Serial Measurements Research Articles

819 ELLIPSE: Electrical Impedance Analysis in Patients Undergoing Emergency Abdominal Surgery

Abstract Introduction An ageing population represents greater operative risk; therefore, preoperative risk stratification is required to allow patients to make an informed decision. One method of risk stratification is bioelectrical impedance analysis (BIA) which can provide information such as muscle and fat mass, providing a proxy for patient metabolic health. Aim Metabolic health is intrinsically linked to outcomes following surgery. We hypothesised that BIA is a feasible method of assessing patients undergoing emergency abdominal surgery and predicting postoperative outcomes. Method A BIA analyser was used to measure patients body composition. All adult patients who met the National Emergency Laparotomy Audit (NELA) inclusion criteria were prospectively recruited and followed up until 30 days postoperatively. These patients had serial BIA measurements and compared with a healthy population. The phase angle (PA) is a raw variable which can be standardised to a healthy reference population and matched for age and gender. In summary, a higher phase angle is associated with improved outcomes. Results 31 patients were recruited and BIA analysis in patients undergoing emergency abdominal surgery was feasible. Patients with a phase angle lower than the reference population had a greater incidence of complications (p = 0.03) and had more severe complications (p = 0.023). Furthermore, the same patients also had a significantly higher NELA morbidity percentage (p = 0.022). Conclusions Our study shows that conducting BIA analysis in patients undergoing emergency abdominal surgery is feasible. The presence and severity of complications correlates with the phase angle. This represents a successful proof of concept study of BIA to predict postoperative outcomes.

Serial measurements of SIRS criteria to identify unique phenotypes of sepsis: A Microbiologic Approach

Introduction: The utility of serial scoring systems in identifying distinct sepsis phenotypes remains unknown. Methods: Eligible adults were classified into culture-positive (Cx+) and culture-negative (Cx-) groups alongside pre-defined culture subgroups. Average SIRS & SEP (novel scoring system) scores were calculated at t = 0 and hours 3,6,12 & 24 before and after t = 0. The primary outcome was a difference in SIRS/SEP scores amongst those that were Cx+ or Cx- at any time point. Secondary outcomes were comparing total and component SIRS/SEP scores in microbiologic subgroups over serial time points. Results: 4,701 Cx+ and 3254 Cx- patients met eligibility criteria. Statistically significant differences were seen in the average SIRS score between Cx + and Cx- groups at hours six (Cx+ 1.40+1.04 vs Cx- 1.35+1.01) & 12 (Cx+ 0.95+0.95 vs Cx- 0.90+0.90) after t = 0. The hematologic, urologic, and neurologic subgroups had significant differences at numerous time points before and after T = 0. Similar findings were observed with the SEP scores. Cx+ and Cx- groups (including subgroups) consistently doubled both SIRS/SEP scores before t = 0 with an eventual return to baseline values after T = 0 but at different gradients. Conclusion: Significant differences in SIRS/SEP scores were seen in Cx+ & Cx- patients at sequential time points. This microbiologic approach in homogenous culture cohorts has the potential to identify distinct phenotypes of sepsis efficiently and practically. Consistent increases in SIRS/SEP scores before t = 0 and sequential decreases after t = 0 may allow for early detection, intervention, and provision for real-time monitoring of therapeutic responses in patients with concerns for sepsis.

Systemic Determinants of Exercise Intolerance in Patients With Fibrotic Interstitial Lung Disease and Severely Impaired DLCO.

The precise mechanisms driving poor exercise tolerance in patients with fibrotic interstitial lung diseases (fibrotic ILDs) showing a severe impairment in single-breath lung diffusing capacity for carbon monoxide (DLCO < 40% predicted) are not fully understood. Rather than only reflecting impaired O2 transfer, a severely impaired DLCO may signal deranged integrative physiologic adjustments to exercise that jointly increase the burden of exertional symptoms in fibrotic ILD. Sixty-seven subjects (46 with idiopathic pulmonary fibrosis, 24 showing DLCO < 40%) and 22 controls underwent pulmonary function tests and an incremental cardiopulmonary exercise test with serial measurements of operating lung volumes and 0-10 Borg dyspnea and leg discomfort scores. Subjects from the DLCO < 40% group showed lower spirometric values, more severe restriction, and lower alveolar volume and transfer coefficient compared to controls and participants with less impaired DLCO (P < .05). Peak work rate was ∼45% (vs controls) and ∼20% (vs DLCO > 40%) lower in the former group, being associated with lower (and flatter) O2 pulse, an earlier lactate (anaerobic) threshold, heightened submaximal ventilation, and lower SpO2 . Moreover, critically high inspiratory constrains were reached at lower exercise intensities in the DLCO < 40% group (P < .05). In association with the greatest leg discomfort scores, they reported the highest dyspnea scores at a given work rate. Between-group differences lessened or disappeared when dyspnea intensity was related to indexes of increased demand-capacity imbalance, that is, decreasing submaximal, dynamic ventilatory reserve, and inspiratory reserve volume/total lung capacity (P > .05). A severely reduced DLCO in fibrotic ILD signals multiple interconnected derangements (cardiovascular impairment, an early shift to anaerobic metabolism, excess ventilation, inspiratory constraints, and hypoxemia) that ultimately lead to limiting respiratory (dyspnea) and peripheral (leg discomfort) symptoms. DLCO < 40%, therefore, might help in clinical decision-making to indicate the patient with fibrotic ILD who might derive particular benefit from pharmacologic and non-pharmacologic interventions aimed at lessening these systemic abnormalities.

