Safety of hydrogel spacers for rectal wall protection in patients with prostate cancer: A retrospective analysis of 200 consecutive cases.

OBJECTIVE: To evaluate the safety and complications of hydrogel spacer implantation. METHODS: This single-center historical cohort study retrospectively analyzed cases of hydrogel spacer implantation between October 2018 and March 2022. The survey items were the rates of possible hydrogel injection implementation, the success rate of hydrogel implantation including asymmetry, higher position, rectal wall infiltration, subcapsular injection, and other adverse events, and width created by the spacer. To investigate the learning curve, 1, 2, and 3 points were assigned to adverse event grades G1, G2, and G3, respectively. Spacer effectiveness obstruction, such as asymmetry was assigned 3 points. A Mann-Whitney U test was performed to assess statistically significant differences. RESULTS: The study included a total of 200 patients with a median (range) age of 70 (44-85) years. In 10 (5%) patients, hydrogel injection implementation was not possible. Of 190 patients who underwent hydrogel spacer placement, 168 (88%) received a satisfactory placement. The median (range) width of hydrogel spacers was 13.1 (4.4-18.7) mm. Spacer asymmetry, higher position, rectal wall infiltration, and prostate subcapsular infiltration occurred in 7 (3.7%), 5 (2.6%), 12 (6.3%), and 1 (0.5%) patients, respectively. G1 and G3 adverse events occurred in 13 (7%) and 4 (2%) patients, respectively. Practitioner #1 who performed the highest number of procedures had significantly (p = 0.04) lower total scores in group B. CONCLUSION: Spacer implantation yielded favorable outcomes with a high percentage of appropriate spacer implantation, and few major complications.

Long term electroencephalography in preterm neonates: Safety and quality of electrode types.

OBJECTIVES: The objective of this study was to compare gold cup and hydrogel electrodes for frequency of electrode replacement, longevity of the original electrodes after initial placement, recording quality, and skin safety issues in long-term EEG studies in preterm neonates. METHODS: We performed a prospective trial with newborns born at ≥23 weeks and ≤30 weeks of gestational age (GA). Two mirror image EEG electrode arrays were utilized on consecutive subjects, where gold cup electrodes alternated with hydrogel electrodes. RESULTS: Our sample included 50 neonates with mean GA of 27 (±1) weeks. The mean recording time was 84 (±15) hours. No difference was present in the frequency of replacement of either type across the total recording time (p = 0.8). We collected the time at which electrodes were first replaced, and found that hydrogel electrodes showed a longer uninterrupted recording time of 28(±2) hours vs. 20(±2) hours for gold cup electrodes (p = 0.01). Recording quality was similar in either type (p = 0.2). None of the patients experienced significant skin irritation from a discrete electrode. CONCLUSION: Long-term EEG studies can be performed with either gold cup or hydrogel electrodes, validating the safety and quality of both electrode types. SIGNIFICANCE: Hydrogel electrodes are a reasonable alternative for use in long-term EEG studies in preterm neonates.

A pH- and temperature-responsive bioresorbable injectable hydrogel based on polypeptide block copolymers for the sustained delivery of proteins in vivo.

Sustained delivery of protein therapeutics is limited owing to the fragile nature of proteins. Despite its great potential, delivery of proteins without any loss of bioactivity remains a challenge in the use of protein therapeutics in the clinic. To surmount this shortcoming, we report a pH- and temperature-responsive in situ-forming injectable hydrogel based on comb-type polypeptide block copolymers for the controlled delivery of proteins. Polypeptide block copolymers, composed of hydrophilic polyethylene glycol (PEG), temperature-responsive poly(γ-benzyl-l-glutamate) (PBLG), and pH-responsive oligo(sulfamethazine) (OSM), exhibit pH- and temperature-induced sol-to-gel transition behavior in aqueous solutions. Polypeptide block copolymers were synthesized by combining N-carboxyanhydride-based ring-opening polymerization and post-functionalization of the chain-end using N-hydroxy succinimide ester activated OSM. The physical properties of polypeptide-based hydrogels were tuned by varying the composition of temperature- and pH-responsive PBLG and OSM in block copolymers. Polypeptide block copolymers were non-toxic to human embryonic kidney cells at high concentrations (2000 µg mL-1). Subcutaneous administration of polypeptide block copolymer sols formed viscoelastic gel instantly at the back of Sprague-Dawley (SD) rats. The in vivo gels exhibited sustained degradation and were found to be bioresorbable in 6 weeks without any noticeable inflammation at the injection site. Anionic characteristics of hydrogels allow efficient loading of a cationic model protein, lysozyme, through electrostatic interaction. Lysozyme-loaded polypeptide block copolymer sols readily formed a viscoelastic gel in vivo and sustained lysozyme release for at least a week. Overall, the results demonstrate an elegant approach to control the release of certain charged proteins and open a myriad of therapeutic possibilities in protein therapeutics.

