[Herpes Simplex Virus Infection in Two Premature Infants - Diagnostic and Therapeutic Management]. / Infektion durch Herpes simplex Virus bei zwei unreifen Frühgeborenen ­ Diagnostisches und therapeutisches Management.

Herpes simplex virus type 1 or 2 (HSV 1/2)-related infections in neonates are rare but associated with high morbidity and mortality, especially if specific treatment is delayed. Due to immaturity of the immunological system, premature infants are particularly at risk. In addition, symptoms of neonatal HSV infections may imitate prematurity-related problems, such as sepsis. So, a thorough patient's history and appropriate diagnostic measures are important to confirm the diagnosis. We present 2 premature infants with systemic HSV infections and discuss diagnostic and therapeutic management. Both were treated with intravenous acyclovir followed by enteral aciclovir suppressive therapy.

Correction to: Severe but not moderate hyperoxia of newborn mice causes an emphysematous lung phenotype in adulthood without persisting oxidative stress and inflammation.

Following publication of the original article [1], the authors flagged that the article had published with an error in 'Table 1'.

Receptor for advanced glycation end-products modulates lung development and lung sensitivity to hyperoxic injury in newborn mice.

The receptor for advanced glycation end-products is mainly expressed in type I alveolar epithelial cells but its importance in lung development and response to neonatal hyperoxia is unclear. Therefore, our study aimed at the analysis of young wildtype and RAGE knockout mice which grew up under normoxic or hyperoxic air conditions for the first 14 days followed by a longer period of normoxic conditions. Lung histology, expression of lung-specific proteins, and respiratory mechanics were analyzed when the mice reached an age of 2 or 4 months. These analyses indicated less but larger and thicker alveoli in RAGE knockout mice, reverse differences in the mRNA and protein amount of pro-surfactant proteins (pro-SP-B, pro-SP-C) and aquaporin-5, and differences in the amount of elastin and CREB, a pro-survival transcription factor, as well as higher lung compliance. Despite this potential disadvantages, RAGE knockout lungs showed less long-term damages mediated by neonatal hyperoxia. In detail, the hyperoxia-mediated reduction in alveoli, enlargement of airspaces, fragmentation of elastic fibers, and increased lung compliance combined with reduced peak airflows was less pronounced in RAGE knockout mice. In conclusion, RAGE supports the alveolarization but makes the lung more susceptible to hyperoxic injury shortly after birth. Blocking RAGE function could still be a helpful tool in reducing hyperoxia-mediated lung pathologies during alveolarization.

Severe but not moderate hyperoxia of newborn mice causes an emphysematous lung phenotype in adulthood without persisting oxidative stress and inflammation.

BACKGROUND: Preterm newborns typically require supplemental oxygen but hyperoxic conditions also damage the premature lung. Oxygen-induced lung damages are mainly studied in newborn mouse models using oxygen concentrations above 75% and looking at short-term effects. Therefore, we aimed at the investigation of long-term effects and their dependency on different oxygen concentrations. METHODS: Newborn mice were exposed to moderate vs. severe hyperoxic air conditions (50 vs. 75% O2) for 14 days followed by a longer period of normoxic conditions. Lung-related parameters were collected at an age of 60 or 120 days. RESULTS: Severe hyperoxia caused lower alveolar density, enlargement of parenchymal air spaces and fragmented elastic fibers as well as higher lung compliance with peak airflow limitations and higher sensitivity to ventilation-mediated damages in later life. However, these long-term lung structural and functional changes did not restrict the voluntary physical activity. Also, they were not accompanied by ongoing inflammatory processes, increased formation of reactive oxygen species (ROS) or altered expressions of antioxidant enzymes (superoxide dismutases, catalase) and lung elasticity-relevant proteins (elastin, pro-surfactant proteins) in adulthood. In contrast to severe hyperoxia, moderate hyperoxia was less lung damaging but also not free of long-term effects (higher lung compliance without peak airflow limitations, increased ROS formation). CONCLUSIONS: Severe but not moderate neonatal hyperoxia causes emphysematous lungs without persisting oxidative stress and inflammation in adulthood. As the existing fragmentation of the elastic fibers seems to play a pivotal role, it indicates the usefulness of elastin-protecting compounds in the reduction of long-term oxygen-related lung damages.

Case report: Otitis media with subsequent mastoiditis and cerebral herniation in a patient with Arnold chiari malformation.

We present the case of a 13-year-old boy who unexpectedly needed to be resuscitated at home after an assumed uncomplicated otitis media. Imaging at our clinic showed mastoiditis and a cystoid mass in the left cerebellopontine angle compressing the brainstem, as well as an Arnold-Chiari-Malformation. Both the laboratory examination of cerebrospinal fluid (CSF) and surgical biopsy with pathological evaluation of the mastoid supported the inflammatory etiology of the mass. Microbiologically, Streptococcus intermedius was detected in the blood culture and CSF. Due to brain death, which most likely already existed preclinically, the organs were released for donation during the course. Our case demonstrates a very rare lethal complication of acute otitis media on the basis of a cerebral malformation and emphasizes the need to stay alert when patients complain of symptoms after assumed resolution.

Monitoring Antibiotic Consumption in Pediatrics. How Close to Reality Are Days of Therapy and Recommended Daily Dose Methods?

