Acute Recurrent Pancreatitis With Exclusion of Biliary Causes in a Young Female Patient.

Biliary pathologies are common causes of acute pancreatitis, including gallbladder cholesterolosis and gallstone pancreatitis. Nevertheless, after these two pathologies have been excluded, a broader differential and less common etiologies must be considered. Here we report an 18-year-old female with preliminary diagnosis of gallstone pancreatitis who underwent cholecystectomy and intraoperative cholangiogram resulting in uneventful recovery and resolution of symptoms. She returned three times within the month with symptoms of acute pancreatitis. We discussed alternative etiologies of her pancreatitis after exclusion of other causes with extensive imaging and laboratory evaluation.

Hypotension-Avoidance Versus Hypertension-Avoidance Strategies in Noncardiac Surgery : An International Randomized Controlled Trial.

BACKGROUND: Among patients having noncardiac surgery, perioperative hemodynamic abnormalities are associated with vascular complications. Uncertainty remains about what intraoperative blood pressure to target and how to manage long-term antihypertensive medications perioperatively. OBJECTIVE: To compare the effects of a hypotension-avoidance and a hypertension-avoidance strategy on major vascular complications after noncardiac surgery. DESIGN: Partial factorial randomized trial of 2 perioperative blood pressure management strategies (reported here) and tranexamic acid versus placebo. (ClinicalTrials.gov: NCT03505723). SETTING: 110 hospitals in 22 countries. PATIENTS: 7490 patients having noncardiac surgery who were at risk for vascular complications and were receiving 1 or more long-term antihypertensive medications. INTERVENTION: In the hypotension-avoidance strategy group, the intraoperative mean arterial pressure target was 80 mm Hg or greater; before and for 2 days after surgery, renin-angiotensin-aldosterone system inhibitors were withheld and the other long-term antihypertensive medications were administered only for systolic blood pressures 130 mm Hg or greater, following an algorithm. In the hypertension-avoidance strategy group, the intraoperative mean arterial pressure target was 60 mm Hg or greater; all antihypertensive medications were continued before and after surgery. MEASUREMENTS: The primary outcome was a composite of vascular death and nonfatal myocardial injury after noncardiac surgery, stroke, and cardiac arrest at 30 days. Outcome adjudicators were masked to treatment assignment. RESULTS: The primary outcome occurred in 520 of 3742 patients (13.9%) in the hypotension-avoidance group and in 524 of 3748 patients (14.0%) in the hypertension-avoidance group (hazard ratio, 0.99 [95% CI, 0.88 to 1.12]; P = 0.92). Results were consistent for patients who used 1 or more than 1 antihypertensive medication in the long term. LIMITATION: Adherence to the assigned strategies was suboptimal; however, results were consistent across different adherence levels. CONCLUSION: In patients having noncardiac surgery, our hypotension-avoidance and hypertension-avoidance strategies resulted in a similar incidence of major vascular complications. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and Research Grant Council of Hong Kong.

Tranexamic Acid in Patients Undergoing Noncardiac Surgery.

BACKGROUND: Perioperative bleeding is common in patients undergoing noncardiac surgery. Tranexamic acid is an antifibrinolytic drug that may safely decrease such bleeding. METHODS: We conducted a trial involving patients undergoing noncardiac surgery. Patients were randomly assigned to receive tranexamic acid (1-g intravenous bolus) or placebo at the start and end of surgery (reported here) and, with the use of a partial factorial design, a hypotension-avoidance or hypertension-avoidance strategy (not reported here). The primary efficacy outcome was life-threatening bleeding, major bleeding, or bleeding into a critical organ (composite bleeding outcome) at 30 days. The primary safety outcome was myocardial injury after noncardiac surgery, nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism (composite cardiovascular outcome) at 30 days. To establish the noninferiority of tranexamic acid to placebo for the composite cardiovascular outcome, the upper boundary of the one-sided 97.5% confidence interval for the hazard ratio had to be below 1.125, and the one-sided P value had to be less than 0.025. RESULTS: A total of 9535 patients underwent randomization. A composite bleeding outcome event occurred in 433 of 4757 patients (9.1%) in the tranexamic acid group and in 561 of 4778 patients (11.7%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.67 to 0.87; absolute difference, -2.6 percentage points; 95% CI, -3.8 to -1.4; two-sided P<0.001 for superiority). A composite cardiovascular outcome event occurred in 649 of 4581 patients (14.2%) in the tranexamic acid group and in 639 of 4601 patients (13.9%) in the placebo group (hazard ratio, 1.02; 95% CI, 0.92 to 1.14; upper boundary of the one-sided 97.5% CI, 1.14; absolute difference, 0.3 percentage points; 95% CI, -1.1 to 1.7; one-sided P = 0.04 for noninferiority). CONCLUSIONS: Among patients undergoing noncardiac surgery, the incidence of the composite bleeding outcome was significantly lower with tranexamic acid than with placebo. Although the between-group difference in the composite cardiovascular outcome was small, the noninferiority of tranexamic acid was not established. (Funded by the Canadian Institutes of Health Research and others; POISE-3 ClinicalTrials.gov number, NCT03505723.).

