The impact of preoperative sarcopenia on postoperative ileus following colorectal cancer surgery.

PURPOSE: Sarcopenia is associated with poor short- and long-term patient outcomes following colorectal surgery. Despite postoperative ileus (POI) being a major complication following colorectal surgery, the predictive value of sarcopenia for POI is unclear. We assessed the association between sarcopenia and POI in patients with colorectal cancer. METHODS: Elective colorectal cancer surgery patients were retrospectively included (2018-2022). The cross-sectional psoas area was calculated using preoperative staging imaging at the level of the 3rd lumbar vertebrae. Sarcopenia was determined using gender-specific cut-offs. The primary outcome POI was defined as not achieving GI-2 by day 4. Demographics, operative characteristics, and complications were compared via univariate and multivariate analyses. RESULTS: Of 297 patients, 67 (22.6%) were sarcopenic. Patients with sarcopenia were older (median 74 (IQR 67-82) vs. 69 (58-76) years, p < 0.001) and had lower body mass index (median 24.4 (IQR 22.2-28.6) vs. 28.8 (24.9-31.9) kg/m2, p < 0.001). POI was significantly more prevalent in patients with sarcopenia (41.8% vs. 26.5%, p = 0.016). Overall rate of complications (85.1% vs. 68.3%, p = 0.007), Calvien-Dindo grade > 3 (13.4% vs. 10.0%, p = 0.026) and length of stay were increased in patients with sarcopenia (median 7 (IQR 5-12) vs. 6 (4-8) days, p = 0.013). Anastomotic leak rate was higher in patients with sarcopenia although the difference was not statistically significant (7.5% vs. 2.6%, p = 0.064). Multivariate analysis demonstrated sarcopenia (OR 2.0, 95% CI 1.1-3.8), male sex (OR 1.9, 95% CI 1.0-3.5), postoperative hypokalemia (OR 3.2, 95% CI 1.6-6.5) and increased opioid use (OR 2.4, 95% CI 1.3-4.3) were predictive of POI. CONCLUSION: Sarcopenia demonstrates an association with POI. Future research towards truly identifying the predictive value of sarcopenia for postoperative complications could improve informed consent and operative planning for surgical patients.

Effect of neuromuscular reversal with neostigmine/glycopyrrolate versus sugammadex on postoperative ileus following colorectal surgery.

BACKGROUND: Postoperative ileus (POI) is a common complication following colorectal surgery and is mediated in part by the cholinergic anti-inflammatory pathway (CAIP). Neostigmine (acetylcholinesterase inhibitor), co-administered with glycopyrrolate, is frequently given for neuromuscular reversal before tracheal extubation and modulates the CAIP. An alternative reversal agent, sugammadex (selective rocuronium or vecuronium binder), acts independently from the CAIP. The aim of our study was to assess the impact of neuromuscular reversal agents used during anaesthesia on gastrointestinal recovery. METHODS: Three hundred thirty-five patients undergoing elective colorectal surgery at the Royal Adelaide Hospital between January 2019 and December 2021 were retrospectively included. The primary outcome was GI-2, a validated composite measure of time to diet tolerance and passage of stool. Demographics, 30-day complications and length of stay were collected. Univariate and multivariate analyses were performed. RESULTS: Two hundred twenty-four (66.9%) patients (129 [57.6%] males and 95 [42.4%] females, median age 64 [19-90] years) received neostigmine/glycopyrrolate and 111 (33.1%) received sugammadex (62 [55.9%] males and 49 [44.1%] females, median age 67 [18-94] years). Sugammadex patients achieved GI-2 sooner after surgery (median 3 (0-10) vs. 3 (0-12) days, p = 0.036), and reduced time to first stool (median 2 (0-10) vs. 3 (0-12) days, p = 0.035). Rates of POI, complications and length of stay were similar. On univariate analysis, POI was associated with smoking history, previous abdominal surgery, colostomy formation, increased opioid use and postoperative hypokalaemia (p < 0.05). POI was associated with increased complications, including anastomotic leak and prolonged hospital stay (p < 0.001). On multivariate analysis, neostigmine, bowel anastomoses and increased postoperative opioid use (p < 0.05) remained predictive of time to GI-2. CONCLUSIONS: Patients who received sugammadex had a reduced time to achieving first stool and GI-2. Neostigmine use, bowel anastomoses and postoperative opioid use were associated with delayed time to achieving GI-2.

