Human Amniotic Epithelial Cell Transplantation is Safe and Well Tolerated in Patients with Compensated Cirrhosis: A First-in-Human Trial.

Placenta-derived human amniotic epithelial cells (hAEC) exhibit anti-inflammatory and anti-fibrotic effects in cirrhosis models. We conducted a first-in-human phase I clinical trial to assess the safety and tolerability of hAEC in adults with compensated cirrhosis. We examined increasing and repeated doses of hAEC in 9 patients in 3 cohorts. Cohort 1 patients received 0.5 × 106/kg hAEC in one IV infusion. Cohort 2 patients received 1 × 106/kg hAEC in one IV infusion. The patients in cohort 3 received 1 × 106/kg hAEC on days 0 and 28. Here, we report follow-up to post-infusion day 56 (D56), during which no serious adverse events occurred. Six patients experienced no study-related adverse events, while 3 patients reported mild (grade 1) headaches that were possibly infusion-related. A transient decrease in serum platelet count occurred in all patients, which returned to baseline screening values by day 5. FIB-4 values to assess fibrosis were significantly lower at D56. Although not statistically significant, serum AST levels and liver stiffness measurements at D56 were lower than those at baseline. The hepatic venous pressure gradient, a measure of portal hypertension, declined in 4 patients, did not change in 3 patients, and increased in 2 patients. In conclusion, intravenous infusion of allogeneic hAEC in patients with compensated cirrhosis at the doses used in this study was safe and well tolerated, with no difference observed between 1 and 2 doses. Decreased hepatic inflammation, liver stiffness, and portal hypertension support larger studies aimed at identifying patients who may benefit from this therapy. Clinical Trial registration: The trial was prospectively entered on the Australian Clinical Trials Registry (ANZCTR12616000437460).

Functional recovery from refractory hepatic encephalopathy following angiographic obliteration of a large, spontaneous portal-umbilical portosystemic shunt: a case report.

BACKGROUND: Hepatic encephalopathy (HE) as a consequence of cirrhosis with portal hypertension has a profound impact on quality of life for both patients and caregivers, has no gold-standard diagnostic test, and is a risk factor for mortality. Spontaneous portosystemic shunts (SPSS) are common in patients with cirrhosis, can be challenging to identify, and in some cases, can drive refractory HE. Cross-sectional shunt size greater than 83mm2 is associated with liver disease severity, overt HE, and mortality. CASE PRESENTATION: We report a patient with refractory HE and frequent hospitalization in the context of an occult spontaneous portal-umbilical portosystemic shunt with an estimated cross-sectional area of 809mm2. Following identification and angiographic retrograde transvenous obliteration of the SPSS using plugs, coils and sclerosant, there was improvement in neurocognitive testing and no further hospitalization for HE. CONCLUSION: SPSS in the context of cirrhosis with portal hypertension can contribute to the debilitating effects of refractory HE. This case highlights the opportunity to search for SPSS in patients with HE unresponsive to therapy as angiographic obliteration is usually safe, well-tolerated, and clinically effective.

Refractory portal hypertension complications successfully managed by parallel transjugular intrahepatic portosystemic shunt (TIPS): a case report.

BACKGROUND: Transjugular intrahepatic portosystemic shunt (TIPS) is an established intervention to treat complicated portal hypertension refractory to medical or endoscopic management. TIPS dysfunction results in the recurrence of portal hypertension symptoms. In cases of TIPS dysfunction or persistent portal hypertension despite a patent primary TIPS, the creation of parallel TIPS may be the only intervention to effectively reduce portal pressure. Since the introduction of dedicated TIPS stents (Viatorr®) the incidence of TIPS dysfunction has reduced profoundly. Nevertheless, the creation of a parallel TIPS can still be necessary in the current dedicated TIPS stent era. CASE PRESENTATION: We report one such patient who experienced ongoing portal hypertension induced upper gastro-intestinal haemorrhage despite multiple TIPS revisions and a patent primary TIPS. CONCLUSION: Following creation of a parallel TIPS, the patient remains in clinical remission with no further bleeding.

Molecular origins of Epoxy-Amine/Iron oxide interphase formation.

