Bard Titanium SlimPort^TM.

Fluoroscopic image of a Bard Titanium SlimPortTM with a 6F single lumen polyurethane catheter in typical location at the distal upper arm.</p

Case characteristics of port pocket infections (PPI) and catheter infections (CI).

Case characteristics of port pocket infections (PPI) and catheter infections (CI).</p

Subgroup analysis of catheter infections (CI).

Group 2.1: CI with matching isolates from blood cultures and the port catheter tip (a). Group 2.2: CI with positive blood culture results and negative culture of the port catheter tip (b). Coagulase-negative staphylococci–CoNS, species–spp.</p

Isolates with distinct susceptibility tests and frequency of strains with acquired resistances in port pocket infections and in catheter infections.

Isolates with distinct susceptibility tests and frequency of strains with acquired resistances in port pocket infections and in catheter infections.</p

Microbiological spectrum of upper arm port associated infections.

Microbiological spectrum of port pocket infections (a, Group 1) and catheter infections (b, Group 2). Coagulase-negative staphylococci–CoNS, species–spp.</p

Case selection flow chart.

ObjectivesInfections are common complications in venous access ports. The presented analysis aimed to investigate the incidence, microbiological spectrum, and acquired resistances of pathogens in upper arm port associated infections to provide a decision aid in the choice of therapy.Materials and methodsIn total, 2667 implantations and 608 explantations were performed at a high-volume tertiary medical center between 2015 and 2019. In cases with infectious complications (n = 131, 4.9%), procedural conditions and results of microbiological testing were reviewed retrospectively.ResultsOf 131 port associated infections (median dwell time 103 days, interquartile range 41–260), 49 (37.4%) were port pocket infections (PPI) and 82 (62.6%) were catheter infections (CI). Infectious complications occurred more often after implantation in inpatients compared to outpatients (P Staphylococcus aureus (S. aureus, 48.3%) and coagulase-negative staphylococci (CoNS, 31.0%). Other gram-positive and gram-negative species were encountered in 13.8% and 6.9%, respectively. CI were caused less frequently by S. aureus (8.6%) than CoNS (39.7%). Other gram-positive and gram-negative strains were isolated in 8.6% and 31.0%, respectively. Candida species were seen in 12.1% of CI. An acquired antibiotic resistance was detected in 36.0% of all significant isolates, occurring especially in CoNS (68.3%) and gram-negative species (24.0%).ConclusionsStaphylococci comprised the largest group of pathogens in upper arm port associated infections. However, gram-negative strains and Candida species should also be considered as a cause of infection in CI. Due to the frequent detection of potential biofilm-forming pathogens, port explantation is an important therapeutic measure, especially in severely ill patients. Acquired resistances must be anticipated when choosing an empiric antibiotic treatment.</div

Case related data of port explantations.

ObjectivesInfections are common complications in venous access ports. The presented analysis aimed to investigate the incidence, microbiological spectrum, and acquired resistances of pathogens in upper arm port associated infections to provide a decision aid in the choice of therapy.Materials and methodsIn total, 2667 implantations and 608 explantations were performed at a high-volume tertiary medical center between 2015 and 2019. In cases with infectious complications (n = 131, 4.9%), procedural conditions and results of microbiological testing were reviewed retrospectively.ResultsOf 131 port associated infections (median dwell time 103 days, interquartile range 41–260), 49 (37.4%) were port pocket infections (PPI) and 82 (62.6%) were catheter infections (CI). Infectious complications occurred more often after implantation in inpatients compared to outpatients (P Staphylococcus aureus (S. aureus, 48.3%) and coagulase-negative staphylococci (CoNS, 31.0%). Other gram-positive and gram-negative species were encountered in 13.8% and 6.9%, respectively. CI were caused less frequently by S. aureus (8.6%) than CoNS (39.7%). Other gram-positive and gram-negative strains were isolated in 8.6% and 31.0%, respectively. Candida species were seen in 12.1% of CI. An acquired antibiotic resistance was detected in 36.0% of all significant isolates, occurring especially in CoNS (68.3%) and gram-negative species (24.0%).ConclusionsStaphylococci comprised the largest group of pathogens in upper arm port associated infections. However, gram-negative strains and Candida species should also be considered as a cause of infection in CI. Due to the frequent detection of potential biofilm-forming pathogens, port explantation is an important therapeutic measure, especially in severely ill patients. Acquired resistances must be anticipated when choosing an empiric antibiotic treatment.</div

Case characteristics of all upper arm port explantations and explantations due to infectious complications.

