Temporary implantable nitinol device for benign prostatic hyperplasia-related lower urinary tract symptoms: over 48-month results.

BACKGROUND: This study (MT02) reports >48-month (50-79 months) results of a prospective, single-arm, multicenter study (NCT02145208) of temporary implantable nitinol device (iTind®) in men with benign prostatic hyperplasia (BPH)-related lower urinary tract symptoms (LUTS). METHODS: Men with symptomatic BPH (International Prostate Symptom Score [IPSS] ≥10, Maximum flow rate [Qmax] <12 mL/s, and prostate volume <75 mL) from 9 centers were enrolled from December 2014 to December 2016. Total 50/81 (62%) patients at 3/9 sites (Italy, Switzerland, and Belgium), pursued the study beyond 36 months following iTind® device, per study protocol. Due to COVID-19, follow-up was amended. Each patient was assessed once during 50-79 months postoperatively for IPSS and IPSS-quality of life (IPSS-QoL), change in medication, need for surgical re-treatment and adverse events telephonically. RESULTS: Post 36 month-follow-up, 5 patients were lost to follow-up and 2 patients died unrelated to iTind® device placement. Two patients (36-48 months follow-up) required surgical re-treatments (1 transurethral resection of prostate, 1 Thulium laser enucleation of prostate). >48 months results were available for 41 patients wherein iTind® device treatment showed significant improvement in symptoms (IPSS: -45.3%, P<0.0001 and IPSS-QoL: -45.1%, P<0.0001) from baseline to 79 months post-procedure; mean±SD of 11.26±7.67 and 2.10±1.41 points, respectively. No complications were recorded between 36 up to 79 months; no patient required additional medication. CONCLUSIONS: iTind® device provided significant and durable symptom reduction and improved IPSS-QoL for >48 months post treatment. No late postoperative complications were reported beyond 36 months of follow-up. Surgical re-treatment rate for >36 months was 4%.

3-Year results following treatment with the second generation of the temporary implantable nitinol device in men with LUTS secondary to benign prostatic obstruction.

BACKGROUND: To report the 3-year results of a prospective, single arm, multicenter, international clinical study with the second generation of the temporary implantable nitinol device (iTIND; Medi-Tate Ltd®, Israel) on men suffering lower urinary tract symptoms (LUTS) secondary to benign prostatic obstruction (BPO). METHODS: Eighty-one men with symptomatic BPO (IPSS ≥ 10, peak urinary flow <12 ml/s, and prostate volume <75 ml) were enrolled in this study between December 2014 and December 2016. Subjects were washed-out 1 month for alpha-blockers and 6 months for 5-ARIs. The implantation was performed under light sedation and the removal 5-7 days later with topical anesthesia. Perioperative results including OR-time, pain (VAS) postoperative complications (Clavien-Dindo-Grading System), functional results (Qmax, IPSS, PVR) and quality of life (QoL) were assessed at 1, 3, 6 months, 1, 2, and 3 years. Sexual and ejaculatory function were evaluated using two yes/no questions. RESULTS: Thirty-six month functional results were available for 50 patients and demonstrated that iTIND efficacy remained stable through 3 years, with averages IPSS, QOL, Qmax and PVR of 8.55 + 6.38, 1.76 + 1.32, 15.2 + 6.59 ml/s and 9.38 + 17.4 ml, improved from baseline by -58.2, -55.6, +114.7, and -85.4% (all significantly different from their corresponding baseline values, p < 0.0001). Even considering the Intention to Treat analysis (ITT), the 36-month results confirmed significant improvements of the functional outcomes if compared with baselines values (all p < 0.0001). No late post-operative complications were observed between 12 and 36 months. Sexual function was stable through 3 years, with no reports of sexual or ejaculatory dysfunctions. No patients underwent alternative treatments between 24 and 36 months. CONCLUSION: Treatment of BPO-related LUTS with iTIND demonstrated a significant and durable reduction in symptoms and improvement of functional parameters and quality of life at 3 years of follow-up. No late post-operative complications, ejaculatory dysfunction or additional treatment failures were observed between 24 and 36 months.

Second generation of temporary implantable nitinol device (iTind) in men with LUTS: 2 year results of the MT-02-study.

