Usefulness of midregional pro-adrenomedullin as a marker of organ damage and predictor of mortality in patients with sepsis.

BACKGROUND: Midregional proadrenomedullin (MR-proADM) is a prognostic biomarker in patients with community-acquired pneumonia (CAP) and sepsis. In this paper, we examined the ability of MR-proADM to predict organ damage and long-term mortality in sepsis patients, compared to that of procalcitonin, C-reactive protein and lactate. METHODS: This was a prospective observational cohort, enrolling severe sepsis or septic shock patients admitted to internal service department. The association between biomarkers and 90-day mortality was assessed by Cox regression analysis and Kaplan-Meier curves. The accuracy of biomarkers for mortality was determined by area under the receiver operating characteristic curve (AUROC) analysis. RESULTS: A total of 148 patients with severe sepsis, according to the criteria of the campaign to survive sepsis, were enrolled. Eighty-five (57.4%) had sepsis according to the new criteria of Sepsis-3. MR-proADM showed the best AUROC to predict sepsis as defined by the Sepsis-3 criteria (AUROC of 0.771, 95% CI 0.692-0.850, p <0.001) and was the only marker independently associated with Sepsis-3 criteria (OR = 4.78, 95% CI 2.25-10.14; p < 0.001) in multivariate analysis. MR-proADM was the biomarker with the best AUROC to predict mortality in 90 days (AUROC of 0.731, CI 95% 0.612-0.850, p <0.001) and was the only marker that kept its independence [hazard ratio (HR) of 1.4, 95% CI 1.2-1.64, p <0.001] in multivariate analysis. The cut-off point of MR-proADM of 1.8 nmol/L (HR of 4.65, 95% CI 6.79-10.1, p < 0.001) was the one that had greater discriminative capacity to predict 90 days mortality. All patients with MR-proADM concentrations ≤0.60 nmol/L survived up to 90 days. In patients with SOFA ≤ 6, the addition of MR-proADM to SOFA score increased the ability of SOFA to identify non-survivors, AUROC of 0.65 (CI 95% 0.537-0.764) and AUROC of 0.700 (CI 95% 0.594-0.800), respectively (p < 0.05 for both). CONCLUSIONS: MR-proADM is a good biomarker in the early identification of high risk septic patients and may contribute to improve the predictive capacity of SOFA scale, especially when scores are low.

Electronic Structures of Mono-Oxidized Copper and Nickel Phosphasalen Complexes.

Non-innocent ligands render the determination of the electronic structure in metal complexes difficult. As such, a combination of experimental techniques and quantum chemistry are required to correctly elucidate them. This paper deals with the one-electron oxidation of copper(II) and nickel(II) complexes featuring a phosphasalen ligand (Psalen), which differs from salen analogues by the presence of iminophosphorane groups (P=N) instead of imines. Various experimental techniques (X-ray diffraction, cyclic voltammetry, NMR, EPR, and UV/Vis spectroscopies, and magnetic measurements) as well as quantum chemical calculations were used to define the electronic structure of the oxidized complexes. These can be modified by a small change in the ligand structure, that is, the replacement of a tert-butyl group by a methoxy on the phenoxide ring. The different techniques have allowed quantifying the amount of spin density located on the metal center and on the Psalen ligands. All complexes were found to possess a multi-configurational ground state, in which the ratio of the +II versus +III oxidation state of the metal center, and therefore the phenolate versus phenoxyl radical ligand character, varies upon the substituents. The tert-butyl group favors a strong localization on the metal center whereas with the methoxy group the metallic configurations decrease and the ligand configurations increase. The importance of the geometrical considerations compared with the electronic substituent effect is highlighted by the differences observed between the solid-state (EPR, magnetic measurements) and solution characterizations (EPR and NMR data).

Statins in HIV-Infected Patients: Potential Beneficial Effects and Clinical Use.

