Search

BackgroundPaediatric acute B-cell lymphoblastic leukaemia is the most common cancer of the paediatric age. Although the advancement of scientific and technological knowledge has ensured a huge step forward in the management of this disease, there are 15%–20% cases of recurrence leading to serious complications for the patient and sometimes even death. It is therefore necessary to identify new and increasingly personalised biomarkers capable of predicting the degree of risk of B-ALL in order to allow the correct management of paediatric leukaemia patients.MethodsStarting from our previously published results, we validate the expression level of LINC00958 in a cohort of 33 B-ALL and 9 T-ALL childhood patients, using in-silico public datasets as support. Expression levels of LINC00958 in B-ALL patients stratified by risk (high risk vs. standard/medium risk) and who relapsed 3 years after the first leukaemia diagnosis were also evaluated.ResultsWe identified the lncRNA LINC00958 as a biomarker of B-ALL, capable of discriminating B-ALL from T-ALL and healthy subjects. Furthermore, we associated LINC00958 expression levels with the disease risk classification (high risk and standard risk). Finally, we show that LINC00958 can be used as a predictor of relapses in patients who are usually stratified as standard risk and thus not always targeted for marrow transplantation.ConclusionsOur results open the way to new diagnostic perspectives that can be directly used in clinical practice for a better management of B-ALL paediatric patients.

Biliary endoprostheses are widely used in the treatment of biliary lithiasis, malignant and benign strictures, and occasionally in long-lasting biliary fistulas. They can be placed endoscopically during endoscopic retrograde cholangiopancreatography and radiologically (percutaneous) when the endoscopic route is not feasible. Complications associated with the endoscopic placement of biliary endoprostheses are well described in the literature, with migration being the most common. Intestinal obstruction is a rare complication associated with the migration of these devices. There are no reports in the literature of this complication occurring after percutaneous placement. We present a case of a patient who arrived at the emergency department with ileal obstruction secondary to the migration and concurrent embedding of a covered stent placed radiologically to treat a biliary leak after surgery. The patient underwent diagnostic laparoscopic and ileal resection, revealing a lithiasic concretion at the tip of the stent, causing the small bowel obstruction.

In the present work, synthetic slags (FeO-SiO2-CaO-P2O5-Al2O3-TiO2-V2O5 system) mimicking the composition of the slag inclusions of Ipanema were solidified at different cooling rates. FactSage software was used to calculate the slag’s phase equilibria from 500ºC to 1600°C to guide the microstructural characterisation. The samples solidified with slower cooling rates featured wüstite dendrites and a eutectic-like matrix, with intradendritic (Al,V,Ti)-containing iron spinel precipitates in the wüstite. The rapidly solidified slag showed refined wüstite dendrites surrounded by a Fe-O-Si-Ca-containing amorphous single-phase matrix without intradendritic (Al,V,Ti)-containing iron spinel precipitation. The comparison of the calculated phase diagram with the as-cast microstructures showed a few discrepancies. For instance, the FactSage’s database must be updated to consider the simultaneous solubility of Al, V and Ti in the thermodynamic description of the spinel phases, such as FToxid-SP-V, FToxid-SPINA, FToxid-TiSp and (FeO)2(TiO2)(s). Finally, the intradendritic precipitation of (Al,V,Ti)-containing iron spinel phases in the wüstite of the slag inclusions indicated that an Ipanema’s iron artefact was exposed to high service temperatures between 750 and 1050ºC.

