Diagnostic accuracy of Xpert ultra for childhood tuberculosis: A preliminary systematic review and meta-analysis.

Diagnosis of childhood tuberculosis (TB) is challenging. Xpert MTB/RIF and the new version Xpert MTB/RIF Ultra (Ultra) are molecular tests currently used to rapidly identify the infection. We reviewed the literature for the accuracy of Ultra assay in the diagnosis of tuberculosis and rifampicin resistance in children. We conducted a full search in PubMed, Web of Science (WOS), Embase, and Scopus, up to April 2021. A bivariate random-effects model was used to determine the pooled sensitivity and specificity of Ultra, with a 95% confidence interval (CI), compared with culturing and the composite reference standard (CRS). In the ten included studies (2,427 participants), the pooled Ultra sensitivity and specificity, in diagnosing pulmonary tuberculosis (PTB), were 78% (95% CI, 73-82) and 92% (95% CI, 91-94), respectively, against culture. Since a high heterogeneity was found between studies, we created subgroups based on different samples and ages. Ultra-pooled sensitivity was consistently lower against CRS (95% CI, 35%, 32-38). Compared to Xpert MTB/RIF, Ultra sensitivity tended toward higher values (Ultra: 73%, 67%-78% vs. Xpert MTB/RIF: 66%, 60%-72%), but specificity was lower (Ultra: 95%, 94%-96% vs. Xpert MTB/RIF: 99%, 98%-99%). Ultra has improved the definitive diagnosis of PTB, particularly in subjects with paucibacillary TB, including children. The lower specificity could be due to the fact that culture is an imperfect reference standard. Further studies are needed to evaluate the accuracy of Ultra in the diagnosis of childhood TB.

Worsening of Congenital Hypothyroidism After Start of Carob-bean Gum Thickened Formula: Is There a Link? A Case Report.

Congenital hypothyroidism (CH), if not correctly treated with L-thyroxine (L-T4), may be responsible for a permanent intellectual disability. If patients treated with L-T4 do not achieve a good TSH control, the possibility of poor compliance and/or poor absorption of L- T4 should be investigated. We describe an infant with CH whose thyroid hormone levels worsened after she started a carob-bean gum thickened formula. A baby girl was diagnosed with CH by newborn screening (at confirmatory blood evaluation TSH was 496.0 µIU/mL and FT4 0.13 ng/dl). Five weeks after beginning L-T4 treatment TSH normalized (TSH 2.72 µIU/mL , FT4 2.08 ng/dl); nevertheless, only another 5 weeks later we noticed a new worsening of thyroid hormone levels (TSH 31.1 µIU/mL , FT4 1.27 ng/dl), which worsened further (TSH 44.8 µIU/mL, FT4 1.16 ng/dl) even if L-T4 dosage was increased. Anamnesis disclosed that she had been given a carob-bean gum thickened formula to combat gastroesophageal reflux disease (GERD) rather than regular type 1 formula milk. The anti-reflux milk formula was discontinued and after 14 days the patient's TSH level dropped to 0.38 µIU/mL and FT4 increased to 2.68 ng/dL, allowing the L-T4 dosage to be reduced. Carob-bean gum thickened formula may influence the absorption of L-T4. If such formulas are used, we recommend a more frequent evaluation of thyroid function. In CH infants, inexplicably high TSH levels could be caused by gastrointestinal disorders or the interference of drugs or other substances, including some types of milk formula, which impair L-T4 absorption.

Effectiveness of Antimicrobial Lock Therapy for the Treatment of Catheter-Related and Central-Line-Associated Bloodstream Infections in Children: A Single Center Retrospective Study.

Antimicrobial lock solutions (ALT) in combination with systemic antibiotics can represent a valid option to attempt central venous catheter (CVC) salvage in the case of catheter-related and central-line-associated bloodstream infections (CRBSI and CLABSI). However, data concerning the effectiveness and safety of ALT in children are limited. We aimed to share our center's experience in order to contribute to investigations into the causes of ALT failure in the pediatric population. All children consecutively admitted to Meyer Children's Hospital, University of Florence, Italy, from 1 April 2016 to 30 April 2022, who received salvage ALT to treat an episode of CRBSI/CLABSI, were reviewed. According to ALT failure or success, children were compared with the aim of identifying the risk factors for unsuccessful ALT outcome. Data from 28 children, 37 CLABSI/CRBSI episodes, were included. ALT was associated with clinical and microbiologic success in 67.6% (25/37) of children. No statistically significant differences were observed between the two groups, successes and failures, considering age, gender, reason for use, duration, insertion, type and presence of insertion site infection of the CVC, laboratory data and number of CRBSI episodes. Nevertheless, a trend towards a higher success rate was observed for a dwell time of 24 h for the entire duration of ALT (88%; 22/25 vs. 66.7%; 8/12; p = 0.1827), while the use of taurolidine and the infections sustained by MDR bacteria were associated with a tendency toward greater failure (25%; 3/12 vs. 4%; 1/25; p = 0.1394; 60%; 6/10 vs. 33.3%; 8/24; p = 0.2522). No adverse events, except one CVC occlusion, were observed. ALT combined with systemic antibiotics appears to be an effective and safe strategy for treating children with CLABSI/CRBSI episodes.

Early anti IL-1 treatment replaces steroids in refractory Kawasaki disease: clinical experience from two case reports.

Refractory Kawasaki disease (KD) is related to a major risk of coronary arteries abnormalities and its treatment is not standardized. In this regard, anakinra (ANA), an interleukin (IL)-1 receptor antagonist, represents an emerging therapeutic option. We report two cases of children, diagnosed with KD, nonresponsive to two doses of intravenous immunoglobulins, successfully treated with ANA, without a prior use of steroids. Patient 2 developed a coronary dilatation, that improved significantly after ANA therapy. Our experience highlights IL-1 blockade effectiveness in reducing KD inflammation and suggests ANA adoption as second-line therapy, with a timesaving and steroid-sparing strategy. Our results, combined with the evidence of the IL-1 key role in KD and coronary arteritis pathogenesis and to the recent clinical evidence reported by the KAWAKINRA trial, encourage an earlier recourse to ANA in patients with refractory KD, in order to fight inflammation, and to treat and prevent the development of coronary artery aneurysms. Further studies are needed to better define the place of IL-1 blockade in KD step-up treatment.