The differential crosstalk of the skin-gut microbiome axis as a new emerging actor in systemic sclerosis.

OBJECTIVES: We characterized the microbiota in SSc, focusing on the skin-oral-gut axis and the serum and faecal free fatty acid (FFA) profile. METHODS: Twenty-five SSc patients with ACA or anti-Scl70 autoantibodies were enrolled. The microbiota of faecal, saliva and superficial epidermal samples was assessed through next-generation sequencing analysis. GC-MS was used to quantify faecal and serum FFAs. Gastrointestinal symptoms were investigated with the University of California Los Angeles Scleroderma Clinical Trial Consortium Gastrointestinal Tract Instrument (UCLA GIT-2.0) questionnaire. RESULTS: The ACA+ and anti-Scl70+ groups displayed different cutaneous and faecal microbiota profiles. The classes of cutaneous Sphingobacteriia and Alphaproteobacteria, the faecal phylum Lentisphaerae, the levels of the classes Lentisphaeria and Opitutae, and the genus NA-Acidaminococcaceae were significantly higher in faecal samples from the ACA+ patients than in samples from the anti-Scl70+ patients. The cutaneous Sphingobacteria and the faecal Lentisphaerae were significantly correlated (rho = 0.42; P = 0.03). A significant increase in faecal propionic acid was observed in ACA+ patients. Moreover, all levels of faecal medium-chain FFAs and hexanoic acids were significantly higher in the ACA+ group than in the anti-Scl70+ group (P < 0.05 and P < 0.001, respectively). In the ACA+ group, the analysis of the serum FFA levels showed an increasing trend in valeric acid. CONCLUSION: Different microbiota signatures and FFA profiles were found for the two groups of patients. Despite being in different body districts, the cutaneous Sphingobacteria and faecal Lentisphaerae appear interdependent.

The role of chest CT in deciphering interstitial lung involvement: systemic sclerosis versus COVID-19.

OBJECTIVE: The aim of this study was to identify the main CT features that may help in distinguishing a progression of interstitial lung disease (ILD) secondary to SSc from COVID-19 pneumonia. METHODS: This multicentric study included 22 international readers grouped into a radiologist group (RADs) and a non-radiologist group (nRADs). A total of 99 patients, 52 with COVID-19 and 47 with SSc-ILD, were included in the study. RESULTS: Fibrosis inside focal ground-glass opacities (GGOs) in the upper lobes; fibrosis in the lower lobe GGOs; reticulations in lower lobes (especially if bilateral and symmetrical or associated with signs of fibrosis) were the CT features most frequently associated with SSc-ILD. The CT features most frequently associated with COVID- 19 pneumonia were: consolidation (CONS) in the lower lobes, CONS with peripheral (both central/peripheral or patchy distributions), anterior and posterior CONS and rounded-shaped GGOs in the lower lobes. After multivariate analysis, the presence of CONs in the lower lobes (P < 0.0001) and signs of fibrosis in GGOs in the lower lobes (P < 0.0001) remained independently associated with COVID-19 pneumonia and SSc-ILD, respectively. A predictive score was created that was positively associated with COVID-19 diagnosis (96.1% sensitivity and 83.3% specificity). CONCLUSION: CT diagnosis differentiating between COVID-19 pneumonia and SSc-ILD is possible through a combination of the proposed score and radiologic expertise. The presence of consolidation in the lower lobes may suggest COVID-19 pneumonia, while the presence of fibrosis inside GGOs may indicate SSc-ILD.

Enthesopathy and involvement of synovio-entheseal complex in systemic sclerosis: an ultrasound pilot study.

