Objectives Acute kidney injury (AKI) is a frequent complication after open repair of abdominal aortic aneurysms (AAA). Little research has been done to determine whether intraoperative hemodynamic ...events may precipitate AKI. Novel biomarkers also may aid in the earlier diagnosis of AKI. Design A pilot prospective observational trial. Setting A single tertiary academic medical center. Participants Participants were 40 adult patients undergoing open repair of infrarenal AAA. Interventions Intraoperative hemodynamic monitoring of heart rate, mean arterial pressure, central venous pressure, and cardiac index was performed on a continuous basis. Blood samples were obtained at baseline and at 24 hours postoperatively for inflammatory biomarkers, including neutrophil gelatinase-associated lipocalin (NGAL). Measurements and Main Results AKI occurred in 20% of patients (8 of 40). Hypotension, including duration (defined as the length of time mean arterial pressure was<65 mmHg) and magnitude (the area under the curve of a mean arterial pressure<65 mmHg), was the only factor associated with postoperative AKI. Urinary NGAL at the conclusion of surgery had excellent ability to predict the development of AKI (area under the curve 0.84, 95% confidence interval = 0.70-0.97). The cytokines pentraxin 3 (PTX3), interleukin-1 receptor antagonist (IL1-RA), macrophage chemotactic protein (MCP), suppressor of tumorigenicity 2 (ST-2), and interleukin-10 (IL-10) also had good ability to predict the development of AKI in the immediate postoperative period. Conclusions AKI occurs frequently in patients undergoing open repair of AAA. Intraoperative hypotension was the only factor that predicted the development of subsequent AKI. Urinary NGAL and several novel inflammatory biomarkers demonstrated good ability to predict its development. Novel biomarkers also may aid in the early diagnosis of AKI.
Platelets play a central role in thrombosis, hemostasis, and inflammation. We show that activated platelets release inorganic polyphosphate (polyP), a polymer of 60–100 phosphate residues that ...directly bound to and activated the plasma protease factor XII. PolyP-driven factor XII activation triggered release of the inflammatory mediator bradykinin by plasma kallikrein-mediated kininogen processing. PolyP increased vascular permeability and induced fluid extravasation in skin microvessels of mice. Mice deficient in factor XII or bradykinin receptors were resistant to polyP-induced leakage. PolyP initiated clotting of plasma via the contact pathway. Ablation of intrinsic coagulation pathway proteases factor XII and factor XI protected mice from polyP-triggered lethal pulmonary embolism. Targeting polyP with phosphatases interfered with procoagulant activity of activated platelets and blocked platelet-induced thrombosis in mice. Addition of polyP restored defective plasma clotting of Hermansky-Pudlak Syndrome patients, who lack platelet polyP. The data identify polyP as a new class of mediator having fundamental roles in platelet-driven proinflammatory and procoagulant disorders.
The relationship between racial and socioeconomic status (SES) disparities and the quality of epithelial ovarian cancer care and survival outcome are unclear.
A population-based analysis of National ...Cancer Data Base (NCDB) records for invasive primary epithelial ovarian cancer diagnosed in the period from 1998 to 2002 was done using data from patients classified as white or black. Adherence to National Comprehensive Cancer Network (NCCN) guideline care was defined by stage-appropriate surgical procedures and recommended chemotherapy. The main outcome measures were differences in adherence to NCCN guidelines and overall survival according to race and SES and were analyzed using binomial logistic regression and multilevel survival analysis.
