Single-session versus two-session placement of chest port and gastrostomy tube in patients with head and neck cancer: Is there any difference in the device-related early infection rates?

BACKGROUND: It is unknown whether placement of a chest port (port) and a gastrostomy tube (G-tube) in a single session increases the risk of the early device infections in patients with head and neck cancer (HNC) undergoing chemoradiation. PURPOSE: To compare the incidence of early (≤30 days) port and G-tube infections placed in a single session compared to two separate sessions in patients with HNC. MATERIAL AND METHODS: Between January 2012 and December 2019, 169 patients with HNC undergoing chemoradiation had a port and a G-tube placed in a single session (single-session group), while 25 had both devices placed in two separate sessions (two-session group) within 30 days of each other. The incidence of early device infections was compared between groups. Logistic regression analysis was conducted to determine if the number of sessions was a variable affecting device infections. RESULTS: A total of 6 (3%) early port infections and 13 (6.7%) early G-tube infections were identified. The two groups did not significantly differ in the incidence of early port infections (3.0%, 5/169 and 4.0%, 1/25, p = 0.59) nor early G-tube infections (7.1%, 12/169 and 4.0%, 1/25, p = 1.0). The number of sessions for device placement was not a variable affecting overall device infections in logistic regression analyses (odds ratio: 1.24, 95% confidence interval: 0.20-7.82, p = 0.82) after controlling for potential confounding variables. CONCLUSIONS: The risk of early device infections in single-session placement appeared to be the same as two-session placement in patients with HNC undergoing chemoradiation.

Copper-binding anticancer peptides from the piscidin family: an expanded mechanism that encompasses physical and chemical bilayer disruption.

In the search for novel broad-spectrum therapeutics to fight chronic infections, inflammation, and cancer, host defense peptides (HDPs) have garnered increasing interest. Characterizing their biologically-active conformations and minimum motifs for function represents a requisite step to developing them into efficacious and safe therapeutics. Here, we demonstrate that metallating HDPs with Cu2+ is an effective chemical strategy to improve their cytotoxicity on cancer cells. Mechanistically, we find that prepared as Cu2+-complexes, the peptides not only physically but also chemically damage lipid membranes. Our testing ground features piscidins 1 and 3 (P1/3), two amphipathic, histidine-rich, membrane-interacting, and cell-penetrating HDPs that are α-helical bound to membranes. To investigate their membrane location, permeabilization effects, and lipid-oxidation capability, we employ neutron reflectometry, impedance spectroscopy, neutron diffraction, and UV spectroscopy. While P1-apo is more potent than P3-apo, metallation boosts their cytotoxicities by up to two- and seven-fold, respectively. Remarkably, P3-Cu2+ is particularly effective at inserting in bilayers, causing water crevices in the hydrocarbon region and placing Cu2+ near the double bonds of the acyl chains, as needed to oxidize them. This study points at a new paradigm where complexing HDPs with Cu2+ to expand their mechanistic reach could be explored to design more potent peptide-based anticancer therapeutics.

Risk Factors for Early Port Infections in Adult Oncologic Patients.

PURPOSE: The purpose of this study was to retrospectively investigate risk factors for chest port (port) infections within 30 days of placement (early port infections) in adult oncologic patients. MATERIALS AND METHODS: This single-institution, three-center retrospective study identified 1,714 patients (868 males, 846 females; median age 60.0 years old) who underwent port placement between January 2013 and August 2017. All patients received an intravenous antibiotic prior to port placement. The median absolute neutrophil count was 5,260 cells/µL, the median white blood cell (WBC) count was 7,700 cells/µL, and the median serum albumin was 4.00 g/dL at the time of port placement. Double-lumen ports were most commonly implanted (74.85%) more frequently in an outpatient setting (72.69%). Risk factors for early port infections were elucidated using univariate and multivariate proportional subdistribution hazard regression analyses. RESULTS: A total of 20 patients (1.2%) had early port infections; 15 patients (0.9%) had positive blood cultures. The mean time to infection was 20 days (range, 9-30 days). The port-related 30-day mortality rate was 0.2% (4 of 1,714 patients). Most bloodstream infections were attributed to Staphylococcus spp. (n = 11). In multivariate analysis, hematologic malignancy (hazard ratio [HR], 2.61; 95% confidence interval (CI), 1.15-5.92.; P = .02), hypoalbuminemia (albumin <3.5 g/dL; HR, 3.52; 95% CI: 1.48-8.36; P = .004), leukopenia (WBC <3,500 cells/µL; HR, 3.00; 95% CI: 1.11-8.09; P = .03), and diabetes mellitus (HR, 3.71; 95% CI: 1.57-8.83) remained statistically significant risk factors for early port infection. CONCLUSIONS: Hematologic malignancy, hypoalbuminemia, leukopenia, and diabetes mellitus at the time of port placement were independent risk factors for early port infections.

Complementary Effects of Host Defense Peptides Piscidin 1 and Piscidin 3 on DNA and Lipid Membranes: Biophysical Insights into Contrasting Biological Activities.

Piscidins were the first antimicrobial peptides discovered in the mast cells of vertebrates. While two family members, piscidin 1 (p1) and piscidin 3 (p3), have highly similar sequences and α-helical structures when bound to model membranes, p1 generally exhibits stronger antimicrobial and hemolytic activity than p3 for reasons that remain elusive. In this study, we combine activity assays and biophysical methods to investigate the mechanisms underlying the cellular function and differing biological potencies of these peptides, and report findings spanning three major facets. First, added to Gram-positive (Bacillus megaterium) and Gram-negative (Escherichia coli) bacteria at sublethal concentrations and imaged by confocal microscopy, both p1 and p3 translocate across cell membranes and colocalize with nucleoids. In E. coli, translocation is accompanied by nonlethal permeabilization that features more pronounced leakage for p1. Second, p1 is also more disruptive than p3 to bacterial model membranes, as quantified by a dye-leakage assay and (2)H solid-state NMR-monitored lipid acyl chain order parameters. Oriented CD studies in the same bilayers show that, beyond a critical peptide concentration, both peptides transition from a surface-bound state to a tilted orientation. Third, gel retardation experiments and CD-monitored titrations on isolated DNA demonstrate that both peptides bind DNA but p3 has stronger condensing effects. Notably, solid-state NMR reveals that the peptides are α-helical when bound to DNA. Overall, these studies identify two polyreactive piscidin isoforms that bind phosphate-containing targets in a poised amphipathic α-helical conformation, disrupt bacterial membranes, and access the intracellular constituents of target cells. Remarkably, the two isoforms have complementary effects; p1 is more membrane active, while p3 has stronger DNA-condensing effects. Subtle differences in their physicochemical properties are highlighted to help explain their contrasting activities.