Comparison of different types of ultrasound probes for lung ultrasound in neonates-A prospective randomized comparison study.

OBJECTIVE: To determine the effect of different types of probes for lung ultrasound in neonates. DESIGN: Prospective, blinded, randomized, comparative study between 2020 and 2022. SETTING: Single-center study at a third level neonatal unit. PATIENTS: Hemodynamically stable infants with either nasal continuous positive airway pressure, high flow nasal cannula or without respiratory support. INTERVENTION: Lung ultrasound using either an echo or microconvex probe. As control, the linear probe was used. MAIN OUTCOME MEASURES: Primary outcome measure was neonatologist performed lung ultrasound (NPLUS) score. Secondary outcome measures were number of B-Lines, thickness of the pleural line and subjective image quality. Furthermore, correlation between NPLUS results and clinical data was assessed. RESULTS: A total of 1584 video loops from 66 patients, with a mean corrected gestational age of 33.8 weeks (SD 4.23) and weight of 1950g (SD 910), respectively, were analyzed. NPLUS score was estimated lower with the echo- and microconvex probe compared to the linear probe, with a coefficient of -2.95 (p < 0.001) and -1.09 (p = 0.19), respectively. Correlation between the pulse oximetric saturation/fraction of inspired oxygen ratio and NPLUS score was moderately strong and best using the microconvex probe (Spearman's rho = -0.63, p<0.001). CONCLUSION: Our results not only confirm the current recommendations, but also demonstrate the extent of the varying results when different probes are used. The differences we discovered call for caution in interpreting scores, especially in the context of guiding therapies and communicating prognoses. Finally, the correlation between NPLUS score and clinical parameters contributes to validating the use of this diagnostic tool.

Oscillometry for personalizing continuous distending pressure maneuvers: an observational study in extremely preterm infants.

RATIONALE: Lung recruitment and continuous distending pressure (CDP) titration are critical for assuring the efficacy of high-frequency ventilation (HFOV) in preterm infants. The limitation of oxygenation (peripheral oxygen saturation, SpO2) in optimizing CDP calls for evaluating other non-invasive bedside measurements. Respiratory reactance (Xrs) at 10 Hz measured by oscillometry reflects lung volume recruitment and tissue strain. In particular, lung volume recruitment and decreased tissue strain result in increased Xrs values. OBJECTIVES: In extremely preterm infants treated with HFOV as first intention, we aimed to measure the relationship between CDP and Xrs during SpO2-driven CDP optimization. METHODS: In this prospective observational study, extremely preterm infants born before 28 weeks of gestation undergoing SpO2-guided lung recruitment maneuvers were included in the study. SpO2 and Xrs were recorded at each CDP step. The optimal CDP identified by oxygenation (CDPOpt_SpO2) was compared to the CDP providing maximal Xrs on the deflation limb of the recruitment maneuver (CDPXrs). RESULTS: We studied 40 infants (gestational age at birth = 22+ 6-27+ 5 wk; postnatal age = 1-23 days). Measurements were well tolerated and provided reliable results in 96% of cases. On average, Xrs decreased during the inflation limb and increased during the deflation limb. Xrs changes were heterogeneous among the infants for the amount of decrease with increasing CDP, the decrease at the lowest CDP of the deflation limb, and the hysteresis of the Xrs vs. CDP curve. In all but five infants, the hysteresis of the Xrs vs. CDP curve suggested effective lung recruitment. CDPOpt_SpO2 and CDPXrs were highly correlated (ρ = 0.71, p < 0.001) and not statistically different (median difference [range] = -1 [-3; 9] cmH2O). However, CDPXrs were equal to CDPOpt_SpO2 in only 6 infants, greater than CDPOpt_SpO2 in 10, and lower in 24 infants. CONCLUSIONS: The Xrs changes described provide complementary information to oxygenation. Further investigation is warranted to refine recruitment maneuvers and CPD settings in preterm infants.

Cut-off values of serum interleukin-6 for culture-confirmed sepsis in neonates.

