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Objective: To investigate the association between interleukin‐8 (IL‐8) levels in gingival crevicular fluid (GCF) and total oral fluid (TOF) and the responsiveness to steps 1 and 2 of periodontal therapy. Materials and Methods: One‐hundred and fifty‐nine patients affected by periodontitis received steps 1 and 2 of periodontal therapy. At baseline, TOF and GCF samples were collected and analysed for IL‐8 (Il‐8TOF/IL‐8GCF) using flow cytometry. Therapy outcomes were relative proportions of residual periodontal pockets (PPD%), pocket closure (PC) rates and pocket probing depth (PPD) reductions; these were associated with IL‐8TOF/IL‐8GCF. Results: High IL‐8TOF was significantly associated with higher residual PPD% (p = 0.044) and lower PPD reduction compared to low IL‐8TOF (high 0.79 ± 1.20 mm vs. low 1.20 ± 1.20 mm, p < 0.001) in non‐smokers, while in smokers high IL‐8GCF was related to lower PPD reduction (high 0.62 ± 1.22 mm vs. low 0.84 ± 1.12 mm, p = 0.009). Furthermore, high baseline IL‐8TOF was significantly associated with poorer PC rates compared to medium and low concentrations in both non‐smokers (high 41% vs. medium 55% vs. low 58%, p < 0.001) and smokers (high 34% vs. medium 44% vs. low 46%, p < 0.001). Conclusion: High IL‐8 concentrations at baseline had a significant impact on residual PPD%, PC rates and PPD reduction. The findings suggest that, especially in non‐smokers, baseline IL‐8 levels collected from the TOF could serve as a component in the estimation of responsiveness to steps 1 and 2 of periodontal therapy. [ABSTRACT FROM AUTHOR]

Introduction: Psoriasis is a T-cell mediated autoimmune skin disease. HLA-C*06:02 is the main psoriasis-specific risk gene. Using a Va3S1/Vb13S1 T-cell receptor (TCR) from a lesional psoriatic CD8+ T-cell clone we had discovered that, as an underlying pathomechanism, HLA-C*06:02 mediates an autoimmune response against melanocytes in psoriasis, and we had identified an epitope from ADAMTS-like protein 5 (ADAMTSL5) as a melanocyte autoantigen. The conditions activating the psoriatic autoimmune response in genetically predisposed individuals throughout life remain incompletely understood. Here, we aimed to identify environmental antigens that might trigger autoimmunity in psoriasis because of TCR polyspecificity. Methods: We screened databases with the peptide recognition motif of the Va3S1/Vb13S1 TCR for environmental proteins containing peptides activating this TCR. We investigated the immunogenicity of these peptides for psoriasis patients and healthy controls by lymphocyte stimulation experiments and peptide-loaded HLA-C*06:02 tetramers. Results: We identified peptides from wheat, Saccharomyces cerevisiae, microbiota, tobacco, and pathogens that activated both the Va3S1/Vb13S1 TCR and CD8+ T cells from psoriasis patients. Using fluorescent HLA-C*06:02 tetramers loaded with ADAMTSL5 or wheat peptides, we find that the same CD8+ T cells may recognize both autoantigen and environmental antigens. A wheat-free diet could alleviate psoriasis in several patients. Discussion: Our results show that due to TCR polyspecificity, several environmental antigens corresponding to previously suspected psoriasis risk conditions converge in the reactivity of a pathogenic psoriatic TCR and might thus be able to stimulate the psoriatic autoimmune response against melanocytes. Avoiding the corresponding environmental risk factors could contribute to the management of psoriasis. [ABSTRACT FROM AUTHOR]

