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1.
Cell ; 160(1-2): 269-84, 2015 Jan 15.
Article in English | MEDLINE | ID: mdl-25594183

ABSTRACT

The stem cells that maintain and repair the postnatal skeleton remain undefined. One model suggests that perisinusoidal mesenchymal stem cells (MSCs) give rise to osteoblasts, chondrocytes, marrow stromal cells, and adipocytes, although the existence of these cells has not been proven through fate-mapping experiments. We demonstrate here that expression of the bone morphogenetic protein (BMP) antagonist gremlin 1 defines a population of osteochondroreticular (OCR) stem cells in the bone marrow. OCR stem cells self-renew and generate osteoblasts, chondrocytes, and reticular marrow stromal cells, but not adipocytes. OCR stem cells are concentrated within the metaphysis of long bones not in the perisinusoidal space and are needed for bone development, bone remodeling, and fracture repair. Grem1 expression also identifies intestinal reticular stem cells (iRSCs) that are cells of origin for the periepithelial intestinal mesenchymal sheath. Grem1 expression identifies distinct connective tissue stem cells in both the bone (OCR stem cells) and the intestine (iRSCs).


Subject(s)
Bone and Bones/cytology , Intercellular Signaling Peptides and Proteins/metabolism , Intestine, Small/cytology , Mesenchymal Stem Cells/cytology , Animals , Cartilage/metabolism , Intestine, Small/metabolism , Mesenchymal Stem Cells/metabolism , Mice , Mice, Inbred C57BL
2.
Am J Perinatol ; 2024 Feb 28.
Article in English | MEDLINE | ID: mdl-38216140

ABSTRACT

OBJECTIVE: Gastroschisis is the most common congenital abdominal wall defect, with an increasing incidence. It results in extrusion of abdominal contents with associated delayed intestinal motility. Abnormal heart rate characteristics (HRCs) such as decreased variability occur due to the inflammatory response to sepsis in preterm infants. This study aimed to test the hypothesis that infants with gastroschisis have decreased heart rate variability (HRV) after birth and that this physiomarker may predict outcomes. STUDY DESIGN: We analyzed heart rate data from and clinical variables for all infants admitted with gastroschisis from 2009 to 2020. RESULTS: Forty-seven infants were admitted during the study period and had available data. Complex gastroschisis infants had reduced HRV after birth. For those with sepsis and necrotizing enterocolitis, abnormal HRCs occurred early in the course of illness. CONCLUSION: Decreased HRV was associated with complex gastroschisis. Infants in this group experienced complications that prolonged time to full enteral feeding and time on total parenteral nutrition. KEY POINTS: · Infants with gastroschisis can be classified into two subcategories, simple and complex disease.. · Those with complex disease often require prolonged stays in the neonatal intensive care unit and costly hospitalizations. We hypothesized that infants with complex gastroschisis are more likely to have abnormal HRC due to intestinal inflammation.. · In this study, we identified associations between abnormal HRV, heart rate characteristicHRC, and the development of gastroschisis complications. Additionally, we described differences in clinical characteristics between infants with complex versus simple gastroschisis..

3.
Pediatr Surg Int ; 39(1): 238, 2023 Jul 24.
Article in English | MEDLINE | ID: mdl-37486585

ABSTRACT

PURPOSE: Computed tomography (CT) is still used in the imaging diagnosis of acute appendicitis in children at many hospitals. We implemented an ultrasound (US) and fast magnetic resonance imaging (MRI) pathway for suspected appendicitis at our institution with the goal of reducing radiation exposure in children. METHODS: All children (< 18 years old) who underwent appendectomy between January 2011 and July 2021 were reviewed. Data were collected on all imaging studies performed. In December 2015, we initiated an imaging pathway for suspected acute appendicitis. US was the initial imaging study, and a rapid protocol MRI was performed if US was equivocal. Those could not tolerate MRI underwent CT. We evaluated the difference in percentage of patients who underwent CT before and after pathway initiation. RESULTS: 554 patients who underwent appendectomy did not have prior imaging studies on presentation to our hospital and were included in analysis. After initiating the pathway, the use of abdominal US increased from 87% (220 of 254) to 97% (291 of 300, p < 0.0001) and the use of MRI increased by 100% (0 MRIs pre-protocol, 90 of 300 patients post-protocol, p < 0.0001). CT utilization decreased significantly from 32% (82 of 254) to 2% (6 of 300, p < 0.0001). CONCLUSION: Embracing a new US and rapid MRI pathway to evaluate pediatric patients with suspected acute appendicitis resulted in significant reduction in CT utilization and therefore radiation exposure.


