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Brain death (BD) provides most of the donor organs destined for lung transplantation (LTx). However, the organs may be affected by inflammatory and oxidative processes. Based on this, we hypothesize that the angiotensin-converting enzyme 2 (ACE2) activation can reduce the lung injury associated with LTx. 3 h after BD induction, rats were injected with saline (BD group) or an ACE2 activator (ACE2a group; 15 mg/kg -1 ) and kept on mechanical ventilation for additional 3 h. A third group included a control ventilation (Control group) prior to transplant. After BD protocol, left LTx were performed, followed by 2 h-reperfusion. ACE2 activation was associated with better oxygenation after BD management (p = 0.01), attenuating edema (p = 0.05) followed by the reduction in tissue resistance (p = 0.01) and increase of respiratory compliance (p = 0.02). Nrf2 expression was also upregulated in the ACE2a group (p = 0.03). After transplantation, ACE2a group showed lower levels of TNF-α (p = 0.02), IL-6 (p = 0.001), IL-1β (p = 0.01), ROS (p = 0.004) and MDA (p = 0.002), in addition to higher CAT activity (p = 0.04). In conclusion, our study suggests that ACE2 activation improves anti-inflammatory and antioxidant activity in a model of LTx., (© 2024. The Author(s).)

Introduction: Brain death (BD) compromises the viability of the lung for donation. Hypertonic saline solution (HSS) induces rapid intravascular volume expansion and immunomodulatory action. We investigated its role in ventilatory mechanics (VMs) and in the inflammatory activity of the lungs of rats subjected to BD., Methods: Wistar rats were divided into four groups: control, n = 10: intact rats subjected to extraction of the heart-lung block; BD, n = 8 (BD): rats treated with isotonic saline solution (4 mL/kg) immediately after BD; hypertonic saline 0 h, n = 9 (Hip.0'): rats treated with HSS (4 mL/kg) immediately after BD; and hypertonic saline 1 h, n = 9 (Hip.60'), rats treated with HSS (4 mL/kg) 60 min after BD. The hemodynamic characteristics, gas exchange, VMs, inflammatory mediators, and histopathological evaluation of the lung were evaluated over 240 min of BD., Results: In VMs, we observed increased airway resistance, tissue resistance, tissue elastance, and respiratory system compliance in the BD group (P < 0.037), while the treated groups showed no impairment over time (P > 0.05). In the histological analysis, the BD group showed a greater area of perivascular edema and a higher neutrophil count than the control group and the Hip.60' group (P < 0.05)., Conclusions: Treatment with HSS was effective in preventing changes in the elastic and resistive pulmonary components, keeping them at baseline levels. Late treatment reduced perivascular and neutrophilic edema in lung tissue., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background/objective: The aim of this study was to explore the associations between nailfold videocapillaroscopy (NVC) and pulmonary function tests (PFTs) in systemic sclerosis (SSc) patients., Methods: This was a longitudinal study with follow-up of unselected Brazilian SSc patients. Baseline clinical examination, serological workup, high-resolution chest tomography, and NVC were performed. Pulmonary function test was performed at baseline and after 24 months. Pulmonary function test worsening over time was defined as either a ΔFVC decline ≥10% or a ΔFVC decline ≥5% and <9%, combined with a ΔDLCO decline ≥15%, at 24 months. The NVC parameters were quantitatively (capillary density number, dimension, morphology, and hemorrhages) and qualitatively (NVC pattern) evaluated according to the consented standardized definitions of the EULAR Study Group on Microcirculation in Rheumatic Diseases., Results: Seventy-nine patients were included. Fifty-nine were rated to have a scleroderma pattern (6 "early"/16 "active"/37 "late"). The mean FVC and DLCO were 76.8% and 67.2% at baseline and 73.8% and 64.3% at 24 months, respectively. After multivariate analysis, we found that a reduced baseline FVC was associated with reduced capillary density (odds ratio [OR], 11; 95% confidence interval [CI], 1.5-90.7; p = 0.03) and a reduced baseline DLCO associated with the late scleroderma pattern (OR, 6.75; 95% CI, 1.09-42; p = 0.03). No association between worsening of PFT over time and NVC was found., Conclusions: The association between NVC and PFTs might corroborate the link between microangiopathy and interstitial lung disease in patients with SSc. This finding might strengthen the idea of incorporating NVC as a tool to predict progressive interstitial lung disease in these patients in the future., Competing Interests: This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior–Brasil (finance code 001). V.S. is a senior clinical investigator of the Research Foundation–Flanders (Belgium; FWO; 1.8.029.20N). The FWO was not involved in the study design, collection, analysis, and interpretation of data; writing of the report; or in the decision to submit the manuscript for publication. V.S. received a research grant from Boehringer Ingelheim, received an unrestricted educational chair on systemic sclerosis of Janssen-Cilag NV, and received research funding from Actelion Pharmaceuticals Ltd, Bayer AG, F. Hoffman–La Roche AG, Galapagos NV, and Sanofi. R.R. is supported by FAPERJ as a scientist from the state of Rio de Janeiro to develop the project. The other authors declare no conflict of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Systemic sclerosis (SSc) is a rare disease, and the presence of pulmonary hypertension can be a determining factor in prognosis. The aim of this study was to evaluate the diagnosis, profile, and prognosis of systemic sclerosis pulmonary hypertension (SSc-PH) diagnosed by systematic screening in a Brazilian population., Methods: A cohort of SSc patients underwent systematic screening for SSc-PH. Patients were referred for right heart catheterization (RHC) according to transthoracic echocardiogram or a combination of diagnostic tools. The clinical, immunological, and hemodynamic features and prognosis after 3 years were evaluated., Results: Twenty patients underwent RHC. SSc pulmonary arterial hypertension (SSc-PAH) was the most common group of SSc-PH. These patients had long disease duration, high urate levels and highly elevated mean pulmonary arterial pressure (mPAP) and peripheral vascular resistance (PVR) on hemodynamics. Patients with mPAP > 20- < 25 mmHg had hemodynamic features of intermediate disease. Patients with SSc-PH associated to interstitial lung disease (SSc-ILD-PH) had signs of vasculopathy on hemodynamics. In patients with no-SSc-PH, the survival at 1, 2, and 3 years was 96%, 92% and 92%, respectively and in patients with SSc-PH it was 86.7%, 60% and 53.3%, respectively., Conclusions: Patients identified with SSc-PAH and SSc-ILD-PH in our screening had severe clinical and hemodynamic features. Mortality remains high in SSc-PH but was more related to Bo-PAH and SSc-ILD-PH, while in SSc-PAH, the prognosis was better., Trial Registration: Current Controlled Trials ISRCTN 72968188, July 8th, 2021. Retrospectively registered., (© 2021. The Author(s).)

