Perioperative Tracking of Intravenous Iron in Patients Undergoing On-Pump Cardiac Surgery: A Prospective, Single-Center Pilot Trial.

BACKGROUND: Preoperative intravenous iron administration is a frequently used patient blood management procedure. If the timeframe of intravenous iron administration before surgery is short, (1) the concentration of the intravenous iron compound might still be high in patients' plasma when undergoing surgery and (2) this iron in patients' plasma is at risk to be lost due to blood loss. The aim of the current study was, therefore, to track the iron compound ferric carboxymaltose (FCM) before, during, and after cardiac surgery requiring cardiopulmonary bypass, with an emphasis on intraoperative iron losses in shed blood and potential recovery through autologous cell salvage. METHODS: Concentrations of FCM were analyzed in patients' blood using a hyphenation of liquid chromatography and inductively coupled plasma-mass spectrometry to distinguish between pharmaceutical compound FCM and serum iron. In this prospective, single-center pilot trial, 13 anemic and 10 control patients were included. Anemic patients with hemoglobin levels ≤12/13 g/dL in women and men were treated with 500 milligrams (mg) intravenous FCM 12 to 96 hours before elective on-pump cardiac surgery. Patients' blood samples were collected before surgery and at days 0, 1, 3, and 7 after surgery. One sample each was taken of the cardiopulmonary bypass, the autologous red blood cell concentrate generated by cell salvage, and the cell salvage disposal bag. RESULTS: Patients who had received FCM <48 hours before surgery had higher FCM serum levels (median [Q1-Q3], 52.9 [13.0-91.6]) compared to ≥48 hours (2.1 [0.7-5.1] µg/mL, P = .008). Of 500-mg FCM administered <48 hours, 327.37 (257.96-402.48) mg were incorporated compared to administration ≥48 hours with 493.60 (487.78-496.70) mg. After surgery, patients' plasma FCM concentration in the FCM <48 hours group was decreased (-27.1 [-30 to -5.9] µg/mL). Little FCM was found in the cell salvage disposal bag (<48 hours, 4.2 [3.0-25.8] µg/mL, equivalent to 29.0 [19.0-40.7] mg total; equivalent to 5.8% or 1/17th of the 500 mg FCM initially administered), almost none in the autologous red blood cell concentrate (<48 hours, 0.1 [0.0-0.43] µg/mL). CONCLUSIONS: The data generate the hypotheses that nearly all FCM is incorporated into iron stores with administration ≥48 hours before surgery. When FCM is given <48 hours of surgery, the majority is incorporated into iron stores by the time of surgery, although a small amount may be lost during surgical bleeding with limited recovery by cell salvage.

Slowly cutting, loose seton ligature and staged fistulotomy for healing of idiopathic perianal fistula and influence on anal continence.

PURPOSE: To investigate the ability of a "slowly cutting, loose seton ligature and staged fistulotomy" to heal perianal fistulas, the time needed with the seton ligature, recurrence rate, influence on anal continence, health-related quality of life (HRQoL), and patient satisfaction. METHODS: Observational single-center study. We reviewed the medical records of all patients with primary surgeries from January 1, 2009, to December 31, 2018. The patients answered a questionnaire pre- and postoperative on anal continence (St. Mark's incontinence score) and HRQoL (The Short Health Scale). Satisfaction with the operation was answered postoperatively. RESULTS: Forty-three patients (37 men, 6 women) were included. Initially 41 of 43 healed (95%). Three patients (7%) had a recurrence, two healed after retreatment. The median follow-up was 55 months (IQR, 4). Thirty-four patients (79%) responded to the questionnaire. At follow-up, forty (93%) patients were healed. The median time treated with a seton ligature in the healed patients was 13 months (IQR, 14). St. Mark's incontinence score preoperative was median 2 (IQR, 9) and after the operation median 1 (IQR, 4). The Short Health Scale improved from median 20 (IQR, 5) preoperatively to 5 (IQR, 5) postoperatively, p < 0.001. Patient satisfaction was median 1 (= very satisfied) (IQR, 1). CONCLUSION: A "slowly cutting, loose seton ligature followed by a staged fistulotomy", heals the vast majority of perianal fistulas with minor or none influence on continence and few recurrences. Patient-reported HRQoL improves greatly, and patient satisfaction is high.

