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.

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.

The effects of pathogen reduction technology on apheresis platelet concentrates stored in PAS.

BACKGROUND: The impact of pathogen reduction technology (PRT) such as Mirasol, and the effect of platelet additive solutions (PAS) on the activity and hemostatic profile of transfused apheresis platelets remain largely unknown. The aim of this study was to assess the in vitro hemostatic and metabolic profile of Mirasol treated platelets in PAS during a 7-day storage period. MATERIAL AND METHODS: Ten split bags containing apheresis platelets stored in PAS were split into two groups; control platelets (No.=10 units) and PRT-treated platelets (No.=10 units). In vitro evaluation of the platelet components was performed on the 1st, 3rd, 5th, and 7th days of the storage period. Several metabolic parameters including pH, glucose, and lactate levels were evaluated, while assessment of their hemostatic capacity was performed using light transmission aggregometry (LTA) and viscoelastic studies such as rotational thromboelastometry (ROTEM) and thromboelastography (TEG). Last, Annexin V levels were measured though flow cytometry for evaluation of platelet activation. RESULTS: Clot strength, as reflected by the maximum clot firmness (MCF) and the maximum amplitude (MA) parameters of the viscoelastic studies was significantly decreased in the PRT-treated platelets compared to the control platelets (p<0.05). Clot strength based on MCF and MA values was also found to be decreasing over storage time in PRT-treated platelets (p<0.001), while this was not evident in control platelets. Moreover, the comparison between pH, glucose, and lactate levels were indicative of increased metabolic activity in PRT-treated platelets compared to control platelets (p<0.001). Last, Annexin-V was significantly higher in PRT-treated platelets compared to control platelets on the 7th day of the storage period (p<0.001). DISCUSSION: The results of this study indicate that increased PSL induced by PRT treatment leads to a decreased in vitro platelet hemostatic efficacy and increased metabolic activity. However, the clinical impact of these alternations needs further investigation.

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.

Racial Disparities in Infliximab Efficacy for Ulcerative Colitis: Evidence Synthesis and Effect Modification Assessment.

An increasing amount of research explores the role of race in clinical phenotypes and outcomes in ulcerative colitis (UC). We aimed to investigate racial differences in infliximab (IFX) treatment efficacy in UC. We used aggregate data from IFX trials and evidence synthesis methods to generate race-specific efficacy estimates. Then, we tested the effect modification by race by comparing the race-specific estimates derived from independent evidence syntheses. We computed ratios of relative risks (RRRs) and performed tests of statistical interaction. We analyzed data from five randomized, placebo-controlled trials evaluating IFX as induction and maintenance therapy for adults with moderate-to-severe UC (875 participants; 45% Asians). We found no substantial evidence of racial differences concerning the efficacy of IFX in inducing clinical response (RRR = 0.89, 95% CI: 0.66-1.20; p = 0.44), clinical remission (RRR = 0.58, 95% CI: 0.24-1.44; p = 0.24), and mucosal healing (RRR = 0.99, 95% CI: 0.69-1.41; p = 0.95), or maintaining clinical remission (RRR = 0.81, 95% CI: 0.46-1.42; p = 0.45) and mucosal healing (RRR = 0.84, 95% CI: 0.48-1.46; p = 0.53), between Asian and Caucasian populations. Future clinical studies should expand the participation of racial minorities to comprehensively assess potential racial differences in the effectiveness of advanced therapies, including IFX, in the context of treating UC.

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.

Nutrition and Growth of Preterm Neonates during Hospitalization: Impact on Childhood Outcomes.

The Special Issue has been completed with the publication of 13 review and research articles [...].

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.

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.

Detection and Quantification of Acrylamide in Second Trimester Amniotic Fluid Using a Novel LC-MS/MS Technique to Determine Whether High Acrylamide Content during Pregnancy Is Associated with Fetal Growth.

INTRODUCTION: Acrylamide, an organic compound, is, chemically speaking, a vinyl-substituted primary amide. It is produced industrially, principally as a precursor to polyacrylamides, for use in such products as plastics and cosmetics. This same compound, however, forms naturally in certain foods, both home-cooked and packaged, especially when prepared at high temperatures. We developed and validated a novel reliable technique for the determination of acrylamide in amniotic fluid. Multiple reaction monitoring (MRM) is a targeted mass spectrometry (MS) technique which enables the detection and quantification of particular molecules in a complex mixture. Thanks to its throughput, selectivity, and sensitivity, MRM-MS has been identified as offering an alternative to antibody-based studies for the purpose of biomarker verification. Our aim was to investigate the presence of acrylamide in amniotic fluid and, via the MRM-MS technique, to determine whether there is any correlation between maternal exposure to acrylamide, through a woman's diet, and fetal growth. METHODS: Our amniotic fluid bank included 40 samples from various fetal growth rates, as objectively denoted by the neonatal weight centile at delivery, while our analytical detection method was based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). Acrylamide was determined with reversed phase chromatography and monitoring of two multiple reaction monitoring (MRM) transitions. Quantification was performed using the matrix-matched calibration curve. RESULTS: Acrylamide was detected at concentrations between 7.1 and 1468 ng/mL in six out of the total of 40 amniotic fluid samples that were used. Our method limit of detection and quantification was 1.4 ng/mL and 4.6 ng/mL, respectively. The repeatability of our method ranged between 11 and 14%, expressed as relative standard deviation levels between 5 and 100 ng/mL. CONCLUSIONS: Detection of acrylamide in early second trimester amniotic fluid, for the first time in the literature to our knowledge, raises concerns about fetal health, given that published data on animal studies have attributed a number of birth defects to acrylamide. Our novel LC-MS/MS method for the determination of acrylamide in amniotic fluid proved to be effective and its performance in practice was very accurate, simple, and fast. Validation of the method revealed that the use of a matrix-matched curve is necessary for the quantification.

