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Background: Endoscopic retrograde cholangiopancreatography (ERCP) is the first-line procedure for choledocholithiasis treatment. However, it is associated with a 10 % rate of adverse events. Spontaneous migration of common bile duct (CBD) stones occurs in 6-33 % of choledocholithiasis cases, making ERCP avoidable. This study aimed to identify predictors of spontaneous CBD stones' migration., Methods: Retrospective study including patients diagnosed with choledocholithiasis and submitted to ERCP. Patients were divided into 2 groups considering spontaneous stone migration (i.e.: the absence of CBD stones on ERCP). Data on patients' characteristics, imaging findings, biochemical analysis, and ERCP procedure were analyzed to identify predictors of spontaneous migration of CBD stones., Results: 334 patients with a mean age of 71.7 years were included in the study: 76.6 % without and 23.4 % with spontaneous migration of CBD stones. Although some patients' features (gender and clinical presentation), imaging findings (diameters of the largest stone and CBD), biochemical analysis (bilirubin levels at diagnosis and pre-ERCP), and ERCP procedure characteristics (time from diagnosis to ERCP) were different between groups, only three variables were defined as predictors: the absence of acute cholangitis, the largest stone diameter ≤5 mm, and the bilirubin levels pre-ERCP ≤ 2mg/dL. When using those variables together there was a chance of 81-86 % to correctly distinguishing patients with and without spontaneous CBD stone migration., Conclusion: The size of the largest stone at diagnosis was validated as a predictor of CBD stones' spontaneous migration. Furthermore, two new predictors were identified: bilirubin levels pre-ERCP ≤ 2 mg/dL, and no acute cholangitis at the clinical presentation of choledocholithiasis. EUS and ERCP in the same session should be considered in patients with factors predictive of stone migration, especially when combined, to minimize unnecessary ERCP and possible complications., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jorge Canena reports a relationship with Boston Scientific Corporation that includes: consulting or advisory. Jorge Canena reports a relationship with Micro-Tech that includes: consulting or advisory. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Masson SAS.)

Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is an uncommon but significant hematological disorder characterized by the presence of lupus anticoagulant (LA) and reduced levels of prothrombin (factor II). This syndrome presents a unique clinical paradox where patients may experience both a bleeding tendency due to hypoprothrombinemia and a prothrombotic state associated with LA. This syndrome should be suspected in the presence of increased coagulation times (prothrombin time and activated partial thromboplastin time) in association with the presence of LA. The dual risk between bleeding and thrombosis poses significant diagnostic and therapeutic challenges, particularly in deciding whether to use anticoagulation therapy, which could exacerbate bleeding, or withhold it, which could increase the risk of thrombosis. The authors report a case of a woman with LAHPS treated with rituximab. This case reinforces the importance of establishing guidelines for this disease., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Gago et al.)

Background: Axial Spondyloarthritis (axSpA) is a chronic inflammatory rheumatic condition affecting the axial skeleton, leading to pain, stiffness, and fatigue. While biologic therapies have improved clinical management, many patients experience partial or no responses, resulting in delays in disease control. Additionally, the risk of adverse events and increased costs remains a concern., Objectives: Our primary objectives are: 1. to identify reliable markers for treatment response to Tumor Necrosis Factor alpha inhibitors (TNFi), in particular Adalimumab, enabling the identification of individuals most likely to benefit; 2. to analyze the impact of TNFi on gene and protein expression., Methods: A multicenter, prospective 14-week study will be conducted with 36 participants aged 18-75 years, meeting the ASAS criteria for axSpA. Patient enrollment will follow the National Guidelines for the use of TNFi in axSpA treatment, with all included patients using TNFi (Adalimumab) as a first-line option. Epidemiological and clinical data will be collected, along with peripheral blood samples, for integrated transcriptome, using RNA Seq (whole genome sequencing) and proteome analysis at various time points (baseline, 3-5 days, weeks 2 and 14), corresponding to the initial administration of TNFi. Patients will be classified as responders and non-responders, primarily based on ASAS20 criteria and secondarily based on ASDAS-C Reactive Protein (CRP), at week 14., Discussion: This project's innovative approach lies in identifying potential biomarkers for TNFi (Adalimumab) response at baseline, paving the way for advancements in precision medicine in this field. Additionally, it seeks to establish evidence of the therapy's impact on gene and protein expression, offering deeper insights into the pathophysiological mechanisms underlying the therapeutic response.

