Repetitive sulfur dioxide exposure in mice models post-deployment respiratory syndrome.

Soldiers deployed to Iraq and Afghanistan have a higher prevalence of respiratory symptoms than nondeployed military personnel and some have been shown to have a constellation of findings on lung biopsy termed post-deployment respiratory syndrome (PDRS). Since many of the subjects in this cohort reported exposure to sulfur dioxide (SO2), we developed a model of repetitive exposure to SO2 in mice that phenocopies many aspects of PDRS, including adaptive immune activation, airway wall remodeling, and pulmonary vascular (PV) disease. Although abnormalities in small airways were not sufficient to alter lung mechanics, PV remodeling resulted in the development of pulmonary hypertension and reduced exercise tolerance in SO2-exposed mice. SO2 exposure led to increased formation of isolevuglandins (isoLGs) adducts and superoxide dismutase 2 (SOD2) acetylation in endothelial cells, which were attenuated by treatment with the isoLG scavenger 2-hydroxybenzylamine acetate (2-HOBA). In addition, 2-HOBA treatment or Siruin-3 overexpression in a transgenic mouse model prevented vascular remodeling following SO2 exposure. In summary, our results indicate that repetitive SO2 exposure recapitulates many aspects of PDRS and that oxidative stress appears to mediate PV remodeling in this model. Together, these findings provide new insights regarding the critical mechanisms underlying PDRS.NEW & NOTEWORTHY We developed a mice model of "post-deployment respiratory syndrome" (PDRS), a condition in Veterans with unexplained exertional dyspnea. Our model successfully recapitulates many of the pathological and physiological features of the syndrome, revealing involvement of the ROS-isoLGs-Sirt3-SOD2 pathway in pulmonary vasculature pathology. Our study provides additional knowledge about effects and long-term consequences of sulfur dioxide exposure on the respiratory system, serving as a valuable tool for future PDRS research.

Clinical, Laboratory, and Imaging Features Between Men and Women With Axial Spondyloarthritis in a Specialized Center in Argentina.

OBJECTIVES: The aims were to estimate the frequency of axial spondyloarthritis (axSpA) in women and to analyze the clinical, laboratory, and imaging differences with respect to men at the time of diagnosis. METHODS: Consecutive patients older than 18 years with a diagnosis of axSpA admitted to the "Reumacheck" SpA program were included between 2017 and 2022. At baseline, all patients underwent clinical assessment, laboratory tests including C-reactive protein and human leukocyte antigen B27, and imaging (plain radiography and magnetic resonance imaging of sacroiliac joints, and ultrasound of heel entheses). All evaluators were blinded to the results of the other evaluations. RESULTS: One hundred sixteen patients with a diagnosis of axSpA were included. The frequency at diagnosis in women was 61.55%. In the univariate analysis, the significant differences between women and men at diagnosis of axSpA were good response to nonsteroidal anti-inflammatory drugs, elevated C-reactive protein, New York Criteria (+), enthesis ultrasound (+), years of education, number of swollen joints, erythrosedimentation rate, and the very low frequency of bone bridges in the magnetic resonance imaging of the sacroiliac joints. In the logistic regression analysis, the dependent variable was "men," and the only feature that was independently associated was having radiographic compromise according to the New York criteria (odds ratio, 2.6). CONCLUSIONS: The frequency of axSpA in women was 61.55%; clinical, laboratory, and imaging differences were observed. Women experienced less radiographic compromise.

Difficult to treat rheumatoid arthritis in a comprehensive evaluation program: frequency according to different objective evaluations.

