Background/Objectives: Idiopathic Carpal Tunnel Syndrome (CTS) can be an early manifestation of systemic amyloidosis, particularly transthyretin cardiac amyloidosis (ATTR-CA). The primary purpose of this retrospective case series was to describe the presence of amyloid deposits in tenosynovial tissue and explore potential cardiac involvement in patients undergoing carpal tunnel release surgery. Methods: From a cohort of 54 patients diagnosed with bilateral idiopathic CTS with surgical indication, 12 patients were selected for tenosynovial tissue samples, which were subsequently evaluated using Congo red staining and proteomic confirmation via mass spectrometry. Before the procedure, patients underwent a clinical assessment of medical history, electrocardiogram, and cardiac scintigraphy with Technetium-99 m 3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD). Transthoracic echocardiogram and cardiac magnetic resonance were subsequently performed in all patients with positive scintigraphy, while a subset of scintigraphy-negative patients underwent an echocardiogram. Results: Congo red staining identified amyloid deposits in 3 of the 12 patients (25%). Proteomic analysis confirmed ATTR amyloidosis deposits in 2 of these patients (17%). One of these 2 patients presented Perugini grade 3 uptake on cardiac scintigraphy, suspicious for ATTR-CA. Complete concordance across histology, proteomics, and cardiac imaging was observed in only 1 patient (8.3%). Three discordances were noted: one case of tenosynovial ATTR without evident cardiac disease, one patient with a discordant Congo red result likely reflecting low amyloid burden or tissue heterogeneity, and one with imaging findings suspicious for ATTR-CA despite a negative tenosynovial biopsy. Conclusions: Tenosynovial biopsy obtained during CTS surgery can reveal early amyloid deposition, which may precede overt cardiac involvement. The variability observed across findings underscores the need for a multimodal diagnostic approach that integrates histological, proteomic, and imaging data, thereby mitigating the risk of amyloidosis misclassification.

Background: Carpal tunnel syndrome (CTS) has emerged as an early indicator of cardiac amyloidosis (CA) caused by transthyretin-associated (ATTR) mutations, possibly linked to adverse cardiovascular outcomes. This case series examines the relationship between idiopathic CTS and CA imaging diagnosis. Methods: Twenty-two patients from the cross-sectional study CarPoS (NCT05409833) were included. These patients underwent physical evaluation, laboratory exams, electrocardiography, echocardiography, cardiac magnetic resonance (CMR) imaging, and scintigraphy with 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid. Results: Four of the twenty-two patients included had ATTR cardiomyopathy. These patients presented left-ventricle hypertrophy and signs of infiltrative cardiomyopathy in echocardiograms and late gadolinium enhancement in CMR images without having any cardiovascular symptoms. Conclusions: Our findings suggest a high prevalence of CA in patients with bilateral idiopathic CTS, highlighting the importance of screening for CA in patients with CTS. Early detection could significantly impact patient prognosis, underscoring the need for further research into diagnostic and therapeutic strategies.

To investigate the association between cardiometabolic factors, obesity, radiographic severity, and symptomatic hand osteoarthritis (HOA), as the role of these factors in HOA remains unclear. A cross-sectional analysis in the EPIPorto cohort included participants with HOA (≥ 1 joint with Kellgren-Lawrence (KL) grade ≥ 2 and/or American College of Rheumatology criteria). Cardiovascular risk factors, anthropometric measures, and radiographic severity (sum of KL hand score [0–128]) and number of affected joints [0–32]) were analysed. We tested the association between these factors and symptomatic HOA (≥ 1 joint with KL ≥ 2 and hand pain in the last month) by multivariable logistic regression. Of the 858 participants with HOA (61

