Purpose
Lumbar spine surgery is associated with significant postoperative pain. The benefits of erector spinae plane blocks (ESPBs) combined with multimodal analgesia has not been adequately studied. ...We evaluated the analgesic effects of bilateral ESPBs as a component of multimodal analgesia after open lumbar laminectomy.
Methods
Analgesic effects of preoperative, bilateral, ultrasound-guided ESPBs combined with standardized multimodal analgesia (
n
= 25) was compared with multimodal analgesia alone (
n
= 25) in patients undergoing one or two level open lumbar laminectomy. Other aspects of perioperative care were similar. The primary outcome measure was cumulative opioid consumption at 24 h. Secondary outcomes included opioid consumption, pain scores, and nausea and vomiting requiring antiemetics on arrival to the post-anesthesia care unit (PACU), at 24 h, 48 h, and 72 h after surgery, as well as duration of the PACU and hospital stay.
Results
Opioid requirements at 24 h were significantly lower with ESPBs (31.9 ± 12.3 mg vs. 61.2 ± 29.9 mg, oral morphine equivalents). Pain scores were significantly lower with ESPBs in the PACU and through postoperative day two. Patients who received ESPBs required fewer postoperative antiemetic therapy (
n
= 3, 12%) compared to those without ESPBs (
n
= 12, 48%). Furthermore, PACU duration was significantly shorter with ESPBs (49.7 ± 9.5 vs. 79.9 ± 24.6 min).
Conclusions
Ultrasound-guided, bilateral ESPBs, when added to an optimal multimodal analgesia technique, reduce opioid consumption and pain scores, the need for antiemetic therapy, and the duration of stay in the PACU after one or two level open lumbar laminectomy.
We assembled the 9.8-Gbp genome of western redcedar (WRC;
Thuja plicata
), an ecologically and economically important conifer species of the Cupressaceae. The genome assembly, derived from a uniquely ...inbred tree produced through five generations of self-fertilization (selfing), was determined to be 86% complete by BUSCO analysis, one of the most complete genome assemblies for a conifer. Population genomic analysis revealed WRC to be one of the most genetically depauperate wild plant species, with an effective population size of approximately 300 and no significant genetic differentiation across its geographic range. Nucleotide diversity, π, is low for a continuous tree species, with many loci showing zero diversity, and the ratio of π at zero- to fourfold degenerate sites is relatively high (approximately 0.33), suggestive of weak purifying selection. Using an array of genetic lines derived from up to five generations of selfing, we explored the relationship between genetic diversity and mating system. Although overall heterozygosity was found to decline faster than expected during selfing, heterozygosity persisted at many loci, and nearly 100 loci were found to deviate from expectations of genetic drift, suggestive of associative overdominance. Nonreference alleles at such loci often harbor deleterious mutations and are rare in natural populations, implying that balanced polymorphisms are maintained by linkage to dominant beneficial alleles. This may account for how WRC remains responsive to natural and artificial selection, despite low genetic diversity.
Background: Multimodal analgesia techniques, including regional analgesia, have been shown to provide effective analgesia and minimize opioid consumption after liver resection surgery. While thoracic ...epidural analgesia (TEA) is considered the gold standard, its role in the current era of enhanced recovery after surgery (ERAS) has been questioned. Erector spinae plane blocks (ESPBs) have the potential to provide effective postoperative analgesia without the risks associated with epidural analgesia. The primary aim of this quality improvement project was to evaluate the analgesic efficacy of ultrasound-guided ESPB in comparison with TEA in patients undergoing open liver resection.Methods: Fifty patients who underwent open liver resection and received TEA (n=25) or ESPB (n=25) as part of an ERAS pathway were retrospectively identified. The primary outcome measure was cumulative postoperative opioid consumption at 24 hours. Secondary outcomes included opioid consumption, pain scores, the incidence of nausea and vomiting requiring antiemetics, lower extremity muscle weakness, and occurrence of hypotension requiring treatment on arrival to the post-anesthesia care unit and at 2, 6, 12, 24 hours, and daily through postoperative day 7. Results: Opioid requirements were significantly lower in the TEA group compared to the ESPB group. Postoperative pain scores at rest and with deep inspiration were significantly lower in the TEA group through postoperative day 5. There were no differences in other outcome measures.Conclusions: These findings suggest that compared with ESPB, TEA provides superior pain relief after open liver resection.
This prospectively designed, clinical quality improvement project compared pain scores and opioid consumption between ultrasound-guided, erector spinae plane blocks (ESPB) and thoracic paravertebral ...blocks (PVB) in patients undergoing total bilateral mastectomies without reconstruction. Twenty-five patients were included in an enhanced recovery pathway and received an ESPB on one side and a PVB on the contralateral side. Numeric rating scores at rest and with movement for each side were recorded in the recovery room at 2, 6, 12, 24, and 48 hours and on days 3 to 7. There were no significant differences in the resting or movement-evoked pain scores between sides receiving ESPB or PVB at any time point up to day 7 after surgery. Both ESPB and PVB confer equal analgesic effects in patients undergoing mastectomies. ESPB provides an alternative to PVB in reducing postoperative pain in patients undergoing mastectomy as part of an enhanced recovery pathway.