Tranexamic acid alters the immunophenotype of phagocytes after lower limb surgery.

BACKGROUND: Tranexamic acid (TXA) is an antifibrinolytic agent frequently used in elective surgery to reduce blood loss. We recently found it also acts as a potent immune-modulator in patients undergoing cardiac surgery. METHODS: Patients undergoing lower limb surgery were enrolled into the "Tranexamic Acid in Lower Limb Arthroplasty" (TALLAS) pilot study. The cellular immune response was characterised longitudinally pre- and post-operatively using full blood examination (FBE) and comprehensive immune cell phenotyping by flowcytometry. Red blood cells and platelets were determined in the FBE and levels of T cell cytokines and the plasmin-antiplasmin complex determined using ELISA. RESULTS: TXA administration increased the proportion of circulating CD141+ conventional dendritic cells (cDC) on post-operative day (POD) 3. It also reduced the expression of CD83 and TNFR2 on classical monocytes and levels of circulating IL-10 at the end of surgery (EOS) time point, whilst increasing the expression of CCR4 on natural killer (NK) cells at EOS, and reducing TNFR2 on POD-3 on NK cells. Red blood cells and platelets were decreased to a lower extent at POD-1 in the TXA group, representing reduced blood loss. CONCLUSION: In this investigation we have extended our examination on the immunomodulatory effects of TXA in surgery by also characterising the end of surgery time point and including B cells and neutrophils in our immune analysis, elucidating new immunophenotypic changes in phagocytes as well as NK cells. This study enhances our understanding of TXA-mediated effects on the haemostatic and immune response in surgery, validating changes in important functional immune cell subsets in orthopaedic patients.

Methylomic and transcriptomic characterization of postoperative systemic inflammatory dysregulation.

In this study, we define and validate a state of postoperative systemic inflammatory dysregulation (PSID) based on postoperative phenotypic extremes of plasma C-reactive protein concentration following major abdominal surgery. PSID manifested clinically with significantly higher rates of sepsis, complications, longer hospital stays and poorer short, and long-term outcomes. We hypothesized that PSID will be associated with, and potentially predicted by, altered patterns of genome-wide peripheral blood mononuclear cell differential DNA methylation and gene expression. We identified altered DNA methylation and differential gene expression in specific immune and metabolic pathways during PSID. Our findings suggest that dysregulation results in, or from, dramatic changes in differential DNA methylation and highlights potential targets for early detection and treatment. The combination of altered DNA methylation and gene expression suggests that dysregulation is mediated at multiple levels within specific gene sets and hence, nonspecific anti-inflammatory treatments such as corticosteroids alone are unlikely to represent an effective therapeutic strategy.

Rationale and design of the PeriOperative ISchemic Evaluation-3 (POISE-3): a randomized controlled trial evaluating tranexamic acid and a strategy to minimize hypotension in noncardiac surgery.

BACKGROUND: For patients undergoing noncardiac surgery, bleeding and hypotension are frequent and associated with increased mortality and cardiovascular complications. Tranexamic acid (TXA) is an antifibrinolytic agent with the potential to reduce surgical bleeding; however, there is uncertainty about its efficacy and safety in noncardiac surgery. Although usual perioperative care is commonly consistent with a hypertension-avoidance strategy (i.e., most patients continue their antihypertensive medications throughout the perioperative period and intraoperative mean arterial pressures of 60 mmHg are commonly accepted), a hypotension-avoidance strategy may improve perioperative outcomes. METHODS: The PeriOperative Ischemic Evaluation (POISE)-3 Trial is a large international randomized controlled trial designed to determine if TXA is superior to placebo for the composite outcome of life-threatening, major, and critical organ bleeding, and non-inferior to placebo for the occurrence of major arterial and venous thrombotic events, at 30 days after randomization. Using a partial factorial design, POISE-3 will additionally determine the effect of a hypotension-avoidance strategy versus a hypertension-avoidance strategy on the risk of major cardiovascular events, at 30 days after randomization. The target sample size is 10,000 participants. Patients ≥45 years of age undergoing noncardiac surgery, with or at risk of cardiovascular and bleeding complications, are randomized to receive a TXA 1 g intravenous bolus or matching placebo at the start and at the end of surgery. Patients, health care providers, data collectors, outcome adjudicators, and investigators are blinded to the treatment allocation. Patients on ≥ 1 chronic antihypertensive medication are also randomized to either of the two blood pressure management strategies, which differ in the management of patient antihypertensive medications on the morning of surgery and on the first 2 days after surgery, and in the target mean arterial pressure during surgery. Outcome adjudicators are blinded to the blood pressure treatment allocation. Patients are followed up at 30 days and 1 year after randomization. DISCUSSION: Bleeding and hypotension in noncardiac surgery are common and have a substantial impact on patient prognosis. The POISE-3 trial will evaluate two interventions to determine their impact on bleeding, cardiovascular complications, and mortality. TRIAL REGISTRATION: ClinicalTrials.gov NCT03505723. Registered on 23 April 2018.

