COVID-19: from epidemiology to treatment.

The COVID-19 pandemic has greatly impacted the daily clinical practice of cardiologists and cardiovascular surgeons. Preparedness of health workers and health services is crucial to tackle the enormous challenge posed by SARS-CoV-2 in wards, operating theatres, intensive care units, and interventionist laboratories. This Clinical Review provides an overview of COVID-19 and focuses on relevant aspects on prevention and management for specialists within the cardiovascular field.

Cytomegalovirus infection in HIV-infected patients in the era of combination antiretroviral therapy.

BACKGROUND: Cytomegalovirus infection dramatically decreased with the introduction of antiretroviral therapy. Whether incidence, clinical characteristics and prognosis of cytomegalovirus in HIV infected patients, has changed over time is. scarcely known. METHODS: Retrospective single-center study. Patients included in this study were all HIV infected patients that went to our center for any disease, and were diagnosed with cytomegalovirus, during the period 2004-2015. epidemiological, clinical and laboratory patients variables were collected in a clinical database. Clinical characteristics, incidence of cytomegalovirus and predictors of mortality during the study were assessed. Results were considered statistically significant when p < 0.05. All statistical analyses were calculated by SPSS version 20.0 (Chicago, IL,USA). RESULTS: Fifty-six cases of cytomegalovirus infection, in HIV infected patients were identified during the study period (incidence rate-1.7 cases per 1000 persons/year). The most frequent presentation was systemic illness in 43% of cases. Of note,no patients presented with ophthalmic manifestations. The 30-days mortality was 18%. Predictors of mortality were, in the univariate analysis, admission to the intensive care unit OR 32.4 (3.65-287.06) p = 0.0001, and mechanic ventilation 84 OR (8.27-853.12) p = 0.0001, and ART OR 4.1 (0.97-17.31) p = 0.044. These variables were assessed by multivariate analysis, and only mechanical ventilation was statistically significant (p < 0.05) CONCLUSION: Incidence of cytomegalovirus infection was higher than described in the antiretroviral therapy era. Clinical presentation has changed. Mechanic ventilation predicted mortality.

Full blood count values as a predictor of poor outcome of pneumonia among HIV-infected patients.

BACKGROUND: To evaluate the predictive value of analytical markers of full blood count that can be assessed in the emergency department for HIV infected patients, with community-acquired pneumonia (CAP). METHODS: Prospective 3-year study including all HIV-infected patients that went to our emergency department with respiratory clinical infection, more than 24-h earlier they were diagnosed with CAP and required admission. We assessed the different values of the first blood count performed on the patient as follows; total white blood cells (WBC), neutrophils, lymphocytes (LYM), basophils, eosinophils (EOS), red blood cells (RBC), hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin concentration, mean corpuscular hemoglobin, red blood cell distribution width (RDW), platelets (PLT), mean platelet volume, and platelet distribution width (PDW). The primary outcome measure was 30-day mortality and the secondary, admission to an intensive care unit (ICU). The predictive power of the variables was determined by statistical calculation. RESULTS: One hundred sixty HIV-infected patients with pneumonia were identified. The mean age was 42 (11) years, 99 (62%) were male, 79 (49%) had ART. The main route of HIV transmission was through parenteral administration of drugs. Streptococcus pneumonia was the most frequently identified etiologic agent of CAP The univariate analysis showed that the values of PLT (p < 0.009), EOS (p < 0.033), RDW (p < 0.033) and PDW (p < 0.09) were predictor of mortality, but after the logistic regression analysis, no variable was shown as an independent predictor of mortality. On the other hand, higher RDW (OR = 1.2, 95% CI 1.1-1.4, p = 0.013) and a lower number of LYM (OR 2.2, 95% CI 1.1-2.2; p = 0.035) were revealed as independent predictors of admission to ICU. CONCLUSION: Red blood cell distribution and lymphocytes were the most useful predictors of disease severity identifying HIV infected patients with CAP who required ICU admission.

Integrase strand-transfer inhibitor polymorphic and accessory resistance substitutions in patients with acute/recent HIV infection.