Objectives: Neutrophil granulocytes have been proposed to play a major role in the mediation of periodontitis‐associated tissue destruction. Their recruitment and activation are regulated by the chemokine CXCL8. This study aimed to delineate the dependency of CXCL8 expression in gingival crevicular fluid (GCF) and saliva on periodontal status, bacterial infection, and smoking, in patients with periodontitis. Methods: The study cohort comprised 279 subjects with untreated periodontitis. Probing pocket depth (PPD), gingival recession, bleeding on probing (BOP), plaque index, and bone loss were evaluated. CXCL8 was determined in saliva and GCF using flow cytometry. Results: Considering the entire study sample, CXCL8 levels were correlated with the mean PPD (ρ = 0.131; p = 0.029), severity of periodontitis (ρ = 0.121; p = 0.043), BOP (ρ = 0.204; p = 0.001), and smoking (ρ = −0.219; p < 0.0001) in GCF; and, in whole saliva, with mean PPD (ρ = 0.154; p = 0.010) severity of periodontitis (ρ = 0.140; p = 0.020), gender (ρ = 0.178; p = 0.003), and smoking (ρ = −0.156; p = 0.010). Subgroup analysis among non‐smokers revealed significantly higher amounts of CXCL8 in GCF (p = 0.012) and saliva (p = 0.026) comparing subjects with mean PPD ≤3mm and >3mm. Conclusion: The current study revealed a strong dependency of CXCL8 expression in GCF on the severity and activity of periodontal disease. Smoking causes a significant reduction in CXCL8 expression in saliva and GCF. [ABSTRACT FROM AUTHOR]

Background: Skin reactions to the glucose monitoring systems Dexcom G5 and G6 have been rare. In 2019, the components of the adhesive were exchanged for better skin fixation. Since then, more and more patients experienced severe skin reactions. A few months ago, 2,2′‐methylenebis(6‐tert‐butyl‐4‐methylphenol) monoacrylate (MBPA) was identified as a new component in the adhesive of the G6 model. Furthermore, it was suspected that isobornyl acrylate (IBOA) was also a component of the exchanged adhesive. Objectives: Our objective was to investigate if MBPA plays a major role in the increasing skin problems of patients without a history of IBOA‐sensitization. Furthermore, our aim was to examine whether IBOA is contained in the newer model adhesive and may also contribute to allergic contact dermatitis (ACD). Patients and Methods: Five patients with a newly occurred ACD caused by the glucose monitoring system Dexcom G6 were investigated. Patch testing including MBPA in three different concentrations, as well as IBOA, were performed. Gas chromatography–mass spectrometry of the newer system Dexcom G6 was carried out. Results: All patients were shown to be sensitized to MBPA, while MBPA 0,5% showed the strongest reaction. On the other hand, IBOA was tested negative. Conclusion: In our study group, MBPA was observed to be the triggering allergen of the recently changed adhesive. [ABSTRACT FROM AUTHOR]

Background: Little is known about sensitization to iron (Fe) in private, occupational, and medical settings, particulary implantology. Objectives: To investigate sensitization to metals, particularly to Fe, both in preimplant individuals with presumed metal allergy and in patients with suspected metal implant allergy. To further characterize Fe-sensitized individuals. Methods: Analysis of patch test reactions to an Fe (II) sulfate-containing metal series in 183 consecutive patients (41 pre-implant, 142 metal implant bearers). Test readings were on day (D)2, D3, and D6. Evaluation of questionnaire-aided history of metal reactivity patterns and demographics of Fe reactors. Results: Metal reactivity in pre-implant/implant/total group was: to nickel 39%/30%/32%; to cobalt 17%/15%/15%; and to chromium 7%/13%/11%. Co-sensitizations cobalt/nickel (19/58) and cobalt/chromium (11/21) were significant at P < .001; co-sensitizations Fe/nickel (4/10) and chromium/knee arthroplasty (11/73) at P = .03. Ten of 183 (5.5%) reacted to Fe (2 of 41 pre-implant patients, 8 of 142 implant bearers), with 10 reacting only on D6. Fe reactivity was highest in complicated knee arthroplasty (7/73). Further peculiarities of Fe reactors included frequent isolated Fe reactivity (6/10), occupational metal exposure (7/10), previous (par)enteral Fe substitution (6/10). Conclusions: The 5.5% prevalence of Fe reactions suggests a potentially underestimated role of this metal allergen in general and in implant bearers. The latter also shows a distinct metal sensitization pattern. [ABSTRACT FROM AUTHOR]

