CE: Febrile Neutropenia in the Chemotherapy Patient.

ABSTRACT: Febrile neutropenia is a serious complication of chemotherapy treatment and may present as the only clinical sign of infection. If not addressed in a timely manner, it may progress to multisystem organ failure and may be fatal. Initial assessment of fever in those receiving chemotherapy requires prompt administration of antibiotics, ideally within one hour of presentation. Depending on the clinical status of the patient, antibiotic treatment may occur in the inpatient or outpatient setting. Nurses play an important role in the identification and treatment of patients at high risk for febrile neutropenia through assessment and adherence to clinical practice guidelines. In addition, nurses play an active role in patient education regarding risk factors, protective measures, and signs and symptoms of infection in the immunocompromised oncology patient.

Assessment of Video Capsule Endoscopy in the Management of Acute Gastrointestinal Bleeding During the COVID-19 Pandemic.

Importance: Evaluation of acute gastrointestinal (GI) bleeding using invasive endoscopic procedures comprising the standard of care (SOC)-upper endoscopy and colonoscopy-can expose the endoscopy staff to SARS-CoV-2. Video capsule endoscopy (VCE) does not generate aerosols and only requires 1 person to manage the procedure. Objective: To examine the safety of VCE for the initial evaluation of GI bleeding at the peak of the COVID-19 pandemic to identify signs of active bleeding while minimizing patient and personnel exposure, saving personal protective equipment, and avoiding invasive or unnecessary procedures. Design, Setting, and Participants: A multicenter (UMass Memorial Medical Center and Louisiana State University Health Sciences Center) retrospective cohort study including 146 patients with COVID-19 who received VCE as the first-line diagnostic modality was conducted from March 15 to June 15, 2020, compared with SOC in January 2020 for evaluation of GI bleeding. The association between treatment and outcomes was estimated using multivariable regression adjusting for potential confounders. Propensity score matching was used to verify the results. Main Outcomes and Measures: The primary end point was detection of active bleeding or stigmata of recent bleeding. Secondary end points included the number of patients requiring any invasive procedures, number of additional procedures, rates of rebleeding and rehospitalization, transfusion requirements, and mortality. Results: Among 146 patients, 92 (63.0%) were men; mean (SD) age was 64.93 (14.13) years in the COVID-19 group and 61.33 (13.39) years in the SOC group. Active bleeding or stigmata of recent bleeding was observed in 44 (59.5%) patients in the COVID-19 group compared with 18 (25.0%) in the SOC group (adjusted odds ratio, 5.23; 95% CI, 2.23 to 12.27). Only 36 patients (48.7%) in the COVID-19 group required any invasive procedure during the hospitalization compared with 70 (97.2%) in the SOC group (adjusted odds ratio, 0.01; 95% CI, 0.001 to 0.08). The mean (SD) number of invasive procedures was 0.59 (0.77) per patient in the COVID-19 group compared with 1.18 (0.48) per patient in the SOC group (adjusted difference, -0.54; 95% CI, -0.77 to -0.31). Both approaches appeared to be safe and there was no significant difference in transfusion requirements, rebleeding, rehospitalization, or in-hospital mortality. No mortality was attributed to GI bleeding in either group. Conclusions and Relevance: In this cohort study, first-line diagnostic evaluation of acute GI bleeding using VCE appeared to be a safe and useful alternative to the traditional approach of upper endoscopy and colonoscopy. Use of VCE was associated with increased detection of active bleeding and a reduced number of invasive procedures and unnecessary exposure of personnel to SARS-CoV-2 and use of personal protective equipment.

A randomized controlled trial comparing efficacy of early video capsule endoscopy with standard of care in the approach to nonhematemesis GI bleeding (with videos).

BACKGROUND AND AIMS: Patients presenting with nonhematemesis GI bleeding (NHGIB) represent a diagnostic challenge for physicians. We performed a randomized controlled trial to assess the benefits of deployment of a video capsule soon after admission in the management of patients presenting with melena, hematochezia, or severe anemia compared with standard of care management. METHODS: Patients admitted with NHGIB were randomized and placed into 1 of 2 study groups. In the experimental group, patients ingested a video capsule soon after admission to the hospital. These patients had further endoscopic workup based on the findings from the capsule. Patients in the control group underwent endoscopic evaluation (ie, upper endoscopy, capsule endoscopy, and/or colonoscopy) to identify the source of bleeding as directed by the attending gastroenterologist's interpretation of their clinical presentation. The primary endpoint for this study was the rate of localization of bleeding during hospitalization. RESULTS: Eighty-seven patients were included in this study: 45 randomized to the standard of care arm and 42 to the early capsule arm. A bleeding source was localized in 64.3% of the patients in the early capsule arm and in 31.1% of the patients in the standard of care arm (P < .01). The likelihood of endoscopic localization of bleeding over time was greater for patients receiving early capsule endoscopy compared with those in the standard of care arm (adjusted hazard ratio, 2.77; 95% confidence interval, 1.36-5.64). CONCLUSIONS: For patients admitted to the hospital for NHGIB, early capsule endoscopy is a safe and effective alternative for the detection of the source of bleeding. (Clinical trial registration number: NCT02442830.).

Lower Endoscopic Diagnostic Yields Observed in Non-hematemesis Gastrointestinal Bleeding Patients.

