Modeling Self-Rollable Elastomeric Films for Building Bioinspired Hierarchical 3D Structures.

In this work, an innovative model is proposed as a design tool to predict both the inner and outer radii in rolled structures based on polydimethylsiloxane bilayers. The model represents an improvement of Timoshenko's formula taking into account the friction arising from contacts between layers arising from rolling by more than one turn, hence broadening its application field towards materials based on elastomeric bilayers capable of large deformations. The fabricated structures were also provided with surface topographical features that would make them potentially usable in different application scenarios, including cell/tissue engineering ones. The bilayer design parameters were varied, such as the initial strain (from 20 to 60%) and the bilayer thickness (from 373 to 93 µm). The model matched experimental data on the inner and outer radii nicely, especially when a high friction condition was implemented in the model, particularly reducing the error below 2% for the outer diameter while varying the strain. The model outperformed the current literature, where self-penetration is not excluded, and a single value of the radius of spontaneous rolling is used to describe multiple rolls. A complex 3D bioinspired hierarchical elastomeric microstructure made of seven spirals arranged like a hexagon inscribed in a circumference, similar to typical biological architectures (e.g., myofibrils within a sarcolemma), was also developed. In this case also, the model effectively predicted the spirals' features (error smaller than 18%), opening interesting application scenarios in the modeling and fabrication of bioinspired materials.

Evaluation of intraoperative slow-release dexamethasone implant combined with idiopathic epiretinal membrane removal.

PURPOSE: To evaluate the efficacy of intraoperative slow-release dexamethasone implant (DEX) combined with removal of idiopathic epiretinal membrane (ERM). METHODS: In this observational retrospective study, data of 40 patients with phakic eyes affected by idiopathic ERM were analysed. All patients underwent cataract phacoemulsification, 25-gauge (G) pars plana vitrectomy (PPV), ERM removal with DEX implant ("DEX YES" group, #20) or without DEX implant ("DEX NO" group, #20). We collected data on best-corrected visual acuity (BCVA) < 20/40 Snellen charts, central macular thickness (CMT) ≤ 400 µm (measured by SD-OCT) and integrity of sub-foveal ellipsoid/myoid zone. BCVA, CMT and intraocular pressure (IOP) were evaluated at baseline as well as 15, 30 and 90 days after surgery. RESULTS: In the "DEX YES" group, statistically significant BCVA improvement was observed at 15, 30 and 90 days (p < 0.001), while in the "DEX NO" group, improvements were observed only at 30 and 90 days (p < 0.001). In both groups, CMT significantly decreased at each follow-up visit (p < 0.001), and no statistically significant increase of IOP was detected at each follow-up visit. CONCLUSIONS: In this study, DEX accelerated the improvement of BCVA at 15 days after surgery. However, no evidence of further anatomical (CMT) and functional (BCVA) DEX effectiveness combined with removal of idiopathic ERM by 25-G PPV at 30 and 90 days follow-up was observed.

Thermal Analysis of Paraffin-Embedded Tissue Blocks for Anatomic Pathology Processes.

We analyze temperature dynamics in anatomic pathology samples to identify the most efficient refrigeration method and to predict the time available for optimal sectioning before sample heating, thus getting appropriate information for a correct diagnosis by anatomopathologists. A thermal finite element (FE) analysis was carried out with comsolmultiphysics to evaluate temperature variations in paraffin-embedded tissues, i.e., muscle, bone and fat, and the corresponding thermal stresses. Experiments with different tissues and thermocouple-based measurements allowed validating the FE simulations. Simulations allowed to estimate the time needed to bring the sample at the optimal temperature for sectioning (-8 to -4 °C) in different conditions: refrigeration on a cold plate, refrigeration in a cooled environment, and refrigeration in an environment with forced convection. Among the three cooling methods tested, the forced convection at -20 °C and with an air-flow speed of 5 m/s resulted in the shortest cooling time. As compared to the other methods, thermal stresses can be modulated by varying the air-flow speed. For the different conditions, the time needed for the surface of the tissue block to exit from a temperature corresponding to an optimal cutting, when leaving the sample exposed to room temperature after refrigeration, ranged from 12 to 310 s. We quantify the time needed to adequately refrigerate paraffin-embedded tissue samples and the time available before they leave the optimal temperature window for sectioning. We also evaluate the maximum stress attained in the paraffin block during the cooling and the heating transients. This information will help optimize anatomic pathology processes.

