A Computational Tool for the Microstructure Optimization of a Polymeric Heart Valve Prosthesis.

Styrene-based block copolymers are promising materials for the development of a polymeric heart valve prosthesis (PHV), and the mechanical properties of these polymers can be tuned via the manufacturing process, orienting the cylindrical domains to achieve material anisotropy. The aim of this work is the development of a computational tool for the optimization of the material microstructure in a new PHV intended for aortic valve replacement to enhance the mechanical performance of the device. An iterative procedure was implemented to orient the cylinders along the maximum principal stress direction of the leaflet. A numerical model of the leaflet was developed, and the polymer mechanical behavior was described by a hyperelastic anisotropic constitutive law. A custom routine was implemented to align the cylinders with the maximum principal stress direction in the leaflet for each iteration. The study was focused on valve closure, since during this phase the fibrous structure of the leaflets must bear the greatest load. The optimal microstructure obtained by our procedure is characterized by mainly circumferential orientation of the cylinders within the valve leaflet. An increase in the radial strain and a decrease in the circumferential strain due to the microstructure optimization were observed. Also, a decrease in the maximum value of the strain energy density was found in the case of optimized orientation; since the strain energy density is a widely used criterion to predict elastomer's lifetime, this result suggests a possible increase of the device durability if the polymer microstructure is optimized. The present method represents a valuable tool for the design of a new anisotropic PHV, allowing the investigation of different designs, materials, and loading conditions.

The cardiac torsion as a sensitive index of heart pathology: A model study.

The torsional behaviour of the heart (i.e. the mutual rotation of the cardiac base and apex) was proved to be sensitive to alterations of some cardiovascular parameters, i.e. preload, afterload and contractility. Moreover, pathologies which affect the fibers architecture and cardiac geometry were proved to alter the cardiac torsion pattern. For these reasons, cardiac torsion represents a sensitive index of ventricular performance. The aim of this work is to provide further insight into physiological and pathological alterations of the cardiac torsion by means of computational analyses, combining a structural model of the two ventricles with simple lumped parameter models of both the systemic and the pulmonary circulations. Starting from diagnostic images, a 3D anatomy based geometry of the two ventricles was reconstructed. The myocytes orientation in the ventricles was assigned according to literature data and the myocardium was modelled as an anisotropic hyperelastic material. Both the active and the passive phases of the cardiac cycle were modelled, and different clinical conditions were simulated. The results in terms of alterations of the cardiac torsion in the presence of pathologies are in agreement with experimental literature data. The use of a computational approach allowed the investigation of the stresses and strains in the ventricular wall as well as of the global hemodynamic parameters in the presence of the considered pathologies. Furthermore, the model outcomes highlight how for specific pathological conditions, an altered torsional pattern of the ventricles can be present, encouraging the use of the ventricular torsion in the clinical practice.

Structural changes of block copolymers with bi-modal orientation under fast cyclical stretching as observed by synchrotron SAXS.

Load-bearing tissues are composite materials that depend strongly on anisotropic fibre arrangement to maximise performance. One such tissue is the heart valve, with orthogonally arranged fibrosa and ventricularis layers. Their function is to maintain mechanical stress while being resilient. It is postulated that while one layer bears the applied stress, the orthogonal layer helps to regenerate the microstructure when the load is released. The present paper describes changes in the microstructure of a block copolymer with cylindrical morphology, having a bio-inspired microstructure of anisotropic orthogonally oriented layers, under uniaxial strain. To allow structural observations during fast deformation, equivalent to the real heart valve operation, we used a synchrotron X-ray source and recorded 2D SAXS patterns in only 1 ms per frame. The deformation behaviour of the composite microstructure has been reported for two arrangements of the cylinders in skin and core layers. The behaviour is very different to that observed either for uniaxially oriented or isotropic samples. Deformation is far from being affine. Cylinders aligned in the direction of stretch show fragmentation, but complete recovery of the spacing between cylinders on removal of the load. Those oriented perpendicular to the direction of stretch incline at an angle of approximately 25° to their original direction during load.

