Impact of Covid-19 pandemic on injection-based practice: report from an Italian multicenter and multidisciplinary survey.

Background: There are no papers exploring the impact of COVID-19 pandemic on the injection-based practice in patients affected by different rheumatic diseases, including osteoarthritis. The aim was to investigate the impact of COVID-19 pandemic on injection-based practice trough the Italian country. Study design: A survey-based retrospective cross-sectional study. Methods: An Italian-language questionnaire was developed by a group of senior researchers and distributed by e-mail to some Rheumatology, Orthopedic and Rehabilitation Units from different geographic areas of Italy. The survey included information about the number of injections performed during COVID-19 pandemic (stratified by injected agents and injected joint), in comparison to the pre-pandemic period, and the possible reasons behind an eventual reduction. Responses were collected and descriptive analysis calculated. Results: Eleven centers of the National Health Service completed the survey. The activities of the injections services significantly decreased across the country with a percentage of reduction of 60% compared to the pre-pandemic period. A significant reduction of both intra-articular and peri-articular injections was registered. Among intra-articular. treatments, the most affected ones were the hyaluronic acid injections, when compared to corticosteroids. A significant decrease of the total amount of peri-articular injections was observed. The strict government restrictions and the fear of patients to become infected represented the most limiting factors. Conclusions: The reported decrease of the injection-based practice in our country during the COVID-19 pandemic highlights the detrimental effects of the COVID-19 pandemic on the management of chronic musculoskeletal diseases with possible negative consequences in terms of disability and quality of life.

Methylsulfonylmethane and mobilee prevent negative effect of IL-1ß in human chondrocyte cultures via NF-κB signaling pathway.

Nutraceuticals are compounds that serve as nutrition with an easy accessibility and favourable safety profile. Recent studies showed their potential activity on osteoarthritis (OA) inflammation and cartilage metabolism. We investigated the effect of methylsulfonylmethane (MSM) and mobilee in human OA chondrocyte cultures exposed to interleukin (IL)-1ß. OA cartilage was obtained from femoral heads of five patients undergoing total replacement surgery. Chondrocytes were incubated with mobilee (200 and 500 µM) and MSM (2000 and 6000 µM) in presence of IL-1ß (10 ng/mL) and nuclear factor (NF)-κB inhibitor (BAY 11-7082, 1 µM), for 24 and 48 h. Viability and apoptosis were performed by MMT and flow cytometry. The metalloproteinase (MMP)-1,-3,-13 and type II collagen (Col2a1) were analyzed by qRT-PCR and ELISA, and NF-κB activation by immunofluorescence. IL-1ß stimulus determined a significant regulation of survival, apoptotic ratio, as well as of gene expression and serum levels of MMP-1,-3,-13 and Col2a1 in OA chondrocytes compared to baseline. Mobilee and MSM incubation significantly reversed the effect of IL-1ß. IL-1ß significantly induced NF-κB p50 nuclear translocation, which was significantly counteracted by the pre-treatment of OA chodrocytes with the tested compounds. BAY11-7082 significantly modulated MMPs and Col2a1 expression respectively to basal state. Co-treatment of IL-1ß with mobilee, MSM and BAY11-7082 didn't cause changes of MMPs or Col2a1 beyond that caused by each single treatment. We demonstrated that MSM and mobilee have a beneficial effect on OA chondrocytes metabolism, probably due to the modulation of NF-κB pathway, providing a powerful rationale for the use of these substances in OA treatment.

Can adipokines serum levels be used as biomarkers of hand osteoarthritis?

PURPOSE: To evaluate serum levels of visfatin, resistin and adiponectin in patients with erosive (E) and non-erosive (NE) osteoarthritis (OA) of the hand (HOA) compared to normal controls (NC). METHODS: 94 outpatients with E HOA and NE HOA and 21 NC were enrolled. The radiological assessment of both hands was performed according to the Kellgren-Lawrence and Kallman score. Patients were divided into two subsets (lone HOA or generalized OA) based on clinically OA involvement of knee and hip. Serum visfatin, resistin and adiponectin levels were determined by ELISA assay. RESULTS: Visfatin was significantly higher in E HOA patients in comparison to NC and NE HOA group. Resistin showed a significant increase in both E HOA and NE HOA groups versus NC, in particular in generalized OA. No significant differences among groups were found in adiponectin. The Kallman score was more severe in the two subsets of E HOA patients compared to NE HOA. CONCLUSIONS: This study showed increased levels of resistin in erosive and non-erosive HOA, and higher visfatin levels in E HOA in comparison to NE HOA. These data suggest the adipokines possible role in the pathogenesis of HOA and their potential usefulness as biomarkers of the disease.

Can balneotherapy modify microRNA expression levels in osteoarthritis? A comparative study in patients with knee osteoarthritis.

