Microvascular damage of skin and internal organs is a hallmark of systemic sclerosis (SSc). Serum uric acid (UA) represents a marker of inflammation and endothelial dysfunction. The aims of this ...study were to evaluate the correlation between serum UA and intrarenal arterial stiffness evaluated by Doppler ultrasound in SSc patients with normal renal function. We also evaluated the correlation between serum UA and other clinical variables of the disease.
Forty-five SSc patients underwent clinical assessment, Doppler ultrasound of intrarenal arteries with evaluation of resistive index (RI), pulsatile index (PI), and systolic/diastolic ratio (S/D), echocardiography with systolic pulmonary artery pressure (PAPs), baseline pulmonary function tests, and nailfold videocapillaroscopy (NVC). In all patients serum UA was measured.
The serum UA showed a significant positive correlation with sCr (r=0.33, p<0.0001) and PAPs (r=0.38, p<0.01) >and negative correlation with CKD-EPI (r=−0.35, p<0.01). The mean value of serum UA increased with severity of NVC damage. Using this cut-off value of 4.7mg/dl, the mean value of Doppler indices of intrarenal stiffness is significantly different (p<0.05) in SSc patients with low normal or high normal serum UA.
Serum UA concentration is higher in patients with high microvascular damage than in patients with low microvascular damage. These preliminary data must be confirmed in large prospective studies.
•In SSc patients serum UA shows a positive correlation with sCr•In SSc patients serum UA shows a negative correlation with CKD-EPI•In SSc patients serum UA shows a positive correlation with intrarenal arterial stiffness and with PAPs•The serum UA increased with capillaroscopic damage severity evaluated by NVC•Serum UA represents a marker of endothelial dysfunction and damage in SSc patients.
Objective
Patients with COVID-19 presented with an elevated prevalence of antiphospholipid antibodies (aPL) but the relationship with thrombosis is controversial. We analysed the persistence of aPL ...and their association with the clinical outcomes during hospitalisation in a cohort of COVID-19 patients.
Patients and Methods
We conducted a prospective study including consecutive hospitalised patients with COVID-19 from Hospital Clínic of Barcelona between March 28th and April 22nd, 2020. Clinical outcomes during hospitalisation were thrombosis, intensive care unit (ICU) admission, and severe ventilatory failure. We determined both criteria and non-criteria aPL. Of note, in those patients with a positive result in the first determination, a second sample separated by at least 12 weeks was drawn to test the persistence of aPL.
Results
One hundred and fifty-eight patients (59.5% men) with a mean age of 61.4 ± 14.9 years old were included. Thrombosis was present in 28 (17.7%) patients, severe respiratory failure in 47 (30.5%), and 30 (18.9%) patients were admitted to ICU. Sixteen (28.6%) patients were positive for the criteria aPL at both determinations and only two (3.6%) of them suffered from thrombosis during hospitalisations (both had aCL IgG). However, they presented with low titers of aCL. Of note, aPL were not related to thrombosis, ICU admission or severe respiratory failure.
Conclusion
Although aPL were prevalent in our cohort of hospitalised COVID-19 patients and they were persistent in half of tested patients, most determinations were at low titers and they were not related to worse clinical outcomes.
Hyperbaric oxygen therapy (HBOT) has been investigated as a primary/adjunctive treatment for a number of injuries and medical conditions including traumatic ischemia, necrotizing soft tissue ...injuries, non-healing ulcers and osteoradionecrosis, but the results are controversial. There is insufficient evidence to support or reject the use of HBOT to quicken healing or to treat the established non-union of fractures. However, in patients with fibromyalgia, HBOT reduces brain activity in the posterior cortex and increases it in the frontal, cingulate, medial temporal and cerebellar cortices, thus leading to beneficial changes in brain areas that are known to function abnormally. Moreover, the amelioration of pain induced by HBOT significantly decreases the consumption of analgesic medications. In addition, HBOT has anti-inflammatory and oxygenatory effects in patients with primary or secondary vasculitis. This review analyzes the efficacy and limitations of HBOT in orthopedic and rheumatologic patients.
