Hematological Neoplasms with Eosinophilia.

Eosinophils in peripheral blood account for 0.3-5% of leukocytes, which is equivalent to 0.05-0.5 × 109/L. A count above 0.5 × 109/L is considered to indicate eosinophilia, while a count equal to or above 1.5 × 109/L is defined as hypereosinophilia. In bone marrow aspirate, eosinophilia is considered when eosinophils make up more than 6% of the total nuclear cells. In daily clinical practice, the most common causes of reactive eosinophilia are non-hematologic, whether they are non-neoplastic (allergic diseases, drugs, infections, or immunological diseases) or neoplastic (solid tumors). Eosinophilia that is associated with a hematological malignancy may be reactive or secondary to the production of eosinophilopoietic cytokines, and this is mainly seen in lymphoid neoplasms (Hodgkin lymphoma, mature T-cell neoplasms, lymphocytic variant of hypereosinophilic syndrome, and B-acute lymphoblastic leukemia/lymphoma). Eosinophilia that is associated with a hematological malignancy may also be neoplastic or primary, derived from the malignant clone, usually in myeloid neoplasms or with its origin in stem cells (myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions, acute myeloid leukemia with core binding factor translocations, mastocytosis, myeloproliferative neoplasms, myelodysplastic/myeloproliferative neoplasms, and myelodysplastic neoplasms). There are no concrete data in standardized cytological and cytometric procedures that could predict whether eosinophilia is reactive or clonal. The verification is usually indirect, based on the categorization of the accompanying hematologic malignancy. This review focuses on the broad differential diagnosis of hematological malignancies with eosinophilia.

Reassessment of the electrical connection between the pulmonary veins and the left atrium: A study to determine the different contributions of myocardial fibers along the standard ablation circumference.

Background: Circumferential ablation around the ipsilateral pulmonary veins (PVs) is the standard strategy for atrial fibrillation ablation. The present study seeks to assess which regions of the standard ablation circumference are the main contributors to the venoatrial electrical connection. Methods: A total of 41 patients were included under a specific atrial fibrillation ablation protocol in which the anterior and posterior segments of the standard circumference, between the equatorial line of the superior and the inferior ipsilateral PVs, were ablated first. If PV isolation was not achieved, ablation was extended superiorly or inferiorly, on the basis of the earliest atrial activation recorded during pacing from inside the PV. Complete PV isolation and the length of the areas not requiring ablation (ANRA) at the time of electrical isolation were evaluated. Results: Ablation of the anterior and posterior segments of the standard circumference led to the isolation of 77% left-PV pairs and 51% right-PV pairs (p = 0,015). A superior extension was required in 23% left-PV pairs and in 46% right-PV pairs, while an inferior extension was required only in 10% left-PV pairs and in 11% right-PV pairs. PV isolation was achieved before completing the standard ablation circumference in 97% left-PV pairs and in 94% right-PV pairs, with a median ANRA of 36.9 (IQR: 30.9-42.1) mm in the left PVs [16.0 (IQR: 12.0-19.0) mm superior and 18.8 (IQR: 16.1-24.9) mm inferior, p < 0.01] and 36.9 (IQR: 30.2-41.0) mm in the right PVs [15.1 (IQR: 10.7-19.1) mm superior and 20.6 (IQR: 16.9-23.3) mm inferior, p < 0.01]. Conclusions: The myocardial fibers along the anterior and posterior regions of the standard ablation circumference are the main contributors to the electrical connection between the pulmonary veins and the left atrium. Ablation of these regions results in PV isolation in the majority of patients.

Prognostic Value of Measurable Residual Disease in Patients with AML Undergoing HSCT: A Multicenter Study.