Case characteristics of all upper arm port explantations and explantations due to infectious complications.</p

DataSheet1.DOCX

<p>The mammalian Diaphanous-related (mDia) formins are cytoskeletal regulators that assemble and, in some cases, bundle filamentous actin (F-actin), as well as stabilize microtubules. The development of small molecule antagonists and agonists that interrogate mDia formin function has allowed us to investigate the roles of formins in disease states. A small molecule inhibitor of FH2 domain (SMIFH2) inhibits mDia-dependent actin dynamics and abrogates tumor cell migration and cell division in vitro and ex vivo tissue explants. mDia formin activation with small molecule intramimics IMM01/02 and mDia2-DAD peptides inhibited glioblastoma motility and invasion in vitro and ex vivo rat brain slices. However, SMIFH2, IMMs, and mDia2 DAD efficacy in vivo remains largely unexplored and potential toxicity across a range of developmental phenotypes has not been thoroughly characterized. In this study, we performed an in vivo screen of early life-stage toxicity in Danio rerio zebrafish embryos 2 days post-fertilization (dpf) in response to SMIFH2, IMM01/02, and mDia2 DAD. SMIFH2 at concentrations ≥5–10 μM induced significant defects in developing zebrafish, including shorter body lengths, tail curvature and defective tail cellularity, craniofacial malformations, pericardial edema, absent and/or compromised vasculature function and flow, depressed heart rates and increased mortality. Conversely, IMM and mDia2 DAD peptides were minimally toxic at concentrations up to 10–20 and 50 μM, respectively. SMIFH2's therapeutic potential may therefore be limited by its substantial in vivo toxicity at functional concentrations. mDia formin agonism with IMMs and mDia2 DADs may therefore be a more effective and less toxic anti-invasive therapeutic approach.</p

Video2.MOV

<p>The mammalian Diaphanous-related (mDia) formins are cytoskeletal regulators that assemble and, in some cases, bundle filamentous actin (F-actin), as well as stabilize microtubules. The development of small molecule antagonists and agonists that interrogate mDia formin function has allowed us to investigate the roles of formins in disease states. A small molecule inhibitor of FH2 domain (SMIFH2) inhibits mDia-dependent actin dynamics and abrogates tumor cell migration and cell division in vitro and ex vivo tissue explants. mDia formin activation with small molecule intramimics IMM01/02 and mDia2-DAD peptides inhibited glioblastoma motility and invasion in vitro and ex vivo rat brain slices. However, SMIFH2, IMMs, and mDia2 DAD efficacy in vivo remains largely unexplored and potential toxicity across a range of developmental phenotypes has not been thoroughly characterized. In this study, we performed an in vivo screen of early life-stage toxicity in Danio rerio zebrafish embryos 2 days post-fertilization (dpf) in response to SMIFH2, IMM01/02, and mDia2 DAD. SMIFH2 at concentrations ≥5–10 μM induced significant defects in developing zebrafish, including shorter body lengths, tail curvature and defective tail cellularity, craniofacial malformations, pericardial edema, absent and/or compromised vasculature function and flow, depressed heart rates and increased mortality. Conversely, IMM and mDia2 DAD peptides were minimally toxic at concentrations up to 10–20 and 50 μM, respectively. SMIFH2's therapeutic potential may therefore be limited by its substantial in vivo toxicity at functional concentrations. mDia formin agonism with IMMs and mDia2 DADs may therefore be a more effective and less toxic anti-invasive therapeutic approach.</p