Medicated ocular bandages and corneal health: potential excipients and active pharmaceutical ingredients.

Corneal blindness can occur due to improper healing of the corneal tissues after induced injury or abrasion which can be accidental, pathogenic, or after corneal surgery. Abnormal regulation of the healing mechanisms can lead to corneal opacity. Reducing inflammation and promoting epithelial wound healing are crucial for scar-free corneal recovery without eyesight complications. Current approaches for corneal wound healing involve amniotic membrane (AM) bandages, bandage contact lenses (BCL), and collagen shields in conjunction with frequent administration of therapeutic eye drops. The problem with eye drops is poor bioavailability and patient incompliance that might lead to corneal wound healing complications and poor clinical outcomes. Various methods have been proposed for loading drugs into medicated bandage lenses. There are advantages and limitations associated with each technique regarding the ease of manufacture, drug loading, release kinetics, and suitability with various therapeutics and hydrogel types. There is still, however, no drug-eluting corneal bandage on the market despite the need for such a convenient and cost-efficient strategy for corneal wound healing. This review will highlight materials and therapeutics that can be used in medicated ocular bandages and various ways of incorporating drugs, while discussing the limitations and challenges associated with bringing medicated ocular bandages in the market.

Evaluation of the hemocompatibility of RADA 16-I peptide.

RADA 16-I is an ionic self-assembling peptide that can form macroscopic scaffolds through ß-sheet structures which are used in favor of cell growth and tissue engineering. This peptide has also the ability to stop bleeding effectively and quickly (∼20 seconds) when applied directly to the injuries. This study is focused on coagulation process, platelet aggregation, C3 and C4 concentrations, CBC counting, hemolysis, and white blood cell morphology tests to analyze hemocompatibility of RADA 16-I at different concentrations - 0.1, 0.2, 0.3 and 0.5%. According to the results, RADA 16-I hydrogel decreased the number of blood cells, slightly increased clot formation time and platelet aggregation, and yielded negligible hemolysis and only small changes in C3 and C4 concentrations and white blood cell morphology. All by all, the in vitro tests of hemocompatibility showed no perturbation in the blood composition when the peptides were in contact with the blood. The observed rapid hemostasis might be a result of increasing local concentrations of molecules involved in the formation of clot near the peptide hydrogel, thereby making a barrier which ended up with complete hemostasis. In conclusion, our experiments strongly supported further development of biomaterials based on RADA 16-I peptide.

Hydrogel spacer distribution within the perirectal space in patients undergoing radiotherapy for prostate cancer: Impact of spacer symmetry on rectal dose reduction and the clinical consequences of hydrogel infiltration into the rectal wall.

