A Delphi Consensus Approach for the Management of Chronic Pain during and after the COVID-19 Era.

Due to a lack of published evidence on the topic, a modified Delphi approach was used to develop recommendations useful for chronic pain management during and after the COVID-19 pandemic. Focusing on the available literature and personal clinical expertise, an Italian board of nine professionals from different disciplines identified four main topics: prevention of chronic pain, treatment of chronic pain, consequences of inadequate treatment, and perspectives. They elaborated a semi-structured questionnaire. A multidisciplinary panel of experts in the field of pain management was requested to comment on the statements. Based on the answers provided, a structured questionnaire was prepared (Round 1). It included 21 statements divided into three categories (organizational issues; diagnosis and therapies; telemedicine and future perspectives). A five-point Likert scale was adopted. The threshold for consensus was set at a minimum of 70% of the number of respondents (level of agreement ≥ 4, Agree or Strongly Agree). A final questionnaire with rephrasing of the statements that did not reach the consensus threshold was elaborated (Round 2). A total of 29 clinicians were included in the panel. Twenty clinicians (69%) responded in both the first and second round. After two rounds, consensus (≥70%) was achieved in 20 out of 21 statements. The lack of consensus was recorded for the statement regarding the management of post-COVID pain (55%; Median 4; IQR 2.3). Another statement on telemedicine reached the threshold in the first round (70%), but the value was not confirmed in Round 2 (65%; Median 4; IQR 2). Most of the proposed items reached consensus, suggesting the need to make organizational changes, the structuring of careful diagnostic and therapeutic pathways, and the application of new technologies in pain medicine. Long-COVID-19 care is an issue that needs further research. Remote assistance for chronic pain must be regulated.

Mud-bath therapy and oral glucosamine sulfate in patients with knee osteoarthritis: a randomized, controlled, crossover study.

OBJECTIVES: To evaluate the efficacy and safety of combined treatment of mud-bath therapy and glucosamine crystalline sulfate (GlcN-S) in patients with knee osteoarthritis (OA). METHODS: This study was a randomised, controlled, crossover investigation. Patients were randomly assigned (1:1) by the investigators to two groups, named group 1 and 2. Group 1 included twenty-three patients receiving oral GlcN-S treatment from the beginning of the study (T0) to the end of the 3rd month of treatment (T3) and a combined treatment of both mud-bath therapy and GlcN-S from T3 to the end of the study at six months (T6). Group 2 included twenty-two patients receiving a combined treatment of both mud-bath therapy and GlcN-S from T0 to T3 and that discontinued mud-bath therapy, receiving GlcN-S treatment alone, from T3 to T6. Primary endpoints of the study consisted of evaluating OA severity and activity at baseline and at follow-up visits. RESULTS: All 45 patients, eligible for the study, completed the period of the crossover. In group 1, no significant difference was shown in the comparison from T0 to T3, while from T3 to T6 most variables were significantly improved. In group 2, instead, the comparison between T0 and T3 showed a significant difference in different parameters. When comparing T3 and T6, despite an improvement of all the variables, no significant difference was shown. CONCLUSIONS: The association of GlcN-S and mud-bath therapy has a positive and safe role in improving pain, function and quality of life in knee OA patients.

Fragility Fractures in Patients with Psoriatic Arthritis.

Psoriatic arthritis (PsA) can have peculiar effects on bone, including mechanisms of bone loss such as erosions, but also of bone formation, such as ankylosis or periostitis. The aim of the present study was to describe the prevalence of fractures in patients with PsA as compared to healthy controls and to investigate determinants of fractures among cases. For both cases and controls, radiographs were read to identify vertebral fractures (VF), and the presence of femoral neck or other nonvertebral fractures was obtained from patients' medical history. The prevalence of fragility fractures on radiographic readings did not differ between cases and controls. The number of subjects showing a VF was 33 (36%) among PsA patients and 36 (36%) among controls, with a prevalence of severe VF of 8% among cases and 4% among controls. Controlling for covariates in a logistic model, the only variables showing a significant correlation with the presence of nonvertebral fractures (NVF) were disease duration (p=0.02), age (p=0.03), and bone mineral density at femoral neck (inverse correlation, p=0.04). Fractures should be carefully considered when evaluating the global picture of the patient with PsA for their contribution to the "fragility" profile.

Nail and distal interphalangeal joint in psoriatic arthritis.