Difficult-to-treat Rheumatoid Arthritis (RA-D2T) is a condition in which patients do not achieve the treatment target despite multiple advanced therapies, more others features. Aims: to estimate the frequency of RA-D2T in a cohort comprehensively evaluated (clinical, serology, imaging), and to analyze the associated characteristics. In a second part, the frequency of RA-D2T after 1 year of follow-up, analyzing the predictive variables at baseline and therapeutic behavior. Cross-sectional and prospective study, consecutive RA were included, then those who completed the one-year follow-up were evaluated. RA-D2T frequency was estimated (DAS28-CDAI-SDAI-Ultrasonography (US)-HAQ) at baseline and 1 year. The variables associated and those baseline predictive characteristics of D2T at 1 year, and their independent association by logistic regression were analyzed. The treatment approach was described. Two hundred seventy-six patients completed the evaluation, frequency of RA-D2T (all scores): 27.5%. Anemia, RF high titers and higher HAQ score were independent associated. At year, 125 competed follow-up. RA-D2T (all scores): 33%, D2T-US and D2T-HAQ were 14 and 18.4% (p 0.001). Predictive baseline characteristics D2T (all score): ACPA + (OR: 13.7) and X-ray erosion (OR: 2.9). D2T-US: X-ray erosion (OR: 19.7). Conventional DMARDs, corticosteroids and TNF-blockers were the drugs most used by D2T patients, Jaki were the most used in the switch. We showed different frequencies of RA-D2T according to different objective parameters (scores, images) and their association with patient characteristics. In turn, predictive variables (erosions-ACPA) for RA-D2T at 1 year were analyzed. It was shown that the Jaki were the most used drug in these patients.

The Role of HLA-B27 in Argentinian Axial Spondyloarthritis Patients.

BACKGROUND: The prevalence of human leukocyte antigen B27 (HLA-B27) is variable around the world. Our objectives were to estimate the frequency of HLA-B27 in an Argentinian cohort of axial spondyloarthritis (axSpA), to evaluate the differences between HLA-B27-positive and HLA-B27-negative patients, and to analyze its performance as a diagnostic biomarker. METHODS: Observational study including patients older than 18 years, with axSpA diagnosis assessed in a fast track program (Reuma-Check SpA). All patients underwent the following: blood tests, HLA-B27, sacroiliac images, and enthesitis ultrasound. Sociodemographic data and SpA symptoms were also collected. The clinical assessor was blinded to complementary studies. For the sensitivity and specificity analysis, patients with chronic low back pain without axSpA who performed the same circuit in the same period were used as control, paired 1:1 (sex and age). RESULTS: One hundred fifty patients were included, 75 axSpA and 75 controls. The frequency of HLA-B27 was 43% (95% confidence interval [CI], 30-53). The differences between HLA-B27-positive and HLA-B27-negative patients were observed in age of low back pain onset (36 vs 46 years), BASFI (Bath Ankylosing Spondylitis Functional Index) (4 vs 5), and extra-articular SpA features such as uveitis and inflammatory bowel disease (29% vs 50%). When this frequency was compared (low back pain control group), the difference was 43% versus 9% (odds ratio, 7.7; 95% CI, 2.8-24), and HLA-B27 had a sensitivity of 43%, specificity of 91%, positive predictive value of 85%, negative predictive value of 58%, and likelihood ratio of 4.9 (95% CI, 3-8). CONCLUSIONS: The frequency of HLA-B27 in axSpA was 43%; positive patients had an earlier age of onset (36), a higher BASFI, and more SpA features. For the diagnosis of SpA, HLA-B27 had a good specificity but low sensitivity.

Validation of Spanish version of 15-item myasthenia gravis quality-of-life questionnaire.

OBJECTIVES: The aim of this study was to achieve the translation and cross-cultural adaptation of the MG-QOL15R questionnaire into Spanish and the analysis of its psychometric properties. MATERIALS AND METHODS: We recruited patients with MG, ≥18 years old, whose mother tongue was Spanish. After the translation and cross-cultural adaptation of the MG-QOL15-R, the following tests were performed: internal consistency using the Cronbach-α coefficient and corrected item-total correlations; reproducibility with a test-retest analysis using intraclass correlation coefficients; and concurrent validity using Spearman's correlation coefficient of the Spanish language MG-QOL15R-S, Myasthenia Gravis Activity of Daily Living (MG-ADL) and Quantitative Myasthenia Gravis (QMG) scores. As an approximation to construct validity, the nonparametric Mann-Whitney U test was performed between MG-QOL15R-S scores according to the Myasthenia Gravis Foundation of America classification. RESULTS: A total of 83 MG patients were enrolled, mean age 48.19 ± 17.25 years; 58 (69.9%) were women. The mean MG-QOL15R-S score was 11.3 ± 7.1. Cronbach-α coefficient was 0.92. Item-total correlation ranged between 0.43 and 0.75. Intraclass correlation coefficient was 0.80. The Spearman correlation coefficient was 0.637 (p-value < .001) for MG-ADL and 0.487 (p-value < .001) for QMG. Mann-Whitney U tests of the mean MG-QOL15R-S scores were significantly different according to the clinical severity (p-value < .001). CONCLUSIONS: The Spanish version of the MG-QOL15R is a valid and reliable instrument and potentially useful for measuring health-related quality of life in Spanish-speaking MG patients.