Allogeneic hematopoietic stem cell transplantation (HSCT) represents the best therapeutic option for many patients with acute myeloid leukemia (AML). However, relapse remains the main cause of mortality after transplantation. The detection of measurable residual disease (MRD) by multiparameter flow cytometry (MFC) in AML, before and after HSCT, has been described as a powerful predictor of outcome. Nevertheless, multicenter and standardized studies are lacking. A retrospective analysis was performed, including 295 AML patients undergoing HSCT in 4 centers that worked according to recommendations from the Euroflow consortium. Among patients in complete remission (CR), MRD levels prior to transplantation significantly influenced outcomes, with overall (OS) and leukemia free survival (LFS) at 2 years of 76.7% and 67.6% for MRD-negative patients, 68.5% and 49.7% for MRD-low patients (MRD < 0.1), and 50.5% and 36.6% for MRD-high patients (MRD ≥ 0.1) (p < 0.001), respectively. MRD level did influence the outcome, irrespective of the conditioning regimen. In our patient cohort, positive MRD on day +100 after transplantation was associated with an extremely poor prognosis, with a cumulative incidence of relapse of 93.3%. In conclusion, our multicenter study confirms the prognostic value of MRD performed in accordance with standardized recommendations.

Cardiovascular disease in women: Do we need new diagnostic and therapeutic strategies?

Cardiovascular disease (CVD) is the leading cause of death worldwide affecting both sexes equally. However, in comparison to men, in women, it often is underrecognized and undertreated in both primary and secondary prevention settings. It is clear, that in the healthy population, there are profound differences both anatomically and biochemically between women and men, and this may impact how both groups present when they become ill. Moreover, some diseases affect more frequently women than men such as myocardial ischemia or infarction without obstructive coronary disease, Takotsubo syndrome, some atrial arrhythmias, or heart failure with preserved ejection fraction. Therefore, diagnostic and therapeutic strategies that have been established largely on the basis of clinical studies with a predominantly male population must be adapted before being applied to women. There is a paucity of data regarding cardiovascular disease in women. It is inadequate to only perform a subgroup analysis evaluating a specific treatment or invasive technique when women constitute fifty percent of the population. In this regard, this may affect the time of clinical diagnosis and severity assessments of some valvulopathies. In this review, we will focus on the differences in the diagnosis, management, and outcomes for women with the most frequent cardiovascular pathologies including coronary artery disease, arrhythmia, heart failure, and valvopathies. In addition, we will describe diseases that exclusively affect women that are related to pregnancy, and some of them are life-threatening. Although the lack of research on women plays a role in the poorer outcomes in women, especially in ischemic heart disease, some techniques such as transcatheter aortic valve implantation and transcatheter edge-to-edge therapy seem to have better outcomes in women.

Prevalence and Risk for Bundle Branch Block, Atrioventricular Block and Pacemaker Implantation in Spondyloarthritis. A Systematic Review of the Literature.

Objective: To evaluate the evidence regarding the prevalence and risk of bundle branch block (BBB), atrioventricular block (AVB) and pacemaker implantation (PMI) in patients with spondyloarthritis compared to a control group without spondyloarthritis. Methods: A systematic review of the literature was performed using Pubmed (Medline), EMBASE (Elsevier) and Cochrane Library (Wiley) databases until December 2021. The prevalence and risk for AVB, BBB and PMI were analyzed. Cohort, case control and cross-sectional studies in patients ≥18 years meeting the classification criteria for spondyloarthritis were included. The Odds ratio (OR), risk ratio (RR), or Hazard ratio (HR) and prevalence difference were considered as outcomes. Data was synthesized in a previously defined extraction form which included a risk of bias assessment using the Newcastle-Ottawa Scale. Results: In total, eight out of 374 studies were included. None of the studies provided results regarding the risk of low grade AVB and BBB in SpA patients. Only indirect results comparing prevalences from low to medium quality studies were found. According to population based registries, the sex and age adjusted HR of AVB was 2.3 (95% CI 1.6-3.3) in ankylosing spondylitis, 2.9 (95% CI 1.8-4.7) in undifferentiated spondyloarthritis and 1.5 (95% CI 1.1 a 1.9) in psoriatic arthritis. The absolute risk for AVB was 0.4% (moderate to high; 95% CI 0.34%-0.69%) for AS, 0.33% (moderate to high; 95% CI 0.21%-0.53%) for uSpA and 0.34% (moderate to high; 95% CI 0.26%-0.45%) for PsA.The RR for PMI in AS patients was 1.3 (95% CI 1.16-1.46) for groups aged between 65 and 69 years, 1.33 (95% CI 1.22-1.44) for 70-75 years, 1.24 (95% CI 1.55-1.33) for 75-79 years and 1.11 (95% CI 1.06-1.17) for groups older than 80 years. The absolute risk for PMI in AS patients was 0.7% (moderate to high risk; 95% CI 0.6-0.8%) for groups aged between 65-69, 1.44% (high risk; 95% CI 1.33-1.6%) for 70-75 years, 2.09% (high risk; 95% CI 2.0-2.2%) for 75-79 years and 4.15% (high risk; 95% CI 4.0-4.3%) for groups older than 80 years. Conclusions: Very few cases of low grade AVB and BBB were observed in observational studies. No study evaluated association measures for low grade AVB and BBB but the differences of prevalence were similar in SpA and control groups even though studies lacked the power to detect statistical differences. According to population based registries there was an approximately two fold-increased risk of high grade AVB in SpA patients. RR for PMI was higher in younger age groups.