Effectiveness of TNF-α blockade in the treatment of refractory non-infectious scleritis: a multicentre study.

OBJECTIVES: To evaluate the efficacy of tumour necrosis factor (TNF)-α inhibitors in refractory non-infectious scleritis. METHODS: We carried out a retrospective study assessing the efficacy of TNF-α inhibitors in the treatment of scleritis, scleritis relapses, glucocorticoid (GC)-sparing effect, impact on best-corrected visual acuity (BCVA) and safety profile. RESULTS: Nineteen patients (28 eyes) were eligible for analysis. Scleritis inflammatory grading significantly improved from baseline to the last follow-up (median ± IQR 2±4 and 0±0 respectively, p=0.0006). Scleritis relapses significantly decreased between the 12 months preceding and following biologic therapy (p=0.001). Mean GC dosage decreased from baseline (19.00±13.56 mg) to the last follow-up (7.59±5.56 mg) (p=0.003). No significant differences regarding BCVA were observed. Two AEs were recorded (1 severe urticaria and 1 case of pneumonia and paradoxical psoriasis). CONCLUSIONS: TNF-α inhibitors are effective in the treatment of scleritis while allowing a GC-sparing effect and preserving BCVA.

Efficacy of monoclonal anti-tumour necrosis factor-α antibodies in uveitic macular oedema.

OBJECTIVES: To assess the efficacy of anti-tumour necrosis factor (TNF)-α agents in the treatment of refractory uveitic macular oedema (UME). METHODS: Patients with refractory UME treated with TNF-α blockers were retrospectively enrolled. Central macular thickness (CMT) was assessed at optical coherence tomography (OCT) at the start of TNF-α inhibition, after 3 and 12 months, and at the last follow-up visit. RESULTS: Thirty-six patients (56 eyes with UME) were enrolled. The mean follow-up period was 29.9±40.8 (4-184) months. A statistically significant decrease was observed in the frequency of UME (p<0.0001) and in the mean CMT values (p<0.0001) during the study period. Best corrected visual acuity improved in 35 eyes (62.5%), remained stable in 12 eyes (21.4%), reduced in 9 eyes (16.1%). The mean corticosteroid dosage significantly decreased during the study period (p=0.016). CONCLUSIONS: TNF-α inhibitors represent a useful treatment in patients with severe or resistant UME.

New Potential Weapons for Refractory Scleritis in the Era of Targeted Therapy.

OBJECTIVE: To assess the efficacy of biologic drugs, beyond tumor necrosis factor- (TNF-) α inhibitors, in the management of noninfectious refractory scleritis, either idiopathic or associated with systemic immune-mediated disorders. Patients and Methods. This is a retrospective study assessing the efficacy of several biologic agents (rituximab, anakinra, tocilizumab, and abatacept) and the small molecule tofacitinib in the treatment of scleritis through assessment of scleral inflammation and relapses, as well as treatment impact on best-corrected visual acuity (BCVA) and safety profile. RESULTS: Fourteen patients (19 eyes) were enrolled in the study. Scleritis inflammatory grading significantly improved from baseline to 3 months (p = 0.002) and from baseline to the last follow-up visit (p = 0.002). Scleritis relapses significantly decreased between the 12 months preceding and following biologic therapy (p = 0.007). No differences regarding BCVA were observed (p = 0.67). Regarding adverse events, only one patient developed pneumonia and septic shock under rituximab treatment. CONCLUSIONS: Our results, though limited to a low number of patients, highlight the effectiveness of different biologic therapies in the treatment of noninfectious refractory scleritis, showing to control scleral inflammation and allowing a significant reduction in the number of relapses.

Adalimumab effectively controls both anterior and posterior noninfectious uveitis associated with systemic inflammatory diseases: focus on Behçet's syndrome.