Background: This research is recommended by the Myopathy Committee of the Brazilian Society of Rheumatology for the investigation and diagnosis of systemic autoimmune myopathies. BODY: A systematic literature review was performed in the Embase, Medline (PubMed) and Cochrane databases, including studies published until October 2018. PRISMA was used for the review, and the articles were evaluated, based on the Oxford levels of evidence. Ten recommendations were developed addressing different aspects of systemic autoimmune myopathy investigation and diagnosis., Conclusions: The European League Against Rheumatism/ American College of Rheumatology (EULAR/ACR) classification stands out for the diagnosis of systemic autoimmune myopathies. Muscular biopsy is essential, aided by muscular magnetic resonance images and electroneuromyography in complementary research. Analysis of the factors related to prognosis with the evaluation of extramuscular manifestations, and comorbidities and intense investigation regarding differential diagnoses are mandatory.

Objective: The aim of this work was to produce a consensus-based report for capillaroscopy in rheumatology to be used in daily clinical practice., Methods: A written Delphi questionnaire regarding capillaroscopy report was developed from a literature review and expert consensus. The Delphi questionnaire was sent to an international panel including 25 rheumatologists experts in capillaroscopy, asking them to rate their level of agreement or disagreement with each statement. The exercise consisted of three online rounds and a face-to-face (live meeting) that took place in the PANLAR 2018 congress held in Buenos Aires, Argentina., Results: The participants to the first, second, third, and face-to-face round were 22, 21, 21, and 16 rheumatologists, respectively. Fifty-five items were discussed in the first round, 58 in the second, 22 in the third, and 9 in the face-to-face meeting. At the end of the exercise, 46 recommendations for the capillaroscopy report in rheumatology reached a consensus., Conclusion: This is the first consensus-based report in capillaroscopy. It will be useful in daily clinical practice and to address the effort of the standardization in the technique., Key Points: • The current lack of consensus for the capillaroscopy report makes difficult the interpretation of findings as well as follow-up of rheumatic diseases. • This study produced the first international consensus for the format and content of the naifold capillaroscopy report in rheumatology. • The report is an integral part of the capillaroscopy examination and its use in a homogeneous form can help in the correct interpretation of findings in daily practice.