Brain-Derived Neurotrophic Factor Levels in Cord Blood from Growth Restricted Fetuses with Doppler Alteration Compared to Adequate for Gestational Age Fetuses.

Background and Objectives: Fetal growth restriction (FGR) is a severe obstetric disease characterized by a low fetal size entailing a set of undesired consequences. For instance, previous studies have noticed a worrisome association between FGR with an abnormal neurodevelopment. However, the precise link between FGR and neurodevelopmental alterations are not yet fully understood yet. Brain-derived neurotrophic factor (BDNF) is a critical neurotrophin strongly implicated in neurodevelopmental and other neurological processes. In addition, serum levels of BDNF appears to be an interesting indicator of pathological pregnancies, being correlated with the neonatal brain levels. Therefore, the aim of this study is to analyze the blood levels of BDNF in the cord blood from fetuses with FGR in comparison to those with weight appropriate for gestational age (AGA). Materials and Methods: In this study, 130 subjects were recruited: 91 in group A (AGA fetuses); 39 in group B (16 FGR fetuses with exclusively middle cerebral artery (MCA) pulsatility index (PI) < 5th percentile and 23 with umbilical artery (UA) PI > 95th percentile). Serum levels of BDNF were determined through ELISA reactions in these groups. Results: Our results show a significant decrease in cord blood levels of BDNF in FGR and more prominently in those with UA PI >95th percentile in comparison to AGA. FGR fetuses with exclusively decreased MCA PI below the 5th percentile also show reduced levels of BDNF than AGA, although this difference was not statistically significant. Conclusions: Overall, our study reports a potential pathophysiological link between reduced levels of BDNF and neurodevelopmental alterations in fetuses with FGR. However, further studies should be conducted in those FGR subjects with MCA PI < 5th percentile in order to understand the possible implications of BDNF in this group.

Determinants of fibrotic atrial cardiomyopathy in atrial fibrillation. A multicenter observational study of the RETAC (reseau européen de traîtement d'arrhythmies cardiaques)-group.

