Statin use and lung cancer risk in chronic obstructive pulmonary disease patients: a population-based cohort study.

BACKGROUND: Patients living with chronic obstructive pulmonary disease (COPD) are at an increased risk of lung cancer. A common comorbidity of COPD is cardiovascular disease; as such, COPD patients often receive statins. This study sought to understand the association between statin exposure and lung cancer risk in a population-based cohort of COPD patients. METHODS: We identified a population-based cohort of COPD patients based on having filled at least three prescriptions for an anticholinergic or short-acting beta-agonist (SABA). We used an array of methods of defining medication exposure including three conventional methods (ever statin exposure, cumulative duration of use, and cumulative dose) and two novel methods (recency-weighted cumulative duration of use and recency-weighted cumulative dose). To assess residual confounding, a negative control exposure was used to test the validity of our results. All exposure variables were time-dependent. RESULTS: The population-based cohort of COPD had 39,879 patients with mean age of 70.6 (SD: 11.2) years and, of which, 53.5% were female. There were 12,469 patients who received at least one statin prescription. Results from the reference case multivariable analysis indicated a reduced risk from statin exposure (HR: 0.85 (95% CI: 0.73-1.00) in COPD patients, but this result not statistically significant. Using the two recency-weighted modelling approaches, statin exposure was associated with a statistically significant reduction in lung cancer risk (recency-weighted cumulative dose, HR: 0.85 (95% CI: 0.77-0.93) and recency-weighted cumulative duration of use, HR: 0.97 (95% CI: 0.96-0.99). Multivariable analysis incorporating the negative control exposure was not statistically significant (HR: 0.89 (95% CI: 0.75-1.10). CONCLUSIONS: The results of this population-based analysis indicate that statin use in COPD patients may reduce the risk of lung cancer. While the effect was not statistically significantly across all exposure definitions, the overall results support the hypothesis that COPD patients might benefit from statin therapy.

Cerebrospinal Fluid Ceruloplasmin, Haptoglobin, and Vascular Endothelial Growth Factor Are Associated with Neurocognitive Impairment in Adults with HIV Infection.

Dysregulated iron transport and a compromised blood-brain barrier are implicated in HIV-associated neurocognitive disorders (HAND). We quantified the levels of proteins involved in iron transport and/or angiogenesis-ceruloplasmin, haptoglobin, and vascular endothelial growth factor (VEGF)-as well as biomarkers of neuroinflammation, in cerebrospinal fluid (CSF) from 405 individuals with HIV infection and comprehensive neuropsychiatric assessments. Associations with HAND [defined by a Global Deficit Score (GDS) ≥ 0.5, GDS as a continuous measure (cGDS), or by Frascati criteria] were evaluated for the highest versus lowest tertile of each biomarker, adjusting for potential confounders. Higher CSF VEGF was associated with GDS-defined impairment [odds ratio (OR) 2.17, p = 0.006] and cGDS in unadjusted analyses and remained associated with GDS impairment after adjustment (p = 0.018). GDS impairment was also associated with higher CSF ceruloplasmin (p = 0.047) and with higher ceruloplasmin and haptoglobin in persons with minimal comorbidities (ORs 2.37 and 2.13, respectively; both p = 0.043). In persons with minimal comorbidities, higher ceruloplasmin and haptoglobin were associated with HAND by Frascati criteria (both p < 0.05), and higher ceruloplasmin predicted worse impairment (higher cGDS values, p < 0.01). In the subgroup with undetectable viral load and minimal comorbidity, CSF ceruloplasmin and haptoglobin were strongly associated with GDS impairment (ORs 5.57 and 2.96, respectively; both p < 0.01) and HAND (both p < 0.01). Concurrently measured CSF IL-6 and TNF-α were only weakly correlated to these three biomarkers. Higher CSF ceruloplasmin, haptoglobin, and VEGF are associated with a significantly greater likelihood of HAND, suggesting that interventions aimed at disordered iron transport and angiogenesis may be beneficial in this disorder.