A total of 47 160 patients (white = 43 995; black = 3165) were identified. Non-NCCN-guideline-adherent care was an independent predictor of inferior overall survival (hazard ratio HR = 1.43, 95% confidence interval CI = 1.38 to 1.47). Demographic characteristics independently associated with a higher likelihood of not receiving NCCN guideline-adherent care were black race (odds ratio OR = 1.36, 95% CI = 1.25 to 1.48), Medicare payer status (OR = 1.20, 95% CI = 1.12 to 1.28), and not insured payer status (OR = 1.33, 95% CI = 1.19 to 1.49). After controlling for disease and treatment-related variables, independent racial and SES predictors of survival were black race (HR = 1.29, 95% CI = 1.22 to 1.36), Medicaid payer status (HR = 1.29, 95% CI = 1.20 to 1.38), not insured payer status (HR = 1.32, 95% CI = 1.20 to 1.44), and median household income less than $35 000 (HR = 1.06, 95% CI = 1.02 to 1.11).
These data highlight statistically and clinically significant disparities in the quality of ovarian cancer care and overall survival, independent of NCCN guidelines, along racial and SES parameters. Increased efforts are needed to more precisely define the patient, provider, health-care system, and societal factors leading to these observed disparities and guide targeted interventions.
Sars-CoV-2, the causative agent of COVID-19, has led to more than 226,000 deaths in the UK and multiple risk factors for mortality including age, sex and deprivation have been identified. This study ...aimed to identify which individual indicators of the Scottish Index of Multiple Deprivation (SIMD), an area-based deprivation index, were predictive of mortality.
This was a prospective cohort study of anonymised electronic health records of 710 consecutive patients hospitalised with Covid-19 disease between March and June 2020 in the Lothian Region of Southeast Scotland. Data sources included automatically extracted data from national electronic platforms and manually extracted data from individual admission records. Exposure variables of interest were SIMD quintiles and 12 indicators of deprivation deemed clinically relevant selected from the SIMD. Our primary outcome was mortality. Age and sex adjusted univariable and multivariable analyses were used to determine measures of association between exposures of interest and the primary outcome.
After adjusting for age and sex, we found an increased risk of mortality in the more deprived SIMD quintiles 1 and 3 (OR 1.75, CI 0.99-3.08, p = 0.053 and OR 2.17, CI 1.22-3.86, p = 0.009, respectively), but this association was not upheld in our multivariable model containing age, sex, Performance Status and clinical parameters of severity at admission. Of the 12 pre-selected indicators of deprivation, two were associated with greater mortality in our multivariable analysis: income deprivation rate categorised by quartile (Q4 (most deprived): 2.11 (1.20-3.77) p = 0.011)) and greater than expected hospitalisations due to alcohol per SIMD data zone (1.96 (1.28-3.00) p = 0.002)).
SIMD as an aggregate measure of deprivation was not predictive of mortality in our cohort when other exposure measures were accounted for. However, we identified a two-fold increased risk of mortality in patients residing in areas with greater income-deprivation and/or number of hospitalisations due to alcohol. In areas where aggregate measures fail to capture pockets of deprivation, exploring the impact of specific SIMD indicators may be helpful in targeting resources to residents at risk of poorer outcomes from Covid-19.
Circulating fatty acids (FA) are associated with a multitude of chronic diseases. However, a major gap in establishing such relationships is the lack of accepted fatty acid reference ranges ...representing healthy individuals. Data on validated FA reference ranges would provide a better understanding of study baseline measures and aid in the evaluation and interpretation of pharmaceutical or dietary interventions. Reference ranges for plasma FA levels have been reported in a few small studies and on a limited number of FA. Therefore, we determined the average and percentiles of a broad set of 61 FA (C14 - C24:1) from plasma total lipids from an ethnically diverse population of healthy young Canadian males and females (Total