Anemia in β-thalassemia is related to ineffective erythropoiesis and reduced red cell survival. Excess free heme and accumulation of unpaired α-globin chains impose substantial oxidative stress on β-thalassemic erythroblasts and erythrocytes, impacting cell metabolism. We hypothesized that increased pyruvate kinase activity induced by mitapivat (AG-348) in the Hbbth3/+ mouse model for β-thalassemia would reduce chronic hemolysis and ineffective erythropoiesis through stimulation of red cell glycolytic metabolism. Oral mitapivat administration ameliorated ineffective erythropoiesis and anemia in Hbbth3/+ mice. Increased ATP, reduced reactive oxygen species production, and reduced markers of mitochondrial dysfunction associated with improved mitochondrial clearance suggested enhanced metabolism following mitapivat administration in β-thalassemia. The amelioration of responsiveness to erythropoietin resulted in reduced soluble erythroferrone, increased liver Hamp expression, and diminished liver iron overload. Mitapivat reduced duodenal Dmt1 expression potentially by activating the pyruvate kinase M2-HIF2α axis, representing a mechanism additional to Hamp in controlling iron absorption and preventing β-thalassemia-related liver iron overload. In ex vivo studies on erythroid precursors from patients with β-thalassemia, mitapivat enhanced erythropoiesis, promoted erythroid maturation, and decreased apoptosis. Overall, pyruvate kinase activation as a treatment modality for β-thalassemia in preclinical model systems had multiple beneficial effects in the erythropoietic compartment and beyond, providing a strong scientific basis for further clinical trials.

Background: Acute small bowel obstruction (aSBO) is the most common cause (76%) of acute intestinal obstruction. Laparoscopy use is still controversial in aSBO and indications not yet clearly defined. The aim of this study was to demonstrate the effectiveness and safety of a laparoscopic approach in aSBO by using specific pre-operative criteria for appropriate patient selection. Methods: We retrospectively analyzed medical records of patients accepted at the Emergency Department for aSBO between January 2016 and March 2021 and performed a comparative analysis between types of treatment, considering demographics, clinical and radiological presentation, non-operative vs. operative management, intraoperative outcome, and postoperative course. We used a logistic regression to identify the variables related to surgical approach and built a predictive score upon the multivariable predictive model: the “SABO score”. Results: 198 patients were included in the study, of which 145 underwent surgery and 43 were successfully treated laparoscopically. Age and comorbidities were associated with open surgery (OR 3.2, 95% CI: 1.4–7.2, p = 0.006 and OR 2.7, 95% CI: 1.1–6.5, p = 0.023). A SABO score ≥ 0 identified an open approach with a sensitivity of 75.4% and a specificity of 69.8%. Conclusions: Laparoscopy is growing in importance even in emergency settings. Our analysis suggests that a laparoscopic approach can be safe and feasible in aSBO management. Correct patient selection appears to be the key for a successful minimally invasive approach. SABO score therefore could be helpful in choosing the correct surgical strategy for patients with aSBO.

Abstract Background Long non-coding RNAs are RNAs longer than 200 bps that do not encode any proteins and are able to alter gene expression by acting on different steps of regulation, including DNA methylation and chromatin structure. They represent a class of biomarkers of crescent interest in the hematologic and oncologic fields. Recent studies showed that the expression levels of specific lncRNAs correlate with the prognosis of paediatric patients with Acute Lymphoblastic Leukaemia. Methods We used NGS approaches to analyse the transcriptome of 9 childhood B-ALL patients and 6 childhood T-ALL patients, in comparison with B and T healthy lymphocytes from cord blood. We validate our findings both ex vivo, in a different cohort of 10 B-ALL and 10 T-ALL patients, and in silico using public datasets. Results We characterised the lncRNA landscape for B-ALL, T-ALL, healthy B, and T cell progenitors. From the characterised signature, we selected candidate lncRNAs able to discriminate not only B-ALL and T-ALL from healthy subjects but also between the two types of leukaemia, and subsequently validated their potential as a diagnostic tool in an additional cohort of paediatric patients. We confirmed our finding with open access transcriptomic data, comparing ALL lncRNAs with AML lncRNA landscape as well. Finally, expression correlation analyses of T-ALL selected lncRNA biomarkers suggested a possible role in lymphocyte activation and the β-catenin signalling pathway for AC247036.1 and involvement in hedgehog signalling for HHIP-AS1. Conclusions Our work identified a lncRNA signature discriminating paediatric B-ALL and T-ALL from healthy subjects, between them and from AML. This study provides the keystone to future clinical studies determining the theragnostic value of the characterised long non coding transcriptome panorama in a clinical setting for childhood patient management.

