Development of a patient-specific model of the human coronary system for percutaneous transluminal coronary angioplasty balloon catheter training and testing.

BACKGROUND: To treat stenosed coronary arteries, percutaneous transluminal coronary angioplasty (PTCA) balloon catheters must combine pushability, trackability, crossability, and rewrap behavior. The existing anatomic track model (ASTM F2394) for catheter testing lacks 3D morphology, vessel tortuosity, and compliance, making evaluating performance characteristics difficult. This study aimed to develop a three-dimensional patient-specific phantom (3DPSP) for device testing and safe training for interventional cardiologists. METHODS: A range of silicone materials with different shore hardnesses (00-30-45 A) and wall thicknesses (0.5 mm, 1 mm, 2 mm) were tested to determine compliance for creating coronary vessel phantoms. Compliance was assessed using optical coherence tomography (OCT) and compared to values in the literature. Stenosis was induced using multilayer casting and brushing methods, with gypsum added for calcification. The radial tensile properties of the samples were investigated, and the relationship between Young's modulus and compliance was determined. Various methods have been introduced to approximate the friction between silicone and real coronary vessel walls. Computerized tomography (CT) scans were used to obtain patient-specific anatomy from the femoral artery to the coronary arteries. Artery lumens were segmented from the CT scans to create dissolvable 3D-printed core models. RESULTS: A 15A shore hardness silicone yielded an experimental compliance of 12.3-22.4 m m 2 mmHg · 10 3 for stenosed tubes and 14.7-57.9 m m 2 mmHg · 10 3 for uniform tubes, aligning closely with the literature data (6.28-40.88 m m 2 mmHg · 10 3 ). The Young's modulus ranged from 43.2 to 75.5 kPa and 56.6-67.9 kPa for the uniform and calcified materials, respectively. The dependency of the compliance on the wall thickness, Young's modulus, and inner diameter could be shown. Introducing a lubricant reduced the silicone friction coefficient from 0.52 to 0.13. The 3DPSP was successfully fabricated, and comparative analyses were conducted among eight commercially available catheters. CONCLUSION: This study presents a novel method for crafting 3DPSPs with realistic mechanical and frictional properties. The proposed approach enables the creation of comprehensive and anatomically precise setups spanning the right femoral artery to the coronary arteries, highlighting the importance of such realistic environments for advancing medical device development and fostering safe training conditions.

Design of percutaneous transluminal coronary angioplasty balloon catheters.

BACKGROUND: Eight commercially available percutaneous transluminal coronary angioplasty (PTCA), including semi-compliant and non-compliant balloons, have been assessed in detail on their tip, balloon, shaft, RX-Port, and hypotube design. Important performance characteristics such as tip deformation, balloon elongation, and deflation rate have been quantified. METHODS: Five catheters of each model were evaluated during various tests. The robustness of the tips was evaluated through compression, measuring any occurrence of damage. The longitudinal growth of the balloons was recorded during inflation up to Rated Burst Pressure (RBP). The forces required to move the catheter forward and retract it into the guide catheter were measured in a simulated use test setup. The deflation behavior was studied by measuring extracted contrast media over time. Furthermore, balloon compliance and catheter dimensions were investigated. RESULTS: The outer dimensions of the catheter were found to be smallest at the hypotube (0.59-0.69 mm) and highest at the balloon, respectively, the crossing profile (0.9-1.2 mm). The tip diameter increased after compression by 1.7-22%. Cross-sections of the folded balloons revealed a tri- and two-fold, respectively. The measured balloon elongation ranged from 0.6 to 2.0 mm. After the inflation of the balloon, an increase in friction between the guide wire and the catheter was observed on four catheters. A maximum increase of 0.12 N to 1.07 N was found. Cross-sections of the RX-Port revealed a semicircular-shaped inflation lumen and a circular guide wire lumen. The measured deflation rate ranged from 0.004 to 0.013 µL/s, resulting in an estimated balloon deflation time of 10.2-28.1 s. CONCLUSION: This study provides valuable insights into the design characteristics of RX PTCA balloon catheters, which can contribute to facilitating the development of improved catheter designs and enhancing clinical outcomes. Distinctions between SC and NC catheters, such as balloon performance and dimensions, are evident. It is important to note that no single catheter excels in all aspects, as each possesses unique strengths. Therefore, it is essential to consider individual intervention requirements when selecting a catheter. The research also identifies specific catheter weaknesses, such as reduced wall thickness, fringes at the tip, and reduced performance characteristics.

