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1.
Anesthesiology ; 136(1): 93-103, 2022 01 01.
Article En | MEDLINE | ID: mdl-34843618

BACKGROUND: Age- and sex-specific reference nomograms for intraoperative blood pressure have been published, but they do not identify harm thresholds. The authors therefore assessed the relationship between various absolute and relative characterizations of hypotension and acute kidney injury in children having noncardiac surgery. METHODS: The authors conducted a retrospective cohort study using electronic data from two tertiary care centers. They included inpatients 18 yr or younger who had noncardiac surgery with general anesthesia. Postoperative renal injury was defined using the Kidney Disease Improving Global Outcomes definitions, based on serum creatinine concentrations. The authors evaluated potential renal harm thresholds for absolute lowest intraoperative mean arterial pressure (MAP) or largest MAP reduction from baseline maintained for a cumulative period of 5 min. Separate analyses were performed in children aged 2 yr or younger, 2 to 6 yr, 6 to 12 yr, and 12 to 18 yr. RESULTS: Among 64,412 children who had noncardiac surgery, 4,506 had creatinine assessed preoperatively and postoperatively. The incidence of acute kidney injury in this population was 11% (499 of 4,506): 17% in children under 6 yr old, 11% in children 6 to 12 yr old, and 6% in adolescents, which is similar to the incidence reported in adults. There was no association between lowest cumulative MAP sustained for 5 min and postoperative kidney injury. Similarly, there was no association between largest cumulative percentage MAP reduction and postoperative kidney injury. The adjusted estimated odds for kidney injury was 0.99 (95% CI, 0.94 to 1.05) for each 5-mmHg decrease in lowest MAP and 1.00 (95% CI, 0.97 to 1.03) for each 5% decrease in largest MAP reduction from baseline. CONCLUSIONS: In distinct contrast to adults, the authors did not find any association between intraoperative hypotension and postoperative renal injury. Avoiding short periods of hypotension should not be the clinician's primary concern when trying to prevent intraoperative renal injury in pediatric patients.


Acute Kidney Injury/physiopathology , Blood Pressure/physiology , Hypotension/physiopathology , Intraoperative Complications/physiopathology , Monitoring, Intraoperative/methods , Acute Kidney Injury/diagnosis , Adolescent , Child , Child, Preschool , Cohort Studies , Female , Humans , Hypotension/diagnosis , Infant , Intraoperative Complications/diagnosis , Male , Retrospective Studies
2.
Brain ; 144(7): 1974-1984, 2021 08 17.
Article En | MEDLINE | ID: mdl-33757115

Although multiple sclerosis has traditionally been considered a white matter disease, extensive research documents the presence and importance of grey matter injury including cortical and deep regions. The deep grey matter exhibits a broad range of pathology and is uniquely suited to study the mechanisms and clinical relevance of tissue injury in multiple sclerosis using magnetic resonance techniques. Deep grey matter injury has been associated with clinical and cognitive disability. Recently, MRI characterization of deep grey matter properties, such as thalamic volume, have been tested as potential clinical trial end points associated with neurodegenerative aspects of multiple sclerosis. Given this emerging area of interest and its potential clinical trial relevance, the North American Imaging in Multiple Sclerosis (NAIMS) Cooperative held a workshop and reached consensus on imaging topics related to deep grey matter. Herein, we review current knowledge regarding deep grey matter injury in multiple sclerosis from an imaging perspective, including insights from histopathology, image acquisition and post-processing for deep grey matter. We discuss the clinical relevance of deep grey matter injury and specific regions of interest within the deep grey matter. We highlight unanswered questions and propose future directions, with the aim of focusing research priorities towards better methods, analysis, and interpretation of results.


Brain/pathology , Gray Matter/pathology , Multiple Sclerosis/pathology , Humans
3.
Contemp Clin Trials ; 95: 106009, 2020 08.
Article En | MEDLINE | ID: mdl-32320842

Multiple Sclerosis (MS) is a common cause of neurological disability among young adults and has a high economic burden. Currently there are 18 disease modifying agents for relapsing MS, which were tested in clinical trials versus placebo or an active comparator in a pairwise manner. However, there is currently no consensus on the fundamental principles of treatment approach and initial therapy selection. These factors result in variable use of disease modifying therapies. Here we describe the study protocol for Determining the Effectiveness of earLy Intensive Versus Escalation approaches for the Treatment of Relapsing-remitting Multiple Sclerosis (DELIVER-MS). The main objective of the study is to determine whether an early highly effective treatment approach, defined as use of one of four monoclonal antibodies as initial therapy, is more effective than an escalation treatment approach (any other approved medication as initial therapy with subsequent escalation to higher efficacy treatments guided by radiological and clinical evaluation). The primary endpoint of the study is reduction in normalized brain volume loss from baseline visit to month 36 visit using MRI. Brain volume loss was selected as the best short-term predictor of long-term clinical disability. A total of 400 participants will be randomized 1:1 using minimization to account for age and sex by site, and 400 will be enrolled into a parallel observational cohort. The study results will help guide overall treatment philosophy and will have important implications for patient choice, clinical practice, and treatment access.


Multiple Sclerosis, Relapsing-Remitting , Multiple Sclerosis , Humans , Magnetic Resonance Imaging , Multiple Sclerosis, Relapsing-Remitting/drug therapy , Recurrence , Young Adult
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