INTRODUCTION: Neonatal sepsis accounts for 0.97% of all disability-adjusted life years worldwide. Interleukin-6 has been used in sepsis diagnosis, but cut-off values are missing. METHODS: Neonates admitted to the neonatal wards with measurements of serum interleukin-6 born between September 2015 and September 2019 were retrospectively analysed. Mean serum interleukin-6 values of patients who never had increased laboratory parameters of infection nor died during their stay and mean interleukin-6 values on the day of blood sampling for a later positive culture in patients with culture-confirmed sepsis were analysed for each time period. RESULTS: In all, 8.488 values in 1.695 neonates, including 752 very-preterm-infants and 701 very-low-birthweight infants, were analysed. The AUC for interleukin-6 was 0.84-0.91 in all neonates, 0.88-0.89 in very-preterm and 0.89-0.91 in very-low-birthweight infants. Using interleukin-6 cut-off values of 80 pg/ml on day of life 1, 40 pg/ml on day of life 2-7 and 30 pg/ml after day of life 7, a sensitivity of 75% and a specificity of 81% for culture-confirmed sepsis were achieved. In very-preterm infants, the corresponding values were 74% for sensitivity and 83% for specificity and in very-low-birthweight infants 74% and 86%, respectively. CONCLUSION: Serum interleukin-6 has high accuracy for the detection of neonatal sepsis. IMPACT: Serum interleukin-6 can be used with high accuracy to detect sepsis in neonates with the cut-off values of 80 pg/ml on day of life 1, 40 pg/ml on day of life 2-7 and 30 pg/ml after day of life 7. Serum interleukin-6 can be used with high accuracy to detect sepsis in neonates and very-preterm as well as very-low-birthweight infants. Interleukin-6 values display distinct cut-off values depending on the chronological age of the infant. Our article provides the first cut-off values for interleukin-6 in the first days of life in neonates.

Incidence of Post-extubation Stridor in Infants With Cuffed vs. Uncuffed Endotracheal Tube: A Retrospective Cohort Analysis.

Background: Endotracheal intubation is a common procedure in Neonatal Intensive Care. While cuffed endotracheal tubes (ETT) are the standard of care in adults and children, their use in infants is controversial. The aim of this study was to compare the incidence of post-extubation stridor between uncuffed and cuffed ETTs in infants. We further evaluated the safety of cuffed ETTs in infants with a bodyweight between 2 and 3 kg and performed baseline analysis on development of subglottic stenosis. Methods: In this retrospective study, we screened all infants admitted to two NICUs of the Medical University of Vienna between 2012 and 2019.The study cohort was screened twice: In the first screening we selected all infants who underwent the first intubation when attaining a bodyweight >2 kg (but <6 kg) to analyze the incidence of post-extubation stridor and only considered the first intubation of each included infant. Post-extubation stridor was defined as the administration of either epinephrine aerosol or any corticosteroid within 6 h post-extubation. In the second screening we searched for all infants diagnosed with acquired severe subglottic stenosis during the study period regardless their bodyweight and numbers of intubations. Results: A total of 389 infants received at least one intubation during the study period. After excluding infants who underwent the first intubation below a bodyweight of 2 kg, 271 infants remained for final analysis with an average gestational age of 38.7 weeks at the time of intubation. Among those, 92 (33.9%) were intubated with a cuffed and 179 (66.1%) with an uncuffed ETT. Seven infants (2.6%) developed a clinically significant stridor: five of those were intubated with a cuffed and two with an uncuffed ETT (71.4 vs. 28.6%, p = 0.053). All of them had a bodyweight >3 kg at the time of intubation. Infants who developed subglottic stenosis were more often intubated with an uncuffed ETT. Conclusion: In this study, no difference in the incidence of post-extubation stridor between cuffed and uncuffed ETTs in infants with a bodyweight from 2 to 6 kg could be found. The use of uncuffed ETTs does not exhibit higher risk for the acquired subglottic stenosis in this cohort.

The Role of Lung Ultrasound in the Management of the Critically Ill Neonate-A Narrative Review and Practical Guide.

Lung ultrasound makes use of artifacts generated by the ratio of air and fluid in the lung. Recently, an enormous increase of research regarding lung ultrasound emerged, especially in intensive care units. The use of lung ultrasound on the neonatal intensive care unit enables the clinician to gain knowledge about the respiratory condition of the patients, make quick decisions, and reduces exposure to ionizing radiation. In this narrative review, the possibilities of lung ultrasound for the stabilization and resuscitation of the neonate using the ABCDE algorithm will be discussed.

Directed Transport of CRP Across In Vitro Models of the Blood-Saliva Barrier Strengthens the Feasibility of Salivary CRP as Biomarker for Neonatal Sepsis.

