Validation of the CSRFENCE score for prediction of febrile neutropenia during chemotherapy cycles 2-6.

PURPOSE: Though febrile neutropenia (FN) risk prediction models are important in clinical practice, their external validation is limited. In this study, we validated the Cycle-Specific Risk of FEbrile Neutropenia after ChEmotherapy (CSRFENCE) score for predicting FN. METHODS: We reviewed the medical records of patients with solid malignancies and diffuse large B-cell lymphoma during chemotherapy cycles 2-6 and recorded if patients developed FN, defined as absolute neutrophil counts less than 500 cells/microL with fever more than or equal to 38.2 â„ƒ. The CSRFENCE score was determined by adding the risk factors' coefficients described by the original study; subsequently, the score was used to classify chemotherapy cycles into the following risk groups for developing FN: low, intermediate, high, and very high risk. The discriminatory ability of the score was assessed using area under the receiver operating characteristics curve (AUROCC) and incidence rate ratios (IRR) within each CSRFENCE risk group. RESULTS: We analyzed 2870 chemotherapy cycles, of which 42 (1.5%) were associated with FN. Among those, 3 (7.1%), 14 (33.3%), 5 (12%), and 20 (47.6%) were classified as low, intermediate, high, and very high risk for developing FN, respectively. The AUROCC was 0.72 (95% CI 0.64-0.81). Compared with the low risk group (n = 666), the IRR of developing FN was 1.01 (95% CI 0.15-43.37), 0.69 (95% CI 0.08-32.46) and 1.17 (95% CI 0.17-49.49) in the intermediate (n = 1431), high (n = 498) and very high (n = 275) risk groups, respectively. CONCLUSION: The CSRFENCE model can moderately stratify patients into four risk groups for predicting FN prior to chemotherapy cycles 2-6.

Validation of the FENCE Risk Groups for Prediction of Febrile Neutropenia With First-Cycle Chemotherapy.

BACKGROUND: The FEbrile Neutropenia after ChEmotherapy (FENCE) score was developed to estimate the risk of febrile neutropenia (FN) at first cycle of chemotherapy but has not been externally validated. We aimed to validate the FENCE score based on its risk groups in patients treated at a comprehensive cancer center. METHODS: We conducted a retrospective study of treatment-naïve adult patients with solid tumors and diffuse large B-cell lymphoma who received first-cycle chemotherapy between January and November 2019. Patients were followed until the second cycle of chemotherapy to identify any FN events (neutrophil count <0.5 × 109/L with fever ≥38.2°C). The FENCE score was determined and patients classified as low, intermediate, high, and very high risk. The discriminatory ability of classifying patients into FENCE risk groups was calculated as the area under the receiver operating characteristics curve and incidence rate ratios within each FENCE risk group. RESULTS: FN was documented during the first cycle of chemotherapy in 45 of the 918 patients included (5%). The area under the receiver operating characteristics curve was 0.66 (95% confidence interval [CI] = 0.58 to 0.73). Compared with the low-risk group (n = 285), the incidence rate ratio of developing FN was 1.58 (95% CI = 0.54 to 5.21), 3.16 (95% CI = 1.09 to 10.25), and 3.93 (95% CI = 1.46 to 12.27) in the intermediate (n = 293), high (n = 162), and very high (n = 178) risk groups, respectively. CONCLUSIONS: In this study, classifying patients into FENCE risk groups demonstrated moderate discriminatory ability for predicting FN. Further validation in multicenter studies is necessary to determine its generalizability.

PPAR agonists as effective adjuvants for COVID-19 vaccines, by modifying immunogenetics: a review of literature.