Temperature-dependent tensile properties of polyamide 12 for the use in percutaneous transluminal coronary angioplasty balloon catheters.

BACKGROUND: Percutaneous transluminal coronary angioplasty (PTCA) balloon catheters must withstand high pressures required for the lesion treatment, pushing loads during insertion, and pulling loads during withdrawal. These loads pose a challenge especially for polymeric tubular shafts with small cross sections. In order to enable new design innovations and to better understand the mechanics of current catheter technologies, the tensile properties of polyamide (PA) 12 were investigated. PA 12 dog bone specimens and medical PA 12 tubes were either stored at ambient temperature and humidity or conditioned in water, and subjected to tensile loads at different temperatures. In addition, the effect on the tensile properties of the necking process, a forming process to reduce the wall thickness of the tubes, was determined. RESULTS: The tested tubes showed a reduction in both Young's Modulus (- 41.5%) and yield stress (- 29.2%) compared to standardized specimens. Furthermore, an increase in temperature and water absorption softens the material and reduces the mechanical properties like the Young's Modulus and the yield stress. It was found that the material strengthens during the necking process. Likely due to the orientation of the polymers chain molecules in load direction (Rösler et al., 2007), the Young's Modulus of the material could be increased by 43.5%. Furthermore, the absence of a yield point after necking allows for a greater loading capacity of the material without unstable neck growth. Besides the strengthening, the ultimate strain is reduced by 50%. This indicates that the necking process induces plastic deformation. CONCLUSION: The investigation showed that the environmental conditions like temperature and humidity can influence mechanical properties. It could also be shown that pre-forming processes such as necking can enhance the mechanical properties, such as the Young's Modulus, while reducing the wall thickness. These findings suggest possible further development of catheters with a small cross section and higher mechanical strength and highlight the importance to account for the targeted operating temperature during the design process.

[Long-Term Outcome in Patients with Intravitreal Anti-VEGF Therapy for Exudative AMD]. / Langzeit-Verlauf bei Patienten mit intravitrealer Anti-VEGF Therapie für neovaskuläre AMD.

BACKGROUND: Randomized controlled phase III studies have shown that intravitreal anti-VEGF therapy is effective for exsudative age-related macular degeneration (AMD) over two years. Recently, the seven-year outcomes in ranibizumab-treated patients of the ranibizumab phase III studies have been published. Only a few other studies with such a long follow-up for intravitreal anti-VEGF therapy in patients with exsudative AMD have been published so far. We report on the outcome of patients receiving intravitreal anti-VEGF therapy for exudative AMD at the Department of Ophthalmology, University Hospital of Zurich with follow-up of 3 to 7 years. PATIENTS: Retrospective chart review of all patients treated at our institution for exudative AMD with begin of treatment since 2006. RESULTS: The numbers of patients with a follow-up of 3 to 4, 4 to 5, 5 to 6, 6 to 7, and more than 7 years were 430, 277, 151, 87, and 47, respectively. Mean follow-up time was 4.9 years, and median was 4.6 years. Changes in visual acuity for these patients were -5.0, -7.8, -11.7, -12.8, and -19.2 ETDRS letters, respectively. CONCLUSIONS: Whereas in patients with exudative AMD during the first two years of intravitreal anti-VEGF treatment visual acuity can at least be stabilised, after three and more years visual acuity decreases in spite of continued treatment.

Preliminary results of aflibercept in treatment-naive choroidal neovascularization of wet age-related macular degeneration.

BACKGROUND: The aim of this study was to evaluate the early response of aflibercept as first-line therapy in treatment-naive patients with newly diagnosed choroidal neovascularization (CNV) in age-related macular degeneration (AMD). PATIENTS AND METHODS: An analysis of 35 eyes (35 patients, 28 female, 7 male) with treatment-naive active CNV was undertaken. Lesion activity was determined based on fluorescein angiography, clinical and optical coherence tomography (OCT) findings, including the presence of sub-, intraretinal fluid, retinal pigment epithelial (RPE) detachment and hemorrhage. Logarithm of the minimum angle of resolution (LogMAR) charts were used for testing best corrected or best available visual acuity (BCVA). Treatment response was evaluated based on changes in BCVA and lesion activity. RESULTS: Classic or predominantly classic CNV was diagnosed in 7 eyes (20.0%), occult or minimally classic in 21 eyes (60.0%), retinal angiomatous proliferation in 5 eyes (14.3%) and polypoidal choroidal vasculopathy in 2 eyes (5.7%). Lesion activity was evaluated as unchanged in only one eye. In all other eyes, a definite treatment response was observed with complete resolution of fluid in 20 eyes after a single injection. Three eyes did not show improved sub-RPE fluid with smaller pigment epithelial detachments. A rip of the RPE was seen in 3 eyes. All patients maintained vision, 7 patients (7 eyes) gained >15 letters from baseline to month 2 follow-up, of whom 4 reached this level of visual acuity after one injection. The visual acuity gains in this study were maintained through 6 months. CONCLUSION: There seems to be a rapid treatment response to aflibercept independent of the underlying CNV. Aflibercept may be beneficial even in eyes with large pigment epithelial detachments due to exudative AMD.

