RESUMO
Systemic sclerosis (SSc) is a rare autoimmune disease characterized by a tripod combining vasculopathy, fibrosis, and immune-mediated inflammatory processes. The prevalence of interstitial lung disease (ILD) in SSc varies according to the methods used to detect it, ranging from 25 to 95%. The fibrotic and vascular pulmonary manifestations of SSc, particularly ILD, are the main causes of morbidity and mortality, contributing to 35% of deaths. Although early trials were conducted with cyclophosphamide, more recent randomized controlled trials have been performed to assess the efficacy and tolerability of several medications, mostly mycophenolate, rituximab, tocilizumab, and nintedanib. Although many uncertainties remain, expert consensus is emerging to optimize the therapeutic management and to provide clinicians with evidence-based clinical practice guidelines for patients with SSc-ILD. This article provides an overview, in the light of the latest advances, of the available evidence for the diagnosis and management of SSc-ILD.
Assuntos
Imunossupressores , Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Humanos , Doenças Pulmonares Intersticiais/etiologia , Escleroderma Sistêmico/complicações , Imunossupressores/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Guias de Prática Clínica como Assunto , IndóisRESUMO
Based on the results of randomized clinical trials (RCT) assessing direct oral anticoagulants (DOACs) for the treatment of patients with cancer-associated thrombosis (CAT), DOACs have been proposed as alternative to low molecular weight heparin by several international guidelines. However, the proportion of CAT patients who would have not been eligible for such trials is currently unknown. Our primary aim was to assess the proportion of patients seen in clinical practice for acute CAT who would not have been eligible for CARAVAGGIO or HOKUSAI-VTE RCT. Secondary aim was to describe patients outcomes according to eligibility. In a multicenter, observational study, all patients consecutively admitted from January 2017 to December 2019 for an acute CAT event were retrospectively analyzed. Patients were classified according to the presence or absence of non-inclusion criteria for CARAVAGGIO or HOKUSAI-VTE RCT. Event free survival during a 6-month follow-up were analyzed as secondary endpoints. Among the 302 patients (women: 53 %, mean age: 67.9 ± 13.2) analyzed, 138 (46 %) for HOKUSAI-VTE cancer and 161 (53 %) for CARAVAGGIO met one or more non-inclusion criteria. Main criteria were upper limb and unsual site thrombosis (n = 63, 18.5 %), anemia/thrombopenia (n = 43, 14.2 %), brain tumors (n = 33, 10.9 %), ECOG PS >2 (n = 28, 9.3 %), severe renal failure (n = 16, 5.3 %). At 6 months, the event-free survival rate was not statistically different between the two groups. Almost half of CAT patients would have not been able to participate to a modern DOAC RCT. Evaluation of DOACs safety and efficacy in this subset of patients deserves further research.
Assuntos
Anticoagulantes , Neoplasias , Ensaios Clínicos Controlados Aleatórios como Assunto , Trombose , Humanos , Feminino , Masculino , Idoso , Neoplasias/complicações , Estudos Retrospectivos , Pessoa de Meia-Idade , Trombose/etiologia , Trombose/epidemiologia , Anticoagulantes/uso terapêutico , Anticoagulantes/administração & dosagem , Administração Oral , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Idoso de 80 Anos ou mais , Seleção de PacientesRESUMO
BACKGROUND: Interstitial lung disease (ILD) and pulmonary hypertension (PH) represent the major causes of mortality in systemic sclerosis (SSc). Patients with systemic sclerosis and combined PH and ILD (SSc-PH-ILD) generally have a poor prognosis. Predictors of survival and of potential benefit of treatment are lacking in patients with SSc-PH-ILD. OBJECTIVE: To identify specific plasma protein expression patterns associated with survival in patients with SSc-PH-ILD. MATERIALS AND METHODS: Post-hoc analysis of a prospective multicenter French study in patients with PH-ILD. An untargeted proteomic analysis using mass spectrometry was performed to identify plasma protein changes associated with long-term overall survival in patients with SSc-PH-ILD. RESULTS: Thirty two patients were included in the analysis, of whom 13 died during follow-up (median survival: 76.5 months). At baseline, survivors had less severe hemodynamic impairment [pulmonary vascular resistance of 4.4 Wood Units (IQR 3-5.2) vs. 6.2 Wood Units (IQR 4.2-10.7)] and higher carbon monoxide diffusing capacity [median 39% (IQR 35-44%) vs. 25% (IQR 22-30.5%)], than the 13 patients who died. Seven proteins, associated with haemostasis and fibrosis, were differentially expressed according to patients' survival. In the survivor group, two proteins were increased (ADAMTS13, SERPIND1) and five were decreased (PTGDS, OLFM1, C7, IGFBP7, FBN1) compared to the non-survivor groups. CONCLUSION: The prognosis of SSc-PH-ILD patients is poor. This proteomic approach found 7 plasma proteins (involved in haemostasis and fibrosis pathways) associated with survival. These potential biomarkers may be good candidates to prognostic enrichment.
