Ductal ligation timing and neonatal outcomes: a 12-year bicentric comparison.

Funder: Alma Mater Studiorum - Università di BolognaPatent ductus arteriosus (PDA) is common among extremely preterm infants. In selected cases, surgical PDA ligation may be required. The timing for PDA ligation may depend upon a variety of factors, with potential clinical implications. We aimed to investigate the impact of different surgical PDA managements on ligation timing and neonatal outcomes. Inborn infants < 32 weeks of gestation and < 1500 g admitted at two tertiary Neonatal Intensive Care Units that underwent PDA ligation between 2007 and 2018 were enrolled in this retrospective cohort study and split into the following groups based on their surgical management: on-site bedside PDA ligation (ONS) vs. referral to an off-site pediatric cardiac surgery (OFS). Neonatal characteristics, surgical timing, and clinical outcomes of the enrolled infants were compared between the groups. Multivariate analysis was performed to evaluate the impact of PDA ligation timing on significantly different outcomes. Seventy-eight neonates (ONS, n = 39; OFS, n = 39) were included. Infants in the ONS group underwent PDA ligation significantly earlier than those in the OFS group (median age 12 vs. 36 days, p < 0.001) with no increase in postoperative mortality and complications. The multivariate analysis revealed a significant association between PDA ligation timing, late-onset sepsis prevalence (OR 1.045, 0.032), and oxygen need at discharge (OR 1.037, p = 0.025).Conclusions: Compared with off-site surgery, on-site bedside ligation allows an earlier surgical closure of PDA, with no apparent increase in mortality or complications. Earlier PDA ligation may contribute to reduced rates of late-onset sepsis and post-discharge home oxygen therapy, with possible cost-benefit implications. What is known: • Ineffective or contraindicated pharmacological closure of a hemodynamically significant PDA may require a surgical ligation. • Available literature comparing the effect of early vs. late PDA ligation on the main neonatal morbidities has yield contrasting results. What is new: • The availability of a cardiac surgery service performing bedside PDA ligation allows an earlier intervention compared to patient referral to an off-site center, with no difference in postoperative mortality and complications compared to off-site surgery. • Earlier PDA ligation was associated with a lower prevalence of late-onset sepsis and of oxygen need at discharge, with possible cost-benefit implications

Primary lymphoma of the internal auditory canal - Case report and review of the literature

We report a rare case of a primary intracranial B cell lymphoma originating in the internal auditory canal. The clinical manifestations were indistinguishable from those of other, more common tumors of the same region. We achieved total gross tumor removal with preservation of the facial nerve. A detailed histologic examination and a systemic workup confirmed the primary nature of this tumor. To our knowledge, this is the second case reported in the literature of a primary malignant lymphoma originating in the internal auditory canal. This is the first instance that includes immunohistochemical and cytometric studies of fresh tissue. We discuss the management of primary lymphomas of the central nervous system, with special emphasis on their association with acquired immunodeficiency syndrome and other immune system diseases. Awareness of primary central nervous system lymphomas is important, since a greater occurrence of these rare tumors in the cerebellopontine angle is probable in the future

Dexamethasone Protects Against Apoptotic Cell Death of Cisplatin-exposed Auditory Hair Cells In Vitro

Dexamethasone (DXM) protects against cisplatin-induced auditory hair cell (HC) loss in rat organ of Corti (OC) explants in vitro by reducing levels of oxidative stress and NADPH-Oxidase-3 (NOX-3). Intratympanic DXM has demonstrated protective effects against cisplatin-induced hearing loss in a few animal studies and one clinical trial. However, levels of protection with intratympanic DXM vary significantly between studies, which may not be a result of the intrinsic properties of DXM but rather reflect the diffusion of DXM into the cochlea. The molecular mechanisms and degree of DXM protection against cisplatin ototoxicity are currently unknown. OC explants from 3-day-old rats were cultured with no treatment or various concentrations of cisplatin (2, 5, or 10 μM) and DXM (75, 150, or 300 μg/mL) in vitro. HC viability and TUNEL assay were performed after 72 hours in vitro and levels of oxidative stress and NOX-3 were evaluated with confocal microscopy after 48 hours in vitro. Analysis of variance with Tukey's post hoc testing was performed. Cisplatin initiated dose-dependent losses of outer HCs (OHCs) in the basal turns of exposed explants (p < 0.001). DXM protected against cisplatin (2 μM)-induced OHC loss in a dose-dependent manner with complete protection at 300 μg/mL of DXM (p < 0.001). DXM (150 μg/mL) significantly reduced levels of oxidative stress, NOX-3, and apoptosis in the basal turn of explants exposed to cisplatin (2 μM). DXM protects against cisplatin-induced loss of OHCs in the basal turn of rat OC explants as demonstrated by reductions in oxidative stress and NOX-3 production and decreased levels of apoptotic cell death

