The aim of this study was to investigate the incidence and clinical presentation of SARS-CoV-2 infections in a Systemic Lupus Erythematosus (SLE) cohort; to assess correlations with disease ...characteristics and rheumatic therapy; and to evaluate the occurrence of treatment discontinuation and its impact on disease activity.
SLE patients monitored by a single Italian centre were interviewed between February and July 2020. Patients were considered to be positive for SARS-CoV-2 infections in case of 1) positive nasopharyngeal swab; 2) positive serology associated with COVID19 suggesting symptoms. The following data were also recorded: clinical symptoms, adoption of social distancing measures, disease activity and treatment discontinuation.
332 patients were enrolled in the study. Six patients (1.8%) tested positive for SARS-CoV-2 infection, with the incidence being significantly higher in the subgroup of patients treated with biological Disease-Modifying Anti-Rheumatic Drugs (p = 0.005), while no difference was observed for other therapies, age at enrollment, disease duration, type of cumulative organ involvement or adoption of social isolation. The course of the disease was mild. Thirty-six patients (11.1%) discontinued at least part of their therapy during this time period, and 27 (8.1%) cases of disease flare were recorded. Correlation between flare and discontinuation of therapy was statistically significant (p<0.001). No significant increase of rate of flare in a subgroup of the same patients during 2020 was observed.
Treatment discontinuation seems to be an important cause of disease flare. Our findings suggest that abrupt drug withdrawal should be avoided or evaluated with caution on the basis of individual infection risk and comorbidities.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Treat-to-target is a therapeutic approach based on adjustments to treatment at set intervals in order to achieve well-defined, clinically relevant targets. This approach has been successfully applied ...to many chronic conditions, and in rheumatology promising results have emerged for rheumatoid arthritis. For systemic lupus erythematosus (SLE), defining the most meaningful treatment targets has been challenging, due to disease complexity and heterogeneity. Control of disease activity, the reduction of damage accrual and the patient's quality of life should be considered as the main targets in SLE, and several new drugs are emerging to achieve these targets. This review is focused on describing the target to achieve in SLE and the methods to do so, and it is also aimed at discussing if treat-to-target could be a promising approach also for this complex disease.
In this paper, we reject commonly accepted views on fundamentality in science, either based on bottom-up construction or top-down reduction to isolate the alleged
fundamental entities
. We do not ...introduce any new scientific methodology, but rather describe the current scientific methodology and show how it entails an inherent search for foundations of science. This is achieved by phrasing (minimal sets of) metaphysical assumptions into falsifiable statements and define as fundamental those that survive empirical tests. The ones that are falsified are rejected, and the corresponding philosophical concept is demolished as a prejudice. Furthermore, we show the application of this criterion in concrete examples of the search for fundamentality in quantum physics and biophysics.
Heteropolymers are important examples of self-assembling systems. However, in the design of artificial heteropolymers the control over the single chain self-assembling properties does not reach that ...of the natural bio-polymers, and in particular proteins. Here, we introduce a sufficiency criterion to identify polymers that can be designed to adopt a predetermined structure and show that it is fulfilled by polymers made of monomers interacting through directional (anisotropic) interactions. The criterion is based on the appearance of a particular peak in the radial distribution function, that we show being a universal feature of all designable heteropolymers, as it is present also in natural proteins. Our criterion can be used to engineer new self-assembling modular polymers that will open new avenues for applications in materials science.
Isolating the properties of proteins that allow them to convert sequence into the structure is a long-lasting biophysical problem. In particular, studies focused extensively on the effect of a ...reduced alphabet size on the folding properties. However, the natural alphabet is a compromise between versatility and optimisation of the available resources. Here, for the first time, we include the impact of the relative availability of the amino acids to extract from the 20 letters the core necessary for protein stability. We present a computational protein design scheme that involves the competition for resources between a protein and a potential interaction partner that, additionally, gives us the chance to investigate the effect of the reduced alphabet on protein-protein interactions. We devise a scheme that automatically identifies the optimal reduced set of letters for the design of the protein, and we observe that even alphabets reduced down to 4 letters allow for single protein folding. However, it is only with 6 letters that we achieve optimal folding, thus recovering experimental observations. Additionally, we notice that the binding between the protein and a potential interaction partner could not be avoided with the investigated reduced alphabets. Therefore, we suggest that aggregation could have been a driving force in the evolution of the large protein alphabet.