OBJECTIVES: The most recent guidelines suggest using integrase strand-transfer inhibitors (InSTIs) as the preferred antiretroviral regimens for naive HIV-infected individuals. However, resistance to InSTIs is not monitored in many centres at baseline. This study aimed to evaluate the prevalence of InSTI resistance substitutions in newly diagnosed patients with acute/recent HIV infection. METHODS: Genotypic drug resistance tests were performed in all consecutive patients prospectively enrolled with a documented infection of <6 months, from 12 May 2015 to 12 May 2016. Sequences were obtained by high-throughput sequencing. RESULTS: Five out of 36 consecutive patients (13.89%, 95% CI = 4.67-29.5) with acute/recent HIV infection were detected to have strains carrying InSTI polymorphisms or substitutions conferring low-level resistance to raltegravir and elvitegravir. Four patients had the 157Q polymorphism and one patient had the Q95K substitution. All cases were MSM patients infected with subtype B strains. Viral loads ranged from 2.92 to 6.95 log10 copies/mL. In all cases, the mutational viral load was high. Three patients initiated dolutegravir-based regimens and became undetectable at first viral load control. There were no major viral or epidemiological differences when compared with patients without InSTI substitutions. CONCLUSIONS: Although signature InSTI substitutions (such as Y143R/C, N155H or Q148K/R/H) were not detected, polymorphisms and substitutions conferring low-level resistance to raltegravir and elvitegravir were frequently found in a baseline genotypic test. All cases were infected with subtype B, the most frequent in Europe. In the context of primary HIV infection, virological response should be carefully monitored to evaluate the impact of these InSTI polymorphisms and substitutions.

Glycemic index, glycemic load, and pulse wave reflection in adults.

BACKGROUND AND AIMS: Diets with a high glycemic index (GI), high glycemic load (GL), or both, increase the risk of cardiovascular disease. This study examined the association of GI and GL in a regular diet with the peripheral augmentation index (i.e., a marker of vascular aging) in a sample of adults. METHODS AND RESULTS: Cross-sectional study. The findings presented in this manuscript are a subanalysis of the EVIDENT study whose purpose was to analyze the relationship between lifestyle and arterial aging. For the sample population, 1553 individuals aged 20-80 years were selected through random sampling from the patients of general practitioners at six health centers in Spain. GI and GL for each patient's diet were calculated from a previously validated, semi-quantitative, 137-item food frequency questionnaire. The peripheral augmentation index corrected for a heart rate of 75 bpm (PAIx75) was measured with pulse-wave application software (A-Pulse CASP). Based on a risk factor adjusted regression model, for every 5 unit increase in GI, the PAIx75 increased by 0.11 units (95% CI: 0.04-0.19). Similarly, for every increase in 10 units in GL, the PAIx75 increased by 1.13 (95% CI: 0.21-2.05). High PAIx75 values were observed in individuals with diets in the third GI tertile (i.e., the highest), and lower PAIx75 values in those with diets in the first tertile (i.e., the lowest), (93.1 vs. 87.5, respectively, p = 0.001). CONCLUSIONS: GI and GL were directly associated with PAIx75 values in adults without cardiovascular diseases regardless of age, gender, physical activity, and other confounders.

Viral infections of the central nervous system in Spain: a prospective study.

The aim of the study was to determine the incidence of viruses causing aseptic meningitis, meningoencephalitis, and encephalitis in Spain. This was a prospective study, in collaboration with 17 Spanish hospitals, including 581 cases (CSF from all and sera from 280): meningitis (340), meningoencephalitis (91), encephalitis (76), febrile syndrome (7), other neurological disorders (32), and 35 cases without clinical information. CSF were assayed by PCR for enterovirus (EV), herpesvirus (herpes simplex [HSV], varicella-zoster [VZV], cytomegalovirus [CMV], Epstein-Barr [EBV], and human herpes virus-6 [HHV-6]), mumps (MV), Toscana virus (TOSV), adenovirus (HAdV), lymphocytic choriomeningitis virus (LCMV), West Nile virus (WNV), and rabies. Serology was undertaken when methodology was available. Amongst meningitis cases, 57.1% were characterized; EV was the most frequent (76.8%), followed by VZV (10.3%) and HSV (3.1%; HSV-1: 1.6%; HSV-2: 1.0%, HSV non-typed: 0.5%). Cases due to CMV, EBV, HHV-6, MV, TOSV, HAdV, and LCMV were also detected. For meningoencephalitis, 40.7% of cases were diagnosed, HSV-1 (43.2%) and VZV (27.0%) being the most frequent agents, while cases associated with HSV-2, EV, CMV, MV, and LCMV were also detected. For encephalitis, 27.6% of cases were caused by HSV-1 (71.4%), VZV (19.1%), or EV (9.5%). Other positive neurological syndromes included cerebellitis (EV and HAdV), seizures (HSV), demyelinating disease (HSV-1 and HHV-6), myelopathy (VZV), and polyradiculoneuritis (HSV). No rabies or WNV cases were identified. EVs are the most frequent cause of meningitis, as is HSV for meningoencephalitis and encephalitis. A significant number of cases (42.9% meningitis, 59.3% meningoencephalitis, 72.4% encephalitis) still have no etiological diagnosis.

