Complex systems and the technology of variability analysis

Characteristic patterns of variation over time, namely rhythms, represent a defining feature of complex systems, one that is synonymous with life. Despite the intrinsic dynamic, interdependent and nonlinear relationships of their parts, complex biological systems exhibit robust systemic stability. Applied to critical care, it is the systemic properties of the host response to a physiological insult that manifest as health or illness and determine outcome in our patients. Variability analysis provides a novel technology with which to evaluate the overall properties of a complex system. This review highlights the means by which we scientifically measure variation, including analyses of overall variation (time domain analysis, frequency distribution, spectral power), frequency contribution (spectral analysis), scale invariant (fractal) behaviour (detrended fluctuation and power law analysis) and regularity (approximate and multiscale entropy). Each technique is presented with a definition, interpretation, clinical application, advantages, limitations and summary of its calculation. The ubiquitous association between altered variability and illness is highlighted, followed by an analysis of how variability analysis may significantly improve prognostication of severity of illness and guide therapeutic intervention in critically ill patients

Predictive Factors for Postoperative Pancreatic Fistula—A Swedish Nationwide Register-Based Study

Background: A serious complication after pancreatoduodenectomy (PD) is postoperative pancreatic fistula (POPF). The aim of this study was to analyse the incidence and predictive factors for POPF by using a large nationwide cohort. Methods: Data from the Swedish National Registry for Pancreatic and Periampullary Cancer for all patients undergoing a PD from 2010 until 30th June 2018 were collected. The material was analysed in two groups, no POPF and clinically relevant (grade B and C) POPF. Results: A total of 2503 patients underwent PD, of which 245 (10%) developed POPF. Patients with POPF had significantly more overall complications (Clavien Dindo ≥3a, 75% vs. 21%, p < 0.001) and longer hospital stay (median 23 [16–35] vs. 11 [8–15], p < 0.001) than patients without POPF. The risk of POPF was higher with increased BMI (OR 1.08, p < 0.001). Preoperative presence of diabetes (OR 0.52, p = 0.012) and preoperative biliary drainage (OR 0.34, p < 0.001) reduced the risk of POPF. Reconstruction with pancreaticojejunostomy caused a more than two folded increase in POPF compared with pancreaticogastrostomy (OR 2.41, p < 0.001). Weight gain ≥2 kg on postoperative day 1 was also a risk factor (OR 1.76, p < 0.001). Conclusion: A high BMI, a pancreaticojejunostomy and postoperative weight gain were risk factors for developing POPF. Diabetes or preoperative biliary drainage was protective

Reinforced versus standard stapler transection on postoperative pancreatic fistula in distal pancreatectomy : multicentre randomized clinical trial

BACKGROUND: Postoperative pancreatic fistula is the leading cause of morbidity after distal pancreatectomy. Strategies investigated to reduce the incidence have been disappointing. Recent data showed a reduction in postoperative pancreatic fistula with the use of synthetic mesh reinforcement of the staple line. METHODS: An RCT was conducted between May 2014 and February 2016 at four tertiary referral centres in Sweden. Patients scheduled for distal pancreatectomy were eligible. Enrolled patients were randomized during surgery to stapler transection with biological reinforcement or standard stapler transection. Patients were blinded to the allocation. The primary endpoint was the development of any postoperative pancreatic fistula. Secondary endpoints included morbidity, mortality, and duration of hospital stay. RESULTS: Some 107 patients were randomized and 106 included in an intention-to-treat analysis (56 in reinforced stapling group, 50 in standard stapling group). No difference was demonstrated in terms of clinically relevant fistulas (grade B and C): 6 of 56 (11 per cent) with reinforced stapling versus 8 of 50 (16 per cent) with standard stapling (P = 0.332). There was no difference between groups in overall postoperative complications: 45 (80 per cent) and 39 (78 per cent) in reinforced and standard stapling groups respectively (P = 0.765). Duration of hospital stay was comparable: median 8 (range 2-35) and 9 (2-114) days respectively (P = 0.541). CONCLUSION: Biodegradable stapler reinforcement at the transection line of the pancreas did not reduce postoperative pancreatic fistula compared with regular stapler transection in distal pancreatectomy. Registration number: NCT02149446 (http://www.clinicaltrials.gov)

