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Background: Septic shock is a life-threatening organ dysfunction caused by a dysregulated host response to infection. The reduction of pro-inflammatory and anti-inflammatory mediators by hemoadsorption represents a new tool in the treatment of sepsis. In the present case series, we evaluated the impact of CytoSorb on adult patients with septic shock. Method(s): Patients with septic shock, admitted to Intensive Care Unit (ICU) from March 1, 2021 to February 28, 2022 who received CytoSorb therapy within 72 hours of admission were enrolled in the study. The severity of clinical conditions at admission was assessed by the SAPS II and SOFA scores;The magnitude of the inflammatory response was estimated using the plasmatic levels of C reactive protein (CRP) and interleukin-6 (IL-6). The effect of CytoSorb therapy on the inflammatory state, was evaluated measuring the percentage reduction of IL-6 and CRP. Time elapsed from ICU admission and the start of CytoSorb therapy was also assessed. T-test was used to compare the means of the groups of Survivors and No survivors. Fisher's test was used to evaluated the difference in mortality between Covid and No covid patients. Result(s): Twelve patients were evaluated. Six patients tested positive for covid-19, while the other six did not. Table 1 shows the values of age, SAPSII, SOFA, IL-6, CRP, PCT and timing between the survivors and the no survivors. Overall, there was no significant difference between the two groups in terms of SAPSII, SOFA, age, CRP. There was a significant difference in the timing of Cytosorb start and percentage of IL-6 removal: In surviving patients the timing of intervention was shorter (3,3+/-1,8 vs 23,5+/-18,9 hours) than in non- survivors. The IL-6 removal rate was significantly higher in the survivor group (70,8+/-15,87 vs 33,2+/-12,26). Conclusion(s): In survivors the timing of CytoSorb therapy was shorter and the IL-6 removal rate was higher than in non-survivors. This suggest that the early applying of CytoSorb adsorber in combination with Continuous Renal Replacement Therapy (CRRT) techniques, could increase the survival rate of septic shock patients. Using CytoSorb was safe and well tolerated with no device-related adverse events during or after the treatment.
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Systemic lupus erythematosus (SLE) is a chronic multisystem auto-immune disease with extremely varied clinical manifestations and a complex pathogenesis. New insights in SLE about pathogenetic pathways, biomarkers, and data on clinical manifestations are progressively emerging, and new drugs and new therapeutic strategies have been proposed to improve the control of disease activity. Thus, this review is aimed to summarise the most relevant data about SLE emerged during 2021, following the previous annual review of this series. © Copyright Clinical and Experimental Rheumatology 2022.
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Background: The COVID-19 pandemic, with its uncertainties, fears of contagion, mass lockdowns and containment measures, has dramatically impacted on people's everyday lives leading to an increased risk of mental disorders, particularly Post-Traumatic Stress Disorder (PTSD). Despite evidence in general population and healthcare workers1,2, scant data emerged on vulnerable populations, such as of patients with chronic illness, particularly rheumatic and musculoskeletal diseases (RMDs)3,4, who also underwent difficulties in the management and treatment of their disorders. Objectives: To assess PTSD and post-traumatic stress symptoms in a sample of patients with RMDs, during the COVID-19 pandemic in Italy. Methods: PERMAS is a monocentric prospective observational study led by the Rheumatology Unit, the Psychiatric Clinic and the Institute of Management of the School of Advanced Studies. Patients with a RMD diagnosis, were consecutively enrolled from May 2021 to January 2022. During the visit, sociodemographic characteristics and psychopathological data were collected through online survey, whereas clinical data were collected by physician. The survey included the Trauma and Loss Spectrum-Self Report (TALS-SR) and the Impact of Event Scale-Revised (IES-R), aimed to assess symptomato-logical PTSD and post-traumatic stress symptoms related to the impact of the COVID-19 pandemic. Results: A total of 194 eligible patients, with a mean age of 50.3±12.17 years, was included: 142 (73.19%) were females;112 (57.74%) patients reported connective tissue diseases (CTD), 63 (32.47%) arthritis and 19 (9.8%) vasculitis. A total of 33 (17%) subjects reported a symptomatological PTSD by means of the TALS-SR. The prevalence of Partial PTSD (defned by at least 2 out of the 4 criteria for DSM-5 diagnosis of the disorder) was 56.7%, with signifcant higher rates among females (90, 81.8%) with respect to males (20, 18.2%) (p=.013). Accordingly, a IES-R mean total score of 21.90 ±15.98 was found in the total sample and a gender difference emerged, with higher mean scores among females rather than males (23.42 ±16.26 vs 21.90 ±15.98, p=.031). Conclusion: The present fndings point out high prevalence rates of symptoma-tological PTSD among patients suffering from RMDs, highlighting the potentially traumatic burden of the COVID-19 pandemic in this particular population, especially among females, suggesting the need of further investigations to address tailored prevention and intervention strategies.