Background: Recommendations of the Myopathy Committee of the Brazilian Society of Rheumatology for the management and therapy of systemic autoimmune myopathies (SAM)., Main Body: The review of the literature was done in the search for the Medline (PubMed), Embase and Cochrane databases including studies published until June 2018. The Prisma was used for the systematic review and the articles were evaluated according to the levels of Oxford evidence. Ten recommendations were developed addressing the management and therapy of systemic autoimmune myopathies., Conclusions: Robust data to guide the therapeutic process are scarce. Although not proven effective in controlled clinical trials, glucocorticoid represents first-line drugs in the treatment of SAM. Intravenous immunoglobulin is considered in induction for refractory cases of SAM or when immunosuppressive drugs are contra-indicated. Consideration should be given to the early introduction of immunosuppressive drugs. There is no specific period determined for the suspension of glucocorticoid and immunosuppressive drugs when individually evaluating patients with SAM. A key component for treatment in an early rehabilitation program is the inclusion of strength-building and aerobic exercises, in addition to a rigorous evaluation of these activities for remission of disease and the education of the patient and his/her caregivers.

Objective: To investigate the effect of rituximab on microcirculation in long-term SSc., Results: Four patients with diffuse SSc over 3 years of disease received rituximab cycles of two 1-g infusions every 6 months for 2 years. Videocapillaroscopy was performed at baseline, 12 months, and 24 months and semi-quantitative scoring of videocapillaroscopy abnormalities was performed and the microangiopathy evolution score (MES: range 0-9) was calculated. The mean disease duration was 5 years (range 3-15). On videocapillaroscopy, giant capillaries and hemorrhages remained stable from baseline to 24 months. Capillary loss, abnormally-shaped capillaries, and MES stabilized at 12 months and increased by 24.5% and 28% at 24 months. Rituximab improves microcirculation in long-term SSc. Stabilization and reduced progression of microcirculation abnormalities were achieved at 12 and 24 months, respectively.

Background: In scleroderma, excessive collagen production can alter tracheal geometry, and computed tomography (CT) volumetry of this structure may aid in detecting possible abnormalities. The objectives of this study were to quantify the morphological abnormalities in the tracheas of ​​patients with scleroderma and to correlate these findings with data on clinical and pulmonary function., Methods: This was a cross-sectional study in which 28 adults with scleroderma and 27 controls matched by age, gender and body mass index underwent chest CT with posterior segmentation and skeletonization of the images. In addition, all participants underwent pulmonary function tests and clinical evaluation, including the modified Rodnan skin score (mRSS)., Results: Most patients (71.4%) had interstitial lung disease on CT. Compared to controls, patients with scleroderma showed higher values ​​in the parameters measured by CT trachea volumetry, including area, eccentricity, major diameter, minor diameter, and tortuosity. The tracheal area and equivalent diameter were negatively correlated with the ratio between forced expiratory flow and forced inspiratory flow at 50% of forced vital capacity (FEF50%/FIF50%) (r = -0.44, p = 0.03 and r = -0.46, p = 0.02, respectively). The tracheal tortuosity was negatively correlated with peak expiratory flow (r = -0.51, p = 0.008). The mRSS showed a positive correlation with eccentricity (r = 0.62, p < 0.001) and tracheal tortuosity (r = 0.51, p = 0.007), while the presence of anti-topoisomerase I antibody (ATA) showed a positive correlation with tracheal tortuosity (r = 0.45, p = 0.03)., Conclusions: In a sample composed predominantly of scleroderma patients with associated interstitial lung disease, there were abnormalities in tracheal geometry, including greater eccentricity, diameter and tortuosity. In these patients, abnormalities in the geometry of the trachea were associated with functional markers of obstruction. In addition, tracheal tortuosity was correlated with cutaneous involvement and the presence of ATA., Competing Interests: The authors have declared that no competing interests exist.

