Meningeal lymphatic vessels in the human head: Examples of in vivo visualization with high-resolution 3T MRI

In 2015, meningeal lymphatic vessels (mLVs) were (re)discovered in mice and human dura specimens. Two years later, the first report was published showing that mLVs can be detected in humans in vivo by high-resolution 3 Tesla magnetic resonance imaging (MRI). In 2017 and 2018, two further studies reported the successful MRI-based detection of mLVs in vivo in humans. The aim of our study was to provide further evidence of the possibility to detect mLVs in vivo with MRI in humans. To this end, MR images already available from one subject (the first author) were analyzed. We detected mLVs in the coronal plane at the bilateral superior lateral corners of the superior sagittal sinus (SSS) as well as below the SSS, in agreement with the two other published reports about the in vivo detection of mLVS in humans with MRI. Our report is thus, to the best of our knowledge, the fourth published report about in vivo MR imaging of human mLVs

Effective ventilation and chest compressions during neonatal resuscitation – the role of the respiratory device

Background: The success of cardiopulmonary resuscitation (CPR) in newborns largely depends on effective lung ventilation; however, a direct randomized comparison using different available devices has not yet been performed. Methods: Thirty-six professionals were exposed to a realistic newborn CPR scenario. Ventilation with either a bag-valve mask (BVM), T-piece, or ventilator was applied in a randomized manner during CPR using a Laerdal manikin. The primary outcome was the number of unimpaired inflations, defined as the peak of the inflation occurring after chest compression and lasting at least 0.35 s before the following chest compression takes place. The secondary outcomes were tidal volume delivered and heart compression rate. To simulate potential distractions, the entire scenario was performed with or without a quiz. Statistically, a mixed model assessing fixed effects for experience, profession, device, and distraction was used to analyze the data. For direct comparison, one-way ANOVA with Bonferroni's correction was applied. Results: The number of unimpaired inflations was highest in health care professionals using the BVM with a mean ± standard deviation of 12.8 ± 2.8 (target: 15 within 30 s). However, the tidal volumes were too large in this group with a tidal volume of 42.5 ± 10.9 ml (target: 25-30 ml). The number of unimpaired breaths with the mechanical ventilator and the T-piece system were 11.6 (±3.6) and 10.1 (±3.7), respectively. Distraction did not change these outcomes, except for the significantly lower tidal volumes with the T-piece during the quiz. Conclusions: In summary, for our health care professionals, ventilation using the mechanical ventilator seemed to provide the best approach during CPR, especially in a population of preterm infants prone to volutrauma

Case report: Intrapulmonary tidal volumes in a preterm infant with chest wall rigidity

BACKGROUND Chest wall rigidity is a known side effect of fentanyl use, which is why fentanyl is usually combined with a muscle relaxant such as mivacurium. Verifying endotracheal intubation is difficult in case of a rigid chest wall. CASE PRESENTATION We present the case of a preterm infant (29 completed weeks gestation, birth weight 1,150 g) with a prolonged chest wall rigidity after fentanyl administration for intubation despite adequate doses of mivacurium. This resulted in a pronounced desaturation without any effect on heart rate. Clinically, the infant showed no chest wall movement despite intubation and common tools to verify intubation (including end-tidal carbon dioxide measurement and auscultation) were inconclusive. However, using electrical impedance tomography (EIT), we were able to demonstrate minimal tidal volumes at lung level and thereby, EIT was able to accurately show correct placement of the endotracheal tube. CONCLUSIONS This case may increase vigilance for fentanyl-induced chest wall rigidity in the neonatal population even when simultaneously administering mivacurium. Higher airway pressures exceeding 30 mmHg and the use of μ-receptor antagonists such as naloxone should be considered to reverse opioid-induced chest wall rigidity. Most importantly, our data may imply a relevant clinical benefit of using EIT during neonatal intubation as it may accurately show correct endotracheal tube placement