Purpose: To determine the effects of stratified primary care for low back pain (SPLIT program) in decreasing back-related disability for patients with low back pain (LBP) in primary care., Methods: We conducted a before-and-after study. We compared health-related outcomes for 2 sequential, independent cohorts of patients with LBP recruited at 7 primary care units in Portugal. The first prospective cohort study characterized usual care (UC) and collected data from February to September 2018. The second was performed when the SPLIT program was implemented and collected data from November 2018 to October 2021. Between cohorts, physical therapists were trained in the implementation of the SPLIT program, which used the STarT Back Screening Tool to categorize patients for matched treatment. We compared back-related disability (Roland-Morris Disability Questionnaire, 0-24 points), pain (Numeric Pain Rating Scale, 0-10 points), perceived effect of treatment (Global Perceived Effect Scale, -5 to +5 points), and health-related quality of life (EuroQoL 5 dimensions 3 levels index, 0-1 points)., Results: We enrolled a total of 447 patients: 115 in the UC cohort (mostly treated with pharmacologic treatment) and 332 in the SPLIT cohort (all referred for a physical therapy intervention program). Over the study period of 6 months, patients in the SPLIT program showed significantly greater improvements in back-related disability (ß, -2.94; 95% CI, -3.63 to -2.24; P ≤ .001), pain (ß, -0.88; 95% CI, -1.18 to -0.57; P ≤ .001), perceived effect of treatment (ß, 1.40; 95% CI, 0.97 to 1.82; P ≤ .001), and health-related quality of life (ß, 0.11; 95% CI, 0.08 to 0.14; P ≤ .001) compared with UC., Conclusions: Patients in the SPLIT program for LBP showed greater benefits regarding health-related outcomes than those receiving UC., (© 2024 Annals of Family Medicine, Inc.)

This study aims at identifying molecular biomarkers differentiating responders and non-responders to treatment with Tumor Necrosis Factor inhibitors (TNFi) among patients with axial spondyloarthritis (axSpA). Whole blood mRNA and plasma proteins were measured in a cohort of biologic-naïve axSpA patients ( n = 35), pre and post (14 weeks) TNFi treatment with adalimumab. Differential expression analysis was used to identify the most enriched pathways and in predictive models to distinguish responses to TNFi. A treatment-associated signature suggests a reduction in inflammatory activity. We found transcripts and proteins robustly differentially expressed between baseline and week 14 in responders. C-reactive protein (CRP) and Haptoglobin (HP) proteins showed strong and early decrease in the plasma of axSpA patients, while a cluster of apolipoproteins (APOD, APOA2, APOA1) showed increased expression at week 14. Responders to TNFi treatment present higher levels of markers of innate immunity at baseline, and lower levels of adaptive immunity markers, particularly B-cells. A logistic regression model incorporating ASDAS-CRP, gender, and AFF3 , the top differentially expressed gene at baseline, enabled an accurate prediction of response to adalimumab in our cohort (AUC = 0.97). In conclusion, innate and adaptive immune cell type composition at baseline may be a major contributor to response to adalimumab in axSpA patients. A model including clinical and gene expression variables should also be considered.

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disorder which may affect the gastrointestinal system. Half of the patients with SLE experience gastrointestinal symptoms, with the most common being nausea, vomiting, anorexia, and abdominal pain. Mesenteric vasculitis is a severe and rare complication of SLE and one of the most frequent causes of severe acute abdominal pain. The authors present a case of a 57-year-old woman with SLE who was diagnosed with necrotizing mesenteric vasculitis following a urinary septic shock. The patient was treated with high-dose corticosteroid therapy and cyclophosphamide, with resolution of the clinical picture.

Hypereosinophilia is unusual in rheumatoid arthritis (RA), but can occur in severe long-lasting disease, especially in patients with extra-articular manifestations and high titers of rheumatoid factor (RF). The association of RA and hypereosinophilic syndrome (HES) remains yet poorly known. We present a case of a 46 years old woman with long-standing untreated RA, that presented to emergency department with severe symptoms of constrictive pericarditis with cardiac tamponade and bilateral pleural effusion, that progressed to cardiac arrest, associated to symmetrical polyarthritis and pruritic erythematous skin papules. She was submitted to urgent pericardial drainage and partial pericardiotomy. Laboratory analyses revealed hypereosinophilia, and elevated inflammatory parameters and immunoglobulin E. The histological study of the pericardium showed results consistent with inflammatory fibrinous pericarditis. Taking into account the presence of some characteristics that are usually present in cases of reactive HES instead of idiopathic HES, and after an intensive diagnostic study, that could rule out other potential causes of secondary HES, the diagnosis of HES associated with RA was made. She started glucocorticoids during hospitalization and methotrexate 15mg per week at the first outpatient rheumatology visit. After 12 weeks of treatment, we considered that she was in clinical and analytical remission, consistently maintaining that after a complete tapering of glucocorticoids. This case illustrates that clinicians should be aware that HES (including severe life-threatening cases) can occur in patients with RA, especially in cases of long-lasting disease with high titters of RF and without treatment, even in the absence of extra-articular features.

