METHODS: A 3D model of the liver tissue was developed. Saline infusion was described using the dual porosity model, while RFA was described using the electrostatic and bioheat transfer equations. Three infusion locations were investigated, namely at the proximal end, the middle and the distal end of the electrode. Investigations were carried out numerically using the finite element method.
RESULTS: Results indicated that greater thermal coagulation was found in the region of tissue occupied by the saline bolus. Infusion at the middle of the electrode led to the largest coagulation volume followed by infusion at the proximal and distal ends. It was also found that the ability to delay roll-off, as commonly associated with saline-infused RFA, was true only for the case when infusion is carried out at the middle. When infused at the proximal and distal ends, the occurrence of roll-off was advanced. This may be due to the rapid and more intense heating experienced by the tissue when infusion is carried out at the electrode ends where Joule heating is dominant.
CONCLUSION: Altering the location of saline infusion can influence the shape of the coagulation zone following saline-infused RFA. The ability to 'shift' the coagulation zone to a desired location opens up great opportunities for the development of more precise saline-infused RFA treatment that targets specific regions within the tissue.
METHODS: In the present study, 2D axisymmetric models were developed to investigate how saline backflow influence saline-infused RFA and whether the aforementioned concerns are warranted. Saline-infused RFA was described using the dual porosity-Joule heating model. The hydrodynamics of backflow was described using Poiseuille law by assuming the flow to be similar to that in a thin annulus. Backflow lengths of 3, 4.5, 6 and 9 cm were considered.
RESULTS: Results showed that there is no concern of thermally ablating the tissue in the backflow region. This is due to the Joule heating being inversely proportional to distance from the electrode to the fourth power. Results also indicated that larger backflow lengths led to larger growth of thermal damage along the backflow region and greater decrease in coagulation volume. Hence, backflow needs to be controlled to ensure an effective treatment of saline-infused RFA.
CONCLUSIONS: There is no risk of ablating tissues around the needle insertion track due to backflow. Instead, the risk of underablation as a result of the loss of saline due to backflow was found to be of greater concern.
METHODS: The aforesaid computational TCA framework for sequential injection was applied and adapted to simulate TCA with simultaneous injection of acid and base at equimolar and equivolume. The developed framework, which describes the flow of acid and base, their neutralisation, the rise in tissue temperature and the formation of thermal damage, was solved numerically using the finite element method. The framework will be used to investigate the effects of injection rate, reagent concentration, volume and type (weak/strong acid-base combination) on temperature rise and thermal coagulation formation.
RESULTS: A higher injection rate resulted in higher temperature rise and larger thermal coagulation. Reagent concentration of 7500 mol/m3 was found to be optimum in producing considerable thermal coagulation without the risk of tissue overheating. Thermal coagulation volume was found to be consistently larger than the total volume of acid and base injected into the tissue, which is beneficial as it reduces the risk of chemical burn injury. Three multivariate second-order polynomials that express the targeted coagulation volume as functions of injection rate and reagent volume, for the weak-weak, weak-strong and strong-strong acid-base combinations were also derived based on the simulated data.
CONCLUSIONS: A guideline for a safe and effective implementation of TCA with simultaneous injection of acid and base was recommended based on the numerical results of the computational model developed. The guideline correlates the coagulation volume with the reagent volume and injection rate, and may be used by clinicians in determining the safe dosage of reagents and optimum injection rate to achieve a desired thermal coagulation volume during TCA.
METHODS: To verify this hypothesis, a computational model was developed to simulate the thermochemical processes involved during TCA with sequential injection. Four major processes that take place during TCA were considered, i.e., the flow of acid and base, their neutralisation, the release of exothermic heat and the formation of thermal damage inside the tissue. Equimolar acid and base at 7.5 M was injected into the tissue intermittently. Six injection intervals, namely 3, 6, 15, 20, 30 and 60 s were investigated.
