DESIGN: This was a single-center prospective observational study that compared resting energy expenditure estimated by 15 commonly used predictive equations against resting energy expenditure measured by indirect calorimetry at different phases. Degree of agreement between resting energy expenditure calculated by predictive equations and resting energy expenditure measured by indirect calorimetry was analyzed using intraclass correlation coefficient and Bland-Altman analyses. Resting energy expenditure values calculated from predictive equations differing by ± 10% from resting energy expenditure measured by indirect calorimetry was used to assess accuracy. A score ranking method was developed to determine the best predictive equations.
SETTING: General Intensive Care Unit, University of Malaya Medical Centre.
PATIENTS: Mechanically ventilated critically ill patients.
INTERVENTIONS: None.
MEASUREMENTS AND MAIN RESULTS: Indirect calorimetry was measured thrice during acute, late, and chronic phases among 305, 180, and 91 ICU patients, respectively. There were significant differences (F= 3.447; p = 0.034) in mean resting energy expenditure measured by indirect calorimetry among the three phases. Pairwise comparison showed mean resting energy expenditure measured by indirect calorimetry in late phase (1,878 ± 517 kcal) was significantly higher than during acute phase (1,765 ± 456 kcal) (p = 0.037). The predictive equations with the best agreement and accuracy for acute phase was Swinamer (1990), for late phase was Brandi (1999) and Swinamer (1990), and for chronic phase was Swinamer (1990). None of the resting energy expenditure calculated from predictive equations showed very good agreement or accuracy.
CONCLUSIONS: Predictive equations tend to either over- or underestimate resting energy expenditure at different phases. Predictive equations with "dynamic" variables and respiratory data had better agreement with resting energy expenditure measured by indirect calorimetry compared with predictive equations developed for healthy adults or predictive equations based on "static" variables. Although none of the resting energy expenditure calculated from predictive equations had very good agreement, Swinamer (1990) appears to provide relatively good agreement across three phases and could be used to predict resting energy expenditure when indirect calorimetry is not available.
METHODS: To discover novel pancreatic cancer risk loci and possible causal genes, we performed a pancreatic cancer transcriptome-wide association study in Europeans using three approaches: FUSION, MetaXcan, and Summary-MulTiXcan. We integrated genome-wide association studies summary statistics from 9040 pancreatic cancer cases and 12 496 controls, with gene expression prediction models built using transcriptome data from histologically normal pancreatic tissue samples (NCI Laboratory of Translational Genomics [n = 95] and Genotype-Tissue Expression v7 [n = 174] datasets) and data from 48 different tissues (Genotype-Tissue Expression v7, n = 74-421 samples).
RESULTS: We identified 25 genes whose genetically predicted expression was statistically significantly associated with pancreatic cancer risk (false discovery rate < .05), including 14 candidate genes at 11 novel loci (1p36.12: CELA3B; 9q31.1: SMC2, SMC2-AS1; 10q23.31: RP11-80H5.9; 12q13.13: SMUG1; 14q32.33: BTBD6; 15q23: HEXA; 15q26.1: RCCD1; 17q12: PNMT, CDK12, PGAP3; 17q22: SUPT4H1; 18q11.22: RP11-888D10.3; and 19p13.11: PGPEP1) and 11 at six known risk loci (5p15.33: TERT, CLPTM1L, ZDHHC11B; 7p14.1: INHBA; 9q34.2: ABO; 13q12.2: PDX1; 13q22.1: KLF5; and 16q23.1: WDR59, CFDP1, BCAR1, TMEM170A). The association for 12 of these genes (CELA3B, SMC2, and PNMT at novel risk loci and TERT, CLPTM1L, INHBA, ABO, PDX1, KLF5, WDR59, CFDP1, and BCAR1 at known loci) remained statistically significant after Bonferroni correction.
CONCLUSIONS: By integrating gene expression and genotype data, we identified novel pancreatic cancer risk loci and candidate functional genes that warrant further investigation.
AIM: This study aimed to determine the prevalence of use of PP in ARDS patients (primary endpoint), the physiological effects of PP, and the reasons for not using it (secondary endpoints).
