Ultrasound-guided percutaneous insertion of Broviac lines in infants less than 5kg: Prospective study of 100 consecutive procedures.

AIM: Ultrasound-guided (USG) percutaneous insertion of Broviac lines (cuffed tunnelled silastic central venous catheters, TCVC) has increasingly been adopted throughout the UK. However, vascular access remains a challenge in small babies and in some units is still performed by open cutdown. Our vascular access team, established in 2004, consists of consultant surgeons, anaesthetists and interventional radiologists, who provide all permanent vascular access by the USG technique. We reviewed the outcome in our last 100 patients less than 5 kg. METHOD: A prospective database of TCVC insertions in patients <5 kg weight recorded age, gestation, weight, diagnosis, type of catheter and complications within 28 days of insertion. A standardised technique of USG insertion is used by all operators. RESULTS: One-hundred patients <5 kg had TCVC inserted between 1/1/2018 and 31/3/2020. Median age 46(range0-316)days, gestation 36.5(23-42)weeks, weight 3(0.66 to 5)kg. INDICATION: parenteral nutrition(75), long term antibiotics(14), cardiac medication(6), chemotherapy(3), other(2). All were tunnelled silicone lines of single 2.7fr(51) and 4.2fr(46) or double lumen 7fr(3). Uncomplicated insertion in 94/100 cases. In 6 patients difficulties were encountered with cannulating the vein. In 4 cases an experienced colleague was called and managed to cannulate the vein; in 1 case a new successful attempt was made on the opposite internal jugular vein, and in 1 the femoral vein was used. No patient required an open cutdown. There were no cases of line sepsis requiring removal but 1 replacement was required for blockage within 28days. CONCLUSION: The USG approach in infants<5 kg is safe and can be used exclusively for venous access even in the most tiny babies. It is, however, a technically challenging procedure therefore we would recommend establishing a consultant delivered vascular access team to provide this service. Open venous cutdown in a tertiary children's hospital is no longer necessary for the insertion of TCVC and should be abandoned altogether. LEVELS OF EVIDENCE: Level I Prognosis Study.

Exomphalos major: Conservative management using Manuka honey dressings and an outreach surgical nursing team.

INTRODUCTION: Controversy exists over the best dressing for conservative management of exomphalos major. Here we describe our experience of using Manuka Honey. METHODS: Our regimen involved covering the sac with Manuka honey (Advancis Medical™) wrapped with gauze and crepe bandage. Initially, dressings were changed 3 times a week and then twice weekly until full epithelialisation. Babies went home after reaching full feeds, with our outreach nurses continuing dressings in clinic until the parents were trained to do them alone. Only patients needing management of co-morbidities were transferred to our unit. Patients would be reviewed by video consultation. Data was prospectively collected. RESULTS: From 2011-2019, 24 consecutive patients (11:13 M:F; median gestation 37 weeks, birth weight 3.1 kg) with exomphalos major were managed with honey dressings. Fourteen babies had significant associated anomalies of which 10 died of problems unrelated to the exomphalos. Time to full feeds 6 (2-58) days; time to discharge 21(7-66) days if no associated anomalies; time to epithelialisation 73 (27-199) days. Dressings were well tolerated. Definitive closure occurred at 17(11-38) months and was uneventful. No patient required fundoplication and all patients were orally fed. Only one patient developed a clinically significant infection. CONCLUSION: This is the largest report of using Manuka honey for the management of exomphalos major. Benefits include early feeding, early discharge and a 'normalisation' of the neonatal period. Key to our success was the surgical outreach service supporting parents doing the dressings, first at the local hospital and then at home.

Synthesis and evaluation of substrate-mimicking cytosolic phospholipase A2 inhibitors--reducing the lipophilicity of the arachidonyl chain isostere.

The high lipophilicity of a series of cytosolic phospholipase A(2) inhibitors has been reduced by the modification of a decyloxyphenyl chain designed to mimic the arachidonyl group of the natural substrate. These changes have resulted in an improvement in the whole cell potency of the inhibitors.

Design and synthesis of a novel and potent series of inhibitors of cytosolic phospholipase A(2) based on a 1,3-disubstituted propan-2-one skeleton.

Using knowledge of the substrate specificity of cPLA(2) (phospholipases A(2)), a novel series of inhibitors of this enzyme were designed based upon a three point model of inhibitor binding to the enzyme active site comprising a lipophilic anchor, an electrophilic serine "trap", and an acidic binding moiety. The resulting 1,3-diheteroatom-substituted propan-2-ones were evaluated as inhibitors of cPLA(2) in both aggregated bilayer and soluble substrate assays. Systematic variation of the lipophilic, electrophilic, and acidic groups revealed a well-defined structure-activity relationship against the enzyme. Optimization of each group led to compound 22 (AR-C70484XX), which contains a decyloxy lipophilic side chain, a 1,3-diaryloxypropan-2-one moiety as a unique serine trap, and a benzoic acid as the acidic binding group. AR-C70484XX was found to be among the most potent in vitro inhibitors of cPLA(2) described to date being more than 20-fold more active against the isolated enzyme (IC(50) = 0.03 microM) than the standard cPLA(2) inhibitor, arachidonyl trifluoromethyl ketone (AACOCF(3)), and also greater than 10-fold more active than AACOCF(3) against the cellular production of arachidonic acid by HL60 cells (IC(50) = 2.8 microM).