n = 826). Plasma concentrations of some of the major FA ranged from 0.3 to 4.1 mmol/L for palmitic acid, 0.1 to 1.0 mmol/L for stearic acid, 0.03 to 3.2 mmol/L for oleic acid, 0.2 to 5.0 mmol/L for linoleic acid (LA), 12.0 to 186.9 μmol/L for α-linolenic acid, and 7.2 to 237.5 μmol/L for docosahexaenoic acid (DHA). Males had significantly higher plasma concentrations of γ-linolenic acid (GLA) and n-3 docosapentaenoic acid and lower concentrations of palmitoleic acid, LA and DHA than females. Comparison of FA concentrations between Caucasians, East Asians and South Asians revealed that South Asians had significantly lower levels of palmitoleic acid (p < 0.01) and oleic acid (p = 0.01) while East Asians had lower levels of GLA (p = 0.02) and dihomo-γ-linolenic acid (p = 0.03). Overall, these data provide a comprehensive set of quantitative values that profiles a small cohort of Canadians which highlights the utility of establishing validated FA reference ranges that may be used to understand how deficient, suboptimal, or excess amounts of a given FA may be associated with chronic disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Biologically variable mechanical ventilation (Vbv)-using a computer-controller to mimic the normal variability in spontaneous breathing-improves gas exchange in a model of severe lung injury ...(Lefevre, G. R., S. E. Kowalski, L. G. Girling, D. B. Thiessen, W. A. C. Mutch. Am. J. Respir. Crit. Care Med. 1996;154:1567-1572). Improved oxygenation with Vbv, in the face of alveolar collapse, is thought to be due to net volume recruitment secondary to the variability or increased noise in the peak inspiratory airway pressures (Ppaw). Biologically variable noise can be modeled as an inverse power law frequency distribution (y approximately 1/f(a)) (West, B. J., M. Shlesinger. Am. Sci. 1990;78:40-45). In a porcine model of atelectasis-right lung collapse with one-lung ventilation-we studied if Vbv (n = 7) better reinflates the collapsed lung compared with conventional monotonously regular control mode ventilation (Vc; n = 7) over a 5-h period. We also investigated the influence of sigh breaths with Vc (Vs; n = 8) with this model. Reinflation of the collapsed lung was significantly enhanced with Vbv-greater Pa(O(2)) (502 +/- 40 mm Hg with Vbv versus 381 +/- 40 mm Hg with Vc at 5 h; and 309 +/- 79 mm Hg with Vs; mean +/- SD), lower Pa(CO(2)) (35 +/- 4 mm Hg versus 48 +/- 8 mm Hg and 50 +/- 8 mm Hg), lower shunt fraction (9.7 +/- 2.7% versus 14.6 +/- 2.0% and 22.9 +/- 6.0%), and higher respiratory system compliance (Crs) (1.15 +/- 0.15 ml/cm H(2)O/kg versus 0.79 +/- 0.19 ml/cm H(2)O/kg and 0.77 +/- 0.13 ml/cm H(2)O/kg)-at lower mean Ppaw (15.7 +/- 1.4 cm H(2)O versus 18.8 +/- 2.3 cm H(2)O and 18.9 +/- 2.8 cm H(2)O). Vbv resulted in an 11% increase in measured tidal volume (VT(m)) over that seen with Vc by 5 h (14.7 +/- 1.2 ml/kg versus 13. 2 ml/kg). The respiratory rate variability programmed for Vbv demonstrated an inverse power law frequency distribution ( y approximately 1/f(a)) with a = 1.6 +/- 0.3. These findings provide strong support for the theoretical model of noisy end-inspiratory pressure better recruiting atelectatic lung. Our results suggest that using natural biologically variable noise has enhanced the performance of a mechanical ventilator in control mode.
OBJECTIVESWe compared biologically variable ventilation (BVV) (as previously described) () with conventional control mode ventilation (CV) in a model of acute respiratory distress syndrome (ARDS) ...both at 10 cm H2O positive end-expiratory pressure.
DESIGNRandomized, controlled, prospective study.
SETTINGUniversity research laboratory.
SUBJECTSFarm-raised 3- to 4-month-old swine.
INTERVENTIONSOleic acid (OA) was infused at 0.2 mL/kg/hr with Fio2 = 0.5 and 5 cm H2O positive end-expiratory pressure until Pao2 was ≤60 mm Hg; then all animals were placed on an additional 5 cm H2O positive end-expiratory pressure for the next 4 hrs. Animals were assigned randomly to continue CV (n = 9) or to have CV computer controlled to deliver BVV (variable respiratory rate and tidal volume; n = 8). Hemodynamic, expired gas, airway pressure, and volume data were obtained at baseline (before OA), immediately after OA, and then at 60-min intervals for 4 hrs.
