Variazioni dell'acqua extravascolare polmonare (EVLW) valutati con l'ecografia toracica in corso di terapia renale sostitutiva (CRRT) in UTI

Questo studio clinico osservazionale, ha come obiettivo quello di stabilire se c'è una correlazione, e se è quantificabile, tra il volume di liquidi rimossi con le terapie renali sostitutive continue (CRRT) e lo stato di imbibizione dell'interstizio polmonare, nei pazienti critici, servendosi del monitoraggio ecografico pleuropolmonare che mette in risalto i movimenti dell'acqua extravascolare (EVLW) tramite la presenza o l'assenza di Blines. Lo scopo è quello di stabilire se la scomparsa delle linee B può essere utilizzato come segno precoce di miglioramento del quadro clinico oltre le attuali valutazioni cliniche e laboratoristiche, al fine di supportare e migliorare la gestione delle CRRT e le terapie infusionali. Molte sono le cause che possono ridurre la sopravvivenza di un paziente in terapia intensiva in quanto molteplici sono le comorbidità che possono occorrere. Compito del Medico Anestesista Rianimatore è quello di prevenire l'inesorabile discesa verso una condizione clinica dal quale è difficile poi tornare indietro, partendo da una tempestiva e corretta impostazione dell'algoritmo diagnostico, che subirà modifiche in corso, ma che ha una base solida per poter iniziare altrettanto rapidamente le terapie del caso. Questo studio, insieme a molti altri in letteratura, ha lo scopo di fornire le prove sulla effettiva validità di uno strumento di rapida esecuzione, accessibile a molti in quanto di facile utilizzo e apprendimento, non invasivo, e soprattutto con costi molto contenuti, che si può integrare ulteriormente nell'algoritmo diagnostico, risultando un potente sussidio per la terapia intensiva. Benché allo stato attuale dell'arte non si trovino protocolli condivisi, quello che si è verificato in questo studio, è che le condizioni cliniche sono migliorate nella totalità dei casi a seguito della riduzione dell'EVLW, ma soprattutto che l'ecografia è stata statisticamente significativa nel rivelarlo

Aberrant BLM cytoplasmic expressionassociates with DNA damage stress and hypersensitivity to DNA-damaging agents in colorectal cancer

Background Bloom syndrome is a rare and recessive disorder characterized by loss-of-function mutations of the BLM gene, which encodes a RecQ 30–50 DNA helicase. Despite its putative tumor suppressor function, the contribution of BLM to human sporadic colorectal cancer (CRC) remains poorly understood. Methods The transcriptional regulation mechanism underlying BLM and related DNA damage response regulation in independent CRC subsets and a panel of derived cell lines was investigated by bioinformatics analysis, the transcriptomic profile, a CpG island promoter methylation assay, Western blot, and an immunolocalization assay. Results In silico analysis of gene expression data sets revealed that BLM is overexpressed in poorly differentiated CRC and exhibits a close connection with shorter relapsefree survival even after adjustment for prognostic factors and pathways that respond to DNA damage response through ataxia telangiectasia mutated (ATM) signaling. Functional characterization demonstrated that CpG island promoter hypomethylation increases BLM expression and associates with cytoplasmic BLM mislocalization and increased DNA damage response both in clinical CRC samples and in derived cancer cell lines. The DNA-damaging agent S-adenosylmethionine suppresses BLM expression, leading to the inhibition of cell growth following accumulation of DNA damage. In tumor specimens, cytoplasmic accumulation of BLM correlates with DNA damage and cH2AX and phosphorylated ATM foci and predicts long-term progression-free survival in metastatic patients treated with irinotecan. Conclusions Taken together, the findings of this study provide the first evidence that cancer-linked DNA hypomethylation and cytosolic BLM mislocalization might reflect compromised levels of DNA-repair activity and enhanced hypersensitivity to DNA-damaging agents in CRC patients

Emergency contraception: unresolved clinical, ethical and legal quandaries still linger