Brain morphometric correlates of metabolic variables in HIV: the CHARTER study.

Obesity and other metabolic variables are associated with abnormal brain structural volumes and cognitive dysfunction in HIV-uninfected populations. Since individuals with HIV infection on combined antiretroviral therapy (CART) often have systemic metabolic abnormalities and changes in brain morphology and function, we examined associations among brain volumes and metabolic factors in the multisite CNS HIV AntiRetroviral Therapy Effects Research (CHARTER) cohort, cross-sectional study of 222 HIV-infected individuals. Metabolic variables included body mass index (BMI), total blood cholesterol (C), low- and high-density lipoprotein C (LDL-C and HDL-C), blood pressure, random blood glucose, and diabetes. MRI measured volumes of cerebral white matter, abnormal white matter, cortical and subcortical gray matter, and ventricular and sulcal CSF. Multiple linear regression models allowed us to examine metabolic variables separately and in combination to predict each regional volume. Greater BMI was associated with smaller cortical gray and larger white matter volumes. Higher total cholesterol (C) levels were associated with smaller cortex volumes; higher LDL-C was associated with larger cerebral white matter volumes, while higher HDL-C levels were associated with larger sulci. Higher blood glucose levels and diabetes were associated with more abnormal white matter. Multiple atherogenic metabolic factors contribute to regional brain volumes in HIV-infected, CART-treated patients, reflecting associations similar to those found in HIV-uninfected individuals. These risk factors may accelerate cerebral atherosclerosis and consequent brain alterations and cognitive dysfunction.

Management of immunosuppression and antiviral treatment before and after heart transplant for HIV-associated dilated cardiomyopathy.

Infection with HIV may lead to the development of cardiomyopathy as improved antiretroviral regimens continue to prolong patient life. However, advanced therapeutic options, such as heart transplant, have until recently been precluded to HIV-positive persons. A favorable long-term outcome has been obtained after kidney or liver transplant in HIV-positive recipients fulfilling strict virological and clinical criteria. We recently reported the first heart transplant in a HIV-infected patient carried out in our center. In this article, we detail the major challenges we faced with the management of antiretroviral and immunosuppressive treatments over the first 3 years post-transplant. The patient had developed dilated cardiomyopathy while on antiretroviral treatment with zidovudine, lamivudine and efavirenz. He was in WHO Stage 1 of HIV infection and had normal CD4+ count and persistently undetectable HIV-RNA. In spite of cardiac resynchronization therapy and maximal drug therapy, the patient progressed to end stage heart failure, requiring heart transplant. He was placed on a standard immune suppressive protocol including cyclosporine A and everolimus. Despite its potential pharmacokinetic interaction with efavirenz, everolimus was chosen to reduce the long-term risk of opportunistic neoplasia. Plasma levels of both drugs were monitored and remained within the target range, although high doses of everolimus were needed. There were no infectious, neoplastic or metabolic complications during a 3-year follow-up. In summary, our experience supports previous data showing that cardiac transplantation should not be denied to carefully selected HIV patients. Careful management of drug interactions and adverse events is mandatory.

Effect of copper overload on the survival of HepG2 and A-549 human-derived cells.

We investigated the effect of copper (Cu) overload (20-160 µM/24 h) in two cell lines of human hepatic (HepG2) and pulmonary (A-549) origin by determining lipid and protein damage and the response of the antioxidant defence system. A-549 cells were more sensitive to Cu overload than HepG2 cells. A marked increase was observed in both the cell lines in the nitrate plus nitrite concentration, protein carbonyls and thiobarbituric acid reactive substances (TBARS). The TBARS increase was consistent with an increment in saturated fatty acids at the expense of polyunsaturated acids in a Cu concentration-dependent fashion. Antioxidant enzymes were stimulated by Cu overload. Superoxide dismutase activity increased significantly in both the cell lines, with greater increases in HepG2 than in A-549 cells. A marked increase in ceruloplasmin and metallothionein content in both the cell types was also observed. Dose-dependent decreases in α-tocopherol and ferric reducing ability were observed. Total glutathione content was lower in A-549 cells and higher in HepG2. Calpain and caspase-3 were differentially activated in a dose-dependent manner under copper-induced reactive oxygen species production. We conclude that Cu exposure of human lung- and liver-derived cells should be considered a reliable experimental system for detailed study of mechanism/mechanisms by which Cu overload exerts its deleterious effects.

