Triage and Prognostication of Cancer Patients Admitted to the Intensive Care Unit.

Cancer remains a leading cause of morbidity and mortality. Advances in cancer screening, early detection, targeted therapies, and supportive care have led to improvements in outcomes and quality of life. The rapid increase in novel cancer therapies can cause life-threatening adverse events. The need for intensive care unit (ICU) care is projected to increase. Until 2 decades ago, cancer diagnosis often precluded ICU admission. Recently, substantial cancer survival has been achieved; therefore, ICU denial is not recommended. ICU resources are limited and expensive; hence, appropriate utilization is needed. This review focuses on triage and prognosis in critically ill cancer patients requiring ICU admission.

Tricuspid annular plane systolic excursion is a predictor of mortality for septic shock.

BACKGROUND: Cardiac dysfunction is a common sequela in patients with sepsis and multi-organ dysfunction. Echocardiography is commonly used in the investigation of circulatory failure. AIMS: We aimed to evaluate the prognostic value of echocardiographic parameters in patients with septic shock. METHODS: This study was a retrospective trial. We included patients who were admitted to intensive care unit (ICU) with septic shock. The patients' echocardiograms, clinical data and outcomes were obtained from their medical records. Associations between echocardiogram variables and mortality were assessed using logistic regression, controlled for age, sex, body mass index and the interval between the ICU admission and echocardiogram. The utility of statistically significant echocardiogram variables to predict mortality were assessed using receiver operating characteristic (ROC) curves. RESULTS: The outcomes presented that tricuspid annular plane systolic excursion (TAPSE) was statistically significantly associated with both ICU (P = 0.02) and 90-day (P = 0.001) mortality. From the ROC curves, TAPSE emerged a significant and moderate predictor for 90-day (area under curve (AUC) = 0.69, 95% CI = 0.565-0.814) and in-ICU mortality (AUC = 0.762, 95% CI = 0.652-0.871). The optimal cut-off for TAPSE was 2.1 cm for both 90-day mortality (sensitivity of 80% and specificity and 58%) and in-ICU mortality (sensitivity of 69% and specificity of 77%). CONCLUSIONS: TAPSE was associated with increased mortality in those with sepsis and suspicion of cardiac dysfunction. This is a hypothesis generating article that an association may be present and requires significant more work with expansion to the entire population base.

Critical Care Admission of an HIV Patient with Diabetic Ketoacidosis Secondary to Pembrolizumab.

BACKGROUND: Pembrolizumab is a checkpoint inhibitor that targets the programmed cell death-1 receptor (PD-1) and has shown to be effective against several malignancies, including lung cancer. However, life-threatening immune-related adverse events can result from these immunotherapy treatments. Case presentation. A 62-year-old man with HIV, metastatic adenocarcinoma of the lung, and no previous history of diabetes presented to the emergency department with new-onset nausea, vomiting, and generalized weakness. Glucose was 1191 mg/dl, hemoglobin A1c 11%, and potassium 6.9 mEq/L. He had metabolic acidosis with a lactate of 6.6 mmol/L and anion gap of 38 mEq/L, and ketones were detected on the urinalysis. Severe diabetic ketoacidosis was diagnosed, and the patient was admitted to the intensive care unit. Additional investigations showed low C-peptide and negative anti-glutamic acid decarboxylase antibody, anti-insulin antibody, and anti-islet-antigen 2Ab antibody. After ruling out other possible etiologies, pembrolizumab was considered to be the cause of the diabetes and ketoacidosis. CONCLUSIONS: Life-threatening adverse drug events associated with checkpoint inhibitors such as pembrolizumab are on the rise. We recommend to closely follow and monitor patients receiving these immunotherapies. This strategy could lead to early detection and prevention, as well as reduction of more serious life-threatening complications requiring intensive care.

Vascular ligand-receptor mapping by direct combinatorial selection in cancer patients.