Effect of a Perioperative Hypotension-Avoidance Strategy Versus a Hypertension-Avoidance Strategy on the Risk of Acute Kidney Injury: A Clinical Research Protocol for a Substudy of the POISE-3 Randomized Clinical Trial.

BACKGROUND: Most patients who take antihypertensive medications continue taking them on the morning of surgery and during the perioperative period. However, growing evidence suggests this practice may contribute to perioperative hypotension and a higher risk of complications. This protocol describes an acute kidney injury substudy of the Perioperative Ischemic Evaluation-3 (POISE-3) trial, which is testing the effect of a perioperative hypotension-avoidance strategy versus a hypertension-avoidance strategy in patients undergoing noncardiac surgery. OBJECTIVE: To conduct a substudy of POISE-3 to determine whether a perioperative hypotension-avoidance strategy reduces the risk of acute kidney injury compared with a hypertension-avoidance strategy. DESIGN: Randomized clinical trial with 1:1 randomization to the intervention (a perioperative hypotension-avoidance strategy) or control (a hypertension-avoidance strategy). INTERVENTION: If the presurgery systolic blood pressure (SBP) is <130 mmHg, all antihypertensive medications are withheld on the morning of surgery. If the SBP is ≥130 mmHg, some medications (but not angiotensin receptor blockers [ACEIs], angiotensin receptor blockers [ARBs], or renin inhibitors) may be continued in a stepwise manner. During surgery, the patients' mean arterial pressure (MAP) is maintained at ≥80 mmHg. During the first 48 hours after surgery, some antihypertensive medications (but not ACEIs, ARBs, or renin inhibitors) may be restarted in a stepwise manner if the SBP is ≥130 mmHg. CONTROL: Patients receive their usual antihypertensive medications before and after surgery. The patients' MAP is maintained at ≥60 mmHg from anesthetic induction until the end of surgery. SETTING: Recruitment from 108 centers in 22 countries from 2018 to 2021. PATIENTS: Patients (~6800) aged ≥45 years having noncardiac surgery who have or are at risk of atherosclerotic disease and who routinely take antihypertensive medications. MEASUREMENTS: The primary outcome of the substudy is postoperative acute kidney injury, defined as an increase in serum creatinine concentration of either ≥26.5 µmol/L (≥0.3 mg/dL) within 48 hours of randomization or ≥50% within 7 days of randomization. METHODS: The primary analysis (intention-to-treat) will examine the relative risk and 95% confidence interval of acute kidney injury in the intervention versus control group. We will repeat the primary analysis using alternative definitions of acute kidney injury and examine effect modification by preexisting chronic kidney disease, defined as a prerandomization estimated glomerular filtration rate <60 mL/min/1.73 m2. RESULTS: Substudy results will be analyzed in 2022. LIMITATIONS: It is not possible to mask patients or providers to the intervention; however, objective measures will be used to assess acute kidney injury. CONCLUSIONS: This substudy will provide generalizable estimates of the effect of a perioperative hypotension-avoidance strategy on the risk of acute kidney injury.

