Liver transplantation (LT) has a 4-fold higher risk of periprocedural cardiac arrest and ventricular arrhythmias (CA/VAs) compared with other noncardiac surgeries. Prolongation of the corrected QT interval (QTc) is common in patients with liver cirrhosis. Whether it is associated with an increased risk of CA/VAs following LT is unclear. Rates of 30-day CA/VAs post-LT were assessed in consecutive adults undergoing LT between 2010 and 2017. Pretransplant QTc was measured by a cardiologist blinded to clinical outcomes. Among 408 patients included, CA/VAs occurred in 26 patients (6.4%). QTc was significantly longer in CA/VA patients (475 ± 34 vs 450 ± 34 ms, P < .001). Optimal QTc cut-off for prediction of CA/VAs was ≥480 ms. After adjustment, QTc ≥480 ms remained the strongest predictor for the occurrence of CA/VAs (odds ratio [OR] 5.2, 95% confidence interval [CI] 2.2-12.6). A point-based cardiac arrest risk index (CARI) was derived with the bootstrap method for yielding optimism-corrected coefficients (2 points: QTc ≥480, 1 point: Model for End-Stage Liver Disease [MELD] ≥30, 1 point: age ≥65, and 1 point: male). CARI score ≥3 demonstrated moderate discrimination (c-statistic 0.79, optimism-corrected c-statistic 0.77) with appropriate calibration. QTc ≥480 ms was associated with a 5-fold increase in the risk of CA/VAs. The CARI score may identify patients at higher risk of these events. Whether heightened perioperative cardiac surveillance, avoidance of QT prolonging medications, or beta blockers could mitigate the risk of CA/VAs in this population merits further study.

Background: Thoracic surgery often results in severe postoperative pain. Regional analgesia via surgically placed extrapleural local anaesthetic (LA) and continuous infusion (CI) is an effective technique, however usually requires supplemental opioid to achieve satisfactory patient analgesia. We hypothesized that high frequency, low background rate extrapleural programmed intermittent boluses (PIB) of LA by could achieve superior patient analgesia and reduced oral morphine equivalent daily dosage (OMEDD) requirements for up to 3 days after thoracic surgery vs. CI. Methods: We retrospectively analysed data from 84 adult patients receiving extrapleural analgesia after thoracic surgery in a single tertiary teaching hospital. The primary outcome measure was the effect of PIB vs. CI on maximum daily 11-point numerical rating scale (NRS-11) ratings as determined by multivariate linear regression analysis, corrected for OMEDD use, total daily LA dose, surgery type, age, opioid type, and use of ketamine analgesia. Secondary outcome measures were the effect on OMEDD use, the effect of total 'rescue' LA boluses, and univariate analyses of the above outcomes and variables. Results: PIB on day 0, and a higher proportion of LA given as rescue boluses on day 1 were associated with reduced maximum NRS-11 ratings [standardized/ [unstandardized] beta coefficient -0.34/ [-0.92 NRS-11 if PIB] (P = 0.007); and -0.26/ [-0.029 NRS-11 per mg/kg extrapleural ropivacaine] (P = 0.03)], respectively. Only patient age was associated with reduced OMEDD use [day 0: -0.58/ [-4.4 OMEDDs per year of age] (P ≤ 0.005); day 1: -0.49/ [-3.56 OMEDDs per year of age] (P ≤ 0.005); day 2: -0.32/ [-1.9 OMEDDs per year of age] (P = 0.04)]. OMEDD use on day 2, however, was associated with slightly higher maximum NRS-11 ratings [+0.28/ +0.006 NRS-11 per mg OMEDD (P = 0.036)]. On univariate analysis, PIB patients achieved the largest difference in OMEDD use [-98 mg (95% CI -73 to -123 mg)] and NRS-11 ratings [-1.1 (-0.4 to -1.8)] against CI patients on day 3. Conclusions: Use of high frequency, low background rate PIB extrapleural LA after thoracic surgery appears to have a modest beneficial effect on acute pain, but not OMEDD use, over CI when adjusted for patient, surgical and other analgesic factors after thoracic surgery. Further work is required to elucidate the potential magnitude of effect that extrapleural LA given by PIB over CI can achieve.

