Review of Palliative 223Ra in Metastatic Castration-Resistant Prostate Cancer: Experience at West Virginia University Cancer Center.

The ALSYMPCA trial of the α-emitter 223Ra in symptomatic bone-predominant metastatic castration-resistant prostate cancer (mCRPC) reported a median overall survival (OS) of 14.9 mo, versus 11.3 mo for placebo. However, subsequently reported real-world experience with 223Ra in smaller mCRPC patient cohorts has appeared less successful. We performed a retrospective observational study to review our own 223Ra experience at West Virginia University (WVU). Methods: Demographic, clinical, laboratory, and imaging data were reviewed in all bone-predominant mCRPC patients treated with 223Ra at WVU from 2014 to 2019. The number of bone metastases per patient at the start of treatment with 223Ra was quantified via nuclear bone scans (12 scans, 5 of which also included SPECT/CT), body CT scans (8 scans), and PET/CT scans (4 scans). Standard descriptive statistics were used to study institutional review board-exempted, deidentified patient data. Median survival in ALSYMPCA and WVU patients was compared using a 2-sided, 1-sample log-rank test based on the exponential distributions. The primary endpoint was patient OS after initiating 223Ra. Results: Twenty-four patients received 98 infusions of 223Ra; 83% of these patients were referred from outside WVU. Before the first infusion, all 24 had received androgen deprivation therapy. In total, 73 sequential combinations of androgen deprivation therapy were used, 68 of which (93%) preceded the first 223Ra infusion. Also, before 223Ra, 19 (79%) patients had received docetaxel and 19 (79%) had received 33 courses of radiation, 24 of which targeted nonprostatic sites. Eleven patients (46%) completed all 6 planned 223Ra infusions; 13 (54%) stopped early because of clinical deterioration. As of August 2020, only 1 patient remained alive after completing 6 cycles of 223Ra. Median OS from the first 223Ra infusion to the last follow-up or death was 8.3 mo (range, 0-44 mo)-nearly 50% less than the ALSYMPCA median survival of 14.9 mo (P = 0.01). Compared with ALSYMPCA, more WVU patients received bisphosphonates and docetaxel, more had an Eastern Cooperative Oncology Group performance status of at least 2, more used opiates for pain, more had a greater bone metastasis burden by imaging, and more had lower hemoglobin, albumin, alkaline phosphatase, and prostate-specific antigen levels. Conclusion: Although the science supporting the development and clinical use of 223Ra is compelling, optimal clinical benefit will likely require earlier referral for 223Ra, before patients have exhausted most conventional therapies. At WVU, we found that practically all our referred patients had androgen deprivation therapy, radiation, and cytotoxic therapy before starting 223Ra. We continue to offer 223Ra therapy to patients with symptomatic bone-predominant mCRPC but are encouraging earlier patient referral.

Educational Case: Warm Autoimmune Hemolytic Anemia.

The following fictional case is intended as a learning tool within the Pathology Competencies for Medical Education (PCME), a set of national standards for teaching pathology. These are divided into three basic competencies: Disease Mechanisms and Processes, Organ System Pathology, and Diagnostic Medicine and Therapeutic Pathology. For additional information, and a full list of learning objectives for all three competencies, see http://journals.sagepub.com/doi/10.1177/2374289517715040.1.

Inpatient management strategies in a severe case of heparin-induced thrombocytopenia.

We present important laboratory testing and clinical management strategies used to safely discharge home a 69-year old woman with heparin-induced thrombocytopenia (HIT) from the hospital. She was admitted for a coronary artery bypass graft procedure for which she was anticoagulated with heparin. Shortly after the procedure she developed thrombocytopenia and was diagnosed with HIT using the 4Ts scoring system, a latex-enhanced immunoassay (LEI) screen and confirmatory serotonin release assay. Her anticoagulation was switched from heparin to argatroban, and response to treatment was monitored in the laboratory using LEI. Unfortunately, she also received platelet transfusions and subsequently developed multifocal deep vein thrombosis with worsening platelet counts with nadir less than 10 x 10^3/µL. After five therapeutic plasma exchange procedures we noted an improvement in platelet counts, which plateaued into the 50s x 10^3/µL. Furthermore, the LEI remained positive. At this juncture we decided to transition from argatroban to fondaparinux so that she could leave the hospital in stable condition. Upon follow-up with hematology she exhibited no worsening clinical signs or symptoms of disease, and platelet counts markedly improved to within normal limits of detection. In this report we examine the utility of LEI in monitoring patients with HIT, therapeutic plasma exchange in the management of severe HIT (with thrombosis), and the use of subcutaneous fondaparinux in managing HIT in the outpatient setting.

