Characteristics and predictors of venous thrombosis recurrence in patients with cancer and catheter-related thrombosis.

Background: Central venous catheters raise the risk of catheter-related thrombosis (CRT) in patients with cancer, typically affecting the upper extremity. Management of CRT involves catheter removal and anticoagulation. However, robust evidence is lacking on the optimal timing of anticoagulation relative to catheter removal. Objectives: Our goal is to provide a better understanding of the factors that increase the risk of recurrent venous thromboembolism (VTE) in these patients. Patients and Methods: We conducted a retrospective chart review of all consecutive patients with cancer in our hospital affected by CRT between January 1, 2015, and December 31, 2017. We measured recurrence of VTE as thrombosis in any vascular bed or pulmonary embolism, for up to 2 years after diagnosis. Logistic and competing risk regression analyses were used to determine the association between different clinical factors and any VTE recurrence in patients with cancer and CRT. Results: Of the 257 individuals meeting the inclusion criteria, 80.2% had their catheter removed; of these, 50.5% did not receive anticoagulation before the removal. Patients who did not receive anticoagulation before the removal had increased 3-month and 1-year risks of recurrent VTE (odds ratio, 5.07 [95% confidence interval [CI], 1.53-23.18]; and hazard ratio, 3.47 [95% CI, 1.34-9.01]), respectively. Conclusions: Our study supports the use of anticoagulants before catheter removal in patients with CRT. Randomized clinical trials are recommended to establish stronger evidence pertaining to the long-term risk of VTE recurrence and the effect of catheter reinsertion.

Clinical characteristics, management, and outcome of incidental pulmonary embolism in cancer patients.

Incidental pulmonary embolisms (IPEs) are common in cancer patients. Examining the characteristics and outcomes of IPEs in cancer patients can help to ensure proper management, promoting better outcomes. To determine the clinical characteristics, management, and outcomes of IPEs for cancer patients, we conducted a 1:2 ratio case-control study and identified all consecutive patients with IPE who visited the emergency department at The University of Texas MD Anderson Cancer Center between 1 January 2006 and 1 January 2016. Each IPE case was matched with 2 controls using a propensity score obtained using logistic regression for IPE status with other factors affecting overall survival. A total of 904 confirmed cases were included in the analysis. IPE frequently occurred during the first year after cancer diagnosis (odds ratio [OR], 2.79; 95% confidence interval [95% CI], 2.37-3.29; P < .001). Patients receiving cytotoxic chemotherapy had a nearly threefold greater risk of developing IPE (OR, 2.87; 95% CI, 2.42-3.40; P < .001). In-hospital mortality was 1.9%. The 7- and 30-day mortality rates among the cases were 1.8% and 9.9%, respectively, which was significantly higher than in the control groups: 0.2% and 3.1%, respectively (P < .001). IPE was associated with reduced overall survival (hazard ratio [HR], 1.93; 95% CI, 1.74-2.14; P < .001). Concurrent incidental venous thromboembolism was identified in 189 of the patients (20.9%) and was also associated with reduced overall survival (HR, 1.65; 95% CI, 1.21-2.25; P = .001). Our results show that IPE events are associated with poor outcomes in cancer patients. Proper management plans similar to those of symptomatic pulmonary embolisms are essential.

Evaluation of Cancer Patients With Suspected Pulmonary Embolism: Performance of the American College of Physicians Guideline.

BACKGROUND: Accurate risk stratification of pulmonary embolism (PE) can reduce unnecessary imaging. We investigated the extent to which the American College of Physicians (ACP) guideline for evaluation of patients with suspected PE could be applied to cancer patients in the emergency department of a comprehensive cancer center. MATERIALS AND METHODS: Data from cancer patients who underwent CT pulmonary angiography (CTPA) between August 1, 2015, and October 31, 2015, were collected. We assessed each patient's diagnostic workup for its adherence to the ACP guideline in terms of clinical risk stratification and age-adjusted d-dimer level and the degree to which these factors were associated with PE. RESULTS: Of the 380 patients identified, 213 (56%) underwent CTPA indicated per the ACP guideline, and 78 (21%) underwent CTPA not indicated per the guideline. Only one of the patients who underwent nonindicated CTPA had a PE. Fifty-seven patients underwent unnecessary d-dimer evaluation, and 71 patients with negative d-dimer test results underwent nonindicated CTPA. PEs were found in 6 of 108 (6%) low-risk patients, 22 of 219 (10%) intermediate-risk patients, and 13 of 53 (25%) high-risk patients. The ACP guideline had negative predictive value of 99% (95% confidence interval: 93%-100%) and sensitivity of 97% (95% confidence interval: 86%-100%) in predicting PE. CONCLUSION: The ACP guideline has good sensitivity for detecting PE in cancer patients and thus can be applied in this population. Compliance with the ACP guideline when evaluating cancer patients with suspected PE could reduce the use of unnecessary imaging and laboratory studies.