OBJECTIVES: SSc is a chronic autoimmune disease characterized by inflammation of the skin and multiple internal organs. Articular involvement is one of the main features of SSc, and typical hallmarks of SpA have been found in SSc patients. The aim of the present study was to estimate the prevalence of entheseal and synovio-entheseal complex (SEC) alterations in a cohort of SSc patients. METHODS: One hundred SSc patients and 25 healthy subjects were included in this cross-sectional study. The enthesis sites of lateral epicondylar common extensor tendons (CET) and the enthesis of the Glasgow Ultrasound Enthesis Scoring System were evaluated. SEC involvement was evaluated only at CET enthesis. RESULTS: In SSc, the Glasgow Ultrasound Enthesis Scoring System score was significantly higher (median 4.0, interquartile range 2.0-7.0) than in controls (median 1.0, interquartile range 0.0-3.0) (P < 0.0001). CET enthesis of SSc patients showed more frequent US B-mode alterations than that of controls (χ2 = 11.47, P = 0.0007 for size; χ2 = 13.79, P = 0.0002 for cortical irregularity, χ2 = 5.24, P = 0.022 for calcification/enthesophytes). Power Doppler US signal at CET enthesis was significantly more frequent in SSc patients than in healthy controls (χ2 = 9.11, P = 0.0025), as was the concomitant SEC involvement (χ2 = 8.52, P = 0.0035). CONCLUSION: These data show that SSc patients frequently present US features of enthesopathy. Moreover, CET enthesopathy was correlated with SEC inflammation, suggesting that entheseal inflammation in SSc may share the same micro-anatomical targets as found in SpA.

Targeting anticoagulant protein S to improve hemostasis in hemophilia.

Improved treatments are needed for hemophilia A and B, bleeding disorders affecting 400 000 people worldwide. We investigated whether targeting protein S could promote hemostasis in hemophilia by rebalancing coagulation. Protein S (PS) is an anticoagulant acting as cofactor for activated protein C and tissue factor pathway inhibitor (TFPI). This dual role makes PS a key regulator of thrombin generation. Here, we report that targeting PS rebalances coagulation in hemophilia. PS gene targeting in hemophilic mice protected them against bleeding, especially when intra-articular. Mechanistically, these mice displayed increased thrombin generation, resistance to activated protein C and TFPI, and improved fibrin network. Blocking PS in plasma of hemophilia patients normalized in vitro thrombin generation. Both PS and TFPIα were detected in hemophilic mice joints. PS and TFPI expression was stronger in the joints of hemophilia A patients than in those of hemophilia B patients when receiving on-demand therapy, for example, during a bleeding episode. In contrast, PS and TFPI expression was decreased in hemophilia A patients receiving prophylaxis with coagulation factor concentrates, comparable to osteoarthritis patients. These results establish PS inhibition as both controller of coagulation and potential therapeutic target in hemophilia. The murine PS silencing RNA approach that we successfully used in hemophilic mice might constitute a new therapeutic concept for hemophilic patients.

Low bone mass and hypovitaminosis D in haemophilia: A single-centre study in patients with severe and moderate haemophilia A and B.

INTRODUCTION: Haemophilia (H) is frequently associated with a multifactorial reduction in bone mineral density (BDM), but little is known about possible differences between HA and HB according to their severity. AIM: To evaluate the association between low bone mineral density (BMD), 25-hydroxyvitamin D [25(OH)D] concentrations and bone turnover markers in patients with HA and HB younger or older than 50 years. METHODS: In 78 patients <50 years and 33 patients >50 years with severe (S) or moderate (M) HA and HB, BMD was measured by dual-energy X-ray absorptiometry at femoral neck (FN) and lumbar spine and then correlated to annual bleeding rate (ABR), World Federation of Haemophilia orthopaedic joint scale (WFH score), 25(OH)D concentrations, parathyroid hormone (PTH), amino-terminal telopeptide of type 1 collagen (NTx), urinary pyridinolines, osteocalcin and bone-specific alkaline phosphatase. RESULTS: Overall, a high prevalence of hypovitaminosis D was diagnosed. In patients <50 years, low FN-BMD was significantly more frequent in HA than in HB, while PTH, pyridinolines, ABR and WFH score were associated with H type and severity. In patients >50 years, similarly low FN-BMD was observed in HA and HB, while ABR and WFH score were associated with H type and severity, being milder in HB. CONCLUSIONS: Low bone mass is a frequent comorbidity in haemophilic patients of all ages, apart from those with MHB. Clinical and laboratory assessments confirm a higher bone impairment and faster bone resorption in HA compared with HB. Looking at H type and severity, MHB seems to have a normal bone metabolism and a less severe disease.

