of 137 participants were analyzed: 88 (64%) were new TB cases, 49 (36%) were re-treatment cases. The TB-CX test detected M.tb and DST in an average of 13 days compared to 50 days for the conventional DST result. The sensitivity and specificity of the TB-CX test for detecting M.tb were 94% and 98%, respectively (concordance, 96%; kappa 0.91). The sensitivity of the TB-CX test to detect drug resistance to INH, RIF, and MDR-TB was 91%, 100%, and 90% respectively. The specificity of the TB-CX test for detecting INH, RIF, and MDR-TB was 94%, 40%, and 94% respectively. Overall agreement between TB-CX test and LJ DST for detection of MDR-TB was 93%. The TB-CX test showed strong agreement with the GeneXpert test for detecting M.tb (89%, kappa 0.76) but low agreement for the detection of RIF resistance (57%, kappa 0.28). The TB-CX test was found to be a good alternative method for screening of TB and selective drug resistant-TB in a timely and cost-efficient manner.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0215679PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6538369PMC
January 2020

Effect of PolyGlycopleX (PGX) Consumption on Blood Lipid Profiles in Healthy, Low CVD Risk Overweight Adults.

Nutrients 2019 Mar 27;11(4). Epub 2019 Mar 27.

School of Public Health, Faculty of Health Sciences, Curtin University, Perth, WA 6845, Australia.

Raised blood lipid levels are associated with a risk of a cardiovascular disease (CVD). Moderate reductions in several CVD factors such as total, low-density lipoprotein (LDL) cholesterol and non-high-density lipoprotein (non-HDL) cholesterol concentrations may be more effective in reducing overall risk than a major reduction in just one. A blind, randomised controlled trial was conducted with 120 healthy overweight (BMI 25⁻30) adults aged 25⁻70 years who were non-smokers, not diabetic and of low risk of cardiovascular disease, as assessed by the Framingham risk equation. Participants consumed 4.5 g PolyGlycopleX (PGX) as softgel capsules (PGXS) or 5 g PGX granules (PGXG) or 5 g rice flour (RF) with meals three times a day for 12 weeks. Total, LDL and non-HDL cholesterol were all significantly reduced (-6%, -5% and -3.5%, respectively) post the PGX granule treatment; however, PGX in softgel capsule form did not affect blood lipid profiles. Daily consumption of PGX granules in overweight low CVD risk adults produced lipid changes indicating a CVD preventative benefit.
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http://dx.doi.org/10.3390/nu11040717DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6520870PMC
March 2019

Systemic agents for psoriasis and their relevance to primary care.

Br J Gen Pract 2019 Feb;69(679):96-97

Department of Dermatology, University Hospitals Coventry and Warwickshire NHS Trust, Coventry.

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http://dx.doi.org/10.3399/bjgp19X701225DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355284PMC
February 2019

Visceral adipose tissue is associated with poor diet quality and higher fasting glucose in adults with cystic fibrosis.

J Cyst Fibros 2019 05 18;18(3):430-435. Epub 2019 Jan 18.

Division of Endocrinology, Metabolism and Lipids, Department of Medicine, Emory University School of Medicine; Atlanta, GA, USA; Nutrition and Health Sciences Doctoral Program, Emory University Rollins School of Public Health, Atlanta, GA, USA; Center for Cystic Fibrosis and Airways Disease Research; Atlanta, GA, USA. Electronic address:

Background: Body fat distribution and diet quality influence clinical outcomes in general populations but are understudied in individuals with cystic fibrosis (CF). The aim of this pilot study was to assess body fat distribution and diet quality in relation to fasting glucose and lung function in adults with CF.

Methods: Subjects were 24 adults (ages 18-50) with CF and 25 age-matched controls. The Healthy Eating Index 2015 (HEI-2015) was calculated from 3-day food records and data were adjusted per 1000 kcal. Whole and regional body composition, including visceral adipose tissue (VAT), was assessed by dual energy X-ray absorptiometry.

Results: Subjects with CF reported more added sugar intake [26.1 (IQR 18.1) vs. 12.9 (12.5) g/1000 kcal, p < 0.001] and had lower HEI-2015 scores [48.3 (IQR 9.9) vs. 63.9 (27.3), p < 0.001] compared to controls. There were no differences in BMI, total body fat, or lean body mass (LBM) between subjects with CF and controls (p > 0.05 for all), although subjects with CF had higher VAT than control subjects [0.3 (IQR 0.3) vs 0.1 (0.3) kg, p = 0.02]. Among subjects with CF, VAT was positively associated with added sugar intake (p < 0.001) and fasting blood glucose (p = 0.04). Lung function was positively associated with BMI (p = 0.005) and LBM (p = 0.03) but not with adiposity indicators.

