Simultaneous breast implant infection and acute myocardial infarction-A tricky combination.

We present the case of a 57-year-old woman with a history of breast implants after augmentation mastopexy and persistent breast pain for six months. Despite a previous implant exchange with capsulectomy, the patient experienced a recurrence of symptoms for the last six months with a sudden worsening during the last night. Clinical examination revealed an asymmetry in favour of the left breast, but otherwise no clear evidence of implant-associated complication.

Characteristics of chronic lymphocytic leukemia in Japan: Comprehensive analysis of the CLLRSG-01 study.

Chronic lymphocytic leukemia (CLL) is rare in Japan. We conducted the nationwide, prospective observational study CLLRSG-01 to clarify the current state of CLL in Japan and to make accurate international comparisons by preparing naturally air-dried smears like those used in other countries. Of the 201 untreated patients enrolled and evaluated, 119 were diagnosed with CLL and 82 with non-CLL mature B-cell neoplasms, based on the WHO classification.

A 52-week multicenter retrospective real-world study on effectiveness and safety of dupilumab in children with atopic dermatitis aged from 6 to 11 years.

Dupilumab has been shown to be a safe and effective drug for the treatment of atopic dermatitis (AD) in children from 6 months to 11 years in randomized clinical trials. Aim: The aim of this real-life study was to determine the effectiveness in disease control and safety of dupilumab at W52 in moderate-to-severe AD children aged 6-11 years. All data were collected from 36 Italian dermatological or paediatric referral centres.

In Vivo Modeling of CLL Transformation to Richter Syndrome Reveals Convergent Evolutionary Paths and Therapeutic Vulnerabilities.

Unlabelled: Transformation to aggressive disease histologies generates formidable clinical challenges across cancers, but biological insights remain few. We modeled the genetic heterogeneity of chronic lymphocytic leukemia (CLL) through multiplexed in vivo CRISPR-Cas9 B-cell editing of recurrent CLL loss-of-function drivers in mice and recapitulated the process of transformation from indolent CLL into large cell lymphoma [i.e.

Dupilumab Treatment in Children Aged 6-11 Years With Atopic Dermatitis: A Multicentre, Real-Life Study.

Background: The management of paediatric atopic dermatitis (AD) is challenging, mostly relying on emollients and topical corticosteroids. Dupilumab, a fully human monoclonal antibody, has been recently approved for the treatment of children aged 6-11 years with moderate-to-severe AD not adequately controlled with topical therapies or when those therapies are not advisable.

Objectives: The aim of this study was to evaluate in real life the effectiveness and safety of dupilumab in the treatment of children aged from 6 to 11 years.

Preneoplastic Alterations Define CLL DNA Methylome and Persist through Disease Progression and Therapy.

Most human cancers converge to a deregulated methylome with reduced global levels and elevated methylation at select CpG islands. To investigate the emergence and dynamics of the cancer methylome, we characterized genome-wide DNA methylation in pre-neoplastic monoclonal B cell lymphocytosis (MBL) and chronic lymphocytic leukemia (CLL), including serial samples collected across disease course. We detected the aberrant tumor-associated methylation landscape at CLL diagnosis and found no significantly differentially methylated regions in the high-count MBL-to-CLL transition.

CRISPR/Cas9-generated models uncover therapeutic vulnerabilities of del(11q) CLL cells to dual BCR and PARP inhibition.

The deletion of 11q (del(11q)) invariably comprises ATM gene in chronic lymphocytic leukemia (CLL). Concomitant mutations in this gene in the remaining allele have been identified in 1/3 of CLL cases harboring del(11q), being the biallelic loss of ATM associated with adverse prognosis. Although the introduction of targeted BCR inhibition has significantly favored the outcomes of del(11q) patients, responses of patients harboring ATM functional loss through biallelic inactivation are unexplored, and the development of resistances to targeted therapies have been increasingly reported, urging the need to explore novel therapeutic approaches.

Growth dynamics in naturally progressing chronic lymphocytic leukaemia.

How the genomic features of a patient's cancer relate to individual disease kinetics remains poorly understood. Here we used the indolent growth dynamics of chronic lymphocytic leukaemia (CLL) to analyse the growth rates and corresponding genomic patterns of leukaemia cells from 107 patients with CLL, spanning decades-long disease courses. We found that CLL commonly demonstrates not only exponential expansion but also logistic growth, which is sigmoidal and reaches a certain steady-state level.

