Blood Products, Crystalloids, and Rapid Infusion: An Experimental Study With Magnesium.

OBJECTIVES: Calcium and magnesium are concentration-dependent pro- and anticoagulant cofactors, and magnesium behaves similarly to calcium in the presence of citrate. The authors hypothesized that magnesium can cause clot formation (primary objective) when mixed with coagulation factor-containing blood products diluted with different crystalloids in a rapid- infuser reservoir. A secondary objective was the observation of any infuser alarms and stops in the event of clotting. DESIGN: An experimental in vitro study with blood products, crystalloids, magnesium, and calcium in a rapid infuser with a reservoir using a closed-loop system. SETTING: Anesthesia research laboratory at an urban academic tertiary medical center PARTICIPANTS: Not applicable. INTERVENTIONS: Exposure of fresh frozen plasma (FFP) and packed red blood cells alone (control) or in combination with either normal saline (NS), lactated Ringer's solution (LR), or Plasma-Lyte A (PL) to increasing concentrations of magnesium sulphate (MgSO4) up to 1 g. After each incremental MgSO4 change, the authors applied a specific pump-flow sequence in a closed-loop system with a rapid-infuser reservoir, and if no clot was observed, the authors incrementally added calcium chloride (CaCl2) up to 1 g. MEASUREMENTS AND MAIN RESULTS: Observation of macroscopic clot and time to event, as well as occurrence and type of any pump alarms or stops. LR experiments resulted in clot observation in the reservoir by a dedicated observer after MgSO4 275 ± 206 mg (95% confidence interval [CI], 9-541). Adding MgSO4 1 g in the NS, PL, or the control experiments did not result in clot observation. Only when CaCl2 166.7 ± 51.64 mg (95% CI, 112.0-22.01) was added to the combination of blood products alone or mixed with NS and PL, clotting occurred. The mean FFP volume was 281 ± 48.6 mL (range, 204-340 mL) and was not different between groups (p = 0.44). Pump alarms and stops were inconsistent. CONCLUSIONS: The addition of magnesium to a combination of LR with coagulation factor- containing blood products consistently resulted in a visible blood clot in the rapid-infuser reservoir in the authors' experimental setup. In addition to MgSO4 1 g in the control, NS, and PL experiments, CaCl2 is needed before a clot can be observed.

The effect of age on anastomotic leakage in colorectal cancer surgery: A population-based study.

BACKGROUND: The aim of this study was to investigate the effect of age on CAL and its associated mortality. METHODS: Data were derived from the Dutch ColoRectal Audit. All patients undergoing resection for colorectal cancer in the Netherlands between January 2011 and December 2016 were included. Univariable and multivariable logistic regressions were performed to test the effect of age on CAL and its associated mortality. RESULTS: In total, 45 488 patients were included. The incidence of CAL was 6.4% in patients <60 years old, 5.5% in patients 60-69 years old, 5.4% in patients 70-80 years old, and 4.9% in patients ≥80 years old (P < 0.001). Multivariate analysis showed that age was protective for CAL (OR 0.965 per 5 years, 95% CI 0.941-0.985, P < 0.001). Mortality after CAL was 1.3% in patients <60 years old, 4.8% in patients 60-69 years old, 12.3% in patients 70-80 years old, and 27.0% in patients >80 years old (P < 0.001). Older age was associated with mortality following CAL (OR 1.497 per 5 years 95% CI 1.364-1.647, P < 0.001). CONCLUSIONS: This population-based study suggests a protective effect of increased age on CAL after colorectal cancer resection. However, older age is strongly associated with mortality after CAL.

An Analysis of Guideline Consensus for the Prevention, Diagnosis, and Management of Diabetic Foot Ulcers.

BACKGROUND: Multiple organizations have issued guidelines to address the prevention, diagnosis, and management of diabetic foot ulcers (DFUs) based on evidence review and expert opinion. We reviewed these guidelines to identify consensus (or lack thereof) on the nature of these recommendations, the strength of the recommendations, and the level of evidence. METHODS: Ovid, PubMed, Web of Science, Cochrane Library, and Embase were searched in October 2018 using the MESH term diabetic foot, the key word diabetic foot, and the filters guideline or practice guideline. To minimize recommendations based on older literature, guidelines published before 2012 were excluded. Articles without recommendations characterized by strength of recommendation and level of evidence related specifically to DFU were also excluded. A manual search for societal recommendations yielded no further documents. Recommendations were ultimately extracted from 12 articles. Strength of evidence and strength of recommendation were noted for each guideline recommendation using the Grading of Recommendations Assessment, Development, and Evaluation system or the Centre for Evidence-Based Medicine system. To address disparate grading systems, we mapped the perceived level of evidence and strength of recommendations onto the American Heart Association guideline classification schema. RESULTS: Recommendations found in two or more guidelines were collected into a clinical checklist characterized by strength of evidence and strength of recommendation. Areas for future research were identified among recommendations based on minimal evidence, areas of controversy, or areas of clinical care without recommendations. CONCLUSIONS: Through this work we developed a multidisciplinary set of DFU guidelines stratified by strength of recommendation and quality of evidence, created a clinical checklist for busy practitioners, and identified areas for future focused research. This work should be of value to clinicians, guideline-issuing bodies, and researchers. We also formulated a method for the review and integration of guidelines issued by multiple professional bodies.

Cell force-mediated matrix reorganization underlies multicellular network assembly.

