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INTRODUCTION: Inflammatory bowel disease (IBD)-related arthritis is recognized as the most prevalent extraintestinal manifestation (EIM) of IBD. The objective of this study was to determine the prevalence and characteristics of undiagnosed IBD-related arthritis and to compare two screening questionnaires, DETection of Arthritis in Inflammatory boweL diseases (DETAIL) and IBd Identification of Spondyloarthritis Questionnaire (IBIS-q), for early disease detection. METHODS: Between April and October 2023, both the DETAIL and IBIS-q questionnaires were administered to consecutive IBD outpatients visiting the University Hospital of Udine, Italy. During routine gastroenterology evaluations, patients aged > 18 years with Crohn's disease (CD) or ulcerative colitis (UC) were requested to complete both questionnaires. Subsequently, all patients who completed the questionnaires underwent a blinded rheumatological evaluation within 2 weeks. Patients with a previous diagnosis of IBD-related SpA were then excluded. RESULTS: Overall, 203 patients were enrolled, of whom 26 were excluded because of a prior diagnosis of inflammatory arthritis. Among the remaining 177 patients, 10/177 (5.6%) received a new diagnosis of IBD-related arthritis. The median duration of symptoms before diagnosis was 4 (IQR 1.8-10.5) months. Imaging-confirmed enthesitis was the predominant pattern in 8 out 10 cases (80%, with 8 out 8 lacking concomitant peripheral arthritis), axial involvement in 1 out 10 cases (10%), and peripheral arthritis in 1 out 10 cases (10%). The DETAIL questionnaire exhibited higher specificity, but lower sensitivity compared to the IBIS-q, with a sensitivity of 40.0% (12.2-73.8) and specificity of 84.4% (78.0-89.6) versus a sensitivity of 70.0% (34.8-93.3) and specificity of 74.3% (66.9-80.7). Both questionnaires performed less effectively than in other studies. CONCLUSION: This study highlights a significant proportion of undiagnosed IBD-related arthritis (5.6%). Enthesitis emerged as the predominant pattern of newly diagnosed arthritis in our cohort, likely due to the recent onset of symptoms. Our study underscores the importance of entheseal involvement in early IBD-related arthritis and the importance of incorporating entheseal involvement into screening questionnaires.
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INTRODUCTION: Clinical remission is the main target in the management of patients with rheumatoid arthritis (RA). However, several authors found synovitis in patients with RA in clinical remission at ultrasonography (US). Upadacitinib is a selective Janus kinase 1 inhibitor that achieved significantly higher remission rates than adalimumab and abatacept in patients with RA. Here we present the 24-week data of the UPAdacitinib Rheumatoid Arthritis REmission UltraSonography (UPARAREMUS) study. METHODS: This is a longitudinal multicenter observational study, enrolling bio-naïve and bio-inadequate responder patients affected by RA. The primary endpoint was the proportion of patients achieving both clinical and US remission at week 24. The proportion of patients achieving clinical remission with different composite indexes at week 12 and 24 was also evaluated. US of four target joints (wrists and second metacarpophalangeal bilaterally) was performed at baseline and weeks 12/24, and US remission was defined as the absence of power Doppler (PD) signal ≥ 2 in one target joint, or PD ≥ 1 in two target joints. RESULTS: After 12 weeks and 24 weeks, 40% and 63.6% of patients achieved US plus clinical remission. The following parameters were associated with US plus clinical remission: being bio-naïve and having a shorter disease duration, although at multivariate analysis significant odds ratio (OR) was found only for being bio-naïve. CONCLUSIONS: UPARAREMUS is the first study evaluating the efficacy of upadacitinib in reaching both clinical and US remission in patients with RA. At 24 weeks, 63.6% of patients reached the primary endpoint, the only baseline associated parameter was being bio-naïve.
