Cancer can occur in patients with inflammatory myopathies. This association is mainly observed in dermatomyositis, and myositis-specific antibodies have allowed us to delineate patients at an ...increased risk. Malignancy is also reported in patients with necrotizing autoimmune myopathies, but the risk remains elusive. Anti-signal recognition particle or anti-HMGCR antibodies have been specifically associated with necrotizing autoimmune myopathies. We aimed at screening the incidence of cancer in necrotizing autoimmune myopathies. A group of patients (n = 115) with necrotizing autoimmune myopathies with or without myositis-specific antibodies was analysed. Malignancy occurred more frequently in seronegative necrotizing autoimmune myopathies patients and in HMGCR-positive patients compared to anti-signal recognition particle positive patients. Synchronous malignancy was diagnosed in 21.4% and 11.5% of cases, respectively, and incidence of cancer was higher compared to the general population in both groups. No specific type of cancer was predominant. Patients suffering from a synchronous cancer had a decreased median survival time. Cancer screening is necessary in seronegative necrotizing autoimmune myopathies and in HMGCR-positive patients but not in anti-signal recognition particle-positive patients.
Background
High levels of serum interleukin-6 (IL-6) correlate with disease severity in COVID-19. We hypothesized that tocilizumab (a recombinant humanized anti-IL-6 receptor) could improve outcomes ...in selected patients with severe worsening COVID-19 pneumonia and high inflammatory parameters.
Methods
The TOCICOVID study included a prospective cohort of patients aged 16–80 years with severe (requiring > 6 L/min of oxygen therapy to obtain Sp02 > 94%) rapidly deteriorating (increase by ≥ 3 L/min of oxygen flow within the previous 12 h) COVID-19 pneumonia with ≥ 5 days of symptoms and C-reactive protein levels > 40 mg/L. They entered a compassionate use program of treatment with intravenous tocilizumab (8 mg/kg with a maximum of 800 mg per infusion; and if needed a second infusion 24 to 72 h later). A control group was retrospectively selected with the same inclusion criteria. Outcomes were assessed at D28 using inverse probability of treatment weighted (IPTW) methodology.
Results
Among the 96 patients included (81% male, mean (SD) age: 60 (12.5) years), underlying conditions, baseline disease severity, and concomitant medications were broadly similar between the tocilizumab (
n
= 49) and the control (
n
= 47) groups. In the IPTW analysis, treatment with tocilizumab was associated with a reduced need for overall ventilatory support (49 vs. 89%, wHR: 0.39 0.25–0.56;
p
< 0.001). Albeit lacking statistical significance, there was a substantial trend towards a reduction of mechanical ventilation (31% vs. 45%; wHR: 0.58 0.36–0.94;
p
= 0.026). However, tocilizumab did not improve overall survival (wHR = 0.68 0.31–1.748,
p
= 0.338). Among the 85 (89%) patients still alive at D28, patients treated with tocilizumab had a higher rate of oxygen withdrawal (82% vs. 73.5%, wHR = 1.66 1.17–2.37,
p
= 0.005), with a shorter delay before being weaned of oxygen therapy (mean 11 vs. 16 days;
p
< 0.001). At D28, the rate of patients discharged from hospital was higher in the tocilizumab group (70% vs. 40%, wHR = 1.82 1.22–2.75;
p
= 0.003). The levels of CRP and fibrinogen post therapy (
p
< 0.001 for both variables) were significantly lower in the tocilizumab group (interaction test, mixed model). Rates of neutropenia (35% vs. 0%;
p
< 0.001) were higher in the tocilizumab group, yet rates of infections (22% vs. 38%,
p
= 0.089) including ventilator-acquired pneumonia (8% vs. 26%,
p
= 0.022) were higher in the control group.
Conclusion
These data could be helpful for the design of future trials aiming to counter COVID-19-induced inflammation, especially before patients require admission to the intensive care unit.
Objective
To study a muscle-to-muscle standardised uptake value (SUV) ratio with FDG-PET/CT (FDG-PET) as a marker for the detection of disease activity in dermatomyositis (DM).
Methods
Patients with ...DM (
n
= 24) who met the
European Neuro-Muscular Centre
diagnostic criteria were retrospectively identified over a 3-year period through a national survey. Muscle biopsy was performed in all patients. Maximum SUV was measured in proximal muscles (SUV
PROX
) that had the highest radiotracer uptake on visual grading as well as in the musculus longissimus thoracis (SUV
MLT
), whereas mean SUV was measured for the liver (SUV
LIV
). Muscle-to-liver SUV ratios for either muscle group were compared and a SUV
PROX
/SUV
MLT
ratio was calculated. SUV
PROX
/SUV
MLT
of DM patients were compared with age- and sex-matched control subjects (
n
= 24) with melanoma who had received FDG-PET scans.