Defining neurocognitive impairment in HIV: deficit scores versus clinical ratings.

Because HIV-related neurocognitive impairment is usually mild and variable, clinical ratings (CR) and global deficit scores (GDS) are recommended for detecting HIV-associated neurocognitive disorders (HAND). The CR approach requires impairment in at least two ability domains while the GDS considers number and severity of impairments across all measures. We examined classification agreement and clinical correlates of the two methods. Neurocognitive functioning of 1574 HIV-infected participants was assessed via a comprehensive, seven-domain neuropsychological battery. Global neurocognitive impairment was defined for each participant independently by CR and GDS. Participants were classified into four categories (Dually-normal, [impaired by] CR-only, [impaired by] GDS-only, or Dually-impaired). There was 83% concordance between CR and GDS classifications; in total, 56% of participants were deemed impaired by CR and 41% were classified as impaired by GDS. Impairment by GDS virtually guaranteed CR impairment, but 16% of participants were additionally classified as impaired only by CR. As compared to Dually-normal participants, those classified as Dually and CR-only impaired were more likely to have AIDS, have more severe co-occurring conditions, have more severe depressive symptoms, be unemployed, and have more everyday functioning complaints (ps < .05). Impairment classifications of the two methods were in high agreement; however, more people were classified as impaired using the CR approach compared to the GDS approach. Those impaired according to CR-only showed fewer neurocognitive and functional deficits than the Dually-impaired participants, but more of these deficits than Dually-normal participants. The CR approach may be most appropriate for detecting more subtle forms of neurocognitive impairment. Clinicians and researchers should recognize the strengths and weaknesses of each method when evaluating neurocognitive complications in HIV.

Role of obesity, metabolic variables, and diabetes in HIV-associated neurocognitive disorder.

OBJECTIVE: To evaluate relationships between HIV-associated neurocognitive disorder and metabolic variables in a subgroup of HIV+ participants examined in a prospective, observational, multicenter cohort study. METHODS: In a cross-sectional substudy of the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) cohort, 130 HIV+ participants provided fasting blood samples. Neurocognitive impairment (NCI) was defined by performance on neuropsychological tests adjusting for age, education, gender, and race/ethnicity. Global ratings and global deficit scores were determined. Demographics, biomarkers of HIV disease, metabolic variables, combination antiretroviral therapy (CART) history, other drug exposures, and self-reported diabetes were examined in multivariate models predicting NCI. Separate models were used for body mass index (BMI) alone (n = 90) and BMI and waist circumference (WC) together (n = 55). RESULTS: NCI (global impairment rating ≥5) was diagnosed in 40%. In univariate analyses, age, longer duration of HIV infection, obesity, and WC, but not BMI, were associated with NCI. Self-reported diabetes was associated with NCI in the substudy and in those >55 in the entire CHARTER cohort. Multivariate logistic regression analyses demonstrated that central obesity (as measured by WC) increased the risk of NCI and that greater body mass may be protective if the deleterious effect of central obesity is accounted for. CONCLUSIONS: As in HIV-uninfected persons, central obesity, but not more generalized increases in body mass (BMI), was associated with a higher prevalence of NCI in HIV+ persons. Diabetes appeared to be associated with NCI only in older patients. Avoidance of antiretroviral drugs that induce central obesity might protect from or help to reverse neurocognitive impairment in HIV-infected persons.

Diagnosing symptomatic HIV-associated neurocognitive disorders: self-report versus performance-based assessment of everyday functioning.

