Development and Optimization of a Machine-Learning Prediction Model for Acute Desquamation After Breast Radiation Therapy in the Multicenter REQUITE Cohort.

Purpose: Some patients with breast cancer treated by surgery and radiation therapy experience clinically significant toxicity, which may adversely affect cosmesis and quality of life. There is a paucity of validated clinical prediction models for radiation toxicity. We used machine learning (ML) algorithms to develop and optimise a clinical prediction model for acute breast desquamation after whole breast external beam radiation therapy in the prospective multicenter REQUITE cohort study. Methods and Materials: Using demographic and treatment-related features (m = 122) from patients (n = 2058) at 26 centers, we trained 8 ML algorithms with 10-fold cross-validation in a 50:50 random-split data set with class stratification to predict acute breast desquamation. Based on performance in the validation data set, the logistic model tree, random forest, and naïve Bayes models were taken forward to cost-sensitive learning optimisation. Results: One hundred and ninety-two patients experienced acute desquamation. Resampling and cost-sensitive learning optimisation facilitated an improvement in classification performance. Based on maximising sensitivity (true positives), the "hero" model was the cost-sensitive random forest algorithm with a false-negative: false-positive misclassification penalty of 90:1 containing m = 114 predictive features. Model sensitivity and specificity were 0.77 and 0.66, respectively, with an area under the curve of 0.77 in the validation cohort. Conclusions: ML algorithms with resampling and cost-sensitive learning generated clinically valid prediction models for acute desquamation using patient demographic and treatment features. Further external validation and inclusion of genomic markers in ML prediction models are worthwhile, to identify patients at increased risk of toxicity who may benefit from supportive intervention or even a change in treatment plan.

Behavior of a Two-Way Lightweight Steel-Concrete Composite Slab Voided with Thin-Walled Core Boxes towards Sustainable Construction.

High-performance engineered structural systems are crucial for sustainable development in the field of construction. In our previous research, a novel steel-concrete composite beam with transverse and longitudinal hidden girders exhibited good flexural behavior and desirable ductility. However, there is a dearth of studies on the flexural response of a steel-concrete composite slab voided with thin-walled core boxes. Therefore, in this study, we investigated the overarching flexural mechanism of the proposed structure when subjected to uniform vertical loads. The experimental detection results illustrated that the deflection value of the composite beam was 95.75% less than the GB/T 50152-2012 recommendation. Numerical results further validated this observation. The recorded data from the strain profile at the mid-span of the frame girder indicated that there was a considerable membrane effect, which delayed the strain growth of rebars, yielding appreciable bearing capacity. Thus, two original approaches to predicting the ultimate load of this novel structure are proposed, considering limit analysis using the upper-bound method and the membrane effect, with the latter closely linked to the experimental results. The findings can promote the extensive application of similar sustainable systems and inspire further advancements in advanced engineering structures.

Proceedings of resources for optimal care of acute care and emergency surgery consensus summit Donegal Ireland.

BACKGROUND: Opportunities to improve emergency surgery outcomes exist through guided better practice and reduced variability. Few attempts have been made to define optimal care in emergency surgery, and few clinically derived key performance indicators (KPIs) have been published. A summit was therefore convened to look at resources for optimal care of emergency surgery. The aim of the Donegal Summit was to set a platform in place to develop guidelines and KPIs in emergency surgery. METHODS: The project had multidisciplinary global involvement in producing consensus statements regarding emergency surgery care in key areas, and to assess feasibility of producing KPIs that could be used to monitor process and outcome of care in the future. RESULTS: Forty-four key opinion leaders in emergency surgery, across 7 disciplines from 17 countries, composed evidence-based position papers on 14 key areas of emergency surgery and 112 KPIs in 20 acute conditions or emergency systems. CONCLUSIONS: The summit was successful in achieving position papers and KPIs in emergency surgery. While position papers were limited by non-graded evidence and non-validated KPIs, the process set a foundation for the future advancement of emergency surgery.

Erratum to: Antimicrobials: a global alliance for optimizing their rational use in intra-abdominal infections (AGORA).

[This corrects the article DOI: 10.1186/s13017-016-0089-y.].

Update on surgical sepsis syndrome.