Impact of STIMUlant and osmotic LAXatives (STIMULAX trial) on gastrointestinal recovery after colorectal surgery: randomized clinical trial.

BACKGROUND: Recovery of gastrointestinal (GI) function is often delayed after colorectal surgery. Enhanced recovery protocols (ERPs) recommend routine laxative use, but evidence of benefit is unclear. This study aimed to investigate whether the addition of multimodal laxatives to an ERP improves return of GI function in patients undergoing colorectal surgery. METHODS: This was a single-centre, parallel, open-label RCT. All adult patients undergoing elective colorectal resection or having stoma formation or reversal at the Royal Adelaide Hospital between August 2018 and May 2020 were recruited into the study. The STIMULAX group received oral Coloxyl® with senna and macrogol, with a sodium phosphate enema in addition for right-sided operations. The control group received standard ERP postoperative care. The primary outcome was GI-2, a validated composite measure defined as the interval from surgery until first passage of stool and tolerance of solid intake for 24 h in the absence of vomiting. Secondary outcomes were the incidence of prolonged postoperative ileus (POI), duration of hospital stay, and postoperative complications. The analysis was performed on an intention-to-treat basis. RESULTS: Of a total of 170 participants, 85 were randomized to each group. Median GI-2 was 1 day shorter in the STIMULAX compared with the control group (median 2 (i.q.r. 1.5-4) versus 3 (2-5.5) days; 95 per cent c.i. -1 to 0 days; P = 0.029). The incidence of prolonged POI was lower in the STIMULAX group (22 versus 38 per cent; relative risk reduction 42 per cent; P = 0.030). There was no difference in duration of hospital day or 30-day postoperative complications (including anastomotic leak) between the STIMULAX and control groups. CONCLUSION: Routine postoperative use of multimodal laxatives after elective colorectal surgery results in earlier recovery of gastrointestinal function and reduces the incidence of prolonged POI. Registration number: ACTRN12618001261202 (www.anzctr.org.au).

A simple web-based risk calculator (www.anastomoticleak.com) is superior to the surgeon's estimate of anastomotic leak after colon cancer resection.

BACKGROUND: Anastomotic leak can be a devastating complication, and early prediction is difficult. The aim of this study is to prospectively validate a simple anastomotic leak risk calculator and compare its predictive value with the estimate of the primary operating surgeon. METHODS: Consecutive patients undergoing elective or emergency colon cancer surgery with a primary anastomosis over a 1-year period were prospectively included. A recently published anastomotic leak risk nomogram was converted to an online calculator ( www.anastomoticleak.com ). The calculator-derived risk of anastomotic leak and the risk estimated by the primary operating surgeon were recorded at the completion of surgery. The primary outcome was anastomotic leak within 90 days as defined by previously published criteria. Area under receiver operating characteristic curve analysis (AUROC) was performed for both risk estimates. RESULTS: A total of 105 patients were screened for inclusion during the study period, of whom 83 met the inclusion criteria. The overall anastomotic leak rate was 9.6%. The anastomotic leak calculator was highly predictive of anastomotic leak (AUROC 0.84, P = 0.002), whereas the surgeon estimate was not predictive (AUROC 0.40, P = 0.243). CONCLUSIONS: A simple anastomotic leak risk calculator is significantly better at predicting anastomotic leak than the estimate of the primary surgeon. Further external validation on a larger data set is required.

Validation of an online risk calculator for the prediction of anastomotic leak after colon cancer surgery and preliminary exploration of artificial intelligence-based analytics.