Opinion statement
Allergen immunotherapy (AIT) is presently the only treatment able to modify the natural history of respiratory allergic disease. The essential condition for AIT to be effective is ...that the right allergen(s) is/are administered. The proportion of allergic patients showing multiple sensitizations to distinct airborne allergen sources has dramatically increased during the last decades, and this fact, along with the frequent co-recognition of highly cross-reacting pollen panallergens (i.e., profilin and polcalcin), may make a correct diagnosis virtually impossible by using the traditional allergen extracts for diagnosis. Many purified recombinant or natural allergens are currently available for the in vitro diagnosis of respiratory allergy. These represent an invaluable tool to prevent the inclusion of inappropriate allergens in AIT extracts, and the present article provides some suggestions for their rational use in everyday clinical practice.
Background
Unprotected and fragile elderly people in nursing homes experienced the highest mortality rates during the initial coronavirus disease 2019 (COVID-19) pandemic.
Objective
Our aim was to ...study the role of two oral anti-inflammatory drugs, colchicine and prednisone, in elderly patients with COVID-19 in geriatric centers.
Methods
A phase II/III, randomized, controlled, multicenter clinical trial was performed in a geriatric population comparing the efficacy and safety of an oral combination of prednisone (60 mg/day for 3 days) and colchicine (at loading doses of 1–1.5 mg/day for 3 days, followed by 0.5 mg/day for 11 days) with the standard treatment, based on intravenous dexamethasone. Primary endpoints assessed the efficacy in reducing death or the modified endpoint death/therapeutic failure to the study drugs over a 28-day period, while secondary endpoints included safety, laboratory changes, and additional therapies used.
Results
Fifty-four patients (35 female/19 male) were enrolled, 25 (46.3%) of whom were allocated to the experimental arm and 29 (53.7%) to the control arm. At day 28, no differences in deaths were observed. The combination of mortality or therapeutic failure occurred in 12 (45.13%) patients receiving dexamethasone and 6 (28.13%) patients receiving colchicine/prednisone, resulting in a reduction of risk difference (RD) of − 17% (
p
= 0.17), with an average reduction of 39% (risk ratio RR 0.61) in patients receiving colchicine/prednisone (
p
= 0.25). Control patients received higher amounts of additional glucocorticoids (
p
= 0.0095) over a longer time frame (
p
= 0.0003). Colchicine/prednisone significantly reduced ferritin levels at day 14, as well as
d
-dimer and lactate dehydrogenase (LDH) levels at day 28. Adverse events were similar in both groups.
Conclusions
The combination colchicine/prednisone compared with intravenous dexamethasone has shown a remarkable trend to increase disease survival over a 28-day period in elderly patients requiring oxygen therapy in geriatric centers, without safety issues.
Clinical Trial Registry
Clinical Trials Registration Number: NCT04492358.
Background: Cardiorenal syndrome type 5 (CRS-5) includes a group of conditions characterized by a simultaneous involvement of the heart and kidney in the course of a systemic disease. Systemic ...sclerosis (SSc) is frequently involved in the etiology of acute and chronic CRS-5 among connective tissue diseases. In SSc patients, left ventricular mass (LVM) can be used as a marker of nutritional status and fibrosis, while altered intrarenal hemodynamic parameters are suggestive of early kidney involvement. Methods: Forty-two consecutive patients with a diagnosis of SSc without cardiac and/or renal impairment were enrolled to assess whether cardiac muscle mass can be related to arterial stiffness. Thirty subjects matched for age and sex were also enrolled as healthy controls (HC). All patients performed echocardiography and renal ultrasound. Results: Doppler indices of intrarenal stiffness and echocardiographic indices of LVM were significantly increased in SSc patients compared to HC. A positive correlation exists between LVM/body surface area and pulsatile index (p < 0.05, r = 0.36), resistive index (p < 0.05, r = 0.33) and systolic/diastolic ratio (p < 0.05, r = 0.38). Doppler indices of intrarenal stiffness and LVM indices were significantly higher in SSc patients with digital ulcers than in SSc patients without a digital ulcer history. Conclusions: SSc is characterized by the presence of microvascular and multiorgan injury. An early cardiac and renal impairment is very common. LVM and intrarenal arterial stiffness can be considered as early markers of CRS onset. The clinical use of these markers permits a prompt identification of organ damage. An early diagnosis allows the appropriate setting of pharmacological management, by slowing disease progression.