Hemojuvelin-mediated hepcidin induction requires both bone morphogenetic protein type I receptors ALK2 and ALK3.

ABSTRACT: Hemojuvelin (HJV) is a glycosylphosphatidylinositol-anchored protein of the repulsive guidance molecule family acting as a bone morphogenetic protein (BMP) coreceptor to induce the hepatic iron regulatory protein hepcidin. Hepcidin causes ubiquitination and degradation of the sole known iron exporter ferroportin, thereby limiting iron availability. The detailed signaling mechanism of HJV in vivo has yet to be investigated. In the current manuscript, we used an established model of adeno-associated virus (AAV)-mediated liver-specific overexpression of HJV in murine models of hepatocyte-specific deficiency of the BMP type I receptors Alk2 or Alk3. In control mice, HJV overexpression increased hepatic Hamp messenger RNA (mRNA) levels, soluble HJV (sHJV), splenic iron content (SIC), as well as phosphorylated small mothers against decapentaplegic protein (pSMAD1/5/8) levels. In contrast, in Alk2fl/fl;Alb-Cre and Alk3fl/fl;Alb-Cre mice, which present with moderate and severe iron overload, respectively, the administration of AAV-HJV induced HJV and sHJV. However, it did not rescue the iron overload phenotypes of those mice. Serum iron levels were induced in Alk2fl/fl;Alb-Cre mice after HJV overexpression. In phosphate-buffered saline-injected Alk3fl/fl;Alb-Cre mice, serum iron levels and the expression of duodenal ferroportin remained high, whereas Hamp mRNA levels were decreased to 1% to 5% of the levels detected in controls. This was reduced even further by AAV-HJV overexpression. SIC remained low in mice with hepatocyte-specific Alk2 or Alk3 deficiency, reflecting disturbed iron homeostasis with high serum iron levels and transferrin saturation and an inability to induce hepcidin by HJV overexpression. The data indicate that ALK2 and ALK3 are both required in vivo for the HJV-mediated induction of hepcidin.

Wac'inyeya: Hope Among American Indian Youth.

This article examines what gives American Indian youth hope. The project included 56 rural tribal youth in focus groups across a Northern Plains reservation. The participants completed a Youth Personal Balance Tool to provide perspective on the balance according to a medicine wheel model of their lives. The focus groups asked questions from a strengths-based perspective about what gives them hope and how they could show others they were hopeful. The project culminated with the youth developing creative representations of hope and presenting these projects to family and community.

Can N-acetylcysteine reverse the antiplatelet effects of clopidogrel? An in vivo and vitro study.

BACKGROUND: The active metabolite of clopidogrel binds the P2Y12 ADP receptor on the platelet surface via a disulfide bond. N-Acetylcysteine (NAC) is able to reduce disulfide bonds. We postulated that NAC might reverse clopidogrel's effect on platelets. METHODS: Two groups of patients were investigated. Group 1 included 11 patients with stable coronary disease who, after discontinuation of aspirin, received 14 days of clopidogrel, 75 mg/day. Bleeding time and whole-blood platelet aggregometry (with 5 micromol/L ADP) were compared before and after the 14 days. Patients were then treated with 6 g of NAC orally, followed by repeat measurement of bleeding time and aggregometry. In group 2, 14 patients were treated with clopidogrel (300 mg) and aspirin before a percutaneous coronary intervention. Blood was drawn 22 +/- 3 hours later and divided into 2 samples. One was sent immediately for platelet-rich plasma aggregometry (using 5 and 2 micromol/L ADP, collagen, and arachidonic acid as agonists), thromboelastography, and aggregometry using the Plateletworks assay (Helena Laboratories, Beaumont, Tex). The other sample was treated with NAC (500 mg/L), after which these same platelet function tests were performed. RESULTS: In group 1, NAC therapy did not significantly change the bleeding time or results of aggregometry. In group 2, neither aggregometry nor the Plateletworks assay suggested reversal of inhibition by NAC. CONCLUSIONS: These studies reveal that a large dose of NAC does not reduce inhibition of platelet aggregation by clopidogrel in vitro or in vivo.