Results
DM patients presented with proximal and symmetrical muscle uptake. Differences in SUV
PROX
/SUV
LIV
and SUV
MLT
/SUV
LIV
ratios in DM subjects were significant (
p
< 0.001). SUV
PROX
/SUV
MLT
ratios in DM and their controls also differed significantly (
p
= 0.0012). The SUV
PROX
/SUV
MLT
ratio threshold between DM subjects and controls was 1.73 with a sensitivity of 50% (CI95%, 29.1 to 70.9%) and specificity at 83.3% (CI95%, 62.6 to 95.3%). When amyopathic DM patients were removed from the analysis, specificity was increased to 95% (CI95%, 75.1 to 99.9%) with a likelihood ratio of 10 and an AUC of 83.4% (CI95%, 71.4 to 95.4%).
Conclusion
A muscle-to-muscle SUV
PROX
/SUV
MLT
ratio with a cut-off value of 1.73 in FDG-PET imaging might serve as a non-invasive marker to determine disease activity in dermatomyositis.
Key Points
• 18F-FDG PET-scanner standardised uptake value (SUV) could reflect disease activity in dermatomyositis (DM).
•
A ratio of SUV in proximal muscles (SUV
PROX
) to SUV in musculus longissimus
thoracis
(SUV
MLT
) could be used to determine active DM.
• Active disease is suspected for SUV
PROX
/SUV
MLT
ratios greater than 1.73.
The ID NOW COVID-19 assay is a promising tool for the rapid identification of COVID-19 patients. However, its performances were questioned. We evaluate the ID NOW COVID-19 in comparison to a ...reference RT-PCR using a collection of 48 fresh nasopharyngeal swabs sampled on universal transport media (UTM). Only 2 false negatives of the ID NOW COVID-19 were identified. They display PCR cycle threshold values of 37.5 and 39.2. The positive percent agreement and the negative percent agreement were 94.9% and 100%, respectively. The Kappa value was 0.88. The ID NOW COVID-19 combines high-speed and accurate processing. Using UTM, the ID NOW COVID-19 could be repeated in the case of invalid result. Further analyses, such as screening of genetic variants or genome sequencing, could also be performed with the same sample. As for all tests, the results should be interpreted according to clinical and epidemiological context.
Dipeptidyl peptidase-4 (DPP4) inhibitors are a novel therapy widespread used in type 2 diabetes mellitus. We describe 3 cases of polyarthritis which delay of appearance strongly suggests a link with ...DPP4 inhibitors. Three patients presented with bilateral, symmetrical, seronegative polyarthritis after introduction of DPP4 inhibitors (sitagliptine (
n
= 2) and vildagliptine (
n
= 1)). Two patients also developed xerostomia and xerostomia, and laboratory test results showed normal values of CRP and erythrocyte sedimentation rate. Joints X-rays were normal. One patient was diagnosed with primary Sjögren’s syndrome and treated with hydroxychloroquine, methotrexate and prednisone, with a poor efficacy. When sitagliptine was stopped, all symptoms disappeared, leading to methotrexate and prednisone discontinuation within a month. There were no immunological abnormalities in the 2 other patients, but a chronic viral hepatitis B was found in one patient. Eventually, discontinuation of DPP4 inhibitors led to resolution of symptoms in 1 and 3 weeks for both patients. DPP4 inhibitors seemed to trigger bilateral, non-erosive, seronegative polyarthritis in our 3 patients. DPP4, also known as CD26, is expressed on many cells including lymphocytes and fibroblasts, and its inhibition may lead to immunomodulating effect as suggested by clinical and in vitro studies.
The 6-minute walk test (6MWT) is an important prognostic tool in various cardiovascular diseases and has been considered as a surrogate endpoint. However, conflicting results have been reported in ...systemic sclerosis (SSc). Our objective was to evaluate the relationships of the 6-min walking distance (6MWD) and organ damage in SSc.
Eighty-seven consecutive patients with SSc were included and prospectively investigated; they underwent 6MWT in addition to conventional assessment of possible lung, heart, kidney, skin, and muscle involvement, and disease activity scoring, severity, and quality of life determination.