Subject(s)
Appendicitis , Child , Humans , Adolescent , Appendicitis/diagnostic imaging , Appendicitis/surgery , Retrospective Studies , Ultrasonography/methods , Tomography, X-Ray Computed/methods , Magnetic Resonance Imaging , Appendectomy , Acute Disease , Hospitals, Pediatric
4.
J Surg Res ; 276: 291-297, 2022 08.
Article in English | MEDLINE | ID: mdl-35413578

ABSTRACT

INTRODUCTION: Given the negative clinical effects opiates can have, the search for alternative forms of analgesia to treat post-operative pain continues. We implemented an opiate reduction strategy using standing intravenous (IV) acetaminophen for infants aged less than 1 y who underwent abdominal or anorectal surgery and recovered on the acute care floor. MATERIALS AND METHODS: Infants were administered standing IV acetaminophen every 6 h for a minimum of 48 h as the main form of post-operative analgesia. Pain severity was objectively scored using the Face, Legs, Activity, Cry, and Consolability (FLACC) scale. A before-and-after retrospective cohort analysis was performed and process control charts were used to examine trends in post-operative opiate use in our pre-intervention (January 2012 to January 2016), roll-out (January 2016 to December 2016), and post-intervention (December 2016 to December 2020) cohorts. RESULTS: A total of 131 infants were included: 56 in the pre-intervention, 17 in the roll-out, and 58 in the post-intervention group. Patient demographics were equivalent. The intervention was associated with a 36-fold reduction in post-operative morphine equivalents (median 0.36 mg/kg in the pre-intervention group versus 0.0 mg/kg in the post-intervention group, P < 0.0001). The median and maximum FLACC pain scores along with clinical safety profiles were statistically equivalent between the groups. The intervention was associated with a 2-d reduction in post-operative length of stay (P < 0.0001). CONCLUSIONS: Standing IV acetaminophen is associated with a reduction of post-operative opioid use in infants being treated on the acute care floor while maintaining equivalent FLACC pain scores. Similar opiate reduction strategies may be of value at other institutions.


Subject(s)
Opiate Alkaloids , Opioid-Related Disorders , Acetaminophen/therapeutic use , Analgesics, Opioid/therapeutic use , Humans , Opiate Alkaloids/therapeutic use , Pain, Postoperative/drug therapy , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Retrospective Studies
5.
Pediatr Surg Int ; 38(2): 277-283, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34709434

ABSTRACT

BACKGROUND: In July 2003, an 80-h work week restriction for residencies was mandated. This was met with skepticism regarding its potential impact on operative training. We hypothesized no difference in outcomes for pediatric surgeons who trained under duty hour restrictions compared to historical complication rates. METHODS: Dual-institutional review of pediatric patients who underwent five of the most common operations (2013-2018) by first-year pediatric surgeons who trained under duty hour restrictions was performed. Tests of proportions were used to compare complication rates to published rates on data collected prior to 2003. RESULTS: Patient mean age was 10.1 years. No significant differences (p values > 0.05) were found in laparoscopic appendectomy rates of infection, bleeding or intra-abdominal abscess compared to previously published rates. Pyloromyotomy rates of infection or duodenal perforation were not different. No differences were detected in rates of infection, recurrence or testicular atrophy for inguinal hernia repair. Umbilical hernia rates of infection, bleeding, and recurrence were also not different. There was no difference in CVC rates of hemopneumothoraces; significantly more bleeding events were detected (1.2% vs. 0.1%; p value = 0.04). CONCLUSION: In this study, first-year complication rates of pediatric surgeons who trained under duty hour restrictions were not significantly different when compared to published rates.


Subject(s)
Hernia, Inguinal , Internship and Residency , Laparoscopy , Surgeons , Appendectomy , Child , Hernia, Inguinal/surgery , Herniorrhaphy , Humans , Postoperative Complications
6.
Behav Res Methods ; 54(1): 94-116, 2022 02.
Article in English | MEDLINE | ID: mdl-34109561

ABSTRACT

The degree of spatial similarity between the gaze of participants viewing dynamic stimuli such as videos has been previously measured using metrics which are based on the NSS (Normalized Scanpath Saliency). Methods currently used to calculate this metric rely upon a numerical grid, which can be computationally prohibitive for a variety of otherwise useful applications such as Monte Carlo analyses. In the present work we derive a new analytical calculation method for the same metric that yields equal or more accurate results, but with speeds than can be orders of magnitude faster (depending on parameters). Our analytical method scales well with dimensionality, and could also be of use for other applications. The drawback is that it can become very slow if the number of participants in the study is very large or if the gaze sampling rate is high. We provide performance benchmarks for a Fortran implementation of our method, and make available the source code developed.