A omalgia crónica é uma condição prevalente que causa impacto significativo na saúde física e psicológica dos doentes, afetando negativamente a sua qualidade de vida. O bloqueio nervoso supraescapular (BNS) ecoguiado tem sido proposto como uma terapêutica eficaz na omalgia crónica refratária a tratamentos convencionais. Contudo, a maioria dos estudos não explora o real benefício desta técnica na intensidade da dor e função do ombro ao longo do tempo. Neste contexto, os principais objetivos deste estudo foram descrever o BNS ecoguiado e explorar qual o seu benefício clínico e funcional na omalgia crónica ao longo de 12 semanas. Realizou-se um estudo piloto observacional prospetivo, que incluiu doentes adultos com omalgia crónica seguidos num centro português de Reumatologia. Os doentes foram avaliados em quatro momentos: um primeiro momento presencial, aquando da realização do BNS; e três momentos posteriores, por telefone, que ocorreram 1, 4 e 12 semanas após o BNS. A Escala Numérica de Dor e a Oxford Shoulder Scale foram aplicadas em todas os momentos, para avaliar a intensidade da omalgia e a funcionalidade do ombro, respetivamente. Um total de 13 doentes com omalgia crónica e patologia da coifa dos rotadores foram incluídos. O BNS ecoguiado associou-se a uma melhoria significativa na intensidade da dor e funcionalidade do ombro até às quatro semanas. Não foram reportados eventos adversos. O BNS demonstrou ser uma abordagem terapêutica bem tolerada pelos doentes e com benefício clínico e funcional na omalgia crónica ao longo do tempo.

Introduction Biological disease-modifying antirheumatic drugs (bDMARD) have improved the clinical course and quality of life of patients with rheumatoid arthritis (RA). However, some patients failed to respond or have an insufficient response to bDMARD early in the course of the treatment. Objectives To determine the percentage of RA patients who need to switch due to ineffectiveness in the first year of treatment and to identify specific baseline features as possible predictors of switch due to ineffectiveness in the first year of treatment. Materials and methods An observational retrospective study was conducted with patients with RA that started their first bDMARD. Demographic data, disease characteristics, disease activity data scores, laboratory parameters and treatment at baseline were collected. The proportion of patients who failed to respond and who switched to another bDMARD in the first year of treatment was calculated. Results A total of 437 (364 females, 83.3%) patients with RA were included. The majority of these patients started an anti-TNF-α agent (n=315, 72.1%). Forty-eight (11.0%) patients failed to respond to the bDMARD in the first year of treatment. There were significantly more current or former smokers (p=0.030), with a history of depression (p=0.003) and positive for RF at baseline (p=0.014) in the switch group.In the multivariate analysis, anti-TNF-α agents use (OR 8.3, 95% CI 2.4–28.8, p=0.001), tobacco exposure (OR 2.3, 95% CI 1.1–4.8, p=0.02) and history of depression (OR 3.1, 95% CI 1.3–7.7) seem to predict the need to switch in the first year of treatment due to ineffectiveness. Discussion and conclusion In our study, tobacco exposure and depression appear to be modifiable risk factors associated with early switching due to ineffectiveness. Addressing these factors in daily clinical practice is crucial to enhance the overall response to therapy and improve the well-being of patients.

Carpal tunnel syndrome (CTS) is the most common type of entrapment neuropathy and affects approximately 1% to 5% of the general population, mostly patients older than 50 years. CTS is present in various conditions and diseases and could also be an early sign of systemic transthyretin amyloidosis (ATTR), associated with amyloid cardiomyopathy and subsequent heart failure. With advances in the treatment of cardiac amyloidosis, patient prognosis could be significantly improved with an early diagnosis. Amyloidosis represents a group of disorders characterized by the extracellular deposition of destabilized protein fragments, aggregating as amyloid fibrils, thereby leading to organ dysfunction. Among these, ATTR is a significant subgroup. This study protocol aims to explore the potential association between CTS and systemic and cardiac ATTR. The study design involves a case-control approach, with assessments including physical examination, laboratory tests, electromyography, electrocardiogram, wrist ultrasound, and scintigraphy with 99mTc-3,3-diphosphono-1,2-propanodicarboxylic acid (99mTc-DPD). Histopathological analysis and genetic testing will be performed when appropriate. Statistical analysis will be conducted to evaluate the relationship between CTS and ATTR. The study seeks to contribute to a better understanding of the diagnostic and therapeutic implications of identifying ATTR in patients with idiopathic CTS (ClinicalTrials.gov identifier: NCT05409833).