BACKGROUND: Several coronavirus vaccine have been fast-tracked to halt the pandemic, the usage of immune adjuvants that can boost immunological memory has come up to the surface. This is particularly of importance in view of the rates of failure of seroconversion and re-infection after COVID-19 infection, which could make the vaccine role and response debatable. Peroxisome proliferator-activated receptors (PPARs) have an established immune-modulatory role, but their effects as adjuvants to vaccination have not been explored to date. It is increasingly recognized that PPAR agonists can upregulate the levels of anti-apoptotic factors such as MCL-1. Such effect can improve the results of vaccination by enhancing the longevity of long-lived plasma cells (LLPCs). The interaction between PPAR agonists and the immune system does not halt here, as T cell memory is also stimulated through enhanced T regulatory cells, antagonizing PD-L1 and switching the metabolism of T cells to fatty acid oxidation, which has a remarkable effect on the persistence of T memory cells. What is even of a more significant value is the effect of PPAR gamma on ensuring a profound secretion of antibodies upon re-exposure to the offending antigen through upregulating lipoxin B4, therefore potentially assisting the vaccine response and deterring re-infection. SHORT CONCLUSION: In view of the above, we suggest the use of PPAR as adjuvants to vaccines in general especially the emerging COVID-19 vaccine due to their role in enhancing immunologic memory through DNA-dependent mechanisms.

Impact of severe oral mucositis in pediatric cancer patients on resource utilization and cancer treatment plans.

BACKGROUND: Oral mucositis is a common chemotherapy-related adverse event that may result in serious complications. Few studies have evaluated mucositis in pediatric patients. OBJECTIVE: To evaluate the impact of severe mucositis on resource utilization and on treatment plans of pediatric cancer patients. SETTING: Comprehensive cancer center in Amman, Jordan. METHOD: Retrospective study on pediatric patients undergoing active cancer treatment with a hospital admission diagnosis of severe oral mucositis (January 2015-December 2019). Patients undergoing bone marrow transplant were excluded. Severe oral mucositis was defined as interfering with oral intake and requiring intravenous opioids. MAIN OUTCOME MEASURE: We reviewed the electronic billing system and patient medical charts to determine the resources utilized during hospitalization, cost, and the impact on subsequent treatment protocols. RESULTS: During the study period, 200 patients were eligible; the average age was 8.6±5.6 years (SD) and 45% had acute lymphoblastic leukemia. The median hospital stay was 6 days (range 2-21) with a total median cost of US$ 2,176 (range 635-13,976) per admission. The median medication cost was US$ 1,075 (range 135-9010), and 85% of the patients received antibiotics during hospitalization, at a median cost of US$ 487 (range 23-2,193). Modification of the chemotherapy treatment protocol was required in 110 patients, which included dose reduction (60%), delay (38%), and discontinuation (2%). CONCLUSION: Severe oral mucositis is associated with significant resource utilization and modification of the treatment protocols. Further studies are needed to identify strategies to reduce the impact of mucositis in this patient population.

Assessment of Vitamin D status in a group of Egyptian children with non alcoholic fatty liver disease (multicenter study).

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the health problems with great burden on the liver that may end with liver cirrhosis and hepatocellular carcinoma. The aim of this work was to assess serum vitamin D level in nonalcoholic fatty liver disease children. METHODS: This cross sectional case control study involved 47 patients with nonalcoholic fatty liver disease selected while recruiting the pediatric hepatology clinics. Their ages ranged from 5-15 years and were compared with 23 healthy age and sex matched children. All involved patients were subjected to careful history taking, clinical examination and for patients and control, anthropometric measures for body mass index (BMI) calculation (plotted on WHO percentile growth charts), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT), bilirubin (total and direct), serum albumin, creatinine, triglycerides, cholesterol, high density lipoprotein (HDL),low density lipoprotein (LDL), fasting blood glucose and fasting insulin (for calculation of insulin resistance), C reactive protein and serum vitamin D all were assayed. NAFLD was detected by ultrasonography and graded as absent, mild, moderate and severe. RESULTS: Ninety-three percent of NAFLD patients were obese. Significant differences were found between patients and control regarding AST, ALT, ALP, GGT, total and direct bilirubin, serum albumin, creatinine, triglycerides, cholesterol, HDL, fasting blood glucose, fasting insulin, the homeostatic model assessment for insulin resistance (HOMA-IR) and serum vitamin D levels. Significant negative correlation was found between serum vitamin D level and grades of steatosis. CONCLUSIONS: Serum vitamin D level decreases in children with NAFLD. This low serum vitamin D level is associated with higher stages of steatosis but not with BMI.