RESULTS: Shortening of the injection interval led to the enlargement of coagulation volume. If one considers only the coagulation volume as the determining factor, then a 15 s injection interval was found to be optimum. Conversely, if one places priority on safety, then a 3 s injection interval would result in the lowest amount of reagent residue inside the tissue after treatment. With a 3 s injection interval, the coagulation volume was found to be larger than that of simultaneous injection with the same treatment parameters. Not only that, the volume also surpassed that of radiofrequency ablation (RFA); a conventional thermal ablation technique commonly used for liver cancer treatment.
CONCLUSION: The numerical results verified the hypothesis that shortening the injection interval will lead to the formation of larger thermal coagulation zone during TCA with sequential injection. More importantly, a 3 s injection interval was found to be optimum for both efficacy (large coagulation volume) and safety (least amount of reagent residue).
METHODS: Children <16 years old with TBI and Glasgow Coma Scale (GCS) ≤13 in an Asian multi-center PICU TBI cohort from January 2014 to October 2017 were included in this study. We defined unfavorable outcome as PCPC ≥3-moderate disability, severe disability, vegetative state, and death. We performed logistic regression to investigate the association between metabolic changes with unfavorable outcome. We divided hyperglycemia (glucose >11.1 mmol/L) during PICU admission into early-onset (within 24 h), late-onset (beyond 48 h) and persistent (throughout first 72 h).
RESULTS: Among the 305 children analyzed, 136 (44.6%) had unfavorable outcome. Children with unfavorable outcome were more likely to have early hyperglycemia (75/136, 55.1% vs. 33/169, 19.5%; P<0.001), high lactate levels >2.0 mmol/L (74/136, 54.4% vs. 56/169, 32.5%; P<0.001) and initial acidosis (85/136, 62.5% vs. 78/169, 56.1%; P=0.003) compared to those with favorable outcome. After adjusting for gender, GCS ≤8 and presence of polytrauma, early hyperglycemia [adjusted odds ratio (aOR) =3.68, 95% CI: 2.12-6.39, P<0.001] and late hyperglycemia (aOR =13.30, 95% CI: 1.64-107.8, P=0.015] were independently associated with unfavorable outcome. All children with persistent hyperglycemia died.
CONCLUSIONS: We described unfavorable outcome in pediatric TBI especially with persistent hyperglycemia. Future trials should investigate the causal relationship between glycemic trends, early intervention and outcome in this cohort.
DESIGN: A retrospective study of the Pediatric Acute and Critical Care Medicine Asian Network moderate to severe traumatic brain injury dataset collected between 2014 and 2017.
SETTING: Patients were from the participating PICUs of Pediatric Acute and Critical Care Medicine Asian Network.
PATIENTS: We included children less than 16 years old with a Glasgow Coma Scale less than or equal to 13.
INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: We obtained data on patient demographics, injury circumstances, and PICU management. We performed a multivariate logistic regression predicting for mortality and poor functional outcomes. We analyzed 380 children with moderate to severe traumatic brain injury. Most injuries were a result of road traffic injuries (174 [45.8%]) and falls (160 [42.1%]). There were important differences in temperature control, use of antiepileptic drugs, and hyperosmolar agents between the sites. Fifty-six children died (14.7%), and 104 of 324 survivors (32.1%) had poor functional outcomes. Poor functional outcomes were associated with non-high-income sites (adjusted odds ratio, 1.90; 95% CI, 1.11-3.29), Glasgow Coma Scale less than 8 (adjusted odds ratio, 4.24; 95% CI, 2.44-7.63), involvement in a road traffic collision (adjusted odds ratio, 1.83; 95% CI, 1.04-3.26), and presence of child abuse (adjusted odds ratio, 2.75; 95% CI, 1.01-7.46).
CONCLUSIONS: Poor functional outcomes are prevalent after pediatric traumatic brain injury in Asia. There is an urgent need for further research in these high-risk groups.