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The validity of psychological measurement is crucially connected to a peculiar form of epistemic circularity. This circularity can be a threat when there are no independent ways to assess whether a certain procedure is actually measuring the intended target of measurement. This paper focuses on how Fechner addressed the measurement circularity that emerged in his psychophysical research. First, I show that Fechner's approach to the problem of circular measurement involved a core idealizing assumption of a shared human physiology. Second, I assess Fechner's approach to this issue against the backdrop of his own epistemology of measurement and the measurement context of his time. Third, I claim that, from a coherentist and historically-situated perspective, Fechner's quantification can be regarded as a first successful step of a longer-term quantification process. To conclude, I draw from these insights some general epistemological reflections that are relevant to current quantitative psychology.
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OBJECTIVE: Several advanced therapies have been licensed across the related conditions of psoriatic arthritis (PsA), Crohn disease (CD), ulcerative colitis (UC), and noninfectious uveitis. We sought to summarize results from randomized controlled trials (RCTs) investigating the efficacy and safety of advanced therapies for these related conditions in patients with PsA. METHODS: We updated the previous systematic search conducted in 2013 with literature reviews of MEDLINE, Embase, and the Cochrane Library (from February 2013 to August 2020) on this subject; only those new studies are presented here. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework. RESULTS: The number of RCTs meeting eligibility criteria were 12 for CD, 15 for UC, and 5 for uveitis. The tumor necrosis factor inhibitor (TNFi) class appears to be efficacious and safe across CD, UC, and uveitis, with the exception of etanercept. Interleukin 12/23 inhibitors (IL-12/23i) are efficacious for CD and UC. Phase II and III RCTs of Janus kinase inhibitors (JAKi) and IL-23i in CD and UC are promising in terms of efficacy and safety. IL-17i must be used with great caution in patients with PsA at high risk of inflammatory bowel disease (IBD). RCTs in uveitis have mainly studied adalimumab. CONCLUSION: We have identified 32 recent RCTs in IBD and uveitis and updated recommendations for managing patients with PsA and these related conditions. A multispecialty approach is essential to effectively, safely, and holistically manage such patients. Advanced therapies are not equally efficacious across these related conditions, with dosing regimens and safety varying.
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Artritis Psoriásica , Colitis Ulcerosa , Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Uveítis , Humanos , AdalimumabRESUMEN
INTRODUCTION: Spondyloarthropathies (SpA) are a group of inflammatory arthritis that can involve the spine and/or peripheral joints. Extra-articular manifestations, such as inflammatory bowel disease (IBD), are frequently observed within the clinical manifestations of SpA and are part of the SpA classification criteria. Evidence of IBD is observed in about 6-7% of SpA patients, and a silent, microscopic gut inflammation, could be present in up to 50% of patients. From a pathogenetic point of view, dysregulated microbiome and migration of T lymphocytes and other cells from gut to the joint ('gut-joint' axis) has been recognized, in the context of a common genetic background. AREAS COVERED: The aim of this paper is to narratively review the recent evidences on the epidemiology, classification, clinical findings, pathogenesis, diagnosis, and treatment of IBD in patients with SpA and to provide advices for both rheumatologist and gastroenterologist in the management of IBD in SpA. EXPERT OPINION: IBD manifestations in SpA frequently increase the burden of the disease and represent a clinical challenge, especially for the diagnosis, assessment, and treatment of patients affected by those conditions. New treatment strategies targeting both articular and intestinal manifestations are now available and may lead to a better outcome.
