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2.
HemaSphere ; 6:1395-1396, 2022.
Article in English | EMBASE | ID: covidwho-2032168

ABSTRACT

Background: Persistent cytopenia due to poor graft function (PGF) is a life-threatening complication in patients undergoing allogeneic HSCT (allo-HSCT). Several therapeutic approaches have been tested in this subset of patients with poor clinical results. Aims: The objective of this multicenter open-label interventional prospective phase II Novartis study (ELTION, ClinicalTrials.gov id: NCT03718533), was to analyze efficacy and safety of EPAG in patients with post-allo-HSCT poor graft function. Methods: Adult patients diagnosed with PGF (defined as severe cytopenia after day +30 post-transplant, with two or more of the following: platelets <20000/μL-mandatory-, ANC <1000/μL, hemoglobin< 10 g/dL), and full donor chimerism, were eligible to enter the trial. Study treatment consisted of EPAG. at 150 mg/day administered up to 36 weeks;dose adjustments were contemplated as per protocol on an individual basis. The primary efficacy endpoint was the overall hematologic response (partial and complete), as determined by platelet, hemoglobin and neutrophil counts by 16 weeks after the initiation of EPAG. Results: Although the aim of the study was to include 33 patients, recruitment stopped prematurely due to the difficulties for hospital visits posed during COVID-19 pandemic, and eventually only 10 patients were included. The decision for this premature termination is not related to any safety concern related to the drug. Patient characteristics are shown in the table 1 attached below. At EPAG. initiation, all 10 patients showed thrombocytopenia (<20000/μcL), 5 presented with anemia (Hgb <10 g/dL), and 4 had neutropenia (ANC <1000/μcL). Four patients discontinued EPAG before week 12 due to: disease progression/relapse (2 patients), protocol deviation (1 patient), and CMV infection (1 patient). In none of the cases, the event was related to study drug. At week 16, 4 patients (4/10, 40%) and at week 24, 5 patients, showed improvement in at least one of the 3 hematologic cell lines (partial response), respectively. Counts pre-and post-EPAG and global response in patients who stayed on treatment > 12 weeks are displayed below: Image: Summary/Conclusion: In our experience, EPAG worked well in subjects with PGF, an otherwise life-threatening condition for patients, and its use at 150 mg/day is safe and well tolerated in this setting. Our data suggest that eltrombopag might improve hematologic cell counts in patients with PGF, especially in those patients who remained on treatment at week 24, however further research is warranted to extend its applicability for larger cohorts.

3.
J Clin Med ; 11(16)2022 Aug 11.
Article in English | MEDLINE | ID: covidwho-2023784

ABSTRACT

Hereditary hemorrhagic telangiectasia (HHT), or Rendu-Osler-Weber syndrome, is a dominantly inheritable rare disease with a prevalence of 1:5000-10,000 inhabitants [...].

