Search Results (6)

Background: Patients with solid cancers and hematopoietic malignancy can experience systemic symptoms compatible with adult-onset Still’s disease (AOSD). The newly described VEXAS, associated with somatic UBA1 mutations, exhibits an overlap of clinical and/or biological pictures with auto inflammatory signs and myelodysplastic syndrome (MDS). Objectives: To describe a cohort of patients with signs of undifferentiated systemic autoinflammatory disorder (USAID) concordant with AOSD and MDS/chronic myelomonocytic leukemia (CMML) and the prevalence of VEXAS proposed management and outcome. Methods: A French multicenter retrospective study from the MINHEMON study group also used for other published works with the support of multidisciplinary and complementary networks of physicians and a control group of 104 MDS/CMML. Results: Twenty-six patients were included with a median age at first signs of USAID of 70.5 years with male predominance (4:1). Five patients met the criteria for confirmed AOSD. The most frequent subtypes were MDS with a blast excess (31%) and MDS with multilineage dysplasia (18%). Seven patients presented with acute myeloid leukemia and twelve died during a median follow-up of 2.5 years. Six out of 18 tested patients displayed a somatic UBA1 mutation concordant with VEXAS, including one woman. High-dose corticosteroids led to a response in 13/16 cases and targeted biological therapy alone or in association in 10/12 patients (anakinra, tocilizumab, and infliximab). Azacytidine resulted in complete or partial response in systemic symptoms for 10/12 (83%) patients including 3 VEXAS. Conclusions: Systemic form of VEXAS syndrome can mimic AOSD. The suspicion of USAID or AOSD in older males with atypia should prompt an evaluation of underlying MDS and assessment of somatic UBA1 mutation. Full article

(1) Background: Ulipristal acetate (UPA) is a selective progesterone receptor modulator (SPRM) widely used for emergency contraception and mid- to long-term leiomyoma treatment. The aim of this study was to identify modifications of miRNA expression in superficial and basal layers of the human endometrium at the end of the UPA treatment for at least 3 months. (2) Methods: Microarray miRNA analysis of formalin-fixed, paraffin-embedded hysterectomy tissue samples was conducted, followed by an Ingenuity Pathway Analysis. Samples were divided into three groups: women having had 3 months of UPA treatment (n = 7); and two control groups of UPA-naïve women in the proliferative (n = 8) or secretory (n = 6) phase. (3) Results: The UPA modified the expression of 59 miRNAs involved in the processes of cell cycle, carcinogenesis, and inflammation. Their expression profiles were different in the basal and superficial layers. Most of the processes influenced by the UPA in the basal layer were connected to the cell cycle and immune regulation. (4) Conclusion: Specific changes were observed in both layers of the endometrium in the UPA group. However, the miRNA expression in the basal layer was not consistent with that in the superficial layer. Other large studies analysing the long-term impact of SPRM on endometrial miRNA expression are necessary. Full article

The molecular responses to hormonal stimuli in the endometrium are modulated at the transcriptional and post-transcriptional stages. Any imbalance in cellular and molecular endometrial homeostasis may lead to gynecological disorders. MicroRNAs (miRNAs) are involved in a wide variety of physiological mechanisms and their expression patterns in the endometrium are currently attracting a lot of interest. miRNA regulation could be hormone dependent. Conversely, miRNAs could regulate the action of sexual hormones. Modifications to miRNA expression in pathological situations could either be a cause or a result of the existing pathology. The complexity of miRNA actions and the diversity of signaling pathways controlled by numerous miRNAs require rigorous analysis and findings need to be interpreted with caution. Alteration of miRNA expression in women with endometriosis has been reported. Thus, a potential diagnostic test supported by a specific miRNA signature could contribute to early diagnosis and a change in the therapeutic paradigm. Similarly, specific miRNA profile signatures are expected for RIF and endometrial cancer, with direct implications for associated therapies for RIF and adjuvant therapies for endometrial cancer. Advances in targeted therapies based on the regulation of miRNA expression are under evaluation. Full article

