Preoperative systemic inflammation and perioperative myocardial injury: prospective observational multicentre cohort study of patients undergoing non-cardiac surgery.

BACKGROUND: Systemic inflammation is pivotal in the pathogenesis of cardiovascular disease. As inflammation can directly cause cardiomyocyte injury, we hypothesised that established systemic inflammation, as reflected by elevated preoperative neutrophil-lymphocyte ratio (NLR) >4, predisposes patients to perioperative myocardial injury. METHODS: We prospectively recruited 1652 patients aged ≥45 yr who underwent non-cardiac surgery in two UK centres. Serum high sensitivity troponin T (hsTnT) concentrations were measured on the first three postoperative days. Clinicians and investigators were blinded to the troponin results. The primary outcome was perioperative myocardial injury, defined as hsTnT≥14 ng L-1 within 3 days after surgery. We assessed whether myocardial injury was associated with preoperative NLR>4, activated reactive oxygen species (ROS) generation in circulating monocytes, or both. Multivariable logistic regression analysis explored associations between age, sex, NLR, Revised Cardiac Risk Index, individual leukocyte subsets, and myocardial injury. Flow cytometric quantification of ROS was done in 21 patients. Data are presented as n (%) or odds ratio (OR) with 95% confidence intervals. RESULTS: Preoperative NLR>4 was present in 239/1652 (14.5%) patients. Myocardial injury occurred in 405/1652 (24.5%) patients and was more common in patients with preoperative NLR>4 [OR: 2.56 (1.92-3.41); P<0.0001]. Myocardial injury was independently associated with lower absolute preoperative lymphocyte count [OR 1.80 (1.50-2.17); P<0.0001] and higher absolute preoperative monocyte count [OR 1.93 (1.12-3.30); P=0.017]. Monocyte ROS generation correlated with NLR (r=0.47; P=0.03). CONCLUSIONS: Preoperative NLR>4 is associated with perioperative myocardial injury, independent of conventional risk factors. Systemic inflammation may contribute to the development of perioperative myocardial injury. CLINICAL TRIAL REGISTRATION: NCT01842568.

Cardiopulmonary exercise testing and cardiopulmonary morbidity in patients undergoing major head and neck surgery.

Cardiopulmonary exercise testing (CPET) is used as a risk stratification tool for patients undergoing major surgery. In this study, we investigated the role of CPET in predicting day five cardiopulmonary morbidity in patients undergoing head and neck surgery. This observational cohort study included 230 adults. We recorded preoperative CPET variables and day five postoperative cardiopulmonary morbidity. Full data from 187 patients were analysed; 43 patients either had incomplete data sets or declined surgery/CPET. One hundred and nineteen patients (63.6%) developed cardiopulmonary morbidity at day five. Increased preoperative heart rate and duration of surgery were independently associated with day five cardiopulmonary morbidity. Those with such morbidity also had lower peak V̇O2 11.4 (IQR 8.4-18.0) vs 16.0 (IQR 14.0-19.7) ml.kg-1.min-1, P<0.0001 and V̇O2 at AT 10.6 (IQR 9.1-13.1) vs 11.5 (IQR 10.5-13.0) ml.kg-1.min-1, p=0.03. Logistic regression model containing peak V̇O2 and duration of surgery demonstrated that increased peak V̇O2 was associated with a reduction in the likelihood of cardiopulmonary complications OR 0.92 (95%CI 0.87 to 0.96), p=0.001. The area under the receiver operating characteristic curve for this model was 0.75(95%CI 0.68 to 0.82), p<0.0001, 64% sensitivity, 81% specificity. CPET can help to predict day five cardiopulmonary morbidity in the patients undergoing head and neck surgery. A model containing peak V̇O2 allowed identification of those with such complications.

Natural human antibodies to pneumococcus have distinctive molecular characteristics and protect against pneumococcal disease.

The molecular and functional characteristics of natural antibody from the preimmune repertoire have not been explored in detail in man. We describe seven human IgM monoclonal antibodies selected on the basis of pneumococcal polysaccharide binding that share both molecular and functional characteristics with natural antibody, suggesting a common B cell lineage origin. Unlike class-switched antibodies, which are serotype-specific, the antibodies were polyreactive and bound all pneumococcal polysaccharide capsular serotypes tested. Some bound endogenous antigens, including blood group antigens and intermediate filament proteins. All the antibodies used unmutated heavy chain V (IGHV) that are expressed at an increased frequency in the elderly and in the preimmune repertoire. The CDR3 was characterized by long length (mean aa 18.4 (+/-4.2) and selective use of IGHD6 (P < 0.001) and IGHJ6 (P < 0.01) family genes. The clones expressing IGHV1-69 and IGHV 3-21 provided significant passive protection against invasive pneumococcal disease in vivo.

Endotoxin immunity and the development of the systemic inflammatory response syndrome in critically ill children.

BACKGROUND: The systemic inflammatory response syndrome (SIRS) may be triggered by endotoxin. Humans have antibodies directed against the core of endotoxin (endotoxin core antibodies, EndoCAb) that appear to be protective following surgery and in sepsis. We hypothesised that children with elevated antibodies to endotoxin core would be less likely to develop SIRS in their initial period on intensive care. Because of the existing literature we defined two sub-groups according to the primary reason for ICU admission: infection and non-infection. METHODS: We recruited 139 consecutive patients admitted to a paediatric intensive care unit (PICU) with more than one organ failure for longer than 12 h as part of another study. Patients were classified on admission to PICU as having an infectious or a non-infections diagnosis. The occurrence of SIRS within 48 h of admission was recorded along with detailed clinical and demographic data, EndoCAb concentration and the potential confounding variables C-reactive protein and mannose-binding lectin. RESULTS: In the 71 patients admitted without infection (primarily post-operative and head injured) IgG EndoCAb was significantly lower in patients who developed SIRS than those who did not (72 vs. 131 MU/ml), independent of potential confounding variables. In patients with infection there was no significant difference in IgG EndoCAb between children developing SIRS and those who did not (111 vs. 80 MU/ml). CONCLUSION: Head injured and post-operative patients admitted to PICU who develop early SIRS have significantly lower serum IgG EndoCAb levels than those who do not.

