Androgen receptor expression in patients with triple negative breast cancer treated with neoadjuvant chemotherapy: a single institution study.

Background: Androgen receptor (AR) expression has emerged as a potential prognostic and predictive marker in patients with triple negative breast cancer (TNBC). We conducted a retrospective analysis to evaluate pathologic complete response (pCR) rates, disease-free survival (DFS) and overall survival (OS) in patients with AR positive and AR negative TNBC treated with neoadjuvant chemotherapy. Methods: 107 patients with TNBC subtype, treated with neoadjuvant chemotherapy between June 2006 and March 2016 were evaluated for AR expression. Androgen receptors were evaluated by immunohistochemical staining (clone AR441, Dilution 1:50, Dako-Agilent, Santa Clara, CA) using whole tissue sections from archived paraffin-embedded formalin-fixed (FFPE) blocks. AR positive was defined as ≥10% nuclear stained cells. Correlation of AR expression was examined with age, BMI, race, menopausal status, tumor grade, tumor size, and lymph node involvement, and response and outcomes. Univariate and multivariate analyses were performed to determine an association with AR expression and pathologic response and survival outcomes. Results: Fifty-eight patients with available tumor specimens were stained, with twenty (34.5%) being AR-positive and thirty-eight (65.5%) being AR negative. Median age was 49 years and median follow up was 5.7 years. All patients received anthracycline based neoadjuvant chemotherapy with 13 patients (23%) receiving an additional platinum chemotherapy. BRCA mutation positivity was 7% for the entire group. No differences in age, menopausal status, BMI, race, tumor size and lymph node involvement were observed between the two groups. However, there was a statistically significant difference in tumor grade between the two groups (p=0.008). Overall pCR rate was 28% with no difference between the two groups (30% vs 26%, p=0.56). There was no statistically significant difference in median DFS (5.9 years vs 5.2 years (p=0.94) and median OS (6.2 years vs 5.4 years, p=0.98) between the AR positive and AR negative groups. Conclusions: Our study did not find an association of AR status and the pathologic responses or survival outcomes in patients with TNBC treated with neoadjuvant chemotherapy. Further studies exploring the prognostic and predictive role of AR in patients with TNBC are warranted.

Administration of Immune Checkpoint Inhibitors Near the End of Life.

PURPOSE: Recent literature suggests an increasing use of systemic treatment in patients with advanced cancer near the end of life (EOL), partially driven by the increasing adoption of immune checkpoint inhibitors (ICIs). While studies have identified this trend, additional variables associated with ICI use at EOL are limited. Our aim was to characterize a population of patients who received a dose of ICI in the last 30 days of life. METHODS: We performed a manual retrospective chart review of patients ≥ 18 years who died within 30 days of receiving a dose of ICI. Metrics such as Eastern Cooperative Oncology Group performance status (ECOG PS), number of ICI doses, need for hospitalization, and numerous other variables were evaluated. RESULTS: Over a 4-year time period, 97 patients received an ICI at EOL. For 40% of patients, the ICI given in the 30 days before death was their only dose. Over 50% of patients had an ECOG PS of ≥ 2, including 17% of patients with an ECOG PS of 3. Over 60% were hospitalized, 65% visited the emergency department, 20% required intensive care unit admission, and 25% died in the hospital. CONCLUSION: Our study contributes to the ongoing literature regarding the risks and benefits of ICI use in patients with advanced cancer near the EOL. While accurate predictions regarding the EOL are challenging, oncologists may routinely use clinical factors such as ECOG PS along with patient preferences to guide recommendations and shared decision making. Ultimately, further follow-up studies to better characterize and prognosticate this population of patients are needed.

Perceptions of Burnout Among Academic Hospitalists.

INTRODUCTION: There is a paucity of data on burnout among academic hospitalists in Wisconsin. OBJECTIVE/METHODS: To evaluate perceptions on burnout among academic hospitalists at an academic center in Wisconsin, a survey was distributed to academic hospitalists at the Medical College of Wisconsin. Questions addressed job satisfaction, factors contributing to burnout and its consequences, and various preventive steps. A section was included for respondents to provide any additional comments. RESULTS: Out of 52 academic hospitalists surveyed, 43 (83%) responded. Sixty-two percent of participants reported feeling burnout. Burnout rates did not differ by gender (males vs females, 58% vs 73%, respectively; P = 0.65), career length as a hospitalist (P = 0.28), or satisfaction as a hospitalist (P = 0.11). High patient census (94%) and unrealistic workload (83%) were the most commonly cited factors for burnout. Possible consequences of burnout included lack of enthusiasm (95%) and mental exhaustion (93%). A majority of respondents (81%) indicated that high clinical demands interfered with their ability to teach medical students. Improving the structure of work (88%) and incorporating respect, care, and compassion as a group culture (88%) were the most common themes reported to prevent burnout. CONCLUSION: This study shows a high prevalence of burnout among academic hospitalists and highlights various opportunities to reduce burnout risk.