Leg fat might be more protective than arm fat in relation to lipid profile.

PURPOSE: The objective of this study was to determine the independent relationships of trunk fat, leg fat and arm fat to cardiovascular (CVD) risk factors, after controlling for relevant confounders such as fat mass index, cardiorespiratory fitness and objectively measured physical activity. METHODS: This is a cross-sectional study involving 683 university students, aged 18-30 years. Total and regional body fat distribution was measured using dual-energy X-ray absorptiometry. The associations of trunk, leg and arm fat with CVD risk factors (triglycerides-TG-, high-density lipoprotein cholesterol-HDL-c-, TG/HDL-c ratio, HOMA(IR), mean arterial pressure, C-reactive protein) were examined using regression linear models, controlling for age, sex, fat mass index [total body fat(kg)/height(m(2))], maximal oxygen consumption and physical activity by accelerometer. RESULTS: After controlling for fat mass index, and other confounders, higher levels of trunk fat were found to be associated with a poorer lipid profile, while higher levels of leg fat were found to be associated with a better lipid profile. We did not find any association between arm fat and lipid profile after controlling for total fatness and other confounders. Neither trunk, leg or arm fat was found to be related to insulin resistance, blood pressure or inflammation markers. CONCLUSIONS: Our data suggest that the region where fat is accumulated might have a differential effect on lipid profile: trunk fat has an adverse effect, leg fat has a protective effect, and arm fat has no effect. The differences observed between upper- and lower-body peripheral fat depots should be further explored.

Severity and outcomes of hospitalised community-acquired pneumonia in COPD patients.

Chronic obstructive pulmonary disease (COPD) is a frequent comorbidity in patients with community-acquired pneumonia (CAP). We investigated the impact of COPD on outcomes of CAP patients. We prospectively studied the clinical presentation of 1,379 patients admitted with CAP during a 4-yr period. A comparative analysis of disease severity and course was performed between 212 patients with COPD, as confirmed by spirometry, and 1,167 non-COPD patients. COPD patients (mean forced expiratory volume in 1 s 47.7 ± 16.3% predicted) were older and more likely to have previously received antibiotics (37.1% versus 28.3%; p<0.01) than those without COPD. They presented with more severe respiratory failure (arterial oxygen tension/inspiratory oxygen fraction 270.4 versus 287.8; p<0.01) and more severe pneumonia (pneumonia severity index 118.3 versus 108.5; p<0.001) compared with non-COPD patients. However, COPD patients had less multilobar infiltration (44 (21%) versus 349 (30%); p<0.01) and fewer pulmonary complications (24 (14%) versus 241 (24%); p<0.01). A total of 89 (6.5%) patients died within 30 days. COPD patients had no significant difference in their 30-day mortality rate compared with non-COPD patients (nine (4.2%) patients versus 81 (7%); p = 0.14). Despite worse clinical presentation, COPD patients had a similar mortality rate compared to non-COPD patients. Previous antibiotic treatment and the decreased incidence of pulmonary complications in COPD may account for these findings.

Influenza pneumonia: a comparison between seasonal influenza virus and the H1N1 pandemic.