Purpose
Etomidate and ketamine are hemodynamically stable induction agents often used to sedate critically ill patients during emergency endotracheal intubation. In 2015, quality improvement data ...from our hospital suggested a survival benefit at Day 7 from avoidance of etomidate in critically ill patients during emergency intubation. In this clinical trial, we hypothesized that randomization to ketamine instead of etomidate would be associated with Day 7 survival after emergency endotracheal intubation.
Methods
A prospective, randomized, open-label, parallel assignment, single-center clinical trial performed by an anesthesiology-based Airway Team under emergent circumstances at one high-volume medical center in the United States. 801 critically ill patients requiring emergency intubation were randomly assigned 1:1 by computer-generated, pre-randomized sealed envelopes to receive etomidate (0.2–0.3 mg/kg,
n
= 400) or ketamine (1–2 mg/kg,
n
= 401) for sedation prior to intubation. The pre-specified primary endpoint of the trial was Day 7 survival. Secondary endpoints included Day 28 survival.
Results
Of the 801 enrolled patients, 396 were analyzed in the etomidate arm, and 395 in the ketamine arm. Day 7 survival was significantly lower in the etomidate arm than in the ketamine arm (77.3% versus 85.1%, difference − 7.8, 95% confidence interval − 13, − 2.4,
p
= 0.005). Day 28 survival rates for the two groups were not significantly different (etomidate 64.1%, ketamine 66.8%, difference − 2.7, 95% confidence interval − 9.3, 3.9,
p
= 0.294).
Conclusion
While the primary outcome of Day 7 survival was greater in patients randomized to ketamine, there was no significant difference in survival by Day 28.
SARS-CoV-2 continues to acquire mutations in the spike receptor-binding domain (RBD) that impact ACE2 receptor binding, folding stability, and antibody recognition. Deep mutational scanning ...prospectively characterizes the impacts of mutations on these biochemical properties, enabling rapid assessment of new mutations seen during viral surveillance. However, the effects of mutations can change as the virus evolves, requiring updated deep mutational scans. We determined the impacts of all single amino acid mutations in the Omicron BA.1 and BA.2 RBDs on ACE2-binding affinity, RBD folding, and escape from binding by the LY-CoV1404 (bebtelovimab) monoclonal antibody. The effects of some mutations in Omicron RBDs differ from those measured in the ancestral Wuhan-Hu-1 background. These epistatic shifts largely resemble those previously seen in the Alpha variant due to the convergent epistatically modifying N501Y substitution. However, Omicron variants show additional lineage-specific shifts, including examples of the epistatic phenomenon of entrenchment that causes the Q498R and N501Y substitutions present in Omicron to be more favorable in that background than in earlier viral strains. In contrast, the Omicron substitution Q493R exhibits no sign of entrenchment, with the derived state, R493, being as unfavorable for ACE2 binding in Omicron RBDs as in Wuhan-Hu-1. Likely for this reason, the R493Q reversion has occurred in Omicron sub-variants including BA.4/BA.5 and BA.2.75, where the affinity buffer from R493Q reversion may potentiate concurrent antigenic change. Consistent with prior studies, we find that Omicron RBDs have reduced expression, and identify candidate stabilizing mutations that ameliorate this deficit. Last, our maps highlight a broadening of the sites of escape from LY-CoV1404 antibody binding in BA.1 and BA.2 compared to the ancestral Wuhan-Hu-1 background. These BA.1 and BA.2 deep mutational scanning datasets identify shifts in the RBD mutational landscape and inform ongoing efforts in viral surveillance.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Genomic analysis of tumours has led to the identification of hundreds of cancer genes on the basis of the presence of mutations in protein-coding regions. By contrast, much less is known about ...cancer-causing mutations in non-coding regions. Here we perform deep sequencing in 360 primary breast cancers and develop computational methods to identify significantly mutated promoters. Clear signals are found in the promoters of three genes. FOXA1, a known driver of hormone-receptor positive breast cancer, harbours a mutational hotspot in its promoter leading to overexpression through increased E2F binding. RMRP and NEAT1, two non-coding RNA genes, carry mutations that affect protein binding to their promoters and alter expression levels. Our study shows that promoter regions harbour recurrent mutations in cancer with functional consequences and that the mutations occur at similar frequencies as in coding regions. Power analyses indicate that more such regions remain to be discovered through deep sequencing of adequately sized cohorts of patients.
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