METHODS: The APRONET study was a prospective international 1-day prevalence study performed four times in April, July, and October 2016 and January 2017. On each study day, investigators in each ICU had to screen every patient. For patients with ARDS, use of PP, gas exchange, ventilator settings and plateau pressure (Pplat) were recorded before and at the end of the PP session. Complications of PP and reasons for not using PP were also documented. Values are presented as median (1st-3rd quartiles).
RESULTS: Over the study period, 6723 patients were screened in 141 ICUs from 20 countries (77% of the ICUs were European), of whom 735 had ARDS and were analyzed. Overall 101 ARDS patients had at least one session of PP (13.7%), with no differences among the 4 study days. The rate of PP use was 5.9% (11/187), 10.3% (41/399) and 32.9% (49/149) in mild, moderate and severe ARDS, respectively (P = 0.0001). The duration of the first PP session was 18 (16-23) hours. Measured with the patient in the supine position before and at the end of the first PP session, PaO2/FIO2 increased from 101 (76-136) to 171 (118-220) mmHg (P = 0.0001) driving pressure decreased from 14 [11-17] to 13 [10-16] cmH2O (P = 0.001), and Pplat decreased from 26 [23-29] to 25 [23-28] cmH2O (P = 0.04). The most prevalent reason for not using PP (64.3%) was that hypoxemia was not considered sufficiently severe. Complications were reported in 12 patients (11.9%) in whom PP was used (pressure sores in five, hypoxemia in two, endotracheal tube-related in two ocular in two, and a transient increase in intracranial pressure in one).
CONCLUSIONS: In conclusion, this prospective international prevalence study found that PP was used in 32.9% of patients with severe ARDS, and was associated with low complication rates, significant increase in oxygenation and a significant decrease in driving pressure.
METHODS: We conducted a large agnostic pathway-based meta-analysis of GWAS data using the summary-based adaptive rank truncated product method to identify gene sets and pathways associated with pancreatic ductal adenocarcinoma (PDAC) in 9040 cases and 12 496 controls. We performed expression quantitative trait loci (eQTL) analysis and functional annotation of the top SNPs in genes contributing to the top associated pathways and gene sets. All statistical tests were two-sided.
RESULTS: We identified 14 pathways and gene sets associated with PDAC at a false discovery rate of less than 0.05. After Bonferroni correction (P ≤ 1.3 × 10-5), the strongest associations were detected in five pathways and gene sets, including maturity-onset diabetes of the young, regulation of beta-cell development, role of epidermal growth factor (EGF) receptor transactivation by G protein-coupled receptors in cardiac hypertrophy pathways, and the Nikolsky breast cancer chr17q11-q21 amplicon and Pujana ATM Pearson correlation coefficient (PCC) network gene sets. We identified and validated rs876493 and three correlating SNPs (PGAP3) and rs3124737 (CASP7) from the Pujana ATM PCC gene set as eQTLs in two normal derived pancreas tissue datasets.
CONCLUSION: Our agnostic pathway and gene set analysis integrated with functional annotation and eQTL analysis provides insight into genes and pathways that may be biologically relevant for risk of PDAC, including those not previously identified.
OBJECTIVE: To analyze the amount of blood loss at different stages of Posterior Instrumented Spinal Fusion (PSF) surgery in adolescent idiopathic scoliosis (AIS) patients.
SUMMARY OF BACKGROUND DATA: Knowing the pattern of blood loss at different surgical stages may enable the surgical team to formulate a management strategy to reduce intraoperative blood loss.
METHODS: One hundred AIS patients who underwent PSF from January 2013 to December 2014 were recruited. The operation was divided into six stages; stage 1-exposure, stage 2-screw insertion, stage 3-release, stage 4-correction, stage 5-corticotomies and bone grafting, and stage 6-closure. The duration and blood loss at each stage was documented. The following values were calculated: total blood loss, blood loss per estimated blood volume, blood loss per minute, blood loss per vertebral level fused, and blood loss per minute per vertebral level fused.
