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

Using the Seventh Rib Length and Depth Measurements as a Method to Estimate Ancestry and Sex in Adults

This study tested the correlation of dimensions of the left seventh rib (L7) to ancestry and sex in adult humans. The first hypothesis, based on Bergmann’s theory, is that Black (African-American) individuals will have smaller L7 dimensions than White individuals (Americans of primarily European descent). The second hypothesis is that males, due to sexual dimorphism, will have larger ribs than females. 299 individuals from the Hamann-Todd Skeletal Collection were used in the study, approximately evenly distributed among sex and ancestry groups. Five variables were examined, including three measurements (length, width, and width point), and two calculations (area and ratio). A Pearson’s correlation tested the precision of the measurements being taken. To further test intraobserver error, 29 individuals measured on the first day of data collection were remeasured on the last day, and those two sets of measurements were analyzed with a paired T-Test. Swarm plots were created to show the distribution of data separated by sex and ancestry, as well as by sex only. Two sample T-Tests were run on all the variables to look for differences in the means with ancestry and sex. Results found significant differences between ancestry groups for both sexes for length, width, width point, and the ratio, with Black individuals smaller than White individuals for all variables except width. Thus, the first hypothesis was only partially supported. The second hypothesis was fully supported; significant differences were found between sexes for all variables, with males being larger. Lastly, non-linear models to estimate ancestry and sex from L7 dimensions were created based on results of the swarm plots, then tested on the main dataset and on a smaller dataset derived from contemporary individuals. From the models, ancestry was correctly estimated in 70% and 91.6% of males, and 65.1% and 66.6% of females, of the test samples, respectively; sex was correctly estimated in ~81% and ~89% of the test samples. Future research should focus on testing inter-observer error, the symmetry of the ribs and applying the models to other population samples

Diagnostic Concordance of Echocardiography and Cardiac Magnetic Resonance-Based Tissue Tracking for Differentiating Constrictive Pericarditis From Restrictive Cardiomyopathy

Background\u2014Variations in longitudinal deformation of the left ventricle have been suggested to be useful for differentiating chronic constrictive pericarditis (CP) and restrictive cardiomyopathy (RCM). We assessed left ventricular mechanics derived from cardiac magnetic resonance (CMR) cine\u2013based and 2-dimensional echocardiography\u2013based tissue tracking to determine intermodality consistency of diagnostic information for differentiating CP from RCM. Methods and Results\u2014We retrospectively identified 92 patients who underwent both CMR and 2-dimensional echocardiography and who had a final diagnosis of CP (n=28), RCM (n=30), or no structural heart disease (n=34). Global longitudinal strain from long-axis views and circumferential strain from short-axis views were measured on 2-dimensional echocardiographic and CMR cine images using the same offline software. Logistic regression models with receiver operating characteristics curves, continuous net reclassification improvement, and the integrated discrimination improvement (IDI) were used for assessing the incremental predictive performance. Global longitudinal strain was higher in patients with CP than in those with RCM (P<0.001), and both techniques were found to have similar diagnostic value (area under the curve, 0.84 versus 0.88 for CMR and echocardiography, respectively). For echocardiography, the addition of global longitudinal strain to respiratory septal shift and early diastolic mitral annular velocity resulted in improved continuous net reclassification improvement (P<0.001 for both) and integrated discrimination improvement (P=0.005 and 0.024) for both models. Similarly, for CMR, the addition of global longitudinal strain to septal shift and pericardial thickness resulted in improved continuous net reclassification improvement (P<0.001 for both) and integrated discrimination improvement (P=0.003 and <0.001). Conclusions\u2014CMR and echocardiography tissue tracking\u2013derived left ventricular mechanics provide comparable diagnostic information for differentiating CP from RCM

Supplementary Material for: Colorectal Cancer with BRAF D594G Mutation Is Not Associated with Microsatellite Instability or Poor Prognosis

<i>Objective:</i><i>BRAF</i> D594G mutations in colorectal cancer patients are not clearly understood. We retrospectively investigated the clinicopathological features of colorectal cancers with <i>BRAF</i> D594G mutations. <i>Methods:</i> We selected 908 colorectal cancer patients who underwent surgical resection from January 2008 to January 2013, and assessed <i>BRAF</i>, <i>KRAS</i>, microsatellite instability, and CpG island methylator phenotype (CIMP). <i>Results:</i> We detected <i>BRAF</i> D594G in 7 patients and <i>BRAF</i> V600E in 45 patients. The clinicopathological features of cancers with <i>BRAF</i> D594G mutation were similar to those with <i>BRAF</i> wild-type, but differed from those with <i>BRAF</i> V600E mutations. Regarding microsatellite instability status, 44.4% of cases with <i>BRAF</i>V600E mutations exhibited high microsatellite instability, compared to 14.3% of those with <i>BRAF</i> D594G mutations and 4.4% of those with <i>BRAF</i> wild-type. There were no CIMP-positive tumors in cancers with <i>BRAF</i> D594G mutations, whereas 67.8% of tumors with <i>BRAF</i> V600E mutations were CIMP-positive. In stage IV cancers, the survival rates of patients at 2 years were 8.5, 50.0, and 68.2% in the <i>BRAF</i> V600E mutation, <i>BRAF</i> D594G mutation, and <i>BRAF</i> wild-type groups, respectively.<i>Conclusion:</i> Colorectal cancers with <i>BRAF</i> D594G mutations exhibit similar clinicopathological features, microsatellite instability status, and prognosis as those with <i>BRAF</i> wild-type