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Background: Patients with systemic autoimmune diseases (SADs) are often treated with drugs that interfere with the immune system and previous data showed a reduced seroconversion rate after anti-SARS-CoV2 vaccine in these subjects compared to healthy controls1. Administration of a booster dose of the vaccine could be particularly important in these patients, but data available to date are still scarce. Objectives: To evaluate the antibody response to the booster dose of mRNA SARS-CoV2 vaccine in patients with SADs and to compare it to the response after completion of the frst vaccination course. Secondly, to fnd possible correlations between a low antibody titre and patients' clinical features, with special regard to ongoing immunosuppressive therapies. Methods: Consecutive patients with an established diagnosis of SADs undergoing SARS-CoV2 vaccine were prospectively enrolled from January 2021;among them, we selected the patients who received the third vaccination dose between September and December 2021. Demographic and clinical data were collected at enrolment (sex, age, diagnosis, disease duration, ongoing therapies, previous SARS-CoV2 infection, presence of hypogammaglobulinemia);the last three elements were reassessed at each follow-up visit. Blood samples were collected 4 weeks both after the second (W4a) and the third (W4b) dose of the vaccine;a minority of patients was also tested 12 weeks after the second dose (W12). IgG antibodies to SARS-CoV2 receptor-binding domain (RBD) and neutralizing antibodies inhibiting the interaction between RBD and angiotensin converting enzyme 2 were evaluated. IgG anti-RBD were detected by solid phase assay on plates coated with recombinant RBD, while neutralising antibodies by using the kit SPIA (Spike Protein Inhibition Assay). Cut-off values were defned as the 97.5th percentile of a pre-vaccine healthy population. Statistical analysis was performed using IBM SPSS Statistics 20 and GraphPad Prism statistical packages. P values <0.05 were considered signifcant. Results: Forty-five patients (95.6% female;mean age ±SD 55.6±14.1 years;mean disease duration 12.9±10.6 years) were enrolled. Diagnosis was in most cases connective tissue disease (31/45, 68.9%), followed by infammatory arthritis (11/45, 24.4%) and systemic vasculitis (3/45, 6.7%). Two patients (4.4%) had a previous SARS-CoV2 infection and three had hypogammaglobulinemia (6.7%). At the time of the second dose, 18/45 patients were treated with glucocorticoids (GCs) [mean daily 6-methylprednisolone (6MP) dose 3.9 mg (min. 2, max. 14)], 17/45 with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) and 12/45 with biologic DMARDs (bDMARDs). At the third dose administration, 19/45 patients were treated with GCs [mean daily 6MP dose 4.1 mg (min. 1.5, max. 10)], 18/45 with csDMARDs and 13/45 with bDMARDs. Anti-RBD IgG were positive in 42/45 patients (93.3%) at W4a, in 16/18 (88.9%) at W12 and in 42/45 (93.3%) at W4b. Neutralizing antibodies were present in 38/45 patients (84.4%) at W4a, in 14/18 (77.8%) at W12 and in 42/45 (93.3%) at W4b. Both anti-RBD IgG titers and neutralizing antibody titers signifcantly increased after the third dose if compared to W4a (p<0.0001 both) (Figure 1). Interestingly, of the 7 patients who had not developed an adequate neutralizing antibody response after the frst vaccination course, 5 mounted an adequate titer after the booster. Two non-responder patients were both on combination therapy (one with low dose of GCs plus mycophenolate mofetil, the other with methotrexate and infiximab). Conclusion: Our data suggest that in patients with SADs there is a decline in the antibody titers developed after COVID-19 vaccination, however the booster dose is effective in restoring an adequate antibody titre. These data consolidate the importance of a booster dose of COVID-19 vaccination in patients with SADs to aid in the generation of an immune response.