Relapse after Allogeneic Hematopoietic Cell Transplantation for Multiple Myeloma: Survival Outcomes and Factors Influencing Them.

Many patients with multiple myeloma (MM) eventually relapse even after allogeneic hematopoietic cell transplantation (alloHCT) for curative intent. Over the past decade, outcomes for patients with MM have improved significantly with the availability of new therapies, including next-generation proteasome inhibitors, immunomodulatory agents, and, more recently, monoclonal antibodies. Although several published studies have evaluated the outcomes of alloHCT for MM, the data on survival outcomes in patients with MM experiencing disease relapse following alloHCT are limited. In addition, the predictors for postrelapse survival in these patients are not known. In this study, we examined the outcomes of a single-center cohort of 60 patients with MM who experienced relapse or progression after alloHCT. In addition, we evaluated the use of salvage regimens for treatment of relapsed MM and analyzed the predictors for improved postrelapse survival. After a median follow-up of 2.2 years from the time of relapse, the median duration of postrelapse survival was 1.8 years (95% confidence interval [CI], 1.2 to 5.0 years). Patients received a median of 3 lines of therapy (range, 0 to 10) for treatment of MM beyond the post-alloHCT relapse/progression. Multivariate analysis identified cytogenetic risk (standard risk versus high risk; hazard ratio [HR], .34; P = .01), time to relapse after alloHCT (>12 months versus ≤12 months: HR, .41; P = .04), and occurrence of acute graft-versus-host disease (GVHD) before relapse (GVHD versus no GVHD: HR, 2.89; P = .01) significantly affected postrelapse survival. These data illustrate that long-term myeloma control and survival is attainable in those relapsing/progressing after alloHCT and suggest that the synergism between novel therapies and the allogeneic immune platform is the key to improved survival in this high-risk patient population.

Immune Checkpoint Inhibitor Use Near the End of Life Is Associated With Poor Performance Status, Lower Hospice Enrollment, and Dying in the Hospital.

BACKGROUND: Immune checkpoint inhibitors have changed the landscape of cancer care by increasing progression-free and overall survival in some patients with cancer. We evaluated use and variables contributing to immune checkpoint inhibitor treatment near the end of life. METHODS: We studied 157 patients who received immune checkpoint inhibitors and died between January 2015 and December 2018. All patients had a palliative care consult any time between starting an immune checkpoint inhibitor and death. Univariate and multivariate models were used to examine variables related to immune checkpoint inhibitor use near the end of life. RESULTS: Among 157 patients studied, 42 (27%) received a dose of immune checkpoint inhibitor in the last 30 days of life. Those who received treatment in the last 30 days of life had lower hospice enrollment (19 [45%] vs 78 [69%], P = .007) and higher rates of dying in the hospital (23 [56%] vs 33 [29%], P = .002). The percentage of patients with Eastern Cooperative Oncology Group (ECOG) ≥3 at the time of last immune checkpoint inhibitor dose was higher in the group that received immune checkpoint inhibitor treatment in the last 30 days of life (11 [26%] vs 9 [8%], P = .003). Lack of traditional chemotherapy after immune checkpoint inhibitor, ECOG ≥3, and lack of hospice enrollment were independently associated with receiving immune checkpoint inhibitor in the last 30 days of life. CONCLUSION: Immune checkpoint inhibitor use in the last 30 days of life is common and associated with poor performance status, lower hospice enrollment, and dying in the hospital.

Immune Checkpoint Inhibitor Use Near the End of Life: A Single-Center Retrospective Study.

Background: Immune checkpoint inhibitors (ICIs) have revolutionized treatment for many patients with advanced cancer. Little is known about ICI use near the end of life. Objective: To describe ICI use near the end of life. Design: Retrospective study of patients who received ICIs and died. Setting/Subjects: Patients treated with ICIs who died between August 2014 and December 2018 (N = 441) at the University of Iowa. Measurements: Comparisons were made between patients who received ICIs ≤30 days versus patients who received ICIs >30 days before death. The same analysis was done using a cutoff of 90 days. Results: Two hundred ninety-four (67%) patients received ICIs in the last 90 days of life and 117 (27%) patients received ICIs in the last 30 days of life. Patients who received ICIs in the last 30 days of life received fewer mean doses and more often ≤3 total doses. They also had higher mean Eastern Cooperative Oncology Group (ECOG) scores, more patients with ECOG ≥3, higher rates of dying in the hospital, and lower hospice enrollment. Patients treated with ICIs in the last 90 days of life received fewer doses, more often ≤3 total doses, had a higher mean ECOG score, more patients with ECOG ≥3, and lower hospice enrollment. $7.1 million USD was spent on ICI medications in the last 90 days of life. Conclusion: ICI use near the end of life is associated with poor performance status, lower hospice enrollment, dying in the hospital, financial toxicity, and minimal clinical benefit.