Molecules differentially expressed in blood vessels among organs or between damaged and normal tissues, are attractive therapy targets; however, their identification within the human vasculature is challenging. Here we screened a peptide library in cancer patients to uncover ligand-receptors common or specific to certain vascular beds. Surveying ~2.35 x 10(6) motifs recovered from biopsies yielded a nonrandom distribution, indicating that systemic tissue targeting is feasible. High-throughput analysis by similarity search, protein arrays, and affinity chromatography revealed four native ligand-receptors, three of which were previously unrecognized. Two are shared among multiple tissues (integrin α4/annexin A4 and cathepsin B/apolipoprotein E3) and the other two have a restricted and specific distribution in normal tissue (prohibitin/annexin A2 in white adipose tissue) or cancer (RAGE/leukocyte proteinase-3 in bone metastases). These findings provide vascular molecular markers for biotechnology and medical applications.

Next-generation phage display: integrating and comparing available molecular tools to enable cost-effective high-throughput analysis.

BACKGROUND: Combinatorial phage display has been used in the last 20 years in the identification of protein-ligands and protein-protein interactions, uncovering relevant molecular recognition events. Rate-limiting steps of combinatorial phage display library selection are (i) the counting of transducing units and (ii) the sequencing of the encoded displayed ligands. Here, we adapted emerging genomic technologies to minimize such challenges. METHODOLOGY/PRINCIPAL FINDINGS: We gained efficiency by applying in tandem real-time PCR for rapid quantification to enable bacteria-free phage display library screening, and added phage DNA next-generation sequencing for large-scale ligand analysis, reporting a fully integrated set of high-throughput quantitative and analytical tools. The approach is far less labor-intensive and allows rigorous quantification; for medical applications, including selections in patients, it also represents an advance for quantitative distribution analysis and ligand identification of hundreds of thousands of targeted particles from patient-derived biopsy or autopsy in a longer timeframe post library administration. Additional advantages over current methods include increased sensitivity, less variability, enhanced linearity, scalability, and accuracy at much lower cost. Sequences obtained by qPhage plus pyrosequencing were similar to a dataset produced from conventional Sanger-sequenced transducing-units (TU), with no biases due to GC content, codon usage, and amino acid or peptide frequency. These tools allow phage display selection and ligand analysis at >1,000-fold faster rate, and reduce costs approximately 250-fold for generating 10(6) ligand sequences. CONCLUSIONS/SIGNIFICANCE: Our analyses demonstrates that whereas this approach correlates with the traditional colony-counting, it is also capable of a much larger sampling, allowing a faster, less expensive, more accurate and consistent analysis of phage enrichment. Overall, qPhage plus pyrosequencing is superior to TU-counting plus Sanger sequencing and is proposed as the method of choice over a broad range of phage display applications in vitro, in cells, and in vivo.

Economic evaluation in critical care: a focus on severe sepsis in oncology.

Hospital care, physician and clinical services, and prescription drugs continue to drive healthcare expenditures across healthcare systems and nations. The critical-care setting, owing to the complexity and intensity of care, is a high user of the resources that drive healthcare spending. Information regarding the cost and effectiveness of critical-care therapies is necessary to properly guide care and policies for this unique population. Many challenges exist for conducting and comparing economic evaluation in critical care. Recently, recommendations on cost and cost-effectiveness analysis in critical care have been developed that will guide future research. A focus area, severe sepsis in oncology, is reviewed to highlight the challenges and opportunities of economic evaluation in this setting.

Steps toward mapping the human vasculature by phage display.

The molecular diversity of receptors in human blood vessels remains largely unexplored. We developed a selection method in which peptides that home to specific vascular beds are identified after administration of a peptide library. Here we report the first in vivo screening of a peptide library in a patient. We surveyed 47,160 motifs that localized to different organs. This large-scale screening indicates that the tissue distribution of circulating peptides is nonrandom. High-throughput analysis of the motifs revealed similarities to ligands for differentially expressed cell-surface proteins, and a candidate ligand-receptor pair was validated. These data represent a step toward the construction of a molecular map of human vasculature and may have broad implications for the development of targeted therapies.