BACKGROUND: Sepsis is a serious complication in surgical patients, and is associated with prolonged hospital stay and high mortality rates. The definitions of sepsis have been revisited recently. This article reviews how definitions have changed over the years, and provides an update on basic pathobiology and essential aspects of treatment. METHODS: PubMed was searched for reports published in English before October 2016, using the search terms 'surgical sepsis' AND 'surgical ICU'. The reference lists of articles identified in the search were also checked. Other relevant literature was selected based on personal knowledge of developments in the field of sepsis. RESULTS: Sepsis is defined as the presence of infection plus associated organ dysfunction. It occurs as the result of a dysregulated host response to the infection. Prevention of infection is an important means of limiting the development of sepsis. Treatment relies on source control, appropriate antibiotics and organ support. Research continues in an attempt to identify effective immunomodulatory therapies. CONCLUSION: Sepsis is an important and serious complication of surgery, and precautions must be taken to try to prevent infection in surgical patients. If sepsis develops, rapid diagnosis is crucial so that appropriate source control, antimicrobial therapy and organ support can be started early in the course of disease. New techniques enabling a better classification of a patient's particular sepsis profile will enable more personalized therapy.

Preoperative abnormalities in serum sodium concentrations are associated with higher in-hospital mortality in patients undergoing major surgery.

BACKGROUND: Abnormal serum sodium concentrations are common in patients presenting for surgery. It remains unclear whether these abnormalities are independent risk factors for postoperative mortality. METHODS: This is a secondary analysis of the European Surgical Outcome Study (EuSOS) that provided data describing 46 539 patients undergoing inpatient non-cardiac surgery. Patients were included in this study if they had a recorded value of preoperative serum sodium within the 28 days immediately before surgery. Data describing preoperative risk factors and serum sodium concentrations were analysed to investigate the relationship with in-hospital mortality using univariate and multivariate logistic regression techniques. RESULTS: Of 35 816 (77.0%) patients from the EuSOS database, 21 943 (61.3%) had normal values of serum sodium (138-142 mmol litre(-1)) before surgery, 8538 (23.8%) had hyponatraemia (serum sodium ≤137 mmol litre(-1)) and 5335 (14.9%) had hypernatraemia (serum sodium ≥143 mmol litre(-1)). After adjustment for potential confounding factors, moderate to severe hypernatraemia (serum sodium concentration ≥150 mmol litre(-1)) was independently associated with mortality [odds ratio 3.4 (95% confidence interval 2.0-6.0), P<0.0001]. Hyponatraemia was not associated with mortality. CONCLUSIONS: Preoperative abnormalities in serum sodium concentrations are common, and hypernatraemia is associated with increased mortality after surgery. Abnormalities of serum sodium concentration may be an important biomarker of perioperative risk resulting from co-morbid disease.

[Pseudo-hyperkalemia and hyperleukocytosis]. / Pseudo-hyperkaliémie et hyperleucocytose.

A pseudo-hyperkalemia may occur with hyperleukocytosis. It is important to recognize it early to avoid unnecessary or even dangerous treatment inducing hypokalemia. The pseudohyperkalemia is due to cell fragility coupled to mechanical phenomena during blood collecting. We report a case of pseudo-hyperkalemia in a context of acute myeloid leukemia.

Time course of iron metabolism in critically ill patients.

BACKGROUND: Altered iron metabolism plays a central role in the development of anaemia in critically ill patients but the time course of iron status in septic and non-septic critically ill patients has not been well defined. METHODS: Prospective study in a 34-bed medico-surgical ICU. The complete blood count, iron, ferritin, transferrin, and transferrin receptor concentrations, transferrin saturation and C-reactive protein (CRP) concentrations were measured on days 1, 3 and 5 of the ICU stay in 95 consecutive ICU patients (33 with sepsis and 62 without). RESULTS: Despite an identical complete blood count on day 1, septic patients had significantly lower iron concentrations (21 [13-34] vs 50[28-75] microg/dL, p<0.001), transferrin concentrations (169[121-215] vs 214[173-247] mg/dL; p=0.003), and transferrin saturation (11[7-15] vs 19[11-25]%; p= 0.004), and higher ferritin concentrations (432[184-773] vs 204[78-354] ng/mL; p=0.002) than non-septic patients. These alterations were associated with a lower reticulocyte count (42[29-61] vs 58[48-77] x 10(3)/mm3; p=0.028). On day 1, CRP concentrations, which were higher in septic than in non-septic patients (20.0[13.5-27.5] vs 2.3[0.7-5.9] mg/dL; p<0.001), were directly correlated with ferritin concentrations (rho=0.55, p<0.001) and inversely correlated with transferrin concentrations (rho=-0.49, p=0.0001) and transferrin saturation (rho=-0.49, p=0.0001). After 3 days, iron and transferrin concentrations were identical in septic and non-septic patients. Iron metabolism remained altered in both populations until the 5th day. CONCLUSIONS: Iron status is rapidly altered in critically ill patients, especially in septic patients. These alterations persist during the course of the disease and are associated with decreased erythropoiesis.