C-reactive protein (CRP) is a commonly used serum biomarker for detecting sepsis in neonates. After the onset of sepsis, serial measurements are necessary to monitor disease progression; therefore, a non-invasive detection method is beneficial for neonatal well-being. While some studies have shown a correlation between serum and salivary CRP levels in septic neonates, the causal link behind this correlation remains unclear. To investigate this relationship, CRP was examined in serum and saliva samples from 18 septic neonates and compared with saliva samples from 22 healthy neonates. While the measured blood and saliva concentrations of the septic neonates varied individually, a correlation of CRP levels between serum and saliva samples was observed over time. To clarify the presence of active transport of CRP across the blood-salivary barrier (BSB), transport studies were performed with CRP using in vitro models of oral mucosa and submandibular salivary gland epithelium. The results showed enhanced transport toward saliva in both models, supporting the clinical relevance for salivary CRP as a biomarker. Furthermore, CRP regulated the expression of the receptor for advanced glycation end products (RAGE) and the addition of soluble RAGE during the transport studies indicated a RAGE-dependent transport process for CRP from blood to saliva.

Risk factors for mortality in infants with congenital diaphragmatic hernia: a single center experience.

BACKGROUND: Despite current progress in research of congenital diaphragmatic hernia, its management remains challenging, requiring an interdisciplinary team for optimal treatment. OBJECTIVE: Aim of the present study was to evaluate potential risk factors for mortality of infants with congenital diaphragmatic hernia. METHODS: A single-center chart review of all patients treated with congenital diaphragmatic hernia over a period of 16 years, at the Medical University of Vienna, was performed. A comparison of medical parameters between survivors and non-survivors, as well as to published literature was conducted. RESULTS: During the observational period 66 patients were diagnosed with congenital diaphragmatic hernia. Overall survival was 84.6%. Left-sided hernia occurred in 51 patients (78.5%) with a mortality of 7.8%. In comparison, right-sided hernia occurred less frequently (n = 12) but showed a higher mortality (33.3%, p = 0.000). Critically instable patients were provided with venoarterial extracorporeal membrane oxygenation (ECMO, 32.3%, n = 21). Survival rate among these patients was 66.7%. Right-sided hernia, treatment with inhaled nitric oxide (iNO) over 15 days and the use of ECMO over 10 days were significant risk factors for mortality. CONCLUSION: The survival rate in this cohort is comparable to the current literature. Parameters such as the side of the diaphragmatic defect, duration of ECMO and inhaled nitric oxide were assessed as mortality risk factors. This analysis of patients with congenital diaphragmatic hernia enhances understanding of risk factors for mortality, helping to improve management and enabling further evaluation in prospective clinical trials.

Mirrored Ribs: A Sign for Pneumothorax in Neonates.

OBJECTIVES: To evaluate if "mirrored ribs"-a mirroring of chest structures-is a sign for pneumothorax in lung ultrasound in neonates. DESIGN: Retrospective study. SETTING: Medical University Vienna/General Hospital, Vienna, Austria. PATIENTS: All neonates admitted with clinical signs of pneumothorax between July 2018 and February 2019. INTERVENTIONS: Chest radiograph and lung ultrasound in succession. MEASUREMENTS AND MAIN RESULTS: Anterior-posterior chest radiograph and lung ultrasound were compared. "Mirrored ribs" were defined as mirroring of at least one rib and intercostal muscles in B-mode in the absence of B-lines. Twenty-nine cases in 26 patients were considered. Pneumothorax was diagnosed in 55% of cases using reported signs for pneumothorax in lung ultrasound and in 31% using chest radiograph. Lung ultrasound identified all pneumothoraces visible in chest radiograph. "Mirrored ribs" were visible in all patients with signs for pneumothorax and in none without signs for pneumothorax in lung ultrasound, representing a specificity and sensitivity of 100% compared with reported signs for pneumothorax in lung ultrasound. CONCLUSIONS: The occurrence of "mirrored ribs" in lung ultrasound in combination with absence of lung sliding, absence of B-lines and lung point might facilitate the rapid recognition of pneumothorax in neonates.

Increased nurse workload is associated with bloodstream infections in very low birth weight infants.

