Citations

Management of febrile neutropenia (FN) is an integral part of supportive care for patients undergoing cancer treatment. The NCCN Guidelines for Hematopoietic Growth Factors provide suggestions for appropriate evaluation, risk determination, prophylaxis, and management of FN. These NCCN Guidelines are intended to guide clinicians in the appropriate use of growth factors for select patients undergoing treatment of nonmyeloid malignancies. These NCCN Guidelines Insights highlight important updates to the NCCN Guidelines regarding the incorporation of newly FDA-approved granulocyte-colony stimulating factor biosimilars for the prevention and treatment of FN.

Background: Type 2 myocardial infarction (T2MI) occurs because of an acute imbalance in myocardial oxygen supply and demand in the absence of atherothrombosis. Despite being frequently encountered in clinical practice, the population-based incidence and trends remain unknown, and the long-term outcomes are incompletely characterized. Methods: We prospectively recruited residents of Olmsted County, Minnesota, who experienced an event associated with a cardiac troponin T >99th percentile of a normal reference population (≥0.01 ng/mL) between January 1, 2003, and December 31, 2012. Events were retrospectively classified into type 1 myocardial infarction (T1MI, atherothombotic event), T2MI, or myocardial injury (troponin rise not meeting criteria for myocardial infarction [MI]) using the universal definition. Outcomes were long-term all-cause and cardiovascular mortality and recurrent MI. T2MI was further subclassified by the inciting event for supply/demand mismatch. Results: A total of 5460 patients had at least one cardiac troponin T ≥0.01 ng/mL; 1365 of these patients were classified as index T1MI (age, 68.5±14.8 years; 63% male) and 1054 were classified as T2MI (age, 73.7±15.8 years; 46% male). The annual incidence of T1MI decreased markedly from 202 to 84 per 100 000 persons between 2003 and 2012 ( P <0.001), whereas the incidence of T2MI declined from 130 to 78 per 100 000 persons ( P =0.02). In comparison with patients with T1MI, patients with T2MI had higher long-term all-cause mortality after adjustment for age and sex, driven by early and noncardiovascular death. Rates of cardiovascular death were similar after either type of MI (hazard ratio, 0.8 [95% CI, 0.7–1.0], P =0.11). Subclassification of T2MI by cause demonstrated a more favorable prognosis when the principal provoking mechanism was arrhythmia, in comparison with postoperative status, hypotension, anemia, and hypoxia. After index T2MI, the most common MI during follow-up was a recurrent T2MI, whereas the occurrence of a new T1MI was relatively rare (estimated rates at 5 years, 9.7% and 1.7%). Conclusions: There has been an evolution in the type of MI occurring in the community over a decade, with the incidence of T2MI now being similar to T1MI. Mortality after T2MI is higher and driven by early and noncardiovascular death. The provoking mechanism of supply/demand mismatch affects long-term survival. These findings underscore the healthcare burden of T2MI and provide benchmarks for clinical trial design.

ABSTRACT Multiple myeloma is caused by abnormal plasma cells that accumulate in the bone marrow and interact with resident cells of the bone microenvironment to drive disease progression and development of an osteolytic bone disease. Bone marrow adipocytes (BMAds) are emerging as having important endocrine functions that can support myeloma cell growth and survival. However, how BMAds respond to infiltrating tumor cells remains poorly understood. Using the C57BL/KaLwRij murine model of myeloma, bone marrow adiposity was found to be increased in early stage myeloma with BMAds localizing along the tumor-bone interface at later stages of disease. Myeloma cells were found to uptake BMAd-derived lipids in vitro and in vivo, although lipid uptake was not associated with the ability of BMAds to promote myeloma cell growth and survival. However, BMAd-derived factors were found to increase myeloma cell migration, viability, and the evasion of apoptosis. BMAds are a major source of adiponectin, which is known to be myeloma-suppressive. Myeloma cells were found to downregulate adiponectin specifically in a model of BMAds but not in white adipocytes. The ability of myeloma cells to downregulate adiponectin was dependent at least in part on TNF-α. Collectively our data support the link between increased bone marrow adiposity and myeloma progression. By demonstrating how TNF-α downregulates BMAd-derived adiponectin, we reveal a new mechanism by which myeloma cells alter the bone microenvironment to support disease progression. © 2019 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Background: Psychotic symptoms are common in Alzheimer’s disease (AD) and related neurodegenerative disorders and are associated with more rapid disease progression and increased mortality. It is unclear to what degree existing criteria are utilized in clinical research and practice. Objective: To establish research criteria for the diagnosis of psychosis in AD. Methods: The International Society to Advance Alzheimer’s Research and Treatment (ISTAART) Neuropsychiatric Symptoms (NPS) Professional Interest Area (PIA) psychosis subgroup reviewed existing criteria for psychosis in AD and related dementias. Through a series of in person and on-line meetings, a priority checklist was devised to capture features necessary for current research and clinical needs. PubMed, Medline and other relevant databases were searched for relevant criteria. Results: Consensus identified three sets of criteria suitable for review including those of Jeste and Finkel, Lyketsos, and the Diagnostic and Statistical Manual for Mental Disorders, 5th edition. It was concluded that existing criteria could be augmented by including a more specific differentiation between delusions and hallucinations, address overlap with related conditions (agitation in particular), adding the possibility of symptoms emerging in the preclinical and prodromal phases, and building on developing research in disease biomarkers. Conclusion: We propose criteria, developed to improve phenotypic classification of psychosis in AD, and advance the research agenda in the field to improve epidemiological, biomarker, and genetics research in the field. These criteria serve as a complement to the International Psychogeriatric Association criteria for psychosis in neurocognitive disorders.