HYPOTHESIS: Interphase properties in composites, adhesives and protective coatings can be predicted on the basis of interfacial interactions between polymeric precursor molecules and the inorganic surface during network formation. The strength of molecular interactions is expected to determine local segmental mobility (polymer glass transition temperature, Tg) and cure degree. EXPERIMENTS: Conventional analysis techniques and atomic force microscopy coupled with infrared (AFM-IR) are applied to nanocomposite specimens to precisely characterise the epoxy-amine/iron oxide interphase, whilst molecular dynamics simulations are applied to identify the molecular interactions underpinning its formation. FINDINGS: Attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy and high-resolution AFM-IR mapping confirm the presence of nanoscale under-cured interphase regions. Interfacial segregation of the molecular triethylenetetraamine (TETA) cross-linker results in an excess of epoxy functionality near synthetic hematite, (Fe2O3) magnetite (Fe3O4) and goethite (Fe(O)OH) particle surfaces. This occurs independently of the variable surface binding energies, as a result of entropic segregation during the cure. Thermal analysis and molecular dynamics simulations demonstrate that restricted segmental motion is imparted by strong interfacial binding between surface Fe sites in goethite, where the position of surface hydroxyl protons enables synergistic hydrogen bonding and electrostatic binding to Fe atoms at specific sites. This provides a strong driving force for molecular orientation resulting in significantly raised Tg values for the goethite composite samples.

Reflectance in AFM-IR: Implications for Interpretation and Remote Analysis of the Buried Interface.

AFM-IR combines the chemical sensitivity of infrared spectroscopy with the lateral resolution of scanning probe microscopy, allowing nanoscale chemical analysis of almost any organic material under ambient conditions. As a result, this versatile technique is rapidly gaining popularity among materials scientists. Here, we report a previously overlooked source of data and artifacts in AFM-IR analysis; reflection from the buried interface. Periodic arrays of gold on glass are used to show that the overall signal in AFM-IR is affected by the wavelength-dependent reflectivity and thermal response of the underlying substrate. Excitingly, this demonstrates that remote analysis of heterogeneities at the buried interface is possible alongside that of an overlying organic film. On the other hand, AFM-IR users should carefully consider the composition and topography of underlying substrates when interpreting nanoscale infrared data. The common practice of generating ratio images, or indeed the normalization of AFM-IR spectra, should be approached with caution in the presence of substrate heterogeneity or variable sample thickness.

Multi-modal plasma focused ion beam serial section tomography of an organic paint coating.

Pigment distributions have a critical role in the corrosion protection properties of organic paint coatings, but they are difficult to image in 3D over statistically significant volumes and at sufficiently high spatial resolutions required for detailed analysis. Here we report, for the first time, large volume analytical serial sectioning tomography of an organic composite coating using a xenon Plasma Focused Ion Beam (PFIB) combined with secondary electron imaging, energy dispersive X-ray (EDX) spectrum imaging (SI) and electron backscattered diffraction (EBSD). Together these techniques provide a comprehensive quantitative description of the physical orientation and distribution of the pigments within a model marine ballast tank coating, as well as their crystallographic and elemental characterisation. Polymers and organic materials are challenging because of their propensity for ion beam damage and possible beam heating effects. Our novel, optimised block preparation technique permits automated data acquisition with minimal operator intervention, and can have significant applications for the structural and chemical characterisation of a wide range of organic materials. Our results revealed that the paint contained 7.5 vol% aluminium flakes and 25 vol% quartz particles. The aluminium flakes were oriented parallel to the substrate surface, which is beneficial in terms of the corrosion protection capability of the coating.

The Unexpected Role of Carbonate Impurities in Polyphosphate Corrosion Inhibition.

