Fit for Surgery-feasibility of short-course multimodal individualized prehabilitation in high-risk frail colon cancer patients prior to surgery.

BACKGROUND: Prehabilitation is a promising modality for improving patient-related outcomes after major surgery; however, very little research has been done for those who may need it the most: the elderly and the frail. This study aimed to investigate the feasibility of a short course multimodal prehabilitation prior to primary surgery in high-risk, frail patients with colorectal cancer and WHO performance status I and II. METHODS: The study was conducted as a single-center, prospective one-arm feasibility study of eight patients with colon cancer between October 4, 2018, and January 14, 2019. The intervention consisted of a physical training program tailored to the patients with both high-intensity interval training and resistance training three times a week in sessions of approximately 1 h in length, for a duration of at least 4 weeks, nutritional support with protein and vitamins, a consultation with a dietician, and medical optimization prior to surgery. Feasibility was evaluated regarding recruitment, retention, compliance and adherence, acceptability, and safety. Retention was evaluated as the number of patients that completed the intervention, with a feasibility goal of 75% completing the intervention. Compliance with the high-intensity training was evaluated as the number of sessions in which the patient achieved a minimum of 4 min > 90% of their maximum heart rate and adherence as the attended out of the offered training sessions. RESULTS: During the study period, 64 patients were screened for eligibility, and out of nine eligible patients, eight patients were included and seven completed the intervention (mean age 80, range 66-88). Compliance to the high-intensity interval training using 90% of maximum heart rate as the monitor of intensity was difficult to measure in several patients; however, adherence to the training sessions was 87%. Compliance with nutritional support was 57%. Half the patients felt somewhat overwhelmed by the multiple appointments and six out of seven reported difficulties with the dosage of protein. CONCLUSIONS: This one-arm feasibility study indicates that multimodal prehabilitation including high-intensity interval training can be performed by patients with colorectal cancer and WHO performance status I and II. TRIAL REGISTRATION: Clinicaltrials.gov : the study current feasibility study was conducted prior to the initiation of a full ongoing randomized trial registered by NCT04167436; date of registration: November 18, 2019. Retrospectively registered. No separate prospectively registration of the feasibility trial was conducted but outlined by the approved study protocol (Danish Scientific Ethical Committee SJ-607).

Prediction of 90-day mortality after surgery for colorectal cancer using standardized nationwide quality-assurance data.

BACKGROUND: Personalized risk assessment provides opportunities for tailoring treatment, optimizing healthcare resources and improving outcome. The aim of this study was to develop a 90-day mortality-risk prediction model for identification of high- and low-risk patients undergoing surgery for colorectal cancer. METHODS: This was a nationwide cohort study using records from the Danish Colorectal Cancer Group database that included all patients undergoing surgery for colorectal cancer between 1 January 2004 and 31 December 2015. A least absolute shrinkage and selection operator logistic regression prediction model was developed using 121 pre- and intraoperative variables and internally validated in a hold-out test data set. The accuracy of the model was assessed in terms of discrimination and calibration. RESULTS: In total, 49 607 patients were registered in the database. After exclusion of 16 680 individuals, 32 927 patients were included in the analysis. Overall, 1754 (5.3 per cent) deaths were recorded. Targeting high-risk individuals, the model identified 5.5 per cent of all patients facing a risk of 90-day mortality exceeding 35 per cent, corresponding to a 6.7 times greater risk than the average population. Targeting low-risk individuals, the model identified 20.9 per cent of patients facing a risk less than 0.3 per cent, corresponding to a 17.7 times lower risk compared with the average population. The model exhibited discriminatory power with an area under the receiver operating characteristics curve of 85.3 per cent (95 per cent c.i. 83.6 to 87.0) and excellent calibration with a Brier score of 0.04 and 32 per cent average precision. CONCLUSION: Pre- and intraoperative data, as captured in national health registries, can be used to predict 90-day mortality accurately after colorectal cancer surgery.

