The objective of this study was to evaluate signal changes in the dentate nucleus on unenhanced T1-weighted MR images after multiple administrations of gadopentetate dimeglumine versus gadobutrol.
...Two study groups were identified, each of which included 25 consecutive patients. Each group received six or more administrations of either gadobutrol only or gadopentetate dimeglumine only, without having had exposure to any other gadolinium-based contrast agent (GBCA). The mean signal intensity (SI) in the dentate nucleus on unenhanced T1-weighted MR images was measured, with the use of the pons and the cerebellar peduncle as references to calculate the DNP SI ratio (i.e., the ratio of the SI in the dentate nucleus to the SI in the pons) and the DCP SI ratio (i.e., the ratio of the SI in the dentate nucleus to the SI in the cerebellar peduncle).
After six administrations of gadopentetate dimeglumine, the SI in the dentate nucleus on unenhanced T1-weighted MR images increased from a DCP SI ratio of 0.997 before administration to 1.034 after the last of six administrations (p = 0.0007) and then to 1.063 after all administrations (p = 0.0004). No statistically significant increase was noted in association with administration of gadobutrol, for which the DCP SI ratio was 0.995 before administration, 1.009 after the last of six administrations (p = 0.1172), and 0.992 after all administrations (p = 0.7592). The change in the DCP SI ratio after administration of gadopentetate dimeglumine correlated with the number of administrations the patient received (p < 0.0001).
Unenhanced T1 signal hyperintensity was observed in the dentate nucleus after multiple administrations of gadopentetate dimeglumine, a linear ionic agent, but not after multiple administrations of gadobutrol, a macrocyclic GBCA.
Atherosclerotic renal-artery stenosis is a common problem in the elderly. Despite two randomized trials that did not show a benefit of renal-artery stenting with respect to kidney function, the ...usefulness of stenting for the prevention of major adverse renal and cardiovascular events is uncertain.
We randomly assigned 947 participants who had atherosclerotic renal-artery stenosis and either systolic hypertension while taking two or more antihypertensive drugs or chronic kidney disease to medical therapy plus renal-artery stenting or medical therapy alone. Participants were followed for the occurrence of adverse cardiovascular and renal events (a composite end point of death from cardiovascular or renal causes, myocardial infarction, stroke, hospitalization for congestive heart failure, progressive renal insufficiency, or the need for renal-replacement therapy).
Over a median follow-up period of 43 months (interquartile range, 31 to 55), the rate of the primary composite end point did not differ significantly between participants who underwent stenting in addition to receiving medical therapy and those who received medical therapy alone (35.1% and 35.8%, respectively; hazard ratio with stenting, 0.94; 95% confidence interval CI, 0.76 to 1.17; P=0.58). There were also no significant differences between the treatment groups in the rates of the individual components of the primary end point or in all-cause mortality. During follow-up, there was a consistent modest difference in systolic blood pressure favoring the stent group (-2.3 mm Hg; 95% CI, -4.4 to -0.2; P=0.03).
Renal-artery stenting did not confer a significant benefit with respect to the prevention of clinical events when added to comprehensive, multifactorial medical therapy in people with atherosclerotic renal-artery stenosis and hypertension or chronic kidney disease. (Funded by the National Heart, Lung and Blood Institute and others; ClinicalTrials.gov number, NCT00081731.).
Purpose To explore the extent of signal hyperintensity in the brain on unenhanced T1-weighted magnetic resonance (MR) images with increasing gadolinium-based contrast agent (GBCA) doses in patients ...who received 35 or more linear GBCA administrations. Materials and Methods In this institutional review board-approved HIPAA-compliant retrospective study, picture archiving and communication systems of two tertiary referral hospitals were searched to identify patients who received 35 or more linear GBCA administrations. Unenhanced T1-weighted images of the brain in patients after six, 12, and 24 GBCA administrations and after the final GBCA administration were independently reviewed by three radiologists to identify sites where T1 signal intensity was increasing. Areas identified by all three observers as increasing in T1 signal intensity when compared with baseline images were further analyzed with a quantitative region of interest analysis measuring the rate of signal increase per injection and the total change after 24 linear GBCA administrations relative to reference tissues that did not show T1 shortening. Results Qualitative analysis of 13 patients with 39-59 linear GBCA administrations showed visually detectable T1 shortening in the dentate nucleus (n = 13), globus pallidus (n = 13), substantia nigra (n = 13), posterior thalamus (n = 12), red nucleus (n = 10), colliculi (n = 10), superior cerebellar peduncle (n = 7), caudate nucleus (n = 4), whole thalamus (n = 3), and putamen (n = 2). Quantitative analysis enable confirmation of signal intensity increases on unenhanced T1-weighted images relative to reference tissues in the dentate nucleus (0.53% signal intensity increase per injection, P < .001), globus pallidus (0.23% increase, P = .009), posterior thalamus (0.26% increase, P < .001), substantia nigra (0.25% increase, P = .01), red nucleus (0.25% increase, P = .01), cerebellar peduncle (0.19% increase, P = .001), and colliculi (0.21% increase, P = .02). Conclusion Increased signal intensity on unenhanced T1-weighted images was seen in the posterior thalamus, substantia nigra, red nucleus, cerebellar peduncle, colliculi, dentate nucleus, and globus pallidus.
