Can lung ultrasound score accurately predict surfactant replacement? A systematic review and meta-analysis of diagnostic test studies.

BACKGROUND: Clinical and radiographic criteria are traditionally used to determine the need for surfactant therapy in preterm infants. Lung ultrasound is a bedside test that offers a rapid, radiation-free, alternative to this approach. OBJECTIVE: To conduct a systematic review and meta-analysis to determine the accuracy of a lung ultrasound score (LUS) in identifying infants who would receive at least one surfactant dose. Secondary aims were to evaluate the predictive accuracy for ≥2 doses and the accuracy of a different image classification system based on three lung ultrasound profiles. METHODS: PubMed, SCOPUS, Biomed Central, and the Cochrane library between January 2011 and December 2021 were searched. Full articles enrolling preterm neonates who underwent lung ultrasound to predict surfactant administration were assessed and analyzed following Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) and QUADAS-2 guidelines. RESULTS: Seven prospective studies recruiting 697 infants met the inclusion criteria. Risk of bias was generally low. Oxygen requirement, clinical and radiographic signs of respiratory distress syndrome were used as reference standards for surfactant replacement. The summary receiver operator characteristic (sROC) curve for LUS predicting first surfactant dose showed an area under the curve (AUC) = 0.88 (95% confidence interval [CI]: 0.82-0.91); optimal specificity and sensitivity (Youden index) were 0.83 and 0.81 respectively. Pooled estimates of sensitivity, specificity, diagnostic odds ratio, negative predictive value, and positive predictive value for LUS predicting the first surfactant dose were 0.89 (0.82-0.95), 0.86 (0.78-0.95), 3.78 (3.05-4.50), 0.92 (0.87-0.97), 0.79 (0.65-0.92). The sROC curve for the accuracy of Type 1 lung profile in predicting first surfactant dose showed an AUC of 0.88; optimal specificity and sensitivity were both 0.86. Two studies addressing the predictive accuracy of LUS for ≥2 surfactant doses had high heterogeneity and were unsuitable to combine in a meta-analysis. DISCUSSION: Despite current significant variation in LUS thresholds, lung ultrasound is highly predictive of the need for early surfactant replacement. This evidence was derived from studies with homogeneous patient characteristics and low risk of bias.

Specific antibody titer decay in neonates prenatally exposed to Toxoplasma gondii and their mothers.

BACKGROUND: For infants exposed in utero to Toxoplasma gondii, current guidelines recommend monitoring the specific antibody titer until 12 months of age. In this study, we investigated the antibody titer decay in the mother-infant dyad. METHODS: This is a single center, population-based cohort study of neonates referred for prenatal exposure to Toxoplasma gondii from January 2014 to December 2020. All infants underwent clinical, laboratory, and instrumental investigation for at least 12 months. RESULTS: A total of 670 eligible neonates were referred to the Perinatal Infection Unit of the University Federico II of Naples. 636 (95%) completed the serological follow up until 12 months. Specific IgG antibodies negativization occurred in 628 (98.7%) within 5 months. At 9 and 12 months, all patients had negative IgG. An initial neonatal IgG antibody titer ≥ 200 IU/ml was associated with a longer time to negativization (184 [177.5;256] days when above threshold vs. 139.5 [101;179] days when below it; p < 0.001). Maternal IgG antibody titer ≥ 200 IU/ml at childbirth was also associated to delayed time to negativization in the infant (179 [163;184] days above the threshold vs 125 [96.8;178] days below it; p < 0.001). Specific antibody negativization was irreversible in all patients. CONCLUSIONS: Lower anti-Toxoplasma antibody titers detected at birth in the mother-infant-dyad lead to an earlier and irreversible negativization. This information allows for customisation of the infant follow up program and avoids invasive and expensive tests.

Ultrasound Guided Catheter Tip Location in Neonates: A Prospective Cohort Study.

OBJECTIVE: To assess point-of-care-ultrasound (POCUS) guided catheter tip location in a neonatal cohort after insertion of percutaneously inserted central catheters (PICCs) from the upper part of the body. STUDY DESIGN: This was a prospective, observational study on PICC tip location. Tip site was assessed by radiological landmarks or direct ultrasound (US) visualization of the cardiovascular structures. RESULTS: One hundred eighteen PICCs (28Gauge/1French) were studied in 102 neonates (mean postmenstrual age 31 weeks, range 25-43 weeks; mean weight at positioning 1365 g, range 420-4180 g). Feasibility of POCUS guided tip location was 92.3% in our population. Failures were significantly associated with mechanical ventilation (aOR 5.33; 95% CI 1.13-29.5; P = .038). Agreement between US and radiographic methods was found in 88 of 109 cases (80.7%). Fifteen of 21 discordant cases led to a change in clinical management. CONCLUSIONS: POCUS guided localization of small bore PICC is a non-invasive and effective alternative to the conventional radiogram. The latter should be recommended when US examination fails to locate the catheter tip.

Clinical, Immunological, and Molecular Features of Typical and Atypical Severe Combined Immunodeficiency: Report of the Italian Primary Immunodeficiency Network.

