Macrocytic anemias.

PURPOSE OF REVIEW: Over the last century, the diseases associated with macrocytic anemia have been changing with more patients currently having hematological diseases including malignancies and myelodysplastic syndrome. The intracellular mechanisms underlying the development of anemia with macrocytosis can help in understanding normal erythropoiesis. Adaptations to these diseases involving erythroid progenitor and precursor cells lead to production of fewer but larger red blood cells, and understanding these mechanisms can provide information for possible treatments. RECENT FINDINGS: Both inherited and acquired bone marrow diseases involving primarily impaired or delayed erythroid cell division or secondary adaptions to basic erythroid cellular deficits that results in prolonged cell division frequently present with macrocytic anemia. SUMMARY OF FINDINGS: In marrow failure diseases, large accumulations of iron and heme in early stages of erythroid differentiation make cells in those stages especially susceptible to death, but the erythroid cells that can survive the early stages of terminal differentiation yield fewer but larger erythrocytes that are recognized clinically as macrocytic anemia. Other disorders that limit deoxynucleosides required for DNA synthesis affect a broader range of erythropoietic cells, but they also lead to macrocytic anemia. The source of macrocytosis in other diseases remains uncertain.

Utility of a Novel Trainee-Level Hematology/Oncology Podcast in Graduate Medical Education: a Pilot Study.

Asynchronous learning continues to gain popularity in medical education. One medium to facilitate asynchronous learning is the podcast. Currently, there are a limited number of hematology/oncology (H/O) podcasts geared towards residents and fellows ("trainees"). To address this need, we created a series of podcasts covering fundamental H/O topics for H/O fellows and internal medicine residents rotating on H/O services. We evaluate the effectiveness of this approach in this pilot study. Between September 2022 and February 2023, residents received recommended episodes via email prior to their rotation. Following their rotation, they received a survey. H/O fellows were encouraged to listen to any available episodes during the study period, after which they also received a survey. The survey collected baseline user information and included a 5-point Likert scale to determine if the podcast episodes were effective educational tools. Summary description was performed by the authors. In total 7 internal medicine residents (27 eligible) and 13 H/O fellows (18 eligible) completed the survey, for a total group of 20 respondents. The trainees found that the podcast helped with inpatient and outpatient management, was clinically relevant, and helped with clinical decision-making. They also agreed that the fundamentals of H/O are amenable to the podcast platform and are likely to continue to use podcasts as learning tools in H/O. This pilot study suggests that podcasts are an effective supplemental learning tool for the fundamentals of H/O in graduate medical education. The use of podcasts as educational tools should be encouraged for trainees.

COVID-19 severity and cardiovascular outcomes in SARS-CoV-2-infected patients with cancer and cardiovascular disease.

Background: Data regarding outcomes among patients with cancer and co-morbid cardiovascular disease (CVD)/cardiovascular risk factors (CVRF) after SARS-CoV-2 infection are limited. Objectives: To compare Coronavirus disease 2019 (COVID-19) related complications among cancer patients with and without co-morbid CVD/CVRF. Methods: Retrospective cohort study of patients with cancer and laboratory-confirmed SARS-CoV-2, reported to the COVID-19 and Cancer Consortium (CCC19) registry from 03/17/2020 to 12/31/2021. CVD/CVRF was defined as established CVD or no established CVD, male ≥ 55 or female ≥ 60 years, and one additional CVRF. The primary endpoint was an ordinal COVID-19 severity outcome including need for hospitalization, supplemental oxygen, intensive care unit (ICU), mechanical ventilation, ICU or mechanical ventilation plus vasopressors, and death. Secondary endpoints included incident adverse CV events. Ordinal logistic regression models estimated associations of CVD/CVRF with COVID-19 severity. Effect modification by recent cancer therapy was evaluated. Results: Among 10,876 SARS-CoV-2 infected patients with cancer (median age 65 [IQR 54-74] years, 53% female, 52% White), 6253 patients (57%) had co-morbid CVD/CVRF. Co-morbid CVD/CVRF was associated with higher COVID-19 severity (adjusted OR: 1.25 [95% CI 1.11-1.40]). Adverse CV events were significantly higher in patients with CVD/CVRF (all p<0.001). CVD/CVRF was associated with worse COVID-19 severity in patients who had not received recent cancer therapy, but not in those undergoing active cancer therapy (OR 1.51 [95% CI 1.31-1.74] vs. OR 1.04 [95% CI 0.90-1.20], pinteraction <0.001). Conclusions: Co-morbid CVD/CVRF is associated with higher COVID-19 severity among patients with cancer, particularly those not receiving active cancer therapy. While infrequent, COVID-19 related CV complications were higher in patients with comorbid CVD/CVRF. (COVID-19 and Cancer Consortium Registry [CCC19]; NCT04354701).

Patients Recently Treated for B-lymphoid Malignancies Show Increased Risk of Severe COVID-19.