BACKGROUND: To compare the efficacy of Adalimumab (ADA) in noninfectious anterior uveitis (AU) and posterior segment (PS) involvement, associated with different conditions, with a focus on Behçet's syndrome (BS). METHODS: In this retrospective, multicenter post-hoc study, we evaluated the efficacy of ADA in terms of ocular control and relapses in 96 patients with AU and PS uveitis, either idiopathic (IU) or associated with BS or with other systemic disorders (OSD) (Juvenile Idiopathic Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, Vogt-Koyanagi-Harada, Inflammatory Bowel Disease), followed in three tertiary referral centers. RESULTS: Ninety-six patients (45 AU; 51 PS uveitis) were included. Eleven had IU, 58 BS, and 27 OSD. All patients with AU achieved complete long-term ocular control. In PS uveitis, 89%, 67% and 100% of patients with BS, IU and OSD achieved ocular control at the last follow-up (> 12 months), respectively. The lowest ocular relapse rate occurred in patients with AU with BS (1/13) or IU (0/2). ADA accounted for long-term disease control, and no predictors of ocular control and relapse were identified; particularly, ocular relapses seemed not related to systemic ones. Macular edema resolved in 75% and 67% of PS uveitis with BS and IU, respectively. CONCLUSIONS: ADA controls both anterior and posterior uveitis, with an efficacy similar in IU, BS and OSD patients. In BS, the efficacy of ADA seems to be independent of demographic and clinical characteristics, and ocular relapses mostly occurred independently from systemic ones. Based on our results, ADA may represent a valid alternative in anterior refractory uveitis.

Efficacy and safety of certolizumab pegol and golimumab in the treatment of non-infectious uveitis.

OBJECTIVES: The aim of the study was to evaluate the efficacy of golimumab (GOL) and certolizumab pegol (CZP) as additional treatment options for the treatment of uveitis. METHODS: Patients with longstanding uveitis receiving either GOL or CZP were retrospectively evaluated in terms of frequency of ocular flares, drug survival, changes in best corrected visual acuity (BCVA) and steroid-sparing effect. RESULTS: Twenty-one patients (30 eyes), 17 of whom being female, were enrolled in the study; 16 out of 21 patients had been previously treated with other tumour necrosis factor (TNF)-α blockers. A significant reduction in ocular flares (from 128.6 bouts for 100 patients-year to 42.9 events for 100 patients-year) was observed between the 12 months prior to the start of GOL or CZP and the 12 months thereafter (p=0.01). The 36-month drug survival was 54.5% for CZP and 50.0% for GOL with no statistically significant differences between the two biologic agents. No differences were detected concerning BCVA values and the mean corticosteroid intake between baseline and the last follow-up. The safety profile was excellent. CONCLUSIONS: GOL and CZP represent effective and safe treatment choices for patients with uveitis also when unsuccessfully treated with other anti-TNF-α drugs, permitting a significant reduction in the frequency of ocular flares and preserving visual function with a good long-term retention rate.

Efficacy of anti-tumour necrosis factor-α monoclonal antibodies in patients with non-infectious anterior uveitis.

OBJECTIVES: To assess the efficacy of monoclonal anti-tumour necrosis factor (TNF)-α agents in patients with anterior uveitis (AU) in terms of decrease of recurrences, variation of visual acuity and steroid sparing effect and to identify any demographic, clinical or therapeutic variables associated with a sustained response to monoclonal TNF-α inhibitors. METHODS: Data from patients suffering from AU treated with adalimumab, infliximab, golimumab or certolizumab pegol were retrospectively collected and statistically analysed. RESULTS: Sixty-nine patients (22 males, 47 females), corresponding to 101 eyes, were enrolled. The mean follow-up period was 29.25±23.51 months. The rate of ocular flares decreased from 42.03 events/100 patients/year recorded during the 12 months preceding the start of TNF-α inhibitors to 2.9 flares/100 patients/year after the start of treatment (p<0.0001). The overall decrease in ocular flares was 93.1%. No statistically significant changes were identified in the best corrected visual acuity during the follow-up period (p>0.99). The number of patients treated with corticosteroids at baseline was significantly higher compared with that referred to the 12-month evaluation (p<0.001) and to the last follow-up visit (p=0.006). Concomitant treatment with conventional disease-modifying anti-rheumatic drugs (cDMARDs) represented the sole clinical, demographic or therapeutic variable associated with long-term treatment duration (p=0.045, R2=0.87). CONCLUSIONS: Monoclonal TNF-α inhibitors induce a remarkable decrease in the recurrence of AU during a long-term follow-up period and lead to a significant steroid sparing effect along with stabilisation of visual acuity. Concomitant treatment with cDMARDs represented the sole variable associated with treatment duration in the long-term.