Combined chemosensitivity and chromatin profiling prioritizes drug combinations in CLL.

The Bruton tyrosine kinase (BTK) inhibitor ibrutinib has substantially improved therapeutic options for chronic lymphocytic leukemia (CLL). Although ibrutinib is not curative, it has a profound effect on CLL cells and may create new pharmacologically exploitable vulnerabilities. To identify such vulnerabilities, we developed a systematic approach that combines epigenome profiling (charting the gene-regulatory basis of cell state) with single-cell chemosensitivity profiling (quantifying cell-type-specific drug response) and bioinformatic data integration.

Splicing modulation sensitizes chronic lymphocytic leukemia cells to venetoclax by remodeling mitochondrial apoptotic dependencies.

The identification of targetable vulnerabilities in the context of therapeutic resistance is a key challenge in cancer treatment. We detected pervasive aberrant splicing as a characteristic feature of chronic lymphocytic leukemia (CLL), irrespective of splicing factor mutation status, which was associated with sensitivity to the spliceosome modulator, E7107. Splicing modulation affected CLL survival pathways, including members of the B cell lymphoma-2 (BCL2) family of proteins, remodeling antiapoptotic dependencies of human and murine CLL cells.

Sex-dependent association of circulating sex steroids and pituitary hormones with treatment-free survival in chronic lymphocytic leukemia patients.

Chronic lymphocytic leukemia (CLL) is not considered a hormone-regulated cancer although sex is a recognized risk factor with men more frequently diagnosed and developing progressive disease. We hypothesized that variable hormonal exposure may have a sexually dimorphic influence on treatment-free survival (TFS). In 156 CLL cases, we quantitatively profiled 29 circulating steroids (progesterone, adrenal precursors, androgens, estrogens, and catechol estrogens) as well as luteinizing hormone (LH) and follicle-stimulating hormone.

Cannabinoid Receptors Are Overexpressed in CLL but of Limited Potential for Therapeutic Exploitation.

The cannabinoid receptors 1 and 2 (CNR1&2) are overexpressed in a variety of malignant diseases and cannabinoids can have noteworthy impact on tumor cell viability and tumor growth. Patients diagnosed with chronic lymphocytic leukemia (CLL) present with very heterogeneous disease characteristics translating into highly differential risk properties. To meet the urgent need for refinement in risk stratification at diagnosis and the search for novel therapies we studied CNR expression and response to cannabinoid treatment in CLL.

Consensus Conference on Clinical Management of pediatric Atopic Dermatitis.

The Italian Consensus Conference on clinical management of atopic dermatitis in children reflects the best and most recent scientific evidence, with the aim to provide specialists with a useful tool for managing this common, but complex clinical condition. Thanks to the contribution of experts in the field and members of the Italian Society of Pediatric Allergology and Immunology (SIAIP) and the Italian Society of Pediatric Dermatology (SIDerP), this Consensus statement integrates the basic principles of the most recent guidelines for the management of atopic dermatitis to facilitate a practical approach to the disease. The therapeutical approach should be adapted to the clinical severity and requires a tailored strategy to ensure good compliance by children and their parents.

Evolving understanding of the CLL genome.

Over the past few years, massively parallel sequencing technologies have revealed with high resolution the tremendous genetic and epigenetic heterogeneity in chronic lymphocytic leukemia (CLL). We have learned how the molecular architecture differs not only between affected individuals but also within samples and over time. These insights have catalyzed our understanding of the pathobiology of CLL and point to critical signaling pathways in the development and progression of the disease.

UDP-glucuronosyltransferase 2B17 genotype and the risk of lung cancer among Austrian Caucasians.

Background: The enzyme uridine diphospho glucuronosyltansferase 2B17 (UGT2B17) glucuronidates several endogenous and exogenous compounds, including carcinogens from tobacco smoke like 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanl (NNAL). UGT2B17 shows a remarkable copy number variation (CNV) and an association between deletion genotype and increased risk of lung adenocarcinoma in women has been previously reported.

Methods: We investigated the UGT2B17 CNV by PCR in 453 Austrian lung cancer patients and in 449 healthy donors and analyzed the impact on lung cancer susceptibility and outcome.

Dysregulated mTORC1 renders cells critically dependent on desaturated lipids for survival under tumor-like stress.

