Impact of Time Point of Extracorporeal Membrane Oxygenation on Mortality and Morbidity in Congenital Diaphragmatic Hernia: A Single-Center Case Series.

Since there are no data available on the influence of the time point of ECMO initiation on morbidity and mortality in patients with congenital diaphragmatic hernia (CDH), we investigated whether early initiation of ECMO after birth is associated with a beneficial outcome in severe forms of CDH. All neonates with CDH admitted to our institution between 2010 until 2020 and undergoing ECMO treatment were included in this study and divided into four different groups: (1) ECMO initiation < 12 h after birth (n = 143), (2) ECMO initiation between 12−24 h after birth (n = 31), (3) ECMO initiation between 24−120 h after birth (n = 48) and (4) ECMO initiation > 120 h after birth (n = 14). The mortality rate in the first (34%) and fourth group (43%) was high and in the second group (23%) and third group (12%) rather low. The morbidity, characterized by chronic lung disease (CLD), did not differ significantly in the three groups; only patients in which ECMO was initiated >120 h after birth had an increased rate of severe CLD. Our data, although not randomized and limited due to small study groups, suggest that very early need for ECMO and ECMO initiation > 120 h after birth is associated with increased mortality.

Non-Typeable Haemophilus influenzae Invade Choroid Plexus Epithelial Cells in a Polar Fashion.

Non-typeable Haemophilus influenzae (NTHI) is a pathogen of the human respiratory tract causing the majority of invasive H. influenzae infections. Severe invasive infections such as septicemia and meningitis occur rarely, but the lack of a protecting vaccine and the increasing antibiotic resistance of NTHI impede treatment and emphasize its relevance as a potential meningitis causing pathogen. Meningitis results from pathogens crossing blood-brain barriers and invading the immune privileged central nervous system (CNS). In this study, we addressed the potential of NTHI to enter the brain by invading cells of the choroid plexus (CP) prior to meningeal inflammation to enlighten NTHI pathophysiological mechanisms. A cell culture model of human CP epithelial cells, which form the blood-cerebrospinal fluid barrier (BCSFB) in vivo, was used to analyze adhesion and invasion by immunofluorescence and electron microscopy. NTHI invade CP cells in vitro in a polar fashion from the blood-facing side. Furthermore, NTHI invasion rates are increased compared to encapsulated HiB and HiF strains. Fimbriae occurrence attenuated adhesion and invasion. Thus, our findings underline the role of the BCSFB as a potential entry port for NTHI into the brain and provide strong evidence for a function of the CP during NTHI invasion into the CNS during the course of meningitis.

Capsule and fimbriae modulate the invasion of Haemophilus influenzae in a human blood-cerebrospinal fluid barrier model.

The Gram-negative bacterium Haemophilus influenzae (H. influenzae) can commensally colonize the upper respiratory tract, but also cause life threatening disease including epiglottitis, sepsis and meningitis. The H. influenzae capsule protects the bacteria against both phagocytosis and opsonization. Encapsulated H. influenzae strains are classified into serotypes ranging from a to f dependent on their distinct polysaccharide capsule. Due to the implementation of vaccination the incidence of invasive H. influenzae type b (Hib) infections has strongly decreased and infections with other capsulated types, including H. influenzae type f (Hif), are emerging. The pathogenesis of H. influenzae meningitis is not clarified. To enter the central nervous system (CNS) the bacteria generally have to cross either the blood-brain barrier (BBB) or the blood-cerebrospinal fluid barrier (BSCFB). Using a cell culture model of the BCSFB based on human choroid plexus papilloma (HIBCPP) cells and different H. influenzae strains we investigated whether Hib and Hif invade the cells, and if invasion differs between encapsulated vs. capsular-deficient and fimbriated vs. non-fimbriated variants. We find that Hib can adhere to and invade into HIBCPP cells. Invasion occurs in a strongly polar fashion, since the bacteria enter the cells preferentially from the basolateral "blood "side. Fimbriae and capsule attenuate invasion into choroid plexus (CP) epithelial cells, and capsulation can influence the bacterial distribution pattern. Finally, analysis of clinical Hib and Hif isolates confirms the detected invasive properties of H. influenzae. Our data point to roles of capsule and fimbriae during invasion of CP epithelial cells.

Renal dysfunction is associated with deep cerebral microbleeds but not white matter hyperintensities in patients with acute intracerebral hemorrhage.

Kidney disease is a risk factor for cerebral microangiopathy and spontaneous intracerebral hemorrhage (ICH). We aimed to determine the association of renal dysfunction (RD) with MRI correlates of different patterns of cerebral microangiopathies including cerebral microbleeds (CMB) and white matter lesions (WML) in patients with ICH. In a prospectively collected, single-center cohort of ICH patients, glomerular filtration rate (eGFR) was estimated using the Modification of Diet in Renal Disease equation. We classified the renal function in five categories: category 1 (eGFR ≥ 90 mL/min/1.73 m(2)), category 2 (eGFR 60-89), category 3 (eGFR 30-59), category 4 (eGFR 15-29), and category 5 (eGFR <15) and dichotomized at an eGFR of 60. Number, location, and extent of CMB and WML were measured on MRI. ICH and CMB locations were classified as lobar or deep. 97 ICH patients with MRI (mean age 65.9 ± 13.9 years) were included. Intracerebral hemorrhage was lobar in 52.6 %. Median eGFR was 85.8 mL/min/1.73 m(2) (IQR 34.3). Renal dysfunction was present in 12.4 % of the patients. At least one CMB was present in 57.7 % of patients, WML were even more frequent (97.7 %). Age and impaired renal function were factors independently associated with the presence of CMB. The presence of CMB was independently associated with the number and extent of WML. RD is a frequent comorbidity in patients with ICH. Associations of RD with hypertension and with CMB in deep location suggest a predominant impact of RD on deep rather than on lobar microangiopathy.