Enhanced recovery after elective spinal surgery: an Australian pilot study.

Background: The principles of enhanced recovery after surgery (ERAS) aim to reduce the physiological stress of surgery which in turn improve clinical and health economic outcomes. There is ample evidence in literature supporting ERAS methodologies in other surgical specialties, but its adoption in spinal surgery, especially in Australia remains in infancy. The aim of this project is to describe the early experience with an evidence-based ERAS pathway for simple spine surgery, a first of its kind in Australia. Methods: An ERAS protocol was designed using an evidenced-based review of the literature. The authors then conducted a prospective cohort analysis looking at outcome of patients undergoing elective spinal (lumbar and cervical) decompression surgery under ERAS principles by a single surgeon on the Westmead Hospital Campus between March 2021 to May 2023. Primary outcomes were patient length of stay (LOS), patient reported pain and disability scores and complications (including readmissions within 30 days and re-operation within 6 months). Secondary outcomes included predictors of failure for same-day discharge. Results: A total of 52 patients underwent spinal decompression surgeries under the ERAS protocol. Overall 43 out of 52 patients (83.7%) were successfully discharged on the same day as their surgery. Patient reported outcomes were improved at 6 weeks and 6 months confirming durability of intervention. The rates of complications were similar to literature reported rates for simple lumbar or cervical decompression procedures and there were no readmissions within 30 days or re-operations within 6 months of surgery. Being of non-English speaking background [odds ratio (OR) =6.08, P=0.04] and from home alone (OR =10.25, P=0.03) were predictors of failure of same day discharge in this small cohort. Conclusions: Implementation of ERAS protocols for simple spinal decompression surgeries is feasible and produces durable improved patient outcomes while reducing LOS in hospitals. Patient social factors can be predictive of lack of compliance.

The embedding problem for markov models of nucleotide substitution.

Continuous-time Markov processes are often used to model the complex natural phenomenon of sequence evolution. To make the process of sequence evolution tractable, simplifying assumptions are often made about the sequence properties and the underlying process. The validity of one such assumption, time-homogeneity, has never been explored. Violations of this assumption can be found by identifying non-embeddability. A process is non-embeddable if it can not be embedded in a continuous time-homogeneous Markov process. In this study, non-embeddability was demonstrated to exist when modelling sequence evolution with Markov models. Evidence of non-embeddability was found primarily at the third codon position, possibly resulting from changes in mutation rate over time. Outgroup edges and those with a deeper time depth were found to have an increased probability of the underlying process being non-embeddable. Overall, low levels of non-embeddability were detected when examining individual edges of triads across a diverse set of alignments. Subsequent phylogenetic reconstruction analyses demonstrated that non-embeddability could impact on the correct prediction of phylogenies, but at extremely low levels. Despite the existence of non-embeddability, there is minimal evidence of violations of the local time homogeneity assumption and consequently the impact is likely to be minor.

A unique H2A histone variant occupies the transcriptional start site of active genes.

Transcriptional activation is controlled by chromatin, which needs to be unfolded and remodeled to ensure access to the transcription start site (TSS). However, the mechanisms that yield such an 'open' chromatin structure, and how these processes are coordinately regulated during differentiation, are poorly understood. We identify the mouse (Mus musculus) H2A histone variant H2A.Lap1 as a previously undescribed component of the TSS of active genes expressed during specific stages of spermatogenesis. This unique chromatin landscape also includes a second histone variant, H2A.Z. In the later stages of round spermatid development, H2A.Lap1 dynamically loads onto the inactive X chromosome, enabling the transcriptional activation of previously repressed genes. Mechanistically, we show that H2A.Lap1 imparts unique unfolding properties to chromatin. We therefore propose that H2A.Lap1 coordinately regulates gene expression by directly opening the chromatin structure of the TSS at genes regulated during spermatogenesis.