Importance of the 'area under the curve' from serial NT-proBNP measurements during treatment with sacubitril/valsartan.

Serial assessment of natriuretic peptides is widely utilized in heart failure clinics. Uncertainty exists regarding the value of multiple natriuretic peptide measurements and how they might be best interpreted. Six hundred thirty-two patients with heart failure with reduced ejection fraction (<40%) and complete biomarker data were enrolled to receive sacubitril/valsartan. Patients underwent periodic study visits during 1-year follow-ups. Echocardiographic data and cardiac biomarkers, including N-terminal pro-B-type natriuretic peptide (NT-proBNP) were collected during study visits. Patients were categorized into three groups based on tertiles of baseline NT-proBNP levels. The area under the curve (AUC) of NT-proBNP measurements across study visits was calculated. Compared with patients with higher AUC (and thus higher concentrations over a longer period of time), those with lower AUC were younger, had a lower prevalence of chronic kidney disease, prior coronary artery bypass graft, atrial fibrillation, and higher body-mass index. A significant interaction existed between baseline NT-proBNP and subsequent AUC for predicting LVEF change across visits (P-value<0.001): among those with lower baseline NT-proBNP, similar improvements in left ventricular (LV) volumes LV ejection fraction, and LV mass index were observed across subsequent AUC (P-value>0.1). However, among those with higher baseline NT-proBNP, those with lower subsequent AUC had a greater improvement in cardiac remodelling indices (P-value<0.05). Serial NT-proBNP monitoring (integrating the totality of measurements as an AUC) during treatment with sacubitril/valsartan informs unique information regarding the future changes in cardiac remodelling indices, especially among those with higher NT-proBNP levels at baseline.

Reducing Lipid Panel Error Allowances to Improve the Accuracy of Cardiovascular Risk Stratification.

The standard lipid panel forms the backbone of atherosclerotic cardiovascular disease risk assessment. Suboptimal analytical performance, along with biological variability, could lead to erroneous risk assessment and management decisions. The current National Cholesterol Education Program (NCEP) performance recommendations have remained unchanged for almost 3 decades despite improvements in assay technology. We investigated the potential extent of risk misclassification when the current recommendations are met and explored the impact of improving analytical performance goals. We extracted lipid panel data for 8506 individuals from the NHANES database and used these to classify subjects into 4 risk groups as recommended by the 2018 US Multisociety guidelines. Analytical bias and imprecision, at the allowable limits, as well as biological variability, were introduced to the measured values to determine the impact on misclassification. Bias and imprecision were systematically reduced to determine the degree of improvement that may be achieved. Using the current performance recommendations, up to 10% of individuals were misclassified into a different risk group. Improving proportional bias by 1%, and fixing imprecision to 3% across all assays reduced misclassifications by up to 10%. The effect of biological variability can be reduced by taking the average of serial sample measurements. The current NCEP recommendations for analytical performance of lipid panel assays allow for an unacceptable degree of misclassification, leading to possible mismanagement of cardiovascular disease risk. Iteratively reducing allowable error can improve this.

Serial Measurements of Serum Glial Fibrillary Acidic Protein in Moderate-Severe Traumatic Brain Injury: Potential Utility in Providing Insights into Secondary Insults and Long-Term Outcome.