Neonatal sepsis is a major cause of morbidity and mortality in very low birth weight infants (VLBWI). Nurse workload considerably affects infection rates in intensive care units. However, data concerning the impact of staff workload on bloodstream infections (BSI) in VLBWI are scarce. The aim of the study was to examine the association between nurse workload and BSI in VLBWI. VLBWI admitted to our neonatal intensive care unit during 2016-2017 were retrospectively analysed. Association between nurse workload, determined by a standardized nursing score, and the BSI occurrence was investigated. A higher nurse workload was significantly associated with higher occurrence of BSI (p = 0.0139) in VLBWI. An assumed workload of 120% or higher, representing the need for additional nurses in our NICU setting, is associated with an elevated risk for BSI in this vulnerable population OR 2.32 (95% CI: 1.42-3.8, p = 0.0005). In conclusion, nurse understaffing is associated with a higher risk for BSI in VLBWI.

Chemotherapeutic options for the treatment of human trichomoniasis.

Trichomonas vaginalis is the causative agent of the most common non-viral sexually transmitted disease worldwide. The infection may be associated with severe complications, including infertility, preterm labour, cancer and an increased risk of human immunodeficiency virus (HIV) transmission. Treatment remains almost exclusively based on 5-nitroimidazoles, but resistance is on the rise. This article provides an overview of clinically evaluated systemic and topical treatment options for human trichomoniasis and summarises the current state of knowledge on various herbal, semisynthetic and synthetic compounds evaluated for their anti-Trichomonas efficacy in vitro.

Intrapulmonary Human Cytomegalovirus Replication in Lung Transplant Recipients Is Associated With a Rise of CCL-18 and CCL-20 Chemokine Levels.

BACKGROUND: In lung transplant recipients (LTRs), human cytomegalovirus (HCMV) DNA detection in the bronchoalveolar lavage fluid (BALF) indicates HCMV replication in the pulmonary compartment. Such local HCMV replication episodes may remain asymptomatic or may lead to symptomatic HCMV disease. Here, we investigated LTRs with intrapulmonary HCMV replication for the chemokines CCL-18 and CCL-20. In particular, we analyzed whether these chemokines rise in the allograft and/or the blood and are associated with HCMV disease. METHODS: CCL-18 and CCL-20 levels were quantitated by ELISA in BALF and serum samples from 60 LTRs. During the posttransplant follow-up, these LTRs displayed HCMV DNA detection in the BALF by PCR, whereas other infectious agents were undetectable. Furthermore, we investigated samples from 10 controls who did not display any HCMV replication episode during the follow-up. RESULTS: HCMV replication in the allograft was associated with a significant increase of CCL-18 and CCL-20 BALF levels (P < 0.001, Wilcoxon signed-rank test) and a significant rise of CCL-20 (P < 0.0001, Wilcoxon signed-rank test) but not of CCL-18 in the blood. In controls, no such chemokine increase was observed. Furthermore, CCL-18 BALF levels were significantly higher in 8 LTRs who additionally developed HCMV disease, as compared with the other 52 patients in whom HCMV replication remained asymptomatic (P < 0.001, Mann-Whitney U test). CONCLUSIONS: HCMV replication in the allograft causes an intrapulmonary increase of CCL-18 and CCL-20 and a systemic rise of CCL-20 serum levels. Strong intrapulmonary CCL-18 responses are associated with symptomatic HCMV disease, proposing that CCL-18 BALF levels could serve as a marker.

In vitro effect of octenidine dihydrochloride against Trichomonas vaginalis.

Trichomoniasis is the most common non-viral sexually transmitted disease. It is associated with a wide spectrum of complications, including infertility and increased susceptibility to human immunodeficiency virus (HIV). A rising number of reports of Trichomonas vaginalis strains resistant to metronidazole has driven the search for new compounds. In the present study, the in vitro effects of the common antiseptic octenidine dihydrochloride against T. vaginalis were tested on metronidazole-resistant and -susceptible strains. Assays were performed under microaerophilic conditions in three different media containing varying concentrations of protein. It was shown that octenidine dihydrochloride is highly effective against T. vaginalis, with no difference between metronidazole-resistant and -susceptible strains. The 50% effective concentration (EC50) values ranged from 5.7 to 21.37µg/mL after 5min, from 6.48 to 10.82µg/mL after 15min and from 0.68 to 2.11µg/mL after 30min of treatment depending on the protein concentration of the test medium. Octenidine dihydrochloride, already approved in some countries for the treatment of bacterial and fungal vaginal infections, appears to be a promising alternative treatment for trichomoniasis, particularly in mixed vaginal infections or in cases caused by metronidazole-resistant strains.