Serum Neuron-Specific Enolase as a Biomarker of Neonatal Brain Injury-New Perspectives for the Identification of Preterm Neonates at High Risk for Severe Intraventricular Hemorrhage.

Neonatal brain injury (NBI) is a critical condition for preterm neonates with potential long-term adverse neurodevelopmental outcomes. This prospective longitudinal case-control study aimed at investigating the levels and prognostic value of serum neuron-specific enolase (NSE) during the first 3 days of life in preterm neonates (<34 weeks) that later developed brain injury in the form of either periventricular leukomalacia (PVL) or intraventricular hemorrhage (IVH) during their hospitalization. Participants were recruited from one neonatal intensive care unit, and on the basis of birth weight and gestational age, we matched each case (n = 29) with a neonate who had a normal head ultrasound scan (n = 29). We report that serum NSE levels during the first three days of life do not differ significantly between control and preterm neonates with NBI. Nevertheless, subgroup analysis revealed that neonates with IVH had significantly higher concentrations of serum NSE in comparison to controls and neonates with PVL on the third day of life (p = 0.014 and p = 0.033, respectively). The same pattern on the levels of NSE on the third day of life was also observed between (a) neonates with IVH and all other neonates (PVL and control; p = 0.003), (b) neonates with II-IV degree IVH and all other neonates (p = 0.003), and (c) between control and the five (n = 5) neonates that died from the case group (p = 0.023). We conclude that NSE could be an effective and useful biomarker on the third day of life for the identification of preterm neonates at high risk of developing severe forms of IVH.

Candida auris Infection, a Rapidly Emerging Threat in the Neonatal Intensive Care Units: A Systematic Review.

(1) Background: In recent years, a global epidemiological shift in candidemia has been observed, marked by the emergence of resistant non-albicans Candida species. Candida auris, in particular, has become a significant global concern, causing infections in both pediatric and adult populations within healthcare settings. Despite its widespread impact, there is a limited understanding of the clinical course and transmission dynamics of neonatal systemic Candida auris infections, hindering effective prevention and management. This study focused on the epidemiologic data, the clinical presentation, risk factors, and outcome of C. auris infection in neonatal population. (2) Methods: A systematic review of the literature using PubMed and Scopus databases until December 2023 was conducted. (3) Results: A total of 24 relevant studies were identified, encompassing 476 documented cases of Candida auris infection in neonates. Prematurity emerged as a primary risk factor, alongside total parenteral nutrition, central line insertion, mechanical ventilation, and prior broad-spectrum antibiotic use. The mortality rate reached approximately 42%, with therapeutic details sparingly reported in 12% of cases. Treatment strategies varied, with amphotericin B predominantly used as monotherapy, while combination antifungal agents were used in 44% of cases. Notably, 97.4% of cases exhibited fluconazole resistance, and 67.1% showed resistance to amphotericin B. Limited data were available on resistance to other antifungal agents. (4) Conclusions: Despite the rarity of neonatal Candida auris infections, their global occurrence necessitates comprehensive preparedness in patient care. A deeper understanding of Candida auris pathogenesis is crucial for developing effective strategies to control and prevent neonatal infections caused by this pathogen.

Sovateltide (ILR-1620) Improves Motor Function and Reduces Hyperalgesia in a Rat Model of Spinal Cord Injury.

BACKGROUND: Spinal cord injury (SCI) presents a major global health challenge, with rising incidence rates and substantial disability. Although progress has been made in understanding SCI's pathophysiology and early management, there is still a lack of effective treatments to mitigate long-term consequences. This study investigates the potential of sovateltide, a selective endothelin B receptor agonist, in improving clinical outcomes in an acute SCI rat model. METHODS: Thirty male Sprague-Dawley rats underwent sham surgery (group A) or SCI and treated with vehicle (group B) or sovateltide (group C). Clinical tests, including Basso, Beattie, and Bresnahan scoring, inclined plane, and allodynia testing with von Frey hair, were performed at various time points. Statistical analyses assessed treatment effects. RESULTS: Sovateltide administration significantly improved motor function, reducing neurological deficits and enhancing locomotor recovery compared with vehicle-treated rats, starting from day 7 post injury. Additionally, the allodynic threshold improved, suggesting antinociceptive properties. Notably, the sovateltide group demonstrated sustained recovery, and even reached preinjury performance levels, whereas the vehicle group plateaued. CONCLUSIONS: This study suggests that sovateltide may offer neuroprotective effects, enhancing neurogenesis and angiogenesis. Furthermore, it may possess anti-inflammatory and antinociceptive properties. Future clinical trials are needed to validate these findings, but sovateltide shows promise as a potential therapeutic strategy to improve functional outcomes in SCI. Sovateltide, an endothelin B receptor agonist, exhibits neuroprotective properties, enhancing motor recovery and ameliorating hyperalgesia in a rat SCI model. These findings could pave the way for innovative pharmacological interventions for SCI in clinical settings.