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Background: Management of the health emergency caused by COVID-19 pandemic majorly disrupted the delivery of healthcare services to patients with chronic conditions like Systemic Autoimmune Diseases (SAD), both because resources were mainly channeled towards the care of infected patients, but also because patients tended to avoid seeking medical care for fear of becoming infected. PER-MAS is a 2-year project aimed at assessing the clinical, psychopathological, and socio-economic impact of COVID-19 in a cohort of patients with SAD. Objectives: To assess the impact of COVID-19 pandemic on drug withdrawal, disease fares and hospitalizations for disease exacerbation in a cohort of patients with SAD through an interim analysis of data from the PER-MAS project. Methods: A sample of 214 consecutive patients was recruited in a reference center for rare and complex autoimmune diseases from April 2021 to January 2022. Inclusion criteria were definite diagnosis of SAD (Connective Tissue Disease (CTD), Inflammatory Arthritis (IA) or Vasculitis), regular follow-up and at least 2 years of disease. Patients were asked to fill out an extensive self-administered questionnaire on disease activity and healthcare resource use during the pandemic (March 2020-moment of assessment). Pre-pandemic (March 2019-February 2020) and early pandemic (March 2020-February 2021) clinical data were recorded through retrospective chart review and patient interview. Results: At enrolment, 119 patients were affected by CTDs (55.6%), 71 by IA (33.18%), 24 by vasculitis (11.21%), with mean age 50.44± 12.97, and mean disease duration 11.17 ± 8.94. 30.37% took steroids, 39.7% hydroxy-chloroquine, 61.68% DMARDs, and 9.3% vasoactive drugs. Overall, disease course was similar in pre-pandemic and early pandemic phase: in the first period, rheumatologic condition was stable in 57.35% of patients, persistently active in 27.3% and 35.61% had ≥ 1 episode of disease exacerbation (mean 0.665±1.15, range 0-6);in the second period, 60.56% of patients was stable, 24.88% persistently active, and 39.44% had ≥1 exacerbation (mean 0.49 ±0.77, range 0-4). Mean number of visits (2.56±2.57 and 2.61±2.79), hos-pitalizations (0.168±0.698 and 0.14±0.473, p=0.6), number of patients with outpatient visits=0 (7.47 vs 7%), and number of patients with ≥ 1 hospital admission (10.28 vs 11.6%) were also similar, while the number of patients with hospital admissions for disease exacerbation was significantly higher in the second period (6.1 vs 11.21%, p=0.001). 170 patients completed the survey: from March 2020 to enrolment, 18.2% suspended ≥1 anti-rheumatic drug (6.25% of them for fear of contracting COVID-19 disease, 15.6% for difficulty in obtaining medications), 20% self-managed ≥ 1 disease exacerbation, and 40% had ≥ 1 telemedicine consult. From March to July 2020, 41.76% had their visit rescheduled (35.23% for hospital access restrictions, 5.3% for travel restrictions, 1.17% for fear). Conversely, only 14.7% of patients had their visit rescheduled (8.23% for hospital access restrictions, 4.7% for other reasons) from July 2020 to enrolment. Conclusion: In the early pandemic phase, overall disease course was similar to the pre-pandemic phase, but we observed an increase in the number of patients with ≥ 1 hospitalization for disease. Moreover, despite our efforts, patients reported a non-negligible rate of drug discontinuation for non-medical indication and difficulty to get access to rheumatologic consultation, highlighting the need of alternative organizational models in case of future pandemics.
