Purpose
Dexmedetomidine is frequently used as a sedative agent for orthopedic surgery patients undergoing total hip or knee arthroplasty. Although the benefits of dexmedetomidine are well described ...in the literature, there is also potential for harm, especially regarding the hemodynamic effects of dexmedetomidine in the postoperative setting.
Methods
This historical cohort study included all primary unilateral total hip or knee arthroplasties conducted from April 2017 to February 2020 in a single, university-affiliated, tertiary care centre (Jewish General Hospital, Montreal, QC, Canada). We used multivariable logistic regression to analyze the predictors for postoperative hypotension, defined as a systolic blood pressure < 90 mm Hg or any systolic blood pressure while on a vasopressor infusion in the postanesthesia care unit. Models were validated using calibration and discrimination with bootstrapping technique.
Results
One thousand five hundred and eighty-eight patients were included in this study. Postoperative hypotension occurred in 413 (26%) patients. Statistically significant predictors for postoperative hypotension included female sex (adjusted odds ratio aOR, 3.24; 95% confidence interval CI, 2.29 to 4.58), a history of transient ischemic attack or cerebrovascular accident (aOR, 1.97; 95% CI, 1.04 to 3.72), and intraoperative dexmedetomidine use (aOR, 2.61; 95% CI, 1.99 to 3.42). Moreover, the risk of postoperative hypotension was approximately two times higher than baseline, with a total intraoperative dexmedetomidine dose above 50 μg (relative risk, 1.99; 95% CI, 1.63 to 2.44;
P
< 0.001). A higher preoperative systolic blood pressure (aOR, 0.98; 95% CI, 0.97 to 0.99) was a protective factor for postoperative hypotension.
Conclusion
In this historical cohort study, dexmedetomidine was a strong risk factor for postoperative hypotension in total hip or knee arthroplasty patients. Dexmedetomidine, and particularly at high cumulative doses above 50 μg, should be administered judiciously in high-risk surgical patients to minimize the risk of postoperative hypotension.
Objectives. Acute pain trajectories are associated with long-term outcomes such as persistent pain and functional disability in adults. However, there are limited data on acute postoperative pain ...trajectories in the pediatric population. The aims of this study were to investigate acute postoperative pain trajectories, their predictors, and their impact on long- term outcomes in adolescents with idiopathic scoliosis. Methods. We evaluated the preoperative pain intensity, use of analgesics, psychosocial measures and physical functioning of adolescents scheduled to undergo spinal fusion, and their average 6-hour self-reported pain intensity scores for their entire hospital stay. Six months after surgery, baseline variables were reassessed. We used growth mixture modeling to conduct acute postoperative pain trajectory analysis and to identify predictors of pain trajectories. Generalized linear models were conducted to determine whether acute pain trajectories predict long-term outcomes. Results. One hundred and six patients were included in the best-fitted acute pain trajectory model that included four classes that differed in initial pain intensity and rates of change over time. Preoperative pain catastrophizer status and use of analgesics significantly predicted pain trajectory membership. Furthermore, at the 6-month follow-up, patients experiencing moderate-to-severe pain in the acute postoperative period were more likely to report higher levels of pain severity, use pain medication, and miss a greater number of school/work days due to back pain in the last three months. Discussion. Preoperative assessment and analyzing the progression of pain in the acute postoperative period can help identify those at risk of negative long-term outcomes after surgery.
Identification of broadly neutralizing antibodies against influenza A viruses has raised hopes for the development of monoclonal antibody—based immunotherapy and "universal" vaccines for influenza. ...However, a substantial part of the annual flu burden is caused by two cocirculating, antigenically distinct lineages of influenza B viruses. Here, we report human monoclonal antibodies, CR8033, CR8071, and CR9114, that protect mice against lethal challenge from both lineages. Antibodies CR8033 and CR8071 recognize distinct conserved epitopes in the head region of the influenza B hemagglutinin (HA), whereas CR9114 binds a conserved epitope in the HA stem and protects against lethal challenge with influenza A and B viruses. These antibodies may inform on development of monoclonal antibody—based treatments and a universal flu vaccine for all influenza A and B viruses.
Interleukin-1 (IL-1)-mediated signaling in T cells is essential for T helper 17 (Th17) cell differentiation. We showed here that SIGIRR, a negative regulator of IL-1 receptor and Toll-like receptor ...signaling, was induced during Th17 cell lineage commitment and governed Th17 cell differentiation and expansion through its inhibitory effects on IL-1 signaling. The absence of SIGIRR in T cells resulted in increased Th17 cell polarization in vivo upon myelin oligodendrocyte glycoprotein (MOG
35-55) peptide immunization. Recombinant IL-1 promoted a marked increase in the proliferation of SIGIRR-deficient T cells under an in vitro Th17 cell-polarization condition. Importantly, we detected increased IL-1-induced phosphorylation of JNK and mTOR kinase in SIGIRR-deficient Th17 cells compared to wild-type Th17 cells. IL-1-induced proliferation was abolished in mTOR-deficient Th17 cells, indicating the essential role of mTOR activation. Our results demonstrate an important mechanism by which SIGIRR controls Th17 cell expansion and effector function through the IL-1-induced mTOR signaling pathway.