Clinical, instrumental, serological and histological findings suggest that hemophilia B may be less severe than hemophilia A.

Recent evidence suggests that patients with severe hemophilia B may have a less severe disease compared to severe hemophilia A. To investigate clinical, radiological, laboratory and histological differences in the arthropathy of severe hemophilia A and hemophilia B, 70 patients with hemophilia A and 35 with hemophilia B with at least one joint bleeding were consecutively enrolled. Joint bleedings (<10, 10-50, >50), regimen of treatment (prophylaxis/on demand), World Federation of Hemophilia, Pettersson and ultrasound scores, serum soluble RANK ligand and osteoprotegerin were assessed in all patients. RANK, RANK ligand and osteoprotegerin expression was evaluated in synovial tissue from 18 hemophilia A and 4 hemophilia B patients. The percentage of patients with either 10-50 or more than 50 hemarthrosis was greater in hemophilia A than in hemophilia B (P<0.001 and P=0.03, respectively), while that with less than 10 hemarthrosis was higher in hemophilia B (P<0.0001). World Federation of Hemophilia (36.6 vs. 20.2; P<0.0001) and ultrasound (10.9 vs. 4.3; P<0.0001) score mean values were significantly higher in hemophilia A patients. Serum osteoprotegerin and soluble RANK ligand were decreased in hemophilia A versus hemophilia B (P<0.0001 and P=0.006, respectively). Osteoprotegerin expression was markedly reduced in synovial tissue from hemophilia A patients. In conclusion, the reduced number of hemarthrosis, the lower World Federation of Hemophilia and ultrasound scores, and higher osteoprotegerin expression in serum and synovial tissue in hemophilia B suggest that hemophilia B is a less severe disease than hemophilia A. Osteoprotegerin reduction seems to play a pivotal role in the progression of arthropathy in hemophilia A.

Angiogenesis is increased in advanced haemophilic joint disease and characterised by normal pericyte coverage.

BACKGROUND: Repeated intra-articular bleedings in patients with haemophilia results in a crippling arthropathy for which no specific treatment is currently available. Recent studies have shown that neoangiogenesis is involved in the pathologic process. The aim of this study was to determine whether angiogenesis is dysregulated in haemophilic joint disease (HJD). METHODS: Synovial tissue and synovial fluid were collected from patients with severe haemophilia undergoing knee or hip replacement and from a control group consisting of non-haemophilic patients undergoing diagnostic procedures. In a second set of patients, blood samples were collected in patients with mild, moderate and severe haemophilia A when free from current bleeding. Analysis of microvascular density, vascular endothelial growth factor (VEGF) expression and pericyte coverage was performed by immunofluorescence. Analyses of VEGF concentrations in plasma, platelet lysates and synovial fluid were performed by ELISA. RESULTS: Microvascular density and VEGF expression were significantly increased in synovial tissue from haemophilic patients compared with controls (P = 0.005 and P = 0.02, respectively). There was no difference in pericyte coverage of synovial vessels or levels of VEGF in plasma, platelet lysates or synovial fluid. CONCLUSIONS: Angiogenesis observed as synovial microvascular density, and VEGF expression is increased in HJD. As pericyte coverage was similar in synovial vessels from haemophilic and non-haemophilic patients, we assume that the vessels were mature, suggesting that the rate of new vessel formation is low in the chronic phase of haemophilic joint disease.

Muscle shortening manoeuvre reduces pain and functional impairment in shoulder impingement syndrome: clinical and ultrasonographic evidence.