RESULTS: There were 89 females and 11 males. The mean age was 17.0 ± 5.8 years old. Majority (50.0%) were Lenke 1 curve type. The mean preoperative major Cobb angle was 64.9 ± 15.0°. The mean number of levels fused was 9.5 ± 2.3 levels. The mean operating time was 188.5 ± 53.4 minutes with a mean total blood loss 951.0 ± 454.0 mLs. The highest mean blood loss occurred at stage 2 (301.0 ± 196.7 mL), followed by stage 4 (226.8 ± 171.2 mL) and stage 5 (161.5 ± 146.6 mL). The highest mean blood loss per minute was at stage 5 (17.1 ± 18.3 mL/min), followed by stage 3 (12.0 ± 10.8 mL/min). The highest mean blood loss per vertebral levels fused was at stage 2 (31.0 ± 17.7 mL/level), followed by stage 4 (23.9 ± 18.1 mL/level) and stage 5 (16.6 ± 13.3 mL/level).
CONCLUSION: All stages were significant contributors to the total blood loss except exposure (stage 1) and closure (stage 6). Blood loss per minute and blood loss per minute per level was highest during corticotomies (stage 5), followed by release (stage 3). However, the largest amount of total blood loss occurred during screw insertion (stage 2).
LEVEL OF EVIDENCE: 2.
METHODS: Ninety-seven patients with adolescent idiopathic scoliosis (AIS) who underwent posterior spinal fusion surgery at a single tertiary institution from March 2019 until June 2020 were enrolled in this retrospective study. Anesthesia was maintained using a target-controlled infusion of remifentanil combined with volatile anesthetic desflurane in 92 patients, while five patients received it as part of total intravenous anesthesia. Intravenous ketamine, paracetamol, and fentanyl were administered as multimodal analgesia. All patients received patient-controlled analgesia (PCA) morphine postoperatively. Pain scores at rest and on movement, assessed using the numerical rating scale, and the cumulative PCA morphine consumption were collected at a six-hourly interval for up to 48 h. According to the median intraoperative remifentanil dose usage of 0.215 µg/kg/min, patients were divided into two groups: low dose and high dose group.
RESULTS: There were no significant differences in the pain score and cumulative PCA morphine consumption between the low and high dose remifentanil group. The mean duration of remifentanil infusion was 134.9 ± 22.0 and 123.4 ± 23.7 min, respectively.
CONCLUSION: Intraoperative use of remifentanil as an adjuvant in AIS patients undergoing posterior spinal fusion surgery was not associated with postoperative hyperalgesia.
METHODS: This single-center prospective observational study was conducted in a general ICU. Mechanically ventilated critically ill adult patients (age ≥18 years) without pre-existing systemic neuromuscular diseases and expected to stay for ≥96 h in the ICU were included. US measurements were performed within 48 h of ICU admission (baseline), at day 7, day 14 of ICU stay and at ICU discharge (if stay >14 days). Quadriceps muscle layer thickness (QMLT), rectus femoris cross sectional area (RFCSA), vastus intermedius pennation angle (PA) and fascicle length (FL), and rectus femoris echogenicity (mean and standard deviation [SD]) were measured. Patients' next-of-kin were interviewed by using established questionnaires for their pre-hospitalization nutritional risk (nutrition risk screening-2002) and functional status (SARC-F, clinical frailty scale [CFS], Katz activities of daily living [ADL] and Lawton Instrumental ADL).
RESULTS: Ninety patients were recruited. A total of 86, 53, 24 and 10 US measures were analyzed, which were performed at a median of 1, 7, 14 and 22 days from ICU admission, respectively. QMLT, RFCSA and PA reduced significantly over time. The overall trend of change of FL was not significant. The only independent predictor of 60-day mortality was the change of QMLT from baseline to day 7 (adjusted odds ratio 0.95 for every 1% less QMLT loss, 95% confidence interval 0.91-0.99; p = 0.02). Baseline measures of high nutrition risk (modified nutrition risk in critically ill ≥5), sarcopenia (SARC-F ≥4) and frailty (CFS ≥5) were associated with lower baseline QMLT, RFCSA and PA and higher 60-day mortality.
CONCLUSIONS: Every 1% loss of QMLT over the first week of critical illness was associated with 5% higher odds of 60-day mortality. SARC-F, CFS and mNUTRIC are associated with quadriceps muscle status and 60-day mortality and may serve as a potential simple and indirect measures of premorbid muscle status at ICU admission.