Twenty-six patients (30%) had an abnormal 6MWT and the mean 6MWD was 461.8 +/- 103.0 m. When considering 6MWT as a binary variable - normal or abnormal - C-reactive protein (CRP) was the only independent variable associated with abnormal 6MWT. Considered as a continuous variable, the 6MWD was associated with measures of lung involvement and inflammation, with the activity and severity of disease, and also with quality of life; nevertheless, calcinosis was the only independent factor associated in multivariate analyses with a trend for an association for CRP.
The 6MWD relates to broad factors in SSc and these results raise doubts about the specificity of the 6MWD in this systemic disease, and its relevance to monitoring therapy.
AbstractObjectiveTo assess the effectiveness of hydroxychloroquine in patients admitted to hospital with coronavirus disease 2019 (covid-19) pneumonia who require oxygen.DesignComparative ...observational study using data collected from routine care.SettingFour French tertiary care centres providing care to patients with covid-19 pneumonia between 12 March and 31 March 2020.Participants181 patients aged 18-80 years with documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia who required oxygen but not intensive care.InterventionsHydroxychloroquine at a dose of 600 mg/day within 48 hours of admission to hospital (treatment group) versus standard care without hydroxychloroquine (control group).Main outcome measuresThe primary outcome was survival without transfer to the intensive care unit at day 21. Secondary outcomes were overall survival, survival without acute respiratory distress syndrome, weaning from oxygen, and discharge from hospital to home or rehabilitation (all at day 21). Analyses were adjusted for confounding factors by inverse probability of treatment weighting.ResultsIn the main analysis, 84 patients who received hydroxychloroquine within 48 hours of admission to hospital (treatment group) were compared with 89 patients who did not receive hydroxychloroquine (control group). Eight additional patients received hydroxychloroquine more than 48 hours after admission. In the weighted analyses, the survival rate without transfer to the intensive care unit at day 21 was 76% in the treatment group and 75% in the control group (weighted hazard ratio 0.9, 95% confidence interval 0.4 to 2.1). Overall survival at day 21 was 89% in the treatment group and 91% in the control group (1.2, 0.4 to 3.3). Survival without acute respiratory distress syndrome at day 21 was 69% in the treatment group compared with 74% in the control group (1.3, 0.7 to 2.6). At day 21, 82% of patients in the treatment group had been weaned from oxygen compared with 76% in the control group (weighted risk ratio 1.1, 95% confidence interval 0.9 to 1.3). Eight patients in the treatment group (10%) experienced electrocardiographic modifications that required discontinuation of treatment.ConclusionsHydroxychloroquine has received worldwide attention as a potential treatment for covid-19 because of positive results from small studies. However, the results of this study do not support its use in patients admitted to hospital with covid-19 who require oxygen.
With recent advances in endovascular treatment, percutaneous endoluminal angioplasty has become particularly attractive for arterial lesions of Takayasu arteritis. However, data came from case ...reports or small series, and the long-term outcome has not been reported. The incidence of potential vascular complications after surgery or endovascular treatment is still to be determined.
This retrospective multicenter study analyzed the results and outcomes of 79 consecutive patients with Takayasu arteritis (median age, 39 years; interquartile range IQR, 25-50 years; 63 women 79.7%) who underwent 166 vascular procedures (surgery, 104 62.7%; endovascular repair, 62 37.3%) for the management of arterial complications. After a follow-up of 6.5 years (IQR, 2.2-11.5 years), 70 complications were observed, including restenosis (n=53), thrombosis (n=7), bleeding (n=6), and stroke (n=4). The overall 1-, 3-, 5-, and 10-year arterial complication-free survival rates were 78% (IQR, 69%-88%), 67% (IQR, 57%-78%), 56% (IQR, 46%-70%), and 45% (IQR, 34%-60%), respectively. Among the 104 surgical procedures, 39 (37.5%) presented a complication compared with 31 of the 62 (50%) with endovascular repair. In multivariate analysis, biological inflammation at the time of revascularization (odds ratio, 7.48; 95% confidence interval, 1.42-39.39; P=0.04) was independently associated with the occurrence of arterial complications after the vascular procedure. Patients who experienced complications had higher erythrocyte sedimentation rates (P<0.001) and C-reactive protein (P<0.001) and fibrinogen (P<0.005) serum levels compared with those without complications.
The overall 5-year arterial complication rate was 44%. Biological inflammation increased the likelihood of complications after revascularization in patients with Takayasu arteritis.
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