Most patients with acute myeloid leukemia (AML) die from complications arising from cytopenias resulting from bone marrow (BM) failure. The common presumption among physicians is that AML-induced BM failure is primarily due to overcrowding, yet BM failure is observed even with low burden of disease. Here, we use large clinical datasets to show the lack of correlation between BM blast burden and degree of cytopenias at the time of diagnosis. We develop a splenectomized xenograft model to demonstrate that transplantation of human primary AML into immunocompromised mice recapitulates the human disease course by induction of BM failure via depletion of mouse hematopoietic stem and progenitor populations. Using unbiased approaches, we show that AML-elaborated IL-6 acts to block erythroid differentiation at the proerythroblast stage and that blocking antibodies against human IL-6 can improve AML-induced anemia and prolong overall survival, suggesting a potential therapeutic approach.

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Background The ability to predict breast implant augmentation complications can significantly inform patient management. Frailty measures such as the modified 5-item frailty index (mFI-5) is becoming an increasingly established risk factor for adverse postoperative outcomes. The authors hypothesized that the mFI-5 is predictive of 30-day postoperative complications in breast augmentation. Objectives To investigate if mFI-5 can predict the likelihood and magnitude of 30-day complications resulting from breast augmentations. Methods Retrospective review study of the National Surgical Quality Improvement Program (NSQIP) database for patients who underwent breast implant augmentation without other concurrent procedures, from 2015 to 2019. Age, body mass index (BMI), number of major comorbidities, American Society of Anesthesiologists (ASA) classifications, smoking status, mFI-5 score, and mCCI score were compared as predictors of all-cause 30-day complications and 30-day surgical site complications using regression analyses. Results Overall, 2478 patients were analyzed, and among them fifty-three patients developed complications (2.14%). mFI-5 score significantly predicted surgical site infection complications (SSI) (OR = 4.24, p = 0.026). Frail patients had a higher occurrence of SSIs than non-frail patients (p = 0.049). Multivariable analyses showed ASA class predicted 30-day SSI complications (OR = 5.77, p = 0.027) and mFI-5 approached, but did not reach full significance in predicting overall 30-day complications (OR = 3.14, p = 0.085). Conclusions To date, the impact of frailty on breast implant procedure outcomes has not been studied. Our analysis demonstrates that the mFI-5 is a significant predictor for surgical site infections in breast implant augmentation surgery and associated with overall complications. By preoperatively identifying frail patients, the surgical team can better account for postoperative support to minimize risk of complications.