Use of Fetal Hemoglobin Quantitation for Rh-Positive Pregnant Females: A National Survey and Review of the Literature.

CONTEXT.­: The Kleihauer-Betke (KB) test is validated for estimating the dose of Rh immune globulin needed for Rh-negative pregnant females. However, some clinicians are also ordering the test for Rh-positive women. The degree to which this practice occurs is unknown. OBJECTIVE.­: To evaluate the number of laboratories that perform the KB test on Rh-positive pregnant women, and to establish current ordering practices for this indication. DESIGN.­: We added 9 supplemental questions regarding KB test use for fetomaternal hemorrhage to the 2016 College of American Pathologists proficiency test survey. We also reviewed the available literature regarding the diagnostic utility of the KB test for Rh-positive women. RESULTS.­: A total of 1578 surveys were evaluated and revealed that 52% (824) of respondents perform these tests for Rh-positive women, and more than 50% (440 of 819; 53.7%) of these laboratories report that the results for Rh-positive women are treated as important or very important. CONCLUSIONS.­: The KB test is commonly used for Rh-positive women, and the information obtained from the test is considered as urgent and important. However, the available literature in support of this practice is still nonconclusive.

Evaluation of a two-sample process for prevention of ABO mistransfusions in a high volume academic hospital.

BACKGROUND: Acute haemolytic transfusion reactions due to ABO incompatible blood transfusion remain a leading cause of transfusion-associated morbidity and mortality in the USA. Erroneous patient identification and specimen labelling account for many errors that lead to ABO mistransfusions; these errors are largely preventable. METHODS: Our hospital requires a two-sample process of ABO/Rh typing prior to transfusion. Both samples must be drawn independently. To prevent simultaneous sample draw, our second sample tube has a unique pink top that is only available from the blood bank and can only be sent to the patient's floor once the first sample arrives in the lab. We performed an audit of this process from 19 March to 30 July 2014 and 19 March to 30 July 2015. RESULTS: We reviewed type and crossmatch orders for 2702 new patients during the audit period and 824 patients (30.5%) required transfusion. All patients evaluated received compatible blood, and no mistransfusions were recorded using this method. Three per cent of testing was performed incorrectly, which safely defaulted to giving type O blood. CONCLUSIONS: The two-sample protocol used by our institution can decrease the risk of mistransfusion. Our protocol was relatively inexpensive, safe, efficient and practical for adaptation by other hospitals.

Whole-thorax irradiation induces hypoxic respiratory failure, pleural effusions and cardiac remodeling.

To study the mechanisms of death following a single lethal dose of thoracic radiation, WAG/RijCmcr (Wistar) rats were treated with 15 Gy to the whole thorax and followed until they were morbid or sacrificed for invasive assays at 6 weeks. Lung function was assessed by breathing rate and arterial oxygen saturation. Lung structure was evaluated histologically. Cardiac structure and function were examined by echocardiography. The frequency and characteristics of pleural effusions were determined. Morbidity from 15 Gy radiation occurred in all rats 5 to 8 weeks after exposure, coincident with histological pneumonitis. Increases in breathing frequencies peaked at 6 weeks, when profound arterial hypoxia was also recorded. Echocardiography analysis at 6 weeks showed pulmonary hypertension and severe right ventricular enlargement with impaired left ventricular function and cardiac output. Histologic sections of the heart revealed only rare foci of lymphocytic infiltration. Total lung weight more than doubled. Pleural effusions were present in the majority of the irradiated rats and contained elevated protein, but low lactate dehydrogenase, when compared with serum from the same animal. Pleural effusions had a higher percentage of macrophages and large monocytes than neutrophils and contained mast cells that are rarely present in other pathological states. Lethal irradiation to rat lungs leads to hypoxia with infiltration of immune cells, edema and pleural effusion. These changes may contribute to pulmonary vascular and parenchymal injury that result in secondary changes in heart structure and function. We report that conditions resembling congestive heart failure contribute to death during radiation pneumonitis, which indicates new targets for therapy.