Positive fluid balance is associated with reduced survival in critically ill patients with cancer.

BACKGROUND: There are no studies that describe the impact of the cumulative fluid balance on the outcomes of cancer patients admitted to intensive care units ICUs. The aim of our study was to evaluate the relationship between fluid balance and clinical outcomes in these patients. METHOD: One hundred twenty-two cancer patients were prospectively evaluated for survival during a 30-day period. Univariate (Chi-square, t-test, Mann-Whitney) and multiple logistic regression analyses were used to identify the admission parameters associated with mortality. RESULTS: The mean cumulative fluid balance was significantly higher in non-survivors than in survivors [1675 ml/24 h (471-2921) vs. 887 ml/24 h (104-557), P = 0.017]. We used the area under the curve and the intersection of the sensibility and specificity curves to define a cumulative fluid balance value of 1100 ml/24 h. This value was used in the univariate model. In the multivariate model, the following variables were significantly associated with mortality in cancer patients: the Acute Physiology and Chronic Health Evaluation II score at admission [Odds ratio (OR) 1.15; 95% confidence interval (CI) (1.05-1.26), P = 0.003], the Lung Injury Score at admission [OR 2.23; 95% CI (1.29-3.87), P = 0.004] and a positive fluid balance higher than 1100 ml/24 h at ICU [OR 5.14; 95% CI (1.45-18.24), P = 0.011]. CONCLUSION: A cumulative positive fluid balance higher than 1100 ml/24 h was independently associated with mortality in patients with cancer. These findings highlight the importance of improving the evaluation of these patients' volemic state and indicate that defined goals should be used to guide fluid therapy.

[Hyperlactataemia : not only useful in circulatory shock]. / L'hyperlactatémie: pas seulement utile en cas de choc circulatoire.

Hyperlactataemia, a marker of poor prognosis in intensive care patients, is most frequently found in cases of acute circulatory failure ; however, it may be due to factors other than cellular hypoxia. The level of blood lactate is determined by the balance between its production and its elimination, which can be influenced by various factors. For example, the influence of medication on blood lactate levels should not be underestimated, whether in anaesthesiology, with the use of propofol, or with certain anti-retrovirals in HIV seropositive patients. And in oncology, blood lactate can derive from anaerobic metabolism, characteristic of tumour cells. The differential diagnosis of hyperlactataemia can, therefore, sometimes be more complex than initially thought.

Dopamine versus norepinephrine: is one better?

Dopamine and norepinephrine are widely used as first line agents to correct hypotension in patients with acute circulatory failure. There has been considerable debate in recent years as to whether one is better than the other. Both drugs can increase blood pressure in shock states, although norepinephrine is more powerful. Dopamine can increase cardiac output more than norepinephrine, and in addition to the increase in global blood flow, has the potential advantage of increasing renal and hepatosplanchnic blood flow. However, dopamine has potentially detrimental effects on the release of pituitary hormones and especially prolactin, although the clinical relevance of these effects is unclear. Observational studies have provided conflicting results regarding the effects of these two drugs on outcomes, and results from a recently completed randomized controlled trial are eagerly waited.

Effects of hydroxyethyl starch administration on renal function in critically ill patients.