The Effect of Oral Iron Supplementation/Fortification on the Gut Microbiota in Infancy: A Systematic Review and Meta-Analysis.

(1) Background: Iron is an essential metal for the proper growth and neurodevelopment of infants. To prevent and treat iron deficiency, iron supplementation or fortification is often required. It has been shown, though, that it affects the synthesis of gut microbiota. (2) Methods: This paper is a systematic review and meta-analysis of the effect of oral iron supplementation/fortification on the gut microbiota in infancy. Studies in healthy neonates and infants who received per os iron with existing data on gut microbiota were included. Three databases were searched: PUBMED, Scopus, and Google Scholar. Randomized controlled trials (RCTs) were included. Quality appraisal was assessed using the ROB2Tool. (3) Results: A total of six RCTs met inclusion criteria for a systematic review, and four of them were included in the meta-analysis using both the fixed and random effects methods. Our results showed that there is very good heterogeneity in the iron group (I2 = 62%), and excellent heterogeneity in the non-iron group (I2 = 98%). According to the meta-analysis outcomes, there is a 10.3% (95% CI: -15.0--5.55%) reduction in the bifidobacteria population in the iron group and a -2.96% reduction for the non-iron group. There is a confirmed difference (p = 0.02) in the aggregated outcomes between iron and non-iron supplement, indicative that the bifidobacteria population is reduced when iron supplementation is given (total reduction 6.37%, 95%CI: 10.16-25.8%). (4) Conclusions: The abundance of bifidobacteria decreases when iron supplementation or fortification is given to infants.

Coagulation Profile in Neonates with Congenital Heart Disease: A Pilot Study.

Background and Objectives: congenital heart disease (CHD), cyanotic and, to a lesser degree, acyanotic, often are accompanied by coagulation abnormalities, impacting substantially morbidity and mortality. Until now, no consistent hemostatic patterns have been demonstrated in neonates and children with CHD because they represent a variable and heterogenous population. The aim of the present study is to investigate the hemostatic profile, as well as the role of ADAMTS-13 (a disintegrin and metalloprotease with thrombospondin type-1 motives), the cleaving protein of von Willebrand factor (VWF) in neonates with CHD and compare them to healthy age-matched controls. Materials and Methods: twenty neonates with a mean gestational age of 37.1 ± 2.5 weeks were included in the CHD group, and 18 healthy neonates with a mean gestational age of 38.2 ± 1.5 weeks were in the control group. Results: prothrombin time was significantly prolonged, and accordingly, factor VII (FVII) levels were significantly decreased in the CHD group in comparison to controls. Factor VIII (FVIII), VWF, and ristocetin cofactor activity (Rcof) levels were significantly higher in the study vs. control group. Concentrations of ADAMTS-13 were decreased in the CHD vs. control group, but the difference was not statistically significant. Our results, in combination, indicate a balanced hemostatic mechanism, although with greater variability in neonates with CHD, while developmental aspects of coagulation are evident in the specific patient population. Conclusions: the coagulation profile is moderately impaired early in the course of CHD, though increased thrombogenicity is already present and should not be ignored.

Laryngotracheoesophageal Cleft Type IV in a Preterm Neonate. A Case Report and Literature Review.

We present a case of a preterm neonate with a type IV laryngo-tracheo-oesophageal cleft, an uncommon congenital malformation, resulting from the failure of separation of the trachea and the oesophagus during fetal development, often associated with other deformities as well. Data in the literature shows that the long-term morbidity from the entity has declined over the last decades, even though prognosis remains unfavourable for types III and IV. This report emphasizes the complex issues neonatologists are faced with, when treating neonates with this rare disorder in the first days of life, what will raise suspicion of this rare medical entity, and that direct laryngoscopy/bronchoscopy finally depicts the exact extension of the medical condition. At the same time extensive evaluation for coexisting congenital anomalies should be performed. For all the above reasons, these neonates should be treated in specialized tertiary pediatric centers for multidisciplinary prompt management, which may improve, the outcome.