BACKGROUND: Recently published data support the use of a web-based risk calculator ( www.anastomoticleak.com ) for the prediction of anastomotic leak after colectomy. The aim of this study was to externally validate this calculator on a larger dataset. METHODS: Consecutive adult patients undergoing elective or emergency colectomy for colon cancer at a single institution over a 9-year period were identified using the Binational Colorectal Cancer Audit database. Patients with a rectosigmoid cancer, an R2 resection, or a diverting ostomy were excluded. The primary outcome was anastomotic leak within 90 days as defined by previously published criteria. Area under receiver operating characteristic curve (AUROC) was derived and compared with that of the American College of Surgeons National Surgical Quality Improvement Program® (ACS NSQIP) calculator and the colon leakage score (CLS) calculator for left colectomy. Commercially available artificial intelligence-based analytics software was used to further interrogate the prediction algorithm. RESULTS: A total of 626 patients were identified. Four hundred and fifty-six patients met the inclusion criteria, and 402 had complete data available for all the calculator variables (126 had a left colectomy). Laparoscopic surgery was performed in 39.6% and emergency surgery in 14.7%. The anastomotic leak rate was 7.2%, with 31.0% requiring reoperation. The anastomoticleak.com calculator was significantly predictive of leak and performed better than the ACS NSQIP calculator (AUROC 0.73 vs 0.58) and the CLS calculator (AUROC 0.96 vs 0.80) for left colectomy. Artificial intelligence-predictive analysis supported these findings and identified an improved prediction model. CONCLUSIONS: The anastomotic leak risk calculator is significantly predictive of anastomotic leak after colon cancer resection. Wider investigation of artificial intelligence-based analytics for risk prediction is warranted.

Three dimensional rotational angiography for assessment of coronary arteries during melody valve implantation: introducing a technique that may improve outcomes.

BACKGROUND: Adverse events from Melody valve implantation may be catastrophic. To date a role for three dimensional rotational angiography of the aortic root (3DRAA) during Melody valve implantation has not been established. OBJECTIVES: To describe the role of 3DRAA in the assessment of Melody valve candidacy and to demonstrate that it may improve outcomes. METHODS: All patients who underwent cardiac catheterisation for Melody valve implantation and 3DRAA between August 2013 and February 2015 were reviewed. RESULTS: 31 patients had 3DRAA with balloon sizing. Ten were deemed not Melody candidates (5 coronary compression, 2 aortic root distortion with cusp flattening, 2 RVOT was too large, and 1 had complex branch stenosis and a short landing zone). Of the 21 patients who were Melody candidates, 12 had conduits, 6 prosthetic valves and 3 native RVOTs. In patients with conduits, the technique of stenting the conduit prior to dilation was used after measuring the distance between the conduit and the coronary arteries on 3DRAA. In the Melody patients, we had 100% procedural success and no serious adverse events (coronary compression, tears, stent fracture or endocarditis). CONCLUSION: As a tool for case selection, 3DRAA may facilitate higher procedural success and decreased risk of serious adverse events. Furthermore, 3D rotational angiography allows stenting of the conduit prior to dilation, which may prevent tears and possibly endocarditis.

Synchronisation and stability in river metapopulation networks.

Spatial structure in landscapes impacts population stability. Two linked components of stability have large consequences for persistence: first, statistical stability as the lack of temporal fluctuations; second, synchronisation as an aspect of dynamic stability, which erodes metapopulation rescue effects. Here, we determine the influence of river network structure on the stability of riverine metapopulations. We introduce an approach that converts river networks to metapopulation networks, and analytically show how fluctuation magnitude is influenced by interaction structure. We show that river metapopulation complexity (in terms of branching prevalence) has nonlinear dampening effects on population fluctuations, and can also buffer against synchronisation. We conclude by showing that river transects generally increase synchronisation, while the spatial scale of interaction has nonlinear effects on synchronised dynamics. Our results indicate that this dual stability - conferred by fluctuation and synchronisation dampening - emerges from interaction structure in rivers, and this may strongly influence the persistence of river metapopulations.

Using scale characteristics and water temperature to reconstruct growth rates of juvenile steelhead Oncorhynchus mykiss.