We compared clinical presentation, complications and outcome in patients with influenza A (H1N1) and seasonal influenza pneumonia. The group of patients with influenza A (H1N1) pneumonia consisted of 75 patients. 52 patients with pneumonia associated with seasonal influenza were included for comparison. Patients with pneumonia associated with novel H1N1 influenza were younger (mean age 39.7 yrs versus 69.6 yrs) and had fewer chronic comorbidities and less alcoholism. Infiltrates were more extensive and frequently interstitial. Respiratory failure was more frequent (those with an arterial oxygen tension/inspiratory oxygen fraction ratio <200 28% versus 12%, p = 0.042), leading to a higher rate of intensive care unit (ICU) admission and mechanical ventilation (29.3% versus 7.7% (p<0.0030) and 18.7% versus 2% (p<0.0045)). Mortality was twice as high in patients with novel H1N1 (12% versus 5.8%; p = 0.238), although this was not significant, and was attributable to pneumonia in most instances (77.8% versus 0%; p = 0.046). Younger age, fewer comorbidities, more extensive radiographic extension and more severe respiratory compromise, and ICU admissions are key features of the clinical presentation of patients with novel H1N1-associated pneumonia compared with seasonal influenza pneumonia.

Influenza A H1N1 in HIV-infected adults.

OBJECTIVES: HIV-infected adults are considered to be at higher risk for influenza A H1N1 complications but data supporting this belief are lacking. We aimed to compare epidemiological data, clinical characteristics, and outcomes of influenza A H1N1 infection between HIV-infected and -uninfected adults. METHODS: From 26 April to 6 December 2009, each adult presenting with acute respiratory illness at the emergency department of our institution was considered for an influenza A H1N1 diagnosis by specific multiplex real-time polymerase chain reaction. For every HIV-infected adult diagnosed, three consecutive adults not known to be HIV-infected diagnosed in the same calendar week were randomly chosen as controls. RESULTS: Among 2106 adults tested, 623 (30%) had influenza A H1N1 infection confirmed. Fifty-six (9%) were HIV-positive and were compared with 168 HIV-negative controls. Relative to HIV-negative controls, HIV-positive patients were older, more frequently male, and more frequently smokers (P≤0.02). In the HIV-positive group, prior or current AIDS-defining events were reported for 30% of patients, 9% and 30% had CD4 counts of <200 and 200-500cells/µL, respectively, and 95% had HIV-1 RNA <50copies/mL. Pneumonia (9%vs. 25%, respectively, in the HIV-positive and HIV-negative groups; P=0.01) and respiratory failure (9%vs. 21%, respectively; P=0.04) were less common in the HIV-positive group. Oseltamivir (95%vs. 71% in the HIV-positive and HIV-negative groups, respectively; P=0.003) was administered more often in HIV-positive patients. Three patients (all HIV-negative) died. In the HIV-positive group, CD4 cell count and plasma HIV-1 RNA did not differ before and 4-6 weeks after influenza A H1N1 diagnosis (P>0.05). CONCLUSIONS: HIV infection did not increase the severity of influenza A H1N1 infection, and influenza A H1N1 infection did not have a major effect on HIV infection.

Tocilizumab reduces the risk of ICU admission and mortality in patients with SARS-CoV-2 infection.

OBJECTIVE: In some patients the immune response triggered by SARS-CoV-2 is unbalanced, presenting an acute respiratory distress syndrome which in many cases requires intensive care unit (ICU) admission. The limitation of ICU beds has been one of the major burdens in the management around the world; therefore, clinical strategies to avoid ICU admission are needed. We aimed to describe the influence of tocilizumab on the need of transfer to ICU or death in non-critically ill patients. METHODS: A retrospective study of 171 patients with SARS-CoV-2 infection that did not qualify as requiring transfer to ICU during the first 24h after admission to a conventional ward, were included. The criteria to receive tocilizumab was radiological impairment, oxygen demand or an increasing of inflammatory parameters, however, the ultimate decision was left to the attending physician judgement. The primary outcome was the need of ICU admission or death whichever came first. RESULTS: A total of 77 patients received tocilizumab and 94 did not. The tocilizumab group had less ICU admissions (10.3% vs. 27.6%, P=0.005) and need of invasive ventilation (0 vs 13.8%, P=0.001). In the multivariable analysis, tocilizumab remained as a protective variable (OR: 0.03, CI 95%: 0.007-0.1, P=0.0001) of ICU admission or death. CONCLUSIONS: Tocilizumab in early stages of the inflammatory flare could reduce an important number of ICU admissions and mechanical ventilation. The mortality rate of 10.3% among patients receiving tocilizumab appears to be lower than other reports. This is a non-randomized study and the results should be interpreted with caution.

