A healthy, active woman in her 70s reported intermittent exertional dyspnoea for 2 months, notable during frequent open-water swimming. Symptoms were similar to an episode of travel-provoked pulmonary embolism 3 years prior. She denied chest pain, cough, fever, extremity complaints and symptoms at rest. Due to the COVID-19 pandemic, her healthcare system was using secure telemedicine to evaluate non-critical complaints. During the initial video visit, she appeared well, conversing normally without laboured breathing. An elevated serum D-dimer prompted CT pulmonary angiography, which identified acute lobar pulmonary embolism. After haematology consultation and telephone conversation with the patient, her physician prescribed rivaroxaban. Her symptoms rapidly improved. She had an uneventful course and is continuing anticoagulation indefinitely. The pandemic has increased the application of telemedicine for acute care complaints. This case illustrates its safe and effective use for comprehensive management of acute pulmonary embolism in the primary care setting.

Bladder cancer is one of the most commonly diagnosed genitourinary malignancies. For many years, the primary treatment for metastatic urothelial cancer (mUC) was predicated on the use of platinum-based chemotherapy. More recently, immune checkpoint inhibitors (ICIs) were approved by regulatory agencies such as the US FDA for use in both the first- and second-line settings. This review outlines the approved ICIs for mUC in the second-line setting and as an alternative to chemotherapy in the first-line setting, as well as the novel agents that have also been incorporated into the treatment of this malignancy. Single-agent ICIs are often used in second-line settings in mUC, and there are three drugs currently approved for those who progress after receiving platinum-based chemotherapy. In the first-line setting, the preferred treatment regimen remains cisplatin-based chemotherapy. However, single-agent ICI can be an alternative first-line treatment for those who are not candidates for cisplatin-based therapy. There are also clinical trials adding ICIs to chemotherapy as combination regimens. However, treatment for mUC has now expanded even beyond immunotherapy. Newer targeted agents such as erdafitinib, a fibroblast growth factor receptor inhibitor, and two antibody–drug conjugates, enfortumab vedotin and sacituzumab govitecan, have been recently approved. As new drug agents are discovered, it will be important to assess both the treatment outcomes as well as the effects on patients’ quality of life. Furthermore, integrating genetic and molecular information can help guide treatment decisions as next-generation sequencing is more commonly acquired during the evaluation of newly diagnosed patients with advanced and metastatic cancer.

Purpose: To evaluate the frequency and severity of irAEs in patients with pre-existing autoimmunity, including irAE-related morbidity and mortality, irAE-related management and resolution, and outcome of ICI rechallenge, to better understand the treatment options for this vulnerablepatient population. Methods: We designed a retrospective, single-center, case-control study at a large, academic medical center to evaluate the incidence and severity of irAEs in patients with pre-existing autoimmunity compared to controls. Controls were matched 2:1 for age, sex, cancer histology, and ICI class. Patients were identified with ICD 9 and 10 codes followed by manual chart extraction. Cases were defined as patients with pre-existing, systemic autoimmunity. The primary outcome was severe irAE (Grade 3 or higher by Common Terminology Criteria for Adverse Events) within 6 months of ICI therapy. Secondary outcomes included response to ICIs, resolution of the irAE, ICI rechallenge success, and survival. Statistical analyses were performed by Chi-square, Fishers exact, Mann-Whitney, and Log-rank tests. Results: Of 3,130 patients treated with ICIs from 2015-2021, 28 cases with pre-existing autoimmune disease were identified and were matched with 56 controls. Pre-existing autoimmune conditions included antiphospholipid syndrome, inflammatory polyarthritis, juvenile rheumatoid arthritis, multiple sclerosis, psoriatic arthritis, rheumatoid arthritis, and type I diabetes. Multiple cancer histologies, including genitourinary, gynecologic, head & neck, hepatobiliary, lung, melanoma, and pancreatic, were represented. Six of 28 cases (21.4%) experienced severe irAEs compared to 9/56 (16.1%) controls; the odds of developing a severe irAE were not significantly different (OR 0.43, 95% CI 0.083-2.33, p = 0.627, ns). Moreover, there were no significant differences in overall survival or tumor response between the two groups. The majority of irAEs resolved without long-term sequelae (66.7% of cases, 55.6% of controls). The majority of patients who were rechallenged with ICIs were successful in continuing therapy (66.7% of cases, 100% of controls). Conclusion: Our study suggests that patients with pre-existing autoimmune disease can be treated with ICI cancer therapies and experience rates of severe irAEs and overall survival that are similar to those of the general population. These data can aid oncologists in discussing risks and benefits of ICIs when treating patients with pre-existing autoimmunity and solid tumors.