Endocannabinoid and steroid analysis in infant and adult nails by LC-MS/MS

A common method to quantify chronic stress is the analysis of stress markers in keratinized matrices such as hair or nail. In this study, we aimed to validate a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the combined quantification of steroid hormones and endocannabinoids (eCBs) in the keratinized matrix nail. Furthermore, we aimed to investigate the suitability of the nail matrix for the detection of these stress markers in a pilot study. An LC-MS/MS method was used for the simultaneous identification and quantification of four eCBs (2-arachidonoylglycerol (2-AG), anandamide (AEA), oleoylethanolamide (OEA), palmitoylethanolamide (PEA)) and five steroid hormones (cortisol, cortisone, androstenedione, progesterone, testosterone) in human nails using a surrogate analyte method for each analyte. The method was validated in terms of selectivity, response factor, linearity, limit of quantification (LOQ), precision, accuracy, matrix effect, recovery, robustness, and autosampler stability. Nail samples were extracted for 1 h with methanol following a clean-up with a fully automated supported liquid extraction (SLE). The influence of nail weight on the quantification was investigated by using 0.5-20 mg of nail sample. As a proof of concept, nail samples (N = 57) were analyzed from a cohort representing newborns (1 month old), children (between 1 and 10 years), and adults (up to 43 years). It could be shown that the established workflow using a 1 hour extraction and clean-up by SLE was very robust and resulted in a short sample preparation time. The LC-MS/MS method was successfully validated. Matrix effects with ion enhancement occurred mainly for 2-AG. Sample weights below 5 mg showed variations in quantification for some analytes. Certain analytes such as PEA and progesterone could be accurately quantified at a sample weight lower than 5 mg. This is the first study where steroids and eCBs could be simultaneously detected and quantified in infant and adult nails. These results show that nails may serve as an alternative keratinized matrix (compared to hair) for the retrospective monitoring of cumulative eCB and steroid hormone levels. The combined assessment of eCBs and steroids from nails could provide a new approach to gain new insights into stress exposure in newborns and adults

Impairment of the Blood-Brain-Barrier: Evaluation of Pharmacological Postconditioning with Sevoflurane

The blood-brain barrier (BBB) strictly limits the flux from the blood to the brain. The BBB thereby protects the brain against harmful blood-derived substances and simultaneously allows the supply with essential nutrients. The disruption of the BBB accompanies many neurological disease conditions, such as those induced by trauma, hypoxia, metabolic abnormalities or inflammation. The grade of brain edema formation, which is one clinical representation of BBB impairment, has been shown to be an independent predictor of unfavorable patient outcome. Treatment options for BBB protection are still rare, partially due to the fact that only few substances can sufficiently cross this barrier. Promising drugs are lipophilic molecules such as volatile anesthetics which have been shown to be beneficial in cases of hypoxia reoxygenation injury (H/R) in the heart, liver, lung and kidney. Whether and how such compounds change intracranial pressure is still a matter of debate. Although of high clinical relevance, only few data are available concerning the action of volatile anesthetics on the BBB. In order to tackle this problem, this dissertation aimed to elucidate whether and how volatile anesthetics impact the BBB through two specific projects addressing the following questions: 1. Does sevoflurane impact brain endothelial cells after H/R injury? And which signaling pathways are involved? 2. Does brain inflammation change in response to sevoflurane treatment in an animal model of sepsis? And which signaling pathways are involved and modified? Immortalized rat brain endothelial cells (RBE4) were used to assess the effect of sevoflurane treatment after H/R injury, in a so called postconditioning setup, where cells are exposed to sevoflurane after initiation of injury. For this reason, permeability as well as tight and adherens junctions’ architecture were further analyzed. In order to detect potential mediators of the response, reactive oxygen species (ROS), inflammatory mediators (IL-6, TNF alpha, MMP9), protein kinase C (PKC) and vascular endothelial growth factor (VEGF) were quantified in the cells’ supernatant. Using this approach, we demonstrated that sevoflurane changes the permeability pattern in rat brain endothelial cells and modifies the architecture of the junctional components ZO-1 and β-catenin. ROS, PKC and VEGF were shown to be downregulated in response to sevoflurane treatment. Interestingly, RBE4 cells did not show any inflammatory response after H/R alone. In experiments in a rat animal model of sepsis, neuroinflammation with and without sevoflurane post-conditioning was assessed in more detail by our team. Inflammatory body response was significantly decreased due to sevoflurane treatment, but neuroinflammation was not affected. Taking those studies together, we conclude that sevoflurane reduces barrier leakage of rat brain endothelial cells, modifies the cytoskeleton and junctional components and reduces important mediators of H/R injury such as ROS, PKC and VEGF. In contrast to its systemic action, sevoflurane does not alleviate early inflammatory response in the brain. Nevertheless, it is tempting to further elucidate the effects of sevoflurane postconditioning in patients