4.
European Neuropsychopharmacology ; 40:S201-S202, 2020.
Article in English | EMBASE | ID: covidwho-987690

ABSTRACT

Background: Epigenetic mechanisms can play a key role in the pathogenesis of depression and its treatment. Specifically, changes in histone acetylation mediated by HDAC5 and SIRT2 can regulate the transcription of genes related to different functions such as brain plasticity [1]. Previous studies in peripheral blood mononuclear cells (PBMCs) [2] and prefrontal cortex (PFC) in patients and murine models show that depressive phenotype is associated with an increase of HDAC5 and SIRT2. On the other hand, Sirt2 and Hdac5 RNAm are decreased by chronic antidepressant treatment [3]. Moreover, drugs that work by inducing an increase in norepinephrine in the synapse, are able to phosphorylate HDAC5 causing a migration from nucleus to cytoplasm and therefore, the enzyme would lose its deacetylase function [3,4,5]. Objectives: To evaluate if HDAC5 and SIRT2 in PBMCs could be peripheral markers for depressive state or antidepressant treatment. More specifically, we would like to discover if major depression illness has a determinant effect in the nucleocytoplasmic distribution of HDAC5 and SIRT2, and also if these features can influence in the phosphorylation capacity of HDAC5 by duloxetine and some adrenergic and serotonergic agonists. Sex and age factors will be also studied. At transcriptional level, we would like to know how depressive state and antidepressant therapy could regulate the expression of genes that are related to HDAC5 and SIRT2 function, as those related to neuroplasticity, angiogenesis and inflammation (Bdnf, Vegf, eNOS, KLF-2, FOXP3, CTLA-3, PD-1). Sex and age factors will be also studied. Methods: Depressive patients (Montgomery-Asberg>=20) and healthy volunteers (MAsberg<7) were recruited by psychiatrists from different hospitals and health care centres. 20 ml of blood were extracted in order to obtain PBMCs (classic, intermediate and non-classic monocytes and T-cells) using Ficoll-paque followed by FACs. Isolated cells were used for culture and immunofluorescence and for RNAm extraction for PCR. Nucleocytoplasmic distribution of SIRT2 and HDAC5 was measured by confocal microscopy, and a ratio of mean intensities between cytoplasm and nucleus was calculated. However, the effect of in vitro treatments were analysed by fluorescence microscopy, looking at the intensity of HDAC5 phosphorylation. Results: Depressed patients showed a lower ratio (cytoplasm/nucleus) for SIRT2 in classic and intermediate monocytes as well as in T-cells, compared to healthy volunteers. In addition, looking at the HDAC5 phosphorylation in monocytes and T-cell cultures induced by the antidepressant duloxetine in vitro, it was observed that depressed patients showed a lower response compared to healthy volunteers. Regarding age and sex factors, female healthy volunteers between 40 and 50 years old showed a lower ratio (cytoplasm/nucleus) for HDAC5 compared to the young, between 20 and 30 years old, and old (between 65 and 80 years old) healthy volunteers. Gene expression studies are on course and hopefully they will be finished after Covid19 crisis and before the congress. Conclusion. It seems that HDAC5 and SIRT2 in monocytes and T-cells could be suitable peripheral biomarkers for depressive state or for evaluating treatment efficacy. These results might also suggest that age and sex are determinant factors. No conflict of interest

5.
Rev Esp Anestesiol Reanim (Engl Ed) ; 67(9): 511-515, 2020 Nov.
Article in English, Spanish | MEDLINE | ID: covidwho-842508

ABSTRACT

We describe the case of a 24-year-old pregnant woman with no history of note who was admitted with a diagnosis of bilateral pneumonia caused by the new coronavirus. Due to clinical worsening, she required urgent cesarean section with general anaesthesia and intubation for decubitus intolerance. After extubation, she presented altered mental state that required a differential diagnosis of encephalitis/meningitis secondary to SARS-CoV-2. CT and CT-angiography were normal, spinal fluid tests were non-specific, and magnetic resonance imaging reported posterior reversible encephalopathy syndrome (PRES) (due to radiological features suggestive of white matter vasogenic edema affecting the parietal, temporal and occipital lobes, along with altered mental state) secondary to gestational hypertension. Eleven days after the cesarean section the patient began to develop hypertension that required treatment. PRES is associated with certain clinical (headache, altered mental state, visual disturbances and convulsions) and radiological (reversible changes in white substance mainly affecting the parietal, temporal, and occipital lobes) characteristics suggestive of vasogenic oedema In pregnant SARS-CoV-2 patients, the differential diagnosis of hypertension and altered mental state is often extremely complicated because complementary tests can be normal and there is no immediate sign of peripartum hypertension. SARS-CoV-2 genome sequencing in spinal fluid could have provided a definitive diagnosis, but the treatment would not have differed.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Pneumonia, Viral/complications , Posterior Leukoencephalopathy Syndrome/etiology , Pregnancy Complications, Infectious , Puerperal Disorders/etiology , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Consciousness Disorders/diagnostic imaging , Consciousness Disorders/etiology , Coronavirus Infections/diagnosis , Coronavirus Infections/diagnostic imaging , Diagnosis, Differential , Female , Humans , Magnetic Resonance Imaging , Pandemics , Pneumonia, Viral/diagnostic imaging , Posterior Leukoencephalopathy Syndrome/diagnostic imaging , Pregnancy , Puerperal Disorders/diagnostic imaging , SARS-CoV-2 , Young Adult
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