Background and purpose — Metal sensitivity might provoke complications after arthroplasty. Correspondingly, coated "hypoallergenic" implants are of interest but long-term follow-up data are missing. Thus, we assessed immunological and clinical parameters in such patients. Patients and methods — 5 years' follow-up data were obtained from 3 centers, which used either a standard total knee replacement (TKR) or the identical implant with multilayer surface zirconium nitride based coating. Of the 196 patients (mean age 68 years (44-84), 110 females) 97 had arthroplasty with a coated surface, and 99 were treated by a standard TKR of the same type. Investigations were Knee Society Score (KSS), Knee injury and Osteoarthritis Outcome Score (KOOS), radiographic analysis, and cytokine measurement in peripheral blood. Pro- and anti-inflammatory cytokines were evaluated by cytometric beads assay and RT-PCR. Results — Survival rate (Kaplan-Meier) was 98% for coated and 97% for uncoated implants after 5 years. Mechanical axis and KSS pain score (42 vs. 41 (0-50)) were comparable. Most serum cytokine levels were comparable, but mean interleukin-8 and interleukin-10 levels were higher in the group with an uncoated implant. IL-8: 37 (SD 7.5) pg/mL vs. 1.1 (SD 4.3) (p < 0.001); IL-10: 3.6 (SD 2.5) vs. 0.3 (SD 1.8) pg/mL (p < 0.001). Interpretation — There was similar clinical outcome 5 years after standard and surface-coated TKR. In peripheral blood there was an increased pro-inflammatory status, i.e., significant elevation of IL-8 and the anti-inflammatory IL-10, after standard uncoated prosthesis. Any long-term effects of these cytokine changes are unknown. [ABSTRACT FROM AUTHOR]

Background The patch test is considered to be the gold standard for diagnosing nickel ( Ni) allergy. The lymphocyte transformation test ( LTT) can also be used to detect Ni sensitization. However, little is known about the correlation between patch test and LTT reactions to Ni. Objective To establish and validate an LTT for Ni sensitization by comparison with patch test reaction and history. Methods Fifty individuals without self-reported ' Ni allergy' (controls) and 50 patients with self-reported suspicion of Ni allergy were included. A questionnaire-aided history was taken, and patch tests with at least the baseline series and LTTs with various Ni SO4 dilutions were performed. Results In the patch tests, 2 of 50 controls and 18 of 50 patients with self-reported suspicion of Ni allergy showed positive reactions to Ni. In the LTTs, 2 of 50 controls and 26 of 50 patients with self-reported suspicion of Ni allergy showed positive reactions to Ni SO4 2.5 × 10−5 m, and 2 of 50 controls and 17 of 50 patients with self-reported suspicion of Ni allergy showed positive reactions to Ni SO4 1 × 10−5 m. Sixteen of the 18 history-positive and patch test-positive patients (i.e. 88% sensitivity) were also LTT-positive, in contrast to only 2 positive LTT reactors within the 48 PT and history negative individuals (i.e. 96% specificity). [Correction added on 16 February 2017, after first online publication: The preceding sentence has been edited for language and this has been amended in this version.] Conclusion Performing the LTT with optimized stimulating conditions might be a useful additional tool for the diagnosis of Ni allergy if non-sensitized controls are included. [ABSTRACT FROM AUTHOR]

Nickel, chromium, and cobalt in stainless steel and Cobalt-chrome-molybdenum (CoCrMo) alloys may induce allergy. The objectives of this study were to evaluate surface coating regarding ion release, patch test reactivity, and arthroplasty performance. Materials and methods included patch test in 31 patients with metal allergy and 30 patients with no allergy to stainless steel and CoCrMo disks that are uncoated or coated by titanium nitride/zirconium nitride (TiN/ZrN). Assessment include atomic absorption spectrometry of released nickel, cobalt, and chromium from the disks after exposure to distilled water, artificial sweat and culture medium. Results showed that both coatings reduced the nickel and chromium release from stainless steel and CoCrMo disks and mostly the cobalt release from the disks (maximally 11.755 µg/cm(2)/5 d to 1.624 by Ti-N and to 0.442 by ZrN). Six of the 31 patients with metal allergy reacted to uncoated disks, but none reacted to the coated disks. The current authors report on exemplary patients with metal allergy who had symptom relief by revision with surface-coated arthroplasty. The authors concluded that the surface coating may prevent cutaneous and peri-implant allergic reactions. [Orthopedics. 2016; 39(3):S24-S30.]. [ABSTRACT FROM AUTHOR]