[Unilateral renal denervation and the renal kallikrein-bradykinin system in the rat]. / La dénervation rénale unilatérale et le système kallikréine-bradykinine rénal chez le rat.

AIM: The antihypertensive effect of renal denervation in hypertensive patients is partially explained by increased tubular natriuresis. To study the possible contribution of the kallikrein-kinin system (KKS) to this natriuretic effect in rats, we measured kallikrein activity (KA) and bradykinin concentrations (BK) in plasma and tissues. METHODS: To measure KA, we adapted and validated an enzymatic assay that cleaves para-nitroaniline (pNA) from the tripeptide H-D-Pro-Phe-Arg-pNA. The coefficients of variation (CV) within- and between-assays were less than 8% for plasma and tissue KA (plasma n=6 and 13; tissue n=4). Linear results for serially diluted samples confirmed the assay specificity. Tissue BK determinations were based on an established assay for plasma BK: tissue was homogenized and kinins extracted in ethanol, and BK was isolated by high-performance (HPLC) liquid chromatography and quantitated by radioimmunassay. Within- and between-assay CV for plasma BK were 18% (n=8 and n=35, respectively) and for BK in various tissues less than 16% (n=5-8). RESULTS: In male Wistar rats (n=3), plasma BK was 8.2 ± 6.6 fmol/mL (mean ± SD), and tissue BK (fmol/g) in 14 tested organs varied between brain (14 ± 3) and submaxillary gland (521 ± 315). Six days after left-sided unilateral renal denervation, left renal tissue BK (89 ± 9) was not different from right renal BK (75 ± 23). Similarly, KA was comparable in the two kidneys (left 18.0 ± 1.5, right 15.8 ± 1.4 µkat/g). CONCLUSION: Any possible effect of unilateral renal denervation on the kidney's KKS would have to be bilateral.

Response to ranibizumab therapy in neovascular AMD - an evaluation of good and bad responders.

BACKGROUND: Treatment of neovascular age-related macular degeneration (AMD) with Lucentis shows a broad spectrum regarding the course of visual acuity (VA). While some patients show a good response (increase in VA), others disclose much less promising results. PATIENTS AND METHODS: A retrospective data analysis of all eyes treated for neovascular AMD at the University Hospital of Zurich, Switzerland for at least 12 months was carried out. The courses of VA between the 90th (good responders, GR) and the 10th (bad responders, BR) percentiles were compared at 3, 12 and 24 months from baseline. An analysis regarding demographic data, lesion type and size as well as injection frequency and visits was done and predictive factors for GR and BR were evaluated. RESULTS: Marked differences in the course of VA between GR (n = 30) and BR (n = 30) are already observed 3 months from baseline. In GR the gains in VA after 3, 12 and 24 were 15.7 +/- 9 letters ETDRS, 25.3 +/- 7 and 14.0 +/- 14. BR showed a deterioration of 8.3 +/- 11 letters ETDRS after 3, 22.1 +/- 8 after 12 and 23.6 +/- 13 after 24 months. The gender distribution was equal with a higher percentage of female patients (64 % in BR and 66 % in GR). The baseline VA was statistically significantly lower in GR (45.7 +/- 10 vs. 55.4 +/- 11, p < 0.05) than in BR. No other significant differences in baseline data were found, and no predictor for group membership could be identified. CONCLUSIONS: Only the course of VA in the first three months seems to be of value for an estimation of the response to treatment. In the future the response to treatment in the early phase may influence the treatment algorithm and the injection frequency.

[Diagnostic pitfalls about a specific case of low back pain]. / Pièges diagnostiques à propos d'un cas de lombalgie spécifique.