Adalimumab Accounts for Long-Term Control of Noninfectious Uveitis Also in the Absence of Concomitant DMARD Treatment: A Multicenter Retrospective Study.

OBJECTIVE: This study was aimed at assessing the long-term ocular control of adalimumab (ADA) in a large real-world population with noninfectious primary or secondary uveitis, focusing on the steroid-sparing effect and on disease-modifying antirheumatic drug (DMARD) cotreatment. METHODS: In this retrospective, multicenter study, the efficacy of ADA was evaluated in terms of ocular control, changes in best-corrected visual acuity (BCVA), corticosteroid-sparing effect, and drug retention rate, overall and stratified according to DMARD cotreatment. RESULTS: 106 patients were included. 88.7% had an associated systemic disease. After 6 and 12 months, proportions of patients with effective ocular control were 83.7% and 83.3%, respectively. At last the follow-up, 94.6% of patients had satisfactory ocular control. No difference in terms of ocular control at all time points emerged among patients starting ADA for ocular vs. systemic involvements. Patients with poor baseline BCVA remained stable or improved, while those with good BCVA hardly worsened. At 6 and 12 months, the median dose of prednisone significantly reduced to 5 mg/day (0-5) and 2.5 mg/day (0-5) (p < 0.001). Over a median follow-up of 36 months, 38 subjects discontinued ADA treatment. Mild to moderate side effects were reported in 7 patients (6.6%). ADA ocular control, corticosteroid-sparing effect, and drug retention rate were not influenced by the concomitant use of DMARDs. CONCLUSION: The long-term ocular control of ADA in noninfectious primary or secondary uveitis is confirmed, also for BCVA preservation. Concomitant use of DMARDs does not provide additional benefits to ADA alone in terms of ocular control, steroid spare, and drug retention rate.

Intravitreal Dexamethasone Implant as an Adjunct Weapon for Severe and Refractory Uveitis in Behçet's Disease.

BACKGROUND: The evidence on the use of dexamethasone implants in the treatment of Behçet's disease (BD)-related uveitis is limited to a few cases. OBJECTIVES: To evaluate the efficacy of dexamethasone implants on ocular functional, morphological, and clinical parameters in BD patients with severe refractory uveitis. METHODS: Five eyes from five BD patients were enrolled. A single intravitreal dexamethasone injection was applied to each eye. Best corrected visual acuity (BCVA), central macular thickness (CMT) assessed with optical coherence tomography, retinal vasculitis assessed by fluorescein angiography, vitreous haze score (Nussenblatt scale), intraocular pressure (IOP), and lens status (LOCS III, Lens Opacities Classification System III) were recorded at baseline and at 1, 3, and 6 month follow-up visits. RESULTS: At baseline, all eyes showed marked macular edema and 4/5 had concomitant active retinal vasculitis. Mean BCVA was increased from baseline at each control visit with a mean improvement of 0.26 ± 0.18 lines at 6 months follow-up. Mean CMT decreased from baseline at each control visit with a mean improvement at 6 months follow-up of 198.80 ± 80.08 µm. At the end of the study, none of the eyes showed macular edema and the mean CMT was 276.80 ± 24.94 µm. Retinal vasculitis resolved in all eyes. One eye experienced an IOP spike during treatment that resolved spontaneously, and one eye developed a clinically significant lens opacity at 6 months follow-up. CONCLUSIONS: Treatment with a dexamethasone implant in BD-uveitis and inflammatory macular edema was safe and effective as an additional treatment combined with systemic immunomodulatory drugs.

Ultrasound Stimulation of Piezoelectric Nanocomposite Hydrogels Boosts Chondrogenic Differentiation in Vitro, in Both a Normal and Inflammatory Milieu.