Impact of oral preoperative and perioperative immunonutrition on postoperative infection and mortality in patients undergoing cancer surgery: systematic review and meta-analysis with trial sequential analysis.

BACKGROUND: Infectious complications occur in 4-22 per cent of patients undergoing surgical resection of malignant solid tumours. Improving the patient's immune system in relation to oncological surgery with immunonutrition may play an important role in reducing postoperative infections. A meta-analysis was undertaken to evaluate the potential clinical benefits of immunonutrition on postoperative infections and 30-day mortality in patients undergoing oncological surgery. METHODS: PubMed, Embase and Cochrane Library databases were searched to identify eligible studies. Eligible studies had to include patients undergoing elective curative surgery for a solid malignant tumour and receiving immunonutrition orally before surgery, including patients who continued immunonutrition into the postoperative period. The main outcome was overall infectious complications; secondary outcomes were surgical-site infection (SSI) and 30-day mortality, described by relative risk (RR) with trial sequential analysis (TSA). Risk of bias was assessed according to Cochrane methodology. RESULTS: Some 22 RCTs with 2159 participants were eligible for meta-analysis. Compared with the control group, immunonutrition reduced overall infectious complications (RR 0·58, 95 per cent c.i. 0·48 to 0·70; I2 = 7 per cent; TSA-adjusted 95 per cent c.i. 0·28 to 1·21) and SSI (RR 0·65, 95 per cent c.i. 0·50 to 0·85; I2 = 0 per cent; TSA-adjusted 95 per cent c.i. 0·21 to 2·04). Thirty-day mortality was not altered by immunonutrition (RR 0·69, 0·33 to 1·40; I2 = 0 per cent). CONCLUSION: Immunonutrition reduced overall infectious complications, even after controlling for random error, and also reduced SSI. The quality of evidence was moderate, and mortality was not affected by immunonutrition (low quality). Oral immunonutrition merits consideration as a means of reducing overall infectious complications after cancer surgery.

ANTECEDENTES: Entre un 4-22% de los pacientes a los que se realiza una resección quirúrgica de tumores sólidos malignos presentan complicaciones infecciosas. Mejorar el sistema inmunitario del paciente quirúrgico oncológico mediante inmunonutrición puede tener un papel relevante en la reducción de las infecciones postoperatorias. Se realizó un metaanálisis para evaluar los posibles beneficios clínicos de la inmunonutrición en las infecciones postoperatorias y la mortalidad a los 30 días en pacientes sometidos a cirugía oncológica. MÉTODOS: Se realizó una búsqueda en las bases de datos de Pubmed, Embase y Cochrane para identificar los estudios clave. Se consideraron aquellos estudios que incluyeron pacientes con cirugía curativa electiva de un tumor maligno sólido que recibieron inmunonutrición por vía oral antes de la cirugía, así como también los que siguieron con inmunonutrición en el postoperatorio. La variable principal fueron las complicaciones infecciosas generales y las secundarias fueron la infección de la herida quirúrgica y la mortalidad a los 30 días, presentadas como el riesgo relativo (RR) obtenido a partir en un análisis secuencial de experimentos (trial sequential analysis, TSA). El riesgo de sesgo se evaluó según la metodología Cochrane. RESULTADOS: Para el metaanálisis se identificaron 22 ensayos clínicos con 2.075 participantes. En comparación con el grupo de control, la inmunonutrición redujo las complicaciones infecciosas generales (RR 0,58, i.c. del 95% 0,48-0,70, I2 = 7%, TSA ajustado i.c. del 95% 0,28-1,21) y las infecciones de la herida quirúrgica (RR 0,65, i.c. del 95% 0,50-0,85, I2 = 0%, TSA ajustado, i.c. del 95% 0,21-2,04). No hubo diferencias en la mortalidad a los 30 días (RR 0,69, i.c. del 95% 0,32-1,4, I2 = 0%). CONCLUSIÓN: la inmunonutrición redujo las complicaciones infecciosas generales, incluso después de controlar el error aleatorio. La inmunonutrición también redujo la infección de la herida quirúrgica. La calidad de la evidencia fue moderada y la mortalidad no se vio afectada por la inmunonutrición (baja calidad). La inmunonutrición oral debería ser tenida en cuenta como una forma de reducir las complicaciones infecciosas generales después de la cirugía del cáncer.