Diagnostic pitfalls about a specific case of low back pain Low back pain is classified into two principle categories: specific and non specific. This difference is important in terms of screening, medical care and treatment. Specific low back pain has various etiologies that imply specific treatment. This report describes one case of rare specific low back pain. The purpose of this article is to highlight the pitfalls that can represent such a common pathology, to show that obtaining an early diagnosis can be challenging, and finally to prevent care providers from stereotypes related to low back pain management.

Accuracy of navigated surgery of the pelvis after surface matching with an a-mode ultrasound probe.

Computer-aided surgery (CAS) allows for real-time intraoperative feedback resulting in increased accuracy, while reducing intraoperative radiation. CAS is especially useful for the treatment of certain pelvic ring fractures, which necessitate the precise placement of screws. Flouroscopy-based CAS modules have been developed for many orthopedic applications. The integration of the isocentric flouroscope even enables navigation using intraoperatively acquired three-dimensional (3D) data, though the scan volume and imaging quality are limited. Complicated and comprehensive pathologies in regions like the pelvis can necessitate a CT-based navigation system because of its larger field of view. To be accurate, the patient's anatomy must be registered and matched with the virtual object (CT data). The actual precision within the region of interest depends on the area of the bone where surface matching is performed. Conventional surface matching with a solid pointer requires extensive soft tissue dissection. This contradicts the primary purpose of CAS as a minimally invasive alternative to conventional surgical techniques. We therefore integrated an a-mode ultrasound pointer into the process of surface matching for pelvic surgery and compared it to the conventional method. Accuracy measurements were made in two pelvic models: a foam model submerged in water and one with attached porcine muscle tissue. Three different tissue depths were selected based on CT scans of 30 human pelves. The ultrasound pointer allowed for registration of virtually any point on the pelvis. This method of surface matching could be successfully integrated into CAS of the pelvis.

[A-mode ultrasonic pointer for navigated pelvic surgery]. / A-Mode-Ultraschall-Pointer für die navigierte Beckenchirurgie.

Surgical navigation has proven to be a minimally invasive procedure that enables precise surgical interventions with reduced exposure to irradiation for patient and personnel. Fluoroscopy-based modules have prevailed on the market. For certain operations of the pelvis computed tomography is necessary with its high imaging quality and considerably larger scan volume. To enable navigation in these cases, matching of the CT data set and the patient's real pelvic bone is essential. The common pair point-matching algorithm is complemented by the surface-matching algorithm to achieve an even higher overall precision of the system. For conventional surface matching with a solid pointer, the bone has to be exposed from soft tissue quite extensively, using a solid pointer. This conflicts with the claim of computer-assisted surgery to be minimally invasive. We integrated an A-mode ultrasonic pointer with the intention to perform extended surface matching on the pelvic bone noninvasively. Related to the conventional method, comparable and to some extent even improved precision conditions could be established.

Comparison of rebound tonometry with Goldmann applanation tonometry and correlation with central corneal thickness.

BACKGROUND/AIMS: Rebound tonometry (RT) is performed without anaesthesia with a hand held device. The primary aim was to compare RT with Goldmann applanation tonometry (GAT) and to correlate with central corneal thickness (CCT). The secondary aim was to prove tolerability and practicability of RT under "study conditions" and "routine practice conditions." METHODS: In group 1 (52 eyes/28 patients), all measurements were taken by the same physician, in the same room and order: non-contact optical pachymetry, RT, slit lamp inspection, GAT. Patients were questioned about discomfort or pain. In group 2 (49 eyes/27 patients), tonometry was performed by three other physicians during routine examinations. RESULTS: RT was well tolerated and safe. Intraocular pressure (IOP) ranged between 6 mm Hg and 48 mm Hg. No different trends were found between the groups. RT tended to give slightly higher readings: n = 101, mean difference 1.0 (SD 2.17) mm Hg; 84.1% of RT readings within plus or minus 3 mm Hg of GAT; 95% confidence interval in the Bland-Altman analysis -3.2 mm Hg to +5.2 mm Hg. Both RT and GAT showed a weak positive correlation with CCT (r2 0.028 and 0.025, respectively). CONCLUSIONS: RT can be considered a reliable alternative for clinical screening and in cases where positioning of the head at the slit lamp is impossible or topical preparations are to be avoided.

Follicular conjunctivitis caused by a mantle cell lymphoma.