AIMS: Despite advances in interventional treatment strategies, atrial fibrillation (AF) remains associated with significant morbidity and mortality. Fibrotic atrial myopathy (FAM) is a main factor for adverse outcomes of AF-ablation, but complex to diagnose using current methods. We aimed to derive a scoring system based entirely on easily available clinical parameters to predict FAM and ablation-success in everyday care. METHODS: In this multicenter, prospective study, a new risk stratification model termed AF-SCORE was derived in 220 patients undergoing high-density left-atrial(LA) voltage-mapping to quantify FAM. AF-SCORE was validated for FAM in an external mapping-validation cohort (n = 220) and for success following pulmonary vein isolation (PVI)-only (without adjunctive left- or right atrial ablations) in an external outcome-validation cohort (n = 518). RESULTS: FAM was rare in patients < 60 years (5.4%), but increased with ageing and affected 40.4% (59/146) of patients ≥ 60 years. Sex and AF-phenotype had additional predictive value in older patients and remained associated with FAM in multivariate models (odds ratio [OR] 6.194, p < 0.0001 for ≥ 60 years; OR 2.863, p < 0.0001 for female sex; OR 41.309, p < 0.0001 for AF-persistency). Additional clinical or diagnostic variables did not improve the model. AF-SCORE (+ 1 point for age ≥ 60 years and additional points for female sex [+ 1] and AF-persistency [+ 2]) showed good discrimination to detect FAM (c-statistic 0.792) and predicted arrhythmia-freedom following PVI (74.3%, 54.7% and 45.5% for AF-SCORE ≤ 2, 3 and 4, respectively, and hazard ratio [HR] 1.994 for AF-SCORE = 3 and HR 2.866 for AF-SCORE = 4, p < 0.001). CONCLUSIONS: Age, sex and AF-phenotype are the main determinants for the development of FAM. A low AF-SCORE ≤ 2 is found in paroxysmal AF-patients of any age and younger patients with persistent AF irrespective of sex, and associated with favorable outcomes of PVI-only. Freedom from arrhythmia remains unsatisfactory with AF-SCORE ≥ 3 as found in older patients, particularly females, with persistent AF, and future studies investigating adjunctive atrial ablations to PVI-only should focus on these groups of patients.

Maternal Perinatal Characteristics in Patients with Severe Preeclampsia: A Case-Control Nested Cohort Study.

Preeclampsia is one of the most worrisome complications during pregnancy, affecting approximately 1 out of 20 women worldwide. Preeclampsia is mainly characterized by a sustained hypertension, proteinuria, also involving a significant organ dysfunction. Moreover, 25% of the cases could be classified as severe preeclampsia (SP), a serious condition that could be life-threatening for both the mother and fetus. Although there are many studies focusing on preeclampsia, less efforts have been made in SP, frequently limited to some specific situations. Thus, the present study aims to conduct a comparative analysis of risk factors, maternal characteristics, obstetric and neonatal outcomes and maternal complications in patients with severe preeclampsia versus patients without severe preeclampsia. Hence, 235 cases and 470 controls were evaluated and followed in our study. We described a set of variables related to the development of severe preeclampsia, including maternal age > 35 years (69.8%), gestational (26.8%) or chronic arterial hypertension (18.3%), obesity (22.6%), use of assisted reproduction techniques (12.3%), prior history of preeclampsia (10.2%) and chronic kidney disease (7.7%) All patients had severe hypertension (>160 mmHg) and some of them presented with additional complications, such as acute renal failure (51 cases), HELLP syndrome (22 cases), eclampsia (9 cases) and acute cerebrovascular accidents (3 cases). No case of maternal death was recorded, although the SP group had a higher cesarean section rate than the control group (60% vs. 20.9%) (p < 0.001), and there was a notably higher perinatal morbidity and mortality in these patients, who had a prematurity rate of 58.3% (p < 0.001) and 14 perinatal deaths, compared to 1 in the control group. Overall, our study recognized a series of factors related to the development of SP and related complications, which may be of great aid for improving the clinical management of this condition.

Influence of the Human Development Index on the Maternal-Perinatal Morbidity and Mortality of Pregnant Women with SARS-CoV-2 Infection: Importance for Personalized Medical Care.

Coronavirus disease-19 (COVID-19) is perhaps the most worrisome pandemic in the 21st century, having entailed devastating consequences for the whole society during the last year. Different studies have displayed an existing association between pregnancy and COVID-19 severity due to the various physiological changes that occur during gestation. Recent data identified maternal country of origin as an important determinant of COVID-19 presentation in pregnant women. However, the explanation of this fact remains to be fully elucidated. Therefore, the purpose of this work is to analyze the possible relationship between Human Development Index (HDI) of maternal country of origin with the morbimortality of pregnant women and their newborns. Here, we conducted a multicentric, ambispective, observational case-control study (1:1 ratio) and compare with the HDI of each country (group 1-very high HDI, group 2-high HDI, group 3-medium HDI, and group 4-low HDI). In total, 1347 pregnant women with confirmed SARV-CoV-2 infection (cases) were enrolled, and each was paired with one control to give a total number of 2694 participants from 81 tertiary care centers. Among the women with SARS-CoV-2 infection, more cases were produced of perinatal mortality, overall maternal morbidity, COVID-19 maternal morbidity, C-sections, hypertensive maternal morbidity, and perinatal morbidity. Our results described an inverse association between HDI and maternofetal morbidity and mortality. Moreover, the countries with an HDI lower than 1 showed higher rates of patients with maternal COVID-19-related morbidity (6.0% vs. 2.4%, p < 0.001), a need for oxygen therapy (4.7% vs. 1.8%, p < 0.001), and maternal ICU admission (2.6% vs. 1.0%, p = 0.007). Compared to other risk factors such as overweight, obesity, preexisting and obstetric comorbidities, HDI emerged as an independent risk factor explaining much of the increased maternal-perinatal morbidity and mortality detected in our group of cases. Further research is needed to establish to confirm the real impact of this factor and its components on pregnancy outcomes.