Polyphosphate corrosion inhibitors are increasingly marketed as chromate replacements for coil coated steel. The mechanisms underpinning corrosion prevention by these species is, however, not fully understood; corrosion inhibition is ordinarily assessed using electrochemical techniques, followed by ex-situ surface analysis. As a result, the formation of a clear film over cathodic sites is known to contribute to corrosion prevention, but little is known about its formation. Here, we apply advanced microscopy techniques (in-situ fluid cell AFM, SEM-EDX, and AFM-IR nano-chemical analysis) to examine early cathodic film formation by strontium aluminium polyphosphate (SAPP) in detail. For a model cut edge system, it is found that cathodic inhibition dominates during the first 24 hours of immersion, and surprisingly, that strontium carbonate impurities play a significant role. Rapidly precipitated zinc carbonate provides protection almost immediately after immersion, before the film structure evolves to include (poly)phosphate species. This suggests that the purposeful inclusion of carbonates may provide a new, environmentally sound approach to enhancing inhibitor efficacy.

Insights into Epoxy Network Nanostructural Heterogeneity Using AFM-IR.

The first direct observation of a chemically heterogeneous nanostructure within an epoxy resin is reported. Epoxy resins comprise the matrix component of many high performance composites, coatings and adhesives, yet the molecular network structure that underpins the performance of these industrially essential materials is not well understood. Internal nodular morphologies have repeatedly been reported for epoxy resins analyzed using SEM or AFM, yet the origin of these features remains a contentious subject, and epoxies are still commonly assumed to be chemically homogeneous. Uniquely, in this contribution we use the recently developed AFM-IR technique to eliminate previous differences in interpretation, and establish that nodule features correspond to heterogeneous network connectivity within an epoxy phenolic formulation.

The corrosion protection of AA2024-T3 aluminium alloy by leaching of lithium-containing salts from organic coatings.

Lithium carbonate and lithium oxalate were incorporated as leachable corrosion inhibitors in model organic coatings for the protection of AA2024-T3. The coated samples were artificially damaged with a scribe. It was found that the lithium-salts are able to leach from the organic coating and form a protective layer in the scribe on AA2024-T3 under neutral salt spray conditions. The present paper shows the first observation and analysis of these corrosion protective layers, generated from lithium-salt loaded organic coatings. The scribed areas were examined by scanning and transmission electron microscopy before and after neutral salt spray exposure (ASTM-B117). The protective layers typically consist of three different layered regions, including a relatively dense layer near the alloy substrate, a porous middle layer and a flake-shaped outer layer, with lithium uniformly distributed throughout all three layers. Scanning electron microscopy and white light interferometry surface roughness measurements demonstrate that the formation of the layer occurs rapidly and, therefore provides an effective inhibition mechanism. Based on the observation of this work, a mechanism is proposed for the formation of these protective layers.

Managing central venous obstruction in cystic fibrosis recipients--lung transplant considerations.

BACKGROUND: The superior vena cava (SVC) syndrome in cystic fibrosis (CF) patients is rare, but presents unique challenges in the peri-transplant period. We reviewed our experience of SVC syndrome in CF recipients undergoing lung transplantation. METHODS: This is a retrospective case series from a single center chart-review. SVC obstruction is defined by clinically significant stenosis or obstruction of the SVC as detected by contrast studies. RESULTS: We identified SVC obstruction in seven post-transplant cases and one pre-transplant case. All eight patients had previous or current history of indwelling central venous catheters. Three recipients experienced operative complications. Five of the seven recipients suffered at least one episode of post-operative SVC obstruction or bleeding despite prophylactic anticoagulation. At a median follow-up of 29 months, six of the seven patients transplanted are well. CONCLUSIONS: Strategies are available to minimize the risks of intra/peri-operative acute life-threatening SVC obstruction in CF patients.

A randomized, double-blind, placebo-controlled study of preemptive oral oxycodone with morphine patient-controlled anesthesia for postoperative pain management in patients undergoing uterine artery embolization for symptomatic uterine fibroids.