Knowledge about AIDS among intravenous drug users: an evaluation of an education program.

Increasing intravenous drug users' (IVDUs) knowledge about the etiology and symptoms of the human immunodeficiency virus is a first step in controlling the spread of the virus to the general population. A comparison of pretest and posttest measures of knowledge of acquired immune deficiency syndrome among IVDUs participating in an AIDS education program reveals significant increases in knowledge after a basic one-hour education session. Additional analyses indicate that IVDUs are more ignorant of certain aspects of AIDS than others, and frequently less amenable to education efforts related to these aspects. Finally, the analyses show that the knowledge among IVDUs about AIDS is independent of the IVDU's demographic characteristics and risk-profile.

Afrocentric treatment in residential substance abuse care. The Iwo San.

Alcohol and other drug treatment programs continue to report relatively low success rates among African-American participants. We propose that there is a need to consider treatment approaches that are more culturally competent. An Afrocentric paradigm is suggested and instituted as the central theme of a residential drug treatment program. Elements of an Afrocentric orientation and how these principles are used to guide the development of a treatment philosophy are discussed.

Human immunodeficiency virus (HIV)-related risk-taking behaviors in women attending inner-city prenatal clinics in the mid-west.

OBJECTIVE: Federal guidelines recommend the provision of human immunodeficiency virus education to all attendees of prenatal clinics. The current study was conducted to assess risk-taking behaviors among urban women voluntarily pursuing prenatal care. DESIGN AND SETTING: African American women attending urban prenatal clinics in Cleveland, Ohio were subjected to an extensive interview before receiving an experimental AIDS education curriculum. The interview sought detailed information regarding demographics, lifetime and recent sexual activity, condom use, and lifetime and recent illicit drug use. RESULTS: A total of 1017 women were interviewed; of those women, approximately 73% were single. The majority had a monthly income of less than $500. A total of 66% had only one partner in the past year, and almost 90% had < or = 1 partner in the past 6 months. A total of 98% identified a main partner. Nearly all subjects were at least fairly certain that this partner did not use intravenous drugs, and 71% were at least fairly certain that he was monogamous. Only 19% used condoms most or all the time. Intravenous drug use among study subjects was very infrequent. CONCLUSION: These data indicate that inner-city Cleveland women seeking prenatal care are largely monogamous around the time of their gestation, and that a history of intravenous drug use is infrequent. They suggest that prenatal counseling in urban clinics will need to address women who largely are engaged in single-partner relationships at the time of the intervention.

Effectiveness of HIV/AIDS interventions on drug use and needle risk behaviors for out-of-treatment injection drug users.

Abstract-This study presents an evaluation of the effectiveness of the AIDS Community-Based Outreach/Intervention projects implemented as part of the National Institute on Drug Abuse (NIDA) Cooperative Agreement (CA), which began in 1990 and is currently ongoing. Participants in the CA were randomly assigned to one of two interventions: a NIDA/CA-developed standard intervention (SI); or the SI plus a site-specific enhanced intervention (EI). Analyses of drug use and needle-related risk behaviors were conducted among injection drug users (IDUs) in eight participating cities where follow-up rates of at least 60% were obtained (N=3,743). Results indicated that IDUs significantly reduced their needle-related risk behaviors following delivery of the interventions and that a substantial portion entered substance abuse treatment. However, there was relatively little to support the effectiveness of more expensive and involved enhanced interventions. A number of factors associated with increasing or maintaining high risk behaviors, including an HIV negative serostatus and a greater perceived chance of acquiring AIDS, were also observed. Continued outreach to drug injectors is recommended, as well as the development of new and creative interventions targeting individuals who are HIV negative and those who are aware of their high risk status but have not changed their behaviors in response to risk-reduction interventions.

Injection drug users in the Midwest: an epidemiologic comparison of drug use patterns in four Ohio cities.

Variations in the drug use patterns of injection drug users (IDUs) can have important implications for public health efforts aimed at reducing drug abuse and the transmission of the human immunodeficiency virus. This article describes and compares the characteristics of IDUs living in four Ohio cities and compares African-American and White IDUs at a statewide level. Data from 2,001 IDUs who were recruited for the National AIDS Demonstration Research project between 1989 and 1991 in Columbus, Cleveland, Cincinnati, and Dayton were compared on a number of variables by city and by ethnicity using descriptive statistics and ANCOVA analysis. Significant differences among IDUs in the four cities exist for the use of alcohol, marijuana, cocaine, crack, heroin, speedball, other opioids, shooting gallery use, "safer" needle practices, treatment history, and self-help participation. Differences by ethnicity emerged on all variables except marijuana use, overall injection frequency, and incarceration experience. The results suggest that dramatic differences exist between African-American and White IDUs, and among IDUs in cities relatively close together, regardless of ethnicity. These findings should be considered when developing policy and programs for prevention and treatment activities targeting IDUs.

The addict odyssey: from experimentation to addiction.

This study explores the "honeymoon" period in the addict's life, extending from his first use of narcotics to the point of his addiction. Retrospective interviews with 30 addicts in treatment programs suggest that the process of becoming an addict can be characterized as consisting of at least three elements: (1) increasing physical, psychological, and social rewards from involvement in the street addict life-sytle; (2) increasing commitment to one reference group; and (3) devaluation of any possible negative rewards in the drug life.