Subject(s)
Eye Movements , Fixation, Ocular , Benchmarking , Humans , Monte Carlo Method
7.
Circulation ; 142(6): 546-555, 2020 08 11.
Article in English | MEDLINE | ID: mdl-32654539

ABSTRACT

BACKGROUND: Studies examining the role of factor V Leiden among patients at higher risk of atherothrombotic events, such as those with established coronary heart disease (CHD), are lacking. Given that coagulation is involved in the thrombus formation stage on atherosclerotic plaque rupture, we hypothesized that factor V Leiden may be a stronger risk factor for atherothrombotic events in patients with established CHD. METHODS: We performed an individual-level meta-analysis including 25 prospective studies (18 cohorts, 3 case-cohorts, 4 randomized trials) from the GENIUS-CHD (Genetics of Subsequent Coronary Heart Disease) consortium involving patients with established CHD at baseline. Participating studies genotyped factor V Leiden status and shared risk estimates for the outcomes of interest using a centrally developed statistical code with harmonized definitions across studies. Cox proportional hazards regression models were used to obtain age- and sex-adjusted estimates. The obtained estimates were pooled using fixed-effect meta-analysis. The primary outcome was composite of myocardial infarction and CHD death. Secondary outcomes included any stroke, ischemic stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality. RESULTS: The studies included 69 681 individuals of whom 3190 (4.6%) were either heterozygous or homozygous (n=47) carriers of factor V Leiden. Median follow-up per study ranged from 1.0 to 10.6 years. A total of 20 studies with 61 147 participants and 6849 events contributed to analyses of the primary outcome. Factor V Leiden was not associated with the combined outcome of myocardial infarction and CHD death (hazard ratio, 1.03 [95% CI, 0.92-1.16]; I2=28%; P-heterogeneity=0.12). Subgroup analysis according to baseline characteristics or strata of traditional cardiovascular risk factors did not show relevant differences. Similarly, risk estimates for the secondary outcomes including stroke, coronary revascularization, cardiovascular mortality, and all-cause mortality were also close to identity. CONCLUSIONS: Factor V Leiden was not associated with increased risk of subsequent atherothrombotic events and mortality in high-risk participants with established and treated CHD. Routine assessment of factor V Leiden status is unlikely to improve atherothrombotic events risk stratification in this population.


Subject(s)
Coronary Disease/genetics , Factor V/genetics , Genotype , Thrombosis/genetics , Atherosclerosis , Clinical Trials as Topic , Coronary Disease/diagnosis , Coronary Disease/mortality , Genetic Predisposition to Disease , Humans , Polymorphism, Single Nucleotide , Precision Medicine , Prognosis , Risk
8.
J Surg Oncol ; 124(1): 16-24, 2021 Jul.
Article in English | MEDLINE | ID: mdl-33788957

ABSTRACT

BACKGROUND: Childhood cancer survivors (CCS) are at elevated risk of secondary malignancies (SM). Enhanced screening for SM is recommended, but compliance is poor. We hypothesized that CCS with adult-onset SM (colorectal cancer [CRC], melanoma, or breast cancer [BC]) would present with more advanced disease and have decreased overall survival (OS). METHODS: The Surveillance, Epidemiology, and End Results Program was queried for patients diagnosed with cancer at age less than or equal to 18 also diagnosed with adult-onset CRC, melanoma, or BC. A cohort without a history of prior malignancy was likewise identified. Tumor features and clinical outcomes were compared. RESULTS: CCS with a SM (n = 224) were compared with patients without a childhood cancer history (n = 1,392,670). CCS were diagnosed younger (BC = 37.6 vs. 61.3, p < 0.01, CRC = 35.0 vs. 67.1, p < 0.01, melanoma = 29.6 vs. 61.3 years old, p < 0.01). CCS with BC were more likely to have Stage III or IV disease (25.2% vs. 16.5%, p = 0.01). Hormone-receptor expression also differed; CCS were less likely to develop Luminal A-type tumors (48.6% vs. 66.9%, p = 0.01). After age-adjustment, CCS had worse OS (Hazard ratio: CRC = 2.449, p < 0.01, melanoma = 6.503, p < 0.01, BC = 3.383, p < 0.01). CONCLUSION: CCS were younger when diagnosed with a SM. After age-adjustment, OS was diminished. Heightened surveillance may be necessary for CCS diagnosed with SM.