Guillain-Barré syndrome in patients with SARS-CoV-2 infection. Report of three cases.

Several cases of Guillain Barre Syndrome (GBS) associated with SARS-CoV-2 have been published, most being acute inflammatory demyelinating polyradiculoneuropathy. Between April and December 2020, 1,499 cases of SARS-CoV-2 infection were admitted to Hospital del Salvador, in Santiago, Chile, serving a population of 521,920 adults. In the same period, seven cases of GBS were admitted. Three females had a demyelinated type of GBS associated with SARS-CoV-2 infection. All three presented with progressive flaccid symmetrical areflexic weakness with inability to walk, one needed intubation and mechanical ventilation due to SARS-CoV2 infection. All had a favorable, rapid response to intravenous immunoglobulin. In two patients, the onset of GBS was almost concomitant with SARS-CoV-2 infection. A causal relationship between SARS-CoV-2 and GBS has been questioned since no increase of GBS has occurred during the pandemic. However, a rise in GBS associated with SARS-CoV-2 infection could be hidden due to a general decrease of GBS due to the decrease of all other infections. Lack of reporting due to the pandemic could be an added factor.

[Monomelic amyotrophy. Report of one case]. / Atrofia monomiélica distal de extremidad superior. Caso clínico.

Monomelic amyotrophy, also known as Hirayama disease, is a rare lower motor neuron syndrome due to localized lower motor neuron loss in the spinal cord at the cervical level. Clinically, monomelic amyotrophy is defined by the insidious onset of unilateral atrophy and weakness involving the hand and forearm, typically beginning in the second or third decade of life. We report 19-year-old man with a two years history of slowly progressive unilateral weakness and atrophy of his right-hand muscles. Neurological examination revealed weakness and atrophy in his intrinsic hand muscles, with sparing of the abductor pollicis brevis muscle. Also, mild atrophy of the ulnar aspect of the forearm was detected with sparing of the brachioradialis muscle. Electromyography showed active and chronic neurogenic changes affecting C8 and T1 myotomes, with mild chronic neurogenic changes on C7 myotome. Magnetic resonance imaging of his cervical spine revealed spinal cord atrophy involving C5 to C7 segments, associated with forward displacement of the posterior wall of the dura in cervical spine flexion. The clinical features associated with the imaging and electrophysiological findings support the diagnosis of monomelic amyotrophy.

"Reuma-Check": Performance of a Comprehensive Fast-Track Program for the Diagnosis of Axial Spondyloarthritis in South America.