BACKGROUND: Key factors for successful porous polyethylene (PPE) implantation are rapid vascularization and low inflammatory response. Dermal fibroblasts produce a variety of pro-angiogenic and immunmodulatory factors. OBJECTIVE: The aim of this tissue engineering study was to investigate whether coating PPE implants with dermal fibroblasts in vitro is sustainable in vivo and whether the kinetics of blood vessel ingrowth and immunological responses are hereby affected. METHODS: PPE implants were cultured with syngeneic GFP-transfected dermal fibroblasts. Cells on the biomaterial were quantified before implantation into dorsal skinfold chamber preparations of C57Bl/6 mice. Uncoated implants served as controls. Angiogenic activity and leukocyte-endothelial cell interactions were repeatedly analyzed. After 10 days, mechanical integration was measured and surviving fluorescently labeled fibroblasts were quantified. Expression of inflammatory cytokines was assessed by quantitative real time-reverse transcription PCR. RESULTS: PPE implants were successfully coated with dermal fibroblasts in vitro and 69% of the cells were still detectable at the end of observation. Angiogenic parameters increased during the observation period in both groups. IL-2, IL17A and IL-10 tended to be increased in coated implants, but did not affect leukocyte-endothelial cell interactions. CONCLUSIONS: Dermal fibroblast-coating of porous polyethylene implants is feasible and sustainable in vivo. Alone it does not improve biocompatibility but may be beneficial in combination with specific growth factor supplements. [ABSTRACT FROM AUTHOR]

The article presents a case study of a 10-year-old who after using the insulin patch pump OmniPod developed a vesicular rash near the glucose monitoring system. It talks about the patient having a history of type 1 diabetes for which he uses the glucose monitoring system FreestyleLibre. It tells about the patient being allergic to isobornyl acrylate present in the insulin patch pump OmniPod which was the cause to contact dermatitis.

Background. Arthroplasty patients with complications may be sensitized to implant components. Objectives. To quantify patch test reactions to implant materials in aseptic cemented arthroplasty patients with complications, and to evaluate the benefit of late patch test reading at D6. Methods. Analyses of patch test reactions to baseline series and bone cement components and of the questionnaire-aided histories of 250 consecutive patientswith suspected implant allergy were performed. Patch tests were read at D2, D3, and D6. Results. There were 187 positive reactions to the 29 allergens of the baseline series, and 52 to the seven allergens of the bone cement series. Forty-nine of 250 patients reacted to the bone cement series. In contrast to 'early allergens' such as fragrance mix, late reading at D6 increased the number of positive reactions by 11/32 for nickel, 1/5 for cobalt, and 2/4 for chromium. With bone cement components, most reactions were to gentamicin (25 of 250 patients), and 17 of 25 appeared only at D6. Conclusion. Late reading is useful for patch tests with metals and bone cement components. With only D2/D3 readings, 32 reactions to nickel, cobalt, chromium and bone cement componentswould have been missed. This underlines the utility of late reading in general and in complicated cemented arthroplasty patients, given the unexpectedly high number of gentamicin reactions. [ABSTRACT FROM AUTHOR]

Cutaneous allergic reactions to implanted metal devices, for example, orthopedic, are well reported in the literature. Also, extracutaneous complications resulting from peri-implant inflammation have been observed in association with metal allergy. Nickel, cobalt, and chromium are the three most common triggers of both cutaneous and extracutaneous allergy-related complications. However, the diagnosis of metal implant allergy remains a challenge, that is, the synopsis of excluding differential diagnoses and the combination of different allergy diagnostic tools is needed. Thus, the management of metal implant allergy is also hampered by clinical uncertainty and unresolved scientific questions. [ABSTRACT FROM AUTHOR]

