Background
This is the fourth updated Enhanced Recovery After Surgery (ERAS
®
) Society guideline presenting a consensus for optimal perioperative care in colorectal surgery and providing graded ...recommendations for each ERAS item within the ERAS
®
protocol.
Methods
A wide database search on English literature publications was performed. Studies on each item within the protocol were selected with particular attention paid to meta-analyses, randomised controlled trials and large prospective cohorts and examined, reviewed and graded according to Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system.
Results
All recommendations on ERAS
®
protocol items are based on best available evidence; good-quality trials; meta-analyses of good-quality trials; or large cohort studies. The level of evidence for the use of each item is presented accordingly.
Conclusions
The evidence base and recommendation for items within the multimodal perioperative care pathway are presented by the ERAS
®
Society in this comprehensive consensus review.
Summary
It is widely recognised that prolonged fasting for elective surgery in both children and adults serves no purpose, adversely affects patient well‐being and can be detrimental. Although ...advised fasting times for solids remain unchanged, there is good evidence to support a 1‐h fast for children, with no increase in risk of pulmonary aspiration. In adults, a major focus has been the introduction of carbohydrate loading before anaesthesia, so that patients arrive for surgery not only hydrated but also in a more normal metabolic state. The latter attenuates some of the physiological responses to surgery, such as insulin resistance. As in children, there is no increase in risk of pulmonary aspiration. Further data are required to guide best practice in patients with diabetes.
The Enhanced Recovery After Surgery Society guideline for intraoperative care in cesarean delivery will provide best practice, evidenced-based, recommendations for intraoperative care, with primarily ...a maternal focus. The “focused” pathway process for scheduled and unscheduled cesarean delivery for this Enhanced Recovery After Surgery cesarean delivery guideline will consider procedure from the decision to operate (starting with the 30–60 minutes before skin incision) through the surgery. The literature search (1966–2017) used Embase and PubMed to search medical subject headings including “cesarean section,” “cesarean section,” “cesarean section delivery,” and all pre- and intraoperative Enhanced Recovery After Surgery items. Study selection allowed titles and abstracts to be screened by individual reviewers to identify potentially relevant articles. Metaanalyses, systematic reviews, randomized controlled studies, nonrandomized controlled studies, reviews, and case series were considered for each individual topic. Quality assessment and data analyses evaluated the quality of evidence and recommendations were evaluated according to the Grading of Recommendations, Assessment, Development and Evaluation system as used and described in previous Enhanced Recovery After Surgery Society guidelines. The Enhanced Recovery After Surgery cesarean delivery guideline/pathway has created a maternal focused pathway (for scheduled and unscheduled surgery starting from 30–60 minutes before skin incision to maternal discharge) with Enhanced Recovery After Surgery–directed preoperative elements, intraoperative elements, and postoperative elements. Specifics of the intraoperative care included the use of prophylactic antibiotics before the cesarean delivery, appropriate patient warming intraoperatively, blunt expansion of the transverse uterine hysterotomy, skin closure with subcuticular sutures, and delayed cord clamping. A number of specific elements of intraoperative care of women who undergo cesarean delivery are recommended based on the evidence. The Enhanced Recovery After Surgery Society guideline for intraoperative care in cesarean delivery will provide best practice, evidenced-based, recommendations for intraoperative care with primarily a maternal focus. When the cesarean delivery pathway (elements/processes) is studied, implemented, audited, evaluated, and optimized by maternity care teams, this will create an opportunity for the focused and optimized areas of care and recommendations to be further enhanced.
Highlights • The enzymatic degradation of ECM stimulates developmental forms of plasticity. • Weakening ECM aids functional recovery in regeneration, stroke, and amblyopia. • ECM molecules shape ...epileptogenesis and might be new valuable therapeutic targets. • Heparan sulfate proteoglycans regulate turnover of beta-amyloid.
The International Campaign for Cures of Spinal Cord Injury Paralysis (ICCP) supported an international panel tasked with reviewing the methodology for clinical trials in spinal cord injury (SCI), and ...making recommendations on the conduct of future trials. This is the first of four papers. Here, we examine the spontaneous rate of recovery after SCI and resulting consequences for achieving statistically significant results in clinical trials. We have reanalysed data from the Sygen trial to provide some of this information. Almost all people living with SCI show some recovery of motor function below the initial spinal injury level. While the spontaneous recovery of motor function in patients with motor-complete SCI is fairly limited and predictable, recovery in incomplete SCI patients (American spinal injury Association impairment scale (AIS) C and AIS D) is both more substantial and highly variable. With motor complete lesions (AIS A/AIS B) the majority of functional return is within the zone of partial preservation, and may be sufficient to reclassify the injury level to a lower spinal level. The vast majority of recovery occurs in the first 3 months, but a small amount can persist for up to 18 months or longer. Some sensory recovery occurs after SCI, on roughly the same time course as motor recovery. Based on previous data of the magnitude of spontaneous recovery after SCI, as measured by changes in ASIA motor scores, power calculations suggest that the number of subjects required to achieve a significant result from a trial declines considerably as the start of the study is delayed after SCI. Trials of treatments that are most efficacious when given soon after injury will therefore, require larger patient numbers than trials of treatments that are effective at later time points. As AIS B patients show greater spontaneous recovery than AIS A patients, the number of AIS A patients requiring to be enrolled into a trial is lower. This factor will have to be balanced against the possibility that some treatments will be more effective in incomplete patients. Trials involving motor incomplete SCI patients, or trials where an accurate assessment of AIS grade cannot be made before the start of the trial, will require large subject numbers and/or better objective assessment methods.