Subject(s)
Breast Neoplasms/mortality , Cancer Survivors/statistics & numerical data , Colorectal Neoplasms/mortality , Melanoma/mortality , SEER Program/statistics & numerical data , Adolescent , Adult , Aged , Breast Neoplasms/pathology , Case-Control Studies , Child , Colorectal Neoplasms/pathology , Female , Follow-Up Studies , Humans , Male , Melanoma/pathology , Prognosis , Retrospective Studies , Survival Rate
9.
Pediatr Surg Int ; 37(5): 627-630, 2021 May.
Article in English | MEDLINE | ID: mdl-33423100

ABSTRACT

PURPOSE: Pediatric surgeons at our institution are often asked by families about a theoretical increased risk of severe common upper respiratory infections in children status post lung resection. No data exist on this topic. We, therefore, aimed to examine the risk of severe respiratory infection in children after pulmonary resection. METHODS: A chart review was conducted on all pediatric patients who underwent pulmonary resection between August 1st, 2009 and January 31st, 2019. Collected data included patient characteristics, operation, complications and any admission for respiratory infection. RESULTS: Fifty-seven patients met inclusion criteria. Resections included lobectomy (45.6%), segmentectomy (14.0%), and wedge resection (40.4%). Twelve (21.1%) were immunocompromised and 6 (10.5%) had post-operative complications. Within 1 year of surgery, 2 (3.5%) patients were hospitalized for a viral upper respiratory illness (URI), 1 (1.8%) for bacterial pneumonia, and none due to influenza. CONCLUSION: In the general pediatric population, the risk of admission for respiratory illness is 3-21%. At this institution, overall risk of respiratory infection after lung resection appears comparable to baseline community risk. Our findings could aid counseling pediatric patients and their families regarding the 1-year risk of infection after lung resection.


Subject(s)
Lung Neoplasms/surgery , Postoperative Complications , Respiratory Tract Infections/etiology , Child , Female , Humans , Infant , Lung/surgery , Male , Pediatrics , Pneumonectomy
10.
Pediatr Surg Int ; 37(9): 1295-1301, 2021 Sep.
Article in English | MEDLINE | ID: mdl-34091749

ABSTRACT

BACKGROUND: The incidence of inguinal hernias in premature infants is approximately 30%. Due to concerns about a high risk of incarceration, early repair is commonly performed. We present a series of patients whose families opted to delay repair until after 55 weeks corrected gestational age (GA) and experienced safe clinical regression of their hernias. METHODS: Between June 2015 and July 2020, premature infants (< 37 weeks GA) diagnosed with inguinal hernias on physical examination were identified. Families of eligible infants were offered either immediate or delayed repair after 55 weeks corrected GA. Infants whose families elected to delay were followed until their hernia(s) clinically regressed, or until older than 55 weeks. RESULTS: Families of 68 infants consented to delay repair. 23 infants (33.8%) had hernias that clinically regressed at median follow up from diagnosis of 14.1 weeks. Univariate analysis demonstrated female sex as a significant predictor of hernia clinical regression (OR: 3.08; p = 0.046). Of the 45 infants who underwent repair, 84.4% safely progressed to 55 weeks corrected GA prior to. CONCLUSION: Delaying inguinal hernia repair in this series of premature infants until after 55 weeks corrected GA revealed that one third of hernias, especially in females, safely regressed upon follow-up examination.


Subject(s)
Hernia, Inguinal , Infant, Premature, Diseases , Female , Hernia, Inguinal/surgery , Herniorrhaphy , Humans , Infant , Infant, Newborn , Infant, Premature , Infant, Premature, Diseases/surgery
11.
Harefuah ; 160(7): 448-454, 2021 Jul.
Article in Hebrew | MEDLINE | ID: mdl-34263573

ABSTRACT

INTRODUCTION: In recent years, nuclear medicine has become a diverse and central profession that influences the diagnosis and treatment of patients with diseases from all fields of medicine. Imaging through nuclear medicine is a significant step in the process of making therapeutic decisions and evaluating patients with malignancy, infectious or inflammatory process, heart problems, neurological disorders and more. The advantages of diagnostic methods from the field of nuclear medicine arise from their non-invasiveness and from the possibility of providing functional and metabolic information at a very early stage during the course of the disease. In the last two decades, hybrid imaging devices, PET-CT (positron emission tomography (PET)-computed tomography (CT)) and then SPECT-CT (single-photon emission computerized tomography (SPECT) - computed tomography (CT)) and PET-MRI (positron emission tomography (PET)- magnetic resonance imaging (MRI)) have been developed. Thereby, the field has undergone a major revolution accompanied by a significant increase in the volume of scans thanks to the improved diagnostic accuracy possible with the latest imaging devices. Recently, another breakthrough has occurred with the successful implementation of a unique method of treatment in nuclear medicine, Theranostics. This is just the beginning. More accurate and faster digital imaging devices have been developed with the ability to reduce patient exposure to radiation, state-of-the-art molecular imaging markers have been developed and new theranostics medications are being developed. Along with the development of artificial intelligence tools, further significant changes are expected to take place in this high-tech field. The main purpose of the review is to provide a source of information to the reading public, even if they are unfamiliar with the subject, for innovations in this field and demonstrating the role of nuclear medicine in diagnosing a number of diseases and planning personalised medical treatment for patients with a view on nuclear medicine in Israel.


