BACKGROUND.After the occurrence of two cases of bloodstream infection with vancomycin-resistant enterococci (VRE) in our regional neonatal intensive care unit, we studied the epidemiology of VRE and ...applied extensive infection control measures to the unit to control VRE transmission.
METHODS.Infection control measures applied to the unit included weekly surveillance for VRE colonization; education; cohorting of VRE-positive, VRE-negative and VRE-exposed babies with separate personnel and equipment for each group; use of gowns and gloves on room entry; and hand washing before and after each patient contact. Risk factors for VRE colonization were determined with a stepwise logistic regression model.
RESULTS.Thirty-three (40.2%) babies became colonized with VRE. The VRE colonization rate was reduced from 67% to 7% after implementation of infection control measures. Prolonged antimicrobial treatment and low birth weight were significantly associated with an increased risk of VRE colonization.
CONCLUSION.VRE can spread rapidly among newborns in a regional neonatal intensive care unit. Strict infection control measures can reduce the rate of VRE colonization among neonates.
Abstract only
8505
Background: Multi-lineage myelosuppression is an acute toxicity of cytotoxic chemotherapy leading to hematologic adverse events and dose reductions and delays. Current therapies ...are lineage specific and administered after chemotherapy damage.Trilaciclib (T), a highly selective, reversible CDK4/6 inhibitor, is designed to preserve hematopoietic stem and progenitor cells and immune system function during chemotherapy (myelopreservation). We have shown that T mitigates myelosuppression in patients with newly diagnosed extensive-stage small cell lung cancer (ES-SCLC) receiving 1
st
-line chemotherapy. Methods: In this blinded, placebo-controlled, multicenter Phase 2 study, patients with previously treated ES-SCLC were randomized to T (240 mg/m
2
) + 0.75 mg/m
2
topotecan, T (240 mg/m
2
) + 1.5 mg/m
2
topotecan, or placebo (P) + 1.5 mg/m
2
topotecan IV on days 1-5 of 21-day cycles. Patients had access to standard supportive care, except in cycle 1 where prophylactic growth factors were not allowed. Eligible patients had adequate organ function, measurable disease, ECOG PS 0-2, and disease progression during or after prior 1
st
/2
nd
-line chemotherapy. Objectives included safety, tolerability, measures of myelosuppression and tumor efficacy. Results: 91 patients were randomized: 30 patients received T + 0.75 mg/m
2
topotecan, 32 patients received T + 1.5 mg/m
2
topotecan and 28 patients received P + 1.5 mg/m
2
topotecan. In patients receiving 1.5 mg/m
2
topotecan, T treatment reduced occurrence 40.6% (T) vs 75.6% (P), p = 0.016, and duration in cycle 1 2 days (T) vs 8 days (P), p = < 0.0001 of severe neutropenia. T-treated patients had fewer RBC transfusions on/after 5 weeks on study, GCSF administrations, and all-cause dose reductions. Chemotherapy efficacy was comparable in both arms (P and T) treated with 1.5 mg/m
2
topotecan (median PFS (T) 4.2 months vs (P) 4.2 months, HR = 0.83). OS data is immature. Conclusions: T combined with topotecan mitigated chemotherapy-induced myelosuppression and improved tolerability of topotecan vs P. Results suggest the addition of T to cytotoxic chemotherapy for the treatment of ES-SCLC is clinically beneficial. Clinical trial information: NCT02514447.
Interaction of the cell surface integrin receptors with extracellular matrix proteins results in the activation of intracellular signaling pathways, including activation of the p42/p44 ...mitogen-activated protein kinases. The protein tyrosine kinase focal adhesion kinase, or FAK, is linked to integrin signaling and interacts with several molecules involved in signal transduction. Here we report that exposure of fibroblast cells to extracellular matrix proteins activates the p70/p85 ribosomal S6 kinase (S6K) pathway in a ligand dependent manner. Treatment of cells with inhibitors of phosphatidylinositol 3-kinase, or FRAP (FKBP 12/rapamycin-associated protein) blocks integrin-mediated activation of S6K. In contrast to the integrin-directed activation of the mitogen-activated protein kinases, cytochalasin D treatment does not inhibit S6K activation. Treatment with the protein tyrosine kinase inhibitors herbimycin A and genistein completely blocks S6K activation, indicating a requirement for tyrosine kinase activity. Overexpression of the COOH-terminal noncatalytic domain of FAK, FRNK (FAK-related non-kinase) in chick embryo cells results in a significant reduction in the integrin-mediated activation of S6K and a concomitant reduction in FAK tyrosine phosphorylation. These results indicate at least a partial requirement for FAK in the S6K activation pathway.