Assuntos
Hipertensão Pulmonar , Doenças Pulmonares Intersticiais , Hipertensão Arterial Pulmonar , Escleroderma Sistêmico , Humanos , Hipertensão Pulmonar/diagnóstico , Hipertensão Pulmonar/etiologia , Estudos Prospectivos , Proteômica , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/diagnóstico , Biomarcadores , Fibrose , Proteínas Sanguíneas , PulmãoRESUMO
In cancer patients, pulmonary embolism (PE) is the second leading cause of death after the cancer itself, most likely because of difficulties in diagnosing the disease due to its nonclassical presentation. The risk of PE recurrence and possibly the case-fatality rate depends on whether the patient presents a symptomatic PE, an unsuspected PE, a subsegmental PE, or a catheter-related PE. Choosing the best therapeutic option is challenging and should consider the risk of both the recurrence of thrombosis and the occurrence of bleeding. The purpose of this review is to provide an overview of the clinical characteristics and the treatment of cancer-associated PE, which could benefit clinicians to better manage the deadliest form of thrombosis associated with cancer. After a brief presentation of the epidemiological data, we will present the current attitude towards the diagnosis and the management of cancer patients with PE. Finally, we will discuss the perspectives of how the medical community can improve the management of this severe medical condition.
RESUMO
We report the case of a 48-year-old woman under dialysis from chronic renal failure (CRF) since the age of 27, due to Alport syndrome. The patient underwent routine chest X-ray on which diffuse micronodules were shown. Chest computed tomography showed partially calcified micronodules with centrilobular distribution respecting the subpleural spaces and predominant in the upper lobar regions. Metastatic pulmonary calcinosis was confirmed by the bone scan with an overall course of 29 years. This is the first reported case of pulmonary calcinosis from CRF due to Alport syndrome.
RESUMO
During the past decade, emergence of direct oral anticoagulants (DOACs) has drastically improved the prevention of thrombosis. However, several unmet needs prevail in the field of thrombosis prevention, even in the DOACs' era. The use of DOACs is still constrained and the drugs cannot be administered in every clinical scenario, such as an increased anticoagulant-associated bleeding risk, particularly in some specific populations (cancer - notably those with gastrointestinal or genitourinary cancer - and frail patients), the impossibility to be used in certain patients (eg, end-stage kidney failure during hemodialysis, pregnancy and breastfeeding), and their lack of efficacy in certain clinical scenarios (eg, mechanical heart valves, triple-positive antiphospholipid syndrome). Efforts to find a factor that upon antagonization prevents thrombosis but spares haemostasis have resulted in the identification of coagulation factor XI (FXI) as a therapeutic target. After briefly recapitulating the role of factor XI in the balance of haemostasis, we propose a narrative review of the key data published to date with compounds targeting factor XI to prevent thrombosis as well as the main ongoing clinical studies, opening up prospects for improving the care of patients requiring thrombosis prevention.
Assuntos
Síndrome Antifosfolipídica , Fator XI , Trombose , Tromboembolia Venosa , Anticoagulantes/efeitos adversos , Síndrome Antifosfolipídica/tratamento farmacológico , Fator XI/antagonistas & inibidores , Humanos , Trombose/tratamento farmacológico , Trombose/etiologia , Trombose/prevenção & controle , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/prevenção & controleRESUMO
Obstructive sleep apnea (OSA) is characterized by repeated episodes of intermittent hypoxia (IH) and is recognized as an independent risk factor for vascular diseases that are mediated by a multitude of mechanistic pathophysiological cascades including procoagulant factors. The pro-coagulant state contributes to the development of blood clots and to the increase in the permeability of the blood-brain barrier (BBB). Such alteration of BBB may alter brain function and increase the risk of neurodegenerative diseases. We aim to provide a narrative review of the relationship between the hypercoagulable state, observed in OSA and characterized by increased coagulation factor activity, as well as platelet activation, and the underlying neural dysfunction, as related to disruption of the BBB. We aim to provide a critical overview of the existing evidence about the effect of OSA on the coagulation balance (characterized by increased coagulation factor activity and platelet activation) as on the BBB. Then, we will present the emerging data on the effect of BBB disruption on the risk of underlying neural dysfunction. Finally, we will discuss the potential of OSA therapy on the coagulation balance and the improvement of BBB.