In patients with traumatic brain injury (TBI), serum biomarkers may have utility in assessing the evolution of secondary brain injury. A panel of nine brain-injury- associated biomarkers was measured in archived serum samples over 10 days post-injury from 100 patients with moderate-severe TBI. Among the biomarkers evaluated, serum glial fibrillary acidic protein (GFAP) had the strongest associations with summary measures of acute pathophysiology, including intracranial pressure (ICP), cerebral perfusion pressure (CPP), and brain tissue pO2 (PbtO2). Group based trajectory (TRAJ) analysis was used to identify three distinct GFAP subgroups. The low TRAJ group (n = 23) had peak levels of 9.4 + 1.2 ng/mL that declined rapidly. The middle TRAJ group (n = 48) had higher peak values (31.5 + 5.0 ng/mL) and a slower decline over time. The high TRAJ group (n = 26) had very high, sustained peak values (59.6 + 12.5 ng/mL) that even rose among some patients over 10 days. Patients in the high TRAJ group had significantly higher mortality rate than patients in low and middle TRAJ groups (26.9% vs. 7.0%, p = 0.028). The frequency of poor neurological outcome (Glasgow Outcome Score Extended [GOS-E] 1-4) was 88.5% in the high TRAJ group, 54.2% in the middle TRAJ group, and 30.4% in the low TRAJ group (p < 0.001). ICP was highest in the high TRAJ group (median 17.6 mm Hg), compared with 14.4 mmHg in the low and 15.9 mm Hg in middle TRAJ groups (p = 0.002). High TRAJ patients spent the longest time with ICP >25 mm Hg, median 23 h, compared with 2 and 6 h in the low and middle TRAJ groups (p = 0.006), and the longest time with ICP >30 mm Hg, median 5 h, compared with 0 and 1 h in the low and middle TRAJ groups, respectively (p = 0.013). High TRAJ group patients more commonly required tier 2 or 3 treatment to control ICP. The high TRAJ group had the longest duration when CPP was <50 mm Hg (p = 0.007), and PbtO2 was <10 mm Hg (p = 0.002). Logistical regression was used to study the relationship between temporal serum GFAP patterns and 6-month GOS-E. Here, the low and middle TRAJ groups were combined to form a low-risk group, and the high TRAJ group was designated the high-risk group. High TRAJ group patients had a greater chance of a poor 6-month GOS-E (p < 0.0001). When adjusting for baseline injury characteristics, GFAP TRAJ group membership remained associated with GOS-E (p = 0.003). When an intensive care unit (ICU) injury burden score, developed to quantify physiological derangements, was added to the model, GFAP TRAJ group membership remained associated with GOS-E (p = 0.014). Mediation analysis suggested that ICU burden scores were in the causal pathway between TRAJ group and 6-month mortality or GOS-E. Our results suggest that GFAP may be useful to monitor serially in moderate-severe TBI patients. Future studies in larger cohorts are needed to confirm these results.

Intrauterine growth pattern in Butajira HDSS, Southern Ethiopia: BUNMAP pregnancy cohort

BackgroundAbnormal fetal growth pattern during pregnancy including excessive fetal size and intrauterine growth restrictions are the major determinants for perinatal outcomes and postnatal growth. Ultrasonography is a useful tool in monitoring fetal growth for appropriate care and interventions. However, there are few longitudinal studies using serial ultrasonography in low and middle-income countries. Moreover, the reference charts used for fetal growth monitoring in low-income countries comes from high income countries with distinct population features. Therefore, the purpose of this study was to evaluate the intrauterine growth pattern of the fetus using serial ultrasonography.MethodsWe conducted a prospective community-based cohort study from March 2018 to December 2019. Pregnant women with gestational age of 24 weeks or below living in the Butajira HDSS were enrolled. We followed the pregnant women until delivery. Serial ultrasound measurements were taken, and fetal weight was estimated using the Hadlock algorithm based on biparietal diameter, head circumference, abdominal circumference, and femur length. The z-scores and percentiles of biometric measurements were calculated and compared to the INTERGROWTH-21st International Standards for Fetal Growth.ResultsWe reviewed a total of 2055 ultrasound scans and 746 women who fulfill the inclusion criteria were involved”. We found similar distribution patterns of biometric measurements and estimated fetal weight compared to the previous study done in Ethiopia, the WHO and INTERGROWTH-21st references. In our study, the 5th,50th and 95th percentiles of estimated fetal weight distribution have a similar pattern to the WHO and INTERGROWTH-21st charts. The 50th and 95th percentile had also a similar distribution pattern with the previous study conducted in Ethiopia. We found that 10% of the fetus were small for gestational age (below the 10th percentile) based on the Z-score of estimated fetal weight.ConclusionOur study evaluated the fetal growth patterns in rural community of Ethiopia using serial ultrasound biometric measurements. We found similar IUG patterns to the WHO and INTERGROWTH-21st reference standards as well as the previous study conducted in Ethiopia.