BackgroundSLE is an autoimmune disease that predominantly affects women. As most epidemiological and interventional studies are on populations with a clear female prevalence, the influence of gender ...in disease course, drug response and damage accrual is yet to be fully explored and comprehended.ObjectivesTo describe gender differences in disease course, comorbidities, use of medications and long-term outcomes of a large cohort of patients with SLE.MethodsRetrospective gender-based analysis of prospectively collected data from a monocentric cohort of Caucasian patients with SLE with at least 1 year of follow-up.Results417 patients were included, 51 men and 366 women. Men displayed a significantly higher median age at disease onset and diagnosis and a higher prevalence of late-onset SLE, serositis at disease onset, antiphospholipid syndrome (APS) and use of mycophenolate within the first year of disease. Women had a higher prevalence of haematological abnormalities, a higher cumulative exposure to azathioprine and higher cumulative dose of glucocorticoids at 5 years. Male patients had a shorter time to first damage item and a higher prevalence of damage at 1 and 5 years, but this association was no longer significant when late-onset patients were excluded. No differences were found in prevalence of childhood onset, delay between onset and diagnosis, time to renal involvement and histology, cumulative autoantibody positivity, number of flares and hospitalisations, median SLE Damage Index score, type of damage, age and time to first cardiovascular event, chronic kidney disease and death.ConclusionsIn our cohort, clinical manifestations and disease course were similar in male and female patients; however, male patients displayed higher prevalence of APS and early damage accrual probably due to the later disease onset. These data highlight the importance of an intensive follow-up, prevention and treatment of complications in this category of patients, especially in the first years of disease.
ObjectivesUndifferentiated connective tissue diseases (UCTDs) are systemic autoimmune conditions that cannot be diagnosed nor classified as defined CTD; the majority maintains an undifferentiated ...profile (stable UCTD, sUCTD) over time. Data on long-term outcomes of sUCTD are lacking.MethodsRetrospective longitudinal analysis of an inception cohort of 141 patients with sUCTD.Disease evolution and damage accrual were evaluated at 1, 5 and 10 years. Partial least square (PLS) regression was used to identify the basal variables contributing to damage accrual at 1, 5 and 10 years of follow-up. Trend of damage over time was compared with a cohort of age-matched and sex-matched patients with systemic lupus erythematosus (SLE) by means of Nelson-Aalen analysis.Results11.3% of patients evolved to a definite CTD after a median 11 years (IQR 6–25) from the first symptom. At last visit, 10% were on glucocorticoids and 6% on immunosuppressive therapy. In 27.3%, at least one item of organ damage was recorded according to the SLICC/DI score (mean score 1.19±0.46). At PLS analysis, age at diagnosis and age at first symptoms were related to damage at 1 year, not taking antimalarials and taking immunosuppressants were associated with damage at 5 years.The mean survival without damage was 9.3 years in sUCTD and 8.4 years in SLE. The 10-year probability without damage was 62% and 23% in SLE and sUCTD, respectively (p=0.015).ConclusionsAlthough less significantly impacted than in patients with SLE, in the long-term UCTDs can accumulate organ damage and evolve into defined connective tissue diseases.
ObjectiveThe objective is to evaluate perscriptions of belimumab (BEL), how these have changed over the years and their impact on clinical outcomes in patients with systemic lupus erythematosus ...(SLE).MethodsThis is a retrospective analysis of prospectively collected data. We retrieved demographic and clinical data and concomitant therapies at BEL starting (baseline). Disease activity was assessed at baseline and after 6 and 12 months and organ damage at baseline and at the last visit.ResultsFrom 422 patients followed in the Pisa SLE cohort, 102 patients received BEL and were included and 22 (21.6%) were immunosuppressant (IS)-naïve. Lupus Low Disease Activity State (LLDAS) with a glucocorticoid (GC) dosage ≤5 mg/day (LLDAS5) and remission were achieved by 47% and 38% of patients at 6 months, and by 75% and 66% at 12 months. Comparing IS-naïve patients with those who received BEL after at least one conventional IS, we did not find significant differences in baseline characteristics and in the achievement of LLDAS5 and remission. Despite at baseline we did not observe significant differences in mean GC daily dosage, IS-naïve patients were taking a significantly lower GC daily dose at 6 and 12 months. Interestingly, IS-naïve patients were more common in the most recent years.ConclusionsOur data confirm that BEL is effective in controlling disease activity, and in recent years BEL has been considered as an earlier treatment option before other IS. Early introduction of BEL can be at least as effective as a step-up approach and can help to reduce the GC dosage.