CONTEXTE: La plupart des patients qui prennent des médicaments antihypertenseurs continuent de les prendre le matin d'une intervention chirurgicale et pendant la période périopératoire. De plus en plus de preuves suggèrent que cette pratique pourrait entraîner l'hypotension périopératoire et augmenter le risque de complications. Ce protocole décrit une sous-étude sur l'insuffisance rénale aiguë (IRA) découlant de l'essai Perioperative Ischemic Evaluation-3 (POISE-3). Cet essai teste l'effet d'une stratégie d'évitement de l'hypotension périopératoire par rapport à une stratégie d'évitement de l'hypertension chez des patients qui subissent une chirurgie non cardiaque. OBJECTIFS: Cette sous-étude de l'essai POISE-3 vise à déterminer si une stratégie d'évitement de l'hypotension périopératoire réduit le risque d'IRA comparativement à la stratégie d'évitement de l'hypertension. TYPE D'ÉTUDE: Essai clinique randomisé à répartition 1:1 au groupe intervention (stratégie d'évitement de l'hypotension périopératoire) ou au groupe témoin (stratégie d'évitement de l'hypertension). GROUPE INTERVENTION: Si la pression artérielle systolique (PAS) avant l'opération est <130 mmHg, tous les médicaments antihypertenseurs sont suspendus le matin de la chirurgie. Si la PAS est ≥130 mmHg, certains médicaments (excluant les inhibiteurs de l'enzyme de conversion de l'angiotensine [IECA], les antagonistes du récepteur de l'angiotensine [ARA] ou les inhibiteurs de la rénine) peuvent être poursuivis de façon graduelle. Pendant la chirurgie, la pression artérielle moyenne (PAM) du patient est maintenue à ≥80 mmHg. Dans les 48 heures suivant l'intervention chirurgicale, certains médicaments antihypertenseurs (excluant les IECA, les ARA ou les inhibiteurs de la rénine) peuvent être réintroduits par étapes si la PAS est ≥130 mmHg. GROUPE TÉMOIN: Les patients reçoivent leurs médicaments antihypertenseurs habituels avant et après la chirurgie. La PAM du patient est maintenue à ≥60 mmHg de l'induction de l'anesthésie à la fin de l'intervention chirurgicale. CADRE: Recrutement à partir de 108 centres dans 22 pays entre 2018 à 2021. SUJETS: Des patients (~6 800) âgés de 45 ans et plus atteints d'athérosclérose, ou présentant un risque de l'être, devant subir une chirurgie non cardiaque et prenant des médicaments antihypertenseurs sur une base régulière. MESURES: Le principal critère d'évaluation de cette sous-étude est une IRA postopératoire définie par une hausse d'au moins 26,5 µmol/L (≥0,3 mg/dL) de la créatinine sérique dans les 48 heures suivant la randomisation ou d'au moins 50 % dans les 7 jours suivant la randomisation. MÉTHODOLOGIE: L'analyse primaire (par intention de traiter) examinera le risque relatif d'une IRA et l'intervalle de confiance à 95 % dans le groupe intervention par rapport au groupe témoin. Nous répéterons l'analyse primaire en utilisant d'autres définitions de l'IRA et nous examinerons la modification de l'effet en présence d'une insuffisance rénale préexistante (définie par un DFGe prérandomisation <60 ml/min/1,73 m2). RÉSULTATS: Les résultats de cette sous-étude seront analysés en 2022. LIMITES: Il n'est pas possible de procéder à l'insu des patients ou des prestataires de soins pour cette intervention; des mesures objectives seront toutefois utilisées pour évaluer l'IRA. CONCLUSION: Cette sous-étude fournira des estimations généralisables de l'effet d'une stratégie visant à éviter l'hypotension périopératoire sur le risque d'insuffisance rénale aiguë.

Understanding Restrictive Versus Liberal Fluid Therapy for Major Abdominal Surgery Trial Results: Did Liberal Fluids Associate With Increased Endothelial Injury Markers?

Liberal fluid strategies in critically ill patients are associated with harm, thought to be due to endothelial and glycocalyx injury. As the restrictive versus liberal fluid therapy for major abdominal surgery trial not only failed to report survival benefit with restrictive fluids but was associated with a higher rate of acute kidney injury, we hypothesized that factors other than endothelial and glycocalyx injury were likely to account for these findings. Consequently, we measured injury biomarkers in a cohort of the restrictive versus liberal fluid therapy for major abdominal surgery trial. DESIGN: The restrictive versus liberal fluid therapy for major abdominal surgery trial was an international, randomized, assessor-blinded trial comparing restrictive with liberal IV fluid regimens that represented traditional care in patients undergoing major abdominal surgery. SETTING AND PATIENTS: Cohort of restrictive versus liberal fluid therapy for major abdominal surgery bloods was collected at a single major site (161 patients) prior to, day 1 and day 3 after surgery. INTERVENTION: Bloods were blindly and randomly batch analyzed for plasma markers of endothelial/glycocalyx injury-angiopoietin-1, angiopoietin-2, soluble tyrosine-protein kinase-2 receptor, soluble intracellular adhesion molecule-1, syndecan, and tumor necrosis factor-α. Data were examined as restrictive versus liberal enrollment groups and high versus low (± 5,000 mL) fluid groups. Differences were examined by linear mixed modeling. MEASUREMENT AND MAIN RESULTS: There were no significant differences in any biomarkers between the restrictive (n = 75) and liberal (n = 86) groups. When examined as low (n = 81) and high (n = 79) fluid groups, plasma angiopoietin-2 (p = 0.009) and soluble intracellular adhesion molecule-1 (p = 0.01) were elevated in the high fluid group. There were no differences in other biomarkers. CONCLUSIONS: Although these results are consistent with previous findings of vascular injury following liberal fluid therapy, they suggest alternative mechanisms underlie the clinical outcomes from restrictive versus liberal fluid therapy for major abdominal surgery study. CLINICALTRIALSGOV IDENTIFIER: NCT01424150.

Anaesthetic depth and complications after major surgery: an international, randomised controlled trial.