Juvenile steelhead Oncorhynchus mykiss from a northern California Central Valley population were reared in a controlled laboratory experiment. Significantly different rates of growth were observed among fish reared under two ration treatments and three temperature treatments (8, 14 and 20°C). Wider circulus spacing and faster deposition was associated with faster growth. For the same growth rate, however, circulus spacing was two-fold wider and deposited 36% less frequently in the cold compared to the hot temperature treatment. In a multiple linear regression, median circulus spacing and water temperature accounted for 68% of the variation in observed O. mykiss growth. These results corroborate previous research on scale characteristics and growth, while providing novel evidence that highlights the importance of water temperature in these relationships. Thus, this study establishes the utility of using scale analysis as a relatively non-invasive method for inferring growth in salmonids.

Sense of agency in health and disease: a review of cue integration approaches.

Sense of agency (SoA) is a compelling but fragile experience that is augmented or attenuated by internal signals and by external cues. A disruption in SoA may characterise individual symptoms of mental illness such as delusions of control. Indeed, it has been argued that generic SoA disturbances may lie at the heart of delusions and hallucinations that characterise schizophrenia. A clearer understanding of how sensorimotor, perceptual and environmental cues complement, or compete with, each other in engendering SoA may prove valuable in deepening our understanding the agency disruptions that characterise certain focal neurological disorders and mental illnesses. Here we examine the integration of SoA cues in health and illness, describing a simple framework of this integration based on Bayesian principles. We extend this to consider how alterations in cue integration may lead to aberrant experiences of agency.

Exploring implicit and explicit aspects of sense of agency.

Sense of agency refers to the sense of initiating and controlling actions in order to influence events in the outside world. Recently, a distinction between implicit and explicit aspects of sense of agency has been proposed, analogous to distinctions found in other areas of cognition, notably learning. However, there is yet no strong evidence supporting separable implicit and explicit components of sense of agency. The so-called 'Perruchet paradigm' offers one of the few convincing demonstrations of separable implicit and explicit learning systems. We adopted this approach to evaluate the implicit-explicit distinction in the context of a simple task in which outcomes were probabilistically caused by actions. In line with our initial predictions, we found evidence of a dissociation. We discuss the implications of this result for theories of sense of agency.

Manipulations of Libet clock parameters affect intention timing awareness.

W judgments are a widely used intention timing awareness estimate. These judgments are typically obtained by using the classic Libet-style paradigm whereby participants are asked to estimate the time they become aware of their intention to act by using the location of a rotating object on a clock face. There is an inconsistency in the Libet clock parameters used in previous studies, and it is unclear whether this variability impacts W judgments and other outcome measures, with implications for the construct validity of this measure and the generalisability of results across studies. Here, we present a four-experiment study that systematically manipulated the Libet clock speed, number of clock markings, length of the clock hand and type of clock radius in order to examine whether these parameter manipulations affect intention timing awareness estimates. Our results demonstrate W judgments can be significantly influenced by the clock speed and number of clock markings. The meaning and implications of these results are discussed.

Development of Anthracnose on Grain Sorghum Hybrids Inoculated with Recently Described Pathotypes of Colletotrichum sublineolum Found in Arkansas.

Sorghum anthracnose, caused by Colletotrichum sublineolum, is found in most grain-sorghum-producing areas, including Arkansas. Yield losses can be severe in susceptible sorghum hybrids, suggesting that host resistance will continue to be critical for maintaining high yields. However, genetic control is often unsuccessful because of haplotype and pathotype variability within the C. sublineolum population. The objective of this research was to assess the levels of resistance of selected grain sorghum hybrids to isolates of the recently described pathotypes of C. sublineolum found in Arkansas. Field experiments were conducted in 2005 and 2006 to evaluate the reaction of 10 sorghum hybrids to eight C. sublineolum pathotypes by collecting anthracnose severity ratings at 7, 14, 21, and 28 days after inoculation. Based on these disease severity ratings, the area under the disease progress curve was calculated for each pathotype by hybrid interaction. These data showed that different levels of resistance are available in the current grain sorghum hybrids to different pathotypes. Cargill 888Y was resistant to all pathotypes in both years. However, Asgrow A571, DEKALB DKS53-11, FFR 318, and Pioneer 84G62 were moderately susceptible to susceptible to all pathotypes tested in both years. Pathotype 9 caused the most disease on 7 of the 10 hybrids evaluated in 2005 but, in 2006, pathotypes 12 and 13 surpassed pathotype 9 for disease severity on 9 of the 10 hybrids. More work is needed to assess host resistance and the effect of sorghum anthracnose on yield parameters of grain sorghum hybrids planted in Arkansas.