The Role of Methemoglobin and Carboxyhemoglobin in COVID-19: A Review

Following the outbreak of a novel coronavirus (SARS-CoV-2) associated with pneumonia in China (Corona Virus Disease 2019, COVID-19) at the end of 2019, the world is currently facing a global pandemic of infections with SARS-CoV-2 and cases of COVID-19. Since severely ill patients often show elevated methemoglobin (MetHb) and carboxyhemoglobin (COHb) concentrations in their blood as a marker of disease severity, we aimed to summarize the currently available published study results (case reports and cross-sectional studies) on MetHb and COHb concentrations in the blood of COVID-19 patients. To this end, a systematic literature research was performed. For the case of MetHb, seven publications were identified (five case reports and two cross-sectional studies), and for the case of COHb, three studies were found (two cross-sectional studies and one case report). The findings reported in the publications show that an increase in MetHb and COHb can happen in COVID-19 patients, especially in critically ill ones, and that MetHb and COHb can increase to dangerously high levels during the course of the disease in some patients. The medications given to the patient and the patient’s glucose-6-phospate dehydrogenase (G6PD) status seem to be important factors determining the severity of the methemoglobinemia and carboxyhemoglobinemia. Therefore, G6PD status should be determined before medications such as hydroxychloroquine are administered. In conclusion, MetHb and COHb can be elevated in COVID-19 patients and should be checked routinely in order to provide adequate medical treatment as well as to avoid misinterpretation of fingertip pulse oximetry readings, which can be inaccurate and unreliable in case of elevated MetHb and COHb levels in the blood

Microbial Colonization From the Fetus to Early Childhood—A Comprehensive Review

The development of the neonatal gastrointestinal tract microbiota remains a poorly understood process. The interplay between neonatal (gestational age, genetic background), maternal (mode of delivery, nutritional status) and environmental factors (antibiotic exposure, available nutrition) are thought to influence microbial colonization, however, the exact mechanisms are unclear. Derangements in this process likely contribute to various gastrointestinal diseases including necrotizing enterocolitis and inflammatory bowel disease. As such, enhanced understanding of microbiota development may hold the key to significantly reduce the burden of gastrointestinal disease in the pediatric population. The most debatable topics during microbial seeding and possible future treatment approaches will be highlighted in this review

Newborn Incubators Do Not Protect from High Noise Levels in the Neonatal Intensive Care Unit and Are Relevant Noise Sources by Themselves

BACKGROUND While meaningful sound exposure has been shown to be important for newborn development, an excess of noise can delay the proper development of the auditory cortex. AIM The aim of this study was to assess the acoustic environment of a preterm baby in an incubator on a newborn intensive care unit (NICU). METHODS An empty but running incubator (Giraffe Omnibed, GE Healthcare) was used to evaluate the incubator frequency response with 60 measurements. In addition, a full day and night period outside and inside the incubator at the NICU of the University Hospital Zurich was acoustically analyzed. RESULTS The fan construction inside the incubator generates noise in the frequency range of 1.3-1.5 kHz with a weighted sound pressure level (SPL) of 40.5 dB(A). The construction of the incubator narrows the transmitted frequency spectrum of sound entering the incubator to lower frequencies, but it does not attenuate transient noises such as alarms or opening and closing of cabinet doors substantially. Alarms, as generated by the monitors, the incubator, and additional devices, still pass to the newborn. CONCLUSIONS The incubator does protect only insufficiently from noise coming from the NICUThe transmitted frequency spectrum is changed, limiting the impact of NICU noise on the neonate, but also limiting the neonate's perception of voices. The incubator, in particular its fan, as well as alarms from patient monitors are major sources of noise. Further optimizations with regard to the sound exposure in the NICU, as well as studies on the role of the incubator as a source and modulator, are needed to meet the preterm infants' multi-sensory needs

Ansätze zur Prävention einer Hirnschädigung bei Früh- und Reifgeborenen

Die Hirnschädigung eines Neugeborenen verändert das ganze Leben des Kindes und das seiner Familie. Obwohl die Ursachen vielfältig sind, sind die evidenzbasierten Präventionsmaßnahmen überschaubar und die Therapieoptionen limitiert. Der Artikel fasst die häufigsten Ursachen der Hirnschädigung zusammen, zeigt Risikofaktoren auf und vermittelt Ansätze zur Prävention bei Termin- und Frühgeborenen