Epidemiology, risk factors, clinical presentation and complications of late-onset neonatal sepsis among preterm neonates in Cyprus: a prospective case-control study.

BACKGROUND: Late-onset neonatal sepsis (LOS) is common in preterm neonates, with increasing incidence in recent years. In the present study, we examined the epidemiology, clinical presentation, and complications of LOS in Cyprus and quantified possible risk factors for the development of this condition. METHODS: The study subjects were preterm neonates admitted in the Neonatal Intensive Care Unit (NICU) of Archbishop Makarios III Hospital, the only neonatal tertiary centre in Cyprus. A prospective, case-control study was designed, and carried out between April 2017-October 2018. Depending on blood culture results, preterm neonates were classified as "Confirmed LOS": positive blood culture - microorganism isolated and LOS symptoms, "Unconfirmed LOS": negative blood culture and LOS symptoms, and "Controls" group: negative blood culture and absence of LOS symptoms. Comparisons between the 3 groups were performed and the associations between demographic, clinical and treatment characteristics with the likelihood of LOS were assessed using univariate and multivariate logistic regression. RESULTS: A total of 350 preterm neonates were included in the study and the incidence of LOS was 41.1%. 79 (22.6%) and 65 (18.6%) neonates were classified as "Confirmed LOS", and "unconfirmed LOS" cases respectively while 206 (58.9%) served as controls. The rate of confirmed LOS ranged from 12.2% in moderate to late preterm neonates to 78.6% in extremely preterm neonates. In the multivariate model, we demonstrated an independent association between LOS and duration of hospitalization (OR: 1.06, 95%CI: 1.01-1.10), duration of ventilation (OR: 1.23, 95%CI: 1.07-1.43) and necrotising enterocolitis (OR: 3.41, 95%CI: 1.13-10.25). CONCLUSIONS: The present study highlights the epidemiology of LOS in preterm neonates in Cyprus and its association with the duration of ventilation and hospitalization as well as with necrotizing enterocolitis. Establishment of protocols for the prevention of nosocomial infections during hospitalization in the NICUs and mechanical ventilation of preterm neonates is recommended.

Hemostatic Profile of Intrauterine Growth-Restricted Neonates: Assessment with the Use of NATEM Assay in Cord Blood Samples.

BACKGROUND: Intrauterine growth restriction (IUGR) is associated with hemorrhagic and thrombotic complications during the perinatal period. Thrombocytopenia, platelet dysfunction, and prolonged standard coagulation tests are observed in this population. The aim of this study is to examine the hemostatic profile of IUGR neonates with the use of a non-activated assay (NATEM) in cord blood samples. METHODS: During an 18 month period, a NATEM ROTEM assay was performed on cord blood samples of 101 IUGR neonates. A total of 189 appropriate for gestational age (AGA) neonates were used as a control group. The NATEM variables recorded include the following: clotting time (CT); clot formation time (CFT); clot amplitude at 5, 10, and 20 min (A5, A10, A20); α-angle (a°); maximum clot firmness (MCF); lysis index at 30 and 60 min (LI30, LI60); and maximum clot elasticity (MCE). RESULTS: IUGR neonates demonstrate a hypocoagulable state, with lower A5, A10, A2, MCF, and MCE values when compared to AGA. Using multiple linear regression, we determined IUGR as an independent factor influencing all NATEM parameters (except CT and LI30) exhibiting a hypocoagulable and hypofibrinolytic profile. Platelet count was positively correlated with A5, A10, A20, MCF, alpha angle, and MCE, and negatively correlated with CFT. CONCLUSION: IUGR neonates appear with lower clot strength and elasticity and prolonged clot kinetics, as illustrated by ROTEM variables.

Assessment of Hemostatic Profile in Neonates with Intrauterine Growth Restriction: A Systematic Review of Literature.