Inefficacy of simulator-based training on anaesthesiologists' non-technical skills.

BACKGROUND: Analysis of critical incidents in anaesthesia practice emphasizes the important role of non-technical skills (NTS) in improving patient safety. Therefore, debriefing with regard to NTS has been added to medical management (MM) simulator training to improve acute crisis competencies of anaesthesiologists. The purpose of this study was to compare the NTS and MM performance of two groups of anaesthesiologists in a simulated anaesthesia crisis after undergoing different types of training. METHODS: Forty-two anaesthesiologists were randomly assigned to two different training groups, with each group participating in two simulation training sessions. One group's (NTS+MMG) training included extensive debriefing of NTS (resource management, planning, leadership and communication) and MM, while the other group (MMG) received a simpler debriefing that focused solely on MM. The quality and quantity of NTS and quality of MM performance were rated by reviewing the videotapes of the scenarios. RESULTS: NTS+MMG did not prove superior to MMG with regard to behavioural and MM markers. The quality of NTS performances correlated significantly (P<0.01) with the quantity of NTS demonstration, and also correlated significantly with the MM actions (P<0.01) in both groups. CONCLUSION: A single session of training including debriefing of NTS and MM did not improve the NTS performances of anaesthesiologists when compared with anaesthesiologists who only received MM training. This might indicate that a more frequent or individual training is needed to improve participants' NTS performance.

Simulation as an additional tool for investigating the performance of standard operating procedures in anaesthesia.

BACKGROUND: In medicine, the use of standard operating procedures (SOPs) is often evaluated using questionnaires (QUES). However, QUES can have limitations with regard to method, thus leading to errors. Simulation (SIM) offers another opportunity for evaluation. We hypothesized that medical errors in the evaluation of SOPs using QUES could be detected by SIM, and that SIM is better qualified to demonstrate applied medicine. METHODS: We investigated the use of SOPs in anaesthesia, rapid sequence induction (RSI), by means of a QUES (n=42) or SIM (n=42) among 84 anaesthesiologists. Seven measures for preventing aspiration during induction of anaesthesia were examined and evaluated according to a predetermined points system. RESULTS: The average number of times that precautionary measures to prevent aspiration were mentioned in the QUES [4.8 (0.9)] or performed during SIM [5.0 (1.1)] did not differ between the two groups. Pre-oxygenation was the most frequently described or performed measure (95% vs 93%). However, other measures, such as avoidance of positive pressure ventilation (45% vs 85%), differed significantly between the two groups. CONCLUSIONS: QUES and SIM are powerful instruments for evaluating the implementation of SOPs such as RSI. SIM demonstrates automated behaviours and thus more clearly represents behaviours used in clinical practice than is possible to demonstrate using QUES. Using a combination of these two instruments, method errors resulting from the individual instruments can be reduced.

Surface properties and sensitivity to protein-inhibition of a recombinant apoprotein C-based phospholipid mixture in vitro--comparison to natural surfactant.