Systemic auto-inflammatory or autoimmune diseases (SIADs) develop in up to a quarter of patients with myelodysplastic syndromes (MDS) or chronic myelomonocytic leukemia (CMML). With or without the occurrence of SIADs, the distribution of MDS subtypes and the international or CMML-specific prognostic scoring systems have been similar between MDS/CMML patients. Moreover, various SIADs have been described in association with MDS, ranging from limited clinical manifestations to systemic diseases affecting multiple organs. Defined clinical entities including systemic vasculitis, connective tissue diseases, inflammatory arthritis and neutrophilic diseases are frequently reported; however, unclassified or isolated organ impairment can also be seen. Although the presence of SIADs does not impact the overall survival nor disease progression to acute myeloid leukemia, they can help with avoiding steroid dependence and make associated adverse events of immunosuppressive drugs challenging. While therapies using steroids and immunosuppressive treatment remain the backbone of first-line treatment, increasing evidence suggests that MDS specific therapy (hypomethylating agents) and sparing steroids may be effective in treating such complications based on their immunomodulatory effect. The aim of this review was to analyze the epidemiological, pathophysiological, clinical and therapeutic factors of systemic inflammatory and immune disorders associated with MDS. Full article

The incidence of pulmonary embolism (PE) is high during severe Coronavirus Disease 2019 (COVID-19). We aimed to identify predictive and prognostic factors of PE in non-ICU hospitalized COVID-19 patients. In the retrospective multicenter observational CLOTVID cohort, we enrolled patients with confirmed RT-PCR COVID-19 who were hospitalized in a medicine ward and also underwent a CT pulmonary angiography for a PE suspicion. Baseline data, laboratory biomarkers, treatments, and outcomes were collected. Predictive and prognostics factors of PE were identified by using logistic multivariate and by Cox regression models, respectively. A total of 174 patients were enrolled, among whom 86 (median [IQR] age of 66 years [55–77]) had post-admission PE suspicion, with 30/86 (34.9%) PE being confirmed. PE occurrence was independently associated with the lack of long-term anticoagulation or thromboprophylaxis (OR [95%CI], 72.3 [3.6–4384.8]) D-dimers ≥ 2000 ng/mL (26.3 [4.1–537.8]) and neutrophils ≥ 7.0 G/L (5.8 [1.4–29.5]). The presence of these two biomarkers was associated with a higher risk of PE (p = 0.0002) and death or ICU transfer (HR [95%CI], 12.9 [2.5–67.8], p < 0.01). In hospitalized non-ICU severe COVID-19 patients with clinical PE suspicion, the lack of anticoagulation, D-dimers ≥ 2000 ng/mL, neutrophils ≥ 7.0 G/L, and these two biomarkers combined might be useful predictive markers of PE and prognosis, respectively. Full article

Although pulmonary events are considered to be frequently associated with malignant haemopathies, they have been sparsely studied in the specific context of myelodysplastic syndromes (MDS). We aimed to describe their different types, their relative proportions and their relative effects on overall survival (OS). We conducted a multicentre retrospective cohort study. Patients with MDS (diagnosed according to the 2016 WHO classification) and pulmonary events were included. The inclusion period was 1 January 2007 to 31 December 2017 and patients were monitored until August 2019. Fifty-five hospitalized patients were included in the analysis. They had 113 separate pulmonary events. Thirteen patients (23.6%) had a systemic autoimmune disease associated with MDS. Median age at diagnosis of MDS was 77 years. Median time to onset of pulmonary events was 13 months. Pulmonary events comprised: 70 infectious diseases (62%); 27 interstitial lung diseases (23.9%), including 13 non-specific interstitial pneumonias and seven secondary organizing pneumonias or respiratory bronchiolitis–interstitial lung diseases; 10 pleural effusions (8.8%), including four cases of chronic organizing pleuritis with exudative effusion; and six pulmonary hypertensions (5.3%). The median OS of the cohort was 29 months after MDS diagnosis but OS was only 10 months after a pulmonary event. The OS was similar to that of the general myelodysplastic population. However, the occurrence of a pulmonary event appeared to be either an accelerating factor of death or an indicator for the worsening of the underlying MDS in our study. More than a third of pulmonary events were non-infectious and could be systemic manifestations of MDS. Full article