The utilization of a Pacific salmon Oncorhynchus nerka subsidy by three populations of charr Salvelinus spp.

The L(F) -at-age trajectories differentiated two populations of Dolly Varden charr Salvelinus malma and a population of Arctic charr Salvelinus alpinus from the eastern end of Iliamna Lake, Alaska. Salvelinus malma from the Pedro Bay ponds were the smallest for a given age, followed by Salvelinus alpinus from the lake, and S. malma from the Iliamna River were much larger. The utilization of a large sockeye salmon Oncorhynchus nerka subsidy by the three Salvelinus spp. populations was then investigated by comparing diet data and mixing model (MixSIR) outputs based on carbon and nitrogen stable isotopes. Stomach contents indicated that both S. malma populations fed on O. nerka products, especially eggs and larval Diptera that had scavenged O. nerka carcasses, whereas S. alpinus fed on a variety of prey items such as three-spined sticklebacks Gasterosteus aculeatus and snails. Stable-isotope analysis corroborated the diet data; the two S. malma populations incorporated more O. nerka-derived nutrients into their tissues than did S. alpinus from the lake, although all populations showed substantial utilization of O. nerka-derived resources. Salvelinus alpinus also seemed to be much more omnivorous, as shown by stable-isotope mixing models, than the S. malma populations. The dramatic differences in growth rate between the two S. malma populations, despite similar trophic patterns, indicate that other important genetic or environmental factors affect their life history, including proximate temperature controls and ultimate predation pressures.

Safety and efficacy of laxatives after major abdominal surgery: systematic review and meta-analysis.

BACKGROUND: Recovery of gastrointestinal function is often delayed after major abdominal surgery, leading to postoperative ileus (POI). Enhanced recovery protocols recommend laxatives to reduce the duration of POI, but evidence is unclear. This systematic review aimed to assess the safety and efficacy of laxative use after major abdominal surgery. METHODS: Ovid MEDLINE, Embase, Cochrane Library and PubMed databases were searched from inception to May 2019 to identify eligible RCTs focused on elective open or minimally invasive major abdominal surgery. The primary outcome was time taken to passage of stool. Secondary outcomes were time taken to tolerance of diet, time taken to flatus, length of hospital stay, postoperative complications and readmission to hospital. RESULTS: Five RCTs with a total of 416 patients were included. Laxatives reduced the time to passage of stool (mean difference (MD) -0·83 (95 per cent c.i. -1·39 to -0·26) days; P = 0·004), but there was significant heterogeneity between studies for this outcome measure. There was no difference in time to passage of flatus (MD -0·17 (-0·59 to 0·25) days; P = 0·432), time to tolerance of diet (MD -0·01 (-0·12 to 0·10) days; P = 0·865) or length of hospital stay (MD 0·01(-1·36 to 1·38) days; P = 0·992). There were insufficient data available on postoperative complications for meta-analysis. CONCLUSION: Routine postoperative laxative use after major abdominal surgery may result in earlier passage of stool but does not influence other postoperative recovery parameters. Better data are required for postoperative complications and validated outcome measures.