OBJECTIVES: Assessing medium-term functional results of a novel minimally-invasive treatment for lower urinary tract symptoms due to BPO with the second generation of the temporary implantable nitinol device (iTind; Medi-Tate Ltd®, Israel): 2-year follow-up of a single-arm, prospective, international multicenter study. Further, we aimed to identify preoperative baseline parameters predicting response to iTind treatment. METHODS: Following local ethical committee approval in every participating centre, 81 men with symptomatic BPO (IPSS ≥ 10, peak urinary flow < 12 ml/s, and prostate volume < 75 ml) were enrolled in this study. Patients with PVR > 250 ml, obstructive median lobe, previous prostatic surgery, confounding bladder or sphincter dysfunction based on medical history, active urinary infection and unable to interrupt antithrombotic or antiplatelet treatment were exclusion criteria. A wash-out period of 1 month for alpha-blockers and 6 months for 5-ARIs was mandatory to avoid confounders. The procedure was performed as previously described: implantation under light sedation and removal 5-7 days later with topical sedation. Patients were assessed for perioperative results including OR-time, pain (VAS) and complications (Clavien-Dindo-Grading System); and for functional results (PVR, Qmax, IPSS) and quality of life (QoL) including sexual and ejaculatory function using two yes/no questions. Follow-up assessments were done at 1, 3, and 6 months, and 1 and 2 years. RESULTS: Of the 81 patients initially enrolled in this study, follow-up included 67 men at 1 year and 51 men at 2 years. For the 51 men included in the present analysis, the median age was 65 years, median prostate volume 37 ml (range 16-65 ml). Baseline values for IPSS and QoL were 20.51 ± 4.58, 3.96 ± 0.87. Qmax and PVR were 7.62 ± 2.25 ml/s and 65.84 ± 38.46, respectively. No intraoperative complications were observed and the average pain level recorded on the visual analogue scale (VAS) was 3.2 ± 1.6. A significant reduction in symptoms and improvement in urinary flow was observed (p < 0.0001) at all assessment points: IPSS-score and QoL improved to 8.51 ± 5.51 and 1.76 ± 1.32, respectively; and Qmax increased to 16.00 ± 7.43 ml/s. None of the patients who were previously sexually active reported a deterioration in sexual or ejaculatory functions according to two yes/no questions over the follow-up period. Excluding the patients lost at follow-up, five patients underwent surgery between 12 and 24 months. Upon investigation, it was discovered that four of the five patients requiring surgery had median lobes and were protocol deviators. A failure analysis was carried out for all 81 patients in order to identify baseline parameters that could predict treatment failure. 58.33% of patients in the failure group (7 out of 12) had median lobes which was found to be statistically significant (p < 0.0001). None of the other preoperative variables (age, prostate volume, IPSS scores, Qmax, PVR, and PSA) were found to predict response to iTind treatment. CONCLUSION: iTind treatment for BPO-related LUTS showed marked and durable reduction in symptoms and improvement of functional parameters and quality of life at 24 months of follow-up. It was found that median lobe may predict failure of iTind treatment. According to the yes/no questions, ejaculatory and sexual functions do not seem to be effected following treatment, however, this finding must be supported with further studies using the accepted tools.

Second-generation of temporary implantable nitinol device for the relief of lower urinary tract symptoms due to benign prostatic hyperplasia: results of a prospective, multicentre study at 1 year of follow-up.

OBJECTIVES: To report the clinical experience with a second-generation of temporary implantable nitinol device (iTIND; Medi-Tate Ltd, Or-Akiva, Israel) for the treatment of lower urinary tract symptoms (LUTS) due to benign prostatic hyperplasia (BPH) after 1 year of follow-up. PATIENTS AND METHODS: In all, 81 patients with LUTS, International Prostate Symptom Score (IPSS) ≥10, maximum urinary flow rate (Qmax ) ≤12 mL/s, and prostate volume <75 mL, were enrolled in this prospective Research Ethics Committee-approved multicentre study. The main exclusion criteria were: haemostatic disorders, post-void residual urine volume (PVR) >250 mL, obstructive median lobe, and previous prostate surgery. The iTIND was implanted within the bladder neck and the prostatic urethra under light sedation, using a rigid cystoscope. The device was removed 5-7 days later in an outpatient setting. Demographics, perioperative results, complications (according to the Clavien-Dindo system), functional results and quality of life (QoL) were evaluated. Follow-up assessments were conducted at 1, 3, 6 and 12 months postoperatively. RESULTS: The mean (sd) patient age was 65 (8.9) years, prostate volume was 40.5 (12.25) mL, Qmax was 7.3 (2.6) mL/s, IPSS was 22.5 (5.6), and the median (interquartile range) IPSS QoL score was 4 (2-5). All the implantations were successful, with no intraoperative complications recorded; all patients were discharged on the same day of surgery. The devices were retrieved at a mean (SD) of 5.9 (1.1) days after implantation, typically under topical anaesthesia. No Clavien-Dindo Grade >II complications were recorded. The mean (SD) Qmax at the 1 month follow-up visit was 11.2 (5.7) mL/s and continued to improve thereafter, reaching 14.7 (8.1) mL/s at the 12-month follow-up visit (+100%). The mean (SD) IPSS urinary symptom scores were 11.7 (8.0) after 1 month and further improved to 8.8 (6.4) at the 12-month follow-up (-60%). In parallel, the mean (SD) IPSS QoL score drop reached 1.6 (1.3) by the end of the study. During the 12-month period, two patients (2.4%) required medical therapy for BPH, two patients (2.4%) required transurethral resection of the prostate, whilst 10 patients were lost to follow-up (12.3%). As compared to baseline, none of the 61 sexually active patients who completed the 12-month follow-up period reported sexual or ejaculatory dysfunction. CONCLUSION: iTIND implantation is feasible, safe and effective in providing relief of BPH-related symptoms, at least until 12 months postoperatively. Sexual and ejaculatory functions are fully preserved. Further studies with a longer follow-up period are needed to assess the durability of these results and to clearly define the indications for iTIND implantation.