OBJECTIVES: To evaluate the short-term efficacy of muscle shortening manoeuvre (MSM), by inducing an increase in strength of the shoulder muscles, for the treatment of shoulder impingement syndrome (SIS). METHODS: Sixty subjects (mean age: 58.6 years) with SIS were assigned to one of 3 different treatment interventions: 1) MSM: a series of fast accelerations in the upward direction was applied to the upper limb that was also submitted to forces acting in the opposite direction (added mass); 2) traditional physiotherapeutic technique: scapulothoracic gliding; 3) simple traction: the added mass was applied to the limb without the series of fast accelerations. Pain intensity, Neer's impingement sign, range of motion and muscle strength were assessed. Ultrasound (US) examination was performed before, immediately after and 30 days after each treatment to study the width of the subacromial-subdeltoid bursa, long biceps tendon sheath and acromioclavicular joint. Impingement was evaluated by dynamic examination. RESULTS: After treatment with MSM, pain was significantly reduced (p<0.001), Neer's impingement sign was negative, range of motion and muscle strength were increased. US examination showed that the widths of the subacromial-subdeltoid bursa (p<0.001), long biceps tendon sheath (p<0.001) and acromioclavicular joint (p<0.001) were significantly reduced; impingement was no more detected. After 30 days, improvement in clinical and US findings was maintained. In the two control groups, no significant changes were observed after treatment. CONCLUSIONS: Clinical and US findings demonstrate that MSM, by inducing an increase in muscle strength, is effective in the short-term treatment of SIS.

The effect of a combined rehabilitation program on the temporomandibular joint in systemic sclerosis evaluated by ultrasound exam.

PURPOSE: Temporomandibular joint (TMJ) involvement is frequent in Systemic Sclerosis (SSc). Dysfunction and X-ray changes of TMJ were described only in few observational studies. Treatment as well has been seldom considered. Aim of the present study was to evaluate the effects on TMJ of two specifically designed physiotherapy protocols. METHODS: The study group included 26 SSc outpatients (22 females and 4 males with mean age ± SD 59.08 ± 10.31 years). Thirteen patients were randomly assigned to a treatment (protocol 1) including home exercises for TMJ and thirteen to a treatment (protocol 2) including home exercises and a combined procedure. The rehabilitation effects on the TMJ were evaluated by ultrasound examination (UE) in static and dynamic phases. UE was performed in all patients before and at the end of the treatment and after a follow up (8 weeks). RESULTS: Both rehabilitation protocols induced a significant improvement (protocol 1: p < 0.01 and protocol 2: p < 0.005) of mouth opening with a long-lasting effect. Protocol 2 was more effective than protocol 1. A significant increase of bilateral condyle-head temporal bone distance was detected by UE at the end of both treatments. It was maintained at follow-up in patients treated with Protocol 2. CONCLUSIONS: The present investigation shows that a rehabilitation program characterized by home exercises with a combined procedure is useful to recover the function of TMJ. The data also show that UE is helpful in the evaluation of TMJ in SSc and in the assessment of the efficacy of the rehabilitation programs.

Clinical and radiological evaluation of sacroiliac joints compared with ultrasound examination in early spondyloarthritis.

OBJECTIVE: To compare clinical and X-ray examinations with US findings of SI joints (SIJ) in early SpA patients. METHODS: Twenty-three early SpA patients, diagnosed according to Assessment of SpondyloArthritis international Society criteria, were investigated clinically [sacral sulcus tenderness, BASMI, BASFI, BASDAI, pain and fatigue visual analogue scale (VAS), morning stiffness and sleep disturbance], with SIJ X-rays (New York score) and with My Lab70 US 7-10 MHz US (Esaote, Genoa, Italy), evaluating the width of the SIJ capsule and posterior sacroiliac (PSL) and sacrotuberosus (STL) ligament thickness and comparing the results with 23 healthy controls. RESULTS: SIJ width [right 2.2 (0.6) and left 2.3 (0.7) in SpA vs 1.6 (0.1) and 1.7 (0.2) in healthy controls, respectively, expressed as mean (s.d.)] and STL thickness [right 3.9 (1.3) and left 3.4 (1.0) vs 1.8 (0.1) and 1.8 (0.1), respectively, expressed as mean (s.d.)] were higher in SpA patients than in controls (P < 0.001 and P < 0.05, respectively). PSL thickness was similar in patients and controls. Only STL thickness was higher when SIJ was tender at clinical examination (P < 0.01) and correlated with pain VAS (P < 0.001) and BASFI (P < 0.05). Furthermore, SIJ US results were unrelated to X-ray findings (similar when X-ray sacroiliitis was present and not). CONCLUSION: Our exploratory study suggested that in early SpA patients US might be a promising method, complementary to other imaging techniques, to study articular and soft tissue periarticular involvement of SIJ, independent of clinical and X-ray examination.