Patients with B-lymphoid malignancies have been consistently identified as a population at high risk of severe COVID-19. Whether this is exclusively due to cancer-related deficits in humoral and cellular immunity, or whether risk of severe COVID-19 is increased by anticancer therapy, is uncertain. Using data derived from the COVID-19 and Cancer Consortium (CCC19), we show that patients treated for B-lymphoid malignancies have an increased risk of severe COVID-19 compared with control populations of patients with non-B-lymphoid malignancies. Among patients with B-lymphoid malignancies, those who received anticancer therapy within 12 months of COVID-19 diagnosis experienced increased COVID-19 severity compared with patients with non-recently treated B-lymphoid malignancies, after adjustment for cancer status and several other prognostic factors. Our findings suggest that patients recently treated for a B-lymphoid malignancy are at uniquely high risk for severe COVID-19. SIGNIFICANCE: Our study suggests that recent therapy for a B-lymphoid malignancy is an independent risk factor for COVID-19 severity. These findings provide rationale to develop mitigation strategies targeted at the uniquely high-risk population of patients with recently treated B-lymphoid malignancies. This article is highlighted in the In This Issue feature, p. 171.

Combining Osimertinib With Chemotherapy in EGFR-Mutant NSCLC at Progression.

BACKGROUND: Osimertinib is a third-generation EGFR tyrosine kinase inhibitor that has improved survival and central nervous system (CNS) outcomes in patients with non-small cell lung cancer (NSCLC) with activating EGFR mutations. However, little is known about the efficacy and safety of combining osimertinib with chemotherapy. METHODS: This was a retrospective study performed at 3 institutions. Patients with advanced EGFR-mutated NSCLC who received concurrent osimertinib with chemotherapy in the third-line or beyond were identified by chart review. Efficacy outcomes including duration on treatment (DOT), overall survival (OS), and CNS outcomes were assessed. Safety outcomes were also evaluated. RESULTS: A total of 44 patients met inclusion criteria. Median DOT with osimertinib plus platinum doublet (n = 28) was 6.1 months (95% CI 4.1 months-not reached), and with osimertinib plus single-agent chemotherapy (n = 29) was 2.6 months (95% CI 1.8-4.8 months). Median OS from the start of osimertinib plus chemotherapy was 10.4 months (95% CI 7.0-13.2 months). At initiation of osimertinib plus chemotherapy, 37 patients (84%) had CNS metastases; 9 of these (24%) had CNS disease progression on osimertinib plus chemotherapy. Chemotherapy was delayed or dose reduced due to toxicity in 8 patients (18%); osimertinib was discontinued in 1 patient (2%) for reduced cardiac ejection fraction, and dose reduced in 2 patients (5%). CONCLUSIONS: The combination of osimertinib plus chemotherapy appeared safe and showed favorable control of CNS disease in this cohort of patients who had progressed systemically with multiple prior lines of therapy, with DOT and survival outcomes similar to historical chemotherapy controls.

Intraoperative rerupture during surgical treatment of aneurysmal subarachnoid hemorrhage is not associated with an increased risk of vasospasm.

OBJECT: Intraoperative rerupture during open surgical clipping of cerebral aneurysms in subarachnoid hemorrhage (SAH) is a relatively frequent and potentially catastrophic occurrence. Patients who suffer rerupture have been shown to have worse outcomes at discharge compared with those who do not have rerupture. Perioperative injury likely plays a large part in the clinical worsening of these patients. However, due to the increased vessel manipulation and repeat exposure to acute hemorrhage, it is possible that secondary injury from increased incidence of vasospasm also contributes. Identifying an increased rate of vasospasm in these patients would justify early aggressive treatment with measures to prevent delayed cerebral ischemia. The authors investigated whether patients who suffer intraoperative rerupture during surgical treatment of ruptured cerebral aneurysms are at increased risk of developing vasospasm. METHODS: Five hundred consecutive patients treated with open surgical clipping for SAH were reviewed, and clinical and imaging data were collected. Angiographic vasospasm was defined as vessel narrowing believed to be consistent with vasospasm on angiography. Symptomatic vasospasm was defined as angiographic vasospasm in the setting of a clinical change attributable to vasospasm. Rates of angiographic and symptomatic vasospasm among patients with and without intraoperative rerupture were compared. RESULTS: There were no significant differences between the groups with and without rupture with respect to age, sex, modified Fisher grade, history of hypertension, or smoking. The group with intraoperative rupture had more patients with Hunt and Hess Grade I. Angiographic vasospasm was noted in 279 (66%) of the 425 patients without rerupture compared with 49 (65%) of the 75 patients with rerupture (p = 1.0, Fisher's exact test). Symptomatic vasospasm was noted in 154 (36%) of the 425 patients without rerupture, compared with 31 (41%) of the 75 patients with rerupture (p = 0.44, Fisher's exact test). In multivariate analysis, higher modified Fisher grade was significantly predictive of vasospasm, whereas older age and male sex were protective. CONCLUSIONS: This study found no significant influence of intraoperative rerupture during open surgical clipping on the rate of angiographic or symptomatic vasospasm. Brief exposure to acute hemorrhage and vessel manipulation associated with rerupture events did not affect the rate of vasospasm. Risk of vasospasm was related to increased modified Fisher grade, and inversely related to age and male sex. These results do not justify early, targeted vasospasm therapy in patients with intraoperative rerupture.