(1) Background: Preeclampsia (PE) usually presents with hypertension and proteinuria, related to poor placentation. Reduced maternal–fetal immunological tolerance is a possible trigger of inadequate placentation. Aberrant antigen expression of HLA-DR has been observed in the syncytiotrophoblast of PE patients. In this study, we analyzed plasma levels of Human Leukocyte Antigen (HLA)-DR+ syncytiotrophoblast-derived extracellular vesicles (STEVs) during the three trimesters of pregnancy in relation to PE onset. (2) Methods: Pregnant women underwent venous blood sampling during the three trimesters. STEVs were collected from plasma via ultracentrifugation (120,000 g) and characterized by Western blot, nanotracking analysis and flow cytometry for the expression of Placental Alkaline Phosphatase (PLAP), a placental-derived marker, and HLA-DR. (3) Results: Out of 107 women recruited, 10 developed PE. STEVs were detected in all three trimesters of pregnancy with a zenith in the second trimester. A significant difference was found between the non-PE and PE groups in terms of plasma levels of HLA-DR+ STEVs during all three trimesters of pregnancy. (4) Conclusions: More research is needed to investigate HLA-DR+ as a potential early marker of PE.

The prevalence of mitral (MR) and tricuspid regurgitation (TR), especially in heart failure (HF) populations, is high. However, the distinct role of atrioventricular valve diseases in HF, whether they are merely indicators of disease status or rather independent contributors in a vicious disease cycle, is still not fully understood. For decades, tricuspid regurgitation (TR) was considered an innocent bystander subsequent to other heart or lung pathologies, thus, not needing dedicated treatment. Recent increasing awareness towards the role of atrioventricular valve diseases has revealed that MR and TR are, in fact, independent predictors of outcome in HF, thus, warranting attention in the HF treatment algorithm. This awareness arose, especially, with the development of minimally invasive transcatheter solutions providing new treatment options, which can also be used for patients considered as having increased surgical risk. However, outcomes of such transcatheter treatments have, in part, been sub-optimal and likely influenced by the status of the concomitant HF disease. Thus, this review aims to summarize data on the current understanding regarding the role of MR and TR in HF, how HF impacts outcomes of transcatheter MR and TR interventions, and how the understanding of this relationship might help to identify patients that benefit most from these therapies, which have proven to be lifesaving in properly selected candidates.

Over the past few years, transcatheter aortic valve implantation (TAVI) imposed itself as the first-choice therapy for symptomatic aortic stenosis (AS) in elderly patients at surgical risk. There have been continuous technological advancements in the latest iterations of TAVI devices and implantation techniques, which have bolstered their adoption. Moreover, the favorable outcomes coming out from clinical trials represent an indisputable point of strength for TAVI. As indications for transcatheter therapies now include a low surgical risk and younger individuals, new challenges are emerging. In this context, the matter of prosthesis durability is noteworthy. Initial evidence is beginning to emerge from the studies in the field, but they are still limited and compromised by multiple biases. Additionally, the physiopathological mechanisms behind the valve's deterioration are nowadays somewhat clearer and classified. So, who outlasts who—the valve or the patient? This review aims to explore the available evidence surrounding this intriguing question, examining the various factors affecting prosthesis durability and discussing its potential implications for clinical management and current interventional practice. [ABSTRACT FROM AUTHOR]

Lung ultrasound has been recognized as a valid imaging method for diagnosing and monitoring COVID-19 pneumonia in pregnant women. The present review aimed to summarize the main findings reported in the literature and international guidelines on the role of lung ultrasound in the care of pregnant women affected by COVID-19. A search strategy was developed and applied to PubMed, Scopus, Web of Science and EMBASE to identify previous papers reporting the utility of ultrasound in diagnosing and monitoring COVID-19 pneumonia. The search retrieved 369 articles and 23 of these were selected for analysis. The articles mainly focused on the definition of the procedure, development of training programs for obstetricians managing pregnant women with suspicion of COVID-19 and definition of scoring systems. The clinical applications of lung ultrasound in this setting have also been described. This review could encourage obstetricians to learn lung ultrasound to use during critical events like a pandemic.