Introduction: Systemic sclerosis (SSc) is characterized by progressive fibrosis of the skin and internal organs, microvascular damage and cellular and humoral immunity abnormalities. Microvascular damage can be easily detected through nailfold videocapillaroscopy (NVC). Materials and methods: A retrospective study of patients with SSc and a NVC performed within the first 6 months after diagnosis was conducted. Visceral involvement in the first 3 years of the disease and NVC findings were collected. The severity of microvascular damage was classified into four categories, according to the worsening of the NVC patterns. The severity of organ involvement was assessed by the disease severity scale of Medsger for each organ and as a global measure of disease severity, the simple summation was used. Results: A total of 86 patients with SSc were included. A moderate correlation was found between the severity of microvascular damage and the global measure of disease severity (r = 0.55, p < 0.001), the severity of peripheral vascular involvement (r = 0.43, p < 0.001) and the severity of skin involvement (r = 0.34, p = 0.001). The presence of a late scleroderma pattern in NVC were predictive in univariate analysis of digital ulcers (OR 6.03, 95% CI 1.52-23.86, p = 0.01), muscular involvement (OR 13.09, 95% CI 1.09-156.78, p = 0.04), calcinosis (OR 27.22, 95% CI 5.56-133.33, p < 0.001) and worse global disease severity score (OR 1.67, 95% CI 1.17-2.38, p = 0.005). Multivariate analysis adjusted for disease duration and gender confirmed late pattern as an independent predictor of calcinosis (OR 42.89, 95% CI 5.53-332.85, p < 0.001). Discussion and conclusion: In this study, the worsening of NVC pattern in SSc was associated with the overall disease severity, the severity of peripheral vascular involvement and extension of skin involvement. This study highlights the importance of NVC as a prognostic tool and a possible predictor of systemic visceral involvement.

Introduction Psoriatic arthritis (PsA) is a chronic, progressive inflammatory joint disease that is associated with higher prevalence of depression. There is limited literature about the impact of depression, particularly regarding the response to therapy. Methods A retrospective cohort study with PsA patients that started their first biologic disease-modifying antirheumatic drugs (bDMARD) was conducted. In the majority of cases, a cutoff score of ≥ 8 in Hospital Anxiety and Depression Scale (HADS) was used to define cases of depression. In cases where patients did not complete the questionnaire, a previous diagnosis made by a psychiatrist was used to establish the presence of depression. Response to therapy 12 months after the start of bDMARD was evaluated and the switch rate to another bDMARD due to inefficacy was assessed at month 12. Results A total of 129 patients (66 females, 51.2%; mean age of 47.7 ± 11.0 years and mean disease duration of 10.0 ± 7.7 years) with PsA were included. Thirty-two (24.8%) patients had depression. Patients with depression and peripheral involvement had a significantly lower ACR20/50/70 responses ( p = 0.001, p = 0.002, and p = 0.001 respectively) after 12 months of therapy and a significantly worse EULAR response ( p = 0.002). Furthermore, patients with depression and axial involvement had a significantly worse response based on ASDAS response criteria ( p = 0.031). Switch due to ineffectiveness in the first 12 months was significantly higher in patients with depression ( p = 0.002). Conclusion Depression in PsA is a frequent yet often understudied comorbidity. The causal relationship between depression and PsA is difficult to decrypt and further research is needed. Recognition of depressive symptoms is crucial and a multidisciplinary approach should be provided to individuals with this comorbidity. Key Points • Depression in PsA is a frequent yet often understudied comorbidity. In our study, the prevalence of depression was 24.8%. • Depression in PsA seems to be associated to lower response to therapy and higher discontinuation rates of bDMARD. • Recognition of depressive symptoms is crucial and a multidisciplinary approach should be provided to individuals with this comorbidity.

