On the necessity of a customized knee spacer in peri-prosthetic joint infection treatment: 3d numerical simulation results

Peri-prosthetic joint infections (PJIs) dramatically affect human health, as they are associated with high morbidity and mortality rates. Two-stage revision arthroplasty is currently the gold standard treatment for PJI and consists of infected implant removal, an accurate debridement, and placement of antimicrobial impregnated poly-methyl-metha-acrylate (PMMA) spacer. The use of antibiotic-loaded PMMA (ALPMMA) spacers have showed a success rate that ranges from 85% to 100%. ALPMMA spacers, currently available on the market, demonstrate a series of disadvantages, closely linked to a low propensity to customize, seen as the ability to adapt to the patients’ anatomical characteristics, with consequential increase of surgical complexity, surgery duration, and postoperative complications. Conventionally, ALPMMA spacers are available only in three or four standard sizes, with the impossibility of guaranteeing the perfect matching of ALPMMA spacers with residual bone (no further bone loss) and gap filling. In this paper, a 3D model of an ALPMMA spacer is introduced to evaluate the cause-effect link between the geometric characteristics and the correlated clinical improvements. The result is a multivariable-oriented design able to effectively manage the size, alignment, stability, and the patients’ anatomical matching. The preliminary numerical results, obtained by using an “ad hoc” 3D virtual planning simulator, clearly point out that to restore the joint line, the mechanical and rotational alignment and the surgeon’s control on the thicknesses (distal and posterior thicknesses) of the ALPMMA spacer is mandatory. The numerical simulations campaign involved nineteen patients grouped in three different scenarios (Case N◦ 1, Case N◦ 2 and Case N◦ 3) whose 3D bone models were obtained through an appropriate data management strategy. Each scenario is characterized by a different incidence rate. In particular, the observed rates of occurrence are, respectively, equal to 17% (Case N◦ 1), 74% (Case N◦ 2), and 10% (Case N◦ 3)

A customized knee antibiotic-loaded pmma spacer: A preliminary design analysis

A preliminary design of customized antibiotic-loaded poly-methyl-methacrylate (ALP-MMA) spacer characterized by an appropriate footprint according to the specific patient’s anatomy and a reliable mechanical response to severe functional loads (i.e., level walking and 45◦ bent knee) is reported. The targeted virtual prototyping process takes origin from a novel patented 3D geometrical conceptualization characterized by added customization features and it is validated by a preliminary FEM-based analysis. Mechanical and thermomechanical properties of the antibiotic-doped orthopedic PMMA cement, which will be used for the future prototype manufacturing, were measured experimentally by testing samples taken during a real day-running orthopedic surgery and manufactured according to the surgeon protocol. FEM analysis results indicate that small area is subjected to intensive stresses, validating the proposed geometry from the mechanical point of view, under the two loading scenarios, moreover the value of safety margins results positive, and this is representa-tive of the lower stress magnitude compared to the critical material limits. The experimental data confirm that the presence of antibiotic will last during the surgeon period moreover, the temperature dependent modulus of the bone cement is slightly affected by the body range temperature whereas it will drastically drop for higher temperature out the range of interest. A complete customization, according to a patient anatomy, and the corresponding real prototype spacer will be manufactured by 3D printing techniques, and it will be validated by destructive testing during the second stage of this activity before commercialization

A simple scheme for the inversion of a Preisach like hysteresis operator in saturation conditions

A class of operators based on a Prandtl-Ishilinskii operator with inverse in a closed form is presented. Conversely to those considered in the past, they describe the B - H constitutive equation and not the usual J - H link. This allows its application in numerical schemes for the description of nonlinear dynamic circuits in transient conditions, with low formulation effort and computational weight, with respect to the standard inversion of the operator. The model has been implemented into a numerical scheme describing a RL nonlinear and hysteretic circuit, outlining the effects of residual magnetization and coercive field on the global current dynamics. The model performances are preliminary compared to numerical model based on the standard numerical inversion of the operator, along with the experimental results of transient current analysis