BACKGROUND: The influence of hydroxyethyl starch (HES) solutions on renal function is controversial. We investigated the effect of HES administration on renal function in critically ill patients enrolled in a large multicentre observational European study. METHODS: All adult patients admitted to the 198 participating intensive care units (ICUs) during a 15-day period were enrolled. Prospectively collected data included daily fluid administration, urine output, sequential organ failure assessment (SOFA) score, serum creatinine levels, and the need for renal replacement therapy (RRT) during the ICU stay. RESULTS: Of 3147 patients, 1075 (34%) received HES. Patients who received HES were older [mean (SD): 62 (SD 17) vs 60 (18) years, P = 0.022], more likely to be surgical admissions, had a higher incidence of haematological malignancy and heart failure, higher SAPS II [40.0 (17.0) vs 34.7 (16.9), P < 0.001] and SOFA [6.2 (3.7) vs 5.0 (3.9), P < 0.001] scores, and less likely to be receiving RRT (2 vs 4%, P < 0.001) than those who did not receive HES. The renal SOFA score increased significantly over the ICU stay independent of the type of fluid administered. Although more patients who received HES needed RRT than non-HES patients (11 vs 9%, P = 0.006), HES administration was not associated with an increased risk for subsequent RRT in a multivariable analysis [odds ratio (OR): 0.417, 95% confidence interval (CI): 0.05-3.27, P = 0.406]. Sepsis (OR: 2.03, 95% CI: 1.37-3.02, P < 0.001), cardiovascular failure (OR: 6.88, 95% CI: 4.49-10.56, P < 0.001), haematological cancer (OR: 2.83, 95% CI: 1.28-6.25, P = 0.01), and baseline renal SOFA scores > 1 (P < 0.01 for renal SOFA 2, 3, and 4 with renal SOFA = 0 as a reference) were all associated with a higher need for RRT. CONCLUSIONS: In this observational study, haematological cancer, the presence of sepsis, cardiovascular failure, and baseline renal function as assessed by the SOFA score were independent risk factors for the subsequent need for RRT in the ICU. The administration of HES had no influence on renal function or the need for RRT in the ICU.

Preliminary results of prolonged target controlled infusion of sufentanil adjusted to an effort pain score after cardiac surgery.

Repeated boluses of i.v. morphine are often used for analgesia after cardiac surgery, but this procedure frequently provides inadequate pain relief. Target controlled infusion (TCI) of opioid drugs has been proposed as an alternative. The objective of this study was to evaluate the effects of prolonged sufentanil TCI adjusted to an effort pain score on the postoperative course after cardiac surgery. Twenty-six patients scheduled for cardiac surgery were anaesthetised using TCI of propofol and sufentanil, followed by early extubation. In the postoperative period, patients were randomly allocated to receive either boluses of i.v. morphine (Bolus group), adapted to a pain score at rest, or sufentanil TCI with a low target concentration (0.08-0.1 ng/ml), adapted to a pain score during deep inspiration (TCI group). Postoperative pain was assessed using a Verbal Numerical Score (VNS) before and during three stimuli: extubation, lateral positioning and physiotherapy. In 15 patients, inspiratory capacity was evaluated by incentive spirometry (IS) on postoperative day 1. Three patients in each group were withdrawn because of delayed extubation. Clinical characteristics, mean time to extubation and PaCO2 were similar in both groups. Analgesia was adequate at rest in both groups as indicated by low pain scores. Pain intensity increased significantly during the three stimuli (p < 0.01). VNS were lower in the TCI than in the Bolus group (3.8 +/- 0.5 versus 4.8 +/- 0.5, p = 0.03). Nine of 10 patients in the TCI group but only 4 of 10 patients in the bolus group gave a VNS below 5 during the stimuli. IS performance was better preserved in the TCI than in the Bolus group (53 +/- 5% versus 35 +/- 5% of preoperative values, p < 0.05). These observations indicate that after cardiac surgery, postoperative pain management with prolonged TCI of sufentanil adapted to a pain score during deep inspiration can achieve better analgesia during routine bedside procedures and higher pulmonary volumes than on-demand boluses of morphine.

Platelet function in sepsis.