Adverse Cardiovascular Events Arising From Atherosclerotic Lesions With and Without Angiographic Disease Progression

OBJECTIVES The aim of this study was to use angiography and grayscale and intravascular ultrasound virtual histology to assess coronary lesions that caused events during a median follow-up period of 3.4 years. BACKGROUND Vulnerable plaque-related events are assumed to be the result of substantial progression of insignificant lesions. METHODS In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, 697 patients with acute coronary syndromes underwent treatment of all culprit lesions followed by 3-vessel imaging to assess the natural history of culprit and untreated nonculprit (NC) lesions. Future adverse cardiovascular events adjudicated to NC lesions were divided into those with versus without substantial lesion progression (SLP) (>= 20% angiographic diameter stenosis increa RESULTS NC lesion events occurred in 72 patients, 44 (61%) with and 28 (39%) without SLP. Myocardial infarctions (n = 6) occurred only in patients with SLP. Conversely, patients without SLP presented only with unstable or increasing angina requiring rehospitalization. Lesions with versus without SLP occurred later (median time to event 401 vs. 223 days, p = 0.07); were less severe at baseline (median diameter stenosis 26.4% vs. 53.8%, p < 0.0001) but more severe at the time of the event (mean di CONCLUSIONS NC lesions responsible for future cardiovascular events showed angiographic increase during 3.4 years of follow-up, whereas SLP underlay many but not all of them. NC events due to lesions with SLP were angiographically less severe and presented with a delayed time course but were otherwise indistinguishable from NC events that were not associated with SLP. (J Am Coll Cardiol lmg 2012;5:S95-105) (C) 2012 by the American College of Cardiology Foundatio

Clinical Outcome of Nonculprit Plaque Ruptures in Patients With Acute Coronary Syndrome in the PROSPECT Study

OBJECTIVES The aim of this study was to report the frequency, patient and lesion-related characteristics, and outcomes of subclinical, nonculprit plaque ruptures in the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study. BACKGROUND Plaque rupture and subsequent thrombosis is the most common cause of acute coronary syndrome (ACS). Secondary, subclinical, nonculprit plaque ruptures have been seen in both stable patients and patients with ACS; however, reports of the natural history of these secondary plaque ruptures are limited. METHODS After successful stenting in 697 patients with ACS, 3-vessel grayscale and intravascular ultrasound virtual histology (IVUS-VH) was performed in the proximal-mid segments of all 3 coronary arteries as part of a prospective multicenter study. RESULTS Among 660 patients with complete IVUS data, 128 plaque ruptures were identified in 105 nonculprit lesions in 100 arteries from 93 patients (14.1%). Although the minimum lumen area (MLA) was similar, the plaque burden was significantly greater in nonculprit lesions with a plaque rupture compared with nonculprit lesions without a plaque rupture (66.0% [95% confidence interval: 64.5% to 67.4%] vs. 56.0% [95% confidence interval: 55.6% to 56.4%]; p < 0.0001). IVUS-VH analysis revealed that a nonculprit lesion with a plaque rupture was more often classified as a fibroatheroma than a nonculprit lesion without a plaque rupture (77.1% vs. 51.4%; p < 0.0001). Independent predictors of a plaque rupture were lesion length (per 10 mm; odds ratio: 1.30; p < 0.0001), plaque burden at the MLA site (per 10%; odds ratio: 2.56; p < 0.0001), vessel area at the MLA site (per 1 mm2; odds ratio: 1.13; p < 0.0001), and VH thin-cap fibroatheroma (odds ratio: 1.80; p = 0.016). During 3 years of follow-up, the incidence of overall major adverse cardiac events did not differ significantly between the patients with and patients without subclinical, nonculprit plaque ruptures. CONCLUSIONS Secondary, nonculprit plaque ruptures were seen in 14% of patients with ACS and were associated with a fibroatheroma phenotype with a residual necrotic core but not with adverse outcomes if patients were treated with optimal medical therapy as part of a multicenter study. (Providing Regional Observations to Study Predictors of Events in the Coronary Tree [PROSPECT]; NCT00180466) (J Am Coll Cardiol Img 2014;7:397-405) (C) 2014 by the American College of Cardiology Foundatio