Conclusions: These novel data link body fat distribution with diet quality and fasting glucose levels in adults with CF, whereas LBM was associated with lung function. This study highlights the importance of increasing diet quality and assessing body composition and fat distribution in the CF population.
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http://dx.doi.org/10.1016/j.jcf.2019.01.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6545253PMC
May 2019

Spatial variation in a top marine predator's diet at two regionally distinct sites.

PLoS One 2019 2;14(1):e0209032. Epub 2019 Jan 2.

MaREI Centre, Environmental Research Institute, University College Cork, Cork, Ireland.

In ecological studies it is often assumed that predator foraging strategies and resource use are geographically and seasonally homogeneous, resulting in relatively static trophic relationships. However, certain centrally placed foragers (e.g. seals) often have terrestrial sites for breeding, resting, and moulting that are geographically distinct, and associated with different habitat types. Therefore, accurate estimations of predator diet at relevant spatial and temporal scales are key to understanding energetic requirements, predator-prey interactions and ecosystem structure. We investigate geographic variation in the diet of grey seals (Halichoerus grypus), a relatively abundant and widely distributed central place forager, to provide insights into geographic variation in resource use. Prey composition was identified using scat samples collected over concurrent timescales and a multivariate approach was used to analyse diet from two contrasting habitats. Regional differences in prey assemblages occurred within all years (2011-2013) and all seasons (ANOSIM, all p<0.05), apart from in winter. Telemetry data were used to identify core foraging areas and habitats most likely associated with scat samples collected at the two haul-out sites. Regional differences in the diet appear to reflect regional differences in the physical habitat features, with seals foraging in deeper waters over sandy substrates showing a higher prevalence of pelagic and bentho-pelagic prey species such as blue whiting and sandeels. Conversely, seals foraging in comparatively shallow waters had a greater contribution of demersal and groundfish species such as cephalopods and flatfish in their diet. We suggest that shallower waters enable seals to spend more time foraging along the benthos while remaining within aerobic dive limits, resulting in more benthic species in the diet. In contrast, the diet of seals hauled-out in areas adjacent to deeper waters indicates that either seals engage in a more pelagic foraging strategy, or that seals can spend less time at the benthos, resulting in comparatively more pelagic prey recovered in the diet. The substantial differences in prey assemblages over a small spatial scale (<300 km) demonstrates the importance of using regionally-specific diet information in ecosystem-based models to better account for different trophic interactions.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0209032PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6314570PMC
September 2019

The reproducibility of cardiac magnetic resonance imaging measures of aortic stiffness and their relationship to cardiac structure in prevalent haemodialysis patients.

Clin Kidney J 2018 Dec 21;11(6):864-873. Epub 2018 Jun 21.

Department of Cardiovascular Sciences, University of Leicester, Leicester, UK.

Background: Aortic stiffness is one of the earliest signs of cardiovascular disease (CVD) in patients with chronic kidney disease and an independent predictor of mortality. It is thought to drive left ventricular (LV) remodelling, an established biomarker for mortality. The relationship between direct and indirect measures of aortic stiffness and LV remodelling is not defined in dialysis patients, nor are the reproducibility of methods used to assess aortic stiffness using cardiac magnetic resonance (CMR) imaging.

Methods: Using 3T CMR, we report the results of (i) the interstudy, interobserver and intra-observer reproducibility of ascending aortic distensibility (AAD), descending aortic distensibility (DAD) and aortic pulse wave velocity (aPWV) in 10 haemodialysis (HD) patients and (ii) the relationship between AAD, DAD and aPWV and LV mass index (LVMi) and LV remodelling in 70 HD patients.

Results: Inter- and intra-observer variability of AAD, DAD and aPWV were excellent [intraclass correlation (ICC) > 0.9 for all]. Interstudy reproducibility of AAD was excellent {ICC 0.94 [95% confidence interval (CI) 0.78-0.99]}, but poor for DAD and aPWV [ICC 0.51 (-0.13-0.85) and 0.51 (-0.31-0.89)]. AAD, DAD and aPWV associated with LVMi on univariate analysis (β = -0.244, P = 0.04; β =-0.315, P < 0.001 and β = 0.242, P = 0.04, respectively). Only systolic blood pressure, serum phosphate and a history of CVD remained independent determinants of LVMi on multivariable linear regression.

Conclusions: AAD is the most reproducible CMR-derived measure of aortic stiffness in HD patients. CMR-derived measures of aortic stiffness were not independent determinants of LVMi in HD patients. Whether one should target blood pressure over aortic stiffness to mitigate cardiovascular risk still needs determination.
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http://dx.doi.org/10.1093/ckj/sfy042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6275449PMC
December 2018