Subject(s)
Nuclear Medicine , Artificial Intelligence , Humans , Israel , Magnetic Resonance Imaging , Positron Emission Tomography Computed Tomography , Positron-Emission Tomography
12.
Pediatr Transplant ; 23(3): e13374, 2019 05.
Article in English | MEDLINE | ID: mdl-30786108

ABSTRACT

BACKGROUND: Gastrostomy tube (GT) placement is a common pediatric surgical procedure typically indicated for oral aversion. This may develop in patients with congenital heart disease (CHD) who require an orthotopic heart transplant (OHT). The safety profile of GT placement in OHT patients who are immunosuppressed is unknown. Given the potential increased risk of wound site complications on a patient receiving immunosuppression, we sought to determine the safety profile of GT placement in pediatric patients with OHT. MATERIALS AND METHODS: We performed a retrospective case series of all pediatric OHT recipients who subsequently underwent GT placement from January 1, 2009, to August 1, 2018, at the University of Virginia Children's Hospital. Major GT complications of wound breakdown, wound infection, peristomal GT leakage, ileus, or persistent emesis, and minor GT complication including the presence of granulation tissue are reported. RESULTS: Six patients who had a pediatric OHT subsequently underwent GT placement over the study period. There were no major 30-day or 90-day GT complications. One patient had excessive granulation tissue at their GT site. There were no accounts of acute kidney injury, urinary tract infection, sepsis, or pneumonia. CONCLUSION: Gastrostomy tube (GT) placement appears to be safe in pediatric OHT patients who are on immunosuppressive medications and unable to feed orally. This is the first study documenting the safety profile of GTs in pediatric OHT patients and may aid clinicians to make decisions regarding this intervention.


Subject(s)
Catheters, Indwelling , Gastrostomy/methods , Heart Failure/surgery , Heart Transplantation , Immunosuppression Therapy , Female , Hospitals, Pediatric , Humans , Immunosuppressive Agents/therapeutic use , Infant , Male , Patient Safety , Postoperative Complications/etiology , Retrospective Studies , Risk , Virginia , Wound Healing
13.
Conscious Cogn ; 74: 102781, 2019 09.
Article in English | MEDLINE | ID: mdl-31319238

ABSTRACT

In some cases, people overestimate how much they can see. This can produce a metacognitive blind spot that may lead participants to devote fewer cognitive resources than a visual task demands. However, little research has tested whether individuals who are particularly optimistic about their visual capabilities are susceptible to poor visual performance. We tested whether optimistic metacognitive judgments would predict poor performance in a visual task, especially when it placed a large attentional load on the participant, and when it required balancing between multiple sources of information. We tested participants in a simplified battle command simulation in which they were asked to detect visual changes. Participants who predicted spatially expansive visual attention performance performed more poorly in the change detection task when the task required tracking larger numbers of aircraft, and when it included a secondary change-list display.


Subject(s)
Attention/physiology , Metacognition/physiology , Optimism , Pattern Recognition, Visual/physiology , Psychomotor Performance/physiology , Space Perception/physiology , Adult , Aged , Awareness/physiology , Female , Humans , Judgment/physiology , Male , Middle Aged , Young Adult
14.
Radiology ; 287(3): 795-804, 2018 06.
Article in English | MEDLINE | ID: mdl-29714681

ABSTRACT

Purpose To quantify the burden and distribution of asymptomatic atherosclerosis in a population with a low to intermediate risk of cardiovascular disease. Materials and Methods Between June 2008 and February 2013, 1528 participants with 10-year risk of cardiovascular disease less than 20% were prospectively enrolled. They underwent whole-body magnetic resonance (MR) angiography at 3.0 T by using a two-injection, four-station acquisition technique. Thirty-one arterial segments were scored according to maximum stenosis. Scores were summed and normalized for the number of assessable arterial segments to provide a standardized atheroma score (SAS). Multiple linear regression was performed to assess effects of risk factors on atheroma burden. Results A total of 1513 participants (577 [37.9%] men; median age, 53.5 years; range, 40-83 years) completed the study protocol. Among 46 903 potentially analyzable segments, 46 601 (99.4%) were interpretable. Among these, 2468 segments (5%) demonstrated stenoses, of which 1649 (3.5%) showed stenosis less than 50% and 484 (1.0%) showed stenosis greater than or equal to 50%. Vascular stenoses were distributed throughout the body with no localized distribution. Seven hundred forty-seven (49.4%) participants had at least one stenotic vessel, and 408 (27.0%) participants had multiple stenotic vessels. At multivariable linear regression, SAS correlated with age (B = 3.4; 95% confidence interval: 2.61, 4.20), heart rate (B = 1.23; 95% confidence interval: 0.51, 1.95), systolic blood pressure (B = 0.02; 95% confidence interval: 0.01, 0.03), smoking status (B = 0.79; 95% confidence interval: 0.44, 1.15), and socioeconomic status (B = -0.06; 95% confidence interval: -0.10, -0.02) (P < .01 for all). Conclusion Whole-body MR angiography identifies early vascular disease at a population level. Although disease prevalence is low on a per-vessel level, vascular disease is common on a per-participant level, even in this low- to intermediate-risk cohort. © RSNA, 2018 Online supplemental material is available for this article.


