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

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)

Crosstalk between skin inflammation and adipose tissue-derived products: pathogenic evidence linking psoriasis to increased adiposity.

INTRODUCTION: Psoriasis is a chronic skin disorder associated with several comorbid conditions. In psoriasis pathogenesis, the role of some cytokines, including TNF-α and IL-17, has been elucidated. Beside their pro-inflammatory activity, they may also affect glucose and lipid metabolism, possibly promoting insulin resistance and obesity. On the other hand, adipose tissue, secreting adipokines such as chemerin, visfatin, leptin, and adiponectin, not only regulates glucose and lipid metabolism, and endothelial cell function regulation, but it may contribute to inflammation. AREAS COVERED: This review provides an updated 'state-of-the-art' about the reciprocal contribution of a small subset of conventional cytokines and adipokines involved in chronic inflammatory pathways, upregulated in both psoriasis and increased adiposity. A systematic search was conducted using the PubMed Medline database for primary articles. Expert commentary: Because psoriasis is associated with increased adiposity, it would be important to define the contribution of chronic skin inflammation to the onset of obesity and vice versa. Clarifying the pathogenic mechanism underlying this association, a therapeutic strategy having favorable effects on both psoriasis and increased adiposity could be identified

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

a review

Primary total knee arthroplasty (TKA) is a reliable procedure with reproducible long-term results. Nevertheless, there are conditions related to the type of patient or local conditions of the knee that can make it a difficult procedure. The most common scenarios that make it difficult are discussed in this review. These include patients with many previous operations and incisions, and those with severe coronal deformities, genu recurvatum, a stiff knee, extra-articular deformities and those who have previously undergone osteotomy around the knee and those with chronic dislocation of the patella. Each condition is analysed according to the characteristics of the patient, the pre-operative planning and the reported outcomes. When approaching the difficult primary TKA surgeons should use a systematic approach, which begins with the review of the existing literature for each specific clinical situation. Cite this article: Bone Joint J 2015;97-B(10 Suppl A):30–9

Effectiveness and safety of secukinumab in Italian patients with psoriasis: an 84 week, multicenter, retrospective real-world study

Background: Long term data on the real-life use of secukinumab are scant. The aim of this study was to investigate the real-life effectiveness, safety and treatment persistence of secukinumab in patients with moderate-to-severe psoriasis. Research design and methods: This 84-week, multicenter (n = 7) retrospective study analyzed data from patients who initiated and received at least 6 months of secukinumab treatment between June 2016 and June 2018 in the Campania region of Italy. Patient demographic and treatment characteristics, duration of treatment and reasons for discontinuation as well as Psoriasis Area and Severity Index (PASI), Body Surface Area (BSA), and Dermatology Life Quality Index (DLQI) scores were assessed. Results: 324 patients (63% male, mean age 50.2 years) were enrolled and received a mean 11.7 months of secukinumab treatment. Overall, 9.5% discontinued secukinumab, including 5.2% who discontinued due to secondary inefficacy and 1.8% due to adverse events. PASI, BSA and DLQI scores were significantly improved from baseline at every follow-up visit (p < 0.001) and mean PASI decreased from 15.3 ± 6.3 at baseline to 0.5 ± 1.0 at week 84. Secukinumab had comparable effectiveness in biologic naïve and non-naïve patients. Conclusions: This study confirmed the effectiveness and safety of secukinumab in real-world patients with psoriasis

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&nbsp;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&nbsp;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&nbsp;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

Correlation between time from injury to surgery and the prevalence of ramp and hidden lesions during anterior cruciate ligament reconstruction. A new diagnostic algorithm

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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