Evaluation of Blood Lactate Concentrations as a Marker for Resuscitation and Prognosis in Patients with Major Burns

Background Severe burns require appropriate fluid management in the acute phase. A massive volume of intravenous fluid is usually required to ensure adequate end-organ perfusion. Lactate is a product of anaerobic metabolism. A high level of lactate in tissue is direct indication of tissue hypoxia. The correlation between serum lactate and clinical outcome has been well accepted in hemorrhagic and septic shock. However, studies on its use in predicting mortality and morbidity of major burn patients in particular is sparse. Early prediction of outcome in patients with major burn is very likely to aid suitable modification of management strategies. Objective To assess the role of serum lactate measurement as the predictor burn patient's outcome (survivors and non-survivors). Patients and Methods 30 patients with major burn (more than 20% of TBSA) were included. This includes operated/ non-operated patients. Of the 30 patients, 20 were males and 10 were females. All adult burned patients admitted within the first 24h post burn were included in the study. Patients admitted after 24h from the thermal injury, or those who were discharged or died 48h after admission were excluded. Results Serial blood lactate measures were better as a prognostic tool than isolated measure. Reduction or normalization of lactate levels 24 hours after admission was significantly associated with a higher probability of survival. This study confirms the prognostic value of serum lactate for mortality in patients with major burns as serial blood lactate measurements predict mortality in these patients. Conclusion Although many studies reiterate the importance of blood lactate and lactate clearance in predicting mortality in burn patients, the role of these markers in therapy titration is ambiguous. Overzealous fluid resuscitation can cause fluid overload and acute respiratory distress syndrome. little regional data are available to establish the importance of blood lactate. We have demonstrated the association of blood lactate in the first 36 hours of the burn injury with mortality. Further large multicenter prospective studies are required.

Elevated high-sensitivity cardiac troponin T serum concentration in subjects with spinal cord injury

BackgroundThe biochemical analysis of high-sensitivity cardiac troponins (hs-cTn) from peripheral blood specimens has been established as biomarker for myocardial injury. Independently of myocardial injury, increased serum hs-cTn concentrations have been described in patients with myopathies. The relevance and frequency of noncardiac hs-cTn elevations in spinal cord injury (SCI) is unknown. Our study aimed to 1) determine the frequency of increased hs-cTn concentrations of supposedly noncardiac origin above the 99th percentile (upper reference limit, URL) in an unselected SCI population and 2) compare the two protagonist analytes cTnT and cTnI with respect to these noncardiac elevations. MethodsIn this monocentric, cross-sectional study, we sampled blood from n = 30 SCI subjects without cardiac symptoms to test for hs-cTnT and hs-cTnI serum concentrations. Results18/30 (60%) of SCI subjects showed increased hs-cTnT concentrations above the URL of 14 ng/l (p < 0.001). In 4 subjects (22.2%) concentrations were >50 ng/l. Moreover, 3 of these four subjects fulfilled the 6-h troponin dynamics criterion for acute myocardial injury in serial hs-cTnT testing. In contrast, no subject demonstrated increased hs-cTnI concentrations according to the URL of 40 ng/l. 6-h troponin dynamics were also unremarkable for hs-cTnI testing. ConclusionsSCI subjects frequently have increased hs-cTnT concentrations without clinical and hs-cTnI evidence of myocardial injury. Clinicians must be aware of cTnT “skeletal muscle false-positives” in SCI, which applies to elevated baseline cTnT concentrations and troponin dynamics in serial measurements. In case of diagnostic uncertainty, simultaneous analysis of cTnI might be helpful.

Neurofilament light chain in spinal fluid and plasma in multiple system atrophy: a prospective, longitudinal biomarker study.

There is a critical need for reliable diagnostic biomarkers as well as surrogate markers of disease progression in multiple system atrophy (MSA). Neurofilament light chain (NfL) has been reported to potentially meet those needs. We therefore sought to explore the value of NfL in plasma (NfL-p) in contrast to cerebrospinal fluid (NfL-c) as a diagnostic marker of MSA, and to assess NfL-p and NfL-c as markers of clinical disease progression. Well-characterized patients with early MSA (n = 32), Parkinson's disease (PD; n = 21), and matched controls (CON; n = 15) were enrolled in a prospective, longitudinal study of synucleinopathies with serial annual evaluations. NfL was measured using a high-sensitivity immunoassay, and findings were assessed by disease category and relationship with clinical measures of disease progression. Measurements of NfL-c were highly reproducible across immunoassay platforms (Pearson, r = 0.99), while correlation between NfL-c and -p was only moderate (r = 0.66). NfL was significantly higher in MSA compared with CON and PD; the separation was essentially perfect for NfL-c, but there was overlap, particularly with PD, for NfL-p. While clinical measures of disease severity progressively increased over time, NfL-c and -p remained at stable elevated levels within subjects across serial measurements. Neither change in NfL nor baseline NfL were significantly associated with changes in clinical markers of disease severity. These findings confirm NfL-c as a faithful diagnostic marker of MSA, while NfL-p showed less robust diagnostic value. The significant NfL elevation in MSA was found to be remarkably stable over time and was not predictive of clinical disease progression.