The muscle shortening maneuver in individuals with stroke: a consideration-of-concept randomized pilot trial.

BACKGROUND AND PURPOSE: The Muscle Shortening Maneuver (MSM) is derived from Feldman's λ model of motor control, and seems to induce a more balanced agonist- antagonist-muscular action. The hypothesized mechanism of action is a modulation of the Tonic Stretch Reflex Threshold (TSRT). We designed a pilot, randomized trial aimed to explore the mechanisms of action of the technique. An ancillary objective was to research the implementation of the MSM as a stroke rehabilitation intervention. METHODS: A sample of 10 participants with chronic stroke was enrolled and randomly assigned to MSM (n, 5) or conventional physical therapy (CPT) (n, 5) treatments. The TSRTs were assessed by the Montreal Spasticity Measure device. A selection of clinical and instrumental outcome measures was taken to investigate function and activity levels. Data were collected at baseline, end-of-treatment, and one month after the end-of-treatment. RESULTS: No adverse events were observed. In both between- and within-group post-treatment assessments, in the affected ankle the MSM group showed decreased TSRTs of the plantar flexor, increased strength of the dorsiflexor and active range of motion; also, the time needed to perform the Timed Up and Go test decreased. No changes were evident across assessments in the CPT group. DISCUSSION AND CONCLUSIONS: The MSM seems able to modulate the TSRTs in individuals with stroke. Although with the limitations due to the pilot design, the variation in participants' responses appear to be promising. Many methodological issues have to be clarified and specified conceiving the progression toward a confirmatory trial.

The Muscle Shortening Maneuver: a noninvasive approach to the treatment of peroneal nerve injury. A case report.

BACKGROUND: The treatment of peripheral nerve injuries is a debated topic. The Muscle Shortening Maneuver (MSM), a physiotherapy approach, is noninvasive and free of side effects; it consists of a muscle shortening and a solicitation in traction applied simultaneously. OBJECTIVE: The focus of this report is to describe the effects of the MSM combined with walking retraining in a patient with incomplete injury of the peroneal nerve. DESCRIPTION: The patient was a 17-year-old man, who underwent osteotomy surgery of the proximal two-thirds of the fibula, due to an Ewing sarcoma that caused a partial injury of the left peroneal nerve. Our assessment plan of the left ankle movement ability comprised range of movement, muscle strength, and surface electromyography (EMG); and a gait analysis was conducted by using an iPhone application. MSM and walking retraining were administered twice and once a week, respectively, for 4 weeks. OUTCOMES: The active range of movement substantially improved in dorsiflexion (≥15°), whereas slightly decreased in plantar flexion (-5°). Aside from the tibialis anterior, an increase in muscle strength was detected. Surface EMG showed an increased activation, particularly in the peroneus longus. A decrease in gait speed and step length was recorded from the gait analysis, with a better bilateral symmetry. CONCLUSIONS: Positive outcomes were reported without evidence of risk or adverse events for the participant.

Shoulder impingement syndrome in water polo players: muscle shortening manoeuvre controls pain intensity, recovers function and normalizes sonographic parameters.