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Enfermedades Inflamatorias del Intestino , Espondiloartritis , Enfermedad Crónica , Humanos , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Articulaciones/patología , Espondiloartritis/diagnóstico , Espondiloartritis/epidemiología , Espondiloartritis/patología , Linfocitos TRESUMEN
Introduction: Data about the clinical presentation and management of early and mild spondyloarthritis (SpA) are limited. Objectives: The objective of this study was to describe the baseline characteristics of disease-modifying antirheumatic drug (DMARD)-naïve patients with axial or peripheral SpA. Methods: The Spondyloarthritis Italian Registry: Evidence from a National Pathway (SIRENA) study is an ongoing, Italian, multicenter, prospective registry of patients with a first or newly confirmed diagnosis of SpA according to the Assessment of SpondyloArthritis International Society (ASAS) criteria. To be included, patients had to be naïve to conventional, targeted, and biological DMARDs for SpA. Patients were enrolled between June 2017 and June 2019 and classified into groups according to disease presentation: predominantly axial or peripheral manifestations. The study is ongoing, and patients are being followed for 2 years, with an evaluation every 6 months according to clinical practice. Differences in baseline demographics, lifestyle, and clinical characteristics between axial and peripheral SpA were evaluated. Results: In this study, 350 patients were enrolled, of which 123 (35.1%) were axial and 227 (64.9%) were peripheral patients. Patients with axial SpA were significantly younger at enrollment (median age: 44 vs. 53 years), had significantly more anxiety/depression (13 vs. 2.6%), and expressed higher disease activity compared to patients with peripheral SpA. Patients with peripheral SpA had significantly more cardiometabolic disorders (33 vs. 18.7%), skin psoriasis (65.2 vs. 21.1%), and nail psoriasis (35.5 vs. 17.1%) than patients with axial SpA. Dactylitis, enthesitis, and fibromyalgia were observed, respectively, in 17.6, 51.2, and 5.7% of patients with axial SpA and 24.3, 40, and 3.1% of patients with peripheral SpA. In both disease groups, women tended to report depression, joint tenderness, and higher disease activity more frequently than their male counterparts. At inclusion, a new diagnosis of SpA was performed in 58% of axial and 77% of peripheral patients, with a median time from symptom onset to diagnosis of 36 and 24 months, respectively. At baseline, most patients with axial SpA (77%) started a biological DMARD, while over half of the peripheral patients started a conventional DMARD. Conclusions: Based on a well-characterized clinical registry of SpA, we provided real-world insights on the clinical features of DMARD-naïve SpA patients, pointing out major differences between axial and peripheral disease in terms of clinical characteristics and treatment pattern. Future prospective evaluations within the SIRENA study will improve knowledge on SpA and contribute to defining the best therapeutic approach.
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Psoriatic arthritis (PsA) is a complex, multiform and chronic inflammatory disease characterized by the association of psoriasis and arthritis with other musculoskeletal and extra-articular manifestations. The treatment of PsA is rapidly evolving due to the introduction of new biologic and small-molecule drugs, and the aim of treatment is to induce a condition of remission or low disease activity in all disease domains. However, unmet treatment needs still persist for those patients with impaired function, reduced quality of life or comorbidities. In this context, physical therapy and rehabilitation could provide additional benefits by reducing disease activity and improving function. Although a large number of studies have assessed the role of physical therapy and exercise in other forms of chronic inflammatory arthritis, such as axial spondyloarthritis and rheumatoid arthritis, evidence on their effect on persons with PsA is still lacking. However, some studies have reported the potential positive role of physical therapy on the different disease domains of PsA, in helping to improve disease activity, prevent or improve articular impairment, improve pain management and improve quality of life. Here, we review current evidence on physical therapy, exercise and rehabilitation in patients with PsA. In particular, we review the literature focusing on each domain, to provide evidence of efficacy and effectiveness of exercise and rehabilitation on skin, peripheral arthritis, axial involvement, dactylitis, enthesitis and comorbidities.