A comparison of bleeding patterns and cycle control using two transdermal contraceptive systems: a multicenter, open-label, randomized study.

OBJECTIVE(S): To investigate the bleeding pattern and cycle control parameters of a contraceptive patch containing 0.55 mg ethinyl estradiol (EE) and 2.1 mg gestodene (GSD) compared with a patch containing 0.6 mg EE and 6 mg norelgestromin (NGMN). STUDY DESIGN: In this phase III, open-label, randomized, parallel-group trial, healthy women aged 18-35 years (smokers aged 18-30 years) received either the EE/GSD patch (n=200) or the EE/NGMN patch (n=198). Treatment consisted of one patch per week for 3 weeks followed by a 7-day, patch-free interval for seven cycles. Bleeding control was assessed in two 90-day reference periods. RESULTS: In reference period 1, mean number of bleeding/spotting days was comparable across treatment groups (p>0.05). However, in reference period 2, there were fewer bleeding/spotting days in the EE/GSD patch group (15.7 versus 18.4; p<0.0001). Mean number of bleeding/spotting episodes was comparable across groups for both reference periods, but bleeding/spotting episodes were shorter for the EE/GSD patch than the EE/NGMN patch during reference period 1 (5.13 days versus 5.53 days, respectively; p<0.05) and reference period 2 (5.07 versus 5.66; p=0.0001). Both treatment groups showed a similar frequency of withdrawal bleeding episodes; however, across all seven cycles, the length of these episodes was consistently shorter with the EE/GSD patch (p<0.01). There were no notable treatment differences in intracyclic bleeding. CONCLUSION(S): Bleeding pattern and cycle control achieved with the EE/GSD patch was similar to that of the EE/NGMN patch. IMPLICATIONS STATEMENT: The paper presents data on the bleeding pattern and cycle control parameters of an investigational transdermal contraceptive patch containing EE and GSD compared with an approved contraceptive patch containing EE and NGMN. This descriptive study found that bleeding patterns associated with the EE/GSD patch were similar to those of an EE/NGMN patch providing higher EE exposure.

Contrast enhancement and elastography in endoscopic ultrasound: an overview of clinical applications in pancreatic diseases.

Endoscopic ultrasound is a very accurate imaging technique with a relevant clinical impact in the diagnosis and staging of various conditions such as pancreaticobiliary lesions, esophageal cancer, lung cancer, submucosal lesions and lymph nodes. Despite its increasing importance in everyday clinical routine, endoscopic ultrasound outcomes are still highly operator-dependent and tissue confirmation with fine needle aspiration is very often required for definitive differential diagnosis of tumors. Several techniques of image enhancement have been developed in recent years in the attempt to make the technique less operator-dependent. Among them the most important appear to be contrast harmonic-endoscopic ultrasound and endoscopic ultrasound-elastography. Contrast harmonic-endoscopic ultrasound is performed with a dedicated harmonic which displays the fine vascular network of both normal and pathological tissues after injection of an ultrasound contrast agent. Endoscopic ultrasound-elastography displays with different colors the differences in hardness between tissues, thus estimating elasticity in soft normal tissues which appear red and hard neoplastic tissues which appear blue. While contrast harmonic-endoscopic ultrasound has been introduced into clinical practice, endoscopic ultrasound-elastography mainly represents an investigational tool. The purpose of this paper was to review the mechanism of action and the clinical outcomes of contrast harmonic-endoscopic ultrasound and endoscopic ultrasound-elastography in pancreatic diseases. Both techniques show promising applications in the study of pancreatic tumors including differential diagnosis and providing guidance to fine needle aspiration.

Effects of a combined oral contraceptive containing oestradiol valerate/dienogest on hormone withdrawal-associated symptoms: results from the multicentre, randomised, double-blind, active-controlled HARMONY II study.