We performed a combined approach to identify suspected allergy to knee arthroplasty (TKR): patch test (PT), lymphocyte transformation test (LTT), histopathology (overall grading; T- and B-lymphocytes, macrophages, and neutrophils), and semiquantitative Real-time-PCR-based periprosthetic inflammatory mediator analysis (IFNγ, TNFα, IL1-β, IL-2, IL-6, IL-8, IL-10, IL17, and TGFβ). We analyzed 25 TKR patients with yet unexplained complications like pain, effusion, and reduced range of motion. They consisted of 20 patients with proven metal sensitization (11 with PT reactions; 9 with only LTT reactivity). Control specimens were from 5 complicated TKR patients without metal sensitization, 12 OA patients before arthroplasty, and 8 PT patients without arthroplasty. Lymphocytic infiltrates were seen and fibrotic (Type IV membrane) tissue response was most frequent in the metal sensitive patients, for example, in 81% of the PT positive patients. The latter also had marked periprosthetic IFNγ expression. 8/9 patients with revision surgery using Ti-coated/oxinium based implants reported symptom relief. Our findings demonstrate that combining allergy diagnostics with histopathology and periprosthetic cytokine assessment could allow us to design better diagnostic strategies. [ABSTRACT FROM AUTHOR]

Hypersensitivity reactions to titanium (Ti) are very rare. Thus, we assessed the proinflammatory response and also potential tolerance favoring in vitro reactivity ofhuman blood lymphocytes and monocytes (PBMC) to Ti in healthy individuals (14 without, 6 with complication-free dental Ti implants). The proliferation index (SI) in lymphocyte transformation test (LTT) and production of cytokines linked to innate immune response (IL-1β, IL-6, and TNFα) or immune regulation (IL-10) were assessed in response to TiO2 particles or Ti discs. In both groups, the Ti-LTT reactivity was not enhanced (e.g., SI < 3). The control antigen tetanus toxoid (TT) gave adequate reactivity (median SI individuals without/with implant: 20.6 ± 5.97/19.58 ± 2.99). Individuals without implant showed higher cytokine response to Ti materials than individuals with symptom-free implants; for example, TiO2 rutile particle induced increase of IL-1β 70.27-fold/8.49-fold versus control medium culture. PBMC of 5 of the 6 individuals with complicationfree Ti implants showed an ex vivo ongoing production of IL-10 (mean 4.18 ± 2.98 pg/mL)-but none of the 14 controls showed such IL-10 production. Thus in vitro IL-1β-, IL-6-, and TNF-α production reflects "normal" unspecific immune response to Ti. This might be reduced by production of tolerogenic IL-10 in individuals with symptom-free Ti dental implants. [ABSTRACT FROM AUTHOR]

Discusses a study which assessed the extent to which peripheral blood mononuclear cells from nickel-allergic and from non-allergic individuals would proliferate in response to nickel stimulation in vitro. Manifestations of nickel contact allergy; Way in which delayed-type hypersensitivity to nickel is reflected; Methodology.

Because of a suspicion of acrylate allergy, patch testing was performed with the baseline series, and dental metal and dental technician series including acrylate preparations, according to the recommendations of the German Contact Dermatitis Research Group. In patients with acrylate allergy, uncemented arthroplasty and non-acrylate-releasing dental materials should be preferred. Acrylate allergy induced by acrylic nails resulting in prosthesis failure. [Extracted from the article]

The article presents a case study of a 50-year-old woman with unilateral erythema and oedema of the left eyelid and accompanying discomfort and patient had tolerated jewellery, cosmetics and medicines. Her lymphocyte transformation test (LTT) showed lymphocyte reactivity to gold in two concentrations and patient developed isolated hypersensitivity to gold. It also mentions histopathologicalexamination can help to confirm the diagnosis of allergy to gold.

The article presents case study of a 79-year-old patient synovitis and allergic contact dermatitis resulting from intra-articular gentamicin application leading to complications in knee arthroplasty. Topics discussed include observation of joint effusion; information on use of the lymphocyte transformation test (LTT); and information on evaluation of peri-implant tissues or implant-associated skin changes.