Intrauterine growth restriction (IUGR) affects nearly 10 to 15% of pregnancies and is responsible for many short- and long-term adverse consequences, including hemostatic derangement. Both thrombotic and hemorrhagic events are described in the perinatal period in these neonates. The aim of this study was to systematically review the literature on the laboratory studies used to evaluate the hemostatic system of the IUGR small for gestational age neonate. We reviewed the current literature via PubMed and Scopus until September 2022. Following our inclusion/exclusion criteria, we finally included 60 studies in our review. Thrombocytopenia, characterized as hyporegenerative and a kinetic upshot of reduced platelet production due to in utero chronic hypoxia, was the main finding of most studies focusing on growth-restricted neonates, in most cases is mild and usually resolves spontaneously with the first 2 weeks of life. In regard to coagulation, growth-restricted newborns present with prolonged standard coagulation tests. Data regarding coagulation factors, fibrinolytic system, and anticoagulant proteins are scarce and conflicting, mainly due to confounding factors. As thromboelastography/rotational thromboelastometry (TEG/ROTEM) provides a more precise evaluation of the in vivo coagulation process compared with standard coagulation tests, its use in transfusion guidance is fundamental. Only one study regarding TEG/ROTEM was retrieved from this population, where no difference in ROTEM parameters compared with appropriate for gestational age neonates was found. Despite the laboratory aberrations, no correlation could be achieved with clinical manifestations of bleeding or thrombosis in the studies included. More studies are needed to assess hemostasis in IUGR neonates and guide targeted therapeutic interventions.

Thromboelastometry and prediction of in-hospital mortality in neonates with sepsis.

INTRODUCTION: This study aimed at evaluating the role of rotational thromboelastometry (ROTEM) assays in the prediction of in-hospital mortality of neonates with sepsis. METHODS: Over a 6-year period, 129 neonates with confirmed sepsis, hospitalized in our neonatal intensive care unit (NICU) were included in the study. Demographics, clinical, and laboratory data were recorded at the sepsis onset and ROTEM assays were performed. Modified neonatal multiple organ dysfunction (NEOMOD) and neonatal sequential organ failure assessment (nSOFA) were calculated simultaneously. Mortality during in-hospital stay was the main outcome measure. RESULTS: In-hospital mortality was associated with patient intense hypocoagulability expressed by lower ROTEM MCF in the INTEM assay. The INTEM MCF demonstrated the best prognostic performance for NICU mortality in septic neonates among the other ROTEM parameters but without statistical significance (area under the curve [AUC] = 0.731; 95% confidence interval [CI]: 0.593-0.869). CONCLUSION: Our results indicate that ROTEM INTEM MCF parameter has good predictive capacity for in-hospital mortality of septic neonates, similar to that of modified NEOMOD score, nSOFA score, and platelet count, highlighting the integral role of coagulation in sepsis pathophysiology. Hence, ROTEM could serve as a valuable monitoring tool to identify neonates at risk.

Contemporary tools for evaluation of hemostasis in neonates. Where are we and where are we headed?

The assessment of hemostatic disorders in neonates is crucial, but remains challenging for clinicians. Although the concept of developmental hemostasis is widely accepted among hemostasis specialists globally, it is probably under-recognized by clinicians and laboratory practitioners. In parallel with age-dependent hemostatic status maturation, comprehension of the differences between normal values is crucial for the accurate diagnosis of potential hemorrhagic and thrombotic disorders of the vulnerable neonatal population. This review outlines the basics of developmental hemostasis and the features of the available coagulation testing methods, with a focus on novel tools for evaluating the neonatal hemostatic profile. Common errors, issues, and pitfalls during the assessment of neonatal hemostasis are discussed, along with their impact on patient management. Current knowledge gaps and research areas are addressed. Further studying to improve our understanding of developmental hemostasis and its reflection on everyday clinical practice is warranted.

Assessment of hemostatic profile in neonates with necrotizing enterocolitis using Rotational Thromboelastometry (ROTEM).