BACKGROUND: An association between increasing anaesthetic depth and decreased postoperative survival has been shown in observational studies; however, evidence from randomised controlled trials is lacking. Our aim was to compare all-cause 1-year mortality in older patients having major surgery and randomly assigned to light or deep general anaesthesia. METHODS: In an international trial, we recruited patients from 73 centres in seven countries who were aged 60 years and older, with significant comorbidity, having surgery with expected duration of more than 2 h, and an anticipated hospital stay of at least 2 days. We randomly assigned patients who had increased risk of complications after major surgery to receive light general anaesthesia (bispectral index [BIS] target 50) or deep general anaesthesia (BIS target 35). Anaesthetists also nominated an appropriate range for mean arterial pressure for each patient during surgery. Patients were randomly assigned in permuted blocks by region immediately before surgery, with the patient and assessors masked to group allocation. The primary outcome was 1-year all-cause mortality. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12612000632897, and is closed to accrual. FINDINGS: Patients were enrolled between Dec 19, 2012, and Dec 12, 2017. Of the 18 026 patients screened as eligible, 6644 were enrolled, randomly assigned to treatment or control, and formed the intention-to-treat population (3316 in the BIS 50 group and 3328 in the BIS 35 group). The median BIS was 47·2 (IQR 43·7 to 50·5) in the BIS 50 group and 38·8 (36·3 to 42·4) in the BIS 35 group. Mean arterial pressure was 3·5 mm Hg (4%) higher (median 84·5 [IQR 78·0 to 91·3] and 81·0 [75·4 to 87·6], respectively) and volatile anaesthetic use was 0·26 minimum alveolar concentration (30%) lower (0·62 [0·52 to 0·73] and 0·88 [0·74 to 1·04], respectively) in the BIS 50 than the BIS 35 group. 1-year mortality was 6·5% (212 patients) in the BIS 50 group and 7·2% (238 patients) in the BIS 35 group (hazard ratio 0·88, 95% CI 0·73 to 1·07, absolute risk reduction 0·8%, 95% CI -0·5 to 2·0). Grade 3 adverse events occurred in 954 (29%) patients in the BIS 50 group and 909 (27%) patients in the BIS 35 group; and grade 4 adverse events in 265 (8%) and 259 (8%) patients, respectively. The most commonly reported adverse events were infections, vascular disorders, cardiac disorders, and neoplasms. INTERPRETATION: Among patients at increased risk of complications after major surgery, light general anaesthesia was not associated with lower 1-year mortality than deep general anaesthesia. Our trial defines a broad range of anaesthetic depth over which anaesthesia may be safely delivered when titrating volatile anaesthetic concentrations using a processed electroencephalographic monitor. FUNDING: Health Research Council of New Zealand; National Health and Medical Research Council, Australia; Research Grant Council of Hong Kong; National Institute for Health and Research, UK; and National Institutes of Health, USA.

45.5-tesla direct-current magnetic field generated with a high-temperature superconducting magnet.

Strong magnetic fields are required in many fields, such as medicine (magnetic resonance imaging), pharmacy (nuclear magnetic resonance), particle accelerators (such as the Large Hadron Collider) and fusion devices (for example, the International Thermonuclear Experimental Reactor, ITER), as well as for other diverse scientific and industrial uses. For almost two decades, 45 tesla has been the highest achievable direct-current (d.c.) magnetic field; however, such a field requires the use of a 31-megawatt, 33.6-tesla resistive magnet inside 11.4-tesla low-temperature superconductor coils1, and such high-power resistive magnets are available in only a few facilities worldwide2. By contrast, superconducting magnets are widespread owing to their low power requirements. Here we report a high-temperature superconductor coil that generates a magnetic field of 14.4 tesla inside a 31.1-tesla resistive background magnet to obtain a d.c. magnetic field of 45.5 tesla-the highest field achieved so far, to our knowledge. The magnet uses a conductor tape coated with REBCO (REBa2Cu3Ox, where RE = Y, Gd) on a 30-micrometre-thick substrate3, making the coil highly compact and capable of operating at the very high winding current density of 1,260 amperes per square millimetre. Operation at such a current density is possible only because the magnet is wound without insulation4, which allows rapid and safe quenching from the superconducting to the normal state5-10. The 45.5-tesla test magnet validates predictions11 for high-field copper oxide superconductor magnets by achieving a field twice as high as those generated by low-temperature superconducting magnets.

Social Support and Other Factors Associated with HIV Testing by Hispanic/Latino Gay, Bisexual, and Other Men Who Have Sex with Men in the U.S. South.

Cognitive-psychosocial and other factors may affect participation in HIV testing, particularly by Hispanic/Latino gay, bisexual, and other men who have sex with men (MSM) in the U.S. South, a region hard-hit by HIV. We used univariate and multivariable logistic regression analyses to examine the association between social support and other cognitive-psychosocial factors; sociodemographic characteristics; risk behaviors; and self-reported HIV testing in a sample of 304 Hispanic/Latino MSM in North Carolina. In the multivariable logistic regression analysis, general and HIV-related social support and HIV-related knowledge were associated with greater odds of testing; speaking only Spanish was associated with reduced odds of testing. Social support and aspects of social connectedness may constitute community-based resources for use in HIV prevention efforts with Hispanic/Latino MSM. However, harnessing these resources for HIV prevention will require a better understanding of how social support relationships and processes shape HIV risks and protective actions by these vulnerable MSM.

