Inferior Vena Cava Reconstruction in Symptomatic Patients Using Palmaz Stents: A Retrospective Single-Center Experience.

BACKGROUND: The use of stents for treating central venous occlusion is well described. Limited evidence exists related to Palmaz balloon-expandable stent use in inferior vena cava (IVC) reconstruction. We analyzed patency and complication rates after IVC reconstruction using Palmaz stents. METHODS: From 2002 to 2019, 37 patients (mean age: 51 year) underwent IVC reconstruction with 68 Palmaz stents. Indications were symptomatic chronic venous obstruction in the infrarenal (n = 25) and intrahepatic (n = 12) IVC. Demographic, operative, and imaging data were evaluated. Clinical data, abdominal CT, and/or duplex ultrasound were used to determine patency at follow-up. RESULTS: Restoration of caval patency was achieved in all patients, with complications in 2/37 (5.4%) patients (thrombus formation within the stent; stent embolization eight days after placement). Follow-up data were available for 27 patients. Primary patency was maintained through last follow-up in 19/27 (70%) patients (mean: 1.1 year), with successful stent redilation performed in 6 patients. Mean duration of primary-assisted patency (n = 5) was 1.2 year. Late lumen loss was (n = 13) was 40% during a mean time to follow-up of 2.0 years. Primary patency in patients with occlusion secondary to malignancy was 109 day (range: 1 day-1.0 year), whereas primary patency in patients with occlusion from other etiologies was 1.1 year (range: 2 day-5.9 year). The Kaplan-Meier analysis demonstrated primary and primary-assisted patency of 66% and 84%, respectively, at 24 and 48 months. CONCLUSIONS: Palmaz balloon-expandable stents for IVC reconstruction is feasible and effective for symptomatic IVC occlusion. Risk of stent migration was low.

Complication rates of percutaneous biliary drainage in the presence of ascites.

BACKGROUND: Ascites is a relative contraindication to percutaneous biliary drainage (PBD), but patients with biliary obstruction presenting with ascites may still undergo PBD insertion. We hypothesized that ascites increases the major complication rate of PBD. MATERIALS: PBDs placed between January 2005 and August 2016 were identified (n = 491). Etiology and location of obstruction, the presence, and distribution of ascites based on abdominal imaging within 2 weeks of PBD, INR, WBCE, and peri-procedural complications were reviewed in the EMR. RESULTS: A total of 491 PBD were placed during the study period of which 26.2% had ascites (n = 129), and 73.7% did not have ascites (n = 362). Ascites was categorized as perihepatic in 41 patients (32%), diffuse in 82 patients (64%), and non-perihepatic in 6 patients (4%). Overall, a significantly higher rate of major complications occurred in patients with ascites (19%) compared to that in patients without ascites (7.7%, P = 0.0004). Diffuse ascites was associated with a significantly higher major complication rate (26%) when compared to perihepatic ascites (7.3%, P = 0.014). In ascites patients, no association between the etiology of biliary obstruction or laterality of the PBD and the rate of major complications was identified. CONCLUSIONS: The major complication rate in patients with ascites not only exceeds SIR suggested threshold of 10% but is also significantly higher than that patients without ascites. The distribution of ascites had a significant effect on complication rate, with diffuse ascites being associated with increased major complication rates compared to those with perihepatic. These findings suggest careful consideration of patients for PBD with ascites, particularly diffuse ascites.

Injectable thermogelling chitosan for the local delivery of bone morphogenetic protein.

The aim of the present study was to evaluate the in vivo biocompatibility of injectable thermo gelling chitosan-ammonium hydrogen phosphate solution (chitosan-AHP) and its efficacy to deliver recombinant human bone morphogenetic protein-2 (rhBMP-2) in a bioactive form. The thermogel showed a typical foreign body response upon subcutaneous implantation surrounded by a fibrous capsule. Even at 4 and 8 weeks post implantation, significant neutrophil infiltration was observed within the gel. Chitosan-AHP gel retained most of the loaded rhBMP-2 after a small initial release. The bioactivity of the released protein was demonstrated in vitro by the increase in alkaline phosphatase activity of mouse pre osteoblast cells (MC3T3-E1). Histological and micro-computed tomography (µCT) evaluation showed evidence of ectopic bone formation upon 4 µg/mL rhBMP-2 loaded chitosan-AHP injection. The study demonstrated a neutrophil mediated local tissue response to chitosan-AHP gel and its ability to encapsulate and maintain the bioactivity of rhBMP-2.

Curcumin-loaded poly(epsilon-caprolactone) nanofibres: diabetic wound dressing with anti-oxidant and anti-inflammatory properties.

1. Curcumin is a naturally occurring poly-phenolic compound with a broad range of favourable biological functions, including anti-cancer, anti-oxidant and anti-inflammatory activities. The low bioavailability and in vivo stability of curcumin require the development of suitable carrier vehicles to deliver the molecule in a sustained manner at therapeutic levels. 2. In the present study, we investigated the feasibility and potential of poly(caprolactone) (PCL) nanofibres as a delivery vehicle for curcumin for wound healing applications. By optimizing the electrospinning parameters, bead-free curcumin-loaded PCL nanofibres were developed. 3. The fibres showed sustained release of curcumin for 72 h and could be made to deliver a dose much lower than the reported cytotoxic concentration while remaining bioactive. Human foreskin fibroblast cells (HFF-1) showed more than 70% viability on curcumin-loaded nanofibres. 4. The anti-oxidant activity of curcumin-loaded nanofibres was demonstrated using an oxygen radical absorbance capacity (ORAC) assay and by the ability of the fibres to maintain the viability of HFF-1 cells under conditions of oxidative stress. 5. The curcumin-loaded nanofibres also reduced inflammatory induction, as evidenced by low levels of interleukin-6 release from mouse monocyte-macrophages seeded onto the fibres following stimulation by Escherichia coli-derived lipopolysaccharide. 6. The in vivo wound healing capability of the curcumin loaded PCL nanofibres was demonstrated by an increased rate of wound closure in a streptozotocin-induced diabetic mice model. 7. These results demonstrate that the curcumin-loaded PCL nanofibre matrix is bioactive and has potential as a wound dressing with anti-oxidant and anti-inflammatory properties.

Activity screening of carrier domains within nonribosomal peptide synthetases using complex substrate mixtures and large molecule mass spectrometry.

For screening a pool of potential substrates that load carrier domains found in nonribosomal peptide synthetases, large molecule mass spectrometry is shown to be a new, unbiased assay. Combining the high resolving power of Fourier transform mass spectrometry with the ability of adenylation domains to select their own substrates, the mass change that takes place upon formation of a covalent intermediate thus identifies the substrate. This assay has an advantage over traditional radiochemical assays in that many substrates, the substrate pool, can be screened simultaneously. Using proteins on the nikkomycin, clorobiocin, coumermycin A1, yersiniabactin, pyochelin, and enterobactin biosynthetic pathways as proof of principle, preferred substrates are readily identified from substrate pools. Furthermore, this assay can be used to provide insight into the timing of tailoring events of biosynthetic pathways as demonstrated using the bromination reaction found on the jamaicamide biosynthetic pathway. Finally, this assay can provide insight into the role and function of orphan gene clusters for which the encoded natural product is unknown. This is demonstrated by identifying the substrates for two NRPS modules from the pksN and pksJ genes that are found on an orphan NRPS/PKS hybrid cluster from Bacillus subtilis. This new assay format is especially timely for activity screening in an era when new types of thiotemplate assembly lines that defy classification are being discovered at an accelerating rate.