METHODS: In this open-label, phase 3, multicentre randomised trial, patients aged 21-80 years with cT3 or cT4 gastric cancer undergoing curative resection were enrolled at 22 centres from South Korea, China, Japan, Malaysia, Hong Kong, and Singapore. Patients were randomly assigned to receive surgery and EIPL (EIPL group) or surgery alone (standard surgery group) via a web-based programme in random permuted blocks in varying block sizes of four and six, assuming equal allocation between treatment groups. Randomisation was stratified according to study site and the sequence was generated using a computer program and concealed until the interventions were assigned. After surgery in the EIPL group, peritoneal lavage was done with 1 L of warm (42°C) normal 0·9% saline followed by complete aspiration; this procedure was repeated ten times. The primary endpoint was overall survival. All analyses were done assuming intention to treat. This trial is registered with ClinicalTrials.gov, NCT02140034.
FINDINGS: Between Sept 16, 2012, and Aug 3, 2018, 800 patients were randomly assigned to the EIPL group (n=398) or the standard surgery group (n=402). Two patients in the EIPL group and one in the standard surgery group withdrew from the trial immediately after randomisation and were excluded from the intention-to-treat analysis. At the third interim analysis on Aug 28, 2019, the predictive probability of overall survival being significantly higher in the EIPL group was less than 0·5%; therefore, the trial was terminated on the basis of futility. With a median follow-up of 2·4 years (IQR 1·5-3·0), the two groups were similar in terms of overall survival (hazard ratio 1·09 [95% CI 0·78-1·52; p=0·62). 3-year overall survival was 77·0% (95% CI 71·4-81·6) for the EIPL group and 76·7% (71·0-81·5) for the standard surgery group. 60 adverse events were reported in the EIPL group and 41 were reported in the standard surgery group. The most common adverse events included anastomotic leak (ten [3%] of 346 patients in the EIPL group vs six [2%] of 362 patients in the standard surgery group), bleeding (six [2%] vs six [2%]), intra-abdominal abscess (four [1%] vs five [1%]), superficial wound infection (seven [2%] vs one [<1%]), and abnormal liver function (six [2%] vs one [<1%]). Ten of the reported adverse events (eight in the EIPL group and two in the standard surgery group) resulted in death.
INTERPRETATION: EIPL and surgery did not have a survival benefit compared with surgery alone and is not recommended for patients undergoing curative gastrectomy for gastric cancer.
FUNDING: National Medical Research Council, Singapore.
PATIENTS AND METHODS: Data of 2360 patients from APASL-ACLF Research Consortium (AARC) was analysed. Multivariate logistic regression model (PIRO score) was developed from a derivation cohort (n=1363) which was validated in another prospective multicentric cohort of acute on chronic liver failure patients (n=997).
RESULTS: Factors significant for P component were serum creatinine[(≥2 mg/dL)OR 4.52, 95% CI (3.67-5.30)], bilirubin [(<12 mg/dL,OR 1) vs (12-30 mg/dL,OR 1.45, 95% 1.1-2.63) vs (≥30 mg/dL,OR 2.6, 95% CI 1.3-5.2)], serum potassium [(<3 mmol/LOR-1) vs (3-4.9 mmol/L,OR 2.7, 95% CI 1.05-1.97) vs (≥5 mmol/L,OR 4.34, 95% CI 1.67-11.3)] and blood urea (OR 3.73, 95% CI 2.5-5.5); for I component nephrotoxic medications (OR-9.86, 95% CI 3.2-30.8); for R component,Systemic Inflammatory Response Syndrome,(OR-2.14, 95% CI 1.4-3.3); for O component, Circulatory failure (OR-3.5, 95% CI 2.2-5.5). The PIRO score predicted acute kidney injury with C-index of 0.95 and 0.96 in the derivation and validation cohort. The increasing PIRO score was also associated with mortality (P