Interleukin 2 abrogates the nonresponsive state of T cells expressing a forbidden T cell receptor repertoire and induces autoimmune disease in neonatally thymectomized mice.

Under physiological conditions, the vast majority of T cells differentiate in the thymus, an organ that provides an optimal microenvironment for T cell maturation and shapes the T cell repertoire via positive and negative selection processes. In the present report, we demonstrate that neonatal thymectomy of CBA/H mice results in a diminution of T cells in peripheral lymphoid organs (spleen, lymph nodes), but is followed by a marked transient (12 wk) increase in Thy-1+ CD3+ cells in the peritoneal cavity. These cells exhibit predominantly a double-negative (CD4-CD8-) phenotype among which products of the T cell receptor (TCR) V beta 11 gene family (i.e., an I-E-reactive TCR normally deleted in I-E-bearing CBA/H mice) are selectively overexpressed. This observation suggests that, under athymic conditions, T cell differentiation and/or accumulation may occur in the peritoneal cavity. Intraperitoneal inoculation of an interleukin 2 (IL-2) vaccinia virus construct that releases high titers of human IL-2 in vivo induces conversion of these double-negative T cells to either CD4+ CD8- or CD4- CD8+ single positives, and allows in vitro stimulation of TCR V beta 11-bearing cells with a clonotypic anti-V beta antibody. Since IL-2 induces autoimmune manifestations (DNA autoantibodies, rheumatoid factors, and interstitial nephritis) in thymectomized CBA/H mice, but not in sham-treated littermates, this lymphokine is likely to enhance the autoaggressive function of T cells that bear forbidden, potentially autoreactive TCR gene products and that are normally deleted in the thymus.

Isolation and characterization of (gamma, delta) CD4+ T cell clones derived from human fetal liver cells.

Lymphocytes isolated from human fetal liver and expanded in vitro in IL-2-containing media reveal the existence of CD4+ gamma, delta T cells. These cells display differential features of double-negative and CD8+ gamma, delta T cells as well as of CD4+ alpha, beta T cells. Thus, they failed to lyse targets in lectin-mediated killing assays and to perform classical helper functions. These results add new information necessary for a better understanding of the physiological role of the gamma, delta T cells.

Involvement of the interleukin 2 pathway in the rearrangement and expression of both alpha/beta and gamma/delta T cell receptor genes in human T cell precursors.

In this report, we have undertaken the phenotypic, functional and molecular characterization of a minor (less than 5%) subpopulation of adult thymocytes regarded as the earliest intrathymic T-cell precursors. Pro-T cells were immunoselected and shown to express different hematopoietic cell markers (CD45, CD38, CD7, CD5) and some activation-related molecules (4F2, Tr, HLA class II), but lack conventional T cell antigens (CD2-1-3-4-8-). TCR-gamma RNA messages are already expressed at this early ontogenic stage, while alpha and beta chain TCR genes remain in germline configuration. In vitro analyses of the growth requirements of pro-T cells demonstrated the involvement of the IL-2 pathway in promoting their proliferation and differentiation into CD3+ CD4+ or CD8+ mature thymocytes. Moreover, during the IL-2-mediated maturation process rearrangements and expression of both alpha and beta chain TCR genes occurred, and resulted in the acquisition of alpha/beta as well as gamma/delta (either disulphide-linked or non-disulphide-linked) heterodimeric TCR among the pro-T cell progeny.

Development of Ly-1+ B cells in immunodeficient CBA/N mice.

Spleen cells from CBA/N mice developing a systemic autoimmune disease after daily injection of CsA during an autologous bone marrow reconstitution were transferred into unmanipulated syngeneic recipients. Adoptive transfer allowed the development of Ly-1+ B cells, which shared Mac-1 differentiation antigen expression with the myelomonocytic lineage. Interestingly, expansion of formerly absent Ly-1+ B cells was paralleled by a severe reduction in common, Ly-1-, B cell development in the recipient. We conclude that precursors for Ly-1+ B lineage do exist in CBA/N mice.

Nursing home-acquired pneumonia: a 10 year single-centre experience.