A survey of anaesthetists' use of tranexamic acid in noncardiac surgery.

Major bleeding in noncardiac surgery is common and associated with serious complications. The antifibrinolytic agent tranexamic acid (TXA) reduces bleeding and may reduce the risk of these complications. TXA also may have immunomodulatory effects that could reduce surgical site infection. Clinical trials of TXA in noncardiac surgery have been insufficiently powered to evaluate its efficacy and safety. Therefore, large randomised controlled trials of its use in noncardiac surgery are required. To ensure that future clinical trials are feasible and acceptable, we undertook a survey of Fellows of the Australian and New Zealand College of Anaesthetists (ANZCA). Our aims were to ascertain current patterns of TXA administration and to assess the acceptability of randomising patients to intravenous TXA or placebo. A 12-item survey was electronically mailed to 1001 ANZCA Fellows. Two hundred and eighty nine responses were received and analysed (response rate 29%). Ninety-eight percent of respondents had used intravenous TXA in noncardiac surgery; 67% give TXA routinely for lower limb arthroplasty, with smaller proportions giving TXA for spinal surgery (40%) and other major orthopaedic surgery (28%). Almost half (49%) give TXA routinely for major trauma surgery. Thirty-six percent indicated that they did not give TXA for major vascular, abdominal, pelvic or thoracic surgery. The majority administered TXA as a single, fixed dose. Fifty-seven percent agreed that there is uncertainty about the relative risks and benefits of perioperative TXA in noncardiac surgery and 87% agreed that large definitive trials determining the safety and efficacy of perioperative TXA in noncardiac surgery are required. These results indicate that for ANZCA Fellows the use of TXA in noncardiac surgery is highly variable, that there is uncertainty about the safety and efficacy of TXA, and that a large trial would be acceptable.

Aspirin in coronary artery surgery: 1-year results of the Aspirin and Tranexamic Acid for Coronary Artery Surgery trial.

BACKGROUND: Aspirin may reduce the risk of vascular graft thrombosis after cardiovascular surgery. We previously reported the 30-day results of a trial evaluating aspirin use before coronary artery surgery. Here we report the 1-year outcomes evaluating late thrombotic events and disability-free survival. METHODS: Using a factorial design, we randomly assigned patients undergoing coronary artery surgery to receive aspirin or placebo and tranexamic acid or placebo. The results of the aspirin comparison are reported here. The primary 1-year outcome was death or severe disability, the latter defined as living with a modified Katz activities of daily living score < 8. Secondary outcomes included a composite of myocardial infarction, stroke and death from any cause through to 1 year after surgery. RESULTS: Patients were randomly assigned to aspirin (1059 patients) or placebo (1068 patients). The rate of death or severe disability was 4.1% in the aspirin group and 3.5% in the placebo group (relative risk, 1.17; 95% confidence interval, 0.76-1.81; P = .48). There was no significant difference in the rates of myocardial infarction (P = .11), stroke (P = .086), or death (P = .24), or a composite of these cardiovascular end points (P = .68). With the exception of those with a low European System for Cardiac Operative Risk Evaluation score (P = .03), there were no interaction effects on these outcomes with tranexamic acid (all tests of interaction P > .10). CONCLUSIONS: In patients undergoing coronary artery surgery, preoperative aspirin did not reduce death or severe disability, or thrombotic events through to 1 year after surgery.

Tranexamic acid in coronary artery surgery: One-year results of the Aspirin and Tranexamic Acid for Coronary Artery Surgery (ATACAS) trial.

BACKGROUND: Tranexamic acid reduces blood loss and transfusion requirements in cardiac surgery but may increase the risk of coronary graft thrombosis. We previously reported the 30-day results of a trial evaluating tranexamic acid for coronary artery surgery. Here we report the 1-year clinical outcomes. METHODS: Using a factorial design, we randomly assigned patients undergoing coronary artery surgery to receive aspirin or placebo and tranexamic acid or placebo. The results of the tranexamic acid comparison are reported here. The primary 1-year outcome was death or severe disability, the latter defined as living with a modified Katz activities of daily living score of less than 8. Secondary outcomes included a composite of myocardial infarction, stroke, and death from any cause through to 1 year after surgery. RESULTS: The rate of death or disability at 1 year was 3.8% in the tranexamic acid group and 4.4% in the placebo group (relative risk, 0.85; 95% confidence interval, 0.64-1.13; P = .27), and this did not significantly differ according to aspirin exposure at the time of surgery (interaction P = .073). The composite rate of myocardial infarction, stroke, and death up to 1 year after surgery was 14.3% in the tranexamic acid group and 16.4% in the placebo group (relative risk, 0.87; 95% CI, 0.76-1.00; P = .053). CONCLUSIONS: In this trial of patients having coronary artery surgery, tranexamic acid did not affect death or severe disability through to 1 year after surgery. Further work should be done to explore possible beneficial effects on late cardiovascular events.