Solid tumors exhibit heterogeneous microenvironments, often characterized by limiting concentrations of oxygen (O2), glucose, and other nutrients. How oncogenic mutations alter stress response pathways, metabolism, and cell survival in the face of these challenges is incompletely understood. Here we report that constitutive mammalian target of rapamycin complex 1 (mTORC1) activity renders hypoxic cells dependent on exogenous desaturated lipids, as levels of de novo synthesized unsaturated fatty acids are reduced under low O2.

Lipoprotein lipase in chronic lymphocytic leukaemia - strong biomarker with lack of functional significance.

In chronic lymphocytic leukaemia (CLL), lipoprotein lipase (LPL) mRNA overexpression is an established poor prognostic marker, its function, however, is poorly understood. Measuring extracellular LPL enzymatic activity and protein, we found no difference between levels in CLL patients and those of controls, both before and after heparin treatment in vivo and in vitro. Investigating LPL knock down effects, we determined five potential downstream targets, of which one gene, STXBP3, reportedly is involved in fatty acid metabolism.

Overexpression of uridine diphospho glucuronosyltransferase 2B17 in high-risk chronic lymphocytic leukemia.

Uridine diphospho glucuronosyltransferase 2B17 (UGT2B17) glucuronidates androgens and xenobiotics including certain drugs. The UGT2B17 gene shows a remarkable copy number variation (CNV), which predisposes for solid tumors and influences drug response. Here, we identify a yet undescribed UGT2B17 mRNA overexpression in poor-risk chronic lymphocytic leukemia (CLL).

BNip3 regulates mitochondrial function and lipid metabolism in the liver.

BNip3 localizes to the outer mitochondrial membrane, where it functions in mitophagy and mitochondrial dynamics. While the BNip3 protein is constitutively expressed in adult liver from fed mice, we have shown that its expression is superinduced by fasting of mice, consistent with a role in responses to nutrient deprivation. Loss of BNip3 resulted in increased lipid synthesis in the liver that was associated with elevated ATP levels, reduced AMP-regulated kinase (AMPK) activity, and increased expression of lipogenic enzymes.

Prolonged progression-free survival in patients with chronic lymphocytic leukemia receiving granulocyte colony-stimulating factor during treatment with fludarabine, cyclophosphamide, and rituximab.

The clinical benefit of the addition of granulocyte colony-stimulating factor (G-CSF) to standard immunochemotherapy of chronic lymphocytic leukemia (CLL) with fludarabine, cyclophosphamide, and rituximab (FCR) is still unclear. In this retrospective study we analyzed the outcome of 32 consecutive patients with CLL during treatment with FCR. Sixteen patients received G-CSF for treatment of CTC grade 3 or 4 neutropenia or febrile neutropenia at some point during therapy and 16 did not.

EPAS1 Is Required for Spermatogenesis in the Postnatal Mouse Testis.

Spermatogenesis, a process involving the differentiation of spermatogonial stem cells into mature spermatozoa, takes place throughout masculine life. A complex system in the testis, including endocrine signaling, physical interactions between germ and somatic cells, spermatocyte meiosis, and timely release of spermatozoa, controls this cycle. We demonstrate herein that decreased O(2) levels and Epas1 activation are critical components of spermatogenesis.

The transcription factor HIF-1alpha plays a critical role in the growth factor-dependent regulation of both aerobic and anaerobic glycolysis.

Mammalian cells are believed to have a cell-intrinsic ability to increase glucose metabolism in response to hypoxia. Here we show that the ability of hematopoietic cells to up-regulate anaerobic glycolysis in response to hypoxia is dependent on receptor-mediated signal transduction. In the absence of growth factor signaling, hematopoietic cells fail to express hypoxia-inducible transcription factor (Hif-1alpha) mRNA.

Acute postnatal ablation of Hif-2alpha results in anemia.

Adaptive transcriptional responses to oxygen deprivation (hypoxia) are mediated by the hypoxia-inducible factors (HIFs), heterodimeric transcription factors composed of two basic helix-loop-helix-PAS family proteins. The transcriptional activity of HIF is determined by the hypoxic stabilization of the HIF-alpha proteins. HIF-1alpha and HIF-2alpha exhibit high sequence homology but have different mRNA expression patterns; HIF-1alpha is expressed ubiquitously whereas HIF-2alpha expression is more restricted to certain tissues, e.