Emergency contraception (EC) has been prescribed for decades, in order to lessen the risk of unplanned and unwanted pregnancy following unprotected intercourse, ordinary contraceptive failure, or rape. EC and the linked aspect of unintended pregnancy undoubtedly constitute highly relevant public health issues, in that they involve women's self-determination, reproductive freedom and family planning. Most European countries regulate EC access quite effectively, with solid information campaigns and supply mechanisms, based on various recommendations from international institutions herein examined. However, there is still disagreement on whether EC drugs should be available without a physician's prescription and on the reimbursement policies that should be implemented. In addition, the rights of health care professionals who object to EC on conscience grounds have been subject to considerable legal and ethical scrutiny, in light of their potential to damage patients who need EC drugs in a timely fashion. Ultimately, reproductive health, freedom and conscience-based refusal on the part of operators are elements that have proven extremely hard to reconcile; hence, it is essential to strike a reasonable balance for the sake of everyone's rights and well-being

An exploration of the potential utility of fetal cardiovascular MRI as an adjunct to fetal echocardiography

Objectives: Fetal cardiovascular magnetic resonance imaging (MRI) offers a potential alternative to echocardiography, although in practice, its use has been limited. We sought to explore the need for additional imaging in a tertiary fetal cardiology unit and the usefulness of standard MRI sequences. Methods: Cases where the diagnosis was not fully resolved using echocardiography were referred for MRI. Following a three‐plane localiser, fetal movement was assessed with a balanced steady‐state free precession (bSSFP) cine. Single‐shot fast spin echo and bSSFP sequences were used for diagnostic imaging. Results: Twenty‐two fetal cardiac MRIs were performed over 12 months, at mean gestation of 32 weeks (26–38 weeks). The majority of referrals were for suspected vascular abnormalities (17/22), particularly involving the aortic arch (n = 10) and pulmonary vessels (n = 4). Single‐shot fast spin echo sequences produced ‘black‐blood’ images, useful for examining the extracardiac vasculature in these cases. BSSFP sequences were more useful for intracardiac structures. Real‐time SSFP allowed for dynamic assessment of structures such as cardiac masses, with enhancement patterns also allowing for tissue characterisation in these cases. Conclusions: Fetal vascular abnormalities such as coarctation can be difficult to diagnose by using ultrasound. Fetal MRI may have an adjunctive role in the evaluation of the extracardiac vascular anatomy and tissue characterisation. © 2016 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd

A novel splicing variant of col2a1 in a fetus with achondrogenesis type ii: Interpretation of pathogenicity of in-frame deletions

Achondrogenesis type II (ACG2) is a lethal skeletal dysplasia caused by dominant pathogenic variants in COL2A1. Most of the variants found in patients with ACG2 affect the glycine residue included in the Gly-X-Y tripeptide repeat that characterizes the type II collagen helix. In this study, we reported a case of a novel splicing variant of COL2A1 in a fetus with ACG2. An NGS analysis of fetal DNA revealed a heterozygous variant c.1267-2_1269del located in intron 20/exon 21. The variant occurred de novo since it was not detected in DNA from the blood samples of parents. We generated an appropriate minigene construct to study the effect of the variant detected. The minigene expression resulted in the synthesis of a COL2A1 messenger RNA lacking exon 21, which generated a predicted in-frame deleted protein. Usually, in-frame deletion variants of COL2A1 cause a phenotype such as Kniest dysplasia, which is milder than ACG2. Therefore, we propose that the size and position of an in-frame deletion in COL2A1 may be relevant in determining the phenotype of skeletal dysplasia

Y RNA: an overview of their role as potential biomarkers and molecular targets in human cancers

Y RNA are a class of small non-coding RNA that are largely conserved. Although their discovery was almost 40 years ago, their function is still under investigation. This is evident in cancer biology, where their role was first studied just a dozen years ago. Since then, only a few contributions were published, mostly scattered across different tumor types and, in some cases, also suffering from methodological limitations. Nonetheless, these sparse data may be used to make some estimations and suggest routes to better understand the role of Y RNA in cancer formation and characterization. Here we summarize the current knowledge about Y RNA in multiple types of cancer, also including a paragraph about tumors that might be included in this list in the future, if more evidence becomes available. The picture arising indicates that Y RNA might be useful in tumor characterization, also relying on non-invasive methods, such as the analysis of the content of extracellular vesicles (EV) that are retrieved from blood plasma and other bodily fluids. Due to the established role of Y RNA in DNA replication, it is possible to hypothesize their therapeutic targeting to inhibit cell proliferation in oncological patients

