Tocilizumab therapy reduced intensive care unit admissions and/or mortality in COVID-19 patients.

INTRODUCTION: No therapy has yet proven effective in COVID-19. Tocilizumab (TCZ) in patients with severe COVID-19 could be an effective treatment. METHOD: We conducted a retrospective case-control study in the Nord Franche-Comté Hospital, France. We compared the outcome of patients treated with TCZ and patients without TCZ considering a combined primary endpoint: death and/or ICU admissions. RESULTS: Patients with TCZ (n=20) had a higher Charlson comorbidity index (5.3 [±2.4] vs 3.4 [±2.6], P=0.014), presented with more severe forms (higher level of oxygen therapy at 13L/min vs 6L/min, P<0.001), and had poorer biological findings (severe lymphopenia: 676/mm3 vs 914/mm3, P=0.037 and higher CRP level: 158mg/L vs 105mg/L, P=0.017) than patients without TCZ (n=25). However, death and/or ICU admissions were higher in patients without TCZ than in the TCZ group (72% vs 25%, P=0.002). CONCLUSION: Despite the small sample size and retrospective nature of the work, this result strongly suggests that TCZ may reduce the number of ICU admissions and/or mortality in patients with severe SARS-CoV-2 pneumonia.

Early decrease of serum biomarkers of type II collagen degradation (Coll2-1) and joint inflammation (Coll2-1 NO2 ) by hyaluronic acid intra-articular injections in patients with knee osteoarthritis: a research study part of the Biovisco study.

To measure the evolution of the serum levels of specific Osteoarthritis (OA) biomarker, Coll2-1 and Coll2-1 NO2 in knee osteoarthritic patients after viscosupplementation (VS). Fifty-one patients with unilateral symptomatic knee were recruited for this prospective open label study. They received three intra-articular injections of 2 ml of hyaluronic acid (Hylan GF-20) and were followed for 3 months. Walking pain was evaluated and serum samples were taken at each visit. Coll2-1 and Coll2-1 NO2 were measured in the serum using specific immunoassays. Variations over time of each parameter and predictive factor of response were studied. Forty-five patients were analyzed. The serum concentrations of Coll2-1 and Coll2-1 NO2 were significantly higher in KL III/IV patients compared to KL I/II patients at baseline and decreased systematically over time after VS. Its effect was ever more pronounced in patients with KL III/IV. The serum concentration of Coll2-1 was significantly lower at baseline in responders than in non-responders. This study suggests a rapid slowdown of type II collagen degradation and joint inflammation after VS with Hylan G-20 and gives additional information for the validation of accurate biomarkers for OA. The serum level of Coll2-1 appeared to be a predictive factor for response to treatment.

Continuing medical education for rheumatologists in France. Results of a national survey.

OBJECTIVE: To determine how continuing medical education is rated and used by French rheumatologists. MATERIAL AND METHODS: All French rheumatologists (n = 2579) were sent a questionnaire in September 1998. Results were evaluated using the test for differences between two proportions, with the significance level set at 0.05. RESULTS: 46% of the questionnaires (n = 1197) were returned completed. Mean age of respondents was 45 +/- 8 years; 41.2% of respondents were in full-time office practice, 14.8% were in full-time hospital practice, and 32.7% divided their time between the office and hospital. Nineteen percent worked in the Paris area. Nearly all the respondents (99.6 to 100%) attended continuing education meetings. Respondents working in Paris were significantly (P < 0.05) more likely than those working elsewhere to attend national conventions (99.6% vs 88.4%), whereas a difference in the other direction was found for regional and local conventions. The mean score assigned by respondents to national, regional and local conventions was 60/100. Respondents in full-time hospital practice were more likely than other respondents to attend international conventions; they were the only subgroup that assigned a score greater than 50/100 to this resource. University classes were attended by 44.4% of respondents and obtained a mean score of 65/100. Rheumatology journals were used by 99.2% of respondents and obtained scores greater than 65/100 in all subgroups. Respondents in full-time hospital practice were more likely to read international rheumatology journals than the other subgroups; they were the only subgroup that assigned a score greater than 50/100 to this resource. CD ROMs, videocassettes, and the Internet were used by less than one-fourth of respondents and were assigned low scores. The proportion of respondents who participated in the provision of education ranged from 23.6% to 53.3%. Opinions on the usefulness of the various educational resources varied across type-of-practice subgroups. CONCLUSIONS: Most respondents attended meetings and used resources for independent learning. The findings from our study could be used to plan further investigations into the use of continuing medical education by French rheumatologists, particularly those who did not send back our questionnaire.