Surfactant alterations due to protein leakage are implicated in the pathogenesis of the adult respiratory distress syndrome. In the present study, surface properties of a palmitic acid containing phospholipid mixture (DPPC: PG: PA/68.5:22.5:9) supplemented with 2% recombinant human surfactant apoprotein C (PLM-Crec) were compared to those of the lipids alone (PLM) and to those of calf lung surfactant extract (CLSE). Experiments were performed in a Wilhelmy balance and in a pulsating bubble surfactometer. Adsorption facilities and dynamic surface tension-lowering properties of the surfactants alone, their sensitivity to the inhibitory effect of fibrinogen (fbg), and their capacity to restore surface properties of fbg-inhibited CLSE were investigated. PLM revealed limited surface activity, was very sensitive to inhibition by fbg and had moderate effect on the surface properties of fbg-inhibited CLSE. In contrast, PLM-Crec and CLSE revealed similar excellent adsorption kinetics and dynamic surface tension lowering properties. Higher percentage of SP-C within the synthetic mixture (up to 10%) or additional admixture of human purified or recombinant SP-A (up to 10%) did not further improve these surface properties. However, PLM-Crec was markedly more sensitive to inactivation by fbg than CLSE. The surface activity of fbg-inhibited CLSE was fully restored by additional admixture of CLSE or PLM-Crec in both the Wilhelmy and the bubble system, with slight superiority of the natural surfactant extract. We conclude that the surface properties of PLM-Crec are clearly superior to those of the apoprotein-free lipid mixture and are similar to those of the natural surfactant extract CLSE. PLM-Crec is markedly more sensitive to inhibition by fibrinogen than CLSE, but possesses nearly equivalent efficacy in restoring the surface properties of fbg-inhibited CLSE as compared to the natural material.

[Irreversible electroporation: the new generation of local ablation techniques for renal cell carcinoma]. / Irreversible Elektroporation : Die neue Generation lokaler Ablationsverfahren beim Nierenzellkarzinom.

BACKGROUND: Local ablation techniques are a major focus of current developments in oncology. The primary aim is to retain organs and preserve organ functions without compromising the oncological outcome. METHOD: Irreversible electroporation (IRE) is a novel ablation technique that involves the application of high-voltage pulses to induce cell apoptosis without causing thermal damage to the target tissue or adjacent structures. AIM: First published in 2005 IRE is currently undergoing preclinical and clinical trials in several areas of oncology and the initial results have been promising. The IRE technique could be a significant development in ablation treatment for renal cell carcinoma (RCC) but decisive proof of its effectiveness for local RCC has not yet been provided. This study presents the results of preclinical and initial clinical trials which are discussed and compared with those of other ablation techniques in order to demonstrate the current value of IRE.

Proteolytic cleavage of fibrinogen: amplification of its surfactant inhibitory capacity.

Severe deterioration of surfactant function is noted under conditions of plasma protein leakage into the alveolar space; moreover, fibrinogen has previously been reported to possess strong surfactant inhibitory capacity. Dissolution of alveolar deposits of fibrinogen and fibrin (e.g., hyaline membranes) requires enzymatic degradation by the plasminogen/plasmin system or by leukocyte-derived proteases. We investigated the surfactant inhibitory properties of differently prepared sets of fibrinogen cleavage products. Proteolysis was performed with plasmin, with predominant split products D (mol wt 85,000) and E (mol wt 50,000). In addition, fibrinogen was cleaved by leukocyte elastase and trypsin, with fragments ranging mainly between mol wt of 30,000 and 50,000. To provide split products of even lower molecular weight, fibrinogen was incubated sequentially with trypsin and endoproteinase (split products < mol wt 25,000). Natural surfactant extracts used in clinical replacement studies (CLSE, Alveofact, Curosurf, Survanta) as well as an apoprotein-based phospholipid mixture (PLM-C/B; DPPC:PG:PA = 68.5:22.5:9 with 2% [wt/wt] nonpalmitoylated recombinant human SP-C and 1% [wt/wt] natural bovine SP-B) were employed. Experiments were performed in a pulsating bubble surfactometer (standard phospholipid concentration 2 mg/ml) with assessment of surfactant activity measuring adsorption and dynamic surface tension. Fibrinogen caused dose-dependent, severe deterioration of the surface activities of Curosurf and Survanta, whereas CLSE, Alveofact, and PLM-C/B were only moderately affected up to protein-surfactant ratios of 4:1.(ABSTRACT TRUNCATED AT 250 WORDS)

Surfactant inhibition by plasma proteins: differential sensitivity of various surfactant preparations.