RSNA, 2016.
We undertook a systematic review and meta-analysis of published papers assessing dietary protein and bone health. We found little benefit of increasing protein intake for bone health in healthy ...adults but no indication of any detrimental effect, at least within the protein intakes of the populations studied. This systematic review and meta-analysis analysed the relationship between dietary protein and bone health across the life-course. The PubMed database was searched for all relevant human studies from the 1st January 1976 to 22nd January 2016, including all bone outcomes except calcium metabolism. The searches identified 127 papers for inclusion, including 74 correlational studies, 23 fracture or osteoporosis risk studies and 30 supplementation trials. Protein intake accounted for 0–4% of areal BMC and areal BMD variance in adults and 0–14% of areal BMC variance in children and adolescents. However, when confounder adjusted (5 studies) adult lumbar spine and femoral neck BMD associations were not statistically significant. There was no association between protein intake and relative risk (RR) of osteoporotic fractures for total (RR
(random)
= 0.94; 0.72 to 1.23, I
2
= 32%), animal (RR
(random)
= 0.98; 0.76 to 1.27, I
2
= 46%) or vegetable protein (RR
(fixed)
= 0.97 (0.89 to 1.09, I
2
= 15%). In total protein supplementation studies, pooled effect sizes were not statistically significant for LSBMD (total
n
= 255, MD
(fixed)
= 0.04 g/cm
2
(0.00 to 0.08,
P
= 0.07), I
2
= 0%) or FNBMD (total
n
= 435, MD
(random)
= 0.01 g/cm
2
(−0.03 to 0.05,
P
= 0.59), I
2
= 68%). There appears to be little benefit of increasing protein intake for bone health in healthy adults but there is also clearly no indication of any detrimental effect, at least within the protein intakes of the populations studied (around 0.8–1.3 g/Kg/day). More studies are urgently required on the association between protein intake and bone health in children and adolescents.
Chronic and recurrent infections occur commonly in both type 1 and type 2 diabetes (T1D, T2D) and increase patient morbidity and mortality. Neutrophils are professional phagocytes of the innate ...immune system that are critical in pathogen handling. Neutrophil responses to infection are dysregulated in diabetes, predominantly mediated by persistent hyperglycaemia; the chief biochemical abnormality in T1D and T2D. Therapeutically enhancing host immunity in diabetes to improve infection resolution is an expanding area of research. Individuals with diabetes are also at an increased risk of severe coronavirus disease 2019 (COVID-19), highlighting the need for re-invigorated and urgent focus on this field. The aim of this review is to explore the breadth of previous literature investigating neutrophil function in both T1D and T2D, in order to understand the complex neutrophil phenotype present in this disease and also to focus on the development of new therapies to improve aberrant neutrophil function in diabetes. Existing literature illustrates a dual neutrophil dysfunction in diabetes. Key pathogen handling mechanisms of neutrophil recruitment, chemotaxis, phagocytosis and intracellular reactive oxygen species (ROS) production are decreased in diabetes, weakening the immune response to infection. However, pro-inflammatory neutrophil pathways, mainly neutrophil extracellular trap (NET) formation, extracellular ROS generation and pro-inflammatory cytokine generation, are significantly upregulated, causing damage to the host and perpetuating inflammation. Reducing these proinflammatory outputs therapeutically is emerging as a credible strategy to improve infection resolution in diabetes, and also more recently COVID-19. Future research needs to drive forward the exploration of novel treatments to improve infection resolution in T1D and T2D to improve patient morbidity and mortality.
Fear of genetic discrimination has led individuals worldwide to avoid medically recommended genetic testing and participation in genomics research, causing potential health effects as research and ...clinical care are stymied. In response, many countries have adopted policies that regulate how insurers, such as life, disability, or critical illness insurers, can underwrite using genetic test results. This article presents a comparison of policies in the United Kingdom, Canada, and Australia, through analysis of interviews with 59 key stakeholders representing insurance, government, advocacy, academia, and genetics. While the ultimate policy of each country is different, the policy motivations and issues raised share commonalities across the countries, particularly around themes of fairness, usefulness of genetic information, and the determination of actuarial fairness.
Diseases of failed inflammation resolution are common and largely incurable. Therapeutic induction of inflammation resolution is an attractive strategy to bring about healing without increasing ...susceptibility to infection. However, therapeutic targeting of inflammation resolution has been hampered by a lack of understanding of the underlying molecular controls. To address this drug development challenge, we developed an in vivo screen for proresolution therapeutics in a transgenic zebrafish model. Inflammation induced by sterile tissue injury was assessed for accelerated resolution in the presence of a library of known compounds. Of the molecules with proresolution activity, tanshinone IIA, derived from a Chinese medicinal herb, potently induced inflammation resolution in vivo both by induction of neutrophil apoptosis and by promoting reverse migration of neutrophils. Tanshinone IIA blocked proinflammatory signals in vivo, and its effects are conserved in human neutrophils, supporting a potential role in treating human inflammation and providing compelling evidence of the translational potential of this screening strategy.
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