Cross-site Monitoring and Evaluation of the Care and Prevention in the United States Demonstration Project, 2012-2016: Selected Process and Short-term Outcomes.

OBJECTIVE: The Care and Prevention in the United States (CAPUS) Demonstration Project was a 4-year (2012-2016) cross-agency demonstration project that aimed to reduce HIV/AIDS-related morbidity and mortality among racial/ethnic minority groups in 8 states (Georgia, Illinois, Louisiana, Mississippi, Missouri, North Carolina, Tennessee, and Virginia). Its goals were to increase the identification of undiagnosed HIV infections and optimize the linkage to, reengagement with, and retention in care and prevention services for people with HIV (PWH). We present descriptive findings to answer selected cross-site process and short-term outcome monitoring and evaluation questions. METHODS: We answered a set of monitoring and evaluation questions by using data submitted by grantees. We used a descriptive qualitative method to identify key themes of activities implemented and summarized quantitative data to describe program outputs and outcomes. RESULTS: Of 155 343 total HIV tests conducted by all grantees, 558 (0.36%) tests identified people with newly diagnosed HIV infection. Of 4952 PWH who were presumptively not in care, 1811 (36.6%) were confirmed as not in care through Data to Care programs. Navigation and other linkage, retention, and reengagement programs reached 10 382 people and linked to or reengaged with care 5425 of 7017 (77.3%) PWH who were never in care or who had dropped out of care. Programs offered capacity-building trainings to providers to improve cultural competency, developed social marketing and social media campaigns to destigmatize HIV testing and care, and expanded access to support services, such as transitional housing and vocational training. CONCLUSIONS: CAPUS grantees substantially expanded their capacity to deliver HIV-related services and reach racial/ethnic minority groups at risk for or living with HIV infection. Our findings demonstrate the feasibility of implementing novel and integrated programs that address social and structural barriers to HIV care and prevention.

Six-Month Outcomes after Restrictive or Liberal Transfusion for Cardiac Surgery.

BACKGROUND: We reported previously that, in patients undergoing cardiac surgery who were at moderate-to-high risk for death, a restrictive transfusion strategy was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis by hospital discharge or 28 days after surgery, whichever came first. We now report the clinical outcomes at 6 months after surgery. METHODS: We randomly assigned 5243 adults undergoing cardiac surgery to a restrictive red-cell transfusion strategy (transfusion if the hemoglobin concentration was <7.5 g per deciliter intraoperatively or postoperatively) or a liberal red-cell transfusion strategy (transfusion if the hemoglobin concentration was <9.5 g per deciliter intraoperatively or postoperatively when the patient was in the intensive care unit [ICU] or was <8.5 g per deciliter when the patient was in the non-ICU ward). The primary composite outcome was death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis occurring within 6 months after the initial surgery. An expanded secondary composite outcome included all the components of the primary outcome as well as emergency department visit, hospital readmission, or coronary revascularization occurring within 6 months after the index surgery. The secondary outcomes included the individual components of the two composite outcomes. RESULTS: At 6 months after surgery, the primary composite outcome had occurred in 402 of 2317 patients (17.4%) in the restrictive-threshold group and in 402 of 2347 patients (17.1%) in the liberal-threshold group (absolute risk difference before rounding, 0.22 percentage points; 95% confidence interval [CI], -1.95 to 2.39; odds ratio, 1.02; 95% CI, 0.87 to 1.18; P=0.006 for noninferiority). Mortality was 6.2% in the restrictive-threshold group and 6.4% in the liberal-threshold group (odds ratio, 0.95; 95% CI, 0.75 to 1.21). There were no significant between-group differences in the secondary outcomes. CONCLUSIONS: In patients undergoing cardiac surgery who were at moderate-to-high risk for death, a restrictive strategy for red-cell transfusion was noninferior to a liberal strategy with respect to the composite outcome of death from any cause, myocardial infarction, stroke, or new-onset renal failure with dialysis at 6 months after surgery. (Funded by the Canadian Institutes of Health Research and others; TRICS III ClinicalTrials.gov number, NCT02042898 .).

Restrictive versus Liberal Fluid Therapy for Major Abdominal Surgery.