Intraoperative hyperglycemia and perioperative outcomes in cardiac surgery patients.

OBJECTIVE: To estimate the magnitude of association between intraoperative hyperglycemia and perioperative outcomes in patients who underwent cardiac surgery. PATIENTS AND METHODS: We conducted a retrospective observational study of consecutive adult patients who underwent cardiac surgery between June 10, 2002, and August 30, 2002, at the Mayo Clinic, a tertiary care center in Rochester, Minn. The primary independent variable was the mean intraoperative glucose concentration. The primary end point was a composite of death and infectious (sternal wound, urinary tract, sepsis), neurologic (stroke, coma, delirium), renal (acute renal failure), cardiac (new-onset atrial fibrillation, heart block, cardiac arrest), and pulmonary (prolonged pulmonary ventilation, pneumonia) complications developing within 30 days after cardiac surgery. RESULTS: Among 409 patients who underwent cardiac surgery, those experiencing a primary end point were more likely to be male and older, have diabetes mellitus, undergo coronary artery bypass grafting, and receive insulin during surgery (P< or =.05 for all comparisons). Atrial fibrillation (n=105), prolonged pulmonary ventilation (n=53), delirium (n=22), and urinary tract infection (n=16) were the most common complications. The initial, mean, and maximal intraoperative glucose concentrations were significantly higher in patients experiencing the primary end point (P<.01 for all comparisons). In multivariable analyses, mean and maximal glucose levels remained significantly associated with outcomes after adjusting for potentially confounding variables, including postoperative glucose concentration. Logistic regression analyses indicated that a 20-mg/dL increase in the mean intraoperative glucose level was associated with an increase of more than 30% in outcomes (adjusted odds ratio, 1.34; 95% confidence Interval, 1.10-1.62). CONCLUSION: Intraoperative hyperglycemia is an independent risk factor for complications, including death, after cardiac surgery.

Institutional characteristics and the connection to college student health.

OBJECTIVE: To examine whether 6 institutional characteristics were associated with health behavior and outcomes among college students. METHODS: Chisquare statistics and ANOVAs were used to determine relationships between institutional characteristics and health issues among undergraduate participants (N = 81,242) for the spring 2011 American College Health Association-National College Health Assessment II. RESULTS: Most institutional characteristics were significantly associated with all health issues. However, Cramer's V and eta 2 were frequently weak. Relationships between institutional characteristics and health outcomes were complex with few clear patterns. CONCLUSIONS: This exploratory study provides insight into environmental influences specific to college health. Future research should consider individual student differences and campus offerings to improve understanding of how the environment affects college student health.

Approaching patient engagement in research: what do patients with cardiovascular disease think?

Movement toward patient-centered health care must be supported by an evidence base informed by greater patient engagement in research. Efforts to better understand patients' interest in and perspectives on involvement in the research process are fundamental to supporting movement of research programs toward greater patient engagement. We describe preliminary efforts to engage members of a community group of patients living with heart disease to better understand their interest and perspectives on involvement in research. A semi-structured focus group guide was developed to probe willingness to participate in the following three phases of research: preparation, execution, and translation. The focus group discussion, and our summary of key messages gleaned from said discussion, was organized around the phases of research that patients may be involved in, with the goal of delineating degrees of interest expressed for engagement in each phase. Consistent with what is known from the literature, a clear preference for engagement during the preparation and translation phase of the research process emerged. This preliminary conversation will guide our ongoing research efforts toward greater inclusion of patients throughout the research process.

Variability of plasma aprotinin concentrations in pediatric patients undergoing cardiac surgery.