Three types of HIV-associated neurocognitive disorders (HAND) exist that are distinguished by presence and severity of impairment in cognitive and everyday functioning. Although well-validated neurocognitive measures exist, determining impairment in everyday functioning remains a challenge. We aim to determine whether Self-Report measures of everyday functioning are as effective in characterizing HAND as Performance-Based measures. We assessed 674 HIV-infected participants with a comprehensive neurocognitive battery; 233 met criteria for a HAND diagnosis by having at least mild neurocognitive impairment. Functional decline was measured via Self-Report and Performance-Based measures. HAND diagnoses were determined according to published criteria using three approaches to assess functional decline: (1) Self-Report measures only, (2) Performance-Based measures only, and (3) Dual-method combining Self-Report and Performance-Based measures. The Dual-method classified the most symptomatic HAND, compared to either singular method. Singular method classifications were 76% concordant with each other. Participants classified as Performance-Based functionally impaired were more likely to be unemployed and more immunosuppressed, whereas those classified as Self-Report functionally impaired had more depressive symptoms. Multimodal methods of assessing everyday functioning facilitate detection of symptomatic HAND. Singular Performance-Based classifications were associated with objective functional and disease-related factors; reliance on Self-Report classifications may be biased by depressive symptoms.

Time-varying incidence of cancer after the onset of type 2 diabetes: evidence of potential detection bias.

AIMS/HYPOTHESIS: Despite the vast body of epidemiological literature on the risk of cancer in people with diabetes, few studies have examined the pattern of cancer risk during different time windows following diabetes onset. The objective of the study was to examine the risks of site-specific cancer in people with incident type 2 diabetes during different time windows following diabetes onset. METHODS: This was a population-based retrospective cohort study. The study period was 1 April 1994 to 31 March 2006; censoring occurred at 31 March 2006, at death or on departure from British Columbia, Canada. Using linked health databases, we identified incident cohorts with and without diabetes, who were matched by age, sex and index year. Following a minimum 2-year cancer washout period, first site-specific cancers were identified prospectively in both cohorts. RESULTS: Within 3 months following diabetes onset, participants with diabetes had significantly increased risks of colorectal, lung, liver, cervical, endometrial, ovarian, pancreatic and prostate cancers. After the initial 3-month period, the risks for colorectal (HR 1.15, 95% CI 1.05, 1.25), liver (HR 2.53, 95% CI 1.93, 3.31) and endometrial (HR 1.58, 95% CI 1.28, 1.94) cancers remained significantly elevated compared with those without diabetes. The diabetes cohort remained at increased risk of pancreatic cancer in later years, but followed a different pattern: HR 3.71 at 3 months-1 year, 2.94 at 1-2 years, 1.78 at 2-3 years and 1.65 at 3-10 years (p value for all <0.01). After an initial period of elevated risk, men with type 2 diabetes subsequently had a decreased risk of prostate cancer (HR 0.82, 95% CI 0.76, 0.88). CONCLUSIONS/INTERPRETATION: People with type 2 diabetes are at increased risk of select cancers; this risk is particularly elevated at the time of diabetes onset, which is likely to be due to increased ascertainment.

Correlations between peripheral blood mononuclear cell production of BDNF, TNF-alpha, IL-6, IL-10 and cognitive performances in multiple sclerosis patients.

The aim of this study was to investigate the role of Brain Derived Neurotrophic Factor (BDNF) and inflammatory factors in the development of cognitive dysfunctions in Multiple Sclerosis (MS). We correlated peripheral blood mononuclear cell (PBMC) production of BDNF, Tumor Necrosis Factor-alpha (TNF-alpha), Interleukin (IL)-6 and IL-10 with performances on specific neuropsychological tasks in a selected series of MS patients. We studied a sample of 30 patients with relapsing-remitting (RR)MS, segregated by gender and matched for age, education, disease duration, type of immunomodulating therapy, degree of disability and overall cognitive status. We found that low BDNF levels were correlated with increased time of execution on a divided attention and visual scanning task whereas high levels of IL-6 were correlated with low Mini Mental State Examination scores. We did not observe any significant correlations between IL-10, TNF-alpha levels and cognitive performances in our patients. In conclusion our study shows a correlation between low BDNF and high IL-6 production by PBMCs and poorer performances in cognitive tasks in RRMS patients suggesting a possible role of these factors in cognitive impairment in MS.