Feasibility Assessment of a Biomarker-Guided Kidney-Sparing Sepsis Bundle: The Limiting Acute Kidney Injury Progression In Sepsis Trial.

To determine the feasibility, safety, and efficacy of a biomarker-guided implementation of a kidney-sparing sepsis bundle (KSSB) of care in comparison with standard of care (SOC) on clinical outcomes in patients with sepsis. Adaptive, multicenter, randomized clinical trial. Five University Hospitals in Europe and North America. Adult patients, admitted to the ICU with an indwelling urinary catheter and diagnosis of sepsis or septic shock, without acute kidney injury (acute kidney injury) stage 2 or 3 or chronic kidney disease. A three-level KSSB based on Kidney Disease: Improving Global Outcomes (KDIGOs) recommendations guided by serial measurements of urinary tissue inhibitor of metalloproteinases-2 and insulin-like growth factor-binding protein 7 used as a combined biomarker [TIMP2]•[IGFBP7]. The trial was stopped for low enrollment related to the COVID-19 pandemic. Nineteen patients enrolled in five sites over 12 months were randomized to the SOC (n = 8, 42.0%) or intervention (n = 11, 58.0%). The primary outcome was feasibility, and key secondary outcomes were safety and efficacy. Adherence to protocol in patients assigned to the first two levels of KSSB was 15 of 19 (81.8%) and 19 of 19 (100%) but was 1 of 4 (25%) for level 3 KSSB. Serious adverse events were more frequent in the intervention arm (4/11, 36.4%) than in the control arm (1/8, 12.5%), but none were related to study interventions. The secondary efficacy outcome was a composite of death, dialysis, or progression of greater than or equal to 2 stages of acute kidney injury within 72 hours after enrollment and was reached by 3 of 8 (37.5%) patients in the control arm, and 0 of 11 (0%) patients in the intervention arm. In the control arm, two patients experienced progression of acute kidney injury, and one patient died. Although the COVID-19 pandemic impeded recruitment, the actual implementation of a therapeutic strategy that deploys a KDIGO-based KSSB of care guided by risk stratification using urinary [TIMP2]•[IGFBP7] seems feasible and appears to be safe in patients with sepsis.

Serial lung mass volume ratios as prognostic indicators of neonatal respiratory morbidity in fetal pulmonary malformations

Several studies have shown that the congenital pulmonary airway malformation volume ratio is a useful prognosticator of neonatal outcome in prenatally diagnosed lung lesions. However, there remains a lack of consensus on which congenital pulmonary airway malformation volume ratio values have the best predictive value because of operator dependence, inherent changes in lung lesion size throughout gestation, and the widespread use of maternal steroids. This study sought to determine the association between serial congenital pulmonary airway malformation volume ratio measurements and neonatal outcomes among fetuses with lung malformations. This was a retrospective cohort study of fetuses with a prenatally diagnosed lung malformation managed at 2 major fetal centers from January 2010 to December 2021. Prenatal variables, including prospectively measured congenital pulmonary airway malformation volume ratio measurements (initial, maximum, and final), were analyzed. The results were correlated with 3 outcome measures, namely surgical resection before 30 days of life, a need for supplemental O2 at birth, and endotracheal intubation at birth. Statistical analyses were performed using receiver operating characteristic curve analyses, Welch 2 sample t tests, and multivariable logistic regressions (P<.05). There were 123 fetuses with isolated lung lesions identified. Eight (6.5%) had hydrops. The mean initial congenital pulmonary airway malformation volume ratio was 0.67±0.61 cm2 at 22.9±3.9 weeks' gestation. The mean maximum congenital pulmonary airway malformation volume ratio was 1.08 ± 0.94 cm2 at 27.0 ± 4.0 weeks' gestation. The mean final congenital pulmonary airway malformation volume ratio was 0.58±0.60 cm2 at 33.2±4.1 weeks' gestation. At a mean gestational age at delivery of 38.3±2.6 weeks, 15 (12.2%) underwent neonatal lung resection for symptomatic disease. In a multivariable regression, all 3 congenital pulmonary airway malformation volume ratio measurements showed a significant correlation with neonatal lung resection (P<.001). Optimal congenital pulmonary airway malformation volume ratio cutoffs were established based on an initial congenital pulmonary airway malformation volume ratio of ≥0.8 cm2, maximum congenital pulmonary airway malformation volume ratio of ≥1.5 cm2, and a final congenital pulmonary airway malformation volume ratio of ≥1.3 cm2 with associated areas under the curve of 0.89, 0.97, and 0.93, respectively. The final congenital pulmonary airway malformation volume ratio had the highest specificity for predicting surgical lung resection in the early postnatal period. Measuring congenital pulmonary airway malformation volume ratios throughout pregnancy in fetuses with pulmonary malformations has clinical value for prenatal counseling and planning care transition after delivery. Fetuses with a final congenital pulmonary airway malformation volume ratio of more than 1.3 cm2 are likely to require neonatal surgery and therefore should be delivered at tertiary care centers with a neonatal intensive care unit and pediatric surgical expertise.