Ureteroscopy (URS) is a procedure which has been constantly evolving since the development of first generation devices 40 years ago. Progress towards smaller and more sophisticated equipment has been particularly rapid in the last decade. We review the significant steps that have been made toward improving outcomes and limiting morbidity with this procedure which is central to the management of urolithiasis and other upper urinary tract pathology.

PURPOSE: To compare the quality of current Internet information on benign prostatic hyperplasia (BPH) and its surgical and medical managements across four Western languages and a comparative analysis of website sponsors. BPH Internet information quality is particularly relevant in an era of expanding, minimally invasive and surgical therapies. However, no comprehensive analysis exists. METHODS: World Health Organization Health on the Net (HON) principles may be applied to websites using an automated toolbar function. Using a search engine (www.google.com), 9,000 websites were assessed using keywords related to BPH and its medical and surgical treatment in English, French, German, and Spanish. The first 150 websites in each language had HON principles measured whilst a further analysis of site sponsorship was undertaken. RESULTS: Very few BPH websites had greater than ten per cent HON accredited with significant differences (P<0.001) based on terms used for BPH, its medical and surgical management. Tertiles (thirds) of the first 150 websites returned differences in accredited websites (P<0.0001). English language had most accredited websites. Odds ratios for different terms returning accredited websites also were significantly different across terms (P<0.001). Websites were largely commercially sponsored. CONCLUSIONS: A lack of validation of most BPH sites should be appreciated with discrepancies in quality and number of websites across diseases, languages and also between medical and alternate terms. Physicians should participate in and encourage the development of informative, ethical and reliable health websites on the Internet and direct patients to them.

BACKGROUND: Mutations in KIT are more frequent in specific melanoma subtypes, and response to KIT inhibition is likely to depend on the identified mutation. METHODS: A total of 32 patients with metastatic acral or mucosal melanoma were screened for mutations in KIT exons 11, 13 and 17. RESULTS: KIT mutations were found in 38% of mucosal and in 6% of acral melanomas. Three patients were treated with imatinib and one with sorafenib. All four patients responded to treatment, but three have since progressed within the brain. CONCLUSION: The observed clinical responses support further investigation of KIT inhibitors in metastatic melanoma, selected according to KIT mutation status.

Many adult patients require temporary inotropic support after cardiac surgery. We reviewed the literature systematically to establish, present and classify the evidence regarding choice of inotropic drugs. The available evidence, while limited in quality and scope, supports the following observations; although all beta-agonists can increase cardiac output, the best studied beta-agonist and the one with the most favourable side-effect profile appears to be dobutamine. Dobutamine and phosphodiesterase inhibitors (PDIs) are efficacious inotropic drugs for management of the low cardiac output syndrome. Dobutamine is associated with a greater incidence of tachycardia and tachyarrhythmias, whereas PDIs often require the administration of vasoconstrictors. Other catecholamines have no clear advantages over dobutamine. PDIs increase the likelihood of successful weaning from cardiopulmonary bypass as compared with placebo. There is insufficient evidence that inotropic drugs should be selected for their effects on regional perfusion. PDIs also increase flow through arterial grafts, reduce mean pulmonary artery pressure and improve right heart performance in pulmonary hypertension. Insufficient data exist to allow selection of a specific inotropic agent in preference over another in adult cardiac surgery patients. Multicentre randomized controlled trials focusing on clinical rather than physiological outcomes are needed.