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In the last decades, the comprehension of the pathophysiology of bone metabolism and its interconnections with multiple homeostatic processes has been consistently expanded. The branch of osteoimmunology specifically investigating the link between bone and immune system has been developed. Among molecular mediators potentially relevant in this field, vitamin D has been recently pointed out, and abnormalities of the vitamin D axis have been described in both in vitro and in vivo models of inflammatory bowel diseases (IBD) and arthritis. Furthermore, vitamin D deficiency has been reported in patients affected by IBD and chronic inflammatory arthritis, thus suggesting the intriguing possibility of impacting the disease activity by the administration vitamin D supplements. In the present review, the complex interwoven link between vitamin D signaling, gut barrier integrity, microbiota composition, and the immune system was examined. Potential clinical application exploiting vitamin D pathway in the context of IBD and arthritis is presented and critically discussed. A more detailed comprehension of the vitamin D effects and interactions at molecular level would allow one to achieve a novel therapeutic approach in gastro-rheumatologic inflammatory diseases through the design of specific trials and the optimization of treatment protocols.
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Artritis Reumatoide/tratamiento farmacológico , Enfermedades Gastrointestinales/tratamiento farmacológico , Enfermedades Inflamatorias del Intestino/tratamiento farmacológico , Deficiencia de Vitamina D/complicaciones , Vitamina D/administración & dosificación , Vitaminas/administración & dosificación , Animales , Artritis Reumatoide/etiología , Artritis Reumatoide/patología , Enfermedades Gastrointestinales/etiología , Enfermedades Gastrointestinales/patología , Humanos , Enfermedades Inflamatorias del Intestino/etiología , Enfermedades Inflamatorias del Intestino/patología , Deficiencia de Vitamina D/inmunologíaRESUMEN
OBJECTIVES: To investigate the diagnostic performance of dual-energy computed tomography (DECT) in detection bone marrow oedema (BME) in patients with sacroiliitis associated with axial spondyloarthritis (axial SpA). METHODS: Patients with axial SpA according to the ASAS criteria underwent DECT and 1.5-T magnetic resonance imaging (MRI). DECT was post-processed for generating virtual non-calcium (VNCa) images. The presence of abnormal bone marrow attenuation was scored on DECT VNCa images and MRI using a four-point classification system: 0-1 = absent or non-significant oedema, 2 = oedema present in a third of the articular surface, 3 = oedema present in 2/3 of the articular surface, 4 = diffuse oedema throughout the articular surface. Diagnostic accuracy values for BME were calculated for DECT images (quantitative assessment) by using receiver operating characteristic (ROC) curves analysis, applying MRI as gold standard. RESULTS: Eighty sacroiliac joints from 40 axial SpA patients were included for study analysis, and 36 sacroiliac joints (45%) were classified as having BME at MRI and compared to DECT. Sensitivity, specificity, and positive likelihood ratio (LR+) in the identification of BME at DECT were 90.0%, 92.8%, and 12.6 respectively. Negative LR was 0.11, positive predictive value 93.1%, and negative predictive value 89.7%. The area under the curve (AUC) was 0.953 in the differentiation of the presence of BME. A cut-off value of -1.6 HU (Youden's index = 0.828) yielded a sensitivity of 90.0% and specificity of 92.8%, with an LR+ of 12.6, in the detection of BME in the sacroiliac joints. CONCLUSIONS: DECT VNCa images had good diagnostic performance in the evaluation of the extent of BME in patients with sacroiliitis associated with axial SpA.
