Noninvasive respiratory support after extubation: a systematic review and network meta-analysis.

BACKGROUND: The effect of noninvasive respiratory support (NRS), including high-flow nasal oxygen, bi-level positive airway pressure and continuous positive airway pressure (noninvasive ventilation (NIV)), for preventing and treating post-extubation respiratory failure is still unclear. Our objective was to assess the effects of NRS on post-extubation respiratory failure, defined as re-intubation secondary to post-extubation respiratory failure (primary outcome). Secondary outcomes included the incidence of ventilator-associated pneumonia (VAP), discomfort, intensive care unit (ICU) and hospital mortality, ICU and hospital length of stay (LOS), and time to re-intubation. Subgroup analyses considered "prophylactic" versus "therapeutic" NRS application and subpopulations (high-risk, low-risk, post-surgical and hypoxaemic patients). METHODS: We undertook a systematic review and network meta-analysis (Research Registry: reviewregistry1435). PubMed, Embase, CENTRAL, Scopus and Web of Science were searched (from inception until 22 June 2022). Randomised controlled trials (RCTs) investigating the use of NRS after extubation in ICU adult patients were included. RESULTS: 32 RCTs entered the quantitative analysis (5063 patients). Compared with conventional oxygen therapy, NRS overall reduced re-intubations and VAP (moderate certainty). NIV decreased hospital mortality (moderate certainty), and hospital and ICU LOS (low and very low certainty, respectively), and increased discomfort (moderate certainty). Prophylactic NRS did not prevent extubation failure in low-risk or hypoxaemic patients. CONCLUSION: Prophylactic NRS may reduce the rate of post-extubation respiratory failure in ICU patients.

Explanation of trial sequential analysis: using a post-hoc analysis of meta-analyses published in Korean Journal of Anesthesiology.

BACKGROUND: Trial sequential analysis (TSA) is a recent cumulative meta-analysis method used to weigh type I and II errors and to estimate when the effect is large enough to be unaffected by further studies. The aim of this study was to illustrate possible TSA scenarios and their significance using meta-analyses published in the Korean Journal of Anesthesiology as working material. METHODS: We performed a systematic medical literature search for meta-analyses published in the Korean Journal of Anesthesiology. TSA was performed on each main outcome, estimating the required sample size on the calculated effect size for the intervention, considering a type I error of 5% and a power of 90% or 99%. RESULTS: Six meta-analyses with a total of ten main outcomes were included in the analysis. Seven TSAs confirmed the results of the meta-analyses. However, only three of them reached the required sample size. In the two TSAs, the cumulative z-lines were not statistically significant. One TSA boundary for effect was reached with the 90% analysis, but not with the 99% analysis. CONCLUSIONS: In TSA, a meta-analysis pooled effect may be established to assess if the cumulative sample size is large enough. TSA can be used to add strength to the conclusions of meta-analyses; however, pre-registration of the TSA protocol is of paramount importance. This study could be useful to better understand the use of TSA as an additional statistical tool to improve meta-analysis quality.

Novel Mutations and Unreported Clinical Features in KBG Syndrome.

KBG syndrome is an autosomal dominant disorder caused by pathogenic variants within ANKRD11 or deletions of 16q24.3 which include ANKRD11. It is characterized by distinctive facial features, developmental delay, short stature, and skeletal anomalies. We report 12 unrelated patients where a clinical diagnosis of KBG was suspected and confirmed by targeted analyses. Nine patients showed a point mutation in ANKRD11 (none of which were previously reported) and 3 carried a 16q24.3 deletion. All patients presented with typical facial features and macrodontia. Skeletal abnormalities were constant, and the majority of patients showed joint stiffness. Three patients required growth hormone treatment with a significant increase of height velocity. Brain malformations were identified in 8 patients. All patients showed behavioral abnormalities and most had developmental delay. Two patients had hematological abnormalities. We emphasize that genetic analysis of ANKRD11 can easily reach a detection rate higher than 50% thanks to clinical phenotyping, although it is known that a subset of ANKRD11-mutated patients show very mild features and will be more easily identified through the implementation of gene panels or exome sequencing. Joint stiffness was reported previously in few patients, but it seems to be a common feature and can be helpful for the diagnosis. Hematological abnormalities could be present and warrant a specific follow-up.