OBJECTIVE: To investigate the effects of height, external pressure, and bladder fullness on the flow rate in continuous, non-continuous cystoscopy and the automated irrigation fluid pumping system (AIFPS). MATERIALS: Each experiment had two 2-litre 0.9% saline bags connected to a continuous, non-continuous cystoscope or AIFPS via irrigation tubing. Other equipment included height-adjustable drip poles, uroflowmetry devices, and model bladders. METHODS: In Experiment 1, saline bags were elevated to measure the increment in flow rate. In Experiment 2, saline bags were placed under external pressures to evaluate the effect on flow rate. In Experiment 3, flow rate changes in response to variable bladder fullness were measured. RESULTS: Elevating saline bags caused an increase in flow rates, however the increment slowed down beyond a height of 80 cm. Increase in external pressure on saline bags elevated flow rates, but inconsistently. A fuller bladder led to a decrease in flow rates. In all experiments, the AIFPS posted consistent flow rates. CONCLUSIONS: Traditional irrigation systems were susceptible to changes in height of irrigation solution, external pressure application, and bladder fullness thus creating inconsistent flow rates. The AIFPS produced consistent flow rates and was not affected by any of the factors investigated in the study.

Acute flaccid paralysis (AFP) has a changing epidemiology with ongoing polio outbreaks and emerging causes such as nonpolio enteroviruses and West Nile virus (WNV). We report a case of AFP from the Horn of Africa that was initially classified as probable polio but subsequently found to be due to WNV.

BACKGROUND: There is limited information on the impact on perioperative fluid intervention on complications and length of hospital stay following pancreaticoduodenectomy. Therefore, we conducted a detailed analysis of fluid intervention in patients undergoing pancreaticoduodenectomy at a university teaching hospital to test the hypothesis that a restrictive intravenous fluid regime and/or a neutral or negative cumulative fluid balance, would impact on perioperative complications and length of hospital stay. METHODS: We retrospectively obtained demographic, operative details, detailed fluid prescription, complications and outcomes data for 150 consecutive patients undergoing pancreaticoduodenectomy in a university teaching hospital. Prognostic predictors for length of hospital stay and complications were determined. RESULTS: One hundred and fifty consecutive patients undergoing pancreaticoduodenectomy were evaluated between 2006 and 2012. The majority of patients were, middle-aged, overweight and ASA class III. Postoperative complications were frequent and occurred in 86 patients (57%). The majority of complications were graded as Clavien-Dindo Class 2 and 3. Postoperative pancreatic fistula occurred in 13 patients (9%), and delayed gastric emptying occurred in 25 patients (17%). Other postoperative surgical complications included sepsis (22%), bile leak (4%), and postoperative bleeding (2%). Serious medical complications included pulmonary edema (6%), myocardial infarction (8%), cardiac arrhythmias (13%), respiratory failure (8%), and renal failure (7%). Patients with complications received a higher median volume of intravenous therapy and had higher cumulative positive fluid balances. Postoperative length of stay was significantly longer in patients with complications (median 25 days vs. 10 days; p < 0.001). After adjustment for covariates, a fluid balance of less than 1 litre on postoperative day 1 and surgeon caseloads were associated with the development of complications. CONCLUSIONS: In the context of pancreaticoduodenectomy, restrictive perioperative fluid intervention and negative cumulative fluid balance were associated with fewer complications and shorter length of hospital stay. These findings provide good opportunities to evaluate strategies aimed at improving perioperative care.

INTRODUCTION: Immune checkpoint inhibition has shifted treatment paradigms in non-small cell lung cancer (NSCLC). Conflicting results have been reported regarding the immune infiltrate and programmed death-ligand 1 (PD-L1) as a prognostic marker. We correlated the immune infiltrate and PD-L1 expression with clinicopathologic characteristics in a cohort of resected NSCLC. METHODS: A tissue microarray was constructed using triplicate cores from consecutive resected NSCLC. Immunohistochemistry was performed for CD8, FOXP3 and PD-L1. Strong PD-L1 expression was predefined as greater than 50% tumor cell positivity. Matched nodal samples were assessed for concordance of PD-L1 expression. RESULTS: Of 522 patients, 346 were node-negative (N0), 72 N1 and 109 N2; 265 were adenocarcinomas (AC), 182 squamous cell cancers (SCC) and 75 other. Strong PD-L1 expression was found in 24% cases. In the overall cohort, PD-L1 expression was not associated with survival. In patients with N2 disease, strong PD-L1 expression was associated with significantly improved disease-free (DFS) and overall survival (OS) in multivariate analysis (HR 0.49, 95%CI 0.36-0.94, p = 0.031; HR 0.46, 95%CI 0.26-0.80, p = 0.006). In this resected cohort only 5% harboured EGFR mutations, whereas 19% harboured KRAS and 23% other. KRAS mutated tumors were more likely to highly express PD-L1 compared to EGFR (22% vs 3%). A stromal CD8 infiltrate was associated with significantly improved DFS in SCC (HR 0.70, 95%CI 0.50-0.97, p = 0.034), but not AC, whereas FOXP3 was not prognostic. Matched nodal specimens (N = 53) were highly concordant for PD-L1 expression (89%). CONCLUSION: PD-L1 expression was not prognostic in the overall cohort. PD-L1 expression in primary tumor and matched nodal specimens were highly concordant. The observed survival benefit in N2 disease requires confirmation.