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Articulación Sacroiliaca , Espondiloartritis , Médula Ósea , Edema/diagnóstico por imagen , Edema/etiología , Humanos , Imagen por Resonancia Magnética , Estudios Prospectivos , Articulación Sacroiliaca/diagnóstico por imagen , Sensibilidad y Especificidad , Espondiloartritis/complicaciones , Espondiloartritis/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND: Psoriatic Arthritis (PsA) is the most common extracutaneous manifestation of psoriasis. This chronic inflammatory arthritis is burdened with significant morbidity, leading to irreversible joint damage and disability. In recent years, a deeper understating of its pathogenesis has led to the development of several new drugs targeting different pathways. OBJECTIVES: This review aims to highlight the clinical efficacy and safety of the novel agents that have become recently available for the treatment of PsA, as well as new promising therapeutic targets that are being evaluated in clinical trials. METHODS: For the purpose of this narrative review, we searched in the MEDLINE and ClinicalTrials. gov databases. RESULTS: After the introduction of the first biological drugs targeting Tumor Necrosis Factor (TNF), several other drugs with different targets have been developed, including anti-Interleukin (IL) 12/23p40, anti-IL17, and, more recently, anti-IL23p19 agents. DISCUSSION: Data supporting the efficacy of different agents in the major domains of PsA, as well as their safety issues, are summarized here. Finally, the current pipeline, including several novel nonbiological small molecules, such as Janus kinase (JAK) inhibitors, that are currently being evaluated in clinical trials are also presented. CONCLUSION: The availability of newer therapeutic agents has substantially changed the treatment strategy for PsA. In the future, a personalized treatment approach will probably achieve better control of disease manifestations.
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Anticuerpos Monoclonales/uso terapéutico , Antirreumáticos/uso terapéutico , Artritis Psoriásica/tratamiento farmacológico , Artritis Psoriásica/inmunología , Humanos , Inflamación , Subunidad p40 de la Interleucina-12/antagonistas & inhibidores , Interleucina-17/antagonistas & inhibidores , Subunidad p19 de la Interleucina-23/antagonistas & inhibidores , Terapia Molecular Dirigida , Factor de Necrosis Tumoral alfa/antagonistas & inhibidoresAsunto(s)
Tratamiento Farmacológico de COVID-19 , COVID-19/epidemiología , Hidroxicloroquina/uso terapéutico , SARS-CoV-2 , Enfermedades de la Piel/tratamiento farmacológico , Anciano , Antimaláricos/uso terapéutico , COVID-19/mortalidad , COVID-19/virología , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
OBJECTIVES: Gut microbiota has been widely reported to be involved in systemic inflammation through microbial translocation and T cell activation in several diseases. In this work we aimed to investigate bacterial infiltration and epithelial impairment in the gut of patients with IBD-associated SpA (SpA-IBD), as well as the relationship of microbial translocation with immune system activation and their putative role in the pathogenesis of joint inflammation in IBD patients. METHODS: Tight-junction proteins (TJPs) occludin and claudin-1/-4 and bacteria were assessed by real-time PCR analysis and immunohistochemical staining of the ileum. Intestinal fatty acid binding protein (I-FABP), lipopolysaccharides (LPS), soluble CD14 (sCD14), sclerostin and anti-sclerostin antibodies (anti-sclerostin-IgG) were assayed with ELISAs and peripheral mononuclear blood cells with flow cytometry. LPS and sCD14 were used in vitro to stimulate a human osteoblast cell line. RESULTS: Compared with IBD, ileal samples from SpA-IBD patients showed bacterial infiltration, epithelial damage and downregulation of TJPs. In sera, they showed higher serum levels of I-FABP, LPS, sCD14 (the latter correlating with sclerostin and anti-sclerostin-IgG) and higher CD80+/CD163+ and lower CD14+ mononuclear cells. In vitro experiments demonstrated that only the LPS and sCD14 synergic action downregulates sclerostin expression in osteoblast cells. CONCLUSION: SpA-IBD patients are characterized by gut epithelium impairment with consequent translocation of microbial products into the bloodstream, immune system activation and an increase of specific soluble biomarkers. These findings suggest that gut dysbiosis could be involved in the pathogenesis of SpA-IBD and it could hopefully prompt the use of these biomarkers in the follow-up and management of IBD patients.