ABSTRACT Aim Materials and Methods Results Conclusion To analyse whether some selected inflammatory biomarkers collected from venous blood and gingival crevicular fluid (GCF) were associated with the outcome of non‐surgical periodontal therapy.Two‐hundred and nine patients affected by periodontitis were enrolled in the study, who had undergone steps I and II therapy as well as a non‐surgical re‐instrumentation (NSRI) of periodontal pockets after 6 months. Serum (SE), plasma (PL) and GCF samples were quantitatively analysed for the following inflammatory biomarkers: active matrix metalloproteinase‐8 (aMMP‐8), prostaglandin E2 (PGE2) and surfactant protein D (SP‐D). Therapy outcomes were evaluated using a ‘treat‐to‐target’ endpoint (T2T) at the patient level, defined as ≤ 4 sites with pocket depth ≥ 5 mm.Patients presented with 23 ± 6 teeth (mean ± SD) at baseline. After steps I and II therapy, 41.6% of the patients reached T2T and after NSRI 47.4%. Univariate analysis identified a potential association between high levels of PL‐SP‐D and more favourable treatment outcomes. Multivariate binary logistic regression adjusted for sex, mean baseline probing depth, diabetes and current smoking status confirmed an independent relationship between baseline PL‐SP‐D and the T2T after steps I and II therapy (aOR 0.432, p = 0.011), implying that a higher level PL‐SP‐D at baseline is associated with a > 50% reduced risk of failing T2T. However, no such association was found for PL‐SP‐D and NSRI.Higher baseline PL‐SP‐D levels might be associated with more favourable treatment outcomes after steps I and II therapy. This may be due to its role in the regulation of neutrophil function. However, further investigation is required to confirm this hypothesis. If proven, PL‐SP‐D could play a role as a biomarker for identifying individuals who respond differentially to primary therapy. [ABSTRACT FROM AUTHOR]

Co-culture studies investigating the role of periprosthetic fibroblasts (PPFs) in inflammatory osteoclastogenesis reveal contrary results, partly showing an osteoprotective function of fibroblasts and high OPG expression in monolayer. These data disagree with molecular analyses of original periosteolytic tissues. In order to find a more reliable model, PPFs were co-cultivated with peripheral blood mononuclear cells (PBMCs) in a transwell system and compared to conventional monolayer cultures. The gene expression of key regulators of osteoclastogenesis (macrophage colony-stimulating factor (MCSF), receptor activator of NF-κB ligand (RANK-L), osteoprotegerin (OPG), and tumor necrosis factor alpha (TNFα)) as well as the ability of bone resorption were analyzed. In monolayer co-cultures, PPFs executed an osteoprotective function with high OPG-expression, low RANK-L/OPG ratios, and a resulting inhibition of osteolysis even in the presence of MCSF and RANK-L. For transwell co-cultures, profound changes in gene expression, with a more than hundredfold decrease of OPG and a significant upregulation of TNFα were observed. In conclusion, we were able to show that a change of culture conditions towards a transwell system resulted in a considerably more osteoclastogenic gene expression profile, being closer to findings in original periosteolytic tissues. This study therefore presents an interesting approach for a more reliable in vitro model to examine the role of fibroblasts in periprosthetic osteoclastogenesis in the future. [ABSTRACT FROM AUTHOR]

Immobilization of proteins has been examined to improve implant surfaces. In this study, titanium surfaces were modified with nanofunctionalized denosumab (cDMAB), a human monoclonal anti-RANKL IgG. Noncoding DNA oligonucleotides (ODN) served as linker molecules between titanium and DMAB. Binding and release experiments demonstrated a high binding capacity of cDMAB and continuous release. Human peripheral mononuclear blood cells (PBMCs) were cultured in the presence of RANKL/MCSF for 28 days and differentiated into osteoclasts. Adding soluble DMAB to the medium inhibited osteoclast differentiation. On nanofunctionalized titanium specimens, the osteoclast-specific TRAP5b protein was monitored and showed a significantly decreased amount on cDMAB-titanium in PBMCs + RANKL/MCSF. PBMCs on cDMAB-titanium also changed SEM cell morphology. In conclusion, the results indicate that cDMAB reduces osteoclast formation and has the potential to reduce osteoclastogenesis on titanium surfaces. [ABSTRACT FROM AUTHOR]