Vascular complication involving the conus medullaris or cauda equina after vertebral manipulation for an L4-L5 disk herniation.

A case of injury to the cauda equina or conus medullaris after lumbar vertebral manipulation is reported. In contrast to all other previously reported cases, no migrated disk fragment was demonstrated. Similar to experience at the cervical spine, lumbar vertebral manipulation may carry a risk of vascular injury. The neurological manifestations in our patient were consistent with compression of the Desproges-Gotteron artery by a small L4-L5 disk herniation.

HLA DRB1* alleles in rheumatoid nodulosis: a comparative study with rheumatoid arthritis with and without nodules.

Rheumatoid nodulosis (RN) is a rare condition associating rheumatoid nodules, episodes of arthritis, cystic bone lesions and, generally, positive rheumatoid factors (RF). It is considered a benign variant of rheumatoid arthritis (RA). In this study, we determined the HLA DRB1* alleles of our RN patients and compared the distribution of these alleles to those of 74 healthy controls and 104 RA patients with and without nodules. Four RN patients were observed. All had subcutaneous nodules and RF were negative in three patients. Of the 104 RA patients, 18 had nodules (nodRA). Systemic manifestation (including vasculitis, peripheral neuropathy or lung involvement) were found in seven of these nodRA cases (33.8%) and most had positive RF and erosive changes on X-rays. Only one RN patient had a RA-associated allele (DRB1*0101). The frequencies of the HLA DRB1* alleles encompassing the "rheumatoid" shared epitope were similar to those of other RA series: *0101, 34.6% (P = 0.03 compared with controls); *0401, 26.9% (P < 0.0001); *0404, 12.5% (P = 0.04); *0405, 4.8% (P = 0.8); *1001, 8.6% (P = 0.5). Of the nodRA and seronegative RA patients, 77.7% and 53.3%, respectively, presented the shared epitope. Thus, there was a tendency to decreased expression of the RA-associated alleles in RN (25%) compared with nodRA and seronegative RA patients. This study is restricted by the small number of tested RN patients, but the results suggest that the RA-associated alleles are poorly expressed in RN.

Progression of digital osteoarthritis: a sequential scintigraphic and radiographic study.

Hand radiographs and scintigraphy were obtained initially and at the 4-year follow-up in 15 patients with symptomatic osteoarthritis (OA) of distal and/or proximal interphalangeal joints. For each joint, a 0-15 score was obtained for the OA radiographic lesions read blind by the same observer. An abnormal isotope retention over a bone reference area was assessed and quantified. The predictive value of scintigraphy for the OA radiographic progression was confirmed and shown to be improved by a second investigation. During the study period, the percentage of radiographic OA joints increased from 66.3 to 76.6%, but joints showing an abnormal scan decreased from 40 to 22.5%. Progression of the OA radiographic score was closely related to scintigraphic changes. The mean difference between the final and initial OA score was -0.08 in joints with two normal scans (N = 115), +0.73 in joints showing a first abnormal and a second normal scan (N = 94) and +1.8 in joints with two abnormal scans (N = 14) or a scan becoming abnormal (N = 47). An abnormal scan appears to represent a transient event, and this event is associated with a period of progression of digital OA. Potentially, anti-OA therapies that suppress joint isotope retention might slow down OA progression. The magnitude of joint isotope retention was positively correlated with the OA radiographic score established at the same time (R = 0.61 and P < 0.001), but showed no predictive value for progression of the latter.

[Serum phospholipase A2 activity in osteoarthritis]. / L'activité sérique de la phospholipase A2 dans l'arthrose.