Subject(s)
Atherosclerosis/diagnostic imaging , Atherosclerosis/epidemiology , Magnetic Resonance Angiography/methods , Whole Body Imaging/methods , Adult , Aged , Aged, 80 and over , Contrast Media , Female , Humans , Image Enhancement/methods , Male , Middle Aged , Prevalence , Prospective Studies , Risk , Scotland/epidemiology
15.
Circ Res ; 119(5): 652-65, 2016 Aug 19.
Article in English | MEDLINE | ID: mdl-27418629

ABSTRACT

RATIONALE: The diabetes mellitus drug metformin is under investigation in cardiovascular disease, but the molecular mechanisms underlying possible benefits are poorly understood. OBJECTIVE: Here, we have studied anti-inflammatory effects of the drug and their relationship to antihyperglycemic properties. METHODS AND RESULTS: In primary hepatocytes from healthy animals, metformin and the IKKß (inhibitor of kappa B kinase) inhibitor BI605906 both inhibited tumor necrosis factor-α-dependent IκB degradation and expression of proinflammatory mediators interleukin-6, interleukin-1ß, and CXCL1/2 (C-X-C motif ligand 1/2). Metformin suppressed IKKα/ß activation, an effect that could be separated from some metabolic actions, in that BI605906 did not mimic effects of metformin on lipogenic gene expression, glucose production, and AMP-activated protein kinase activation. Equally AMP-activated protein kinase was not required either for mitochondrial suppression of IκB degradation. Consistent with discrete anti-inflammatory actions, in macrophages, metformin specifically blunted secretion of proinflammatory cytokines, without inhibiting M1/M2 differentiation or activation. In a large treatment naive diabetes mellitus population cohort, we observed differences in the systemic inflammation marker, neutrophil to lymphocyte ratio, after incident treatment with either metformin or sulfonylurea monotherapy. Compared with sulfonylurea exposure, metformin reduced the mean log-transformed neutrophil to lymphocyte ratio after 8 to 16 months by 0.09 U (95% confidence interval, 0.02-0.17; P=0.013) and increased the likelihood that neutrophil to lymphocyte ratio would be lower than baseline after 8 to 16 months (odds ratio, 1.83; 95% confidence interval, 1.22-2.75; P=0.00364). Following up these findings in a double-blind placebo controlled trial in nondiabetic heart failure (trial registration: NCT00473876), metformin suppressed plasma cytokines including the aging-associated cytokine CCL11 (C-C motif chemokine ligand 11). CONCLUSION: We conclude that anti-inflammatory properties of metformin are exerted irrespective of diabetes mellitus status. This may accelerate investigation of drug utility in nondiabetic cardiovascular disease groups. CLINICAL TRIAL REGISTRATION: Name of the trial registry: TAYSIDE trial (Metformin in Insulin Resistant Left Ventricular [LV] Dysfunction). URL: https://www.clinicaltrials.gov. Unique identifier: NCT00473876.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Diabetes Mellitus/drug therapy , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Aged , Animals , Anti-Inflammatory Agents/pharmacology , Cells, Cultured , Cohort Studies , Diabetes Mellitus/blood , Diabetes Mellitus/diagnosis , Double-Blind Method , Female , Hepatocytes/drug effects , Hepatocytes/metabolism , Hepatocytes/pathology , Humans , Hypoglycemic Agents/pharmacology , Male , Metformin/pharmacology , Mice , Mice, Inbred C57BL , Middle Aged , Piperidines/pharmacology , Retrospective Studies , Sulfonamides/pharmacology
16.
BMC Cardiovasc Disord ; 18(1): 31, 2018 02 13.
Article in English | MEDLINE | ID: mdl-29433433