PURPOSE: Hydrogel prostate-rectum spacers, biomaterials placed between the prostate and rectum, continue to gain interest as a method to reduce or limit rectal dose during dose escalated prostate cancer radiation therapy. Because the spacer is initially injected into the perirectal space as a liquid, the final distribution can vary. The purpose of this study was to evaluate hydrogel spacer (SpaceOAR system) implantation and distribution from a recent prospective randomized control trial and correlate spacer symmetry with rectal dose reduction as well as rectal wall infiltration (RWI) to acute and late toxicity. METHODS AND MATERIALS: T2-weighted magnetic resonance imaging sets of 149 patients enrolled in a prospective clinical trial who received transperineal spacer injection were assessed for hydrogel spacer midline symmetry and RWI using a semiqualitative scoring system. Symmetry was then correlated to rectal dose reduction using a Student t test (1-tailed, paired), whereas a Fisher exact test was used to correlate RWI with acute and late rectal toxicity. All patients had control treatment plans created before spacer injection. RESULTS: Hydrogel spacer was symmetrically placed at midline for 71 (47.7%) patients at the prostate midgland as well as 1 cm superior and inferior to midgland. The remaining 78 (50.9%) patients had some level of asymmetry, with only 2 (1.3%) having far lateral distribution (ie, >2 cm) of hydrogel spacer. As the hydrogel spacer became more asymmetric, the level of rectal dose reduction relative to their control plans decreased. However, all but the most asymmetrical 1.3% had significant rectal dose reduction (P < .05). Rectal wall hydrogel spacer infiltration was seen in 9 (6.0%) patients. There was no correlation between RWI and procedure-related adverse events or acute/late rectal toxicity. CONCLUSIONS: Significant reduction of rectal dose can still be achieved even in the setting of asymmetric hydrogel spacer placement. RWI does not correlate with patient complications.

SpaceOAR Hydrogel in Dose-escalated Prostate Cancer Radiotherapy: Rectal Dosimetry and Late Toxicity.

AIM: To investigate the feasibility, dosimetric benefits and late toxicity of a temporary hydrogel spacer between the rectum and the prostate for prostate intensity-modulated radiotherapy. MATERIALS AND METHODS: Thirty patients with prostate cancer were enrolled on a phase I/II study. All patients underwent magnetic resonance imaging before and after placement of 10 cm(3) of hydrogel. The first 10 patients had an additional magnetic resonance imaging after the completion of radiation treatment. SpaceOAR hydrogel was injected under general anaesthetic using a transperineal approach with transrectal ultrasound guidance. Primary end points were perioperative toxicity and comparison of rectal dosimetry. Secondary end points included cute and late radiation toxicity. All patients were planned on both pre- and post-hydrogel scans to a D95 of 80 Gy in 40 fractions. A contemporary control group of 110 prostate cancer patients treated with the same prescription was identified for comparison. RESULTS: There were no perioperative complications. Rectal doses were significantly lower for the post-hydrogel plans, especially above 65 Gy (V82 = 0.2% versus 1.3%; V80 = 0.8% versus 5.3%; V75 = 2.2% versus 9.5%; V70 = 3.7% versus 12.3%; V65 = 5.4% versus 14.7%; V40 = 22.9% versus 32% and V30 = 42.7% versus 49.4%). There was no significant difference in acute grade 1 and 2 gastrointestinal toxicity, which was 43% versus 51% and 0% versus 4.5% in the hydrogel and control groups, respectively. Late grade 1 was significantly less frequent in the hydrogel group (16.6% versus 41.8%, P = 0.04). CONCLUSION: SpaceOAR hydrogel was inserted with minimal side-effects. Dosimetric benefits were greatest at higher rectal doses (V65 to V82). Late grade 1 gastrointestinal toxicity was significantly lower than that seen in patients treated without hydrogel.

Efficacy and safety of loxoprofen hydrogel patch versus loxoprofen tablet in patients with knee osteoarthritis: a randomized controlled non-inferiority trial.

This study is aimed at comparing the efficacy and safety of loxoprofen sodium hydrogel patch (LX-P) with loxoprofen sodium tablet (LX-T) in patients with knee osteoarthritis (OA). One hundred sixty-nine patients were enrolled in a randomized, controlled, double-blind, double-dummy, multicenter, non-inferiority trial of LX-P. Patients were randomly assigned to either LX-P or LX-T groups for a 4-week treatment. The primary efficacy endpoint was the proportion of patients with an overall improvement of ≥50%, and the secondary efficacy endpoint was the proportion of patients with an improvement of ≥25% from baseline in each of the seven main symptoms. The non-inferiority trial was based on a power of 80% and significance level of 2.5% with a non-inferiority margin of -10%. In both intention-to-treat (ITT) and per-protocol (PP) analyses, LX-P was as effective as LX-T in regard to the primary endpoint. In the ITT analysis, the difference between the two groups was 12.6% [95% confidence interval, -1.7 to 26.9%]. No significant differences were found between the two groups in any of the secondary efficacy outcomes. A lower incidence of adverse events was observed in LX-P group; however, the difference was not statistically significant. No serious adverse events were reported in the LX-P group, whereas one case was reported in LX-T group. Based on the present study, topical loxoprofen patch was non-inferior to oral loxoprofen in patients with knee osteoarthritis.