BACKGROUND: The relationships between the ratios of transfused allogeneic blood products and clinical outcomes in patients with acute intraoperative hemorrhage are poorly defined. METHODS: To better define these ratios, we undertook a single-center, observational cohort study of all surgical patients (≥18 years) who received rapid transfusion defined by a critical administration threshold of 3 or more units of red blood cells (RBCs) intraoperatively within 1 hour between January 1, 2011 and December 31, 2015. Multivariable regression analyses were used to assess relationships between ratios of plasma to RBCs and platelets to RBCs at 3, 12, and 24 hours and clinical outcomes. The primary outcome was hospital mortality, with secondary outcomes of intensive care unit and hospital-free days. RESULTS: The study included 2385 patients, of whom 14.9% had a plasma-to-RBC ratio of 1.0+, and 47.6% had a platelet-to-RBC ratio of 1.0+. Higher plasma-to-RBC and platelet-to-RBC ratios were observed for patients who underwent cardiac, transplant, and vascular surgery and in patients with greater derangements in hemostatic laboratory values. Ratios did not differ by patient age or severity of illness. Higher ratios were not associated with improved clinical outcomes. Mortality differed by platelet-to-RBC but not plasma-to-RBC ratio, with the highest mortality observed with a platelet-to-RBC ratio of 0.1–0.9 at 24 hours (odds ratio, 3.34 [1.62–6.88]) versus no platelets ( P = .001). Higher plasma-to-RBC ratios were associated with decreased hospital-free days, although differences in clinical outcomes were not significant after exclusion of patients receiving only RBCs without component therapies. CONCLUSIONS: Transfusion ratios in surgical patients with critical intraoperative hemorrhage were largely related to surgical and hemostatic features rather than baseline patient characteristics. Higher ratios were not associated with improved outcomes.

Background. The assessment of perioperative risk factors for the development of acute respiratory distress syndrome (ARDS) has been described in various surgical populations. However, there are only limited data among patients undergoing liver transplantation (LT), particularly regarding the influence of intraoperative ventilation parameters. We sought to identify the perioperative risk factors associated with the development of ARDS in LT recipients. Methods. This is a single-center, retrospective cohort study of adult patients who underwent LT at a tertiary academic medical center between January 1, 2006, and January 31, 2016. Postoperative ARDS was identified using the Berlin definition. Multivariable logistic regression analysis was used to identify perioperative risk factors for ARDS. Results. Of 817 eligible patients who underwent an LT during the study period, 20 (2.45%) developed postoperative ARDS. In the preoperative model, ongoing dialysis (odds ratio, 6.41; P < 0.01) was identified as an independent risk factor of ARDS post-LT. A higher mean peak inspiratory pressure per increase of 1 cm H2O (odds ratio, 1.31; P < 0.01) was the only independent risk factor in the intraoperative model. Patients who developed ARDS postoperatively had significantly greater intensive care unit and hospital stay compared to non-ARDS patients (P < 0.001). There were no significant differences in the 30-day (P = 0.16) and 1-year (P = 0.51) mortality between the groups. Conclusions. Dialysis at the time of transplant and elevated intraoperative mean peak inspiratory pressure were associated with the development of ARDS. ARDS post LT was associated with increased intensive care unit and hospital length of stay, but not increased mortality.

Abstract Objective To evaluate the association between hypovitaminosis D and outcomes of symptom severity, mood disorders, fatigue, and quality of life in fibromyalgia (FM) patients. Methods Five hundred ninety-three FM patients were surveyed from May 2012 to November 2013. Patients with serum vitamin D &lt;25 ng/mL were considered to have hypovitaminosis D. The primary outcome was FM symptom severity (FIQ-R questionnaire). Secondary outcomes included quality of life (SF-36), fatigue (MFI-20), anxiety (GAD-7), and depression (PHQ-9). Independent t tests and chi-square tests were performed for continuous and categorical variables, respectively. Regression analysis was performed adjusting for age, gender, body mass index, ethnicity, and season. A post hoc analysis examined for correlation between outcomes and serum vitamin D (ng/mL) as a continuous variable. Results One hundred twenty-two patients (20.6%) had hypovitaminosis D. In our adjusted regression analysis, the total FIQ-R score in patients with hypovitaminosis D was higher compared with control patients with adequate serum vitamin D (57.85 ± 18.09 vs 62.79 ± 18.10, P = 0.04). Adjusted regression analysis revealed higher total GAD-7 (P = 0.01) and higher total PHQ-9 scores (P = 0.04) in patients with hypovitaminosis D compared with control patients. There were no differences based on severity of depression or anxiety. No differences in fatigue or quality of life were identified. Unadjusted post hoc analysis revealed that as serum vitamin D increased, there was an association with lower total FIQ-R (β coefficient = –0.11, P = 0.02) and lower SF-36 subscale scores of role-physical (β coefficient = –0.10, P = 0.03). Adjusted post hoc analysis revealed no significant associations. Conclusions Hypovitaminosis D may be a risk factor for worse symptom severity, anxiety, and depression in FM patients.