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Background: Since the COVID-19 vaccination campaign was launched all over Europe, there has been general agreement on how benefts of SARS-CoV2 vaccines outweigh the risks in patients with rare connective tissue diseases (rCTDs). Yet, there is still limited evidence regarding safety and efficacy of such vaccines in these patients, especially in the long-term. For this reason, in the framework of ERN-ReCONNET, an observational long-term study (VACCINATE) was designed in order to explore the long-term outcome of COVID-19 vaccination in rCTDs patients. The consent form was developed thanks to the involvement of the ERN ReCONNET ePAG Advocates (European Patients Advocacy Group). Objectives: To evaluate the safety profile of COVID-19 vaccination in rCTDs patients and the potential impact on disease activity. Primary endpoints were the prevalence of adverse events (AEs) and of disease exacerbations post-vaccination. Secondary endpoints were the proportion of serious adverse events (SAEs) and adverse events of special interest for COVID-19 (adapted from https://bright-oncollaboration.us/wp-content/uploads/2021/01/SO2-D2.1.2-V1.2-COVID-19- AESI-update-23Dec2020-review-fnal.pdf) Methods: The frst ad-interim analysis of the VACCINATE study involved 9 ERN-ReCONNET Network centres. Patients over 18 years of age with a known rCTD and who received vaccine against COVID-19 were eligible for recruitment. Demographic data and diagnoses were collected at the time of enrolment, while the appearance of AEs and potential disease exacerbations were monitored after one week from each vaccination dose, and then after 4, 12 and 24 weeks from the second dose. A disease exacerbation was defned as at least one of the following: new manifestations attributable to disease activity, hospital-ization, increase in PGA from previous evaluation, addition of corticosteroids or immunosuppressants. Results: A cohort of 300 patients (261 females, mean age 52, range 18-85) was recruited. Systemic lupus erythematosus (44%) and systemic sclerosis (16%) were the most frequent diagnoses, followed by Sjogren's syndrome (SS,12%), idiopathic infammatory myositis (IMM,10%), undifferentiated connective tissue disease (UCTD,8%), mixed connective tissue disease (MCTD,4%), Ehlers-Dan-los's syndrome (EDS,4%), antiphospholipid syndrome (APS,2%). AEs appearing 7 days after the frst and second doses were reported in 93 (31%) and 96 (32%) patients respectively, mainly represented by fatigue, injection site reaction, headache, fever and myalgia. Otitis, urticaria, Herpes Simplex-related rash, stomatitis, migraine with aura, vertigo, tinnitus and sleepiness were reported with very low frequency. Less than 2% of patients experienced AEs within 24 weeks from the second dose. No SAEs or AEs of special interest were observed in the study period. There were 25 disease exacerbations (8%), 7 of which severe. The highest number of exacerbations was observed after 4 weeks from the second dose (12 within week 4, 6 within week 12 and 7 within week 24). Disease exacerbation was most frequent in patients with EDS (33%) and MCTD (25%). Conclusion: This preliminary analysis shows that COVID-19 vaccination is safe in rCTDs patients. AEs appear most often early after vaccination and are usually mild. Disease exacerbations are not frequent, but can be potentially severe and tend to occur most frequently within the frst month after vaccination. Exacerbations can also occur 3-6 months after vaccination, although a causal relationship with the vaccination remains to be established. Our present data underline the importance of long-term observational studies.