For patients with acute pulmonary embolism (PE) diagnosed in the primary care setting, transfer to a higher level of care, like the emergency department, has long been the convention. Evidence is growing that outpatient management, that is, care without hospitalization, is safe, effective, and feasible for selected low-risk patients with acute PE. Whether outpatient care can be provided entirely in the primary care setting has not been well-studied. We report a case of outpatient management of a low-risk patient with acute PE without emergency department transfer. A 74-year-old woman with a history of recent surgery and immobilization presented to a primary care physician with 10 days of mild, non-exertional pleuritic chest pain. Her D-dimer concentration was elevated. Computed tomography pulmonary angiography identified a lobar embolus without right ventricular dysfunction. She declined emergency department transfer but was classified as low risk (class II) on the PE Severity Index and met the criteria of the European Society of Cardiology (ESC) for outpatient care. Her physician provided comprehensive clinic-based PE management, discharging her to home with education, anticoagulation, and close follow-up. She completed her 3-month treatment course without complication. This case describes patient-centred, comprehensive, outpatient PE management in the primary care setting for a woman meeting explicit ESC outpatient criteria. This case illustrates the elements of care that clinics can put in place to facilitate PE management without having to transfer eligible low-risk patients to a higher level of care.

Alisha A Othieno1; Dayna J Isaacs, MPH1; David R Vinson,...

Rationale: The evidence for outpatient pulmonary embolism (PE) management apart from hospitalization is expanding. The availability and ease of direct oral anticoagulants have facilitated this transition. The literature, however, is sparse on the topic of comprehensive management of pulmonary embolism in the primary care clinic setting. As such, the role of the primary care physician in the complete diagnosis, risk stratification for outpatient eligibility, and initiation of treatment is unclear. Case presentations: Case 1: A 33-year-old man with known heterozygous Factor V Leiden mutation and a remote history of deep vein thrombosis presented to his primary care physician's office with 2 days of mild pleuritic chest pain and a dry cough after a recent transcontinental flight. Case 2: A 48-year-old man with a complex medical history including recent transverse myelitis presented to his primary care family physician with dyspnea and pleuritic chest pain for 6 days. Diagnosis: Case 1: Computed tomographic pulmonary angiography that same afternoon showed multiple bilateral segmental and subsegmental emboli as well as several small pulmonary infarcts. Case 2: The patient's D-dimer was elevated at 1148 ng/mL. His physician ordered a computed tomographic pulmonary angiography, performed that evening, which showed segmental and subsegmental PE. Interventions: Both patients were contacted by their respective physicians shortly after their diagnoses and, in shared decision-making, opted for treatment at home with 5 days of enoxaparin followed by dabigatran. Outcomes: Neither patient developed recurrence nor complications in the subsequent 3 months. Lessons: These cases, stratified as low risk using the American College of Chest Physicians criteria and the PE Severity Index, are among the first in the literature to illustrate comprehensive primary care-based outpatient PE management. Care was provided within an integrated delivery system with ready, timely access to laboratory, advanced radiology, and allied health services. This report sets the stage for investigating the public health implications of comprehensive primary care-based PE management, including cost-savings as well as enhanced patient follow-up and patient satisfaction.