MEASUREMENTS AND MAIN RESULTSAt 4 hrs after OA injury, significantly higher Pao2 (213 ± 17 vs. 123 ± 47 mm Hg; mean ± sd), lower shunt fraction (6% ± 1% vs. 18% ± 14%), and lower Paco2 (50 ± 8 vs. 65 ± 11 mm Hg) were seen with BVV than with CV. Respiratory system compliance was greater by experiment completion with BVV (0.37 ± 0.05 vs. 0.31 ± 0.08 mL/cm H2O/kg). The improvements in oxygenation, CO2 elimination, and respiratory mechanics occurred without a significant increase in either mean airway pressure (14.3 ± 0.9 vs. 14.9 ± 1.1 cm H2O) or mean peak airway pressure (39.3 ± 3.5 vs. 44.5 ± 7.2 cm H2O) with BVV. The oxygen index increased five-fold with OA injury and decreased to significantly lower levels over time with BVV.
CONCLUSIONSIn this model of ARDS, BVV with 10 cm H2O positive end-expiratory pressure improved arterial oxygenation over and above that seen with CV with positive end-expiratory pressure alone. Proposed mechanisms for BVV efficacy are discussed.
Background
Fluid management of the surgical patient has undergone a paradigm shift over the past decade. A change from ‘wet’ to ‘dry’ to a ‘goal-directed’ approach has been witnessed. The fluid ...management of patients undergoing free flap reconstruction is particularly challenging. This is typically a long operation with minimal surgical stimulation, and hypotension often ensues. The use of vasopressors in these cases is contra-indicated to maintain adequate flow to the flap. Hypotension is often treated with intravenous fluid boluses. However, aggressive fluid administration to maintain adequate blood pressure can result in flap edema, venous engorgement and, ultimately, flap loss.
Objective
The primary objective of the present study was to determine whether goal-directed fluid therapy, titrated to maintain stroke volume variation ≤13%, with the use of an arterial pulse contour device results in improved postoperative cardiac index (CI) and stroke volume index (SVI) with reduced amounts of intravenous fluid. The primary end points studied were CI, SVI and cumulative crystalloid/colloid administration.
Methods
Twenty female patients undergoing simultaneous microvascular free flap reconstruction immediately following mastectomy were studied. Preoperative and intraoperative care were standardized. Each patient received intra-arterial blood pressure monitoring. In all patients, cardiac output measurement occurred throughout the intraoperative period using the arterial pulse contour device. Control patients had their fluid administered at the discretion of the anesthesiologist (blinded to results from the cardiac output device). Patients in the intervention group had a baseline crystalloid infusion of 5 mL/kg/h, with intravenous colloid boluses to maintain a stroke volume variation ≤13%.
Results
There was no difference in heart rate or mean arterial pressure between groups at the end of the operation. However, at the end of the operation, the intervention group had significantly higher mean (± SD) CI (3.8±0.8 L/min/m2 versus 3.0±0.5 L/min/m2; P=0.02) and SVI (51.4±2.4 mL/m2 versus 43.3±2.3 mL/m2; P=0.03). This improved CI and SVI was achieved with similar amounts of administered intraoperative fluid (5.8±0.5 mL/kg/h versus 5.0±0.7 mL/kg/h, control versus intervention). The intervention group required less postoperative fluid resuscitation during the early postoperative period (total fluid administered from end of operation to midnight of the operative day, 6.4±1.9 mL/kg/h versus 10.2±3.3 mL/kg/h, intervention versus control, respectively, P<0.01).
Discussion
Goal-directed fluid therapy using minimally invasive cardiac output monitoring resulted in improved end-operative hemodynamics, with less ‘rescue’ fluid administration during the perioperative period.
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