The use of piezoelectric nanomaterials combined with ultrasound stimulation is emerging as a promising approach for wirelessly triggering the regeneration of different tissue types. However, it has never been explored for boosting chondrogenesis. Furthermore, the ultrasound stimulation parameters used are often not adequately controlled. In this study, we show that adipose-tissue-derived mesenchymal stromal cells embedded in a nanocomposite hydrogel containing piezoelectric barium titanate nanoparticles and graphene oxide nanoflakes and stimulated with ultrasound waves with precisely controlled parameters (1 MHz and 250 mW/cm2, for 5 min once every 2 days for 10 days) dramatically boost chondrogenic cell commitment in vitro. Moreover, fibrotic and catabolic factors are strongly down-modulated: proteomic analyses reveal that such stimulation influences biological processes involved in cytoskeleton and extracellular matrix organization, collagen fibril organization, and metabolic processes. The optimal stimulation regimen also has a considerable anti-inflammatory effect and keeps its ability to boost chondrogenesis in vitro, even in an inflammatory milieu. An analytical model to predict the voltage generated by piezoelectric nanoparticles invested by ultrasound waves is proposed, together with a computational tool that takes into consideration nanoparticle clustering within the cell vacuoles and predicts the electric field streamline distribution in the cell cytoplasm. The proposed nanocomposite hydrogel shows good injectability and adhesion to the cartilage tissue ex vivo, as well as excellent biocompatibility in vivo, according to ISO 10993. Future perspectives will involve preclinical testing of this paradigm for cartilage regeneration.

Electrical and mechanical characterisation of single wall carbon nanotubes based composites for tissue engineering applications.

This paper presents the realisation of conductive matrices for application to tissue engineering research. We used poly(L-lactide (PLLA)), poly(epsilon-caprolactone) (PCL), and poly(lactide-co-glycolide) (PLGA) as polymer matrix, because they are biocompatible and biodegradable. The conductive property was integrated to them by adding single wall carbon nanotubes (SWNTs) into the polymer matrix. Several SWNTs concentrations were introduced aiming to understand how they influence and modulate mechanical properties, impedance features and electric percolation threshold of polymer matrix. It was observed that a concentration of 0.3% was able to transform insulating matrix into conductive one. Furthermore, a conductive model of the SWNT/polymer was developed by applying power law of percolation threshold.

Case report: 3D intracranial vessel wall MRI in Susac syndrome: potential relevance for diagnosis and therapeutic management.

Background: Susac syndrome (SS) is a rare immune-mediated vasculitis affecting retina, inner ear and brain. Assessment of central nervous system (CNS) involvement is currently based on standard brain magnetic resonance imaging (MRI) sequences. Accuracy of three dimensional (3D)-vessel wall imaging (VWI) was compared to standard sequences and contrast-enhanced-3D T2-fluid attenuated inversion recovery (CE-FLAIR) to assess CNS disease activity in two cases of definite SS. Methods: Brain MRI scan and retinal fluorescein angiogram (RFA) were performed at disease onset and at 1, 3, and 6 months after induction therapy start. CE-FLAIR and VWI based on 3D black-blood proton density weighted (PDW) with and without gadolinium were added to standard sequences on a 3 Tesla MRI scanner. Results: Contrast enhanced-VWI (CE-VWI) detected an abnormal diffuse leptomeningeal enhancement (LME) in both cases at onset and during follow-up. Pathological enhancement on CE-VWI persisted at 6-month brain MRI, despite absence of new lesions and disappearance of LME on CE-FLAIR. Follow-up RFA revealed new arterial wall hyperfluorescence in both cases. Conclusions: VWI may represent a useful tool for diagnosing and monitoring CNS disease activity in SS patients, as confirmed by concordance with RFA, leading treatment's choice and timing. Moreover, CE-VWI seemed at least as sensitive as CE-FLAIR in detecting LME, possibly being superior to the latter in posterior fossa. LME remission might be not accurate in predicting suppression of CNS inflammation in SS.

A Novel Approach for Multiple Material Extrusion in Arthroscopic Knee Surgery.

Articular cartilage defects and degenerative diseases are pathological conditions that cause pain and the progressive loss of joint functionalities. The most severe cases are treated through partial or complete joint replacement with prostheses, even if the interest in cartilage regeneration and re-growth methods is steadily increasing. These methods consist of the targeted deposition of biomaterials. Only a few tools have been developed so far for performing these procedures in a minimally invasive way. This work presents an innovative device for the direct deposition of multiple biomaterials in an arthroscopic scenario. The tool is easily handleable and allows the extrusion of three different materials simultaneously. It is also equipped with a flexible tip to reach remote areas of the damaged cartilage. Three channels are arranged coaxially and a spring-based dip-coating approach allows the fabrication and assembly of a bendable polymeric tip. Experimental tests were performed to characterize the tip, showing the ability to bend it up to 90° (using a force of ~ 1.5 N) and to extrude three coaxial biomaterials at the same time with both tip straight and tip fully bent. Rheometric analysis and fluid-dynamic computational simulations were performed to analyze the fluids' behavior; the maximum shear stresses were observed in correspondence to the distal tip and the channel convergence chamber, but with values up to ~ 1.2 kPa, compatible with a safe extrusion of biomaterials, even laden with cells. The cells viability was assessed after the extrusion with Live/Dead assay, confirming the safety of the extrusion procedures. Finally, the tool was tested arthroscopically in a cadaveric knee, demonstrating its ability to deliver the biomaterial in different areas, even ones that are typically hard-to-reach with traditional tools.

