Peri-operative red blood cell transfusion in neonates and infants: NEonate and Children audiT of Anaesthesia pRactice IN Europe: A prospective European multicentre observational study

BACKGROUND: Little is known about current clinical practice concerning peri-operative red blood cell transfusion in neonates and small infants. Guidelines suggest transfusions based on haemoglobin thresholds ranging from 8.5 to 12 g dl-1, distinguishing between children from birth to day 7 (week 1), from day 8 to day 14 (week 2) or from day 15 (≥week 3) onwards. OBJECTIVE: To observe peri-operative red blood cell transfusion practice according to guidelines in relation to patient outcome. DESIGN: A multicentre observational study. SETTING: The NEonate-Children sTudy of Anaesthesia pRactice IN Europe (NECTARINE) trial recruited patients up to 60 weeks' postmenstrual age undergoing anaesthesia for surgical or diagnostic procedures from 165 centres in 31 European countries between March 2016 and January 2017. PATIENTS: The data included 5609 patients undergoing 6542 procedures. Inclusion criteria was a peri-operative red blood cell transfusion. MAIN OUTCOME MEASURES: The primary endpoint was the haemoglobin level triggering a transfusion for neonates in week 1, week 2 and week 3. Secondary endpoints were transfusion volumes, 'delta haemoglobin' (preprocedure - transfusion-triggering) and 30-day and 90-day morbidity and mortality. RESULTS: Peri-operative red blood cell transfusions were recorded during 447 procedures (6.9%). The median haemoglobin levels triggering a transfusion were 9.6 [IQR 8.7 to 10.9] g dl-1 for neonates in week 1, 9.6 [7.7 to 10.4] g dl-1 in week 2 and 8.0 [7.3 to 9.0] g dl-1 in week 3. The median transfusion volume was 17.1 [11.1 to 26.4] ml kg-1 with a median delta haemoglobin of 1.8 [0.0 to 3.6] g dl-1. Thirty-day morbidity was 47.8% with an overall mortality of 11.3%. CONCLUSIONS: Results indicate lower transfusion-triggering haemoglobin thresholds in clinical practice than suggested by current guidelines. The high morbidity and mortality of this NECTARINE sub-cohort calls for investigative action and evidence-based guidelines addressing peri-operative red blood cell transfusions strategies. TRIAL REGISTRATION: ClinicalTrials.gov, identifier: NCT02350348

Does Lockdown compliance reflect a latent trait?

Imposing and enforcing lockdown rules are effective means to decelerate the spread of SARS-CoV-2. That said, the effectiveness of these rules strongly depends on citizens’ compliance. Here, we investigate the extent to which lockdown compliance varies as a function of (a) time-variant factors (i.e., infection wave), (b) rule-related factors (i.e., length, intensity, and flexibility of lockdown), and/or (c) stable individual differences. Using latent-state trait modeling with panel data from 1,098 German individuals who reported on their willingness to comply with five lockdown scenarios at two time points (April and November, 2020), we show that a substantial amount of variance can be attributed to a latent trait. Using data from a third time point (January 2021; N ¼ 834), we show that this latent trait is associated with honesty/humility and conscientiousness above and beyond social desirability. We discuss the theoretical and practical implications of these findings

Composition of the bacterial community present in the larval midgut of <i>M. hippocastani</i> revealed by cloning and sequencing.

<p>(A) Image of the digestion tract of the L3 larvae. Sections used for fluorescence <i>in situ</i> hybridization (FISH) analysis, labeled as ML3 and HL3 are shown. (B) Relative abundance of bacterial classes found in the L2 and L3 larvae. *Low abundant classes: Actinobacteria, Negativicutes and unclassified Bacterioidetes. (C) Total number of operational taxonomic units (OTUs) belonging to each taxonomical family. Asterisks represent groups (phylotypes) shared among samples: black, common to all; red, shared by L2 larvae and adult; blue, shared by L2 and L3 larvae. (D) Rarefaction curve of the total number of OTUs identified in the midgut of the larvae. (E) Rarefaction analysis of the number of bacterial families identified in the midguts of the larvae. (F) Rarefaction curve of the total number of bacterial classes found in the data set against the total number of clones sampled.</p

Richness and diversity indices calculated with the 16S rRNA gene libraries.

<p>Richness and diversity indices calculated with the 16S rRNA gene libraries.</p

Comparison of the bacteria found in <i>Melolontha hippocastani</i> in this study and those described previously in other organisms.

<p>n.p., not published; n.d., not described.</p

Composition of the bacterial community present in the guts of adult insects.

<p>(A) Image of the digestion tract of the adult gut. Sections used for fluorescence <i>in situ</i> hybridization (FISH) analysis were labeled B1 to B4. (B) Relative abundance of bacterial classes. *Low abundant classes: Acidobacteria, Negativicutes and Alpha proteobacteria. (C) Total of operational taxonomic units (OTUs) belonging to each taxonomical family. Asterisks represent groups (phylotypes) shared among samples: black, common to all; red, shared by L2 larvae and adult; blue, shared by L2 and L3 larvae. (D), (E), and (F) Rarefaction curves of the total number of OTUs, bacterial families and bacterial classes identified in the guts of adult insects.</p

In cis TP53 and RAD51C pathogenic variants may predispose to sebaceous gland carcinomas

Pathogenic variants in TP53 have been classically thought to cause Li-Fraumeni syndrome (LFS), a cancer predisposition with high risks for various childhood- and adult-onset malignancies. However, increased genetic testing has lately revealed, that pathogenic variant carriers exhibit a broader range of phenotypes and that penetrance may be dependent both on variant type and modifiers. Using next generation sequencing and short tandem repeat analysis, we identified germline pathogenic variants in TP53 and RAD51C located in cis on chromosome 17 in a 43-year-old male, who has developed a rare sebaceous gland carcinoma (SGC) but so far no tumors of the LFS spectrum. This course mirrors a Trp53-Rad51c-double-mutant cis mouse-model, which similarly develops SGC, while the characteristic Trp53-associated tumor spectrum occurs with significantly lower frequency. Therefore, we propose that co-occurent pathogenic variants in RAD51C and TP53 may predispose to SGC, reminiscent of Muir-Torre syndrome. Further, this report supports the diversity of clinical presentations associated with germline TP53 alterations, and thus, the proposed expansion of LFS to heritable TP53-related cancer syndrome