OBJECTIVES: Infants and children undergoing cardiopulmonary bypass for repair of congenital heart defects are at substantial risk for excessive bleeding, contributing greatly to morbidity and mortality. Aprotinin significantly reduces bleeding and transfusion requirements in adults but is of indeterminate value for pediatric patients. The aim of this study was to determine plasma aprotinin concentrations in these patients with a functional aprotinin assay. METHODS: Thirty patients less than 16 years of age scheduled for cardiac surgery with aprotinin were enrolled. Aprotinin was administered as a 25,000 KIU/kg bolus, 35,000 KIU/kg cardiopulmonary bypass prime, and 12,500 KIU.kg(-1).h(-1) continuous infusion. Blood samples for aprotinin concentrations (kallikrein-inhibiting units/milliliter) were obtained before aprotinin; 5 minutes post-bolus; 5 minutes after cardiopulmonary bypass initiation; 30 and 60 minutes on cardiopulmonary bypass; on discontinuation of aprotinin; 1 hour after aprotinin discontinuation; and 4 hours after permanent separation from cardiopulmonary bypass. For analysis, patients were grouped according to weight (<10 kg, 10-20 kg, >20 kg). Differences between weight groups were assessed using an exact test for categoric variables and 1-way analysis of variance for continuous variables. RESULTS: Aprotinin concentrations differed significantly across weight groups. Five minutes after aprotinin bolus and initiation of cardiopulmonary bypass, there was significant correlation between weight and aprotinin concentration (r =.57, P =.003; r =.69, P =.001, respectively). CONCLUSION: A functional assay reveals significant variability in aprotinin concentration for pediatric patients using current weight-based aprotinin dosing. Additional investigation is necessary to determine target aprotinin concentration dosing regimens to provide better efficacy.

Microporous Polysaccharide Hemospheres do not enhance abdominal infection in a rat model compared with gelatin matrix.

BACKGROUND: Residual topical hemostatic material can serve as a nidus for infection or enhance infection in an already contaminated wound. A newly approved agent, Microporous Polysaccharide Hemospheres (MPH) (Arista AH), has rapid degradation properties, which may reduce the chance of surgical site infection. MATERIALS AND METHODS: With institutional approval, 170 Wister rats underwent standardized anesthesia and abdominal surgery. An Echerichia coli inoculum was added to the incision, and MPH, gelatin matrix, or no agent (control) was placed in the site. After 72 h, the animals were sacrificed, and colony-forming units (cfu)/g were counted in the harvested tissue. RESULTS: Application of gelatin matrix resulted in more cfu/g of tissue and an 87% infection rate, with fewer cfu/g of tissue and a 14% and 24% infection rate in the control and MPH groups, respectively. CONCLUSION: The use of MPH in this rat abdominal infection model did not enhance infection. Gelatin matrix was associated with a greater infection rate than MPH. The rapid degradation of MPH may account for these results, making it a good hemostat in the presence of infective sources.

An in vitro study comparing the effects of Hextend, Hespan, normal saline, and lactated ringer's solution on thrombelastography and the activated partial thromboplastin time.

OBJECTIVE: The purpose of this study was to determine if 6% HES 450/0.7 (hydroxyethyl starch 450/0.7) in normal saline (Hespan) and 6% HES 450/0.7 in lactated Ringer's solution (Hextend) have the same inhibition of the intrinsic coagulation pathway and platelet function. Multiple studies have suggested that 6% Hespan inhibits coagulation and increases chest tube drainage and transfusion requirements in cardiac surgical patients. There have been few studies of the effects of 6% Hextend, a relatively new plasma volume expander, on coagulation and the results thus far have been mixed. DESIGN: A prospective in vitro study. SETTING: A large academic medical center. PARTICIPANTS: Blood was collected from 30 healthy volunteers. Interventions : The blood was fractionated and diluted by 30% with Hextend, Hespan, normal saline, and lactated Ringer's solutions, with a native sample for a control. MEASUREMENTS AND MAIN RESULTS: Primary outcome measures were thromboelastography and activated partial thromboplastin time (APTT). For each of the TEG parameters, there was no difference between samples diluted with Hextend compared with Hespan (p > or = 0.112 in all cases). APTT did not differ significantly between samples diluted with Hextend compared with Hespan (p = 0.562). CONCLUSIONS: This prospective in vitro study suggests that Hextend and Hespan, hydroxyethyl starch 450/0.7 in different base solutions, exhibit the same effect on platelet function as measured by the TEG.