After CNS injury, axon regeneration is blocked by an inhibitory environment consisting of the highly upregulated tenascin-C and chondroitin sulfate proteoglycans (CSPGs). Tenascin-C promotes growth ...of axons if they express a tenascin-binding integrin, particularly α9β1. Additionally, integrins can be inactivated by CSPGs, and this inhibition can be overcome by the presence of a β1-binding integrin activator, kindlin-1. We examined the synergistic effect of α9 integrin and kindlin-1 on sensory axon regeneration in adult rat spinal cord after dorsal root crush and adeno-associated virus transgene expression in dorsal root ganglia. After 12 weeks, axons from C6-C7 dorsal root ganglia regenerated through the tenascin-C-rich dorsal root entry zone into the dorsal column up to C1 level and above (>25 mm axon length) through a normal pathway. Animals also showed anatomical and electrophysiological evidence of reconnection to the dorsal horn and behavioral recovery in mechanical pressure, thermal pain, and ladder-walking tasks. Expression of α9 integrin or kindlin-1 alone promoted much less regeneration and recovery.
The study demonstrates that long-distance sensory axon regeneration over a normal pathway and with sensory and sensory-motor recovery can be achieved. This was achieved by expressing an integrin that recognizes tenascin-C, one of the components of glial scar tissue, and an integrin activator. This enabled extensive long-distance (>25 mm) regeneration of both myelinated and unmyelinated sensory axons with topographically correct connections in the spinal cord. The extent of growth and recovery we have seen would probably be clinically significant. Restoration of sensation to hands, perineum, and genitalia would be a significant improvement for a spinal cord-injured patient.
Chondroitin sulfate is a glycosaminoglycan composed of N-acetylgalactosamine and glucuronic acid. It attaches to a core protein to form chondroitin sulfate proteoglycan (CSPG). Being a major ...component of the brain extracellular matrix, CSPGs are involved in neural development, axon pathfinding and guidance, plasticity and also regeneration after injury in the nervous system. In this review, we shall discuss the structure, the biosynthetic pathway, its functions in the nervous system and how we can improve regeneration in the nervous system by modulating its structure and binding properties.
Retrospective, longitudinal analysis of motor recovery data from individuals with cervical (C4-C7) sensorimotor complete spinal cord injury (SCI) according to the International Standards for ...Neurological Classification of Spinal Cord Injury (ISNCSCI).
To analyze the extent and patterns of spontaneous motor recovery over the first year after traumatic cervical sensorimotor complete SCI.
Datasets from the European multicenter study about SCI (EMSCI) and the Sygen randomized clinical trial were examined for conversion of American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade, change in upper extremity motor score (UEMS) or motor level, as well as relationships between these measures.
There were no overall differences between the EMSCI and Sygen datasets in motor recovery patterns. After 1 year, up to 70% of subjects spontaneously recovered at least one motor level, but only 30% recovered two or more motor levels, with lesser values at intermediate time points. AIS grade conversion did not significantly influence motor level changes. At 1 year, the average spontaneous improvement in bilateral UEMS was 10-11 motor points. There was only moderate relationship between a change in UEMS and a change in cervical motor level (r(2)=0.30, P<0.05). Regardless of initial cervical motor level, most individuals recover a similar number of motor points or motor levels.
Careful tracking of cervical motor recovery outcomes may provide the necessary sensitivity and accuracy to reliably detect a subtle, but meaningful treatment effect after sensorimotor complete cervical SCI. The distribution of the UEMS change may be more important functionally than the total UEMS recovered.
An international panel reviewed the methodology for clinical trials of spinal cord injury (SCI), and provided recommendations for the valid conduct of future trials. This is the second of four ...papers. It examines clinical trial end points that have been used previously, reviews alternative outcome tools and identifies unmet needs for demonstrating the efficacy of an experimental intervention after SCI. The panel focused on outcome measures that are relevant to clinical trials of experimental cell-based and pharmaceutical drug treatments. Outcome measures are of three main classes: (1) those that provide an anatomical or neurological assessment for the connectivity of the spinal cord, (2) those that categorize a subject's functional ability to engage in activities of daily living, and (3) those that measure an individual's quality of life (QoL). The American Spinal Injury Association impairment scale forms the standard basis for measuring neurologic outcomes. Various electrophysiological measures and imaging tools are in development, which may provide more precise information on functional changes following treatment and/or the therapeutic action of experimental agents. When compared to appropriate controls, an improved functional outcome, in response to an experimental treatment, is the necessary goal of a clinical trial program. Several new functional outcome tools are being developed for measuring an individual's ability to engage in activities of daily living. Such clinical end points will need to be incorporated into Phase 2 and Phase 3 trials. QoL measures often do not correlate tightly with the above outcome tools, but may need to form part of Phase 3 trial measures.
Axon regeneration in the CNS is blocked by inhibitory molecules in the environment and by a developmental loss of regenerative potential in CNS axons. Axon growth is a specialized form of cell ...migration, and for any cell to migrate there must be an adhesion molecule at the growth tip that recognizes a ligand in the environment, and which is linked to signaling and cytoskeletal mechanisms. The reasons for this loss of regenerative ability in CNS axons are several, but important contributors are the developmental loss of integrins that recognize ligands in the mature CNS environment, and selective trafficking of integrins and other molecules to exclude them from axons and direct them to dendrites. Regeneration of sensory axons in the spinal cord can be achieved by expression of tenascin-binding α9-integrin together with the integrin activator kindlin-1. This works because integrins are transported into sensory axons. Transport of integrins into retinal ganglion cell axons is seen in the retina, but may become more restricted in the optic nerve, with a subset of axons containing expressed integrins. Transduction of ganglion cells with α9-integrin and kindlin-1 should promote regeneration of this subset of axons, but attention to transport may be required for regeneration of the remaining axons.
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