JMIR Perioperative Medicine supports the dissemination of technological and data science-driven innovative research conducted by interdisciplinary teams in perioperative medicine. We invite ...contributions on a broad range of topics from clinicians, scientists, and allied health professionals from across the globe.
NF-κB has been reported to both promote and inhibit bone formation. To explore its role in osteolineage cells, we conditionally deleted IKKα, an upstream kinase required for non-canonical NF-κB ...activation, using Osterix (Osx)-Cre. Surprisingly, we found no effect on either cancellous or cortical bone, even following mechanical loading. However, we noted that IKKα conditional knockout (cKO) mice began to lose body weight after 6 months of age with severe reductions in fat mass and lower adipocyte size in geriatric animals. qPCR analysis of adipogenic markers in fat pads of cKO mice indicated no difference in early differentiation, but instead markedly lower leptin with age. We challenged young mice with a high fat diet finding that cKO mice gained less weight and showed improved glucose metabolism. Low levels of recombination at the IKKα locus were detected in fat pads isolated from old cKO mice. To determine whether recombination occurs in adipocytes, we examined fat pads in Osx-Cre;TdT reporter mice; these showed increasing Osx-Cre-mediated expression in peripheral adipocytes from 6 weeks to 18 months. Since Osx-Cre drives recombination in peripheral adipocytes with age, we conclude that fat loss in cKO mice is most likely caused by progressive deficits of IKKα in adipocytes.
Recent studies suggest that mitochondria can be transferred between cells to support the survival of metabolically compromised cells. However, whether intercellular mitochondria transfer occurs in ...white adipose tissue (WAT) or regulates metabolic homeostasis in vivo remains unknown. We found that macrophages acquire mitochondria from neighboring adipocytes in vivo and that this process defines a transcriptionally distinct macrophage subpopulation. A genome-wide CRISPR-Cas9 knockout screen revealed that mitochondria uptake depends on heparan sulfates (HS). High-fat diet (HFD)-induced obese mice exhibit lower HS levels on WAT macrophages and decreased intercellular mitochondria transfer from adipocytes to macrophages. Deletion of the HS biosynthetic gene Ext1 in myeloid cells decreases mitochondria uptake by WAT macrophages, increases WAT mass, lowers energy expenditure, and exacerbates HFD-induced obesity in vivo. Collectively, this study suggests that adipocytes and macrophages employ intercellular mitochondria transfer as a mechanism of immunometabolic crosstalk that regulates metabolic homeostasis and is impaired in obesity.
Display omitted
•Adipocytes transfer their mitochondria to macrophages in vivo•Mitochondria transfer from adipocytes to macrophages is decreased in obesity•Mitochondria uptake by macrophages is mediated by heparan sulfates•Mice that lack heparan sulfates on macrophages exhibit metabolic dysfunction
Brestoff et al. show that adipose-tissue-resident macrophages acquire mitochondria from neighboring adipocytes in a heparan-sulfate-dependent process that is impaired in obesity. Genetic disruption of mitochondria uptake by macrophages reduces energy expenditure and exacerbates diet-induced obesity in mice, indicating that intercellular mitochondria transfer to macrophages mediates systemic metabolic homeostasis.
Delirium is an acute change in mental status affecting 10%-64% of hospitalized patients, and may be preventable in 30%-40% of cases. In October 2013, a task force for delirium prevention and early ...identification in medical-surgical units was formed at our hospital. We studied whether our standardized protocol prevented delirium among high-risk patients.
We studied 105,455 patient encounters between November 2013 and January 2018. Since November 2013, there has been ongoing education to decrease deliriogenic medications use. Since 2014, nurses screen all patients for presence or absence of delirium using the Confusion Assessment Method (CAM). Since 2015, nurses additionally screen all patients for risk of delirium. In 2015, a physician order set for delirium was created. Nonpharmacological measures are implemented for high-risk or CAM positive patients.