Patients living with HIV have an increased risk of cardiovascular disease that is considered to be the result of an interaction between traditional cardiovascular risk factors, particularly smoking and dyslipidemia, and persistent chronic inflammation and immune activation associated with HIV infection, along with side effects of antiretroviral therapy. In the general population, the administration of statins has been associated with a reduction in cardiovascular disease-associated mortality, and these drugs are among the most common class of medication prescribed in high-income countries. The beneficial effect of statins extends beyond reducing cholesterol levels as they have been shown to have anti- inflammatory, antithrombotic, antioxidant, immunomodulatory, and vasodilatory effects, and to improve endothelial function. Despite the widespread use of statins in the general population, cohort studies show that these drugs are underutilized in HIV-infected patients, probably due to safety concerns by clinicians and limited data evaluating clinical outcomes in patients on antiretroviral therapy. In this article we review and update the most important clinical studies of statins in HIV- infected patients, describe their side effects and interaction profiles, and discuss the anti-atherosclerotic and pleiotropic effects of these drugs. Finally, we propose recommendations for clinical use of statins in patients living with HIV.

The CD4/CD8 Ratio is Inversely Associated with Carotid Intima-Media Thickness Progression in Human Immunodeficiency Virus-Infected Patients on Antiretroviral Treatment.

Inversion of the CD4/CD8 ratio (<1) has been identified as a surrogate marker of immunosenescence and an independent predictor of AIDS events in HIV-infected patients and mortality in the general population. We aimed to assess the association between the CD4/CD8 ratio and carotid intima-media thickness (cIMT) progression in treated HIV-infected patients as a marker of coronary heart disease. A longitudinal study was conducted during 3 years in 96 virally suppressed HIV-infected patients receiving antiretroviral treatment (ART). We analyzed the associations between the CD4/CD8 ratio, cardiovascular risk factors, and antiretroviral treatment (ART) and progression of subclinical atherosclerosis assessed using cIMT at baseline and after 3 years. Finally, 96 patients completed the study. Seventy six (79.1%) patients were male, aged 44 ± 10 years; 39 (40.6%) were on treatment with protease inhibitors; 49 (51.04%) with nonnucleoside reverse transcriptase inhibitors, 6 (6.25%) with integrase inhibitors, 3 (3.12%) with maraviroc, and 2 (2.08%) just with nucleoside reverse transcriptase inhibitors. The mean of ART exposition was 6.9 ± 5.9 years. Twenty six (27%) patients had family history of ischemic heart disease, 51 (53.12%) were smokers, 12 (12.5%) were hypertensive, 4 (4.16%) had type 2 diabetes, 23 (23.9%) had dyslipidemia, and 31 (32.3%) were infected with hepatitis C virus. Baseline cIMT was significantly associated with age (rho = 0.497; p < .001), basal glucemia (rho = 0.323; p = .001), triglycerides (rho = 0.232; p = .023), Framingham risk score (rho = 0.324; p = .001), CD4/CD8 ratio (rho = -0.176; p = .05), and dyslipidemia (0.72 ± 0.16 mm vs. 0.63 ± 0.11 mm; p = .029). In multivariable analysis where cardiovascular risk factor and ART were included, cIMT progression was inversely associated with CD4/CD8 ratio [odds ratio (OR) = 0.283; confidence interval (95% CI) 0.099-0.809; p = .019]. In conclusion, the inversion of CD4/CD8 ratio in treated HIV-infected patients is independently associated with cIMT progression, a marker of coronary heart disease. Therefore, it might be clinically useful as predictor of cardiovascular events.

Subacute cutaneous lupus erythematosus starting as linear lupus erythematosus.

BACKGROUND: Cutaneous lupus in childhood is usually associated with systemic lupus erythematosus (LE). Linear cutaneous LE (LCLE) is an unusual presentation mostly seen in children and young adults. METHODS: We report a rare case of cutaneous subacute LE with a segmentary pattern following the lines of Blaschko in an 18-month-old girl with a 2-month history of persistent, linear, asymptomatic, erythematous lesions along the right arm. The clinical diagnosis at presentation was lichen striatus. RESULTS: A biopsy showed an intense, band-like, inflammatory cell infiltrate with perivascular and periadnexal involvement associated with basal cell liquefactive degeneration. The lesions were treated with topical corticosteroids and healed without scarring. Two months later, new lesions manifested as multiple erythematous, edematous, polycyclic plaques. A new biopsy showed a periadnexal infiltrate, a large amount of mucin, and a thickened basement membrane. Direct immunofluorescence was negative. Our definitive diagnosis was subacute cutaneous LE starting as linear LE. The lesions responded slowly to oral corticosteroids. Six months later, only a mild livedoid skin pattern remained on the patient's legs. CONCLUSIONS: Linear cutaneous LE usually presents with erythematous, atrophic, hyperkeratotic, dyschromic circular lesions arranged in a linear pattern; the main differential diagnosis is lichen striatum. In general, LCLE can be considered as discoid lupus following Blaschko's lines, which correspond to the direction of growth in clones of cutaneous cells that arise during embryogenesis. The present patient represents the first pediatric case of subacute cutaneous LE following Blaschko's lines, with posterior progression to a generalized form of subacute LE.