Epidemiology and costs associated with genital warts in Canada.

BACKGROUND: Genital warts (condyloma acuminatum) remain one of the most commonly reported sexually transmitted infections (STI) worldwide. Most genital warts are caused by non-oncogenic human papilloma virus. Recurrence is common and many patients receive several rounds of treatment. There are limited data in the literature on the burden of illness and costs associated with genital warts at a population level. METHODS: Episodes of anogenital warts (AGW) were identified from the physician billing database, hospitalisation records and STI clinics from 1998 to 2006. To be included from the physician billing and STI databases, the person had to have a claim that had a diagnosis of condyloma acuminatum (078.11), viral warts (078.1), viral warts unspecified (078.10) or other unspecified warts (078.19), as well as one of the relevant fee codes associated with the treatment of AGW. To be included from the hospital database, the person could be of any age and have a diagnosis of AGW (A63.0), condyloma acuminatum (078.11), viral warts (078.1 or B07), viral warts unspecified (078.10) or other unspecified warts (078.19) in any of the diagnosis fields, as well as one of the relevant procedure codes associated with the treatment of AGW. RESULTS: A total of 39,493 people was diagnosed with AGW and during this period they had a total of 43,586 episodes. The average cost per episode of AGW was $C190 ($C176 for men; $C207 for women). The majority of treatment was with ablative therapy alone (98%). CONCLUSIONS: AGW are associated with a significant burden of illness and costs to the healthcare system.

Correlates of epidermal nerve fiber densities in HIV-associated distal sensory polyneuropathy.

OBJECTIVE: To demonstrate the relationship between epidermal nerve fiber density (ENFD) in the leg and the phenotype of HIV-associated distal sensory polyneuropathy (HIV-DSP) in a multicenter prospective study (ACTG A5117). METHODS: A total of 101 HIV-infected adults, with CD4 cell count <300 cells/mm(3) and who had received antiretroviral therapy (ART) for at least 15 consecutive weeks, underwent standardized clinical and electrophysiologic assessment. All 101 subjects were biopsied at the distal leg (DL) and 99 at the proximal thigh (PT) at baseline. ENFD was assessed by skin biopsy using PGP9.5 immunostaining. Associations of ENFD with demographics, ART treatment, Total Neuropathy Score (TNS), sural sensory nerve action potential (SNAP) amplitude and conduction velocity, quantitative sensory testing (QST) measures, and neuropathic pain were explored. RESULTS: ENFD at the DL site correlated with neuropathy severity as gauged by TNS (p < 0.01), the level of neuropathic pain quantified by the Gracely Pain Scale (GPS) (p = 0.01) and Visual Analogue Scale (VAS) (p = 0.01), sural SNAP amplitude (p < 0.01), and toe cooling (p < 0.01) and vibration (p = 0.02) detection thresholds. ENFD did not correlate with neurotoxic ART exposure, CD4 cell count, or plasma HIV-1 viral load. CONCLUSIONS: In subjects with advanced HIV-1 infection, epidermal nerve fiber density (ENFD) assessment correlates with the clinical and electrophysiologic severity of distal sensory polyneuropathy (DSP). ENFD did not correlate with previously established risk factors for HIV-DSP, including CD4 cell count, plasma HIV-1 viral load, and neurotoxic antiretroviral therapy exposure.

Retrospective analysis of variables favouring good surgical outcome in posterior epilepsies.