The aim of this study was to evaluate the whole-blood levels of miR-155, miR-223, miR-181a, miR-146a, and miR-let-7e in patients with bilateral knee osteoarthritis (OA) after a cycle of mud-bath therapy (MBT). Thirty-two patients with knee OA defined by the ACR criteria were included. Twenty-one patients (MBT group) were daily treated with a combination of local mud-packs at 42 °C and baths in mineral water, at 37 °C for 15 min, for 12 applications over a period of 2 weeks, in addition to standard therapy; 11 patients (control group) continued their conventional treatment alone. Global pain score evaluated by visual analog scale (VAS), WOMAC subscores, and microRNA expression were evaluated at baseline and after 2 weeks. Peripheral whole blood was collected into PAXgene™ Blood RNA tubes, stored at - 80 °C, and total RNA was extracted. The expression of miR-155, miR-223, miR-181a, miR-146a, and miR-let-7e was determined by qRT-PCR. After MBT, we observed a statistically significant improvement of clinical parameters and a significant decrease of miR-155, miR-181a, miR-146a (p < 0.001), and miR-223 (p < 0.01) expression levels. No clinical and biochemical modifications were detected in the control group. No significant variations of miR-let-7e were shown in both groups after 2 weeks. In conclusion, MBT can modify the expression of miR-155, miR-181a, miR-146a, and miR-223, which are upregulated in OA. It could be due to the heat stress and the hydrostatic pressure, since some miRNAs were found to be temperature- and mechano-responsive. Further studies are needed to better explain the mechanism of action of MBT and the role of miRNAs in OA.

One-year follow-up of mud-bath therapy in patients with bilateral knee osteoarthritis: a randomized, single-blind controlled trial.

The objective of this prospective parallel randomized single-blind study was to assess that a cycle of mud-bath therapy (MBT) provides any benefits over usual treatment in patients with bilateral knee osteoarthritis (OA). Patients with symptomatic primary bilateral knee OA, according to ACR criteria, were included in the study and randomized to one of two groups: one group received a cycle of MBT at spa center of Chianciano Terme (Italy) in addition to the usual treatment, and one group continued their regular care routine alone. Clinical assessments were performed 7 days before enrollment (screening visit), at the time of enrollment (basal time), after 2 weeks, and after 3, 6, 9, and 12 months after the beginning of the study. All assessments were conducted by two researchers blinded to treatment allocation. The primary efficacy outcomes were the global pain score evaluated by Visual Analog Scale (VAS) and the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) subscore for physical function (W-TPFS). Of the 235 patients screened, 103 met the inclusion criteria: 53 patients were included in the MBT group and 50 in the control group. In the group of patients treated with MBT, we observed a statistically significant (p < 0.001) reduction of VAS and W-TPFS score at the end of the treatment; this improvement was significant (p < 0.05) also at 3 months of follow-up. The control group did not show significant differences between baseline time and all other times. The differences between one group were significant for both primary parameters already from the 15th day and persisted up to the 9th month. This beneficial effect was confirmed by the significant reduction of symptomatic drug consumption. Tolerability of MBT seemed to be good, with light and transitory side effects. Our results confirm that a cycle of MBT added to usual treatment provides a beneficial effect on the painful symptoms and functional capacities in patients with knee OA that lasts over time. Mud-bath therapy can represent a useful backup to pharmacologic treatment of knee OA or a valid alternative for patients who do not tolerate pharmacological treatments.

Thermal water of Vetriolo, Trentino, inhibits the negative effect of interleukin-1β on nitric oxide production and apoptosis in human osteoarthritic chondrocyte.

The thermal water of Vetriolo in Trentino, Italy (VW) has been known over 150 years for its therapeutic properties in the treatment of osteoarthritis (OA). This is a highly mineralized water, strongly acidic sulfate, rich in calcium, magnesium and iron and used for balneotherapy after dilution. The aim of our study was to investigate the possible in vitro effects of the VW in human OA chondrocytes cultivated in the presence or in the absence of Interleukin-1 beta (IL-1beta). OA chondrocytes were cultivated in Deionized Water (DW) (DW-DMEM, controls), or in one of three different VW-DMEM media, in which DW had been totally (100 percent) or in part (25 or 50 percent) substituted with VW. All samples were analyzed before and after treatment with IL-1beta at a concentration of 5 ng/ml. After 48 h, we evaluated the cell viability, the release of nitric oxide (NO) in culture medium, the inducible nitric oxide synthase (iNOS) expression, and the percentage of apoptosis and necrosis. Finally, we carried out a morphological assessment using a transmission electron microscope (TEM). Our data showed that VW alone at 25 or 50 percent concentration did not affect the viability of cultured OA chondrocytes, and determined a significant survival recovery rate in cultures stimulated with IL-1beta. On the contrary, the VW alone at 100 percent of concentration reduced, in a significant (P less than 0.05) manner, the cells viability. NO levels were low both in DW-DMEM cultures and in those reconstituted with 25 or 50 percent of VW, and were significantly (P less than 0.05) increased in cultures with 100 percent of VW. VW at 25 or 50 percent concentration significantly (P less than 0.001) reduced the NO production induced by IL-1beta. The data of the NO levels were confirmed by the immunocytochemistry assay for iNOS. Our experiments confirmed the pro-apoptotic effect of IL-1beta and demonstrated a protective effect of VW at 25 or 50 percent concentration. These findings were confirmed by TEM. In conclusion, our study demonstrated that VW alone at 25 or 50 percent concentration modifies neither morphology nor NO production and neither iNOS expression nor apoptosis, but it inhibits the negative effects of IL-1beta in chondrocytes cultures.