The Effect of an Educational Pamphlet on Patient Knowledge of and Intention to Discuss Screening for Obstructive Sleep Apnea in the Acute Ischemic Stroke Population.

BACKGROUND: The relationship between obstructive sleep apnea (OSA) and stroke is well established, thus supporting the importance of secondary prevention via screening and treatment for acute ischemic stroke survivors. Educational pamphlets are commonly used for patient education; however, none currently available on OSA have evaluated. The aim of this study was to evaluate the effect of a brief educational intervention on patient knowledge and interest in OSA screening. METHODS: Adult acute ischemic stroke patients were enrolled into a nonrandomized, single-group, pretest and posttest study. Inclusion criteria included minor or moderate stroke per the National Institutes of Health Stroke Scale score of 1 to 15, with a level of consciousness score of 0. Patients with known dementia or OSA were excluded. After the preintervention survey, patients were given an educational pamphlet reviewing OSA and stroke. A postintervention survey was administered 24 to 72 hours later. Outcomes included an 8-question knowledge test standardized to percentiles, intention to speak with a physician about screening on a 7-point scale (1, not at all likely, to 7, very likely), and perception of the pamphlet's educational value on a 7-point scale (1, not valuable, to 7, quite valuable). RESULTS: Of 124 eligible patients, 36 consented and 26 completed both preintervention and postintervention surveys. Preintervention knowledge scores averaged 69.7% (SD, 21.3%), postintervention scores averaged 80.8% (SD, 21.0%), P = .005, with an effect size of 1.00. Likelihood of speaking with a physician about OSA testing improved from 3.5 (SD, 2.0) to 5.0 (SD, 1.8), P = .001, with an effect size of 0.89. Pamphlet educational value was scored at 5.2 (SD, 1.7). CONCLUSIONS: A brief educational pamphlet written using health literacy concepts was considered valuable and improved patient knowledge and intention to discuss OSA screening with a physician. Further work is needed to determine whether the pamphlet can promote a discussion and referral for OSA screening at the primary care level.

Common variable immunodeficiency, immune thrombocytopenia, rituximab and splenectomy: important considerations.

Common variable immunodeficiency (CVID) is readily considered in patients presenting with recurrent sino-pulmonary infections, however this disease has a broad range of clinical manifestations and diagnosis can be delayed by several years. We present the case of a 44-year-old postpartum female who presented with nausea, vomiting and abdominal distension. Four years prior, she was hospitalized for treatment of immune thrombocytopenia (ITP) with splenectomy and rituximab followed by two episodes of bacterial meningitis despite immunizations. The recurrent meningitis had been attributed to splenectomy and immunotherapy. During this hospitalization, extensive workup for gastrointestinal pathology was negative and she was diagnosed with intestinal pseudo-obstruction. Her hospital course was complicated by development of severe pseudomonas pneumonia, and subsequent immunoglobulin testing and impaired antibody response to vaccines were consistent with CVID. We review the clinical presentation of CVID, its association with autoimmune disease, and treatment implications, specifically the impact of rituximab therapy and splenectomy on immunoglobulin function and risk of serious infection. Intestinal pseudo-obstruction has been reported in children with CVID, but literature search failed to reveal similar presentation in adults. Physicians must consider the heterogeneous clinical manifestations of CVID to avoid delay in diagnosis and treatment. Institution of appropriate therapy with immunoglobulin replacement is important to decrease risk of serious infection.