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Background: Fatigue in SLE has a multifactorial origin and disease activity seems to contribute only minimally to its genesis. Therefore, non-pharmacological therapeutic strategies should also be considered in the management of fatigue. There is some evidence on the effectiveness of aerobic exercise programs in improving fatigue, without a negative impact on disease manifestations. Objectives: the aim of this study was to analyze fatigue and Health Related Quality of Life (HRQoL) in a monocentric cohort of patients with SLE, in a condition of stable remission or low disease activity, before and after a program of physical exercise, through the administration of validated Patient Reported Outcomes (PROs). Methods: this is a cross-sectional interventional study which included patients with SLE, aged between 18 and 55 years, in a condition of stable (≥12 months) remission (DORIS)1 or low disease activity (LLDAS)2. Patients enrolled had a FACIT score ≤40 in the previous 6 months. Patients with other possible causes of fatigue (e.g.: anemia, hypothyroidism, severe vitamin D defciency), active arthritis or physical disabilities were excluded. For each patient, demographics, comorbidities, treatment, clinical and laboratory data were collected. Disease activity was evaluated with the SELENA-SLEDAI and organ damage with the SLICC/DI. Each patient completed the following PROs before and after the interventional program: SF-36, FACIT-Fatigue, LIT, HADS. Due to the limitations related to the COVID-19 pandemic, the physical exercise sessions were carried out using the Google Meet digital platform. Patients were asked to participate to at least 70% of the lessons. The physical exercise program included moderate intensity aerobic exercises (muscle strengthening, joint mobility, breathing, static and dynamic stretching, balance and neuro-dynamics);workouts were performed 3 times a week, consisting of 60 minutes each. The program lasted for 12 weeks. Results: we enrolled 12 female patients, regularly followed at the Rheumatology Unit of Pisa;only 9 of them completed the study (mean age 38.56 ± 9.1 years;median disease duration 7 years (IQR 5,25-9,75)). 8/9 were in stable remission, while 1/9 was in LLDAS for the presence of leukopenia. 2/9 patients presented organ damage, one for cataract and one for renal insufficiency, while none presented damage in the musculoskeletal system. 33.3% of patients had fbromyalgia. 88.8% was on treatment with Hydroxy-chloroquine, 55.5% was on low dose steroids (2±1.9 mg/daily), 33.3% was on Mycophenolate Mofetil;only 1 patient was on Belimumab. All PROs showed a trend to improvement at the end of the 12-week program of physical activity (Table 1). We demonstrated a statistically signifcant improvement of: FACIT, LIT, depression score of the HADS and MCS of the SF-36. The items of role physical (RP), vitality (VT) and mental health (MH) of the SF-36 also showed a signifcant improvement. Conclusion: In a small cohort of SLE patients in remission but with severe fatigue, in the difficult context of COVID-19 pandemic, we demonstrated that an online program of physical exercise may determine a signifcant improvement of fatigue, perception of disease burden and mental health. In the context of a multidisciplinary management, fnding effective intervention programs to improve fatigue and HRQoL in SLE patients appears of utmost importance, with the fnal aim of improving patients' health status.
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In order to address the main challenges related to the rare diseases (RDs) the European Commission launched the European Reference Networks (ERNs), virtual networks involving healthcare providers (HCPs) across Europe. The mission of the ERNs is to tackle low prevalence and RDs that require highly specialised treatment and a concentration of knowledge and resources. In fact, ERNs offer the potential to give patients and healthcare professionals across the EU access to the best expertise and timely exchange of lifesaving knowledge, trying to make the knowledge travelling more than patients. For this reason, ERNs were established as concrete European infrastructures, and this is particularly crucial in the framework of rare and complex diseases in which no country alone has the whole knowledge and capacity to treat all types of patients. It has been five years since their kick-off launch in Vilnius in 2017. The 24 ERNs have been intensively working on different transversal areas, including patient management, education, clinical practice guidelines, patients' care pathways and many other fundamental topics. The present work is therefore aimed not only at reporting a summary of the main activities and milestones reached so far, but also at celebrating the first 5 years of the ERN on Rare and Complex Connective Tissue and Musculo-skeletal Diseases (ReCONNET), in which the members of the network built together one of the 24 infrastructures that are hopefully going to change the scenario of rare diseases across the EU.