Ambulatory emergency oncology: A key tenet of future emergency oncology care.

Ambulatory emergency oncology The challenges of emergency oncology alongside its increasing financial burden have led to an interest in developing optimal care models for meeting patients' needs. Ambulatory care is recognised as a key tenet in ensuring the safety and sustainability of acute care services. Increased access to ambulatory care has successfully reduced ED utilisation and improved clinical outcomes in high-risk non-oncological populations. Individualised management of acute cancer presentations is a key challenge for emergency oncology services so that it can mirror routine cancer care. There are an increasing number of acute cancer presentations, such as low-risk febrile neutropenia and incidental pulmonary embolism, that can be risk assessed for care in an emergency ambulatory setting. Modelling of ambulatory emergency oncology services will be dependent on local service deliveries and pathways, but are key for providing high quality, personalised and sustainable emergency oncology care. These services will also be at the forefront of much needed emergency oncology to define the optimal management of ambulatory-sensitive presentations.

Validation of the EPIPHANY index for predicting risk of serious complications in cancer patients with incidental pulmonary embolism.

PURPOSE: The EPIPHANY index was developed to classify cancer associated pulmonary embolism (PE) into different risk categories using decision tree modeling. In this study, we tried to externally validate this index in a distinct group of patients solely composed of incidental PE (IPE). METHODS: A retrospective study of patients diagnosed with IPE in two Emergency Departments in the USA and South Korea from 2013 to 2014 was performed. The primary outcome was the occurrence of a serious medical complication within 15 days of presentation to ED. Thirty-day complication was the secondary outcome. Cumulative hazard curves for each prognostic category were drawn to show the change in hazards over time. RESULTS: A total of 258 patients with IPE were included (193 from MD Anderson Cancer Center and 65 from Asan Medical Center). Serious complication within 15 days occurred in 23 (8.9%) patients. The risk of overall 15-day and 30-day serious complications increased with each category (low, intermediate, and high risk: 3.4, 8.9, and 23.8%, P = 0.033; 6.9, 9.5, and 33.3%, P = 0.011). Cumulative hazard curves for each prognostic category were drawn and the survival functions factored by prognostic categories were significantly different over 15 days (P = 0.015) and 30 days (P = 0.001). CONCLUSIONS: Our study suggests the EPIPHANY index could be a useful adjunct tool in risk stratification of cancer patients with IPE.

Handoff Tool Enabling Standardized Transitions Between the Emergency Department and the Hospitalist Inpatient Service at a Major Cancer Center.

Communication failures during patient handoff can lead to serious errors. A quality improvement team created a standardized handoff tool/process (DE-PASS: Decisive problem requiring admission, Evaluation time, Patient summary, Acute issues/action list, Situation unfinished/awareness, Signed out to) for admitting patients from the emergency department (ED) to the hospitalist inpatient service of a tertiary cancer center. DE-PASS mirrors the institution's ED workflow, stratifies patients as stable/urgent/emergent, and establishes requirements for verbal and email communications between providers. Comparison of preintervention and postintervention results from the 1-month pilot revealed that within a 24-hour period, DE-PASS reduced the number of intensive care unit transfers by 58% ( P = .393), the number of rapid-response team calls by 39% ( P = .637), and time to inpatient order by 31% ( P = .004). ED physicians' and hospitalists' satisfaction with DE-PASS increased. Reduction in intensive care unit transfers was sustained after the pilot ( P = .029). DE-PASS feasibility was evidenced by 100% uptake. By stratifying patients by risk level, DE-PASS reduced admission-to-evaluation times for unstable patients, potentially improving patient safety.

Comparison of the MASCC and CISNE scores for identifying low-risk neutropenic fever patients: analysis of data from three emergency departments of cancer centers in three continents.