OBJECTIVES: The aim of this study was to evaluate the performance of a comprehensive diagnosis program called "Reuma-check" for the diagnosis of axial spondyloarthritis (SpA) in patients with low back pain (LBP). METHODS: This is a cross-sectional study. Patients with LBP aged 18 years or older were preselected, and those with at least 1 SpA feature completed the circuit. They were referred after 2 strategies: education for orthopedists and a campaign on social networks. All patients underwent a clinical evaluation, laboratory testing, and imaging (including human leukocyte antigen B27 evaluation and magnetic resonance imaging). The diagnosis of axial SpA was established by an expert rheumatologist opinion. Time from onset of symptoms to "Reuma-check," time from patient referral to admission of the checkup, and time from "Reuma-check" to diagnosis were evaluated. RESULTS: A total of 175 of 246 patients were included, most of them came from the social media campaign (55%). Seventy-five (43%) of 175 patients were diagnosed as axial SpA. The median time from referral (or self-referral) to access to the program was 1.3 months. The median time from symptoms onset to access to the program was 31.7 months, and the median time from the performance of "Reuma-check" to final diagnosis was 2 weeks. Features associated with a diagnosis of axial SpA were as follows: inflammatory LBP (odds ratio [OR], 6.64; 95% confidence interval [CI], 1.6-28), clinical enthesopathy (OR, 4.56; 95% CI, 1.1-18.4), positive human leukocyte antigen B27 (OR, 23.02; 95% CI, 3.5-58), and positive magnetic resonance imaging (OR, 14.34; 95% CI, 3.5-58). CONCLUSIONS: "Reuma-check" allowed a high frequency of axial SpA diagnosis and improved access to rapid diagnosis, shortening the time from referral to diagnosis with a shorter acquisition time for the ancillary studies. Patients with a final diagnosis of axial SpA presented distinctive features.

[Medical teleconsultation. Analysis and recommendations from the ethics department of the Chilean medical association]. / Teleconsulta médica. Análisis y recomendaciones del Departamento de Ética del Colegio Médico de Chile.

The possibility of allowing patients access to health professionals, has been greatly facilitated by advances in technology. Indeed, nowadays it is possible not only direct contact between one health professional with another, but also the possibility of sending images and other tests to consult distant colleagues. This has undoubtedly enabled better health care for many patients. It is also possible for a patient to consult a doctor directly in a remote and synchronous way with oral and visual contact, thus establishing a new form of medical consultation. It is this last way of relationship, which has already spread as a practice in normal times, which arouses apprehensions about the ethical requirements that a consultation must meet. This work by the Ethics Department of the Chilean Medical Association seeks to reflect on the ethical demands of a medical consultation and on the shortcomings that teleconsultation has. It also aims to propose several recommendations, so that this new form of doctor-patient relationship serves as a complement to traditional care, without jeopardizing the objectives of a medical action.

[Ethical aspects of the doctors' behavior towards people on hunger strike: position paper from the Ethics Department of the Chilean Medical Association]. / Aspectos éticos de la conducta del médico ante personas en huelga de hambre: opinión del Departamento de Ética del Colegio Médico de Chile.

Every so often, in Chile there is a discussion about the role of physicians in the care of people on hunger strike (HS). In this document, we review the ethical aspects of health care for persons in HS, aiming to provide guidelines to medical doctors who are required to attend them. First, we make an important distinction between HS and suicide, since the former is used as a protest and denunciation tool, while suicide seeks deliberately to end a life. Then we describe the three roles that the health professional can fulfill: as a treating doctor, as an expert or as an official of a prison. The respect for the autonomy and dignity of the person in HS must prevail whatever the role of the physician. Therefore, we maintain that under no circumstances, people who have autonomously decided to be in HS should be fed by force. Due to the complexity of the issue, we make special considerations about the management of minors and the non-competent persons in HS. In conclusion, we adhere to the principles that inspire the Declaration of Malta, which indicate that it would be preferable to "allow a person on hunger strike to die in dignity, rather than subjecting them to repeated interventions against their will".

[Does therapeutic privilege have a place in modern medicine?] / ¿Tiene cabida, hoy, el "privilegio terapéutico"?

During the last years, bioethical discussion has highlighted the role of the patients' autonomy, being informed consent its particular expression, about decisions that they should make about their own health. The Hippocratic tradition, the deontological positions of the Geneva Declaration of the World Medical Association and numerous codes of ethics in various countries, require that the physician, above all, should ensure patients' health. In this context the discussion on pros and cons for the so-called "therapeutic privilege" are discussed. The "therapeutic privilege" refers to the withholding of information by the clinician during the consent process in the belief that disclosure of this information would lead to harm or suffering of the patient. The circumstances and conditions in which this privilege can become valid are discussed. Special reference is made in order to respect multiculturalism and to the possibility of obtaining advice from health care ethics committees. The role of prudence in the doctor-patient relation must be highlighted. Disclosure of information should be subordinated and oriented to the integral well-being of the patient.