ABSTRACT

BACKGROUND: Epicardial adipose tissue (EAT) is an emerging cardio-metabolic risk factor and has been shown to correlate with adverse cardiovascular (CV) outcome; however the underlying pathophysiology of this link is not well understood. The aim of this study was to evaluate the relationship between EAT and a comprehensive panel of cardiovascular risk biomarkers and pulse wave velocity (PWV) and indexed left ventricular mass (LVMI) in a cohort of patients with cardiovascular disease (CVD) and diabetes compared to controls. METHODS: One hundred forty-five participants (mean age 63.9 ± 8.1 years; 61% male) were evaluated. All patients underwent cardiovascular magnetic resonance (CMR) examination and PWV. EAT measurements from CMR were performed on the 4-chamber view. Blood samples were taken and a range of CV biomarkers was evaluated. RESULTS: EAT measurements were significantly higher in the groups with CVD, with or without T2DM compared to patients without CVD or T2DM (group 1 EAT 15.9 ± 5.5 cm2 vs. group 4 EAT 11.8 ± 4.1 cm2, p = 0.001; group 3 EAT 15.1 ± 4.3 cm2 vs. group 4 EAT 11.8 ± 4.1 cm2, p = 0.024). EAT was independently associated with IL-6 (beta 0.2, p = 0.019). When added to clinical variables, both EAT (beta 0.16, p = 0.035) and IL-6 (beta 0.26, p = 0.003) were independently associated with PWV. EAT was significantly associated with LVMI in a univariable analysis but not when added to significant clinical variables. CONCLUSIONS: In patients with cardio-metabolic disease, EAT was independently associated with PWV. EAT may be associated with CVD risk due to an increase in systemic vascular inflammation. Whether targeting EAT may reduce inflammation and/or cardiovascular risk should be evaluated in prospective studies.


Subject(s)
Adipose Tissue/physiopathology , Adiposity , Cardiovascular Diseases/physiopathology , Diabetes Mellitus, Type 2/physiopathology , Inflammation/physiopathology , Vascular Stiffness , Adipose Tissue/diagnostic imaging , Aged , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Case-Control Studies , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/epidemiology , Female , Humans , Inflammation/diagnosis , Inflammation/epidemiology , Magnetic Resonance Imaging, Cine , Male , Middle Aged , Pericardium , Pulse Wave Analysis , Risk Factors , Scotland/epidemiology
17.
Perception ; 47(3): 276-295, 2018 Mar.
Article in English | MEDLINE | ID: mdl-29224446

ABSTRACT

Previous studies concluded that first-time film viewers often had difficulty integrating shots into a coherent representation of the depicted events in the absence of a familiar action through the film cuts or a salient eye-gazing of a character in the film. In this study, we investigated whether diegetic sound (i.e., sound that seems to originate from the depicted cinematic space) could effectively bridge shots for first-time viewers. Across a range of films, both dialog, and salient environmental sound (e.g., barking dogs) helped first-time viewers connect shots. However, sound was not always successful in supporting first-time viewers' interpretations. While experienced viewers were able to understand less-familiar linking sounds and environments, first-time viewers found this difficult. Overall, a range of diegetic sounds helped first-time viewers understand spatiotemporal relations between shots, but these viewers still had difficulty integrating views of unfamiliar environments.


Subject(s)
Auditory Perception/physiology , Comprehension/physiology , Motion Pictures , Visual Perception/physiology , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged
18.
Catheter Cardiovasc Interv ; 90(3): 437-448, 2017 Sep 01.
Article in English | MEDLINE | ID: mdl-28463460

ABSTRACT

OBJECTIVE: We conducted a meta-analysis to compare the incidence of acute kidney injury (AKI) with carbon dioxide (CO2 ) versus iodinated contrast media (ICM). BACKGROUND: Contrast induced-acute kidney injury (CI-AKI) is a known complication following endovascular procedures with ICM. CO2 has been employed as an alternative imaging medium as it is nontoxic to the kidneys. METHODS: Search of indexed databases was performed and 1,732 references were retrieved. Eight studies (7 observational, 1 Randomized Controlled Trial) formed the meta-analysis. Primary outcome was AKI. Fixed effect model was used when possible in addition to analysis of publication bias. RESULTS: In this meta-analysis, 677 patients underwent 754 peripheral angiographic procedures. Compared with ICM, CO2 was associated with a decreased incidence of AKI (4.3% vs. 11.1%; OR 0.465, 95% CI: 0.218-0.992; P = 0.048). Subgroup analysis of four studies that included granular data for patients with chronic kidney disease (CKD) did not demonstrate a decreased incidence of AKI with CO2 (4.1% vs. 10.0%; OR 0.449, 95% CI: 0.165-1.221, P = 0.117). Patients undergoing CO2 angiography experienced a higher number of nonrenal events including limb/abdominal pain (11 vs. 0; P = 0.001) and nausea/vomiting (9 vs. 1; P = 0.006). CONCLUSIONS: In comparison to ICM, CO2 use is associated with a modestly reduced rate of AKI with more frequent adverse nonrenal events. In studies that use CO2 as the primary imaging agent, the average incidence of AKI remained high at 6.2%-supporting the concept that factors other than renal toxicity from ICM may contribute to renal impairment following peripheral angiography. © 2017 Wiley Periodicals, Inc.