Non-coding RNAs and endometrial cancer

Non-coding RNAs (ncRNAs) are involved in the regulation of cell metabolism and neoplastic transformation. Recent studies have tried to clarify the significance of these information carriers in the genesis and progression of various cancers and their use as biomarkers for the disease; possible targets for the inhibition of growth and invasion by the neoplastic cells have been suggested. The significance of ncRNAs in lung cancer, bladder cancer, kidney cancer, and melanoma has been amply investigated with important results. Recently, the role of long non-coding RNAs (lncRNAs) has also been included in cancer studies. Studies on the relation between endometrial cancer (EC) and ncRNAs, such as small ncRNAs or micro RNAs (miRNAs), transfer RNAs (tRNAs), ribosomal RNAs (rRNAs), antisense RNAs (asRNAs), small nuclear RNAs (snRNAs), Piwi-interacting RNAs (piRNAs), small nucleolar RNAs (snoRNAs), competing endogenous RNAs (ceRNAs), lncRNAs, and long intergenic ncRNAs (lincRNAs) have been published. The recent literature produced in the last three years was extracted from PubMed by two independent readers, which was then selected for the possible relation between ncRNAs, oncogenesis in general, and EC in particular

The role of number of copies, structure, behavior and copy number variations (CNV) of the Y chromosome in male infertility

The World Health Organization (WHO) defines infertility as the inability of a sexually active, non-contracepting couple to achieve spontaneous pregnancy within one year. Statistics show that the two sexes are equally at risk. Several causes may be responsible for male infertility; however, in 30–40% of cases a diagnosis of idiopathic male infertility is made in men with normal urogenital anatomy, no history of familial fertility-related diseases and a normal panel of values as for endocrine, genetic and biochemical markers. Idiopathic male infertility may be the result of gene/environment interactions, genetic and epigenetic abnormalities. Numerical and structural anomalies of the Y chromosome represent a minor yet significant proportion and are the topic discussed in this review. We searched the PubMed database and major search engines for reports about Y-linked male infertility. We present cases of Y-linked male infertility in terms of (i) anomalies of the Y chromosome structure/number; (ii) Y chromosome misbehavior in a normal genetic background; (iii) Y chromosome copy number variations (CNVs). We discuss possible explanations of male infertility caused by mutations, lower or higher number of copies of otherwise wild type, Y-linked sequences. Despite Y chromosome structural anomalies are not a major cause of male infertility, in case of negative results and of normal DNA sequencing of the ascertained genes causing infertility and mapping on this chromosome, we recommend an analysis of the karyotype integrity in all cases of idiopathic fertility impairment, with an emphasis on the structure and number of this chromosome

Cervical pessary for preventing preterm birth in twin pregnancies with short cervical length: a systematic review and meta-analysis

OBJECTIVE: To evaluate the effectiveness of cervical pessary for preventing spontaneous preterm birth (SPTB) in twin pregnancies with an asymptomatic transvaginal ultrasound cervical length (TVU CL) in the second trimester. METHODS: We performed a meta-analysis including all randomized clinical trials (RCTs) comparing the use of cervical pessary (i.e. intervention group) with expectant management (i.e. control group). The primary outcome was incidence of SPTB <34 weeks. RESULTS: Three trials, including 481 twin pregnancies with short cervix, were analyzed. Two RCTs defined short cervix as TVU CL ≤25 mm and one as TVU CL ≤38 mm. Pessary was not associated with prevention of SPTB, and the mean gestational age at delivery and the mean latency were similar in the pessary group compared to the control group. Moreover, no benefits were noticed in neonatal outcomes.\ud CONCLUSIONS: Use of the Arabin pessary in twin pregnancies with short TVU CL at 16-24 weeks does not prevent SPTB or improve perinatal outcome