PURPOSE: To evaluate the analgesic efficacy of oral premedication of oxycodone in a group of patients undergoing elective uterine artery embolization under sedation for fibroid disease. METHODS: Thirty-nine patients (mean age 42.3 years) were prospectively randomized 1:1 to receive 20 mg oxycodone or placebo orally immediately before their procedure. At the commencement of the procedure, patients were provided with a patient-controlled analgesia device for 24 h, programmed to deliver 1 mg boluses of intravenous morphine with a 5 min lockout. Mean visual analog scale pain intensity ratings (0-100 mm) were measured from both groups and evaluated over 0 to 6 h as the primary end point. Other measured parameters included opioid-related side effects and eligibility for discharge (NCT00163930; September 12, 2005). RESULTS: Early pain intensity did not vary significantly between the active and placebo groups [mean (standard deviation): 3.2 (2.5) vs. 3.1 (2.2), p = 0.89]. The oxycodone group, however, experienced significantly more nausea (p = 0.035) and a greater incidence of vomiting (p = 0.044). Overall opioid requirement over 24 h, measured as oral morphine equivalent, was greater in the oxycodone group (median [interquartile range]: 64.5 [45-90] mg vs. 22.5 [15-46.5] mg, p < 0.0001). The number of patients first eligible for discharge at 24 h in the oxycodone group was decreased but not significantly (p = 0.07). CONCLUSION: The addition of preprocedural oral oxycodone to morphine patient-controlled analgesia does not offer any analgesic advantage to patients having uterine artery embolization and may cause a greater incidence of nausea and vomiting.

Endovascular closure of ascending aortic pseudoaneurysm with a type II Amplatzer vascular plug.

A 71-year-old man initially presented with an asymptomatic, incidentally detected ascending aortic pseudoaneurysm 25 years following aortic root repair with mechanical aortic valve replacement. This pseudoaneurysm was previously treated with coil embolization but due to coil impaction it reopened 8 years later. Endovascular closure of the pseudoaneurysm was achieved with the off-label use of a type II Amplatzer vascular plug.

Role of interventional radiology in the management of chylothorax: a review of the current management of high output chylothorax.

Chylothorax is an uncommon type of pleural effusion whose etiology may be classified as traumatic or nontraumatic. Low-output chylothoraces usually respond well to conservative management, whereas high-output chylothoraces are more likely to require surgical or interventional treatment. Conservative management focuses on alleviation of symptoms, replacement of fluid and nutrient losses, and reduction of chyle output to facilitate spontaneous healing. Surgical management can be technically difficult due to the high incidence of variant anatomy and the high-risk patient population. Percutaneous treatments have rapidly developed and evolved during the past 14 years to represent a minimally invasive treatment compared with the more invasive nature of surgery. Percutaneous therapies provide a range of treatment options despite difficult or variant anatomy, with a reported high success rate coupled with low morbidity and mortality. This article is a review of etiology, diagnosis, and treatment of chylothorax, with a focus on interventional management techniques.

Variant treatment for gastric varices with polidocanol foam using balloon-occluded retrograde transvenous obliteration: a pilot study.

INTRODUCTION: Treatment of gastric variceal rupture remains difficult with current options including transjugular intrahepatic portosystemic shunt and endoscopic therapies having significant side effects or reduced efficacy. We report five cases of gastric varices that were successfully treated with balloon-occluded retrograde transvenous obliteration of varices (BRTO) using Polidocanol foam as an alternative sclerosant to ethanolamine oleate. METHODS: Patients were recruited with cirrhotic liver disease, a history of upper gastrointestinal bleeding, and large gastric fundal varices confirmed on gastroscopy and CT venogram. BRTO was performed as a same-day procedure using a balloon catheter inserted via a gastro-renal shunt with Polidocanol foam injected and a balloon inflated for 2 h. Follow-up was with repeat CT portovenogram, gastroscopy at 6 weeks post-procedure, and in a gastroenterology liver clinic at 1- to 3-month intervals. RESULTS: Between January and December 2009, five patients safely underwent BRTO therapy of gastric varices without complication. At 6 weeks following the procedure, upper gastrointestinal endoscopy showed complete resolution of varices in 5 out of 5 patients, while CT portovenography showed resolution of varices in 4 out of 5 patients, with results in the last patient inconclusive. Clinical follow-up at 1, 3 and 6 months indicated no further episodes of bleeding. CONCLUSIONS: Our study further supports the use of foam sclerosants including Polidocanol in BRTO, showing it is a safe and effective minimally-invasive procedure to treat gastric fundal varices in the short term.

Pulmonary embolism and the use of vena cava filters after major trauma.