BACKGROUND: This study aimed to explore the hemostatic profile of neonates with necrotizing enterocolitis (NEC) using Rotational Thromboelastometry (ROTEM) and to investigate if ROTEM parameters have the capacity to play a role in the differentiation of NEC from sepsis at the disease onset. METHODS: This observational study included 62 neonates (mean gestational age 31.6 weeks and mean birth weight 1620g) hospitalized in a neonatal intensive care unit. The neonates were categorized in three groups: neonates with NEC (Bell stage II and above), neonates with sepsis and healthy neonates and they were matched 1:1:1 with regards to gestational age, delivery mode, and sex. Clinical, laboratory data as well as measurements of ROTEM parameters at disease onset were recorded. RESULTS: ROTEM parameters differed between neonates with NEC and neonates with sepsis, indicating that NEC results in accelerated clot formation and higher clot strength compared to sepsis. The EXTEM CFT and A10 parameters demonstrated the highest diagnostic performance for NEC in terms of discrimination between NEC and sepsis (AUC, 0.997; 95% CI: 0.991-1.000 and 0.973; 95% CI: 0.932-1.000, respectively). CONCLUSIONS: Neonates with NEC manifested accelerated clot formation and higher clot strength compared to septic and healthy neonates, as these were expressed by ROTEM parameters. IMPACT: This work reports data on the hemostatic profile of neonates with necrotizing enterocolitis (NEC) using Rotational Thromboelastometry (ROTEM) and the capacity of ROTEM parameters in differentiating of NEC from sepsis at the disease onset. Neonates with NEC present acceleration of coagulation and exhibit a hypercoagulable profile, as this is expressed by ROTEM parameters, in comparison to septic and healthy neonates. ROTEM parameters demonstrated a good diagnostic capacity in differentiating NEC from sepsis at the disease onset.

Group A Streptococcus Infection in Neonatal Population: A Systematic Review of The Literature.

(1) Background: The importance of group A streptococcus (GAS) infection severity has been recognized in children and adults. However, to our knowledge, there have been no systematic reviews or pooled assessments of the incidence and outcome of invasive GAS (iGAS) disease in neonates, a potentially high-risk population. Therefore, we performed a systematic review of available data regarding the risk factors, clinical presentation, and outcome of GAS infection in neonates. (2) Methods: An electronic search of the existing literature was carried out during the period July 2023-September 2023 in the PubMed and Scopus databases, considering studies referring to GAS infection in the neonatal population. (3) Results: Overall, 39 studies met all the inclusion criteria and were included in this review, evaluating data from 194 neonates. Unfortunately, there were a lot of missing data among the retrieved studies. Our systematic review highlighted the presence of differences with regards to clinical presentation, infection sites, and outcome of GAS invasive disease between neonates with early-onset (EOS) or late-onset sepsis (LOS). Common characteristics of EOS included respiratory distress, rapid deterioration, and high mortality rate irrespective of the infection site, while rash, gastrointestinal tract symptoms, and fever appeared to be the most frequent symptoms/clinical signs and manifestations of LOS disease. The management of severe invasive iGAS disease consists mainly of specific antimicrobial treatment as well as supportive care with fluids and electrolyte supplementation, minimizing or counteracting the effects of toxins. Furthermore, a mortality rate of approximately 14% was recorded for iGAS disease in the total of all studies' neonates. (4) Conclusions: Although iGAS is a rare entity of neonatal infections, the potential severity of the disease and the rapid deterioration requires the development of quick analysis methods for the detection of GAS allowing the prompt diagnosis and administration of the indicated antibiotic treatment. Furthermore, given the exceptional risk for both the pregnant woman and the neonate, it is very important to raise awareness and create easily accessible guidelines that could facilitate the prevention and management of maternal as well as the subsequent neonatal severe iGAS disease.

Bleeding Scoring Systems in Neonates: A Systematic Review.

We conducted a systematic review aiming to summarize the data on the current hemorrhage prediction models and evaluate their potential for generalized application in the neonatal population. The electronic databases PubMed and Scopus were searched, up to September 20, 2023, for studies that focused on development and/or validation of a prediction model for bleeding risk in neonates, and described the process of model building. Nineteen studies fulfilled the inclusion criteria for the present review. Eighteen bleeding risk prediction models in the neonatal population were identified, four of which were internally validated, one temporally and one externally validated. The existing prediction models for neonatal hemorrhage are mostly based on clinical variables and do not take into account the clinical course and hemostatic profile of the neonates. Most studies aimed at predicting the risk of intraventricular hemorrhage (IVH) reflecting the fact that IVH is the most frequent and serious bleeding complication in preterm neonates. A justification for the study sample size for developing the prediction model was given only by one study. Prediction and stratification of risk of hemorrhage in neonates is yet to be optimized. To this end, qualitative standards for model development need to be further improved. The assessment of the risk of bleeding incorporating platelet count, coagulation parameters, and a set of relevant clinical variables is crucial. Large, rigorous, collaborative cohort studies are warranted to develop a robust prediction model to inform the need for transfusion, which is a fundamental step towards personalized transfusion therapy in neonates.