AIM: to determine variables favouring good surgical outcome in posterior epilepsies. METHODS: Fourteen patients submitted to epilepsy surgery were included in the study. The epileptogenic zone was located in temporo-parieto-occipital areas as assessed by both invasive and non-invasive pre-surgical evaluation. Several variables (age at first seizure; age at surgery; disease duration; type, frequency and clinical semiology of seizures; presence of lesion; scalp ictal and interictal EEG; localization and extension of epileptogenic zone; completeness of surgical resection) were compared (Fisher's exact test) with freedom from seizures to determine whether surgical outcome (Engel's classification) could be related to any of them. RESULTS: Seven patients were seizure free (Ia) and very satisfying results were obtained for 3 patients (2 Ib, 1 Ic). New post-surgical visual deficits occurred only in 3 patients. Surgical outcome was related significantly to two variables: scalp ictal EEG (focal versus non-focal; p: 0.014) and completeness of surgical resection of epileptogenic zone (p: 0.0023). A significant trend towards a better outcome for focal interictal intracranial activity versus a non-focal one (p: 0.07) was found. CONCLUSIONS: The correlation between completeness of epileptogenic zone resection and surgical outcome suggests that a presurgical protocol, allowing a precise definition of the area of resection, could help in obtaining more satisfying results in posterior epilepsies.

The impact of low family income on self-reported health outcomes in patients with rheumatoid arthritis within a publicly funded health-care environment.

OBJECTIVE: Self-rated health (SRH) is an independent, strong predictor of morbidity and mortality. Socio-economic status (SES) is strongly associated with SRH. This study investigated the relationship between SES and SRH outcomes in a sample of patients with rheumatoid arthritis (RA) in Canada. METHODS: Both generic preference-based [Health Utilities Index Mark 3 (HUI3) and Short Form 6D (SF-6D)] and non-preference-based [disease-specific (Rheumatoid Arthritis Quality of Life, RAQoL) and a functional status (Health Assessment Questionnaire, HAQ)] SRH questionnaires were administered to 313 RA patients. Both proximate (education and annual household income) and contextual (neighbourhood income, education and unemployment) measures of SES were captured. Ordinary least squares (OLS) regression was used to adjust for RA severity while assessing the relationship between SRH and SES measures. Two-stage least-squares (TSLS) regression was used to determine if there was an inter-relationship between SES and SRH measures. RESULTS: The sample was well distributed across RA severity and SES measures. Contextual and proximate measures of SES were poorly correlated. Lower levels of proximate SES measures (but not contextual) were associated with poorer SRH outcomes. The OLS regressions showed significant associations between the HUI3 and the SF-6D overall scores and the HAQ for self-reported income. The RAQoL did not differ significantly across SES. TSLS regression confirmed the finding that self-reported income was similarly associated with the SRH measures. CONCLUSIONS: Even in a country with universal access to health-care, the impact of a chronic disease such as RA on SRH is associated with self-reported income. The finding that preference-based measures vary with income independently of RA severity could bias economic evaluation.

Midterm results of a prospective randomized comparison of two different rabbit-antithymocyte globulin induction therapies after heart transplantation.

This prospective randomized study compared the effects in heart transplant recipients of thymoglobulin and ATG, two rabbit polyclonal antithymocyte antibodies available for induction therapy. Among 40 patients (29 men and 11 women, mean age: 40.7 +/- 14 years) undergoing orthotopic heart transplantation, 20 were randomly allocated to receive induction with thymoglobulin (group A) and 20 to ATG-fresenius (group B). Comparisons between the two groups included early posttransplant (6 months) incidence of acute rejection episodes (grade >/= 1B), bouts of steroid-resistant rejection, time to first rejection, survival, graft atherosclerosis, infections, and malignancies. The study groups displayed similar preoperative and demographic variables. No significant difference was found with regard to actuarial survival (P =.98), freedom from rejection (P =.68), number of early rejections > 1B (P =.67), mean time to first early cardiac rejection (P =.13), number of steroid-resistant rejections (P =.69). Cytomegalovirus reactivations were more frequent among group A (65%) than group B (30%; P =.028). New infections due to cytomegalovirus occurred only in group A (four patients; 20%; P =.05). No cases of malignancies were observed at a mean follow-up of 32.8 +/- 8.9 months. Although thymoglobulin and ATG showed equivalent efficacy for rejection prevention, they have different immunological properties. In particular, thymoglobulin seems to be associated with a significantly higher incidence of cytomegalovirus disease/reactivation.

