Correction to: Prognostic assessment for patients with cancer and incidental pulmonary embolism.

[This corrects the article DOI: 10.1186/s12959-017-0157-x.].

Prognostic assessment for patients with cancer and incidental pulmonary embolism.

BACKGROUND: An incidental/unsuspected diagnosis of pulmonary embolism (IPE) in cancer patients is a frequent occurrence. This single-institution analysis of uniformly managed patients investigates short and long-term outcomes and proposes a prognostic risk score, aiming to assist clinical decision-making. METHODS: Data from a prospectively recorded cohort of 234 consecutive cancer patients with IPE were analysed. Multivariate logistic regression and the Cox regression survival methods were used to identify factors with independent association with early (30-day, 3-month, 6-month) mortality and survival. Receiver operator characteristic analysis (ROC) was used to assess appropriate cut-offs for continuous variables and the fitness of prognostic scoring. RESULTS: 30-day, 3-month and 6-month mortality was 3.4% (n = 8), 15% (n = 35) and 31% (n = 72) respectively. Recurrence during anticoagulation occurred in 2.6% (n = 6) and major haemorrhage in 2.1% (n = 5) of the patients. A prognostic score incorporating performance status (0 vs 1-2 vs 3-4) and the presence of new or worsening symptoms, with and without the consideration of the presence of incurable malignancy, correlated with overall survival (p < .001 respectively) as well as early mortality (AUC = .821, p = .004 and AUC = .805, p = 0.006, respectively). CONCLUSION: A simple prognostic score incorporating basic oncologic clinical assessment and self-reported symptomatology could reliably stratify the mortality risk of ambulant cancer patients and IPE. TRIAL REGISTRATION: Audit registration No. 2013.287, Hull and East Yorkshire Hospitals Trust, 29/11/2013.

The risk of venous thromboembolism associated with peripherally inserted central catheters in ambulant cancer patients.

BACKGROUND: Deep vein thrombosis (DVT) is a common complication of peripherally inserted central catheters (PICCs). PICCs are increasingly utilised in the management of cancer patients, a group which carries both additional risks for vascular thromboembolism as well as for complex morbidity. We analysed a cohort of cancer patients subjected to PICC insertion in a single cancer centre for the incidence of all-type vascular thromboembolism (VTE) and investigated relative risk factors. METHODS: In this clinical audit, the records of patients referred for PICC insertion in our centre in the period between 1/1/2011 and 1/4/2014 were retrospectively reviewed. The primary outcomes investigated were a) PICC-related deep vein thrombosis (PRDVT) and b) distant VTE (lower limb DVT and pulmonary embolism). 4Fr single lumen PICCs were placed in all patients. The Kaplan Meier method was used to study time from PICC insertion to PRDVT/VTE. Survival curves were compared using the log rank method. Logistic and Cox regression analyses were used to assess local, distant and combined endpoints. RESULTS: Four hundred ninety patients were included in the analysis of which 27 (5.5%) developed a PRDVT. Statistically significant risk factors for developing PRDVT in multivariate analysis included more than one attempt for insertion (OR 2.61, 95%CI: 1.12-6.05) and the use of fluoropyrimidine containing chemotherapy (OR 4.27, 95%CI 1.3-14.07). Twenty-six patients developed a distant VTE. Male gender was the only significant risk factor for distant VTE. When all-type VTE were considered together fluoropyrimidine containing chemotherapy (OR 4.54, 95% CI 1.63-12.61), male gender (OR 2.03, 95% CI 1.04-3.93) and white cell count (OR 1.12, 95% CI 1.00-1.26) were statistically significant as risk factors in this analysis. CONCLUSIONS: This is a large study of VTE following PICC insertion in cancer patients which also looks at the rate of distant VTE. The observed PRDVT incidence is comparable with available literature. Fluoropyrimidine containing chemotherapy and more than one attempt for PICC insertion were independent predictors of PICC-associated VTE whilst the former remained an independent predictor of all-type VTE. Anticoagulation did not prevent thrombotic events in this cohort.

Developing a complex intervention for the outpatient management of incidentally diagnosed pulmonary embolism in cancer patients.