Comparing Infection Profiles of Expectant Mothers with COVID-19 and Impacts on Maternal and Perinatal Outcomes between the First Two Waves of the Pandemic.

During 2020, Coronavirus Disease-19 (COVID-19) incidence fluctuated in two clear waves across the spring and autumn periods. This study was designed to compare the maternal and perinatal clinical outcomes in obstetrics patients with COVID-19 between the two waves of infection in Spain. We conducted an observational, analytical, ambispective cohort study with longitudinal follow-up of mothers with confirmed SARV-CoV-2 infection from different hospitals in our country between March-November 2020. We recruited 1295 pregnant women with SARS-CoV2 infection from 78 hospitals, 846 (65.3%) of whom were diagnosed during the first wave and 449 (34.7%) during the second wave. Our results show that patients developing COVID-19 during the first wave had more symptoms at triage, early in pregnancy with greater rates of COVID-19-related maternal morbidity; caesarean section and preterm birth in the first wave. We register two cases of maternal mortality and only during the first wave. Maternal morbidity events showed a strong link to perinatal mortality events in the first wave compared to the second wave, in which maternal morbidity was more associated with pneumonia. Likewise, maternal morbidity showed a strong correlation with perinatal morbidity events in both waves. We describe the differences between the patients' profiles and management between the two waves and related to maternal and perinatal outcomes. Differences were also observed in the management of pregnant women with COVID-19. Thus, there were fewer caesarean sections, and maternal and perinatal morbidity events were reduced in the second wave, while the impacts of respiratory symptoms and their severity, including a greater need for maternal treatment, were greater in this last period. Identifying the impact that changes in the profile as well as in the treatment have on maternal-perinatal morbidity and mortality will help improve the well-being of our patients and their newborns.

Influence of Cerebral Vasodilation on Blood Reelin Levels in Growth Restricted Fetuses.

Fetal growth restriction (FGR) is one of the most important obstetric pathologies. It is frequently caused by placental insufficiency. Previous studies have shown a relationship between FGR and impaired new-born neurodevelopment, although the molecular mechanisms involved in this association have not yet been completely clarified. Reelin is an extracellular matrix glycoprotein involved in development of neocortex, hippocampus, cerebellum and spinal cord. Reelin has been demonstrated to play a key role in regulating perinatal neurodevelopment and to contribute to the emergence and development of various psychiatric pathologies, and its levels are highly influenced by pathological conditions of hypoxia. The purpose of this article is to study whether reelin levels in new-borns vary as a function of severity of fetal growth restriction by gestational age and sex. We sub-grouped fetuses in: normal weight group (Group 1, n = 17), FGR group with normal umbilical artery Doppler and cerebral redistribution at middle cerebral artery Doppler (Group 2, n = 9), and FGR with abnormal umbilical artery Doppler (Group 3, n = 8). Our results show a significant association of elevated Reelin levels in FGR fetuses with cerebral blood redistribution compared to the normal weight group and the FGR with abnormal umbilical artery group. Future research should focus on further expanding the knowledge of the relationship of reelin and its regulated products with neurodevelopment impairment in new-borns with FGR and should include larger and more homogeneous samples and the combined use of different in vivo techniques in neonates with impaired growth during their different adaptive phases.