Introduction:Cranial nerve involvement in polyarteritis nodosa(PAN) is underrecognized and rarely reported. The aim of this article is to review the available literature and present an example of oculomotor nerve palsy in the course of PAN.Material and methods:Evaluation of texts describing the analyzed problem using the terms "polyarteritis nodosa", "nerve", "oculomotor", "cranial nerve" and "cranial neuropathy" for searching the PubMed database was done. Only full-text articles in English language with titles and abstracts were included in the analysis. As a guideline for the analysis of articles, the methodology described in the Principles of Individual Patient Data systematic reviews (PRISMA-IPD) was used.Results:After screening articles only 16 reported cases of PAN with cranial neuropathy were included in the analysis. In 10 the cranial neuropathy was reported as the initial manifestation of PAN with optic nerve involvement as the most frequent (62.5%); among these cases the oculomotor nerve was involved in 3 cases. Treatment with glucocorticosteroids and cyclophosphamide was the most common.Conclusions:Although cranial neuropathy, especially oculomotor nerve palsy is a rare first neurological manifestation of PAN, this clinical problem should be considered in the differential diagnosis.Especially patients with peripheral neuropathy, general symptoms, skin lesions and hepatitis B virus infection should be evaluated for cranial nerve involvement in the course of vasculitis.In the case of unclear involvement of the cranial nerves, PAN should also be considered in the differential diagnosis as the cause of symptoms and the first manifestation of the disease.

Macrophage activation syndrome (MAS) is a potentially life-threatening complication of rheumatic diseases. We report a unique case of a previously healthy 20-year-old female presenting with MAS as first presentation of systemic lupus erythematosus. Remission was achieved with hydroxychloroquine, intravenous methylprednisolone pulse followed by oral prednisolone and cyclosporine. However, the management of MAS is still challenging, and the mortality rate remains high.

Introduction. Statins are some of the most widely prescribed medications. Although statins are generally well tolerated, they can lead to musculoskeletal side effects. Statin-induced necrotizing autoimmune myositis (SINAM) is a rare condition and the prevalence is only 1 per 100,000 people. This disorder is characterized by progressive and severe symmetric muscle weakness, marked elevation of creatine kinase and persistent symptoms despite statin discontinuation. Electromyography commonly shows a nonspecific irritable myopathy pattern indistinguishable from other inflammatory myopathies. Muscle biopsy shows the presence of necrotic fibers, regenerating fibers without significant inflammatory cells and diffuse or focal upregulation of major histocompatibility complex class I expression. The anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibodies represent a characteristic serological feature of SINAM. Case report. We present a patient who developed progressive muscle weakness after taking simvastatin for the last seven years. At initial presentation, her creatine kinase level was 2,954 U/L and anti-HMGCR antibodies were positive. The biopsy showed a profound myopathic features with numerous necrotic fibers, some regenerating fibers and perimysial inflammatory cell infiltrate, combined with a diffuse overexpression of major histocompatibility complex class I products. She was diagnosed with SINAM, statin was suspended and a high dose of systemic corticosteroids, intravenous immunoglobulin therapy and methotrexate was started. At three-month follow-up, she had significant improvement in muscle strength and creatine kinase level returned to normal. Conclusion. In this case, exclusion of inflammatory myopathies, metabolic muscle disorders and other neurological diseases is necessary for establishing a reliable diagnosis. In SINAM, simply discontinuing statin is often insufficient and aggressive immunosuppression or immunomodulation therapy is needed to achieve disease remission. This case aims to demonstrate that statins can induce serious muscular diseases that require aggressive immunosuppression.

Statins are some of the most widely prescribed medications. Although statins are generally well tolerated, they can lead to musculoskeletal side effects. Statin-induced necrotizing autoimmune myositis (SINAM) is a rare condition and the prevalence is only 1 per 100,000 people. This disorder is characterized by progressive and severe symmetric muscle weakness, marked elevation of creatine kinase and persistent symptoms despite statin discontinuation. Electromyography commonly shows a nonspecific irritable myopathy pattern indistinguishable from other inflammatory myopathies. Muscle biopsy shows the presence of necrotic fibers, regenerating fibers without significant inflammatory cells and diffuse or focal upregulation of major histocompatibility complex class I expression. The anti-3-hydroxy-3-methylglutaryl-coenzyme A reductase (anti-HMGCR) antibodies represent a characteristic serological feature of SINAM.