BACKGROUND: Major trauma patients are at significant risk of developing pulmonary embolism (PE). We aimed to (i) analyse the current incidence and timing of PE after injury; (ii) identify risk factors that predispose major trauma patients to the occurrence of PE; and (iii) describe the use of vena cava filters (VCFs) following major trauma. METHODS: Prospectively collected data from The Alfred Hospital's Trauma Registry were used to identify all major trauma patients admitted over a 7-year period. A multivariable logistic regression model was used to identify factors associated with the occurrence of PE. A similar model was developed to identify factors associated with the use of VCFs inserted at the discretion of the treating clinician. RESULTS: A total of 6344 major trauma patients were treated during this period, with 73.2% male, mean age of 44.2, 90.2% with a blunt mechanism of injury and mean injury severity score of 24.3. Prophylactic VCFs were inserted in 511 patients (8.1%), with a mean time to insertion of 3.6 days after injury. There were 45 PE, 2 of which were fatal. The mean time to PE was 12 days post-injury. Three variables were independently associated with the occurrence of PE: the absence of a VCF; number of injuries to the lower limb; and central venous catheterization. CONCLUSION: The PE rate was 0.71%. Lower limb injuries and central venous catheterization are independently associated with a higher risk of PE after major trauma and VCFs are associated with a reduced risk.

Radiología intervencional en hemorragia digestiva / Interventional radiology in gastrointestinal bleeding

Gastrointestinal (GI) hemorrhage is characterized into upper and lower bleeding, divided anatomically by the ligament of Treitz. 85 percent of GI bleeding will resolve with supportive measures alone, whil interventions are reserved for those patients failing this treatment. In this first instance upper GI bleeding will go to the endoscopist with high rates of success in both finding the site of hemorrhage and treating. Upper GI bleeders will usually only come to interventional radiologist (IR) when endoscopy fails. Acute lower GI bleeding is more difficult because it is more intermittent, and the efficacy of endoscopy (especially in the unprepared bowel) is much less. Consequently, in most practices the first interventionalist involved in this cohort are the IRs. This presentation will detail which patients should undergo embolization, when and how.

La hemorragia gastrointestinal (HG) se divide en hemorragia alta y baja en base al ligamento de Treitz. Ochenta y cinco por ciento de la HG cesa espontáneamente; las intervenciones están reservadas para aquellos pacientes en que falla el manejo conservador. En primera instancia, la HG alta es de manejo endoscópico con una alta tasa de éxito en el diagnóstico y tratamiento. Los pacientes con HG alta deberán ser intervenidos por radiología intervencional (RI) cuando la endoscopia falla. La HG baja aguda es compleja debido a su intermitencia, y la eficacia de la endoscopia (especialmente en el intestino no preparado) es mucho menor. Consecuentemente, en la mayoría de los casos la RI estará involucrada como primer peldaño en este algoritmo. Esta presentación detalla qué pacientes requieren embolización, cuándo y cómo.

Deep vein thrombosis and pulmonary embolus in patients with traumatic brain injury: a prospective observational study.

BACKGROUND: Intensive care patients with traumatic brain injury (TBI) are at high risk of developing deep vein thrombosis (DVT). A high rate of DVT was reported before routine thromboprophylaxis, but the current DVT rate in TBI patients receiving best-practice mechanical and pharmacological prophylaxis is unknown. OBJECTIVES: To determine the prevalence of DVT among TBI patients. DESIGN, PARTICIPANTS AND SETTING: A prospective observational pilot study of adult patients admitted to the intensive care unit of a level 1 trauma centre within 72 hours of sustaining a TBI (Glasgow Coma Scale score _14). MAIN OUTCOME MEASURES: Rate of DVT determined using twice-weekly compression ultrasound; rate of pulmonary embolism (PE) and length of stay. RESULTS: 36 patients (28 men; mean age, 40.3 years) were included. Six had moderate and 21 had severe TBI. Two patients (6%) developed a DVT and two patients (6%) developed a PE. The proximal leg DVT rate was 3%, but the overall venous thromboembolism rate was 11% (4 patients). CONCLUSIONS: Mechanical and pharmacological prophylaxis appeared to be effective. The incidence of clinically identified PE is of concern and suggests that thromboembolic sources other than large leg veins may not be being adequately controlled by modern thromboprophylaxis regimens.