OBJECTIVE: To study distal interphalangeal (DIP) joints in patients with psoriatic arthritis (PsA) with or without onychopathy, using magnetic resonance imaging (MRI). METHODS: Twenty-three patients with PsA (9/14 F/M, median age 47 yrs), 12 with onychopathy (2/10 F/M, median age 44 yrs) and 11 without (7/4 F/M, median age 52 yrs), and 10 control subjects (5/5 F/M, median age 43.2 yrs) were enrolled. MRI of nail and distal phalanx (DP) including examination of DIP joints was carried out. MRI was performed with a surface coil in a 1.5 T device. For each selected finger, both longitudinal and axial scans were performed. The involvement of nail, DP, and DIP joint was scored. RESULTS: Nail thickening with or without surface irregularity occurred in 95.7% of cases (100% with onychopathy and 90.9% without). MRI nail involvement was more frequent in patients with clinical evidence of onychopathy than in those without (p = 0.003). Similarly, 95.7% of patients showed MRI abnormalities of DP (100% with onychopathy and 90.9% without). MRI DP abnormalities were more marked in patients with clinical evidence of onychopathy than in those without (p = 0.009). Involvement of DIP joints was present in 34.8% of cases (58.3% with onychopathy and 9.1% without), and onychopathic patients showed marked MRI DIP joint involvement in 5 cases and mild in 2, while patients without onychopathy showed minimal changes in one case (p = 0.03). Considering the entire group of patients, MRI involvement of DIP joints was always associated with MRI DP changes, and in no case was it present alone. CONCLUSION: MRI nail involvement was present in almost all patients with PsA studied, even in those without clinically evident onychopathy. MRI involvement of DP always overlapped with nail involvement, since it was present in all psoriatic cases showing MRI nail involvement. In contrast, MRI DIP joint involvement was almost exclusively in a lower percentage of the patients with clinical nail involvement and was always associated with MRI DP changes. Our results suggest that DIP joint involvement is always secondary to nail and DP involvement.

Is the involvement of the distal interphalangeal joint in psoriatic patients related to nail psoriasis?

The aim of this study was to investigate the relationship between onychopathy and distal interphalangeal (DIP) joint involvement in psoriatic patients. Twenty-five consecutive unselected, unrelated patients with psoriatic onychopathy and 25 consecutive unselected, unrelated patients with psoriatic arthritis without onychopathy, were enrolled in the study. X-ray films of the hands were taken to identify DIP arthritic involvement and/or bone changes of the distal phalanx, which were categorized into five classes (0: no lesions; 1: tuftal minimal erosions; 2: tuftal bone resorption; 3: tuftal periosteal osteitis; 4: overlap of erosive and osteitic changes). Ten psoriatic patients with onychopathy and 8 without showed DIP arthritis, with no statistical differences in this distribution ( p=0.556). Bone changes of the distal phalanx were found in all 25 psoriatic patients with onychopathy and in 18 without. The distribution of patients in different categories of involvement of the distal phalanx showed that patients without onychopathy were markedly distributed in the categories with no or minimal lesions, whereas patients with onychopathy had structural changes prevailing included in categories with more severe bone changes (osteitis and overlap of erosive and osteitic changes) ( p=0.002). Onychopathic patients with DIP arthritis were older than those without ( p<0.0001) and showed a longer duration of onychopathy ( p<0.0001). Although the occurrence of DIP arthritis seems to depend on the duration of nail involvement, no statistical difference has been found in the distribution of DIP arthritis in psoriatic patients with or without onychopathy. In contrast, a topographical association between bone changes of the distal phalanx and dystrophy of the adjacent nail may be advanced.

[Osteoarticular scintigraphy in comparison with clinical evidence]. / Scintigrafia osteoarticolare a confronto con l'obiettività clinica.

Bone scintigraphy is a technique which is often resorted to in diagnostic rheumatology. There are few data on the effective relevance of bone scintigraphy in the evaluation of chronic inflammatory diseases of the joints. The aim of this study was to compare the results of bone scintigraphy with clinical evidence in patients with rheumatoid arthritis or osteoarthritis. Seventy-five patients were submitted to total body bone scintigraphy (44 rheumatoid arthritis, 31 osteoarthritis). The nuclear medicine specialist indicated the list of joints showing uptake. For the same patients a rheumatologist indicated the number of affected joints. The laboratory and clinical data were recorded. The patients were first stratified according to the prevalence of the clinical evidence and scintigraphic uptake. The distribution was found to be not significant. Only 5.3% of patients showed no uptake. Thirty-three patients had no clinical evidence of disease; among these, 30 showed joint uptake. Considering only the patients with clinical evidence, 97.6% showed joint uptake. These results were confirmed even when the data were analyzed by sex, disease and therapy. Considering the patients with clinical evidence, the uptake/clinical ratio did not show any significant correlation. The number of joints with clinical evidence correlated with the erythrocyte sedimentation rate. The number of joints showing uptake correlated only with age. In conclusion, on average, scintigraphy, performed in patients with rheumatoid arthritis and osteoarthritis, highlights a significantly higher number of joints involved as compared to what would be expected on the basis of clinical evaluation. It remains to be defined whether this is an overestimation related to the characteristics of the scan or whether it is sign of a higher sensitivity in highlighting the site of inflammation. Against the latter hypothesis is the absence of correlation with the inflammatory indexes.