Multiple eruptive keratoacanthomas associated with leflunomide.

A 78-year-old woman diagnosed with rheumatoid arthritis without a history of skin tumors or immunosuppressive medication, started treatment with leflunomide. One month after the introduction of the drug, and for two consecutive years, she developed multiple crateriform nodules and papules on her lower extremities . Biopsy specimens showed keratoacanthomas and squamous-cell carcinomas. Owing to suspicion that the drug could be implicated in the appearance of these tumors, the patient decided to suspend the drug. No new skin lesions have appeared in seventeen months of clinical follow-up. There have been several published case reports of multiple keratoacanthomas associated with immunosuppressive therapy such as sorafenib and imiquimod. However, we found no mention in the literature of the eruption of multiple keratoacanthomas in patients with rheumatoid arthritis treated with leflunomide. We suggest, that the the sudden appearance of skin tumors in our patient is related to the introduction of leflunomide, but additional case reports are required to confirm this association.

[Hypertriglyceridemic waist phenotype is a risk factor for subclinical atherosclerosis in human immunodeficiency virus-infected patients]. / El fenotipo "hipertrigliceridemia-cintura abdominal aumentada" es un factor de riesgo de aterosclerosis subclínica en pacientes con infección por el virus de la inmunodeficiencia humana.

BACKGROUND AND OBJECTIVE: To study the association between hypertriglyceridemic waist phenotype and the presence of subclinical atherosclerosis in human immunodeficiency virus (HIV) infected patients. PATIENTS AND METHODS: Cross sectional study. Hypertriglyceridemic waist phenotype was considered if the waist was ≥90cm and triglycerides ≥2.0mmol/l (178mg/dl) in men and ≥85cm and ≥1.5mmol/L (133mg/dl) in women, respectively. We used the intima-media thickness (IMT) to detect carotid subclinical atherosclerosis. RESULTS: We analyzed 152 patients, of whom 128 (84.2%) were receiving antiretroviral therapy, 40.7% were receiving protease inhibitors and 38.1% were treated with non-nucleoside reverse transcriptase inhibitors. The prevalence of hypertriglyceridemic waist phenotype was 23.6% (95% confidence interval [CI] 16.8-30.3%). Patients with hypertriglyceridemic waist phenotype had higher cardiovascular risk according to the Framingham score (11.09 [7.6] vs 3.88 [4], P=0.001) and lipodystrophy (33.3 vs. 13.7%, P=0.032) and metabolic syndrome (69.4 vs. 1.9%, P<0.001) were more frequent. The IMT was elevated in 21 (13.8%) patients. Hypertriglyceridemic waist phenotype (odds ratio [OR] 4.66 [95%CI 1.05-20.6; P = 0.043]) and metabolic syndrome (OR 3.74 [95%CI 1.25-11.23; P = 0.018]) were independently associated with higher IMT. CONCLUSIONS: The hypertriglyceridemic waist phenotype is a risk factor for subclinical atherosclerosis in HIV infected patients and it is useful to detect patients with lipodystrophy, metabolic syndrome and high cardiovascular risk.

[Multiple pulmonary nodules and amiodarone. KL-6 as a new diagnostic tool]. / Nódulos pulmonares múltiples y amiodarona. KL-6 como nueva herramienta diagnóstica.

Pulmonary toxicity is an infrequent but serious adverse event in patients treated with amiodarone. The main problem at present is that we lack the necessary tools to detect this event or predict which patients will develop pulmonary toxicity. Serum Krebs von den Lungen-6 (KL-6) has been previously recognized as a marker for the activity of diffuse interstitial lung disease. We describe a patient with pulmonary toxicity due to amiodarone with increased blood levels of this new marker, and discuss the clinical usefulness of this new diagnostic tool.