BACKGROUND: Coagulation abnormalities and thrombocytopenia are common in severe sepsis, but sepsis-related alterations in platelet function are ill-defined. OBJECTIVES: The purpose of this study was to elucidate the effect of sepsis on platelet aggregation, adhesiveness, and growth factor release. PATIENTS AND METHODS: Agonist-induced platelet aggregation was measured in platelet-rich plasma separated from blood samples collected from 47 critically ill patients with sepsis of recent onset. Expression of platelet adhesion molecules was measured by flow cytometry and the release of vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) was measured by ELISA in the supernatant of platelet aggregation. RESULTS: Septic patients had consistently decreased platelet aggregation compared with controls, regardless of the platelet count, thrombin generation, or overt disseminated intravascular coagulation (DIC) status. The severity of sepsis correlated to the platelet aggregation defect. Adhesion molecules, receptor expression (CD42a, CD42b, CD36, CD29, PAR-1), and alpha-granule secretion detected by P-selectin expression remained unchanged but the release of growth factors was differentially regulated with increased VEGF and unchanged PDGF after agonist activation even in uncomplicated sepsis. CONCLUSIONS: Sepsis decreases circulating platelets' hemostatic function, maintains adhesion molecule expression and secretion capability, and modulates growth factor production. These results suggest that sepsis alters the hemostatic function of the platelets and increases VEGF release in a thrombin-independent manner.

[Laparoscopy under local anaesthesia and hypnoanaesthesia about 35 cholecystectomies and 15 inguinal hernia repair]. / Coeliochirurgie sous anesthésie locale et hypnosédation, à propos de 35 cholécystectomies et 15 cures de hernies.

OBJECTIVE: To present hypnosedation and the feasibility of this technique performed for laparoscopic procedure. STUDY DESIGN: Retrospective and descriptive study of feasibility. PATIENTS AND METHODS: Hypnosis can significantly reduce intraoperative requirements of intravenous sedation for surgery under local anaesthesia. Modifications of surgical procedure: laparoscopic surgery under local anaesthesia and hypnosis is performed using a subcutaneous lifting of anterior abdominal wall. Insufflation is only use to push out smoke. If patient or surgical uncomfort happens, moral contract with patient includes convert to general anaesthesia. RESULTS: We performed 35 cholecystectomies; 13 needed convert to general anaesthesia, mainly for peritoneal pain induced by CO(2) insufflation; 22 procedures were completed with patients' satisfaction. Upon 15-hernia repairs, only one patient needed convert to general anaesthesia, for dissection difficulty. CONCLUSION: Probably hypnosis can't be extent to intraperitoneal laparoscopic procedures. On the other hand interest of hypnosis performed for extraperitoneal laparoscopic hernia repair must be explore.

Ventilator-associated pneumonia.

Ventilator-associated pneumonia is the most common nosocomial infection. Mortality rates, morbidity, and costs are all increased in the patient with VAP, and every measure should thus be taken to prevent its development. There are several clearly defined risk factors for VAP, and awareness of these can facilitate early diagnosis and hence treatment. In this article, we discuss the risk factors, strategies for prevention, approaches to diagnosis and management plan for the patient with VAP.

Red blood cell rheology in sepsis.

Changes in red blood cell (RBC) function can contribute to alterations in microcirculatory blood flow and cellular dysoxia in sepsis. Decreases in RBC and neutrophil deformability impair the passage of these cells through the microcirculation. While the role of leukocytes has been the focus of many studies in sepsis, the role of erythrocyte rheological alterations in this syndrome has only recently been investigated. RBC rheology can be influenced by many factors, including alterations in intracellular calcium and adenosine triphosphate (ATP) concentrations, the effects of nitric oxide, a decrease in some RBC membrane components such as sialic acid, and an increase in others such as 2,3 diphosphoglycerate. Other factors include interactions with white blood cells and their products (reactive oxygen species), or the effects of temperature variations. Understanding the mechanisms of altered RBC rheology in sepsis, and the effects on blood flow and oxygen transport, may lead to improved patient management and reductions in morbidity and mortality.

Effects of nucleoside transport inhibition on hepatosplanchnic perfusion, oxygen extraction capabilities, and TNF release during acute endotoxic shock.