Human umbilical cord cells for cardiovascular tissue engineering: a comparative study.

OBJECTIVE: Tissue engineering of viable, autologous cardiovascular replacements with the potential to grow, repair and remodel represents an attractive approach to overcome the shortcomings of available replacements for the repair of congenital cardiac defects. Currently, vascular myofibroblast cells represent an established cell source for cardiovascular tissue engineering. Cell isolation requires the invasive harvesting of venous or arterial vessel segments prior to scaffold seeding, a technique which may not be preferable, especially in pediatric patients. This study evaluates cells isolated from human umbilical cord artery, umbilical cord vein and whole cord as alternative autologous cell sources for cardiovascular tissue engineering. METHODS: Cells were isolated from human umbilical cord artery (UCA), umbilical cord vein (UCV), whole umbilical cord (UCC) and saphenous vein segments (VC), and were expanded in culture. All three expanded cell groups were seeded on bioabsorbable copolymer strips and grown in vitro for 28 days. Isolated cells were characterized by flow cytometry, histology, immunohistochemistry, proliferation assays and compared to VC. Morphological analysis of the seeded polymer strips included histology, immunohistochemistry, sodium dodecyl sulfate-polyacrylamide gel electrophoresis, transmission electron microscopy (TEM), scanning electron microscopy (SEM) and uniaxial stress testing. RESULTS: UCA, UCV and UCC demonstrated excellent cell growth properties comparable to VC. Following isolation, all three cell groups showed myofibroblast-like morphology and characteristics by staining positive for alpha-smooth muscle actin (ASMA) and vimentin. Histology and immunohistochemistry of seeded polymers showed good tissue and extracellular matrix formation containing collagen I, III and elastin. TEM showed viable myofibroblasts and the deposition of collagen fibrils and progressive growing tissue formation, with a confluent surface, was observed in SEM. No difference was found among the mechanical properties of UCA, UCV, UCC and VC tissue engineered constructs. CONCLUSIONS: Tissue engineering of cardiovascular constructs by using UCA, UCV and UCC is feasible in an in vitro environment. Cell growth, morphology, characteristics and tissue formation were comparable between UCA, UCV, UCC and VC. UCC represent an attractive, readily available autologous cell source for cardiovascular tissue engineering offering the additional benefits of utilizing juvenile cells and avoiding the invasive harvesting of intact vascular structures.

Marked reduction and distinct patterns of eye blinking in patients with moderately dry eyes during video display terminal use.

PURPOSE: To analyze the spontaneous eye-blink rate (SEBR) and blinking pattern in patients with moderately dry eyes during video display terminal (VDT) use. METHODS: The SEBR of 30 patients with dry eye syndrome (median age 44.8 years, range 18 - 67 years) was measured using a computer-based video analysis system. Only complete eye blinks were recorded during 10 min of conversation, during initial VDT use and again after a preceding work period of 30 min. RESULTS: In comparison with SEBR during conversation (mean value 16.8 blinks/min, standard deviation 16.8 blinks/min) the SEBR significantly decreased during initial VDT use (6.6+/-4.8; P<0.001) and remained significantly decreased during re-measurement after 30 min (5.9+/-4.6; P<0.001). SEBR was not significantly different between initial VDT use and re-measurement after 30 min ( P=0.65). The SEBR was characterized by marked interindividual variability during conversation and VDT use. No significant correlation was found between SEBR (either during conversation or during VDT use), and the quality (tear break-up time) or quantity (Schirmer I test, Jones test) of the tear film. Typical blinking patterns were found to be (1). a relatively time-independent, irregular pattern, (2). an initial phase of 2-4 min with shorter inter-eye-blink intervals, and (3). alternating periods of higher and lower inter-eye-blink intervals. CONCLUSIONS: Reduction of the SEBR during VDT use is primarily determined by marked visual attention, resulting in an exacerbation of dry eye symptoms in predisposed humans. High interindividual variability and distinct patterns of eye blinking may be key factors in further clarification of VDT-eye interactions and develop individually designed solutions to prevent desiccation during VDT use.