BACKGROUND: Hospitals are advised to monitor antibiotic use. Several approximation methods do exist to perform this task. Adult cohorts can easily be monitored using the defined daily dose method, or its German adaption recommended daily doses (RDD) method, that seems inapplicable in pediatric cohorts due to body weight variations. Guidelines recommend the days of therapy (DOT) method in pediatrics. Still, there is a need for more detailed analysis regarding the performance of both methods. METHODS: Based on data from 4½ years of our fully computerized patient care data managing system in a combined neonatal and pediatric intensive care unit, we compare the results for DOT and RDD per 100 patient days with exact measurement of antibiotic consumption (individual daily dose per 100 patient days) as internal reference. RESULTS: The DOT method reflected antibiotic consumption in our cohort on the level of total consumption, subgroups, and agents with almost always high accuracy (correlation with individual daily dose between 0.73 and 1.00). The RDD method showed poor correlation on the level of total consumption (r = 0.21) and fluctuating results on more detailed levels (correlation, 0.01-0.94). A detailed analysis of body weight distribution and ordered packaging sizes of single agents revealed that RDD seems to work well when only one package size of the agent was ordered in our pharmacy. CONCLUSION: The DOT method is superior to RDD for monitoring antibiotic drug consumption in pediatric cohorts. RDD seems to work satisfactory well for selected antibiotic agents that are administered with little variation in packaging size.

Pediatric ICU Admissions After Adolescent Suicide Attempts During the Pandemic.

BACKGROUND AND OBJECTIVES: The worldwide severe acute respiratory syndrome coronavirus 2 pandemic challenges adolescents' mental health. In this study, we aim to compare the number of pediatric ICU (PICU) admissions after suicide attempts during the first German lockdown and one year later during a second, prolonged lockdown with prepandemic years. METHODS: A retrospective multicenter study was conducted among 27 German PICUs. Cases <18 years admitted to the PICU because of accidents or injuries between March 16 and May 31 of 2017 to 2021 were identified based on International Classification of Diseases, 10th Revision codes (German modification) and patient data entered into a database. This study is a subset analysis on suicide attempts in adolescents aged 12 to 17.9 years. The Federal Statistics Office was queried for data on fatal suicides, which were available only for 2020 in adolescents aged 10 to 17.9 years. RESULTS: Total admissions and suicide attempts declined during the first lockdown in 2020 (standardized morbidity ratio 0.74 (95% confidence interval; 0.58-0.92) and 0.69 (0.43-1.04), respectively) and increased in 2021 (standardized morbidity ratio 2.14 [1.86-2.45] and 2.84 [2.29-3.49], respectively). Fatal suicide rates remained stable between 2017 to 2019 and 2020 (1.57 vs 1.48 per 100 000 adolescent years) with monthly numbers showing no clear trend during the course of 2020. CONCLUSIONS: This study shows a strong increase in serious suicide attempts among adolescents during the course of the pandemic in Germany. More research is needed to understand the relation between pandemic prevention measures and suicidal ideation to help implement mental health support for adolescents.

Co-Culture of Peripheral Blood Mononuclear Cells and Endothelial Colony Forming Cells from Cord Blood of Preterm Born Babies.

Umbilical cord blood of neonates is a precious source for many fields of research because of distinct unique features combined with easy accessibility at the time of birth. The number of applications are vast with an emphasis in the field of stem cell therapy and regenerative medicine since cord blood contains relatively large numbers of pluripotent cells. This chapter provides a protocol for developing an autologous co-culture of endothelial-like cells and peripheral blood mononuclear cells from umbilical cord blood of premature born babies and describes an experimental setting to investigate inflammatory processes that are a cornerstone of pathophysiology in the developing organs of preterm born babies.

Inhibition of Clostridioides difficile Toxins TcdA and TcdB by Ambroxol.

Clostridioides (C.) difficile produces the exotoxins TcdA and TcdB, which are the predominant virulence factors causing C. difficile associated disease (CDAD). TcdA and TcdB bind to target cells and are internalized via receptor-mediated endocytosis. Translocation of the toxins' enzyme subunits from early endosomes into the cytosol depends on acidification of endosomal vesicles, which is a prerequisite for the formation of transmembrane channels. The enzyme subunits of the toxins translocate into the cytosol via these channels where they are released after auto-proteolytic cleavage. Once in the cytosol, both toxins target small GTPases of the Rho/Ras-family and inactivate them by mono-glucosylation. This in turn interferes with actin-dependent processes and ultimately leads to the breakdown of the intestinal epithelial barrier and inflammation. So far, therapeutic approaches to treat CDAD are insufficient, since conventional antibiotic therapy does not target the bacterial protein toxins, which are the causative agents for the clinical symptoms. Thus, directly targeting the exotoxins represents a promising approach for the treatment of CDAD. Lately, it was shown that ambroxol (Ax) prevents acidification of intracellular organelles. Therefore, we investigated the effect of Ax on the cytotoxic activities of TcdA and TcdB. Ax significantly reduced toxin-induced morphological changes as well as the glucosylation of Rac1 upon intoxication with TcdA and TcdB. Most surprisingly, Ax, independent of its effects on endosomal acidification, decreased the toxins' intracellular enzyme activity, which is mediated by a catalytic glucosyltransferase domain. Considering its undoubted safety profile, Ax might be taken into account as therapeutic option in the context of CDAD.