ObjectiveTo describe frequency and characteristics of SLE patients in glucocorticoids (GC)-free remission in a real-life setting.MethodsThis is a retrospective analysis of prospectively collected ...data from a monocentric SLE cohort. The following variables were retrieved: demographic data, cumulative organ involvement; at last observation: disease activity (SLEDAI-2K score), ongoing therapy, disease state (remission defined according to the 2021 DORIS criteria) and organ damage (SDI score).ResultsFrom our cohort, a total of 390 SLE patients (87.4% female, all Caucasian) had at least 1 year of follow-up and complete clinical data to be included in the analysis. At last evaluation, the mean follow-up duration was 11.1 years (min 1-max 42) and 293 patients (75.1%) were in remission. Of these, 141 (36.2%) were in GC-free remission (GC-), and 44 of them (11.2%) were GC-free for 5 years. Characteristics of patients in remission, as well as the comparison between GC- group and remitted patients under GC treatment (GC+) are reported in table 1.No significant differences were found with regard to age, organ involvement and disease duration at last evaluation between the two groups. However, mean cumulative GC dose was significantly higher in GC+ group (24.7±27.7 vs 14.7±13.3, p<0.01).Being GC- at last observation was associated with a significantly lower organ damage with respect to GC+ (mean SDI 0.7±1.1 vs 1.5±2.0, p<0.01). In particular, significant differences regarded cardiovascular events (5.0% vs 13.6%, p=0.01) and osteoporosis (12.1% vs 30.3%, p<0.01) were found, and GC+ patients had also more frequently concomitant diagnosis of hypertension (35.5% vs 22.7%, p=0.01).ConclusionsGC-free remission is an achievable goal in SLE patients and it is sustained over time in a good proportion of patients. Our study also confirms that GC withdrawal has important advantages in term of organ-damage sparing; indeed, GC-patients at last observation were presenting less organ damage, especially GC-related organ damage.Abstract P114 Table 1Characteristics of SLE patients in remission (n=293) Patients in remission N=293 GC-free remission N=141 (48.1%) GC+ remission N=152 (51.9%) P value Female (%) 255 (87.0) 122 (86.5) 133 (87.5) 0.80 Age at diagnosis, years1 32.3±13.0 31.1±13.0 33.5±12.9 0.12 Age at study enrolment, years1 46.7±13.3 45.4±12.6 47.8±13.9 0.13 Disease duration, years1 17.0±9.8 16.9±8.6 17.1±10.8 0.80 Renal involvement (%) 134 (45.7) 60 (42.6) 74 (46.7) 0.29 Joint involvement (%) 215 (73.4) 100 (70.9) 115 (75.7) 0.18 Skin involvement (%) 175 (59.7) 82 (58.1) 93 (61.2) 0.50 Haematological involvement (%) 171 (58.4) 83 (58.9) 88 (57.9) 0.86 Serositis (%) 56 (19.1) 23 (16.3) 33 (21.7) 0.21 Neuropsychiatric involvement (%) 29 (9.9) 10 (7.1) 19 (12.5) 0.11 Cumulative dose of GC, grams1 19.9±22.5 14.7±13.3 24.7±27.7 <0.01 SLICC-Damage Index at last observation1 1.1±1.7 0.7±1.1 1.5±2.0 <0.01 Cardiovascular event (%) 27 (9.2) 7 (5.0) 20 (13.6) 0.01 Osteoporosis (%) 63 (21.5) 17 (12.1) 46 (30.3) <0.01 Diabetes (%) 14 (4.8) 6 (4.3) 8 (5.3) 0.65 Hypertension (%) 86 (29.3) 32 (22.7) 54 (35.5) 0.01 1Mean ± standard deviation
ObjectiveSkin involvement in Systemic Lupus Erythematosus (SLE) is still often a challenge for the rheumatologist, who must consider patients’ perspective in order to ensure the best quality of care. ...The aim of the study was to evaluate the impact of skin involvement on Health-Related Quality of Life (HRQoL) in a monocentric cohort of SLE patients.MethodsThis is a cross-sectional analysis of prospectively collected data of adult consecutive SLE patients (2019 EULAR/ACR criteria) with skin involvement. The following data have been collected for each patient: demographics and clinical data, SLEDAI-2K