Characteristics of spontaneous eyeblink activity during video display terminal use in healthy volunteers.

PURPOSE: To analyse the spontaneous eyeblink rate (SEBR) and inter-eyeblink intervals (IEBI) of normal volunteers before and during video display terminal (VDT) use. METHODS: The SEBR of 51 normal volunteers was measured by counting the absence of the corneal reflex using a computer-based video analysis system. Only complete eyeblinks were recorded within 10 min under three different conditions: during a conversation, during VDT use without corneal anaesthesia, and during VDT use with corneal anaesthesia. The IEBI (in seconds) were determined to study individual time-dependent changes of SEBR. RESULTS: In comparison with SEBR during conversation (mean 15.54 eyeblinks/min, standard deviation +/-13.74 eyeblinks/min) the SEBR decreased significantly during VDT use without corneal anaesthesia (5.34 +/- 4.53 eyeblinks/min). Corneal anaesthesia further significantly reduced SEBR (2.78 +/- 2.77 eyeblinks/min). The SEBR was characterized by marked interindividual variability, ranging between 11 and 664 eyeblinks/10 min during conversation, between 4 and 189 eyeblinks during VDT use without corneal anaesthesia and between 1 and 119 eyeblinks at VDT use with corneal anaesthesia. No significant correlation between SEBR (during conversation or during VDT use) and quality (break-up time) or quantity (Schirmer I test, Jones test) of the tear film could be detected. Evaluation of the IEBI revealed three different types of eyeblink pattern during VDT use without corneal anaesthesia. Type 1 was characterized by a very low SEBR (0-2 eyeblinks/min) and relatively homogeneous distribution of eyeblinks, type 2 showed a moderate SEBR (1.2-8.5 eyeblinks/min) including three further subtypes. Type 3 was characterized by a high SEBR (6.8-18.9 eyeblinks/min) of regular or irregular pattern. CONCLUSIONS: VDT use is associated with a profound decrease of the SEBR in healthy subjects. There are marked interindividual differences in SEBR and no correlation between the SEBR and ocular tear film parameters in normal eyes. The SEBR is further reduced by corneal anaesthesia. The presence of different patterns of eyeblinking may be related to various exogenous and endogenous factors and may lead to a better understanding of ocular reactions during VDT use.

Human umbilical cord cells: a new cell source for cardiovascular tissue engineering.

BACKGROUND: Tissue engineering of viable, autologous cardiovascular constructs with the potential to grow, repair, and remodel represents a promising new concept for cardiac surgery, especially for pediatric patients. Currently, vascular myofibroblast cells (VC) represent an established cell source for cardiovascular tissue engineering. Cell isolation requires the invasive harvesting of venous or arterial vessel segments before scaffold seeding, a technique that may not be preferable, particularly in pediatric patients. In this study, we investigated the feasibility of using umbilical cord cells (UCC) as an alternative autologous cell source for cardiovascular tissue engineering. METHODS: Human UCC were isolated from umbilical cord segments and expanded in culture. The cells were sequentially seeded on bioabsorbable copolymer patches (n = 5) and grown in vitro in laminar flow for 14 days. The UCC were characterized by flow cytometry (FACS), histology, immunohistochemistry, and proliferation assays and were compared to saphenous vein-derived VC. Morphologic analysis of the UCC-seeded copolymer patches included histology and both transmission and scanning electron microscopy. Characterization of the extracellular matrix was performed by immunohistochemistry and quantitative extracellular matrix protein assays. The tissue-engineered UCC patches were biomechanically evaluated using uniaxial stress testing and were compared to native tissue. RESULTS: We found that isolated UCC show a fibroblast-like morphology and superior cell growth compared to VC. Phenotype analysis revealed positive signals for alpha-smooth muscle actin (ASMA), desmin, and vimentin. Histology and immunohistochemistry of seeded polymers showed layered tissue formation containing collagen I, III, and glycoaminoglycans. Transmission electron microscopy showed viable myofibroblasts and the deposition of collagen fibrils. A confluent tissue surface was observed during scanning electron microscopy. Glycoaminoglycan content did not reach values of native tissue, whereas cell content was increased. The biomechanical properties of the tissue-engineered constructs approached native tissue values. CONCLUSIONS: Tissue engineering of cardiovascular constructs using UCC is feasible in an in vitro environment. The UCC demonstrated excellent growth properties and tissue formation with mechanical properties approaching native tissue. It appears that UCC represent a promising alternative autologous cell source for cardiovascular tissue engineering, offering the additional benefits of using juvenile cells and avoiding the invasive harvesting of intact vascular structures.