Etiologic Diagnosis of Nonsyndromic Genetic Hearing Loss in Adult vs Pediatric Populations

OBJECTIVES: Determine the diagnostic yield of a shared genetic testing algorithm in adult and pediatric populations with sensorineural hearing loss (SNHL) and recommend effective testing strategies to evaluate for genetic causes of deafness in patients presenting with idiopathic sensorineural hearing loss. STUDY DESIGN: Hospital-based cohort study. SETTING: University of Miami outpatient otology clinics between 2001 and 2010. SUBJECTS: Two hundred twenty-one adult and 163 pediatric patients with nonsyndromic sensorineural hearing loss. METHODS: Peripheral blood samples were screened for mutations in GJB2 and GJB6 and mitochondrial DNA mutations 1555A>G, 7444G>A, and 3243A>G. Audiometric data and family history were also collected. RESULTS: GJB2/GJB6-related deafness was diagnosed in 23 of 163 pediatric patients (14%) compared with only 3 of 221 adults (1%). All adults had a family history of hearing loss, and 2 patients noted deafness onset at birth. Nineteen GJB2 mutations were identified with 35delG the most common mutation. The 35delG homozygous state was the most common pathogenic genotype (54%). Mitochondrial DNA (mtDNA) mutations were found in 6 adult probands (3%). No mtDNA mutations were found in pediatric patients. CONCLUSION: Testing for common GJB2/GJB6 mutations in pediatric patients has considerable value in establishing an etiologic diagnosis for SNHL. Similar testing in adults is of very low yield except perhaps in cases of early-onset SNHL or strong family history. Mitochondrial DNA testing should be considered in adults with idiopathic SNHL

Dexamethasone Protects Against Radiation-induced Loss of Auditory Hair Cells In Vitro

Dexamethasone (DXM) protects against radiation-induced loss of auditory hair cells (HCs) in rat organ of Corti (OC) explants by reducing levels of oxidative stress and apoptosis. Radiation-induced sensorineural hearing loss (HL) is progressive, dose-dependent, and irreversible. Currently, there are no preventative therapeutic modalities for radiation-induced HL. DXM is a synthetic steroid that can potentially target many of the pathways involved in radiation-induced ototoxicity. Whole OC explants were dissected from 3-day-old rat cochleae exposed to specific dosages of single-fraction radiation (0, 2, 5, 10, or 20 Gy), were either untreated or treated with DXM (75, 150, 300 μg/mL), and then cultured for 48 or 96 hours. Confocal microscopy for oxidative stress (CellRox, 48 h) and apoptosis (TUNEL assay, 96 h) and fluorescent microscopy for viable HC counts (fluorescein isothiocyanate-phalloidin, 96 h) were performed. Analysis of variance and Tukey post hoc testing were used for statistical analysis. Radiation exposure initiated dose-dependent losses of inner and outer HCs, predominantly in the basal turns of the OC explants. DXM protected against radiation-induced HC losses in a dose-dependent manner. DXM significantly reduced levels of oxidative stress and apoptosis in radiation-injured OC explants (p < 0.001). Radiation-initiated HC losses were dose-dependent in OC explants. DXM treatment protected explant HCs against radiation-initiated losses by decreasing the levels of oxidative stress and apoptosis. DXM may potentially be a therapeutic modality for preventing radiation-induced HL; further in vivo studies are necessary