Introduction: The association of hepatitis delta virus (HDV) infection with positive autoantibodies and autoimmune features has been known for decades. However, to date, very few cases of clinical autoimmune hepatitis (AIH) have been reported in association with HDV infection, most of them being in the context of treatment with peginterferon., Case Report: This case refers to a 46-year-old woman born in Guinea-Bissau who moved to Portugal in 2018 to investigate complaints of diffuse abdominal discomfort and nausea. Her initial work-up, including laboratory and liver histology, was consistent with type 1 AIH. She had HBe antigen-negative chronic hepatitis B virus infection with negative DNA and also a positive total anti-HDV antibody, with negative IgM and undetectable RNA. Therefore, after initiating prophylactic tenofovir difumarate, she was started on prednisolone followed by azathioprine, which was later stopped due to presumed hepatotoxicity. Repeated histology showed signs of viral superinfection, and she was treated with acyclovir due to a positive herpes simplex IgM, with HDV RNA remaining negative. A third flare in transaminases prompted the introduction of mycophenolate mofetil (MMF) after a thorough exclusion of additional causes of liver disease. About 6 months later, during another bout of hepatitis, HDV RNA was finally positive and classified as genotype 5. MMF was stopped, and, considering a contraindication to interferon, the patient was offered therapy with bulevirtide, which she refused for personal reasons as she is currently living in her home country., Discussion: This is a challenging case of autoimmune or "autoimmune-like" hepatitis, probably induced by chronic HDV infection. High suspicion of HDV was essential because, had the case been interpreted as refractory AIH, with escalation of immunosuppression, a more severe course of the viral infection might have ensued. Recently, HDV suppression with bulevirtide was shown to reverse autoimmune liver disease. We hypothesize that the same could have happened to our patient, had she accepted this treatment., Competing Interests: The authors have no conflicts of interest to declare., (© 2023 The Author(s).Published by S. Karger AG, Basel.)

Cytomegalovirus (CMV) infection is a common and typically benign disease in immunocompetent individuals. However, immunocompromised patients are at a greater risk of reactivation, leading to more severe outcomes. Patients with rheumatic diseases have a particularly high risk of opportunistic infections due to both the inherent immunosuppressive state conveyed by the disease itself and the use of potent immunosuppressant drugs, such as glucocorticoids, cyclophosphamide, and rituximab. Limited data are available regarding prophylactic or preemptive treatment of CMV infection in patients with rheumatic diseases. In this article the authors present two cases of rheumatic conditions complicated by CMV infection. The first case describes a patient with eosinophilic granulomatosis with polyangiitis, previously treated with glucocorticoids and cyclophosphamide, who developed CMV colitis with bowel perforation. The second case involves a woman with systemic lupus erythematosus who was diagnosed with CMV meningitis. Both cases reinforce the importance of establishing guidelines for surveillance and prophylaxis of CMV infection in these patients.

Objectives: Chronic low back pain (CLBP) is a common health problem and in most patients it is not possible to identify a specific cause (non-specific CLBP). Spondyloarthritis is a musculoskeletal disorder characterized by (often inflammatory) back pain and spinal stiffness. The impact of CLBP and spondyloarthritis on patients' physical function may be different. This study aims to compare physical disability in patients with spondyloarthritis and CLBP, in a population-based setting. Furthermore, we aim to identify modifiable risk factors for physical disability among these two populations., Methods: Data from EpiReumaPt, a national health cohort with 10 661 individuals, conducted from September 2011 to December 2013, was used. Physical function was accessed by the Health Assessment Questionnaire Disability Index (HAQ-DI) and by the physical function dimension of the 36-Item Short Form Survey (SF-36). Univariable and multivariable linear regression analyses were used to assess the differences between groups. Factors associated with physical disability were explored for both diseases., Results: We evaluated 92 patients with spondyloarthritis, 1376 patients with CLBP and 679 subjects without rheumatic and musculoskeletal diseases (RMDs). Spondyloarthritis and CLBP patients reported significantly higher levels of disability in HAQ-DI (ß=0.33; p < 0.001 and ß=0.20; p < 0.001, respectively) than subjects without RMDs. In comparison to CLBP patients, spondyloarthritis patients reported higher disability (ß=0.14; p=0.03). The physical domains of SF-36, bodily pain and general health, where more affected in spondyloarthritis patients than in CLBP patients (ß=-6.61; p=0.02 and ß=-5.94; p=0.001, respectively). Spondyloarthritis and CLBP patients had a worse physical summary score (PCS) than mental summary score (MCS), and only PCS was significantly worse in comparison to subjects without RMDs. Factors associated with physical disability in CLBP were low back pain intensity, older age, obesity, multimorbidity, and retirement. Similarly, in spondyloarthritis physical disability was associated with retirement and multimorbidity. Factors associated with lower disability were alcohol consumption and male gender in CLBP, and regular physical exercise was associated with lower disability in both disorders., Conclusions: In this nationwide cohort, spondyloarthritis and CLBP patients reported significant physical disability. Regular physical exercise was associated with lower disability in both diseases.