Serum phospholipase A2 activity in 67 osteoarthritis patients and 17 controls was determined using a radiolabeled specific substrate. Serum phospholipase A2 activity was significantly higher in osteoarthritis patients (115 +/- 73.6 dpm/h/ml) than in controls (45 +/- 25 dpm/h/ml) (p = 0.002). In 41 osteoarthritis patients, serum phospholipase A2 activity was unrelated to age, time since onset of osteoarthritis symptoms, duration of morning stiffness, Lequesne's index, roentgenographic stage of osteoarthritis, number of joints with osteoarthritis, erythrocyte sedimentation rate, or serum C-reactive protein levels. In 12 osteoarthritis patients who were evaluated twice at a mean interval of 46 days, changes in serum phospholipase A2 activity were unrelated to changes in Lequesne's index. Blind evaluation of long-term joint space loss was performed in 14 patients; serum phospholipase A2 activity increased only in those patients with progressive joint space loss, but the difference was not statistically significant as compared with the controls. These data suggest that serum phospholipase A2 activity is not useful in practice as a marker for osteoarthritis.

Metalloprotease activity, phospholipase A2 activity and cytokine concentration in osteoarthritis synovial fluids.

Collagenase, stromelysin and phospholipase A2 (PLA2) activity as well as interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha) and interleukin 6 (IL-6) concentration were determined in the knee joint synovial fluid (SF) of 26 patients with osteoarthritis (OA) and with rheumatoid arthritis (RA). Collagenase and stromelysin were detected in 80.7 and 69.2% of OA SF, respectively. When present, the mean activity of both enzymes was approximately two times lower in OA than in RA SF. PLA2 activity was present in all SF with no significant difference between OA and RA SF. IL-1 beta, TNF alpha and IL-6 were found in 0, 96.1 and 84.6% of OA SF, respectively. Mean TNF alpha and IL-6 concentration was also lower in OA than in RA SF. Metalloprotease activity correlated weakly with IL-6 level and enzymatic activities were unrelated with TNF alpha in OA SF.

[Serum hyaluronic acid in osteoarthritis]. / L'acide hyaluronique sérique dans l'arthrose.

In this prospective study, serum hyaluronate (SH) was assayed using a radiometric method (Pharmacia) in 73 osteoarthritis patients and 39 controls. All assays were performed between 8 h 00 and 9 h 00 a.m. because SH levels exhibit circadian variations. SH levels were significantly higher in patients with osteoarthritis than in controls (92 +/- 66 micrograms/l and 39 +/- 21 micrograms/l, respectively, p = 0.0001). Among 50 patients with osteoarthritis, including 29 with knee involvement and 21 with hip involvement, SH levels were not correlated with morning stiffness, duration of symptoms, Lequesne's algofunctional index, erythrocyte sedimentation rate, C-reactive protein, severity of roentgenographic changes in the affected knee or hip, disease extension, or severity. The lack of any relationship between changes in SH levels and Lequesne's is index values in 25 patients or between SH levels and joint space narrowing evaluated retrospectively in 16 patients, as well as the prompt return to high SH levels after arthroplasty and synovectomy in 14 patients with hip joint osteoarthritis, suggest that this potential marker is not useful for monitoring osteoarthritis in a single joint.

[Measurement of the hip joint space using automatic digital image analysis]. / Mesure de l'interligne coxofémoral par un analyseur automatique d'images numérisées.

Joint surface area (JSA) and mean joint space width (MJSW) at the hip were measured using a ICMS-Techline computer program to analyze digitalised frontal weight-bearing roentgenograms of the pelvis. With this technique, the portion of joint space studied is always the same in a given patient and is enclosed within an acute ECS angle whose apex C is the center of the head of the femur and whose ends E and S are the lateral rim of the acetabulum and the highest point of the homolateral sacral wing respectively. ECS varies across individuals but remains constant in a given hip. Twenty hips were included in the first part of the study. For each hip, three roentgenograms were taken at five-minute intervals by three different radiologists who used their own constants (settings, position of the subject). JSA and MJSW are determined five times on each film by two different observers who had no information on the films under study. The interobserver coefficient of variation (CV) was 4.7% for JSA and 3.3% for MJSW. Intra-observer CVs were 2.97 and 3.54% for MJSW and 4.32% and 5.13% for JSA. There was a very close correlation between MJSW and JSA (r = 0.87, p < 0.0001). MJSW was then determined for roentgenograms of 30 hips with osteoarthritis. Results were compared with the values obtained using Lequesne's method of joint space measurement at the site of maximum narrowing. Measurements were performed in a double-blind fashion by two observers. The correlation coefficient was r = 0.89 (p < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

[Serum hyaluronic acid and phospholipase A2 in an arthritic population]. / Acide hyaluronique et phospholipase A2 sériques dans une population arthrosique.