► SIGIRR is induced during Th17 cell lineage commitment ► SIGIRR suppresses Th17 cell effector function via inhibition of IL-1 signaling ► IL-1-induced proliferation is abolished in mTOR-deficient Th17 cells ► SIGIRR suppresses Th17 cell proliferation via inhibition of mTOR activation
Summary Background Tretinoin is considered the benchmark prescription topical therapy for improving fine facial wrinkles, but skin tolerance issues can affect patient compliance. In contrast, ...cosmetic antiwrinkle products are well tolerated but are generally presumed to be less efficacious than tretinoin.
Objectives To compare the efficacy of a cosmetic moisturizer regimen vs. a prescription regimen with 0·02% tretinoin for improving the appearance of facial wrinkles.
Methods An 8‐week, randomized, parallel‐group study was conducted in 196 women with moderate to moderately severe periorbital wrinkles. Following 2 weeks washout, subjects on the cosmetic regimen (n = 99) used a sun protection factor (SPF) 30 moisturizing lotion containing 5% niacinamide, peptides and antioxidants, a moisturizing cream containing niacinamide and peptides, and a targeted wrinkle product containing niacinamide, peptides and 0·3% retinyl propionate. Subjects on the prescription regimen (n = 97) used 0·02% tretinoin plus moisturizing SPF 30 sunscreen. Subject cohorts (n = 25) continued treatment for an additional 16 weeks. Changes in facial wrinkling were assessed by both expert grading and image analysis of digital images of subjects’ faces and by self‐assessment questionnaire. Product tolerance was assessed via clinical erythema and dryness grading, subject self‐assessment, and determinations of skin barrier integrity (transepidermal water loss) and stratum corneum protein changes.
Results The cosmetic regimen significantly improved wrinkle appearance after 8 weeks relative to tretinoin, with comparable benefits after 24 weeks. The cosmetic regimen was significantly better tolerated than tretinoin through 8 weeks by all measures.
Conclusions An appropriately designed cosmetic regimen can improve facial wrinkle appearance comparably with the benchmark prescription treatment, with improved tolerability.
After surgery, the adverse effects (AEs) of analgesics are common and critical factors influencing the postoperative experience of pediatric patients. Inadequate management of AEs has been found to ...prolong hospital stay, increase readmission rates and decrease satisfaction with care. The aim of this qualitative descriptive study was to better understand the AEs of analgesics from the perspective of adolescent patients with idiopathic scoliosis after spinal surgery. A total of 7 patients participated in the study. Semistructured interviews were conducted at discharge and 1 week after discharge. Transcribed data were analyzed using qualitative content analysis and themes were identified. Overall, participants most frequently reported gastrointestinal and cognitive AEs, with constipation being the most persistent and bothersome. The pediatric participants used a combination of 3 strategies to mitigate analgesic AEs, namely pharmacologic, nonpharmacologic, and reduction of analgesic intake. Participants demonstrated a lack of understanding of AEs and involvement in their own care. Future studies should be conducted to evaluate the efficacy of nonpharmacological strategies in managing analgesic AEs for pediatric patients after surgery.
Postoperative pain cannot be measured accurately among many children with intellectual and developmental disabilities, resulting in underrecognition or delay in recognition of pain. The Critical-Care ...Pain Observation Tool (CPOT) is a pain assessment tool that has been widely validated in critically ill and postoperative adults.
The objective of this study was to validate the CPOT for use with pediatric patients able to self-report and undergoing posterior spinal fusion surgery.
Twenty-four patients (10-18 years old) scheduled to undergo surgery were consented to this repeated-measure, within-subject study. To examine discriminative and criterion validation, CPOT scores and patients' self-reports of pain intensity were collected prospectively by a bedside rater before, during, and after a nonnociceptive and nociceptive procedure on the day following surgery. Patients' behavioral reactions were video recorded at the bedside and retrospectively viewed by two independent video raters to examine interrater and intrarater reliability of CPOT scores.
Discriminative validation was supported with higher CPOT scores during the nociceptive procedure than during the nonnociceptive procedure. Criterion validation was supported with a moderate positive correlation between the CPOT scores and the patients' self-reported pain intensity during the nociceptive procedure. A CPOT cutoff score of ≥2 was associated with the maximum sensitivity (61.3%) and specificity (94.1%). Reliability analyses revealed poor to moderate agreement between bedside and video raters and moderate to excellent consistency within video raters.
These findings suggest that the CPOT may be a valid tool to detect pain in pediatric patients in the acute postoperative inpatient care unit after posterior spinal fusion.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Temporal control of development is an important aspect of pattern formation that awaits complete molecular analysis. We identified
lin-57 as a member of the
C. elegans heterochronic gene pathway, ...which ensures that postembryonic developmental events are appropriately timed. Loss of
lin-57 function causes the hypodermis to terminally differentiate and acquire adult character prematurely.
lin-57 is
hbl-1, revealing a role for the worm
hunchback homolog in control of developmental time. Significantly, fly
hunchback (
hb) temporally specifies cell fates in the nervous system. The
hbl-1/lin-57 3′UTR is required for postembryonic downregulation in the hypodermis and nervous system and contains multiple putative binding sites for temporally regulated microRNAs, including
let-7. Indeed, we find that
hbl-1/lin-57 is regulated by
let-7, at least in the nervous system. Examination of the
hb 3′UTR reveals potential binding sites for known fly miRNAs. Thus, evolutionary conservation of
hunchback genes may include temporal control of cell fate specification and microRNA-mediated regulation.
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