Small fragments sodium sulfated hyaluronate, more than hyaluronic acid, reduces LPS-induced cytokine/chemokine levels in HaCaT cells

Hyaluronic acid (HA) is a linear non-sulphated glycosaminoglycan, used in dermatology as a biomaterial for bioengineering purposes, temporary dermal filler, stimulation of wound healing as well as drug vehicle in topical formulations. In addition to the well-characterized structural properties, extensive research on HA has revealed a range of vastly immunemodulatory effects, dependent on its size. In this in vitro study we investigated the ability of HA-S3, a small fragment HA (MW, molecular weight: 68 kDa) with degree of sulphatation of 3 and of HA fraction (MW:210 kDa) to reduce the bacterial induced inflammatory response in spontaneous immortalized keratinocytes. To this purpose, HaCaT cells were treated for 24 hours with 25 µg/ml of E. Coli derived bacterial lipopolysaccharide (LPS) in absence or presence of small fragment HA-S3 or HA. Cell viability was thereafter assessed using trypan blue stain and interleukin (IL)-8, IL-1β and tumor necrosis factor alpha (TNF-α) concentrations were determined in cell supernatants by single enzyme-linked immunoadsorbent assay (ELISA). Our results showed that cell viability was not affected either by HA-S3 or HA which in turn were able to reduce LPS-induced mortality. HA and especially HA-S3 were able to significantly reduce LPS-induced pro-inflammatory cytokines. Our observation might suggest new perspectives in the development of HA-S3 containing topical products able to modulate cutaneous inflammatory response

Unsulfated biotechnological chondroitin by itself as well as in combination with high molecular weight hyaluronan improves the inflammation profile in osteoarthritis in vitro model

Several studies suggest that inflammation has a pivotal role during the progression of osteoarthritis (OA) and cytokines have been identified as the main process mediators. This study aimed to explore the ability to modulate the main OA pro-inflammatory biomarkers of novel gels (H-HA/BC) based on high molecular weight hyaluronan (H-HA) and unsulfated biotechnological chondroitin (BC). For the first time, BC was tested also in combination with H-HA on human primary cells isolated from pathological knee joints. Specifically, the experiments were performed using an OA in vitro model based on human chondrocytes and synoviocytes. To evaluate the anti-inflammatory effects of H-HA/BC in comparison with H-HA and BC single gels, NF-kB, COMP-2, MyD88, MMP-13 and a wide range of cytokines, known to be specific biomarkers in OA (e.g., IL-6, IL-8, and TNF-α), were evaluated. In addition, cell morphology and proliferation occurring in the presence of either H-HA/BC or single components were assessed using time-lapse video microscopy. It was shown that synovial fluids and cells isolated from OA suffering patients, presented a cytokine pattern respondent to an ongoing inflammation status. H-HA and BC significantly reduced the levels of 23 biomarkers associated with cartilage damage. However, H-HA/BC decreased significantly 24 biological mediators and downregulated 19 of them more efficiently than the single components. In synoviocytes cultures, cytokine analyses proved that H-HA/BC gels re-established an extracellular environment more similar to a healthy condition reducing considerably the concentration of 11 analytes. Instead, H-HA and BC significantly modulated 7 (5 only with a longer treatment) and 8 biological cytokines, respectively. Our results suggest that H-HA/BC beyond the viscosupplementation effect typical for HA-based gels, can improve the inflammation status in joints and thus could be introduced as a valid protective and anti-inflammatory intraarticular device in the field of Class III medical devices for OA treatments

Modular Hybrid Energy Concept Employing a Novel Control Structure Based on a Simple Analog System

This paper proposes a novel control topology which enables the setup of a low cost analog system leading to the implementation of a modular energy conversion system. The modular concept is based on hybrid renewable energy (solar and wind) and uses high voltage inverters already available on the market. An important feature of the proposed topology is a permanently active current loop, which assures short circuit protection and simplifies the control loops compensation. The innovative analogue solution of the control structure is based on a dedicated integrated circuit (IC) for power factor correction (PFC) circuits, used in a new configuration, to assure an efficient inverter start-up. The energy conversion system (control structure and maximum power point tracking algorithm) is simulated using a new macromodel-based concept, which reduces the usual computational burden of the simulator and achieves high processing speed. The proposed novel system is presented in this article from concept, through the design and implementation stages, is verified through simulation and is validated by experimental results