BACKGROUND: Lymphoma of the conjunctiva as part of a systemic disease is rare. The follicular appearance of the lymphocyte hyperplasia may mimic the clinical picture of infectious or allergic conjunctivitis. We report on a case of marked chronic follicular conjunctivitis, finally diagnosed as mantle cell lymphoma. HISTORY AND SIGNS: A 52-year old male with a history of epiphora for one year, presented with follicular conjunctivitis in both eyes, a nodal mass in the upper right eyelid and nuchal lymphadenopathy. No infectious or allergic aetiology could be found. Conjunctival biopsy revealed a mantle cell lymphoma. Magnetic resonance tomography showed a bilateral spread into the orbital cavity. Other sites of involvement were the epipharynx and the cervical, axillary and paratracheal lymph nodes. THERAPY AND OUTCOME: Chemotherapy with hyper-CVAD (cyclophosphamide, vincristine, doxorubicine, dexamethasone) was initiated. After 4 of 6 cycles, all clinical tumour manifestations had disappeared completely. CONCLUSIONS: Conjunctival lymphoma may clinically resemble follicular conjunctivitis. Conjunctival biopsy may lead to early diagnosis and initiation of therapy.

Plasma bradykinin in angio-oedema.

BACKGROUND: Bradykinin is believed to be the main mediator of symptoms in hereditary (HA) and acquired (AA) angio-oedema due to C1 esterase inhibitor deficiency, as well as in angio-oedema that complicates treatment with inhibitors of angiotensin-converting enzyme (ACE). Difficulties in the measurement of kinin concentrations, however, have so far precluded the demonstration of an incontrovertible change in plasma bradykinin concentrations in these disorders. By developing a reliable assay we have been able to follow bradykinin concentrations during attacks and during remission in HA and in AA, and also in a patient treated with an ACE-inhibitor. METHODS: Liquid-phase extraction, high-performance liquid chromatography, and RIA were used for specific measurement of plasma bradykinin concentrations in 22 patients with HA and in 22 healthy volunteers of similar age and sex distribution. Four patients with AA and one hypertensive patient treated with the ACE inhibitor captopril were also studied. FINDINGS: Among the healthy volunteers plasma bradykinin concentration was inversely proportional to age. The geometric mean plasma bradykinin concentration in the healthy volunteers was 2.2 fmol/mL (SD 2.2), compared with 3.9 fmol/mL (3.7) among patients with HA during remission (p=0.095). Bradykinin was also high in the patients with AA (10.4 fmol/mL [1.6]). During acute attacks of oedema, in both HA and AA, plasma bradykinin rose to two to 12 times the upper limit of normal. Infusion of C1-esterase inhibitor (the deficient factor in both HA and AA) immediately lowered bradykinin concentrations. In the patient receiving the ACE-inhibitor captopril, bradykinin concentration was very high at 47 fmol/mL during an acute attack of angio-oedema, but normal at 3.2 fmol/mL in remission after withdrawal of the drug. INTERPRETATION: A sensitive method for measurement of plasma bradykinin provided the means to show that concentrations of this peptide decrease with age in healthy people. Although the differences between patients in remission and healthy controls did not reach statistical significance, there were substantial rises in bradykinin during acute attacks of hereditary, acquired, or captopril-induced angio-oedema.

Individual measurements of angiotensin II concentrations in aqueous humor of the eye.

The presence of constituents of the renin-angiotensin system (RAS) in ocular tissues and fluids suggests this system is involved in ocular physiology. Angiotensin II (AngII) is the main biological effector of the system, so we measured AngII in plasma and in aqueous humor of the anterior ocular chamber of patients undergoing cataract extraction. Untreated normotensive patients were compared with arterial hypertensive patients taking either diuretics which stimulate the RAS or angiotensin converting enzyme (ACE) inhibitors which reduce the production of AngII. Plasma levels of AngII were higher in patients on diuretics (5.46 +/- 1.04 fmol/ml; mean +/- SEM) than in untreated cataract patients (2.28 +/- 0.32 fmol/ml, p < 0.02), and were very low with ACE inhibitors (0.51 +/- 0.18 fmol/ml). In aqueous humor, AngII was measurable in 7 of 11 patients on diuretics (median 1.1 fmol/ml), and in 6 of 16 normotensive patients (median < 0.55 fmol/ml), but not in aqueous humor of 4 patients receiving enalapril or captopril. These results demonstrate the presence of AngII in the eye but do not exclude either its sequestration in the eye or local production. The possibility of individual measurements of intraocular AngII will permit more precise determination of its role in future studies.