The objective of this multicentre, randomised, double-blind study was to compare a combined oral contraceptive (COC) containing oestradiol valerate/dienogest (E2V/DNG) administered in a dynamic dosing regimen with a monophasic COC containing ethinyloestradiol/levonorgestrel (EE/LNG), with regard to their ability to reduce the frequency and intensity of headache and pelvic pain in women with hormone withdrawal-associated symptoms (HWAS). Women aged 18-50 years received E2V/DNG in an oestrogen step-down and progestin step-up regimen (26/2 regimen; n = 223) or EE 20 µg/LNG 100 µg (21/7 regimen; n = 218) over six cycles. Headache and pelvic pain were assessed using a visual analogue scale (VAS) during cycle days 22-28. Rescue medication use was also assessed. E2V/DNG was superior to EE/LNG with regard to reducing the frequency and intensity of headache and pelvic pain from baseline to cycle 6 (change from baseline in the average of the three highest VAS values [mean ± standard deviation]: 47.7 ± 29.4 vs 34.5 ± 25.7 mm, respectively; p < 0.0001). The use of rescue medication was also significantly reduced with E2V/DNG compared with EE/LNG (p < 0.05). E2V/DNG may be a good option for women who experience HWAS with traditional 21/7-day regimen COCs.

Pilot study: the use of sulfasalazine for the treatment of acute pouchitis.

BACKGROUND: Acute pouchitis, an idiopathic inflammatory condition of the ileal pouch anal anastomosis, is the most frequent complication after proctocolectomy for ulcerative colitis. AIM: To test the hypothesis that sulfasalazine (SASP) might have a synergistic beneficial effect in acute pouchitis, by combining the anti-inflammatory activity of 5-aminosalicylic Acid and the bacteriostatic effect of sulphapyridine. METHODS: Twenty two patients were investigated for acute pouchitis; the Pouchitis Disease Activity Index (PDAI) was calculated and 11 patients with acute pouchitis (PDAI >7) were included in an open study, after obtaining their informed consent. Patients were treated with SASP 500 mg tablets, two tablets three times per day (3000 mg daily), for 2 months. Pouch endoscopy with biopsies was performed at the entry and at the end of the study. RESULTS: According to the PDAI score, 8/11 patients (73%) improved their clinical condition and 7/11 (63%) were in remission at the end of the treatment. At 8 weeks, the median PDAI index decreased from 11.2 +/- 2.3 to 6.6 +/- 4.7 P < 0.01. No adverse events or toxicity were reported and all patients completed the study. CONCLUSIONS: Despite the limitations of the current study, sulfasalazine seems to be a potential treatment for acute pouchitis.

Endoscopic argon plasma coagulation for the treatment of gastric antral vascular ectasia-related bleeding in patients with liver cirrhosis.

BACKGROUND AND AIM: Gastric antral vascular ectasia (GAVE) is a cause of bleeding in patients with liver cirrhosis. Argon plasma coagulation (APC) is the most used endoscopic treatment for GAVE-related bleeding. Treatment failures have been described in patients with haemorrhagic diathesis; post-procedure complications include haemorrhages and septicaemia. The aim of the study was to evaluate efficacy and safety of APC treatment of GAVE-related bleeding in patients with liver cirrhosis. METHODS: Patients included were suffering from GAVE-related bleeding and liver cirrhosis. APC treatment was performed until eradication. Resolution of transfusion-dependent anaemia and evaluation of complications were the primary outcomes. RESULTS: 20 patients (16 Child C and 4 Child B) were enrolled and prospectively followed for a mean period of 28 months. GAVE eradication was achieved in all patients after a median of 3 sessions (range 1-10). Resolution of anaemia was achieved in 18 patients. Six patients had relapse of GAVE after a mean of 7.7 months, successfully retreated by APC. Hyperplastic polyps developed in 3 patients causing active bleeding in 2 cases. Five patients had liver transplants and 1 had a relapse of GAVE after transplantation. CONCLUSION: APC is an effective and safe endoscopic treatment for GAVE in patients with liver cirrhosis.