Background:
Rituximab, an anti-CD20 monoclonal antibody leading to B lymphocyte depletion, is increasingly used as an off-label treatment option for multiple sclerosis (MS).
Objective:
To investigate ...the effectiveness and safety of rituximab in relapsing–remitting (RR) and progressive MS.
Methods:
This is a multicenter, retrospective study on consecutive MS patients treated off-label with rituximab in 22 Italian and 1 Swiss MS centers. Relapse rate, time to first relapse, Expanded Disability Status Scale (EDSS) progression, incidence of adverse events, and radiological outcomes from 2009 to 2019 were analyzed.
Results:
A total of 355/451 enrolled subjects had at least one follow-up visit and were included in the outcome analysis. Annualized relapse rate significantly decreases after rituximab initiation versus the pre-rituximab start year in RRMS (from 0.86 to 0.09, p < .0001) and in secondary-progressive (SP) MS (from 0.34 to 0.06, p < .0001) and had a slight decrease in primary-progressive (PP) MS patients (from 0.12 to 0.07, p = 0.45). After 3 years from rituximab start, the proportion of patients with a confirmed EDSS progression was 14.6% in the RRMS group, 24.7% in the SPMS group, and 41.5% in the PPMS group. No major safety concerns arose.
Conclusion:
Consistently with other observational studies, our data show effectiveness of rituximab in reducing disease activity in patients with MS.
Uncontrolled evidence suggests that autologous hematopoietic stem cell transplantation (AHSCT) can be effective in people with active secondary progressive multiple sclerosis (SPMS). In this study, ...we compared the effect of AHSCT with that of other anti-inflammatory disease-modifying therapies (DMTs) on long-term disability worsening in active SPMS.
We collected data from the Italian Bone Marrow Transplantation Study Group and the Italian Multiple Sclerosis Register. Patients were considered eligible if treatment had been started after the diagnosis of SPMS. Disability worsening was assessed by the cumulative proportion of patients with a 6-month confirmed disability progression (CDP) according to the Expanded Disability Status Scale (EDSS) score. Key secondary endpoints were the EDSS time trend after treatment start and the prevalence of disability improvement over time. Time to first CDP was assessed by means of proportional hazard Cox regression models. A linear mixed model with a time × treatment group interaction was used to assess the longitudinal EDSS time trends. Prevalence of improvement was estimated using a modified Kaplan-Meier estimator and compared between groups by bootstrapping the area under the curve.
Seventy-nine AHSCT-treated patients and 1975 patients treated with other DMTs (beta interferons, azathioprine, glatiramer-acetate, mitoxantrone, fingolimod, natalizumab, methotrexate, teriflunomide, cyclophosphamide, dimethyl fumarate, and alemtuzumab) were matched to reduce treatment selection bias using propensity score and overlap weighting approaches. Time to first CDP was significantly longer in transplanted patients (hazard ratio HR = 0.50; 95% CI = 0.31-0.81;
= 0.005), with 61.7% of transplanted patients free from CPD at 5 years. Accordingly, EDSS time trend over 10 years was higher in patients treated with other DMTs than in AHSCT-treated patients (+0.157 EDSS points per year compared with -0.013 EDSS points per year; interaction
< 0.001). Patients who underwent AHSCT were more likely to experience a sustained disability improvement: 34.7% of patients maintained an improvement (a lower EDSS than baseline) 3 years after transplant vs 4.6% of patients treated by other DMTs (
< 0.001).
The use of AHSCT in people with active SPMS is associated with a slowing of disability progression and a higher likelihood of disability improvement compared with standard immunotherapy.
This study provides Class III evidence that autologous hematopoietic stem cell transplants prolonged the time to CDP compared with other DMTs.
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