Leakage of plasma proteins into the alveolar space may inhibit surfactant function. We compared the surface properties and the sensitivity to inhibitory proteins of different organic solvent surfactant extracts and a synthetic surfactant. Experiments were performed in the pulsating bubble surfactometer, with surfactant concentrations ranging between 0.1 and 2 mg.ml-1. Inhibition profiles towards fibrinogen, albumin and haemoglobin were obtained from calf lung surfactant extracts (CLSE), Alveofact, Curosurf and Survanta (all used in clinical, replacement studies in respiratory distress syndrome (RDS) and of an apoprotein-based synthetic phospholipid mixture (PLM-C/B; DPPC:PG:PA = 68.5:22.5:9, supplemented with 2% wt/wt non-palmitoylated human recombinant SP-C and 1% t/wt natural bovine SP-B). In the absence of inhibitory proteins, all surfactants exhibited dose-dependent rapid adsorption (rank order of relative efficacy PLM-C/B = CLSE > Alveofact > Curosurf > Survanta). Minimal surface tension was reduced to near zero values under dynamic compression (rank order PLM-C/B > CLSE > Alveofact = Curosurf) and to approximately 4 mN.m-1 (Survanta). Curosurf and Survanta were dose-dependently inhibited by fibrinogen > haemoglobin > albumin, with far-reaching loss of surface activity at protein-surfactant ratios above 1:1. In contrast, CLSE and Alveofact were only moderately inhibited by fibrinogen, and were not affected by haemoglobin and albumin, up to protein-surfactant ratios of 2:1. PLM-C/B exhibited resistance to fibrinogen, intermediate sensitivity to albumin, and was severely inhibited by haemoglobin. We conclude that various natural surfactant extracts and an apoprotein-based synthetic surfactant mixture markedly differ in their sensitivity to inhibitory plasma proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

[Man at risk. Preventive strategies and risk management for patient safety]. / Man at Risk. Aktuelle Strategien zum Risikomanagement in der Anästhesie.

Anaesthesia-related risk has been significantly reduced within the last decade. Nevertheless the risk and the possibility of dying or suffering permanent damage still exist. To improve patient safety, risk assessment and analysis must lead to the development of preventive strategies. For this purpose anaesthesia can rely on the concepts of other "high reliability" organisations such as aviation or nuclear power plants. Analyses of critical incidents in the different fields confirm that next to technical problems human factors account for most of the preventable mishaps. Human factors are responsible for individual mistakes as well as for organisational errors. Therefore besides traditional concepts of risk reduction (e.g. guidelines) new strategies (e.g. full-scale simulation) must be applied to minimise the negative impact of human factors on patient safety. Risk management has to consider technical, organisational and human factors to implement a higher standard of patient safety.

N-acetylcysteine induces shedding of selectins from liver and intestine during orthotopic liver transplantation.

In orthotopic liver transplantation (OLT), N-acetylcysteine (NAC) reduces ischaemia/reperfusion (I/R) injury, improves liver synthesis function and prevents primary nonfunction of the graft. To further elucidate the mechanisms of these beneficial effects of NAC, we investigated influence of high-dose NAC therapy on the pattern of adhesion molecule release from liver and intestine during OLT. Nine patients receiving allograft OLT were treated with 150 mg NAC/kg during the first hour after reperfusion; 10 patients received the carrier only. One hour after reperfusion, samples of arterial, portal venous and hepatic venous plasma were taken and blood flow in the hepatic artery and the portal vein was measured. Absolute concentrations of sICAM-1, sVCAM-1, sP-selectin and sE-selectin were not markedly different. However, balance calculations showed release of selectins from NAC-treated livers as opposed to net uptake in controls (P < or = 0.02 for sP-selectin). This shedding of selectins might be a contributing factor to the decrease in leucocyte adherence and improved haemodynamics found experimentally with NAC-treatment.