BACKGROUND: Location of bleeding can present a diagnostic challenge in patients without hematemesis more so than those with hematemesis. AIM: To describe endoscopic diagnostic yields in both hematemesis and non-hematemesis gastrointestinal bleeding patient populations. METHODS: A retrospective analysis on a cohort of 343 consecutively identified gastrointestinal bleeding patients admitted to a tertiary care center emergency department with hematemesis and non-hematemesis over a 12-month period. Data obtained included presenting symptoms, diagnostic lesions, procedure types with diagnostic yields, and hours to diagnosis. RESULTS: The hematemesis group (n = 105) took on average 15.6 h to reach a diagnosis versus 30.0 h in the non-hematemesis group (n = 231), (p = 0.005). In the non-hematemesis group, the first procedure was diagnostic only 53% of the time versus 71% in the hematemesis group (p = 0.02). 25% of patients in the non-hematemesis group required multiple procedures versus 10% in the hematemesis group (p = 0.004). Diagnostic yield for a primary esophagogastroduodenoscopy was 71% for the hematemesis group versus 50% for the non-hematemesis group (p = 0.01). Primary colonoscopies were diagnostic in 54% of patients and 12.5% as a secondary procedure in the non-hematemesis group. A primary video capsule endoscopy yielded a diagnosis in 79% of non-hematemesis patients (n = 14) and had a 70% overall diagnostic rate (n = 33). CONCLUSION: Non-hematemesis gastrointestinal bleeding patients undergo multiple non-diagnostic tests and have longer times to diagnosis and then compared those with hematemesis. The high yield of video capsule endoscopy in the non-hematemesis group suggests a role for this device in this context and warrants further investigation.

Multiplex detection of pancreatic cancer biomarkers using a SERS-based immunoassay.

Early diagnosis of pancreatic cancer (PC) is critical to reduce the mortality rate of this disease. Current biological analysis approaches cannot robustly detect several low abundance PC biomarkers in sera, limiting the clinical application of these biomarkers. Enzyme linked immunosorbent assay and radioimmunoassay are two common platforms for detection of biomarkers; however, they suffer from some limitation. This study demonstrates a novel system for multiplex detection of pancreatic biomarkers CA19-9, MMP7 and MUC4 in sera samples with high sensitivity using surface enhanced Raman spectroscopy. Measuring the levels of these biomarkers in PC patients, pancreatitis patients, and healthy individuals reveals the unique expression pattern of these markers in PC patients, suggesting the great potential of using this approach for early diagnostics of PCs.

At the crossroads: EGFR and PTHrP signaling in cancer-mediated diseases of bone.

The epidermal growth factor receptor is a well-established cancer therapeutic target due to its stimulation of proliferation, motility, and resistance to apoptosis. Recently, additional roles for the receptor have been identified in growth of metastases. Similar to development, metastatic spread requires signaling interactions between epithelial-derived tumor cells and mesenchymal derivatives of the microenvironment. This necessitates reactivation of developmental signaling molecules, including the hypercalcemia factor parathyroid hormone-related protein. This review covers the variations of epidermal growth factor receptor signaling in cancers that produce bone metastases, regulation of parathyroid hormone-related protein, and evidence that the two molecules drive cancer-mediated diseases of bone.

Discovery of 4-azaindoles as novel inhibitors of c-Met kinase.

A series of 4-azaindole inhibitors of c-Met kinase is described. The postulated binding mode was confirmed by an X-ray crystal structure and series optimisation was performed on the basis of this structure. Future directions for series development are discussed.

Discovery of a novel series of quinoxalines as inhibitors of c-Met kinase.

A series of quinoxaline inhibitors of c-Met kinase is described. The postulated binding mode was confirmed by an X-ray crystal structure and optimisation of the series was performed on the basis of this structure. Future directions for development of the series are discussed together with the identification of a novel quinoline scaffold.

A vascular endothelial growth factor receptor-2 kinase inhibitor potentiates the activity of the conventional chemotherapeutic agents paclitaxel and doxorubicin in tumor xenograft models.

Inhibition of angiogenesis may have wide use in the treatment of cancer; however, this approach alone will not cause tumor regression but may only slow the growth of solid tumors. The clinical potential of antiangiogenic agents may be increased by combining them with conventional chemotherapeutics. 4-[4-(1-Amino-1-methylethyl)phenyl]-2-[4-(2-morpholin-4-yl-ethyl)phenylamino]pyrimidine-5-carbonitrile (JNJ-17029259) represents a novel structural class of 5-cyanopyrimidines that are orally available, selective, nanomolar inhibitors of the vascular endothelial growth factor receptor-2 (VEGF-R2) and other tyrosine kinases involved in angiogenesis, such as platelet-derived growth factor receptor, fibroblast growth factor receptor, VEGF-R1, and VEGF-R3, but have little activity on other kinase families. At nanomolar levels, JNJ-17029259 blocks VEGF-stimulated mitogen-activated protein kinase signaling, proliferation/migration, and VEGF-R2 phosphorylation in human endothelial cells; inhibits the formation of vascular sprouting in the rat aortic ring model of angiogenesis; and interferes with the development of new veins and arteries in the chorioallantoic membrane assay. At higher concentrations of 1 to 3 microM, this compound shows antiproliferative activity on cells that may contribute to its antitumor effects. JNJ-17029259 delays the growth of a wide range of human tumor xenografts in nude mice when administered orally as single-agent therapy. Histological examination revealed that the tumors have evidence of reduced vascularity after treatment. In addition, JNJ-17029259 enhances the effects of the conventional chemotherapeutic drugs doxorubicin and paclitaxel in xenograft models when administered orally in combination therapy. An orally available angiogenesis inhibitor that can be used in conjunction with standard chemotherapeutic agents to augment their activity may have therapeutic benefit in stopping the progression of cancer and preventing metastasis.