[Chemical microanalysis of mineral deposits on explanted hydrophilic acrylic intraocular lenses].

AIM: to perform chemical microanalysis of mineral deposits on the surface of explanted hydrophilic acrylic intraocular lenses (IOL). MATERIAL AND METHODS: Two soft IOLs made of hydrophilic acryl (one, however, hydrophobic surface coated) and explanted 3 and 6 years after implantation were examined by scanning electron microscopy (EVO LS10, "Karl Zeiss", Germany). Chemical composition of the lens surface was studied using an energy-dispersive spectrometer (EDS X-Max50, Oxford, Great Britain). RESULTS: Chemical microanalysis allowed identification of the deposits, which turned out to be non-stoichiometric hydroxylapatite (also, hydroxyapatite (HA)) crystals with zinc impurity (up to 1.4%weight). CONCLUSION: The two samples represent two stages of a single process. The early stage is associated with newly formed HA crystals that are unable to cause any significant changes to the lens surface. However, as spherocrystals grow, they exert a crystallization effort that moves their growth centers apart with subsequent lens rupture and deformation. Crystal morphology undergoes dynamic changes: while primary (newly formed) crystals are sheaf-like, mature are spheres. A growing HA is non-stoichiometric. Zinc abundance accounts for appearance of its separate mineral phase. Hydrophilic properties of acrylic polymer determine its high affinity for HA crystals. Hydrophobic coating (sample no.1) does not completely prevent lens opacification due to mineral deposits on its surface.

Poloxamer bioadhesive hydrogel for buccal drug delivery: Cytotoxicity and trans-epithelial permeability evaluations using TR146 human buccal epithelial cell line.

A salbutamol sulfate (SS)-Poloxamer bioadhesive hydrogel specially developed for buccal administration was investigated by studying interactions with TR146 human buccal epithelium cells (i.e. cellular toxicity (i) and trans-epithelial SS diffusion (ii)). The assessment of cell viability (MTT, Alamar Blue), membrane integrity (Neutral Red), and apoptosis assay (Hoechst 33342), were performed and associated to Digital Holographic Microscopy analysis. After the treatment of 2h, SS solution induced drastic cellular alterations that were prevented by hydrogels in relation with the concentrations of poloxamer and xanthan gum. The formulation containing P407 19%/P188 1%/Satiaxane 0.1% showed the best tolerance after single and multiple administrations and significantly reduced the trans-epithelial permeability from 5.00±0.29 (×10(3)) (SS solution) to 1.83±0.22 cm/h. Digital Holographic Microscopy images in good agreement with the viability data confirmed the great interest of this direct technique. In conclusion, the proposed hydrogels represent a safe and efficient buccal drug delivery platform.

[Delayed Hydrocephalus Following Embolization with Hydrogel Coils for an Unruptured Aneurysm at the Tip of the Basilar Artery:A Case Report].

We report the case of a 62-year-old woman with delayed hydrocephalus following endovascular embolization with hydrogel coils for an unruptured aneurysm at the tip of the basilar artery. She underwent the first and second embolizations with bare platinum coils and matrix coils, respectively. However, recanalization and regrowth of the aneurysm was observed, and a successful third embolization with hydrogel coils(2 mm/4 cm×2)was performed. However, progressive ventricular enlargement was observed during 8 months after the third treatment. MRI with fluid-attenuated inversion recovery sequence showed edema in the perianeurysmal white matter, as well as marked communicating hydrocephalus. The aneurysmal wall was enhanced with the administration of gadolinium-DTPA. The cerebrospinal fluid(CSF)protein level was 113 mg/dL. A ventriculo-peritoneal shunt was placed, and the patient was discharged without symptoms. It was postulated that endovascular embolization with hydrogel coils causes inflammation of the aneurysmal wall and perianeurysmal white matter, followed by elevation of CSF protein and subsequent communicating hydrocephalus.