INTRODUCTION: Limited evidence exists on effective interventions to improve knowledge of preventive medications in patients with chronic diseases, such as stroke. We investigated the effectiveness of a nurse-led intervention, where a component was to improve knowledge of prevention medications, in patients with stroke or transient ischemic attack (TIA). METHODS: Prospective sub-study of the Shared Team Approach between Nurses and Doctors for Improved Risk Factor Management, a randomized controlled trial of risk factor management. We recruited patients aged ≥18 years and hospitalized for stroke/TIA. The intervention comprised an individualized management program, involving nurse-led education, and management plan with medical specialist oversight. The outcome, participants' knowledge of secondary prevention medications at 12 months, was assessed using questionnaires. A score of ≥5 was considered as good knowledge. Effectiveness of the intervention on knowledge of medications was determined using logistic regression. RESULTS: Between May 2014 and January 2015, 142 consecutive participants from the main trial were included in this sub-study, 64 to usual care and 78 to the intervention (median age 68.9 years, 68% males, and 79% ischemic stroke). In multivariable analyses, we found no significant difference between intervention groups in knowledge of medications. Factors independently associated with good knowledge (score ≥5) at 12 months included higher socioeconomic position (OR 4.79, 95% CI 1.76, 13.07), greater functional ability (OR 1.69, 95% CI 1.17, 2.45), being married/living with a partner (OR 3.12, 95% CI 1.10, 8.87), and using instructions on pill bottle/package as an administration aid (OR 4.82, 95% CI 1.76, 13.22). Being aged ≥65 years was associated with poorer knowledge of medications (OR 0.24, 95% CI 0.08, 0.71), while knowledge was worse among those taking three medications (OR 0.15, 95% CI 0.03, 0.66) or ≥4 medications (OR 0.09, 95% CI 0.02, 0.44), when compared to participants taking fewer (≤2) prevention medications. CONCLUSION: There was no evidence that the nurse-led intervention was effective for improving knowledge of secondary prevention medications in patients with stroke/TIA at 12 months. However, older patients and those taking more medications should be particularly targeted for more intensive education. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ACTRN12688000166370).

Background. The most significant risk following major hepatectomy is postoperative liver insufficiency. Current preoperative assessment of the future liver remnant relies upon assumptions which may not be valid in the setting of advanced resection strategies. This paper reports the feasibility of the ALIIVE technique which assesses the liver remnant with ICG clearance intraoperatively during vascular exclusion. Methods. 10 patients undergoing planned major liver resection (hemihepatectomy or greater) were recruited. Routine preoperative assessment included CT and standardized volumetry. ICG clearance was measured noninvasively using a finger spectrophotometer at various time points including following parenchymal transection during inflow and outflow occlusion before vascular division, the ALIIVE step. Results. There were one case of mortality and three cases of posthepatectomy liver failure. The patient who died had the lowest ALIIVE ICG clearance (7.1%/min versus 14.4 ± 4.9). Routine preoperative CT and standardized volumetry did not predict outcome. Discussion/Conclusion. The novel ALIIVE technique is feasible and assesses actual future liver remnant function before the point of no return during major hepatectomy. This technique may be useful as a check step to offer a margin of safety to prevent posthepatectomy liver failure and death. Further confirmatory studies are required to determine a safety cutoff level.