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.

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.

A Global Assessment of Coagulation Profile and a Novel Insight into Adamts-13 Implication in Neonatal Sepsis.

Neonatal sepsis is a life-threatening condition associated with significant morbidity and mortality. Sepsis-induced coagulopathy is a well-recognized entity, signifying the strong cross-talk between inflammation and coagulation. The aim of the present study was to compare the coagulation profile between the acute phase of sepsis and recovery in term and preterm neonates. Additional comparisons to healthy neonates were undertaken. Levels of clotting, anti-clotting factors and ADAMTS-13 (A disintegrin and metalloprotease with thrombospondin type-1 motives), the cleaving protein of von Willebrand factor (VWF), were measured in 16 term and preterm neonates in the acute phase of infection and following recovery, as well as in 18 healthy neonates. Clotting times were prolonged, while levels of particular clotting factors were lower in the acute phase of infection compared to controls and recovery. On the other hand, levels of fibrinogen, factor VIII (FVIII) and VWF were significantly higher in the acute phase in comparison to controls and recovery, while they remained persistently higher in the infection group compared to controls. In regard to the anticlotting mechanism, a clear suppression was observed in septic neonates. ADAMTS-13 levels were significantly lower in the acute phase of infection in comparison to controls and recovery (p = 0.015 and 0.004, respectively), while a trend toward superimposed normalization was demonstrated post infection, as higher ADAMTS-13 levels were measured in recovered neonates compared to controls (p = 0.002). The coagulation profile is considerably deranged in neonatal sepsis. ADAMTS-13 deficiency in septic neonates is a novel finding with promising future implications, as ADAMTS-13 substitution may serve as a useful therapeutic option in neonatal sepsis, prompting further investigation in future studies.

Optimizing Clinical Decision Making with Decision Curve Analysis: Insights for Clinical Investigators.

A large number of prediction models are published with the objective of allowing personalized decision making for diagnostic or prognostic purposes. Conventional statistical measures of discrimination, calibration, or other measures of model performance are not well-suited for directly and clearly assessing the clinical value of scores or biomarkers. Decision curve analysis is an increasingly popular technique used to assess the clinical utility of a prognostic or diagnostic score/rule, or even of a biomarker. Clinical utility is expressed as the net benefit, which represents the net balance of patients' benefits and harms and considers, implicitly, the consequences of clinical actions taken in response to a certain prediction score, rule, or biomarker. The net benefit is plotted against a range of possible exchange rates, representing the spectrum of possible patients' and clinicians' preferences. Decision curve analysis is a powerful tool for judging whether newly published or existing scores may truly benefit patients, and represents a significant advancement in improving transparent clinical decision making. This paper is meant to be an introduction to decision curve analysis and its interpretation for clinical investigators. Given the extensive advantages, we advocate applying decision curve analysis to all models intended for use in clinical practice.

Congenital Diaphragmatic Eventration in the Neonatal Period: Systematic Review of the Literature and Report of a Rare Case Presenting with Gastrointestinal Disorders.

BACKGROUND: The term congenital diaphragmatic eventration (CDE) refers to an anatomical abnormality of the diaphragm. It is a very rare condition; however, early and prompt diagnosis is of very great importance due to possible life-threatening complications. Most severely affected patients are neonates, usually presented with respiratory distress symptoms. The aim of this study was to systematically review the existing literature and to consolidate data on CDE in neonates as well as to report a case of a neonate with congenital diaphragmatic eventration of the left hemidiaphragm and clinical signs and symptoms of the gastrointestinal tract. METHODS: An electronic search of the PubMed and Scopus databases was performed regarding studies evaluating the clinical presentation, diagnosis methods, treatments, and outcomes of CDE in the neonatal population. RESULTS: Data from 93 studies were integrated into our review, reporting 204 CDE cases, and according to them, the male/female ratio was 1/1 with a predominance of right-sided eventration. The diagnosis was primarily established by chest X-ray; surgical intervention was the most frequent treatment. The recurrence rate was 8.3% (9/109 cases). CONCLUSIONS: Early and accurate diagnosis of CDE and repair of the diaphragm can prevent complications, reduce morbidity, and improve the quality of patient's life.

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.