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Immunocompromised patients with hematologic diseases may experience life-threatening infections with rather uncommon manifestations. Laryngitis has been described as a potential infection in such vulnerable patients and may result in major complications, ranging from impending airway obstruction to total laryngeal necrosis. Immediate laryngoscopy is of paramount importance, as it provides quantification of laryngeal edema and evidence of necrosis. Documentation of the causative pathogen is usually feasible through tissue culture. In the literature, 14 cases of necrotizing laryngitis have already been published. Here, we present the case of a 38-year-old male with a recent diagnosis of multiple myeloma, who received the first cycle of therapy a few days before admission. The patient presented with neutropenic fever, diarrhea, and multiple organ dysfunction. His course was complicated with hemophagocytic lymphohistiocytosis and stridor. A diagnosis of necrotizing laryngitis attributed to Acinetobacter baumannii invasion of the larynx was established. This manuscript highlights that the management of patients with hematologic disease and necrotizing laryngitis should be coordinated in highly specialized centers and clinicians should have a high level of clinical suspicion and act promptly. [ABSTRACT FROM AUTHOR]

Neonatal brain injury (NBI) is a critical condition for preterm neonates with potential long-term adverse neurodevelopmental outcomes. This prospective longitudinal case–control study aimed at investigating the levels and prognostic value of serum neuron-specific enolase (NSE) during the first 3 days of life in preterm neonates (<34 weeks) that later developed brain injury in the form of either periventricular leukomalacia (PVL) or intraventricular hemorrhage (IVH) during their hospitalization. Participants were recruited from one neonatal intensive care unit, and on the basis of birth weight and gestational age, we matched each case (n = 29) with a neonate who had a normal head ultrasound scan (n = 29). We report that serum NSE levels during the first three days of life do not differ significantly between control and preterm neonates with NBI. Nevertheless, subgroup analysis revealed that neonates with IVH had significantly higher concentrations of serum NSE in comparison to controls and neonates with PVL on the third day of life (p = 0.014 and p = 0.033, respectively). The same pattern on the levels of NSE on the third day of life was also observed between (a) neonates with IVH and all other neonates (PVL and control; p = 0.003), (b) neonates with II–IV degree IVH and all other neonates (p = 0.003), and (c) between control and the five (n = 5) neonates that died from the case group (p = 0.023). We conclude that NSE could be an effective and useful biomarker on the third day of life for the identification of preterm neonates at high risk of developing severe forms of IVH. [ABSTRACT FROM AUTHOR]

Tenofovir disoproxil fumarate (TDF) is a nucleotide reverse transcriptase inhibitor that has been widely used for the treatment of patients with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) infections. Despite the excellent safety records of this regimen, a few cases of acute renal failure and Fanconi syndrome have been reported among HIV patients exposed to TDF. However, in the HBV monoinfection scenario, only five cases of TDF-associated Fanconi syndrome have been reported thus far, two of them providing a confirmatory kidney biopsy. Here, we describe the case of a 68-year-old woman with chronic hepatitis B (CHB) who developed TDF-induced Fanconi syndrome that reverted after TDF withdrawal from tenofovir alafenamide. Though the overall risk of TDF-associated severe renal toxicity in HBV patients appears to be negligible, both glomerular and tubular functions should be monitored in patients exposed to TDF. [ABSTRACT FROM AUTHOR]

Astrocytes arise from multipotent neural stem cells (NSCs) and represent the most abundant cell type of the central nervous system (CNS), playing key roles in the developing and adult brain. Since the differentiation of NSCs towards a gliogenic fate is a precisely timed and regulated process, its perturbation gives rise to dysfunctional astrocytic phenotypes. Inflammation, which often underlies neurological disorders, including neurodevelopmental disorders and brain tumors, disrupts the accurate developmental process of NSCs. However, the specific consequences of an inflammatory environment on the epigenetic and transcriptional programs underlying NSCs' differentiation into astrocytes is unexplored. Here, we address this gap by profiling in mice glial precursors from neural tissue derived from early embryonic stages along their astrocytic differentiation trajectory in the presence or absence of tumor necrosis factor (TNF), a master pro-inflammatory cytokine. By using a combination of RNA- and ATAC-sequencing approaches, together with footprint and integrated gene regulatory network analyses, we here identify key differences during the differentiation of NSCs into astrocytes under physiological and inflammatory settings. In agreement with its role to turn cells resistant to inflammatory challenges, we detect Nrf2 as a master transcription factor supporting the astrocytic differentiation under TNF exposure. Further, under these conditions, we unravel additional transcriptional regulatory hubs, including Stat3, Smad3, Cebpb, and Nfkb2, highlighting the interplay among pathways underlying physiological astrocytic developmental processes and those involved in inflammatory responses, resulting in discrete astrocytic phenotypes. Overall, our study reports key transcriptional and epigenetic changes leading to the identification of molecular regulators of astrocytic differentiation. Furthermore, our analyses provide a valuable resource for understanding inflammation-induced astrocytic phenotypes that might contribute to the development and progression of CNS disorders with an inflammatory component. [ABSTRACT FROM AUTHOR]

The NF-κB signaling pathway is crucial during development and inflammatory processes. We have previously shown that NF-κB activation induces dedifferentiation of astrocytes into neural progenitor cells (NPCs). Here, we provide evidence  that the NF-κB pathway plays also a fundamental role during the differentiation of NPCs into astrocytes. First, we show that the NF-κB pathway is essential to initiate astrocytic differentiation as its early inhibition induces NPC apoptosis and impedes their differentiation. Second, we demonstrate that persistent NF-κB activation affects NPC-derived astrocyte differentiation. Tumor necrosis factor (TNF)-treated NPCs show NF-κB activation, maintain their multipotential and proliferation properties, display persistent expression of immature markers and inhibit astrocyte markers. Third, we analyze the effect of  NF-κB activation on the main known astrocytic differentiation pathways, such as NOTCH and JAK-STAT. Our findings suggest that the NF-κB pathway plays a dual fundamental role during NPC differentiation into astrocytes: it promotes astrocyte specification, but its persistent activation impedes their differentiation. [ABSTRACT FROM AUTHOR]