Enhancing Intermediate Vision in Patients Affected by Epiretinal Membrane Treated by Phaco-Vitrectomy.

BACKGROUND: The aim of this research was to see if a refractive enhanced monofocal IOL (Eyhance IOL, IOL Abbott Medical Optics, Inc., Santa Ana, CA, USA) can provide better intermediate vision in patients undergoing phaco-vitrectomy due to cataract and epiretinal macular membrane (ERM). METHODS: A nonrandomized prospective observational comparative study enrolled patients affected by cataract and ERM undergoing phaco-vitrectomy. A follow up of 6 months was established. Corrected and uncorrected visual acuity of both monocular and binocular types were assessed regarding intermediate and far distances. The CATQUEST 9-SF questionnaire was administered preoperatively and at the last follow-up. RESULTS: Twenty-three eyes of twenty-three patients were enrolled, with 11 in the enhanced monofocal group. The uncorrected and corrected distance visual acuity after 6 months was not statistically different. Both monocular and binocular uncorrected intermediate visual acuity after 6 months were higher in the enhanced monofocal group (p < 0.001). The corrected intermediate visual acuity after 6 months was higher in the enhanced monofocal group (p = 0.01). The CATQUEST-9SF questionnaire showed significant differences in the variation between the preoperative condition and six-month postoperative results (p < 0.001). CONCLUSIONS: This refractive enhanced monofocal IOL can provide better intermediate vision compared to a standard monofocal IOL in patients undergoing phaco-vitrectomy due to cataracts and ERM. Further studies are necessary to confirm these results.

Soft Perfusable Device to Culture Skeletal Muscle 3D Constructs in Air.

Devices for in vitro culture of three-dimensional (3D) skeletal muscle tissues have multiple applications, including tissue engineering and muscle-powered biorobotics. In both cases, it is crucial to recreate a biomimetic environment by using tailored scaffolds at multiple length scales and to administer prodifferentiative biophysical stimuli (e.g., mechanical loading). On the contrary, there is an increasing need to develop flexible biohybrid robotic devices capable of maintaining their functionality beyond laboratory settings. In this study, we describe a stretchable and perfusable device to sustain cell culture and maintenance in a 3D scaffold. The device mimics the structure of a muscle connected to two tendons: Tendon-Muscle-Tendon (TMT). The TMT device is composed of a soft (E ∼ 6 kPa) porous (pore diameter: ∼650 µm) polyurethane scaffold, encased within a compliant silicone membrane to prevent medium evaporation. Two tendon-like hollow channels interface the scaffold with a fluidic circuit and a stretching device. We report an optimized protocol to sustain C2C12 adhesion by coating the scaffold with polydopamine and fibronectin. Then, we show the procedure for the soft scaffold inclusion in the TMT device, demonstrating the device's ability to bear multiple cycles of elongations, simulating a protocol for cell mechanical stimulation. By using computational fluid dynamic simulations, we show that a flow rate of 0.62 mL/min ensures a wall shear stress value safe for cells (<2 Pa) and 50% of scaffold coverage by an optimal fluid velocity. Finally, we demonstrate the effectiveness of the TMT device to sustain cell viability under perfusion for 24 h outside of the CO2 incubator. We believe that the proposed TMT device can be considered an interesting platform to combine several biophysical stimuli, aimed at boosting skeletal muscle tissue differentiation in vitro, opening chances for the development of muscle-powered biohybrid soft robots with long-term operability in real-world environments.

Non-anti TNFα biologic agents for noninfectious uveitis associated with systemic inflammatory diseases: a systematic review.