[A Case of Brainstem Hemorrhage Following Embolization of a Large Basilar Aneurysm with Hydrogel-Coated Coils].

OBJECTIVE: Endovascular coil embolization of intracranial aneurysms is associated with better outcomes and a lower mortality rate compared with surgical clip occlusion. However, a principal disadvantage of endovascular therapy is the higher rate of retreatment compared with neurosurgical clipping. Self-expandable hydrogel-coated coils were developed to reduce recanalization rates of cerebral aneurysms by promoting complete volumetric aneurysm occlusion. Herein, we report a case of brainstem hemorrhage following coil embolization of a large basilar aneurysm with hydrogel-coated coils. CASE PRESENTATION: A 65-year-old female with a history of hypertension, who presented with worsening headaches, right hemiplegia, and left oculomotor palsy, underwent endovascular treatment for a large basilar aneurysm. The aneurysm was treated with both hydrogel-coated coils and bare platinum coils. Hydrogel-coated coils represented 46% of the coil length in the aneurysm. The patient was discharged from the hospital with improvement of neurological deficits 6 days after the procedure. However, the patient was readmitted with perianeurysmal edema in the midbrain 23 days after coil embolization. Follow-up angiography 26 days after the procedure showed complete obliteration of the aneurysm. Two weeks later, the patient presented with a large brainstem hemorrhage and died. Pathological findings revealed intraparenchymal hemorrhage in the pons without rupture of the aneurysm. CONCLUSION: Hydrogel-coated coils may cause a marked inflammatory response that may result in intracerebral hemorrhage.

Masquerading Orbital Abscess Following Attempted Hydrogel Scleral Buckle Removal: Diagnostic Value of Orbital Magnetic Resonance Spectroscopy.

A 59-year-old patient developed acute proptosis, peri-orbital swelling and restriction of ocular movements 2 days after attempted scleral buckle removal. Initial clinical and orbital MRI findings were suggestive for orbital cellulitis and orbital abscess. Empiric intravenous antibiotics were not effective. Proton magnetic resonance spectroscopy (MRS) revealed a distinctive composition and helped rule out suppurative and neoplastic processes. The patient recovered soon after removing clear liquefied and tiny particles of the hydrogel buckle by an effective peristaltic technique.

The use of polyacrylate-polyalcohol copolymer hydrogel in the endoscopic treatment of primary vesicoureteral reflux in children.

BACKGROUND/PURPOSE: It is still under discussion which is the best tissue augmenting substance for the endoscopic treatment of children with vesicoureteral reflux (VUR). We describe our preliminary experience (September 2009-November 2011) with polyacrylate-polyalcohol copolymer hydrogel (PPCH). METHODS: This is an observational, descriptive, prospective study which included 81 female and male patients (age 1-14 years) diagnosed with unilateral (n=45) and bilateral (n=36) primary VUR comprising a total of 117 refluxing renal units (RRU). Complex cases were excluded from the study. All patients were clinically and radiologically evaluated and those who met the inclusion criteria were treated endoscopically with a single subureteral injection of PPCH by a single surgeon. 11 patients (13.5%) had a pathological 99mTc-DMSA before treatment. The volume of injected product was measured in all cases. Results were considered successful if 6months postinjection, conventional voiding cystourethrogram (VCUG) revealed VUR was cured (Grade 0). Follow-up ranged from 7 to 32months. RESULTS: The overall resolution rate based on the number of RRUs studied was 92.3% (108/117). The mean injected volume of PPCH per patient was 0.6ml. One patient with obstructive anuria required vesicoureteral reimplantation. Other complications were persistent, self-limiting hematuria (n=2); lumbar pain (n=4) and urinary tract infection with normal VCUG (n=4). CONCLUSIONS: Our short term data show PPCH provides a high level of reflux resolution in selected patients. Long term follow-up is required.

Lower irritation microemulsion-based rotigotine gel: formulation optimization and in vitro and in vivo studies.