BACKGROUND: Most patients with pulmonary embolism (PE) spend 5-7 days in hospital even though only 4.5% will develop serious complications during this time. In particular, the group of patients with incidentally diagnosed PE (i-PE) includes many patients with low risk features potentially ideal for outpatient management; however the evidence for their optimal management is lacking hence relative practices may vary considerably. We describe the development process, components, links and function of a nurse-led service for the management of patients with i-PE, developed in accordance to the UK Medical Research Council complex intervention guidance. METHODS: Phase 0 (Theoretical underpinning): The Pulmonary Embolism Severity Index (PESI) was selected for patient risk assessment and the American Society of Clinical Oncology (ASCO) guideline for the management of PE in cancer patients (2007) was selected as quality measure. Historical registry and audit data from our centre regarding i-PE incidence and management for the period between 2006 and 2009 illustrating the then current practices were reviewed. Phase 1 (Modelling): Modelling of the pathway included the following: a) Identification of training needs, planning and implementation of training schemes and development of transferable competencies and training materials. b) Mapping patient pathways and flow and c) Production of key documentation and Standard Operating Procedures for the delivery of the service. RESULTS: Phase 2 (Implementation and testing of the intervention): During the initial 12 months of implementation, remedial action was taken to address identified deficiencies regarding patient referral to the pathway, compliance with treatment protocol, patient follow up, selection challenges from the use of PESI in cancer patients and challenges regarding the "first-pass" identification of i-PE. CONCLUSION: We have developed and piloted a complex intervention to manage cancer patients with incidental PE in an outpatient setting. Adherence to evidence- based care, improvement of communication between professionals and patients, and improved quality of data is demonstrated.

Adding bupivacaine to high-potassium cardioplegia improves function and reduces cellular damage of rat isolated hearts after prolonged, cold storage.

BACKGROUND: Bupivacaine retards myocardial acidosis during ischemia. The authors measured function of rat isolated hearts after prolonged storage to determine whether bupivacaine improves cardiac protection compared with standard cardioplegia alone. METHODS: After measuring cardiac function on a Langendorff apparatus, hearts were perfused with cardioplegia alone (controls), cardioplegia containing 500 microm bupivacaine, or cardioplegia containing 2 mm lidocaine; were stored at 4 degrees C for 12 h; and were then reperfused. Heart rate and left ventricular developed pressures were measured for 60 min. Maximum positive rate of change in ventricular pressure, oxygen consumption, and lactate dehydrogenase release were also measured. RESULTS: All bupivacaine-treated, four of five lidocaine-treated, and no control hearts beat throughout the 60-min recovery period. Mean values of heart rate, left ventricular developed pressure, maximum positive rate of change in ventricular pressure, rate-pressure product, and efficiency in bupivacaine-treated hearts exceeded those of the control group (P < 0.001 at 60 min for all). Mean values of the lidocaine group were intermediate. Oxygen consumption of the control group exceeded the other groups early in recovery, but not at later times. Lactate dehydrogenase release from the bupivacaine group was less than that from the control group (P < 0.001) but did not differ from baseline. CONCLUSIONS: Adding bupivacaine to a depolarizing cardioplegia solution reduces cell damage and improves cardiac function after prolonged storage. Metabolic inhibition may contribute to this phenomenon, which is not entirely explained by sodium channel blockade.

Peroxisome proliferator-activated receptor gamma thiazolidinedione agonists increase glucose metabolism in astrocytes.

Activation of peroxisome proliferator-activated receptors (PPARs) can regulate brain physiology and provide protection in models of neurological disease; however, neither their exact targets nor mechanisms of action in brain are known. In many cells, PPAR gamma agonists increase glucose uptake and metabolism. Because astrocytes store glucose and provide lactate to neurons on demand, we tested effects of PPAR gamma agonists on astroglial glucose metabolism. Incubation of cortical astrocytes with the PPAR gamma thiazolidinedione (TZD) agonist pioglitazone (Pio) significantly increased glucose consumption in a time- and dose-dependent manner, with maximal increase of 36% observed after 4 h in 30 microm Pio. Pio increased 2-deoxy-glucose uptake because of increased flux through the type 1 glucose transporter. However, at this time point Pio did not increase type 1 glucose transporter expression, nor were its effects blocked by transcriptional or translational inhibitors. Pio also increased astrocyte lactate production as soon as 3 h after incubation. These effects were replicated by other TZDs; however, the order of efficacy (troglitazone > pioglitazone > rosiglitazone) suggests that effects were not mediated via PPAR gamma activation. TZDs increased astrocyte cAMP levels, and their glucose modifying effects were reduced by protein kinase A inhibitors. TZDs inhibited state III respiration in isolated brain mitochondria, whereas in astrocytes they caused mitochondrial membrane hyperpolarization. Pio protected astrocytes against hypoglycemia-induced cell death. Finally, glucose uptake was modified in brain sections prepared from Pio-fed rats. These results demonstrate that TZDs modify astrocyte metabolism and mitochondrial function, which could be beneficial in neurological conditions where glucose availability is reduced.