PURPOSE: Patients with febrile neutropenia are a heterogeneous group with a minority developing serious medical complications. Outpatient management of low-risk febrile neutropenia has been shown to be safe and cost-effective. Scoring systems, such as the Multinational Association for Supportive Care in Cancer (MASCC) score and Clinical Index of Stable Febrile Neutropenia (CISNE), have been developed and validated to identify low-risk patients. We aimed to compare the performance of these two scores in identifying low-risk febrile neutropenic patients. METHODS: We performed a pooled analysis of patients presenting with febrile neutropenia to three tertiary cancer emergency centers in the USA, UK, and South Korea in 2015. The primary outcome measures were the occurrence of serious complications. Admission to an intensive care unit (ICU) and 30-day mortality were secondary outcomes. The predictive performance of each score was analyzed. RESULTS: Five hundred seventy-one patients presented with febrile neutropenia. With MASCC risk index, 508 (89.1%) were classified as low-risk febrile neutropenia, compared to 60 (10.5%) with CISNE classification. Overall, the MASCC score had a greater discriminatory power in the detection of low-risk patients than the CISNE score (AUC 0.772, 95% CI 0.726-0.819 vs. 0.681, 95% CI 0.626-0.737, p = 0.0024). CONCLUSION: Both MASCC and CISNE scores have reasonable discriminatory value in predicting patients with low-risk febrile neutropenia. Risk scores should be used in conjunction with clinical judgment for the identification of patients suitable for outpatient management of neutropenic fever. Developing more accurate scores, validated in prospective settings, will be useful in facilitating more patients being managed in an outpatient setting.

Acute Oncology Care: A narrative review of the acute management of neutropenic sepsis and immune-related toxicities of checkpoint inhibitors.

Cancer care has become increasingly specialized and advances in therapy have resulted in a larger number of patients receiving care. There has been a significant increase in the number of patients presenting with cancer related emergencies including treatment toxicities and those directly related to the malignancy. Suspected neutropenic sepsis is an acute medical emergency and empirical antibiotic therapy should be administered immediately. The goal of empirical therapy is to cover the most likely pathogens that will cause life-threatening infections in neutropenic patients. Patients with febrile neutropenia are a heterogeneous group with only a minority of treated patients developing significant medical complications. Outpatient management of low risk febrile neutropenia patients identified by the MASCC score is a safe and effective strategy. Immunotherapy with "checkpoint inhibitors" has significantly improved outcomes for patients with metastatic melanoma and evidence of benefit in a wide range of malignancies is developing. Despite these clinical benefits a number of immune related adverse events have been recognised which can affect virtually all organ systems and are potentially fatal. The timing of the onset of the adverse events is dependent on the organ system affected and unlike anti-neoplastic therapy can be delayed significantly after initiation or completion of therapy. The field of Acute Oncology is changing rapidly. Alongside, the traditional challenge of neutropenic sepsis there are many emerging toxicities. Further research into the optimal management, strategies and pathways of acutely unwell patients with cancer is required.

Discharge or admit? Emergency department management of incidental pulmonary embolism in patients with cancer: a retrospective study.

BACKGROUND: Hospitalization and early anticoagulation therapy remain standard care for patients who present to the emergency department (ED) with pulmonary embolism (PE). For PEs discovered incidentally, however, optimal therapeutic strategies are less clear-and all the more so when the patient has cancer, which is associated with a hypercoagulable state that exacerbates the threat of PE. METHODS: We conducted a retrospective review of a historical cohort of patients with cancer and incidental PE who were referred for assessment to the ED in an institution whose standard of care is outpatient treatment of selected patients and use of low-molecular-weight heparin for anticoagulation. Eligible patients had received a diagnosis of incidental PE upon routine contrast enhanced chest CT for cancer staging. Survival data was collected at 30 days and 90 days from the date of ED presentation and at the end of the study. RESULTS: We identified 193 patients, 135 (70%) of whom were discharged and 58 (30%) of whom were admitted to the hospital. The 30-day survival rate was 92% overall, 99% for the discharged patients and 76% for admitted patients. Almost all (189 patients, 98%) commenced anticoagulation therapy in the ED; 170 (90%) of these received low-molecular-weight heparin. Patients with saddle pulmonary artery incidental PEs were more likely to die within 30 days (43%) than were those with main or lobar (11%), segmental (6%), or subsegmental (5%) incidental PEs. In multivariate analysis, Charlson comorbidity index (age unadjusted), hypoxemia, and incidental PE location (P = 0.004, relative risk 33.5 (95% CI 3.1-357.4, comparing saddle versus subsegmental PE) were significantly associated with 30-day survival. Age, comorbidity, race, cancer stage, tachycardia, hypoxemia, and incidental PE location were significantly associated with hospital admission. CONCLUSIONS: Selected cancer patients presenting to the ED with incidental PE can be treated with low-molecular-weight heparin anticoagulation and safely discharged. Avoidance of unnecessary hospitalization may decrease in-hospital infections and death, reduce healthcare costs, and improve patient quality of life. Because the natural history and optimal management of this condition is not well described, information supporting the creation of straightforward evidence-based practice guidelines for ED teams treating this specialized patient population is needed.