A randomized clinical trial of CPI-1189 for HIV-associated cognitive-motor impairment.

BACKGROUND: CPI-1189 is a compound with antioxidant properties that blocks tumor necrosis factor-alpha (TNFalpha) effects in animal models. It has neuroprotective properties in model systems for HIV-associated neurotoxicity and thus is a candidate for neuroprotective therapy in humans with HIV-associated CNS disease. OBJECTIVE: To assess the tolerability and safety of CPI-1189 in treating HIV-associated cognitive-motor impairment. METHODS: Sixty-four subjects with mild to moderate HIV-associated cognitive-motor impairment were randomized to receive either placebo or 50 or 100 mg daily of CPI-1189 in addition to optimal HIV therapy. Subjects were followed prospectively in a double-masked study for 10 weeks. The primary assessment was tolerability and safety of the compound. Secondary objectives examined neuropsychological and functional change associated with this treatment. RESULTS: The study compound was well tolerated, with 91% of CPI-1189-treated subjects and 76% of placebo-treated subjects completing the trial. Skin rash was seen equally in placebo and active arms, but the only study withdrawals due to skin rash occurred in CPI-1189-treated subjects (n = 2). One subject developed a cataract on drug (100 mg/day). CD4 lymphocyte counts and plasma HIV viral load remained stable in all groups throughout the trial. No significant treatment effects were observed on the change in composite Z-scores for eight neuropsychologic measures (NPZ-8). The Grooved Pegboard Test (nondominant) showed improved performance with CPI-1189 at 100 mg/day (p = 0.01), but no other neuropsychometric or functional measures demonstrated significant improvement. CONCLUSIONS: CPI-1189 was well tolerated in HIV subjects with cognitive-motor disorder. This study was not powered to conclusively determine efficacy and showed no consistent treatment-associated improvement in cognitive or functional measures.

Coronary artery bypass grafting in patients with severe left ventricular dysfunction: a prospective randomized study on the timing of perioperative intraaortic balloon pump support.

In this prospective trial the results of preoperative and intraoperative IABP in coronary artery bypass graft (CABG) patients with low left ventricular ejection fraction (LVEF) were compared. Sixty CABG patients with preoperative LVEF < or = 0.30 were enrolled: in group A patients (n=30) IABP was started within 2 hours preoperatively; in group B (n=30) it was instituted intraoperatively before weaning from cardiopulmonary bypass. Cardiac performance was assessed through Swan-Ganz catheter monitoring and daily echocardiography. Hospital survival, length of IABP support, intubation, ICU and hospital stay, need for postoperative inotropic drugs and incidence of myocardial infarction were compared between the two groups. Survival in group A patients proved significantly higher (P=0.047). Cardiac performance after myocardial revascularization improved in both groups with significantly better outcomes in group A patients (P<0.001). Doses of inotropic drugs (dobutamine, enoximone) were lower in group A (P=0.001; P=0.004) and duration shorter (P<0.001; P<0.001). No major IABP-related complication was observed.

Treatment of locally recurrent rectal cancer.

PURPOSE: This study was designed to analyze the outcome for patients with isolated local recurrence after radical treatment of rectal cancer and to identify predictors of curative resection. METHODS: The medical records of 87 patients who developed isolated local recurrence after curative radical surgery for primary rectal cancer were retrospectively reviewed. Survival rates from the time of recurrence were calculated using the Kaplan-Meier method. Tumor stage and histology, patient characteristics, and treatment variables were analyzed using logistic regression to identify predictors of curative surgery. RESULTS: Symptomatic treatment alone or chemotherapy and/or radiation therapy was provided to 23 patients (26 percent), and surgical exploration was performed in 64 patients. In 22 patients (25 percent), the tumor was considered unresectable at surgery (n = 13) or was resected for palliation with gross or microscopic positive margins (n = 9). In 42 patients (48 percent), curative-intent resection was performed. The only independent predictors of resectability were younger age at diagnosis, earlier stage of the primary tumor, and initial treatment by sphincter-saving procedure. There was no difference in survival between patients who had no surgery and those who had palliative surgery. The estimated five-year survival rate for patients who had curative-intent resection was better than for those who had no surgery or palliative surgery (35 vs. 7 percent; P = 0.01). Of the 42 patients who underwent curative-intent resection, 14 (33 percent) developed a second recurrence at a mean of 15 +/- 11 months after reoperation. Twenty-five percent of patients developed major complications. CONCLUSIONS: Salvage surgery for locally recurrent rectal cancer may be helpful in a selected group of patients. The stage and treatment of the primary tumor may help to identify patients with the best chance for curative-intent resection.