Vasculogenesis is the de novo formation of a vascular network from individual endothelial progenitor cells occurring during embryonic development, organogenesis, and adult neovascularization. Vasculogenesis can be mimicked and studied in vitro using network formation assays, in which endothelial cells (ECs) spontaneously form capillary-like structures when seeded in the appropriate microenvironment. While the biochemical regulators of network formation have been well studied using these assays, the role of mechanical and topographical properties of the extracellular matrix (ECM) is less understood. Here, we utilized both natural and synthetic fibrous materials to better understand how physical attributes of the ECM influence the assembly of EC networks. Our results reveal that active cell-mediated matrix recruitment through actomyosin force generation occurs concurrently with network formation on Matrigel, a reconstituted basement membrane matrix regularly used to promote EC networks, and on synthetic matrices composed of electrospun dextran methacrylate (DexMA) fibers. Furthermore, modulating physical attributes of DexMA matrices that impair matrix recruitment consequently inhibited the formation of cellular networks. These results suggest an iterative process in which dynamic cell-induced changes to the physical microenvironment reciprocally modulate cell behavior to guide the formation and stabilization of multicellular networks.

SES and correlated factors do not explain the association between periodontal disease, edentulism, and cancer risk.

PURPOSE: Severe periodontal disease and edentulism have been previously reported to be significantly associated with cancer risk and mortality, including in the Atherosclerosis Risk in Communities study (2018); however, complex sources of confounding by socioeconomic status (SES), and characteristics correlated with SES, could have been present in earlier analyses. METHODS: To capture life course SES and its correlates, we generated a propensity score and included it, along with other potential confounders such as smoking and obesity, into a Cox regression model to examine the association between periodontal disease and cancer risk. In addition, we stratified the model with the propensity score by low and high SES. All statistical tests were two-sided. RESULTS: Compared with our previous study, the associations for severe periodontitis and cancer incidence remained comparable after weighting by the propensity score (e.g., for total cancer: before weighting, hazard ratio = 1.24, 95% confidence interval = 1.07-1.42 vs. after weighting, hazard ratio = 1.23, 95% confidence interval = 1.05-1.44 when comparing severe periodontitis to no or mild periodontitis). Associations were comparable in low and high SES strata and statistically significant among participants with high SES. CONCLUSIONS: Complex sources of confounding by SES and its correlates are unlikely to fully account for the positive associations observed for periodontal disease and edentulism and cancer risk.

Safe laparoscopic cholecystectomy: A systematic review of bile duct injury prevention.

BACKGROUND: Since the introduction of laparoscopic cholecystectomy (LC), a substantial increase in bile duct injury (BDI) incidence was noted. Multiple methods to prevent this complication have been developed and investigated. The most suitable method however is subject to debate. In this systematic review, the different modalities to aid in the safe performance of LC and prevent BDI are delineated. MATERIALS AND METHODS: A systematic search for articles describing methods for the prevention of BDI in LC was conducted using EMBASE, Medline, Web of science, Cochrane CENTRAL and Google scholar databases from inception to 11 June 2018. RESULTS: 90 studies were included in this systematic review. Overall, BDI preventive techniques can be categorized as dedicated surgical approaches (Critical View of Safety (CVS), fundus first, partial laparoscopic cholecystectomy), supporting imaging techniques (intraoperative radiologic cholangiography, intraoperative ultrasonography, fluorescence imaging) and others. Dedicated surgical approaches demonstrate promising results, yet limited research is provided. Intraoperative radiologic cholangiography and ultrasonography demonstrate beneficial effects in BDI prevention, however the available evidence is low. Fluorescence imaging is in its infancy, yet this technique is demonstrated to be feasible and larger trials are in preparation. CONCLUSION: Given the low sample sizes and suboptimal study designs of the studies available, it is not possible to recommend a preferred method to prevent BDI. Surgeons should primarily focus on proper dissection techniques, of which CVS is most suitable. Additionally, recognition of hazardous circumstances and knowledge of alternative techniques is critical to complete surgery with minimal risk of injury to the patient.

Variation in DNA methylation of human blood over a 1-year period using the Illumina MethylationEPIC array.

Assessing DNA methylation profiles in human blood has become a major focus of epidemiologic inquiry. Understanding variability in CpG-specific DNA methylation over moderate periods of time is a critical first step in identifying CpG sites that are candidates for DNA methylation-based etiologic, diagnostic and prognostic predictors of pathogenesis. Using the Illumina MethylationEPIC [850K] BeadArray, DNA methylation was profiled in paired whole blood samples collected approximately 1 year apart from 35 healthy women enrolled in the Nurses Study II cohort. The median intraclass correlation coefficient (ICC) across all CpG loci was 0.19 [Interquartile Range (IQR) 0.00-0.50]; 74.8% of ICCs were in the low range (0-0.5), 16.9% in the mid-range of ICCs (0.5-0.8), and 8.3% in the high-range of ICCs (0.8-1). ICCs were similar for CpG probes on the 450K Illumina array (median 0.17) and the new probes added to the 850K array (median 0.21). ICCs for CpG loci on the sex chromosomes and known metastable epialleles were high (median 0.71, 0.97, respectively), and ICCs among methylation quantitative trait loci (mQTL) CpGs were significantly higher as compared to non-mQTL CpGs (median 0.73, 0.16, respectively, P < 2 × 10-16). We observed wide variation in DNA methylation stability over a 1-year period. Probes considered non-stable, due to substantial variation over a moderate period of time and with minimal variability across individuals could be removed in large epidemiological studies. Moreover, adjusting for technical variation that arises from using high-dimensional arrays is critical.