Problem-based review: Immune-mediated complications of 'Checkpoint Inhibitors' for the Acute Physician.

Immunotherapy with 'checkpoint-inhibitors' has significantly improved outcomes for patients with a range of malignancies. However, significant immune-mediated toxicities of these therapies are well-described. These immune-mediated toxicities can affect virtually all organ systems and are potentially fatal. The timing of onset of the adverse effects is dependent on the organ system affected and can occur after completion of the treatment. The increasing utilisation of 'checkpoint-inhibitors' means that Acute Physicians are likely to see a number of immune-mediated complications presenting to the AMU. The fundamental principles of management of immune-mediated toxicities are early recognition, supportive treatment, escalating steroid therapy (dependent on the severity of the toxicity), close liaison with Oncology and specialist organ team input. Research into the optimal strategies and pathways for the management of immune-mediated toxicity, as well as increased collaboration between Acute Physicians and Oncologists, will be necessary.

Low tissue oxygen saturation at emergency center triage is predictive of intensive care unit admission.

PURPOSE: Timely recognition of critical patients by emergency center triage is an ongoing challenge. Peripheral tissue oxygen saturation (StO2) measurement has been used to monitor shock patients' responses to resuscitation. Interest has developed in evaluating StO2 as a triage tool, but limited studies have addressed critically ill patients. MATERIAL AND METHODS: This is a single-center, retrospective study of 158 emergent cancer patients with hypotension and/or modified systemic inflammatory response syndrome who underwent StO2 spot measurement at triage. RESULTS: Of the 57 patients with StO2 less than 70%, 17 went to the intensive care unit (ICU), whereas only 14 of the 101 patients with StO2 of 70% to 89% (P = .01) went to the ICU. There was no significant difference in non-ICU hospital admission or mortality between the 2 groups. The odds ratio of ICU admission for patients with StO2 less than 70% relative to those with StO2 of 70% to 89% was 2.64 (95% confidence interval, 1.18-5.87) and 2.87 (95% confidence interval, 1.23-6.66) when adjusted for mean arterial pressure, pulse, and temperature. CONCLUSIONS: In this patient population, an StO2 less than 70% significantly increased the risk of ICU admission. Tissue oxygen saturation at triage identifies critical patients who may not be recognized by vital signs alone. Tissue oxygen saturation measurement could help providers make earlier decisions regarding hospital resource allocation.

Implementation of modified early-goal directed therapy for sepsis in the emergency center of a comprehensive cancer center.

PURPOSE: The investigation examines the impact of a standardized sepsis order set and algorithm utilizing non-invasive monitoring for early-goal directed therapy (EGDT) in an emergency center setting on the clinical outcomes of sepsis in cancer patients. METHODS: Single-center, retrospective study comparing clinical outcomes of sepsis before and after routine usage of a standardized order set and algorithm for non-invasive elements of EGDT for sepsis in an emergency center of a comprehensive cancer center. The outcomes measures evaluated were 28-day in-hospital mortality, intensive care unit length of stay, hospital length of stay, goal mean arterial pressure and urine output within the first 6 h of treatment, time to measurement of lactic acid, and appropriateness and timeliness of initial antibiotic therapy. RESULTS: The 28-day in-hospital mortality was significantly lower in the post-intervention group compared to the pre-intervention group (20 vs. 38%, p = 0.005). The percentages of patients who reached their goal mean arterial pressure (74 vs. 90%, p = 0.004) and goal urine output (79 vs. 96%, p = 0.002) during the first 6 h of treatment were higher the after than the before group. No significant differences were detected in the rest of the outcome measures. CONCLUSIONS: Implementation of a standardized sepsis order set and algorithm to improve compliance with the non-invasive elements of EGDT for sepsis in cancer patients in the emergency center setting was associated with a decreased 28-day in-hospital mortality rate.

Peripheral arterial occlusive disease: magnetic resonance imaging and the role of aggressive medical management.