Subject(s)
Acute Kidney Injury/chemically induced , Angiography/adverse effects , Carbon Dioxide/adverse effects , Contrast Media/adverse effects , Iodine Compounds/adverse effects , Peripheral Arterial Disease/diagnostic imaging , Acute Kidney Injury/diagnosis , Acute Kidney Injury/epidemiology , Carbon Dioxide/administration & dosage , Contrast Media/administration & dosage , Humans , Incidence , Iodine Compounds/administration & dosage , Odds Ratio , Peripheral Arterial Disease/therapy , Predictive Value of Tests , Risk Factors
19.
Catheter Cardiovasc Interv ; 89(3): 383-392, 2017 Feb 15.
Article in English | MEDLINE | ID: mdl-27315581

ABSTRACT

OBJECTIVES: The goal of the present study was to survey the Society of Cardiovascular Angiography and Intervention (SCAI) member cardiologists to evaluate contemporary practice patterns with regards to contrast use, acute kidney injury (AKI) risk assessment, and prevention in patients undergoing invasive angiography. We sought to compare the physician responses against guideline statements and evidence-based data from clinical studies. METHODS: A 20-question online survey based on a modified Likert scale was sent out via email to the Society of Cardiovascular Angiography and Intervention (SCAI) member cardiologists. The survey questions focused on prophylaxis methods, medication management, risk assessment, contrast agent use, and postprocedure care. A scoring system was developed which examined the individual responses to analyze the 10 questions with the greatest strength of evidence in the literature and guidelines. RESULTS: The survey was completed by 506 individuals. Selected responses of note included the use of standardized volume expansion protocols: 64.8%, use of iso-osmolar contrast (iodixanol) in the majority of patients at risk of AKI: 55%, and 27% of individuals reported diluting contrast with saline for patients at risk of AKI during coronary angiography. For questions with support from guideline documents, 56.9% of the responses were scored as concordant with evidence-based data. Individuals who reported that the risk of AKI was often or always important in planning angiography for "at risk patients" were more likely to closely monitor renal function (76.7% vs. 40.0%, P = 0.003), obtain nephrology consultation (45.2% vs. 13.3%, P = 0.016) and use iso-osmolar contrast agents (56.0% vs. 26.7%, P = 0.033). CONCLUSIONS: The majority of cardiologists participating in this survey, reported practice patterns consistent with guideline and evidence-based recommendations. However, over 40% of responses to questions were inconsistent with these recommendations, suggesting continued opportunities for education and quality improvement concerning AKI prevention. © 2016 Wiley Periodicals, Inc.


Subject(s)
Acute Kidney Injury/chemically induced , Cardiac Catheterization/adverse effects , Contrast Media/adverse effects , Coronary Angiography/adverse effects , Healthcare Disparities , Practice Patterns, Physicians' , Acute Kidney Injury/diagnosis , Acute Kidney Injury/prevention & control , Cardiac Catheterization/standards , Cardiac Catheterization/trends , Coronary Angiography/standards , Coronary Angiography/trends , Evidence-Based Medicine , Guideline Adherence , Health Care Surveys , Healthcare Disparities/standards , Healthcare Disparities/trends , Humans , Practice Guidelines as Topic , Practice Patterns, Physicians'/standards , Practice Patterns, Physicians'/trends , Risk Assessment , Risk Factors
20.
Rev Cardiovasc Med ; 17(3-4): 100-114, 2016.
Article in English | MEDLINE | ID: mdl-28144017

ABSTRACT

Contrast-induced nephropathy related to cardiac and peripheral vascular procedures is a major problem in the United States and abroad. Measures to prevent and treat this complication have been hampered by the lack of clinical tools to detect acute kidney injury following contrast administration. Emerging novel serum and urinary biomarkers may provide sensitive detection of early kidney injury prior to creatinine elevation and allow for more precise risk stratification and management of patients. This article discusses the biologic and clinical data supporting the development and utility of several promising biomarkers in the management of patients undergoing cardiac catheterization and percutaneous coronary intervention.


Subject(s)
Acute Kidney Injury/diagnosis , Cardiac Catheterization , Percutaneous Coronary Intervention , Biomarkers/analysis , Contrast Media , Creatinine , Humans , Risk Factors
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