BACKGROUND: Rotigotine is a potent and selective D1, D2, and D3 dopaminergic receptor agonist. Due to an extensive first-pass effect, it has a very low oral bioavailability (approximately 0.5% in rats). PURPOSE: The present investigation aimed to develop a microemulsion-based hydrogel for transdermal rotigotine delivery with lower application site reactions. METHODS: Pseudoternary phase diagrams were constructed to determine the region of oil in water (o/w)-type microemulsion. Central composite design was used to support the pseudoternary phase diagrams and to select homogeneous and stable microemulsions with an optimal amount of rotigotine permeation within 24 hours. In vitro skin permeation experiments were performed, using Franz diffusion cells, to compare rotigotine-loaded microemulsions with rotigotine solutions in oil. The optimized formulation was used to prepare a microemulsion-based hydrogel, which was subjected to bioavailability and skin irritancy studies. RESULTS: The selected formulations of rotigotine-loaded microemulsions had enhanced flux and permeation coefficients compared with rotigotine in oil. The optimum microemulsion contained 68% water, 6.8% Labrafil(®), 13.44% Cremophor(®) RH40, 6.72% Labrasol(®), and 5.04% Transcutol(®) HP; the drug-loading rate was 2%. To form a microemulsion gel, 1% Carbomer 1342 was added to the microemulsion. The bioavailability of the rotigotine-loaded microemulsion gel was 105.76%±20.52% with respect to the marketed rotigotine patch (Neupro(®)). The microemulsion gel irritated the skin less than Neupro. CONCLUSION: A rotigotine microemulsion-based hydrogel was successfully developed, and an optimal formulation for drug delivery was identified. This product could improve patient compliance and have broad marketability.

Treatment of alveolar-pleural fistula with endobronchial application of synthetic hydrogel.

BACKGROUND: Alveolar-pleural fistula with persistent air leak is a common problem causing significant morbidity, prolonged hospital stay, and increased health-care costs. When conventional therapy fails, an alternative to prolonged chest-tube drainage or surgery is needed. New bronchoscopic techniques have been developed to close the air leak by reducing the flow of air through the leak. The objective of this study was to analyze our experience with bronchoscopic application of a synthetic hydrogel for the treatment of such fistulas. METHODS: We conducted a retrospective study of patients with alveolar-pleural fistula with persistent air leaks treated with synthetic hydrogel application via flexible bronchoscopy. Patient characteristics, underlying disease, and outcome of endoscopic treatment were analyzed. RESULTS: Between January 2009 and December 2013, 22 patients (14 men, eight women; mean age ± SD, 62 ± 10 years) were treated with one to three applications of a synthetic hydrogel per patient. The primary etiology of persistent air leak was necrotizing pneumonia (n = 8), post-thoracic surgery (n = 6), bullous emphysema (n = 5), idiopathic interstitial pneumonia (n = 2), and sarcoidosis (n = 1). Nineteen patients (86%) had complete resolution of the air leak, leading to successful removal of chest tube a mean ( ± SD) of 4.3 ± 0.9 days after last bronchoscopic application. The procedure was very well tolerated, with two patients coughing up the hydrogel and one having hypoxemia requiring bronchoscopic suctioning. CONCLUSIONS: Bronchoscopic administration of a synthetic hydrogel is an effective, nonsurgical, minimally invasive intervention for patients with persistent pulmonary air leaks secondary to alveolar-pleural fistula.

Severe keratomalacia after 12 months of continuous hydrogel contact lens wear in a psychiatric patient.

A 53-year-old cachectic patient diagnosed with major depressive disorder was referred to our department for evaluation of a visible deformation of the right eye. She had been wearing hydrogel contact lenses on a continuous basis without removal for the last 12 months, influenced by low self-esteem and social isolation. Slit-lamp examination of the right eye showed a conical cornea, extensive neovascularization, severe stromal melting with descemetocele formation and forward bulging of the iris. Examination of the left eye revealed multiple corneal opacities, deep stromal neovascularization and anterior chamber inflammation. No sign of infection was present. Vitamin A deficiency was suspected and later confirmed. The patient required evisceration of the right eye and psychiatric treatment. Inflammatory signs of the left eye resolved within 1 week of initiating treatment. This case illustrates the synergistic effect of soft contact lens abuse and vitamin A deficiency in a psychiatric patient, and emphasizes the importance of instructing vulnerable patients on appropriate lens use and care.