Clinical and genetic aspects of psoriatic arthritis "sine psoriasis".

OBJECTIVE: To characterize the clinical pattern of psoriatic arthritis (PsA) sine psoriasis. METHODS: Fifty-seven patients (31 men, 26 women, mean age 46.32 +/- 14.12 yrs) with undifferentiated spondyloarthropathy (SpA) were studied. Two subsets were defined: (1) 21 patients with familial psoriasis (12 men, 9 women, mean age 49.29 +/- 14.17 yrs); (2) 36 patients without familial psoriasis (19 men, 17 women, mean age 44.58 +/- 14.00 yrs). The prevalence of the following clinical variables was evaluated: low back pain, enthesopathy, dactylitis, distal interphalangeal (DIP) arthritis, spinal involvement, and discitis. In all patients the following HLA haplotypes were tested: B7, B13, B17, B18, B27, B38, Cw6, and DR7. RESULTS: Dactylitis and DIP arthritis were markedly present in the articular subset with familial psoriasis (p < 0.0001) that also showed a high frequency rate of HLA-Cw6 (p < 0.0001 vs controls and patients without familial psoriasis). HLA-B27 was markedly frequent in patients without familial psoriasis (p < 0.0001 vs controls and p = 0.019 vs patients with familial psoriasis). In addition, in patients with familial psoriasis the log-linear model showed that the presence of HLA-Cw6 was related to the presence of DIP arthritis as well as dactylitis (likelihood ratio chi-square change of 5.891 and p = 0.015). CONCLUSION: A subset of patients with PsA "sine psoriasis" is identified by the occurrence of a SpA with dactylitis and/or DIP arthritis, presence of HLA-Cw6, and familial psoriasis in first or second-degree relatives.

Secretory phospholipases A2 induce cytokine release from blood and synovial fluid monocytes.

Secretory phospholipases A2 (sPLA2) are released in the blood of patients with various inflammatory diseases and exert proinflammatory activities by releasing arachidonic acid (AA), the precursor of eicosanoids. We examined the ability of four sPLA2 to activate blood and synovial fluid monocytes in vitro. Monocytes were purified from blood of healthy donors or from synovial fluid of patients with rheumatoid arthritis by negative immunoselection and by adherence to plastic dishes, respectively. The cells were incubated with group IA, IB, IIA and III sPLA2 and the release of TNF-alpha, IL-6 and IL-12 was determined by ELISA. Group IA, IB and IIA sPLA2 induced a concentration-dependent release of TNF-alpha and IL-6 from blood monocytes. These sPLA2 activated IL-12 production only in monocytes preincubated with IFN-gamma. Group IA and IIA sPLA2 also induced TNF-alpha and IL-6 release from synovial fluid monocytes. TNF-alpha and IL-6 release paralleled an increase in their mRNA expression and was independent from the capacity of sPLA2 to mobilize AA. These results indicate that sPLA2 stimulate cytokine release from blood and synovial fluid monocytes by a mechanism at least partially unrelated to their enzymatic activity. This effect may concur with the generation of AA in the proinflammatory activity of sPLA2 released during inflammatory diseases.

Sources of Arachidonic Acid in Human Lung Macrophages.

The aim of this study was to define the lipid pools in which arachidonic acid (AA) is stored and from which it is released upon activation of human lung macrophages (HLM). HLM incorporate exogenous AA into neutral lipids (triglycerides) and into the major phospholipid classes. HLM also possess an AA pool not previously reported in other human cells. Initial characterization of this arachidonate-containing lipid suggests it is bis-(monoacylglyceryl)-phosphate (BMP). HLM labeled with 3H-AA for 24 h released 7.6 and 15.5% of their total radioactivity in the supernatant after 30 min of stimulation with TPA (10--6M) and the Ca2+ ionophore A23187 (10--6M), respectively. AA was released from all phospholipid pools, mostly from phosphatidylethanolamine and phosphatidylcholine. In contrast, the amount of radioactivity in the triglyceride pool rapidly increased in activated HLM. These data demonstrate the existence of a novel AA-containing phospholipid in HLM, tentatively identified as BMP, and that, although these cells contain large stores of AA in triglycerides, the only sources of AA available for eicosanoid synthesis in stimulated HLM are phospholipids.