A Novel Variant in the TP53 Gene Causing Li-Fraumeni Syndrome.

Li-Fraumeni syndrome (LFS) is an autosomal dominant hereditary cancer syndrome associated with germline pathogenic variants in the tumor protein p53 (TP53) gene and elevated risk of a broad range of early-onset malignancies. Patients with LFS are at risk of a second and third primary tumor. A 15-month-old girl consulted for clitoromegaly and pubic hair. Adrenal ultrasound detected a large left adrenal tumor. Left total adrenalectomy confirmed adrenocortical carcinoma. Family history revealed multiple highly malignant neoplasms at an early age across five generations, and a genetic dominant trait seemed probable. Whole-genome sequencing was performed. Multiple members of the family were found positive for a novel likely pathogenic variant (c. 892delGinsTTT, p. Glu298PhefsX48, NM_000546.6) in the TP53 gene, causing the loss of normal protein function through non-sense-mediated mRNA decay. According to the PSV1 supporting criteria and the Auto PVS1 online tool this frameshift variant: hg19/17-7577045-TC-TAAA:NM_000546.6 has a very strong, definitive clinical validity for LFS with autosomal dominant inheritance. Proper guidance resulted in timely diagnosis of a second tumor (primary osteosarcoma) in the index case and in the early detection of breast and cervical cancer in her young mother. Patients with cancer predisposition syndromes like LFS require close multidisciplinary cancer surveillance and appropriate referral to expert centers.

Knowledge Gaps and Current Evidence Regarding Breastfeeding Issues in Mothers with Chronic Diseases.

The prevalence of chronic maternal disease is rising in the last decades in the developed world. Recent evidence indicated that the incidence of chronic maternal disease ranges from 10 to 30% of pregnancies worldwide. Several epidemiological studies in mothers with chronic diseases have mainly focused on the risk for adverse obstetric outcomes. Evidence from these studies supports a correlation between maternal chronic conditions and adverse perinatal outcomes, including increased risk for preeclampsia, cesarean section, preterm birth, and admission in the Neonatal Intensive Care Unit (NICU). However, there is a knowledge gap pertaining to the management of these women during lactation. This review aimed at summarizing the available research literature regarding breastfeeding in mothers with chronic diseases. Adjusted and evidence-based support may be required to promote breastfeeding in women with chronic diseases; however, our comprehension of breastfeeding in this subpopulation is still unclear. The literature related to breastfeeding extends in various scientific areas and multidisciplinary effort is necessary to compile an overview of current evidence and knowledge regarding breastfeeding issues in mothers with chronic diseases.

The Impact of Infant Feeding Regimen on Cow's Milk Protein Allergy, Atopic Dermatitis and Growth in High-Risk Infants during the First 6 Months of Life: The Allergy Reduction Trial.

The development of early-onset cow's milk protein allergy and atopic dermatitis during the first months of life is multifactorial, including both genetic and nutritional aspects. This study aims to assess the impact of different feeding patterns on the incidence of cow's milk protein allergy, atopic dermatitis, and growth among infants with a family history of allergy. A total of 551 high-risk infants were randomly recruited from 3 European countries in three feeding regimens: exclusive breastfeeding, partially hydrolyzed formula, or standard formula with intact protein either exclusively or supplementary to breastfeeding. During the first 6 months of intervention, amongst infants with a family history of atopic dermatitis, 6.5% of partially hydrolyzed formula-fed infants and 22.7% of exclusively breastfed infants (p = 0.007) presented with atopic dermatitis respectively. Growth as assessed by weight increase did not differ between the aforementioned groups. Although cow's milk protein allergy was not related to the different milk feeding regimens in the whole cohort, when adjusting for high breast milk intake, the respective incident was significantly lower in the infants consuming partially hydrolyzed formula (p < 0.001). This data indicates that a specific partially hydrolyzed formula could serve as a more appropriate complement to breast milk compared to a standard intact protein formula in high-risk infants, to reduce the incidence of atopic dermatitis.