BACKGROUND: Guidelines to promote the early recovery of patients undergoing major surgery recommend a restrictive intravenous-fluid strategy for abdominal surgery. However, the supporting evidence is limited, and there is concern about impaired organ perfusion. METHODS: In a pragmatic, international trial, we randomly assigned 3000 patients who had an increased risk of complications while undergoing major abdominal surgery to receive a restrictive or liberal intravenous-fluid regimen during and up to 24 hours after surgery. The primary outcome was disability-free survival at 1 year. Key secondary outcomes were acute kidney injury at 30 days, renal-replacement therapy at 90 days, and a composite of septic complications, surgical-site infection, or death. RESULTS: During and up to 24 hours after surgery, 1490 patients in the restrictive fluid group had a median intravenous-fluid intake of 3.7 liters (interquartile range, 2.9 to 4.9), as compared with 6.1 liters (interquartile range, 5.0 to 7.4) in 1493 patients in the liberal fluid group (P<0.001). The rate of disability-free survival at 1 year was 81.9% in the restrictive fluid group and 82.3% in the liberal fluid group (hazard ratio for death or disability, 1.05; 95% confidence interval, 0.88 to 1.24; P=0.61). The rate of acute kidney injury was 8.6% in the restrictive fluid group and 5.0% in the liberal fluid group (P<0.001). The rate of septic complications or death was 21.8% in the restrictive fluid group and 19.8% in the liberal fluid group (P=0.19); rates of surgical-site infection (16.5% vs. 13.6%, P=0.02) and renal-replacement therapy (0.9% vs. 0.3%, P=0.048) were higher in the restrictive fluid group, but the between-group difference was not significant after adjustment for multiple testing. CONCLUSIONS: Among patients at increased risk for complications during major abdominal surgery, a restrictive fluid regimen was not associated with a higher rate of disability-free survival than a liberal fluid regimen and was associated with a higher rate of acute kidney injury. (Funded by the Australian National Health and Medical Research Council and others; RELIEF ClinicalTrials.gov number, NCT01424150 .).

Social Support Networks: An Underutilized Resource for the Prevention of HIV and other Sexually Transmitted Diseases among Hispanic/Latino Migrants and Immigrants.

Hispanic/Latino migrants and immigrants are vulnerable to infection by HIV and other sexually transmitted diseases (STDs). Participation in social support networks helps them cope with circumstances in the U.S. Studies of Hispanic/Latino migrants suggest that participation may also be protective against HIV/STD infection. However the studies do not satisfactorily explain how participation leads to protective actions, and recommend externally-induced interventions for HIV/STD prevention rather than incorporating the spontaneously occurring forms of social support they describe. Given the potential protective effects of support networks, a database search was conducted to ascertain the extent to which published HIV/STD prevention interventions for these populations incorporate their support networks. Very few interventions were identified and fewer still incorporate support networks. This commentary calls for research to understand more fully how support networks affect HIV/STD risks among Hispanic/Latino migrants and immigrants and identifies potential benefits of incorporating these networks in HIV/STD prevention for these vulnerable populations.

Aspirin in Patients With Previous Percutaneous Coronary Intervention Undergoing Noncardiac Surgery.

Background: Uncertainty remains about the effects of aspirin in patients with prior percutaneous coronary intervention (PCI) having noncardiac surgery. Objective: To evaluate benefits and harms of perioperative aspirin in patients with prior PCI. Design: Nonprespecified subgroup analysis of a multicenter factorial trial. Computerized Internet randomization was done between 2010 and 2013. Patients, clinicians, data collectors, and outcome adjudicators were blinded to treatment assignment. (ClinicalTrials.gov: NCT01082874). Setting: 135 centers in 23 countries. Patients: Adults aged 45 years or older who had or were at risk for atherosclerotic disease and were having noncardiac surgery. Exclusions were placement of a bare-metal stent within 6 weeks, placement of a drug-eluting stent within 1 year, or receipt of nonstudy aspirin within 72 hours before surgery. Intervention: Aspirin therapy (overall trial, n = 4998; subgroup, n = 234) or placebo (overall trial, n = 5012; subgroup, n = 236) initiated within 4 hours before surgery and continued throughout the perioperative period. Of the 470 subgroup patients, 99.9% completed follow-up. Measurements: The 30-day primary outcome was death or nonfatal myocardial infarction; bleeding was a secondary outcome. Results: In patients with prior PCI, aspirin reduced the risk for the primary outcome (absolute risk reduction, 5.5% [95% CI, 0.4% to 10.5%]; hazard ratio [HR], 0.50 [CI, 0.26 to 0.95]; P for interaction = 0.036) and for myocardial infarction (absolute risk reduction, 5.9% [CI, 1.0% to 10.8%]; HR, 0.44 [CI, 0.22 to 0.87]; P for interaction = 0.021). The effect on the composite of major and life-threatening bleeding in patients with prior PCI was uncertain (absolute risk increase, 1.3% [CI, -2.6% to 5.2%]). In the overall population, aspirin increased the risk for major bleeding (absolute risk increase, 0.8% [CI, 0.1% to 1.6%]; HR, 1.22 [CI, 1.01 to 1.48]; P for interaction = 0.50). Limitation: Nonprespecified subgroup analysis with small sample. Conclusion: Perioperative aspirin may be more likely to benefit rather than harm patients with prior PCI. Primary Funding Source: Canadian Institutes of Health Research.