Serum hyaluronic acid (HA) and A2 phospholipase (A2PL) activity were measured by radioimmunoassay (Pharmacia) and using a specific phospholipid substrate respectively, as potential markers of osteoarthritic synovitis. With neither age, treatment nor sample time taken into consideration, the concentration of HA (micrograms/ml) was 585 +/- 1,054 in rheumatoid arthritis, 379 +/- 409 in knee osteoarthrosis, 272 +/- 384 in hip osteoarthrosis, 131 +/- 144 in low back pain and 44 +/- 23 in osteoporosis, with no significant difference between the groups. HA was nevertheless found to be significantly higher in knee osteoarthrosis patients than in normal controls, when samples were drawn at the same time of day. Physical exercise (pedalling), as well as 20 hours lying flat and an intra-articular injection of corticosteroids did not cause any significant variation in serum HA levels in knee osteoarthrosis patients, in contrast to 20 hours of rest in the controls. A2PL activity was significantly higher in osteoarthrosis patients than in the controls, decreased with rest and corticosteroids and was not dependent upon sample time.

[Cytokines, prostaglandin E2, phospholipase A and metalloproteases in synovial fluid in osteoarthritis]. / Cytokines, prostaglandine E2, phospholipase A2 et métalloprotéases duliquide synovial dans l'arthrose.

Concentrations of prostaglandin E2, interleukin 1 beta, interleukin 6 and tumor necrosis factor alpha, phospholipase A2, collagenase and proteoglycanase activity were determined in synovial fluid from 26 patients with osteoarthrosis of the knee and 10 with rheumatoid arthritis. Osteoarthrosis synovial fluid was characterised by the absence of interleukin 1 beta while tumour necrosis factor alpha and interleukin 6 were present in relatively large amounts, by a very high phospholipase A2 activity contrasting with a very low concentration of prostaglandin E2, and by a collagenase/proteoglycanase activity only slightly less constant and high as in rheumatoid arthritis. In osteoarthrosis patients, the interleukin 6 concentration, but not that of tumor necrosis factor alpha, was correlated with the collagenase and proteoglycanase activity of synovial fluid.

[Effects of naproxen (naprosyne) on the metabolism of arthrotic cartilage in man in vivo]. / Effets du naproxène (Naprosyne) sur le métabolisme du cartilage arthrosique chez l'homme in vivo.

Degradative enzyme (proteoglycanase and collagenase) as well as proteoglycan synthesis enzyme (glycosyl-transferase) activity was studied in osteoarthritic fibrillated cartilage. Proteoglycanase activity was significantly lower in 10 patients with hip osteoarthritis treated with Naproxen (1 g/daily for 4 weeks) than in 10 patients treated with acetaminophen. Synthesis enzyme activity was similar in both groups. The results which confirm in vitro studies suggest that naproxen has not toxic effect on human osteoarthritic cartilage and could rather be beneficial.

Treatment of cutaneous T cell lymphoma with intermediate doses of interferon alpha 2a.

In this study we treated 6 patients with epidermotropic cutaneous T cell lymphoma (CTCL) with intermediate doses of recombinant alpha 2a interferon (18-100 x 10(6) IU/week) for 2-6 months. One patient experienced complete clinical remission in spite of a persistent dense lymphocytic skin infiltrate. One patient was markedly improved and 2 patients were moderately improved. The clinical condition of the 2 remaining patients was unchanged by interferon treatment. In all cases lesions relapsed a few weeks after treatment was discontinued. This study shows that interferon can be used to treat epidermotropic CTCL. However, a 2- to 6-month treatment using moderate doses did not lead to the high percentage of remission previously reported by others with high doses of recombinant alpha 2a interferon, for longer periods. This result suggests that interferon should be used at high doses and/or for long time periods for clinical improvement of CTCL patients.