Retinal Vascular Assessment in Psoriasis: A Multicenter Study

Purpose: To investigate the vascular status of the macula in psoriasis patients without history of ocular inflammation by Optical Coherence Tomography Angiography (OCTA). Methods: This prospective cross-sectional multicenter study included 55 psoriasis patients and 55 control healthy subjects. A complete eye examination and 6 mm × 6 mm OCTA imaging were performed. Retinal vascular status was evaluated by analyzing vascular density (VD) of superficial vascular plexus (superficial wVD) and deep vascular plexuses (deep wVD) in a 6 mm × 6 mm area and in foveal (superficial fVD and deep fVD) and parafoveal sectors (superficial pVD and deep pVD). In addition, foveal thickness (FT) and foveal avascular zone (FAZ) and clinical variables, including best corrected visual acuity (BCVA), intraocular pressure and refractive condition, were collected. Results: BCVA, intraocular pressure and refractive condition were comparable between cases and controls. OCTA imaging showed that superficial wVD and superficial pVD were lower in the psoriasis group in comparison with controls (p = 0.009 and p = 0.01, respectively). Similarly, deep wVD and pVD were lower in the psoriasis group in comparison with control subjects (p = 0.03 and p = 0.01, respectively). In a sub-analysis of 47 patients affected by psoriasis without psoriatic arthritis, lower values of wVD and pVD in both superficial and deep capillary plexuses were registered. Conclusion: OCTA is a useful tool which provides data on vascular status of the retina in psoriasis with no ocular involvement. VD data may suggest that vascular changes may occur earlier than clinical onset of posterior inflammation

Long-term effectiveness and tolerability of apremilast in patients with moderate-to- severe plaque psoriasis: A 5-year multicentre retrospective study—IL PSO (Italian landscape psoriasis)

Apremilast is an oral inhibitor of phosphodiesterase (PDE)-4 that has been approved for the treatment of patients with moderate-to- severe plaque psoriasis who have contraindications or inadequate response to conventional systemic treatments. 1,2 It is also indicated for the management of adults with active psoriatic arthritis (PsA) who have failed or are intolerant to other disease-modifying antirheumatic drugs (DMARDs).1,2 In Italy, apremilast is reimbursed for patients with moderate-to- severe plaque psoriasis in case of inadequate response/intolerance to systemic treatments and those with contraindications to biological drugs.3 Despite the wide use of apremilast for the treatment of plaque psoriasis, long-term real-world experiences are still limited.4,

Differential diagnosis of contact dermatitis: A practical-approach review by the EADV Task Force on contact dermatitis.

The diagnosis of eczema ('dermatitis') is mostly clinical and depends on the clinical history and exploratory objective findings (primary lesions, patterns). Contact dermatitis remains as an important condition in the group of eczematous disorders, with important socioeconomic and occupational relevance. Although irritant and allergic contact dermatitis have a different pathogenesis, both are characterized by a rather typical morphology, are triggered by external factors and tend to occur primarily in the area of contact with the exogenous agent. In addition, allergic and irritant dermatitis may also co-exist. The importance of diagnosing contact dermatitis, especially when allergic in nature, is both due to the possibility of avoiding the trigger, and due to its role in aggravating other skin conditions. Nevertheless, the heterogeneity of clinical presentations in daily practice may pose an important challenge for the suspicion and correct diagnosis of contact dermatitis. Furthermore, other conditions, with different pathogenesis and treatment, may clinically simulate contact dermatitis. The Task Force aims to conduct a review of the unifying clinical features of contact dermatitis and characterize its main clinical phenotypes, and its simulators, in order to contribute to an early suspicion or recognition of contact dermatitis and enable a correct differential diagnosis