Atherosclerosis accounts for most peripheral arterial occlusive disease (PAD). Although many of the risk factors for atherosclerotic coronary artery disease (CAD) such as hyperlipidemia have been identified as risk factors for peripheral arterial disease, strong evidence is lacking that risk factor modification is effective in halting progression or improving outcomes. A better understanding is needed regarding the clinical and pathophysiologic responses to risk factor modification. This review describes current advances in the medical management for PAD including lipid modification antiplatelet therapy, angiotensin-converting enzyme (ACE) inhibitors, beta-blockers, exercise, and endovascular intervention. In addition, we discuss our active ELIMIT Trial (Effect of Lipid Modification on Peripheral Arterial Disease after Endovascular Intervention). We test the hypothesis that an aggressive regimen of serum lipid modification will inhibit the progression of atherosclerosis in femoral arteries and reduce the incidence of restenosis of femoral arteries following endovascular stenting by decreasing thrombosis and inflammation. This study will provide a novel strategy for retarding or preventing progression of atherosclerosis and re-stenosis of peripheral arterial disease following arterial revascularization procedures. Importantly, our magnetic resonance imaging studies will provide quantitative data on the vascular lesions in PAD. These studies will advance our understanding of the molecular mechanisms of inflammation and thrombosis associated with aggressive lipid modification.

Optimal medical management of peripheral arterial disease.

Patients with peripheral vascular disease are less likely to receive optimal medical management than patients with coronary artery disease. However, early medical treatment is critical because it is profoundly beneficial and the benefits are maximized. Even in patients with advanced disease requiring invasive intervention, medical management has been proven to improve outcome, prolong the success of the intervention, improve functional capacity, and prolong life. The vascular surgeon should be knowledgeable enough to initiate basic medical therapy and to define for their patients the goals that need to be met to optimize their medical management. The vascular surgeon should be instrumental in assuring that the peripheral vascular patient receives medical therapy of the same standard as the patient with coronary disease. The major modifiable risk factors in the vascular patient are: smoking, high blood pressure, hyperlipidemia, physical inactivity, obesity, and diabetes. In addition, the use of beta blockers for patients with coronary disease and antiplatelet therapy as well as angiotensin-converting enzyme (ACE) inhibitors are recommended for all patients with peripheral vascular disease. Statins have favorable effects on multiple interrelated aspects of vascular biology important in atherosclerosis. In particular they have beneficial effects on inflammation, plaque stabilization, endothelial dysfunction, and thrombosis. Statins have also been shown to be beneficial in acute vascular events. Angiotensin-converting enzyme inhibitors have been shown to reduce cardiovascular morbidity and mortality in patients with peripheral arterial disease regardless of the presence or absence of hypertension. A number of the pleiotropic effects of statins are shared by ACE inhibitors. In summary, patients with known vascular disease should be treated aggressively with a combination of a HMG CoA reductase inhibitor, an angiotensin-converting enzyme inhibitor, an antiplatelet agent and a beta blocker if there is a history of coronary disease. They should also receive tight control of their blood pressure and blood sugar. Smokers should be encouraged to stop smoking and should be provided with pharmaceutical and emotional support by their physicians. All of these patients should have their body mass index as close to normal as possible and be on a therapeutic lifestyle diet. Regular aerobic exercise is also indicated. Patients with symptomatic claudication should be considered for cilostazol. Patients with multiple risk factors for vascular disease, but who do not have documented disease should also be on statin therapy. As more studies define the linear relationship between lower LDL-C levels and lowered risk of vascular events, indicating that the lower the LDL-C level, the lower the risk, experts are advocating more aggressive lipid-lowering therapy. In patients with peripheral arterial disease, some experts now advocate lowering the goal of LDL therapy to 70 mg/dL.

Medical management of peripheral arterial disease: a therapeutic algorithm.

Over half of the people with peripheral arterial disease (PAD) may be asymptomatic. The most common symptom of mild-to-moderate PAD is intermittent claudication, present in about one third of symptomatic patients. Patients with intermittent claudication often have severely impaired functional status. Despite the high prevalence of the disease and the strong association with cardiovascular morbidity and mortality, patients with PAD are less likely to receive appropriate treatment for their atherosclerotic risk factors than are those being treated for coronary artery disease. The goals of treatment are to prevent progression of systemic atherosclerosis and its associated morbidity and mortality, to prevent limb loss, and to improve functional capacity for symptomatic patients. For claudicating patients, medical management includes symptomatic treatment with cilostazol or pentoxifylline. For all patients, it is equally important to pursue risk reduction through exercise programs and promotion of smoking cessation, as well as with the use of statins, antiplatelet therapies, antithrombotic strategies, angiotensin-converting-enzyme inhibitors, beta-blockers, and attention to homocysteine levels. Because not all patients are symptomatic, medical management of peripheral arterial disease may proceed along an algorithmic pathway that recognizes 3 types of patients: those requiring risk reduction only, symptomatic patients with minimal lifestyle limitation, and symptomatic patients with significant lifestyle impairment.