Asymmetric medial degeneration of the intrapericardial aorta in aortic valve disease.

BACKGROUND: A geometrical and functional asymmetry in the normal aortic root has been recently demonstrated. Whether the distribution of medial degeneration (MD) within the wall of the dilated ascending aorta in adult patients reflects such asymmetry, still has to be assessed. METHODS: Nineteen patients with fibrocalcific aortic valve disease and dilatation of the intrapericardial aorta, without clinical signs and familiar history of primary elastic connective tissue disorders, underwent surgery. Biopsies (57 specimens) were taken in each patient from three areas of the ascending aortic wall distal to the three sinuses of Valsalva. MD lesions found at histology in each specimen were classified in three degrees. Comparisons were made between the three sites as to distribution of the three degrees and between one site and the other two as to incidence of the highest degree. RESULTS: A mild degree of MD was found in 26 specimens (45.6%), moderate in 14 (24.6%), severe in 17 (29.8%). The distribution of the three degrees of MD changes was significantly different between one of the three studied wall areas and the other two (P<0.001): a significantly greater incidence of the highest degree of involvement in the aortic wall distal to the non-coronary sinus than in the wall areas corresponding to the coronary sinuses was found (P<0.001). CONCLUSIONS: MD lesions in dilated intrapericardial aorta are more severe in the wall area distal to the non-coronary sinus, likely due to haemodynamic stress asymmetry.

Deep sternal wound infection: the role of early debridement surgery.

OBJECTIVE: This retrospective chart review study aimed to evaluate whether a more aggressive staged approach can reduce morbidity and mortality following post-cardiotomy deep sternal wound infection. METHODS: Between 1979 and 2000, 14620 patients underwent open heart surgery: mediastinitis developed in 124 patients (0.85%). Patients were divided in two groups: in 62 patients (Group A) (1979-1994) an initial attempt of conservative antibiotic therapy was the rule followed by surgical approach in case of failure; in 62 patients (Group B) (1995-2000) the treatment was staged in three phases: (1) wound debridement, removal of wires and sutures, closed irrigation for 10 days; (2) in case of failure open dressing with sugar and hyperbaric therapy (11 patients, 17%); (3) delayed healing and negative wound cultures mandated plastic reconstruction (three patients, 4%). Categorical values were compared using the Chi-square test, continuous data were compared by unpaired t-test. RESULTS: Incidence of mediastinitis was higher in Group B (62 out of 5535; 1.3%) than in Group A (62 out of 9085; 0.7%) (P=0.007). Mean interval between diagnosis and treatment was shorter in Group B (18+/-6 days) than in group A (38+/-7 days) (P=0.001). Hospital mortality was higher in Group A (19/62; 31%) than in Group B (1 out of 62; 1.6%) (P<0.001). Hospital stay was shorter in Group B (30.5+/-3 days) than in group A (44+/-9 days) (P=0.001). In Group B complete healing was observed in all the 61 survivors: 47 cases (76%) after Stage 1; 11 (18%) after Stage 2; three (4.8%) after Stage 3. CONCLUSIONS: Although partially biased by the fact that the two compared groups draw back to different decades, this study showed that an aggressive therapeutic protocol can significantly reduce morbidity and mortality of deep sternal wound infection.