Severe combined immunodeficiencies (SCIDs) are a group of inborn errors of the immune system, usually associated with severe or life-threatening infections. Due to the variability of clinical phenotypes, the diagnostic complexity and the heterogeneity of the genetic basis, they are often difficult to recognize, leading to a significant diagnostic delay (DD). Aim of this study is to define presenting signs and natural history of SCID in a large cohort of patients, prior to hematopoietic stem cell or gene therapies. To this purpose, we conducted a 30-year retro-prospective multicenter study within the Italian Primary Immunodeficiency Network. One hundred eleven patients, diagnosed as typical or atypical SCID according to the European Society for Immune Deficiencies criteria, were included. Patients were subsequently classified based on the genetic alteration, pathogenic mechanism and immunological classification. A positive relationship between the age at onset and the DD was found. SCID patients with later onset were identified only in the last decade of observation. Syndromic SCIDs represented 28% of the cohort. Eight percent of the subjects were diagnosed in Intensive Care Units. Fifty-three percent had an atypical phenotype and most of them exhibited a discordant genotype-immunophenotype. Pre-treatment mortality was higher in atypical and syndromic patients. Our study broadens the knowledge of clinical and laboratory manifestations and genotype/phenotype correlation in patients with SCID and may facilitate the diagnosis of both typical and atypical forms of the disease in countries where newborn screening programs have not yet been implemented.

Otolaryngological features in a cohort of patients affected with 22q11.2 deletion syndrome: A monocentric survey.

Otorhinolaryngologic manifestations are common in 22q11.2 deletion syndrome (22q11.2DS), but poorly described. This study aimed to better define the ear-nose-throat (ENT) phenotype of 22q11.2DS patients, in the attempt to best detect subjects requiring subspecialist intervention. We enrolled 25 patients affected with 22q11.2DS. Anatomic and functional ENT findings were investigated using clinical, laboratory, and instrumental data. Immunophenotype and frequency of infections were evaluated. Univariate and multivariate analyses were performed. ENT anomalies were found in 88% of patients, and in 20% congenital palate defects required surgery. Adenoid or palatine tonsil hypertrophy was noted in 80% and 48%. Forty-eight percent of subjects had rhinolalia/phonia, severe in half of these. We also found nasal regurgitation or laryngeal penetration/aspiration in 20% and 16%, respectively. Instrumental exams revealed a mild conductive hearing loss in 32% (bilateral in most cases), tympanometric anomalies in 28%, and swallowing abnormalities in 16%. Statistical univariate analysis showed a direct association between rhinolalia/phonia and episodes of laryngeal aspiration (p = .016) and between tympanometric anomalies and increased adenoid volume (p = .044). No association between episodes of food aspiration and palatal anomalies was found. Moreover, no statistically significant association was observed between the number of airway infections and the ENT findings. This study contributes to better define the ENT phenotype in patients with 22q11.2DS, helpful to prevent potential complications. Furthermore, the identification of a subcategory of patients may allow the early adoption of specific speech therapy programs to improve the clinical outcome of 22q11.2DS patients.

Severe combined immunodeficiency--an update.

Severe combined immunodeficiencies (SCIDs) are a group of inherited disorders responsible for severe dysfunctions of the immune system. These diseases are life-threatening when the diagnosis is made too late; they are the most severe forms of primary immunodeficiency. SCID patients often die during the first two years of life if appropriate treatments to reconstitute their immune system are not undertaken. Conventionally, SCIDs are classified according either to the main pathway affected by the molecular defect or on the basis of the specific immunologic phenotype that reflects the stage where the blockage occurs during the differentiation process. However, during the last few years many new causative gene alterations have been associated with unusual clinical and immunological phenotypes. Many of these novel forms of SCID also show extra-hematopoietic alterations, leading to complex phenotypes characterized by a functional impairment of several organs, which may lead to a considerable delay in the diagnosis. Here we review the biological and clinical features of SCIDs paying particular attention to the most recently identified forms and to their unusual or extra-immunological clinical features.

Gastrointestinal involvement in patients affected with 22q11.2 deletion syndrome.

OBJECTIVE. Enteropathy is a very common feature in patients with primary immunodeficiencies. In patients with Del22 gastrointestinal (GI) alterations, including feeding disorders and congenital abnormalities have been often reported, mostly in the first year of life. MATERIAL AND METHODS. Aim of this monocentric study is to better define the GI involvement in a cohort of 26 patients affected with Del22 syndrome. Anamnestic information was retrospectively collected for each patient. Weight and height parameters at the time of the screening were recorded. Plasma levels of hemoglobin, iron, ferritin, albumin, total protein, calcium, phosphorus, transaminase levels, antigliadin (AGA) IgA and IgG, and antitissue transglutaminase (anti-TGase) titers were measured. RESULTS. A GI involvement was identified in the 58% of patients. The prominent problems were abdominal pain, vomiting, gastroesophageal reflux and chronic constipation. Weight deficiency, short stature and failure to thrive were reported in 54, 42, and 30% of the patients, respectively. The evidence of sideropenic anemia, in keeping with hypoproteinemia, impaired acid steatocrit or cellobiose/mannitol test suggested an abnormal intestinal permeability. In this cohort, a high prevalence of AGA IgA and IgG positivity was observed. Celiac disease (CD) was suspected in three patients, and in one of them confirmed by histology. In this patient, a long-lasting gluten-free diet failed to restore the intestinal architecture. CONCLUSIONS. In conclusion, GI involvement is a very common feature in Del22 patients. A better characterization of GI involvement would be very useful to improve the management of these patients.