Background: Despite the importance of traditional pulmonary function tests (PFTs) in managing systemic sclerosis (SSc), many patients with pulmonary disease diagnosed by computed tomography (CT) present with normal PFTs., Objective: To evaluate the efficacy of the nitrogen single-breath washout (N 2 SBW) test in diagnosing SSc and to correlate N 2 SBW parameters with the PFT indexes used in the follow-up of these patients, clinical data, and CT findings., Methods: Cross-sectional study in which 52 consecutive SSc patients were subjected to spirometry, body plethysmography, analysis of the diffusing capacity for carbon monoxide (DLCO), analysis of respiratory muscle strength, N 2 SBW testing, and CT analysis., Results: Twenty-eight patients had a forced vital capacity (FVC) that was <70% of the predicted value. In the N 2 SBW test, 44 patients had a phase III slope (Phase III slope N2SBW ) that was >120% of the predicted value, while 15 patients had a closing volume/vital capacity (CV/VC) that was >120% of the predicted value. A significant difference in Phase III slope N2SBW was observed when the patients with predominant traction bronchiectasis and honeycombing were compared to the patients with other CT patterns (p<0.0001). The Phase III slope N2SBW was correlated with FVC (r s =-0.845, p<0.0001) and DLCO (r s =-0.600, p<0.0001), and the CV/VC was correlated with FVC (r s =-0.460, p=0.0006) and residual volume/total lung capacity (r s =0.328, p=0.017)., Conclusion: Ventilation heterogeneity is a frequent finding in SSc patients that is associated with restrictive damage, changes in pulmonary diffusion, and CT patterns. In addition, approximately one-third of the patients presented with findings that were compatible with small airway disease., (Copyright © 2017 Sociedade Portuguesa de Pneumologia. Published by Elsevier España, S.L.U. All rights reserved.)

The term autoimmune/autoinflammatory syndrome induced by adjuvants (ASIA) or Shoenfeld's syndrome refers to a wide group of immune-mediated diseases triggered by external agents. Several substances, such as vaccine adjuvants, squalene and silicone implants, are implied in the pathogenesis of ASIA syndrome. Treatment and prognosis of this complex condition are not completely known due to lack of good quality evidence. After a brief introductory literature review on ASIA, we report here two cases of patients that developed rapidly progressive systemic sclerosis clinical features after multiple intramuscular local injections of a substance recommended by a non-medical professional called ADE. ADE is an oily vitamin complex for veterinary use, and it was used in these cases for cosmetic muscular definition and enhancement purpose. To our knowledge, this is the first paper to describe the relation between injections of ADE and the development of ASIA with severe systemic sclerosis phenotype. Further investigation is needed to better understand the pathophysiology and to provide the basis for the treatment of this condition.

Systemic sclerosis (SSc) is a chronic autoimmune disease with a high morbidity and mortality. Although cyclophosphamide is effective for severe and refractory cases, there is demand for new treatments. The biological treatment with B-cell depletion with rituximab (RTX) has demonstrated efficacy for this demand in open-label studies., Objective: This study was conducted with the aim to retrospectively evaluate all patients who used RTX for the treatment of SSc in our center., Patients and Methods: We retrospectively evaluated medical records of all patients with SSc who used RTX to treat this disease from January 2009 to January 2015. Systemic, cutaneous, and pulmonary involvement data and laboratory results before and six months after the first infusion of RTX were collected., Results: Ten patients received treatment during the study period and were included in this series. All patients had a diffuse form of the disease. Five patients suffered from an early (duration of disease shorter or equal to four years), rapidly progressive disease, and another five received RTX at late stages of the disease. In both groups of patients, stabilization of the pulmonary picture was observed, with a fall in the skin score in those patients with early forms of the disease., Discussion: Similar to findings in previous studies, RTX was effective in treating early and rapidly progressive forms of SSc. We also found that patients with long-term illness may benefit from the treatment., (Copyright © 2016. Published by Elsevier Editora Ltda.)