Variability of longitudinal triglyceride phenotype in patients heterozygous for pathogenic APOA5 variants

Biallelic pathogenic variants in APOA5 are an infrequent cause of familial chylomicronemia syndrome characterized by severe, refractory hypertriglyceridemia (HTG), and fasting plasma triglyceride (TG) >10mmol/L (>875mg/dL). The TG phenotype of heterozygous individuals with one copy of a pathogenic APOA5 variant is less familiar. We evaluated the longitudinal TG phenotype of individuals with a single pathogenic APOA5 variant allele. Medically stable outpatients from Ontario, Canada were selected for study based on having: 1) a rare pathogenic APOA5 variant in a single allele; and 2) at least three serial fasting TG measurements obtained over >1.5 years of follow-up. Seven patients were followed for a mean of 5.3±3.7 years. Fasting TG levels varied widely both within and between patients. Three patients displayed at least one normal TG measurement (<2.0mmol/L or <175mg/dL). All patients displayed mild-to-moderate HTG (2 to 9.9mmol/L or 175 to 875mg/dL) at multiple time points. Five patients displayed at least one severe HTG measurement. 10%, 54%, and 36% of all TG measurements were in normal, mild-to-moderate, and severe HTG ranges, respectively. Heterozygosity for pathogenic variants in APOA5 is associated with highly variable TG phenotypes both within and between patients. Heterozygosity confers susceptibility to elevated TG levels, with secondary factors likely modulating the phenotypic severity.

Prediction of perioperative myocardial infarction/injury in high-risk patients after noncardiac surgery.

Perioperative myocardial infarction/injury (PMI) is a surprisingly common, yet difficult to predict cardiac complication in patients undergoing non-cardiac surgery. We aimed to assess the incremental value of preoperative cardiac troponin (cTn) concentration in the prediction of PMI. Among prospectively recruited patients at high cardiovascular risk (age >65 years OR >45 years with pre-existing cardiovascular disease), PMI was defined as an absolute increase in high-sensitivity cTnT (hs-cTnT) concentration of ≥14ng/L (the 99th percentile) above the preoperative concentration. PMI was centrally adjudicated by two independent cardiologists using serial measurements of hs-cTnT. Using logistic regression, three models were derived: Model 1 included patient- and procedure-related information, Model 2 adding routinely available laboratory values, and Model 3 further adding preoperative hs-cTnT concentration. Models were compared also versus preoperative hs-cTnT alone. Findings were validated in two independent cohorts. Among 6'944 patients, PMI occurred in 1058 patients (15.2%). The predictive accuracy as quantified by the area under the receiver-operating characteristic curve was 0.73 (95%CI 0.71-0.74) for Model 1, 0.75 (95%CI 0.74-0.77) for Model 2, 0.79 (95%CI 0.77-0.80) for Model 3, and 0.74 for hs-cTnT alone. Model 3 included 10 preoperative variables: age, body-mass-index, known coronary artery disease, metabolic equivalent >4, risk of surgery, emergency surgery, planned duration of surgery, haemoglobin, platelet count and hs-cTnT. These findings were confirmed in both independent validation cohorts (n=722, n=966). Preoperative cTn adds incremental value above patient- and procedure-related variables as well as routine laboratory in the prediction of PMI.

Long-term weight loss as a predictor of mortality in haemodialysis patients.