PURPOSE: To evaluate the effects of muscle shortening manoeuvre (MSM) by sonography (US) in professional water polo players with shoulder impingement syndrome (SIS). METHODS: Twenty-four professional water polo players (mean age: 22.13 ± 3.34) with SIS were assigned to one of 2 different treatment interventions: Group (1) MSM: a series of fast accelerations in the upward direction was applied to the upper limb that's connected to a spring through a metal plate with a ring. The ring was linked to a pulley system that was submitted to forces acting in the opposite direction (added mass). Group (2) Simple traction: the series of fast accelerations were performed without the springs. Pain intensity, Yocum and Hawkins tests for SIS, Neer's impingement sign, range of motion, muscle strength and shoulder US were assessed. The examination was performed before, immediately after and 30 days after each treatment to study the US width of subacromial-subdeltoid bursa (SSB), thickness of supraspinatus (ST), long biceps tendons (LBT); hypoechoic halo of surrounding the long biceps (LBH) and subscapular tendons (STH); width of acromio-clavicular joint capsule (ACJ) and the distance between bone heads (ACD). Impingement sign (IS) was evaluated by dynamic examination. RESULTS: Immediately after treatment with MSM, pain was much reduced (p = 0.002); Yocum and Hawkins tests were decreased (p = 0.008, p = 0.031); Neer's impingement sign was negative; range of motion and muscle strength were increased. US showed that the following parameters were significantly reduced: SSB (p = 0.001), LBT (p = 0.014), LBH (p = 0.014), SSH (p = 0.002), ACJ (p = 0.004), ACD (p = 0.001). IS was no more detected. After 30 days, the improvement of clinical and US findings was maintained. In the control group, after simple traction, no clinical amelioration of US parameters was found immediately after the procedure. CONCLUSION: These data show that MSM could be significantly and rapidly effective against pain and the loss of function due to shoulder impingement in water polo players.

THE MUSCLE SHORTENING MANOEUVRE: APPLICABILITY AND PRELIMINARY EVALUATION IN CHILDREN WITH HEMIPLEGIC CEREBRAL PALSY: A RETROSPECTIVE ANALYSIS.

INTRODUCTION: Physiotherapy plays a key role in cerebral palsy rehabilitation, through addressing body function/structure deficits, minimizing activity limitations, and encouraging participation. The muscle shortening manoeuvre is an innovative therapeutic technique, characterized by the ability to induce changes in muscle strength in a short time. OBJECTIVE: To describe the applicability and estimate the effect of the muscle shortening manoeuvre applied to improve motor weakness and joint excursion of the ankle in children with hemiplegic cerebral palsy. METHODS: Nine children with hemiplegic cerebral palsy received 3 intervention sessions in one week. Muscle strength, passive and active range of motion were assessed before, during and after the training, and at 1-week follow-up. RESULTS: The children experienced an immediate increase in muscle strength and joint excursion of the ankle; the improvements were still present at follow-up after 7 days. CONCLUSION: The muscle shortening manoeuvre may be an effective intervention to induce an immediate increase in muscle strength and range of motion of the ankle in children affected by hemiplegia due to cerebral palsy, thus promoting better physical functioning.

When should a rare inherited connective tissue disorder be suspected in bicuspid aortic valve by primary-care internists and cardiologists? Proposal of a score.

Size threshold for aortic surgery in bicuspid aortic valve (BAV) is debated. Connective tissue disorders (CTDs) are claimed as a clinical turning point, suggesting early surgery in BAV patients with CTD. Thus, we aimed at developing a score to detect high risk of carrying CTDs in consecutive BAVs from primary care. Ninety-eight BAVs without ectopia lentis or personal/family history of aortic dissection were studied at the Marfan syndrome Tuscany Referral Center. Findings were compared with those detected in 84 Marfan patients matched for sex and age. We selected traits with high statistical difference between MFS and BAV easily obtainable by cardiologists and primary-care internists: mitral valve prolapse, myopia ≥ 3DO, pectus carenatum, pes planus, wrist and thumb signs, and difference between aortic size at root and ascending aorta ≥ 4 mm. Clustering of ≥ 3 of these manifestations were more frequent in Marfan patients than in BAVs (71.4% vs 6.1%, p < 0.0001) resulting into an Odds Ratio to be affected by MFS of 38.3 (95% confidence intervals 14.8-99.3, p < 0.0001). We propose a score assembling simple clinical and echocardiographic variables resulting in an appropriate referral pattern of BAVs from a primary-care setting to a tertiary center to evaluate the presence of a potential, major CTD.