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Traslocación Bacteriana , Íleon/inmunología , Enfermedades Inflamatorias del Intestino/complicaciones , Mucosa Intestinal/inmunología , Espondiloartritis/microbiología , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Biomarcadores/sangre , Estudios de Casos y Controles , Estudios de Cohortes , Proteínas de Unión a Ácidos Grasos/sangre , Humanos , Íleon/metabolismo , Enfermedades Inflamatorias del Intestino/sangre , Enfermedades Inflamatorias del Intestino/inmunología , Enfermedades Inflamatorias del Intestino/microbiología , Mucosa Intestinal/metabolismo , Receptores de Lipopolisacáridos/sangre , Lipopolisacáridos/sangre , Monocitos/metabolismo , Osteoblastos/metabolismo , Espondiloartritis/sangre , Espondiloartritis/inmunologíaAsunto(s)
Enfermedades Autoinmunes/tratamiento farmacológico , COVID-19/complicaciones , Brotes de Enfermedades , Inmunosupresores/uso terapéutico , Adulto , Anciano , Enfermedades Autoinmunes/complicaciones , Enfermedades Autoinmunes/virología , COVID-19/epidemiología , COVID-19/terapia , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Encuestas y CuestionariosRESUMEN
OBJECTIVE: Spondyloarthritis (SpA) is among the most frequent extraintestinal manifestations of inflammatory bowel diseases (IBD). In this study, we aimed to validate the DETection of Arthritis in Inflammatory boweL diseases (DETAIL) questionnaire in a multicenter cohort of patients with IBD enrolled at 11 gastroenterology units. METHODS: From October 2018 to March 2019, consecutive adult patients with IBD, either Crohn disease or ulcerative colitis, independently filled out the DETAIL questionnaire in the outpatient waiting room. Within 2 weeks a blinded rheumatologist assessed all the patients, irrespective of the DETAIL results, and classified them to be affected or not by SpA. The performance of the questions was evaluated through Bayesian analysis. RESULTS: Overall, 418 patients with IBD filled out the DETAIL questionnaire. Upon rheumatological evaluation, 102 (24.4%) patients received a diagnosis of SpA. Of the 6 questions, the best performances were found in question 6 [positive likelihood ratio (LR)+ 3.77], reporting inflammatory back pain at night, and in question 3 (LR+ 3.31), exploring Achilles enthesitis. The presence of back pain lasting > 3 months (LR+ 2.91), back pain with inflammatory features (LR+ 2.55), and a history of dactylitis (LR+ 2.55), also showed a fairly good performance, whereas a history of peripheral synovitis was slightly worse (LR+ 2.16). The combination of at least 3 questions answered affirmatively yielded a posttest probability of SpA of 80% or more. The presence of alternative diagnoses, such as osteoarthritis or fibromyalgia, represented a minor confounder. CONCLUSION: The DETAIL questionnaire is a useful tool for the early detection of SpA in IBD.
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Enfermedad de Crohn , Enfermedades Inflamatorias del Intestino , Espondiloartritis , Adulto , Teorema de Bayes , Humanos , Enfermedades Inflamatorias del Intestino/complicaciones , Enfermedades Inflamatorias del Intestino/diagnóstico , Espondiloartritis/complicaciones , Espondiloartritis/diagnóstico , Encuestas y CuestionariosRESUMEN
In this paper, I argue for a distinction between two scales of coordination in scientific inquiry, through which I reassess Georg Simon Ohm's work on conductivity and resistance. Firstly, I propose to distinguish between measurement coordination, which refers to the specific problem of how to justify the attribution of values to a quantity by using a certain measurement procedure, and general coordination, which refers to the broader issue of justifying the representation of an empirical regularity by means of abstract mathematical tools. Secondly, I argue that the development of Ohm's measurement practice between the first and the second experimental phase of his work involved the change of the measurement coordination on which he relied to express his empirical results. By showing how Ohm relied on different calibration assumptions and practices across the two phases, I demonstrate that the concurrent change of both Ohm's experimental apparatus and the variable that Ohm measured should be viewed based on the different form of measurement coordination. Finally, I argue that Ohm's assumption that tension is equally distributed in the circuit is best understood as part of the general coordination between Ohm's law and the empirical regularity that it expresses, rather than measurement coordination.