Serial weight decrease can be a prognostic predictor in chronic haemodialysis (HD) patients. We investigated the impact of long-term post-HD body weight (BW) changes on all-cause mortality among HD patients. This longitudinal cohort study and post-hoc analysis evaluated participants of a previous randomised controlled trial conducted between 2006 and 2011 who were followed up until 2018. Weight change slopes were generated with repeated measurements every 6 months during the trial for patients having ≥5 BW measurements. Participants were categorised into four groups based on quartiles of weight change slopes; the median weight changes per 6 months were -1.02 kg, -0.25 kg, +0.26 kg, and +0.86 kg. Cox proportional hazard regression was used to evaluate differences in subsequent survival among the four groups. BW trajectories were plotted with a backward time-scale and multilevel regression analysis to visualise the difference in BW trajectories between survivors and non-survivors. Among the 461 patients, 404 were evaluated, and 168 (41.6%) died within a median follow-up period of 10.2 years. The Cox proportional hazard regression adjusted for covariates and baseline BW showed that a higher rate of weight loss was associated with higher mortality. The hazard ratios were 2.02 (1.28-3.20), 1.77 (1.10-2.85), 1.00 (reference), and 1.11 (0.67-1.83) for the first, second, third (reference), and fourth quartiles, respectively. BW trajectories revealed a significant decrease in BW in non-survivors. Weight loss elucidated by serial BW measurements every 6 months is significantly associated with higher mortality among HD patients.

Incidence and Predictors for Oncologic Etiologies in Chinese Children with Pituitary Stalk Thickening.

With the increasing use of magnetic resonance imaging (MRI) in the evaluation of children with endocrine disorders, pituitary stalk thickening (PST) poses a clinical conundrum due to the potential for underlying neoplasms and challenges in obtaining a tissue biopsy. The existing literature suggests Langerhans cell histiocytosis (LCH) to be the commonest (16%) oncologic cause for PST, followed by germ cell tumors (GCTs, 13%) (CCLG 2021). As the cancer epidemiology varies according to ethnicity, we present herein the incidence and predictors for oncologic etiologies in Hong Kong Chinese children with PST. Based on a territory-wide electronic database, we reviewed patients aged < 19 years who presented to three referral centers with endocrinopathies between 2010 and 2022. Records for patients who underwent at least one MRI brain/pituitary were examined (n = 1670): those with PST (stalk thickness ≥ 3 mm) were included, while patients with pre-existing cancer, other CNS and extra-CNS disease foci that were diagnostic of the underlying condition were excluded. Twenty-eight patients (M:F = 10:18) were identified. The median age at diagnosis of PST was 10.9 years (range: 3.8-16.5), with central diabetes insipidus (CDI) and growth hormone deficiency (GHD) being the most frequent presenting endocrine disorders. At a median follow-up of 4.8 years, oncologic diagnoses were made in 14 patients (50%), including 13 GCTs (46%; germinoma = 11, non-germinoma = 2) and one LCH (4%). Among patients with GCTs, 10 were diagnosed based on histology, two by abnormal tumor markers and one by a combination of histology and tumor markers. Three patients with germinoma were initially misdiagnosed as hypophysitis/LCH. The cumulative incidence of oncologic diagnoses was significantly higher in boys and patients with PST at presentation ≥6.5 mm, CDI or ≥2 pituitary hormone deficiencies at presentation and evolving hypopituitarism (all p < 0.05 by log-rank). A higher rate of GCTs was observed in Chinese children with endocrinopathy and isolated PST. The predictors identified in this study may guide healthcare providers in Asia in clinical decision making. Serial measurement of tumor markers is essential in management.

Comparison of three methods of tonometry in horses presented for ophthalmic disease.

To compare the measurement of intraocular pressure in horses with clinical ocular disease using three tonometry devices. A total of fifty horses were presented to the New Bolton Center Ophthalmology Service. Intraocular pressure was taken on 50 client-owned horses (100 eyes) using the TonoVet, TonoVet Plus and Tono-Pen Avia tonometers. Clinical equine patients included were presented to New Bolton Center for ophthalmic examination. Auriculopalpebral blocks were performed but horses were unsedated. All three tonometers were found to have strong agreement among them. The strongest agreement was between the TonoVet and the TonoVet Plus with the TonoVet on average 1.330 mmHg less than the TonoVet Plus (standard deviation 4.388 mmHg). This was followed by the TonoVet and the Tono-Pen Avia Vet with the TonoVet on average 2.531 mmHg greater than the Tono-Pen Avia Vet (standard deviation 4.124 mmHg). The weakest agreement was between the TonoVet Plus and the Tono-Pen Avia with the TonoVet Plus on average 3.854 mmHg greater than the Tono-Pen Avia (standard deviation 4.724 mmHg). All three tonometers showed strong agreement, however, the TonoVet and the TonoVet Plus carried the strongest agreement with the TonoVet Plus having slightly higher measurements overall compared with the TonoVet. Due to small variations between devices, it is recommended that the same device be used for serial measurements of intraocular pressure. However, all three devices are appropriate to use in horses presented for ophthalmic evaluation.

Comparing maximum diameter and volume when assessing the growth of small abdominal aortic aneurysms using longitudinal CTA data: cohort study.