The Renal Resistive Index: A New Biomarker for the Follow-up of Vascular Modifications in Systemic Sclerosis.

OBJECTIVE: The aim of the present retrospective observational study was to evaluate the change of Renal Resistive Index (RRI) over time (ΔRRI) and under treatment in patients with systemic sclerosis (SSc) as well as to correlate these changes with disease complications. METHODS: Two hundred thirty patients [29 male, median age 57 (IQR 48-67) yrs] were enrolled. At baseline and follow-up (3.43, IQR 2.81-4.45 yrs), we collected the following data: disease variables, nailfold videocapillaroscopy (NVC) pattern, forced vital capacity (FVC), diffusing lung capacity for carbon monoxide (DLCO), systolic pulmonary arterial pressure (sPAP), presence of interstitial lung disease, RRI, evaluation of glomerular filtration rate, and new onset of pulmonary arterial hypertension (PAH). RESULTS: RRI value is high in SSc patients with digital ulcers and anticentromere antibodies, active and late NVC patterns, and limited cutaneous SSc. A significant correlation was observed between ΔRRI and ΔsPAP (R = 0.17, P = 0.02), with statistically higher ΔRRI (0.08 ± 0.02 vs 0.03 ± 0.05, P = 0.04) in patients complicated by PAH onset. No other new-onset complication was associated with ΔRRI. The receiver-operating characteristic curve analysis confirmed the predictive role of ΔRRI in development of new PAH (area under the curve 0.84, 95% CI 0.75-0.93, P = 0.02). In patients with SSc never exposed to sildenafil, ΔRRI was higher (0.04 ± 0.05) compared to both patients exposed to sildenafil during the study period (0.01 ± 0.05, P = 0.03) or in those exposed at the time of baseline evaluation (0.00 ± 0.05, P = 0.01). CONCLUSION: RRI and its variation in time are a reliable marker of SSc-related vasculopathy, both in renal and extrarenal compartments.

Rehabilitation of the face and temporomandibular joint in systemic sclerosis.

BACKGROUND: Systemic sclerosis (SSc) alterations of the face and of the mouth cause aesthetic modifications and disability, impairing self-esteem and quality of life (QoL). The aim of this study was to verify the effects of two rehabilitation protocols on facial mimic and mouth opening. METHODS: A total of 47 SSc patients (40 females and 7 males, mean age ± SD 59.08 ± 10.31 years), were consecutively selected: 22 were randomly assigned to protocol 1 [home exercises for temporomandibular joint (TMJ), mimic, masticatory and cervical spine muscles] and 25 to protocol 2 (home exercises and combined physiotherapeutic procedures performed by a physiotherapist). Each treatment had a duration of 12 weeks with a follow up of 8 weeks. TMJ dysfunction, orofacial involvement, disability, QoL, and safety were assessed at enrollment (T0), at the end of the treatment (T1), and at follow up (T2). RESULTS: Both Protocol 1 and Protocol 2 induced significant improvements of some clinical and clinimetric parameters, but better results were obtained with Protocol 2. In the comparison between the effects of Protocol 1 and Protocol 2 at T1 and T2, a significant difference was observed only for Mouth Handicap in SSc [MHISS; Total (p = 0.00178] and for MHISS Mouth opening (p = 0.0098) at T1. No significant difference of indices of short-form 36 was observed. CONCLUSION: The present data suggest that TMJ involvement in SSc may be managed by rehabilitation treatments. The action of a physiotherapist prescribing and personalizing exercises may induce better therapeutic effects.