and SLICC-DI. Clinical evaluation of skin was performed using the Cutaneous LE Disease Area and Severity Index (CLASI), which we used to define skin disease activity and damage. At each assessment, patients completed the following Patient Reported Outcomes: LIT, SLAQ, FACIT-F, HADS and Skindex-16.ResultsWe included 109 assessments in 59 SLE patients during the period February 2021 – June 2023. Cohort characteristics are shown in table 1. CLASI activity assessment correlated positively with Skindex-16 scores (rs≥0.307, p≤0.002) and to a lesser extent with LIT (rs=0.231, p=0.02); CLASI damage correlated positively con LIT, HADS depression and Skindex-16 functioning subscales (rs≥0.280, p≤0.006) and negatively with FACIT-F (rs=-0.305, p=0.002). Analysing potential differences in the impact of skin activity and damage on QoL, we noted that only the presence of active skin disease seems to influence the patients‘ perception assessed with the Skindex-16, as illustrated in table 2. Considering the overall disease burden, we found significantly higher scores in all Skindex-16 subscales, LIT, SLAQ and HADS anxiety subscale in females compared to males (p≤0.003). We found no further differences in relation to gender and other demographic and clinical features.ConclusionsSkin disease is confirmed as a major determinant of HRQoL in SLE patients. While disease activity has a significant impact on patients’ perception of skin symptoms, our data suggest that the presence of chronic skin damage, rather than activity, may have a more negative impact on HRQoL, significantly influencing the emotional sphere and the patient‘s perception of the burden of disease. Further studies are needed to confirm these preliminary findings.Abstract P122 Table 1Characteristics of the cohort N° of patients 59 Female 52 (88.1%) Age at study entry1years 46 (33–56) Disease duration at study entry1years 12 (7–20) Ethnicity: Caucasian/Asian/African-American 55 (93.2%)/3 (5.1%)/1 (1.7%) Cutaneous subgroup: chronic (CCLE)/subacute (SCLE )/acute (ACLE) 28 (47.4%)/9 (15.3%)/22 (37.3%) Ongoing organ involvement * Mucocutaneous 99/109 (90.8%) Haematological 11/109 (10.1%) Renal 4/109 (3.7%) Articular 12/109 (11.0%) Serositis 0 Neuropsychiatric 0 SLEDAI-2K1 * 4 (2–6) SLICC-DI1 * 0 (0–1) CLASI activity1 * 5 (2–8) CLASI damage1 * 2 (0–8) LIT1 * 22.5 (12.5–47.5) SLAQ1 * 16 (11–26) FACIT-F1 * 38 (28–43) HADS anxiety1 * 6 (4–9) HADS depression1 * 7 (4–10) Skindex-16 symptoms1 * 37.5 (12.5–79.0) Skindex-16 emotions1 * 55.7 (21.4–90.5) Skindex-16 functioning1 * 31.7 (6.7–79.2) 1 Median (IQR) * data on 109 assessmentsAbstract P122 Table 2Comparison of assessments based on the presence or absence of skin disease activity and damage Cutaneous activity Cutaneous damage Yes (N=99) No (N=10) p-value Yes (N=63) No (N=46) p-value SLEDAI-2K 5.05 (±3.22) 2.00 (±1.33) <0.001 4.86 (±2.87) 4.64 (±3.68) 0.737 CLASI activity 7.73 (±6.90) 0 (±0) <0.001 8.49 (±8.10) 4.96 (±4.17) 0.004 CLASI damage 4.42 (±6.3) 7.70 (±7.86) 0.229 8.10 (±6.63) 0 (±0) <0.001 LIT 31.81 (±22.65) 21.80 (±17.68) 0.178 34.04 (±22.81) 25.94 (±20.94) 0.075 SLAQ 19.38 (±12.73) 13.50 (±2.12) 0.519 19.97 (±13.36) 18.35 (±11.80) 0.587 FACIT-F 33.80 (±12.24) 34.50 (±13.22) 0.865 32.20 (±12.59) 36.33 (±11.50) 0.100 HADS anxiety 6.79 (±3.76) 5.11 (±2.67) 0.195 6.46 (±4.27 6.87 (±2.68) 0.569 HADS depression 7.24 (±4.42) 7.00 (±1.94) 0.773 7.73 (±4.55) 6.49 (±3.70) 0.149 Skindex-16 symptoms 48.18 (±34.73) 12.93 (±15.64) <0.001 45.92 (±35.64) 43.18 (±34.22) 0.695 Skindex-16 emotions 59.20 (±33.98) 14.06 (±26.03) <0.001 56.83 (±36.18) 52.07 (±35.45) 0.507 Skindex-16 functioning 44.27 (±36.16) 13.67 (±29.93) 0.011 43.14 (±37.52) 38.76 (±35.60) 0.550
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