We explored the effects of the nucleoside transport inhibitor draflazine on regional blood flow, O2 extraction capabilities, and tumor necrosis factor (TNF) release in acute endotoxic shock. Fourteen anesthetized and mechanically ventilated dogs received 2 mg/kg of Escherichia coli endotoxin and were divided into two groups. Seven dogs received 0.1 mg/kg of draflazine 30 min before endotoxin, and 7 dogs served as a control group. Draflazine decreased arterial pressure without influencing cardiac index. Mesenteric and portal blood flow and ileum mucosal perfusion increased, but renal blood flow dramatically decreased. After endotoxemia, the draflazine-treated dogs had a lesser fall in cardiac index, filling pressures, and left ventricular stroke work index, and a lesser increase in pulmonary vascular resistance. After fluid resuscitation, they had a consistently lower renal blood flow and ileum mucosal perfusion, but a higher mixed venous and hepatic oxygen saturation and arterial pH than the control group. When cardiac index was reduced by tamponade to study the O2 extraction capabilities, renal blood flow and ileum mucosal perfusion remained lower in the draflazine group. Draflazine did not influence whole-body O2 extraction capabilities, but it delayed the occurrence of liver O2 supply dependency as indicated by a significantly lower liver DO2crit (27.7 +/- 3.9 vs. 43.3 +/- 10.8 mL/min) and a higher O2ERcrit (62.7 +/- 9.5 vs. 42.5 +/- 7.1%) than controls (both P< 0.05). On the other hand, draflazine increased intestinal DO2crit (42.4 +/- 15.4 vs. 27.7 +/- 6.5 mL/min, P < 0.05) compared to the control group. TNF levels remained higher in the draflazine group than in the control group, particularly 3 and 4 h after endotoxin administration. We conclude that nucleoside transport inhibition with draflazine does not alter global and hepatosplanchnic hemodynamics but may decrease gut mucosal perfusion and renal blood flow. However, this intervention can improve liver O2 extraction capabilities in acute endotoxic shock.

Effects of alpha - and beta -adrenergic stimulation on hepatosplanchnic perfusion and oxygen extraction in endotoxic shock.

OBJECTIVE: To examine the effects of adrenergic stimulation on hepatosplanchnic perfusion, oxygen extraction, and tumor necrosis factor-alpha production during endotoxic shock. DESIGN: In vivo, prospective, randomized, controlled, repeated-measures, experimental study. SETTING: Experimental physiology laboratory in a university teaching hospital. SUBJECTS: Twenty-one anesthetized and mechanically ventilated dogs. INTERVENTIONS: An intrapericardial catheter was positioned. Catheters for blood sampling were inserted into the right femoral artery, hepatic vein, portal vein, and pulmonary artery. Ultrasonic flow probes were placed around the portal vein, the hepatic artery, the mesenteric artery, the left renal artery, and the left femoral artery. Animals received 2 mg/kg of Escherichia coli endotoxin, followed by fluid resuscitation. Seven dogs received intravenous isoproterenol (0.1 microg/kg x min(-1)), seven received phenylephrine (1 microg/kg x min(-1)), and seven served as controls. Thirty minutes later, cardiac tamponade was introduced to study organ perfusion and tissue oxygen extraction capabilities. MAIN RESULTS: The isoproterenol group had a higher cardiac index and stroke index and lower systemic vascular resistance than the other groups. The phenylephrine group had a higher arterial pressure but a lower cardiac index than the isoproterenol group. The isoproterenol group had a higher hepatic artery blood flow than the other groups and a higher portal and mesenteric flow than the control group. Liver and gut mucosal blood flow was greater in the isoproterenol than in the phenylephrine group. The isoproterenol group had a lower global critical oxygen delivery than the other groups (8.8 +/- 1.3 vs. 13.1 +/- 2.0 (control) and 11.8 +/- 3.3 mL/kg x min(-1) (phenylephrine); both p < .05) and a higher liver critical oxygen extraction ratio than the control group. Isoproterenol tended to attenuate, but phenylephrine significantly increased, blood tumor necrosis factor levels. CONCLUSIONS: During endotoxic shock, beta-stimulation can improve hepatosplanchnic perfusion and enhance tissue oxygen extraction capabilities, whereas alpha-stimulation does not. In addition, alpha-adrenergic stimulation can increase tumor necrosis factor levels.