98.8% of patient encounters had CAM screening, and 99.6% had delirium risk screening. Since 2013, odds of opiate use decreased by 5.0% per year (P < .001), and odds of benzodiazepine use decreased by 8.0% per year (P < .001). There was no change in anticholinergic use. In the adjusted analysis, since 2015, odds of delirium decreased by 25.3% per year among high-risk patients (n = 21,465; P < .001). Among high-risk patients or those diagnosed with delirium (n = 22,121), estimated length of stay decreased by 0.13 days per year (P < .001), odds of inpatient mortality decreased by 16.0% per year (P = .011), and odds of discharge to a nursing home decreased by 17.1% per year (P < .001).
With high clinician engagement and simplified workflows, our delirium initiative has shown sustained results.
Author Affiliation: (1) Division of Hospital Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA (2) Stanford, USA (3) Quantitative Sciences Unit, Division of ...Biomedical Informatics Research, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA (4) Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA (a) nrohatgi@stanford.edu Article History: Registration Date: 12/02/2020 Received Date: 03/10/2020 Accepted Date: 12/01/2020 Online Date: 01/08/2021 Byline:
Author Affiliation: (1) Division of Hospital Medicine, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA (2) Stanford, CA, USA (3) Quantitative Sciences Unit, Division ...of Biomedical Informatics Research, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA (4) Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA, USA (a) nrohatgi@stanford.edu Article History: Registration Date: 12/02/2020 Received Date: 04/21/2020 Accepted Date: 12/01/2020 Online Date: 01/08/2021 Byline:
Treatment of osteoporosis commonly diminishes osteoclast number which suppresses bone formation thus compromising fracture prevention. Bone formation is not suppressed, however, when bone degradation ...is reduced by retarding osteoclast functional resorptive capacity, rather than differentiation. We find deletion of deubiquitinase, BRCA1-associated protein 1 (Bap1), in myeloid cells (Bap1
), arrests osteoclast function but not formation. Bap1
osteoclasts fail to organize their cytoskeleton which is essential for bone degradation consequently increasing bone mass in both male and female mice. The deubiquitinase activity of BAP1 modifies osteoclast function by metabolic reprogramming. Bap1 deficient osteoclast upregulate the cystine transporter, Slc7a11, by enhanced H2Aub occupancy of its promoter. SLC7A11 controls cellular reactive oxygen species levels and redirects the mitochondrial metabolites away from the tricarboxylic acid cycle, both being necessary for osteoclast function. Thus, in osteoclasts BAP1 appears to regulate the epigenetic-metabolic axis and is a potential target to reduce bone degradation while maintaining osteogenesis in osteoporotic patients.
Surgical comanagement (SCM), in which surgeons and hospitalists share responsibility of care for surgical patients, has been increasingly utilized. In August 2012, we implemented SCM in Orthopedic ...and Neurosurgery services in which the same Internal Medicine hospitalists are dedicated year round to each of these surgical services to proactively prevent and manage medical conditions. In this article, we evaluate if SCM was associated with continued improvement in patient outcomes between 2012 and 2018 in Orthopedic and Neurosurgery services at our institution. We conducted regression analysis on 26,380 discharges to assess yearly change in our outcomes. Since 2012, the odds of patients with ≥1 medical complication decreased by 3.8% per year (P = .01), the estimated length of stay decreased by 0.3 days per year (P < .0001), and the odds of rapid response team calls decreased by 12.2% per year (P = .001). Estimated average direct cost savings were $3,424 per discharge.
We explored the relationship of obesity and inflammatory arthritis (IA) by selectively expressing diphtheria toxin in adipose tissue yielding "fat-free" (FF) mice completely lacking white and brown ...fat. FF mice exhibit systemic neutrophilia and elevated serum acute phase proteins suggesting a predisposition to severe IA. Surprisingly, FF mice are resistant to K/BxN serum-induced IA and attendant bone destruction. Despite robust systemic basal neutrophilia, neutrophil infiltration into joints of FF mice does not occur when challenged with K/BxN serum. Absence of adiponectin, leptin, or both has no effect on joint disease, but deletion of the adipokine adipsin (complement factor D) completely prevents serum-induced IA. Confirming that fat-expressed adipsin modulates the disorder, transplantation of wild-type (WT) adipose tissue into FF mice restores susceptibility to IA, whereas recipients of adipsin-deficient fat remain resistant. Thus, adipose tissue regulates development of IA through a pathway in which adipocytes modify neutrophil responses in distant tissues by producing adipsin.
PDF