[Position paper from the Department of Ethics of the Chilean College of Physicians about conscientious objection]. / El médico y la objeción de conciencia: Opinión del Departamento de Ética del Colegio Médico de Chile A. G.

The Chilean bill that regulates abortion for three cases (Bulletin Nº 9895-11) includes the possibility that health professionals may manifest their conscientious objection (CO) to perform this procedure. Due to the broad impact that the issue of C O had, the Ethics Department of the Chilean College of Physicians considered important to review this concept and its ethical and legal basis, especially in the field of sexual and reproductive health. In the present document, we define the practical limit s of CO, both for the proper fulfillment of the medical profession obligations, and for the due respect and non-discrimination that the professional objector deserves. We analyze the denial of some health institutions to perform abortions if it is legalize d, and we end with recommendations adjusted to the Chilean reality. Specifically, we recognize the right to conscientious objection that all physicians who directly participate in a professional act have. But we a lso recognize that physicians have ineludib le obligations towards their patients, including the obligation to inform about the existence of this service, how to access to it and -as set out in our code of ethics- to ensure that another colleague will continue attending the patient.

Thymectomy for non-thymomatous myasthenia gravis.

BACKGROUND: Treatments currently used for patients with myasthenia gravis (MG) include steroids, non-steroid immune suppressive agents, plasma exchange, intravenous immunoglobulin and thymectomy. Data from randomized controlled trials (RCTs) support the use of some of these therapeutic modalities and the evidence for non-surgical therapies are the subject of other Cochrane reviews. Significant uncertainty and variation persist in clinical practice regarding the potential role of thymectomy in the treatment of people with MG. OBJECTIVES: To assess the efficacy and safety of thymectomy in the management of people with non-thymomatous MG. SEARCH METHODS: On 31 March 2013, we searched the Cochrane Neuromuscular Disease Group Specialized Register, CENTRAL (2013, Issue 3), MEDLINE (January 1966 to March 2013), EMBASE (January 1980 to March 2013) and LILACS (January 1992 to March 2013) for RCTs. Two authors (RS and GC) read all retrieved abstracts and reviewed the full texts of potentially relevant articles. These two authors checked references of all manuscripts identified in the review to identify additional articles that were of relevance and contacted experts in the field to identify additional published and unpublished data. Where necessary, authors were contacted for further information. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials of thymectomy against no treatment or any medical treatment, and thymectomy plus medical treatment against medical treatment alone, in people with non-thymomatous MG.We did not use measured outcomes as criteria for study selection. DATA COLLECTION AND ANALYSIS: We planned that two authors would independently extract data onto a specially designed data extraction form and assess risk of bias; however, there were no included studies in the review. We would have identified any adverse effects of thymectomy from the included trials. MAIN RESULTS: We did not identify any RCTs testing the efficacy of thymectomy in the treatment of MG. In the absence of data from RCTs, we were unable to do any further analysis. AUTHORS' CONCLUSIONS: There is no randomized controlled trial literature that allows meaningful conclusions about the efficacy of thymectomy on MG. Data from several class III observational studies suggest that thymectomy could be beneficial in MG. An RCT is needed to elucidate if thymectomy is useful, and to what extent, in MG.

Ultrasound tenosynovitis: A differential feature of patients with seronegative rheumatoid arthritis.

OBJECTIVE: To identify differential features between patients with seropositive and seronegative rheumatoid arthritis (RA). METHOD: Prospective cohort study, including patients who were admitted for polyarthralgia. At baseline was performed: laboratory studies, X-rays of hands and feet, ultrasound of both hands with power Doppler technique, clinical data and clinimetry. In subsequent visits the definitive diagnosis of RA was established or not. It was considered as seronegative RA when patients were negative for both RF and ACPAs. RESULTS: 746 patients were included, of which 128 (17.1%) ended with a final diagnosis of RA. Of these 128 patients, 87 (67.9%) were seropositive RA, while 41 (32%) were seronegative RA. The only feature that showed significant differences was the presence of tenosynovitis detected by ultrasound with a positive power Doppler signal, 13.7% of the patients with seropositive RA vs 41.6% of the patients with seronegative RA (p=0.0028). CONCLUSION: The only differential feature of patients with seronegative RA was the higher proportion of tenosynovitis detected by ultrasound.