RESUMO
Since the earliest works on the understanding of different forms of pulmonary hypertension, thrombosis has been involved in the pathophysiology of the disease, both in pulmonary arterial hypertension (PAH) and in chronic thromboembolic pulmonary hypertension (CTEPH). Autopsy and then pathophysiological data paved the way for the use of anticoagulants as a treatment for PAH and CTEPH. In PAH their role has diminished with the advent of specific targeted therapies, but they are still prescribed in more than half of PAH patients, because of concomitant venous thromboembolism or atrial fibrillation. In CTEPH long-term anticoagulant therapy is the cornerstone of the management. The recent development of direct oral anticoagulants (DOACs) raises the question of the best anticoagulation strategy, both in patients with PAH and in patients with CTEPH. In this review, we present an overview of the history of anticoagulants in the management of patients suffering from PAH or CTEPH, an update of the available data on the underlying rationale of their use in these subjects, an alert on the potential risks of using DOACs in these poorly explored situations, and the setting up of dedicated trials to evaluate the best anticoagulant treatment strategies in patients suffering from PAH or CTEPH.
Assuntos
Anticoagulantes/uso terapêutico , Inibidores do Fator Xa/efeitos adversos , Hemorragia/induzido quimicamente , Hipertensão Pulmonar/tratamento farmacológico , Embolia Pulmonar/tratamento farmacológico , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/etiologia , Fibrilação Atrial/prevenção & controle , Inibidores do Fator Xa/uso terapêutico , Feminino , Cardiopatias Congênitas/complicações , Hemorragia/epidemiologia , Humanos , Hipertensão Pulmonar/mortalidade , Hipertensão Pulmonar/fisiopatologia , Incidência , Masculino , Terapia de Alvo Molecular/métodos , Embolia Pulmonar/fisiopatologia , Análise de Sobrevida , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/prevenção & controleRESUMO
BACKGROUND: Thoracoscopy, either "medical" or "surgical", is the gold standard to reveal the cause of pleural effusion by taking large biopsies. However, in some cases, the histology of pleural biopsies is inconclusive for a specific cause, describing a variable process of inflammation, encompassing for non-specific pleuritis (NSP). Questions are raised whether the surgical (or video-assisted thoracoscopic surgery, VATS) is doing better than the medical thoracoscopy (MT or pleuroscopy), but no direct comparison between the two techniques exist in the current bibliography. The aim of our retrospective study was to compare these two techniques to find whether there is any difference in the false negative cases of NSP. METHODS: We included in our study 295 patients with NSP, 179 patients who underwent VATS comparing to 116 patients who underwent MT for pleural effusion of initially undetermined cause, having a follow-up of at least one year. Analysis of patients' files, history, clinical examinations, further tests, and follow-up were recorded. RESULTS: The mean age of our patients was 58.5±19.1 and M/F gender was 216/79; no difference was observed between the two groups. The mean follow-up period was 47.3±20.7 months. After VATS, only one patient (0.55%) was finally diagnosed with pleural malignancy (false negative) while after MT 2 patients (1.7%). Negative predictive value for pleura-related malignancy for VATS was 0.994 and for MT 0.982. CONCLUSIONS: In patients with histological diagnosis of NSP both VATS and MT showed similar and excellent results of false negative cases and negative predictive value in excluding malignant pleural disease.
RESUMO
Irisin is a newly discovered hormone produced by the muscle. This hormone is involved in glucose metabolism, muscle strength and energy expenditure. As vitamin D is also known as a key player in that field, we aimed to see if a single dose of 100,000 IU of vitamin D would modify circulating levels of irisin in 29 young adults. Irisin was determined with the Phoenix Elisa assay at day 0, day 3, day 7 day 15 and day 28 after the loading dose. If we observed a significant increase in 25(OH)D levels (from 19.8±8.4 ng/mL to 33.0±8.5 ng/mL), irisin levels remained constant throughout the study (median 104.5 ng/mL, with values ranging from 69.9 to 390.9 ng/mL). Interestingly, one subject presented irisin values that were three times higher than all the others.