Dry eye disease (DED) is a multifactorial disease of the tears and ocular surface that causes tear film instability with potential damage to the ocular surface. The prevalence of dry eye in the world population ranges from 6 to 34 %. It is more common in those aged over 50, and affects mainly women. Since the introduction of the Schirmer's test in 1903, other tests have been developed to evaluate dry eye, such as biomicroscopy, the tear film breakup time (BUT), vital dyes (lissamine green and rose bengal), fluorescein, leaf fern test, corneal sensitivity test, conjunctiva impression cytology, optical coherence tomography (OCT), and tear osmolarity measurement. Although there is no gold standard, it is advisable to combine at least two tests. Strategies for treating DED have recently been modified and include patient education, tear substitute, corticosteroids, secretagogues, fatty acids, immunomodulators, occlusion of lacrimal puncta surgery and, tarsorrhaphy. Biological therapy and new topical immunomodulators such as tacrolimus, tofacitinib and IL-1 receptor inhibitor are being tested. In this review, the evaluation tests for dry eye are compared and the main studies on treatment are presented, with emphasis on studies in patients with Sjögren's syndrome. The authors propose an approach for the management of dry eye.

The recommendations proposed by the Sjögren's Syndrome Committee of the Brazilian Society of Rheumatology for the treatment of Sjögren's syndrome were based on a systematic review of literature in Medline (PubMed) and the Cochrane databases until October 2014 and on expert opinion in the absence of studies on the subject. 131 items classified according to Oxford & Grade were included. These recommendations were developed in order to guide the appropriate management and facilitate the access to treatment for those patients with an appropriate indication, considering the Brazilian socioeconomic context and pharmacological agents available in this country., (Copyright © 2015 Elsevier Editora Ltda. All rights reserved.)

The aim of the present study was to explore whether polymyositis may be considered as an isolated, organ-specific disease or more suitably as a secondary or associated entity. A retrospective re-evaluation of all the muscle biopsies performed at the Hospital Clínic of Barcelona showing histopathological pattern of polymyositis from January 1997 to May 2012 was carried out. The medical records of the patients with the aforementioned pathological pattern were also reviewed. From 1.290 muscle biopsies performed during the period evaluated, 36 with polymyositis pattern were identified. At the time of muscle biopsy, polymyositis pattern was secondary or associated with other disease in 26 patients and was classified as isolated in the remaining ten patients. After pathological re-evaluation and long-term clinical follow-up, only one patient remained with this diagnosis. Overall, the main final diagnosis related to the initial polymyositis pattern was inflammatory myopathy associated with connective tissue disease. Several other associated conditions were also identified. Isolated polymyositis is highly uncommon. Ruling out potential associated or confusing entities, like inclusion body myositis, overlap syndromes, infections, and cancer, is mandatory.

We conducted a randomized, controlled study to assess the need for hydroxychloroquine (HCQ) during lupus pregnancy and to assess safety. Twenty consecutive pregnant patients with similar characteristics were enrolled. The HCQ group included eight patients with systemic lupus erythematosus (SLE) and two with discoid lupus erythematosus (DLE). The placebo (PL) group included nine patients with SLE and one with DLE. The HCQ group had no flare-ups. SLEPDAI scores were similar at study entry, and at conclusion the placebo group had significantly higher scores. One patient had improvement of skin lesions and another of arthritis, allowing a decrease of prednisone dose. There were no retinal effects. Three patients in the PL group flared up, two with skin rashes, one also with arthritis and uveitis, and one (previously in remission on HCQ) with hemolytic anemia, polyserositis and anti-dsDNA antibody. Toxemia was diagnosed in only three patients in the PL group (one fetal death). Comparing prednisone dosage change, we noted a decrease in the HCQ and an increase in the PL group. Delivery age and Apgar scores were higher in the HCQ group. Neonatal examination did not reveal congenital abnormalities, nor did a neuro-ophthalmological and auditory evaluation at 1.5-3 y of age. In spite of the small number of patients studied, we noted beneficial effects of HCQ during lupus pregnancy, as measured by SLEPDAI and decrease in prednisone dose with no detriment to patients' health.