Psoriatic Arthritis: Differential Features at the Time of Clinical Presentation in a Large Cohort of Patients with Polyarthralgia.

OBJECTIVE: Most patients with psoriatic arthritis begin with cutaneous psoriasis, which is why all early detection strategies are based on screening in the dermatological consultation and referral to a rheu matologist. However, there are cases of patients who consult initially for musculoskeletal symptoms, mostly joint pain, regardless of family and/or personal history of psoriasis. This study aimed to esti mate the frequency of psoriatic arthritis in a cohort of patients who consulted for polyarthralgia and to determine the differential features, at the time of clinical presentation, in relation to both patients with final diagnosis other than psoriatic arthritis and patients with diagnosis of rheumatoid arthritis. METHODS: Consecutive patients with polyarthralgia (including arthralgia of the hands) were included. Clinical examination, laboratory tests, ultrasound with power Doppler of both hands, and radiography of both hands and feet were performed at baseline. All patients were followed up and the definitive diagnosis of psoriatic arthritis was established. RESULTS: A total of 1055 were included, 88 (8.3%) ended with diagnosis of psoriatic arthritis. Diagnosis of psoriatic arthritis was positively associated with a family history of psoriasis (odds ratio=4.14), pso riasis (odds ratio=78.94), radiographic erosions (odds ratio=5.74), and ultrasound with at least 1 joint with positive power Doppler (odds ratio=7.11). In comparison with rheumatoid arthritis patients, diagnosis of psoriatic arthritis was positively associated with psoriasis (odds ratio=433.42) and family history of psoriasis (odds ratio=41.63). On the other hand, it was negatively associated with positivity, for both rheumatoid factor (odds ratio=0.03) and anti-cyclic citrullinated peptide antibodies (odds ratio=0.06). CONCLUSION: The frequency of psoriatic arthritis was 8.3% and was associated with a personal and/or family history of psoriasis, radiographic erosions, and inflammatory involvement by Power Doppler Ultrasound (PDUS). In comparison with rheumatoid arthritis patients, psoriatic arthritis was associated with a personal and/or family history of psoriasis, while the presence of both rheumatoid factor and/ or anti-cyclic citrullinated peptide antibodies was shown to be a protective factor for the diagnosis of psoriatic arthritis.

How are rheumatologists from Argentina managing patients with arthralgias suspicious for progressing to rheumatoid arthritis?

Patients with arthralgias who could be at risk of progressing to rheumatoid arthritis (RA) represent a clinical challenge. Recommendations for their management and treatment are lacking. The purpose of the present study was to determine how Argentinean rheumatologists deal with these patients. We developed an anonymous ad hoc survey which was sent to 522 Argentinean rheumatologists. The RA study group of our Argentinean Rheumatology National Society assisted in forwarding the surveys to its members via the internet (e-mail or WhatsApp). The findings of the collected data are presented as descriptive statistics. The questionnaires were completed by 255 rheumatologists (overall response rate of 48.9%), and 97.6% confirmed that their practices had received medical consultations to rule out RA in patients with arthralgias. Ultrasound (US) was the method of first choice (93.7%) as part of the evaluation of these patients. For those in whom US power Doppler signal was present in at least one joint, 93.7% of the participants would start treatment and methotrexate was the first choice (58.1%). In patients with tenosynovitis but no synovitis on US, most rheumatologists would start treatment (89.4%), being NSAIDs the drug of first choice (52.3%). Argentinean rheumatologists evaluate patients with imminent RA and treat them based on their clinical judgment and findings from the US evaluation of affected joints; the drug of first choice for these patients among these rheumatologists was methotrexate. Despite published data of recent clinical trials, recommendations for the management and treatment of these patients are necessary.