Coronary Plaque Composition, Morphology, and Outcomes in Patients With and Without Chronic Kidney Disease Presenting With Acute Coronary Syndromes

OBJECTIVES This study sought to evaluate the impact of chronic kidney disease (CKD) on coronary atherosclerotic plaque composition, morphology, and outcomes in patients with acute coronary syndromes (ACS). BACKGROUND CKD patients presenting with ACS are at increased risk for adverse events. Whether or not this increased risk reflects differences in coronary plaque composition remains unknown. METHODS In the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study, patients presenting with ACS in whom percutaneous coronary intervention was successful underwent 3-vessel grayscale and radiofrequency intravascular ultrasound imaging. Lesions were prospectively characterized, and patients were followed for a median of 3.4 years. We conducted a patient-level and lesion-level analysis of study participants by comparing intravascular ultrasound para RESULTS Patients with CKD (n = 73, 11.3%) were older, more often female and diabetic compared to those without CKD (n = 573). Nonculprit lesions in patients with (n = 280) versus without (n = 2,390) CKD were more likely to have plaque burden >= 70% (11.8% vs. 8.5%, p = 0.05) and minimal luminal area >= 4.0 mm(2) (25.9% vs. 19.2%, p = 0.005). The percentage of plaque comprised of necrotic core (15.0% vs. 13.0%, p = 0.0001) and dense calcium (8.2% vs. 6.4%, p < 0.0001) was higher while fibrous tis CONCLUSIONS Following percutaneous coronary intervention of all culprit lesions in ACS, patients with versus without CKD have more extensive and severe atherosclerosis remaining in their coronary tree with plaque composed of greater necrotic core and less fibrous tissue. These influences resulted in nonsignificantly different rates of non-culprit lesion-related adverse events, although cardiac death, arrest, or myocardial infarction were more common in patients with CKD. Am Coll Cardiol Img 201

Relationship Between Palpography and Virtual Histology in Patients With Acute Coronary Syndromes

OBJECTIVES The purpose of this study was to correlate adverse events at long-term follow-up in patients after an acute coronary syndrome with coronary plaque characteristics derived from simultaneous evaluation of their mechanical and compositional properties using virtual histology (intravascular ultrasound virtual histology) and palpography. BACKGROUND Fibroatheroma is the plaque morphology with the highest risk of causing adverse cardiac events. Palpography can potentially assess the local mechanical plaque properties with the possibility of identifying fibroatheroma with the highest risk of rupture. METHODS A total of 114 patients with acute coronary syndrome from the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) trial underwent a single ultrasound imaging investigation of their 3 coronary vessels with the co-registration of intravascular ultrasound virtual histology and palpography. Major adverse cardiac events (MACE) (cardiac death, cardiac arrest, myocardial infarction, or unstable or progressive angina) were collected up to a median follow RESULTS In total, 488 necrotic core-rich plaques were identified and subclassified as thin-cap fibroatheroma (n = 111), calcified thick-cap fibroatheroma (n = 213), and noncalcified thick-cap fibroatheroma (n = 164) and matched to their co-registered palpography data. A total of 16 MACE, adjudicated to untreated nonculprit lesions, were recorded at follow-up. In patients in whom MACE developed, fibroatheroma were larger (plaque area 10.0 mm(2) [range: 8.4 to 11.6 mm(2)] vs. 8.2 mm(2) [range: 7.7 CONCLUSIONS In acute coronary syndromes, patients treated with stents and contemporary pharmacotherapy, palpography did not provide additional diagnostic information for the identification of fibroatheroma with a high risk of rupture and MACE during long-term follow-up. (Providing Regional Observations to Study Predictors of Events in the Coronary Tree [PROSPECT]: An Imaging Study in Patients With Unstable Atherosclerotic Lesions; NCT00180466) (J Am Coll Cardiol Img 2012;5:519-27) (C) 2012 by t