ANTECEDENTES: El retraso en la recuperación de la función gastrointestinal después de una cirugía abdominal mayor es frecuente y conlleva la aparición de un íleo postoperatorio (postoperative ileus, POI). Los protocolos de rehabilitación multimodal recomiendan la utilización de laxantes para reducir la duración del POI, pero su evidencia no es concluyente. Esta revisión sistemática tuvo como objetivo evaluar la seguridad y la eficacia de la utilización de laxantes tras cirugía abdominal mayor. MÉTODOS: Se realizó una búsqueda de los estudio clínicos aleatorizados (randomised controlled trials, RCTs) centrados en la cirugía abdominal mayor electiva, abierta o mínimamente invasiva, en las bases de datos Ovid MEDLINE, EMBASe, Cochrane Library y PubMed, desde el inicio hasta mayo de 2019. La variable principal fue el tiempo transcurrido hasta la primera deposición. Las variables secundarias fueron el tiempo hasta tolerar la dieta, el tiempo hasta la emisión de ventosidades, la duración de la estancia hospitalaria, las complicaciones postoperatorias y los reingresos hospitalarios. RESULTADOS: Se incluyeron cinco RCTs con un total de 416 pacientes. Los laxantes redujeron el tiempo hasta la primera deposición (diferencia media, mean difference, MD − 0,83 (i.c. del 95% −1,39 a −0,26) días; P = 0,004) pero hubo una heterogeneidad significativa entre los estudios para la medida de este resultado. No hubo diferencias en el tiempo hasta la emisión de ventosidades (DM − 0,17 (−0,59 a 0,25) días; P = 0,432), tiempo hasta la tolerancia de la dieta (DM − 0,01 (−0,12 a 0,10) días; P = 0,865) y la duración de la estancia hospitalaria (DM 0,01 (−1,36 a 1,38) días; P = 0,992). No había datos suficientes de las complicaciones postoperatorias para efectuar un metaanálisis. CONCLUSIÓN: El uso rutinario de laxantes en el postoperatorio de una cirugía abdominal mayor puede acelerar el tránsito de heces, pero no influye en otras variables de la recuperación postoperatoria. Se requieren datos de mayor calidad para evaluar las complicaciones postoperatorias y medidas de resultados validadas.

Tetrodotoxin derivatives: chemical structure and blockage of nerve membrane conductance.

The nerve-impuilse-blocking actions of derivatives of tetrodotoxin have been tested on lobster and squid axons. The block produced by deoxytetrodotoxin was similar to that produced by tetrodotoxin and was probably caused by tetrodotoxin contamination. Tetrodaminotoxin and anhydrotetrodotoxin also produced a similar block but at such high concentrations that tetrodotoxin contamination cannot be ruled out. The hydroxyl group of C(4) and the hemilactal oxygen links play an important role for the nerve-blocking action.

Tetrodotoxin does not block excitation from inside the nerve membrane.

Tetrodotoxin does not block the action potential or membrane sodium current when internally perfused through the giant axon of a squid at much higher concentrations than those required for blocking by external application. It is suggested that the gate for the sodium channel is located on the exterior surface of the axon, because tetrodotoxin is not lipid soluble.

Synaptic current at the squid giant synapse.

Transmission in the giant synapse of squid was studied by measuring synaptic currents in the voltage-clamped postsynaptic giant axon. These currents varied linearly with the axon's membrane potential, and showed an intercept on the voltage axis at, or near, the sodium equilibrium potential. The intercept shifted in seawater containing less sodium by even more than the shift in the sodium equilibrium potential. It is concluded that the transmitter at this synapse causes a significant change in the sodium conductance only.

Hemicholinium-3: noncholinergic effects on squid axons.

Hemicholinium-3, when applied to the inside of a squid axon, is effective in blocking the action potential. This action is not antagonized by the addition of choline or acetylcholine to the perfusate. Voltage-clamp experiments show that hemicholinium-3 depresses both the early transient and late steady-state components of membrane ionic conductances, with a greater effect on the peak transient component.

Condylactis toxin: interaction with nerve membrane ionic conductances.

A toxin from the Bermuda anemone Condylactis gigantea causes the early transient conductance change of crayfish giant axon membranes to persist without affecting the shape of its turning-on. The increase in late steadystate conductance is either not affected or slightly suppressed. The effect on the conductance components can adequately account for the prolonged action potential observed in the treated axon.