INTRODUCTION: Noninfectious uveitis related to systemic inflammatory diseases represents a leading cause of blindness. Anti-TNFα agents are the first-line biologic therapy after traditional immunosuppressants, for ocular and systemic involvement. However, some patients fails anti-TNFα agents, due to primary inefficacy, loss of efficacy or adverse events. AREAS COVERED: This systematic review summarizes evidence on the efficacy and safety of non-anti-TNFα biologics in adult patients with noninfectious uveitis associated with systemic inflammatory diseases. The systematic review of PubMed and Embase yielded 3663 records, from which 16 studies were included (13 non-controlled, 3 controlled trials). Most studies focused on Behçet's syndrome (BS) and juvenile idiopathic arthritis (JIA) and assessed the efficacy of tocilizumab (n = 11), rituximab (n = 3), secukinumab (n = 1), or anakinra/canakinumab (n = 1). A body of evidence supports the use of tocilizumab BS and JIA-associated uveitis, for improving visual acuity, reducing central macular thickness, inducing ocular remission, and sparing corticosteroids. Preliminary data suggest that rituximab may represent a valid alternative, particularly in JIA, while anakinra/canakinumab might play a role in BS-associated uveitis. The role of secukinumab appears limited. EXPERT OPINION: Current evidence encourages investigations on the efficacy and safety of non-anti-TNFα agents in noninfectious non-idiopathic uveitis.

The role of anterior segment optical coherence tomography in uveitis-glaucoma-hyphema syndrome.

PURPOSE: To describe features of uveitis-glaucoma-hyphema (UGH) syndrome, using Anterior Segment-Optical Coherence Tomography (AS-OCT) and Ultrasound Biomicroscopy (UBM) and to evaluate the diagnostic role of AS-OCT as an imaging technique alternative to UBM. DESIGN: Retrospective case series. METHODS: Four eyes of 4 patients with UGH syndrome were analyzed. All patients reported previous uncomplicated cataract surgery with in-the-bag implantation of single-piece-intraocular lens (IOL). They underwent at presentation complete ophthalmological examination and imaging with slit-lamp anterior segment photographs, UBM and AS-OCT. RESULTS: Although AS-OCT did not allow to visualize the structures behind the iris, it displayed a contact between IOL (plate and/or haptics) and iris and IOL tilting in 3 out of 4 eyes. AS-OCT directly detected the cause of UGH syndrome in one eye, 2 eyes required some expedients to display the iris chafing, like scans in mydriasis and/or patient's gaze direction change. AS-OCT did not allow to appreciate the IOL-iris contact (showed by UBM technique) only in one eye, probably due to the change of patient position from supine to sitting, and consequent anteriorization of iris diaphragm. Furthermore AS-OCT showed fine details, as capsular bag collapse and indirect signs of haptic malposition in 3 out of 4 eyes. CONCLUSION: AS-OCT is a non-invasive technique that allows to determine IOL position and IOL-uveal contact in selected cases of UGH syndrome. Considering AS-OCT and UBM advantages and limitations, AS-OCT should be used as first imaging modality when clinical diagnosis is uncertain. When UGH diagnosis cannot be verified using AS-OCT, UBM should be performed.

Piezoelectric nanocomposite bioink and ultrasound stimulation modulate early skeletal myogenesis.

Despite the significant progress in bioprinting for skeletal muscle tissue engineering, new stimuli-responsive bioinks to boost the myogenesis process are highly desirable. In this work, we developed a printable alginate/Pluronic-based bioink including piezoelectric barium titanate nanoparticles (nominal diameter: ∼60 nm) for the 3D bioprinting of muscle cell-laden hydrogels. The aim was to investigate the effects of the combination of piezoelectric nanoparticles with ultrasound stimulation on early myogenic differentiation of the printed structures. After the characterization of nanoparticles and bioinks, viability tests were carried out to investigate three nanoparticle concentrations (100, 250, and 500 µg mL-1) within the printed structures. An excellent cytocompatibility was confirmed for nanoparticle concentrations up to 250 µg mL-1. TEM imaging demonstrated the internalization of BTNPs in intracellular vesicles. The combination of piezoelectric nanoparticles and ultrasound stimulation upregulated the expression of MYOD1, MYOG, and MYH2 and enhanced cell aggregation, which is a crucial step for myoblast fusion, and the presence of MYOG in the nuclei. These results suggest that the direct piezoelectric effect induced by ultrasound on the internalized piezoelectric nanoparticles boosts myogenesis in its early phases.