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8568
Background: Chemotherapy (chemo) has significant clinical utility, however consequent damage to hematopoietic stem and progenitor cells (HSPCs) and the immune system may limit ...activity. If chemo-mediated anti-tumor activity was maximized, while minimizing myelosuppression and immunosuppression, patient outcomes would be improved. Trilaciclib (T) is an intravenous CDK4/6 inhibitor in development to reduce myelosuppression and preserve immune system function during chemo. HSPCs are dependent on CDK4/6 for proliferation. Preclinical data demonstrated that transient T-induced G1 cell cycle arrest renders HSPCs resistant to chemo cytotoxicity, allowing faster hematopoietic recovery, preservation of long-term function, and enhancement of anti-tumor immunity and activity. Methods: Objectives of this ongoing multicenter Phase 1b/2a study are to assess dose limiting toxicities (DLTs), safety, tolerability, hematological profile, PK, and anti-tumor activity of T administered prior to EP. Phase 1b was open-label, dose-finding, and the ongoing Phase 2a is randomized (1:1), double-blind. Eligible pts had confirmed diagnosis of ES-SCLC, adequate organ function, ECOG PS 0-2, no prior chemo, and no symptomatic brain metastases. Results: 19 pts were enrolled in the Phase 1b: 10 pts received T 200 mg/m
2
+ EP and 9 pts received T 240 mg/m
2
+ EP. T + EP was well tolerated. 2 pts at T 200 mg/m
2
and 1 pt at T 240 mg/m
2
experienced asymptomatic DLTs in cycle 1. 2 pts (1 at each dose) had an ANC < 1500 on cycle 2 day 1, delaying the start of cycle 2, and 1 pt at the T 200 mg/m
2
dose had grade 4 thrombocytopenia. There were no cases of febrile neutropenia or bleeding. PK analysis showed no drug interactions between T and EP. 17/19 pts were evaluable: 1 pt had CR, 14 had PR (confirmed ORR = 88%); 1 pt had SD (clinical benefit rate = 94%). Conclusions: In the Phase 1b part of the study, T + EP was well tolerated. Early activity results are promising with a confirmed objective response rate of 88%. This novel approach allowing the administration of chemotherapy while preserving HSPC and immune system function could potentially improve treatment outcomes for SCLC pts. Clinical trial information: NCT02499770.
Heart disease remains a leading cause of mortality worldwide, emphasizing the need for accurate and timely prediction to improve patient outcomes and reduce healthcare burdens. In this research, we ...present a novel approach to predict heart disease utilizing Random Forest with Information Gain Entropy (RF-IGE) as the predictive model. The combination of Random Forest and Information Gain Entropy aims to enhance the accuracy and efficiency of heart disease prediction, catering to the complex and heterogeneous nature of the disease. By leveraging the RF-IGE methodology, we analyze and identify the most informative features crucial for heart disease prediction. The model's robustness is evaluated using comprehensive datasets encompassing diverse patient profiles, ensuring its generalizability and applicability across different populations. The proposed predictive model exhibits promising results, demonstrating a high level of accuracy in distinguishing individuals with heart disease from healthy individuals. This research contributes valuable insights into the utilization of Random Forest and Information Gain Entropy in predicting heart disease, showcasing the potential for improved diagnosis and personalized treatment strategies. The ultimate goal is to develop a reliable and practical predictive tool that aids healthcare professionals in making informed decisions for early detection and optimal management of heart disease, ultimately leading to better patient care and outcomes.
Obstructive nephropathy, the primary cause of renal insufficiency in infants, is characterized by progressive renal apoptosis. Ceramide is a sphingolipid known to stimulate apoptosis in the kidney. ...We investigated the effects of unilateral ureteral obstruction (UUO) on endogenous renal ceramide content and apoptosis in neonatal and adult rats. Animals were subjected to UUO or sham operation on the first day of life and were studied 3-28 days later. Adult rats were similarly treated and then studied 3 or 14 days later. In additional neonatal rats, the obstruction was removed after 5 days, with study at 14 or 28 days. Renal ceramide content was measured by diacylglycerol kinase assay, and apoptosis was determined by the terminal deoxynucleotidyl transferase dUTP nick-end-labeling technique. Renal ceramide content was 50-fold higher in the 3-day neonatal compared with the adult kidney and 10-fold higher in the 7-day neonatal compared with the adult kidney, but there was no additional effect of UUO on ceramide content at these ages. However, after 14 or 28 days UUO in the neonate, renal ceramide was elevated compared with sham or intact opposite kidneys, and renal apoptosis was directly related to ceramide content (r = 0.99, P < 0.001). Moreover, renal ceramide was reduced by relief of obstruction (P < 0.05). There was less apoptosis in the obstructed kidney of the adult than the neonate, and UUO had no effect on ceramide content at 14 days in the adult. We conclude that prolonged UUO (at least 14 days duration) increases endogenous renal ceramide in the neonatal but not the adult rat. It is likely that this contributes to the prolonged renal apoptotic response of the neonatal obstructed kidney.
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