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Parto , Conductividad Eléctrica , Femenino , Humanos , Matemática , EmbarazoRESUMEN
BACKGROUND: The pandemic of coronavirus disease 2019 (COVID-19) has emerged as a relevant threat for humans worldwide. Abnormality in liver function tests (LFTs) has been commonly observed in patients with COVID-19, but there is controversy on its clinical significance. The aim of this study was to assess the prevalence, the characteristics and the clinical impact of abnormal LFTs in hospitalized, non-critically ill patients with COVID-19. METHODS: In this multicentre, retrospective study, we collected data about 565 inpatients with COVID-19. Data on LFTs were collected at admission and every 7 ± 2 days during the hospitalization. The primary outcome was a composite endpoint of death or transfer to intensive care unit (ICU). RESULTS: Upon admission 329 patients (58%) had LFTs abnormality. Patients with abnormal LFTs had more severe inflammation and higher degree of organ dysfunction than those without. During hospitalization, patients with abnormal LFTs had a higher rate of transfer to ICU (20% vs 8%; P < .001), acute kidney injury (22% vs 13%, P = .009), need for mechanical ventilation (14% vs 6%; P = .005) and mortality (21% vs 11%; P = .004) than those without. In multivariate analysis, patients with abnormal LFTs had a higher risk of the composite endpoint of death or transfer to ICU (OR = 3.53; P < .001). During the hospitalization, 86 patients developed de novo LFTs abnormality, which was associated with the use of tocilizumab, lopinavir/ritonavir and acetaminophen and not clearly associated with the composite endpoint. CONCLUSIONS: LFTs abnormality is common at admission in patients with COVID-19, is associated with systemic inflammation, organ dysfunction and is an independent predictor of transfer to ICU or death.
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Acetaminofén/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Antivirales/uso terapéutico , COVID-19 , Unidades de Cuidados Intensivos/estadística & datos numéricos , Hepatopatías , Pruebas de Función Hepática , Antipiréticos/uso terapéutico , COVID-19/complicaciones , COVID-19/mortalidad , COVID-19/fisiopatología , COVID-19/terapia , Cuidados Críticos/métodos , Femenino , Humanos , Italia/epidemiología , Hepatopatías/sangre , Hepatopatías/epidemiología , Hepatopatías/etiología , Pruebas de Función Hepática/métodos , Pruebas de Función Hepática/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Mortalidad , Valor Predictivo de las Pruebas , Prevalencia , Pronóstico , Estudios Retrospectivos , Medición de Riesgo/métodos , SARS-CoV-2/aislamiento & purificaciónAsunto(s)
COVID-19/complicaciones , Exantema/virología , Enfermedades Cutáneas Virales/diagnóstico , Piel/virología , COVID-19/diagnóstico por imagen , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Nasofaringe/virología , Piel/patología , Enfermedades Cutáneas Virales/etiología , Tomografía Computarizada por Rayos XRESUMEN
Cancer therapy is limited, in part, by lack of specificity. Thus, identifying molecules that are selectively expressed by, and relevant for, cancer cells is of paramount medical importance. Here, we show that peptidyl-prolyl-cis-trans-isomerase (PPIase) FK506-binding protein 10 (FKBP10)-positive cells are present in cancer lesions but absent in the healthy parenchyma of human lung. FKBP10 expression negatively correlates with survival of lung cancer patients, and its downregulation causes a dramatic diminution of lung tumor burden in mice. Mechanistically, our results from gain- and loss-of-function assays show that FKBP10 boosts cancer growth and stemness via its PPIase activity. Also, FKBP10 interacts with ribosomes, and its downregulation leads to reduction of translation elongation at the beginning of open reading frames (ORFs), particularly upon insertion of proline residues. Thus, our data unveil FKBP10 as a cancer-selective molecule with a key role in translational reprogramming, stem-like traits, and growth of lung cancer.