Monitoring of abdominal aortic aneurysms (AAAs) is currently based on serial measurements of maximum aortic diameter. Additional assessment of aneurysm volume has previously been proposed to possibly improve growth prediction and treatment decisions. To evaluate the use of supplementing volume measurements, the authors aimed to characterise the growth distribution of AAA volume and to compare the growth rates of the maximum diameter and volume at the patient level. Maximum diameter and volume were monitored every 6 months in 84 patients with small AAAs, with a total of 331 computed tomographic angiographies (with initial maximum diameters of 30-68mm). A previously developed statistical growth model for AAAs was applied to assess the growth distribution of volume and to compare individual growth rates for volume and for maximum diameter. The median (25-75% quantile) expansion in volume was 13.4 (6.5-24.7) % per year. Cube root transformed volume and maximum diameter showed a closely linear association with a within-subject correlation of 0.77. At the surgery threshold maximum diameter of 55mm, the median (25-75% quantile) volume was 132 (103-167)ml. In 39% of subjects, growth rates for volume and maximum diameter were equivalent, in 33% growth was faster in volume and in 27% growth was faster in maximum diameter. At the population level, volume and maximum diameter show a substantial association such that the average volume is approximately proportional to the average maximum diameter raised to a power of three. At the individual level, however, in the majority of patient's AAAs grow at different pace in different dimensions. Hence, closer monitoring of aneurysms with sub-critical diameter but suspicious morphology may benefit from complementing maximum diameter by volume or related measurements.

Does the External Pericardial Lateral Tunnel Fontan Pathway Enlarge to Accommodate Somatic Growth? A Preliminary Analysis.

Objectives: An ideal Fontan pathway should be capable of adapting to changes in circulatory demands. The external pericardial lateral tunnel Fontan (EPLTF) is constructed of viable, autologous tissue and may be capable of changing in size. We investigated the ability of the EPLTF to enlarge with increasing physiologic demands of somatic growth. Methods: Retrospective review of echocardiographic images for patients with a minimum of five years follow-up after EPLTF. Serial echocardiographic measurements of the EPLTF pathway were obtained at three distinct locations: the inferior vena cava junction with the EPLTF, midsection of the EPLTF, and cross-sectional area of the EPLTF visualized in a four-chamber view. Body surface area (BSA) was calculated at the time of each echocardiographic measurement. Changes in echocardiographic measurements over time were analyzed and compared with changes in BSA. Results: A total of 332 echocardiographic studies from 38 patients were reviewed. Significant enlargement of the EPLTF pathway is observed at the inferior vena caval junction (P < .001), midsection (P < .01), and cross-sectional area (P < .001). Repeated measures correlation between pathway measurements and BSA is highly significant (P < .001). Conclusions: The EPLTF pathway enlarges over time in correlation with increasing BSA. Further research is needed to define ideal pathway size, differentiate normal physiologic growth from pathologic enlargement, and correlate changes with clinical outcomes.

Serial blood volume measurements in patients with compensated chronic heart failure: How do volume profiles change over time?

Among patients with chronic heart failure (HF) intravascular volume profiles vary significantly despite similar clinical compensation. However, little is known regarding changes in blood volume (BV) profiles over time. The objective of this analysis was to identify the extent and character of changes in volume profiles over time. A prospective analysis was undertaken in patients who were hospitalized and treated for fluid overload. Quantitative BV analyses were obtained in a compensated state at hospital discharge (baseline) and follow-up at 1, 3, and 6 mo. Data were available on 10 patients who remained stable without rehospitalization or medication change over a 6-mo period. Baseline BV profiles were highly variable at hospital discharge with an average deviation of +28% above normal in 6 patients and normal BV in 4 patients. Over the follow-up period, the median change in BV was -201 mL [-3% (-6, +3%)] from baseline with profiles remaining in the same volume category in 9 out of 10 patients. Crossover from normal BV to mild contraction (-13% of normal) occurred in one patient. Red blood cell mass demonstrated the largest change over 6 mo [median -275 (-410, +175) mL] with a deviation from normal of -14 (-20, +8) % (reflecting mild anemia). These findings suggest that BV profiles in clinically compensated patients with HF do not change substantially over a 6-mo period regardless of baseline expanded or normal BV. This lack of change in volume profiles particularly from an expanded BV has implications for long-term volume management, clinical outcomes, and also our understanding of volume homeostasis in HF.NEW & NOTEWORTHY The novel findings of this study demonstrate that blood volume profiles while highly variable in clinically compensated patients with HF on stable medical therapy do not change substantially over a 6-mo period regardless of baseline expanded or normal blood volumes. This lack of change in volume profiles particularly from an expanded blood volume has implications for long-term volume management and also for how we understand the pathophysiology of volume homeostasis in chronic HF.