We demonstrate a proof-of-concept for the analysis of the language of chronic pain for pain intensity estimation. Importantly, we show that focus on specific words/themes is especially correlated with specific pain intensity categories. We interviewed chronic pain patients and collected demographic and clinical data. 65 patients (40 females), averaging $\mathbf{56.4} \pm \mathbf{12.7}$ years of age, participated in the study. Patients reported their current pain intensity on a Visual Analogue Scale, which we discretized into 3 classes: mild, moderate, and severe pain. We extracted language features from the transcribed interview of each patient and used them to classify their pain intensity category. We measured performance with the weighted $\mathbf{F}_{\mathbf{1}}$ score. Finally, we analyzed potential confounding variables for internal validity. The best performing model was the Support Vector Machine with an Early Fusion of select language features, with an $\mathbf{F}_{\mathbf{1}}$ of 0.60, improving 39.5% upon the baseline. Patients with mild pain focused more on verbs, whilst moderate and severe pain patients focused on adverbs, and nouns and adjectives, respectively. We show that language features from patient narratives indeed convey information relevant for pain intensity estimation, and that our models can take advantage of that.

Introduction. Neurodevelopmental disorders have a multifactorial etiology that results from the interaction between biological and environmental factors. The biological basis of many of these disorders is only partially understood, which makes therapeutic interventions, especially pharmacological ones, particularly difficult. The impact of medical cannabis on neurological and psychiatric disorders has been studied for a long time. This study aimed to review the currently available clinical and pre-clinical studies regarding the use of cannabinoids in pediatric neurodevelopmental disorders and to draw attention to the potential therapeutic role of cannabidiol in this field. Development. Cannabidiol is an endocannabinoid system modulator and exerts its effects on both developing and mature brains through numerous mechanisms. Cannabidiol holds a relatively high toxicity limit and current literature suggests that it may have anxiolytic, antipsychotic, and neuroprotective properties. Clinical evidence suggests that early treatment with cannabidiol might be a promising therapy for neurodevelopmental disorders, including intellectual disability, autism spectrum disorders, tics, and attention/deficit hyperactivity disorder. Conclusions. This review hopefully draws attention to an emerging body of evidence concerning cannabidiol’s significant potential to safely improve many of the common symptoms affecting children and adolescents with neurodevelopmental disorders, especially autism spectrum disorder.

We describe a case of a 57-year-old white woman treated for rheumatoid arthritis (RA) with tofacitinib 10mg daily (started one year ago) and prednisolone 5mg daily. She presented to the emergency department with a tight squeezing chest pain and shortness of breath for 7h and the clinical evaluation revealed regional systolic dysfunction of the left ventricle, mimicking a myocardial infarction, in the absence of angiographic evidence of obstructive coronary artery disease or acute plaque rupture. All changes were transient and resolved completely within 4 days. The diagnosis of Takotsubo cardiomyopathy (TKM) was established. This is, as far as we know, the first report of a case of TKM in a RA patient taking tofacitinib. Although the association has not been previously described and the precise cause cannot be identified in this patient, the association with tofacitinib should be considered given the etiopathogenic rationale and the absence of any other identifiable cause.

Although Behçet´s disease (BD) is a systemic inflammatory disease, renal involvement is uncommon and ranges from mild asymptomatic urinary abnormalities to severe disease with progressive renal failure. We describe the case of a 30 years-old woman with multiorgan BD, under ustekinumab, who presented with proteinuria, hematuria and impaired renal function. Kidney biopsy revealed histological findings of active renal vasculitis in the context of IgA nephropathy and tubulointerstitial nephritis and the patient was treated with corticosteroids and cyclophosphamide with excellent response. Our case highlights the importance of recognizing a possible renal involvement in BD patients, reinforcing the need for monitoring renal function and urinalysis in these patients.

Serositis is seen in approximately 12% of patients with systemic lupus erythematosus (SLE), usually in the form of pleuritis or pericarditis. Peritoneal serositis with ascites is an extremely rare manifestation of SLE and ascites as initial manifestation of SLE is even rarer. Here, we describe a previously healthy 48-year-old female with periumbilical abdominal pain, constitutional symptoms, ascites, pleural effusions and raised CA-125 level as an initial manifestation of SLE, which led up to the diagnosis of pseudo-pseudo Meigs syndrome. PPMS is a rare manifestation of SLE and awareness of this entity among clinicians is crucial to ensure an early recognition and prompt treatment.