Urinary NT-proBNP: A Useful Biomarker for the Diagnosis of Respiratory Distress in the Neonatal Population.

OBJECTIVE: To determine the diagnostic accuracy of urinary NT-proBNP levels in the detection and classification of the severity of respiratory distress in neonates after birth. METHODS: We compared the urinary NT- proBNP levels between the respiratory distress (RD) group and the control group on the 1st, 3rd, and 5th day of life (DOL). RESULTS: The RD group (55 neonates) showed higher levels of NT-proBNP compared to the control group (63 neonates) on DOL1 (585.4 pg/ml vs 396.1 pg/ml (p=0.014)), DOL3 (805.1 pg/ml vs 271.9 pg/ml (p<0.001)) and DOL5 (409.7 pg/ml vs 94.4 pg/ml (p<0.001)). Especially, on DOL5, the area under the ROC curve was 0.884 and the NT-proBNP cut-off value (221.8 pg/ml) showed a sensitivity of 71% and specificity of 79%. The RD group was subclassified into neonates with mild (21 neonates), moderate (19 neonates), and severe (15 neonates) disease. NT-proBNP cut-off point of 668 pg/ml for DOL5 can safely differentiate neonates with severe disease from those with mild and moderate disease (combined subgroups) since the sensitivity was 80% and specificity was 77.5% for DOL5. CONCLUSION: Urinary NT-proBNP levels are a useful biomarker in detecting clinical signs of respiratory distress in neonates that are born within the first week of life; they can also detect neonates that are vulnerable to severe forms of the disease.

Anti-SARS-CoV-2 Immunoglobulins in Human Milk after Coronavirus Disease or Vaccination-Time Frame and Duration of Detection in Human Milk and Factors That Affect Their Titers: A Systematic Review.

Human milk (HM) of mothers infected with or vaccinated against SARS-CoV-2 contains specific immunoglobulins, which may protect their offspring against infection or severe disease. The time frame and duration after infection or vaccination, during which these immunoglobulins are detected in HM, as well as the major factors that influence their levels, have not been fully elucidated. This systematic review aimed to collect the existing literature and describe the immune response, specifically regarding the immunoglobulins in HM after COVID-19 disease or vaccination in non-immune women. We conducted a systematic search of PubMed and Scopus databases to identify studies published up until 19 March 2023. In total, 975 articles were screened, and out of which 75 were identified as being relevant and were finally included in this review. Infection by SARS-CoV-2 virus primarily induces an IgA immune response in HM, while vaccination predominantly elevates IgG levels. These immunoglobulins give HM a neutralizing capacity against SARS-CoV-2, highlighting the importance of breastfeeding during the pandemic. The mode of immune acquisition (infection or vaccination) and immunoglobulin levels in maternal serum are factors that seem to influence immunoglobulin levels in HM. Further studies are required to determine the impact of other factors, such as infection severity, lactation period, parity, maternal age and BMI on immunoglobulin level in HM.

Sepsis-Induced Coagulopathy: An Update on Pathophysiology, Biomarkers, and Current Guidelines.

Significant cross talk occurs between inflammation and coagulation. Thus, coagulopathy is common in sepsis, potentially aggravating the prognosis. Initially, septic patients tend to exhibit a prothrombotic state through extrinsic pathway activation, cytokine-induced coagulation amplification, anticoagulant pathways suppression, and fibrinolysis impairment. In late sepsis stages, with the establishment of disseminated intravascular coagulation (DIC), hypocoagulability ensues. Traditional laboratory findings of sepsis, including thrombocytopenia, increased prothrombin time (PT) and fibrin degradation products (FDPs), and decreased fibrinogen, only present late in the course of sepsis. A recently introduced definition of sepsis-induced coagulopathy (SIC) aims to identify patients at an earlier stage when changes to coagulation status are still reversible. Nonconventional assays, such as the measurement of anticoagulant proteins and nuclear material levels, and viscoelastic studies, have shown promising sensitivity and specificity in detecting patients at risk for DIC, allowing for timely therapeutic interventions. This review outlines current insights into the pathophysiological mechanisms and diagnostic options of SIC.