BACKGROUND: Pneumonia among nursing home (NH) residents has increased considerably in recent years, but it remains unclear whether it should be considered as community-acquired pneumonia (CAP) or a new category of infection. METHODS: 150 consecutive cases of NH-acquired pneumonia (NHAP) (from 1 February 1997 to 1 July 2007) were analysed. RESULTS: Patients (median age, 82 years; range, 77-87 years) showed numerous co-morbidities, (neurological, 55%; pulmonary, 38%; cardiac, 35%) and severe disability for daily activities (partial, 32%; total, 31%). Cases of NHAP were mainly classified as mild to moderate according to the CRB-65 score (CRB-65 classes 0-1 and 2, 41% each). In-hospital and 30-day mortality were 8.7% and 20%, respectively. Aetiology was defined in 57 cases (38%). The most common isolates were Streptococcus pneumoniae (58%), Enterobacteriaceae (Gram-negative bacteria (GNB)) (9%), atypical bacteria (7%), respiratory viruses (5%), methicillin-resistant Staphylococcus aureus (MRSA) (5%) and Legionella pneumophila (5%). The most frequent causes of treatment inadequacy were use of beta-lactams alone (25%) and lack of aspiration assessment (15%). Prognostic factors of 1-month mortality were neurological comorbidities (OR 4.5; 95% CI 1.3 to 15.7; p=0.020), septic shock (OR 6.6; 95% CI 1.3 to 34.0; p=0.025), pleural effusion (OR 3.6; 95% CI 1.1 to 11.7; p=0.036) and isolation of GNB or MRSA (OR 16.4; 95% CI 2.1 to 128.9; p=0.008). CONCLUSIONS: The patients show clinical characteristics (eg, age and co-morbidities) comparable with those with hospital-acquired pneumonia. However, microbiological and mortality data of patients with NHAP are more similar to the data of those with CAP. Isolation of GNB or MRSA was associated with increased mortality risk. CAP empirical antibiotic coverage is still indicated in NHAP, although specific risk factors for multidrug-resistant infections should be assessed on an individual basis.

[Differences between the CKD-EPI and the MDRD equations when estimating the glomerular filtration rate in hypertensive patients]. / Diferencias de la ecuación CKD-EPI con la de MDRD para la estimación del filtrado glomerular en pacientes hipertensos.

OBJECTIVE: To analyze the agreement in glomerular filtration rate (GFR) estimated with CKD-EPI and MDRD-IDMS equations in a cohort of hypertensive patients. METHODS: We included consecutively 478 hypertensive patients, mean age 57.58 yr (SD: 12.34), 68.3% males. The estimation of GFR was performed with MDRD-IDMS and CKD-EPI equations and we analyzed the agreement between them. RESULTS: The estimation of GFR with CKD-EPI was 4.37 (95%:3.73-4.19) mL/min/1,73 m2 higher than MDRD-IDMS, overall and by gender (males 3.99; females 5.04). In patients under 65 years the difference was greater, 6.55 (95%:5.95-7.15) mL/min/1.73 m2 in both men 6.07 and women 6.48. However, we found no significant difference over 65 years. Intraclass correlation coefficient was 0.904 (95% CI:0.886-0.919), 0.897 men and 0.917 women and Kappa index 0.848 (95% CI :0.795-0.889), 0.845 men and 0.852 women. CONCLUSION: CKD-EPI equation estimated a higher GFR in hypertensive patients under 65 years and reclassified in stage 1 patients classified in stage 2 by MDRD-IDMS.

[The increase in the speed of the pulse wave is not associated with elevated central blood pressure in hypertensive patients with kidney disease]. / El aumento de la velocidad de la onda de pulso no seasocia con la elevación de la presión arterial centralen hipertensos con enfermedad renal.

OBJECTIVE: To analyze the relationship between pulse wave velocity (PWV) and central blood pressure evaluated by augmentation index (AIx) in hypertensive patients with kidney disease. METHODS: 406 hypertensive patients with normal renal function and 72 with kidney disease. Arterial stiffness was estimated with the PWV and the AIx. We followed the 2007 European Guidelines of Hypertension criteria to assess the presence or absence of kidney disease. RESULTS: PWV was 8.98 ± 2.15 and 10.17 ± 3.01 m/s (p <0.05) and AIx 30.06% ± 12.46 and 30.23% ± 12.56 (p >0.05) in hypertensive patients with normal renal function and kidney disease, respectively. Multiple regression analysis showed the renal function as an important determinant of PWV, but not AIx. CONCLUSION: In hypertensive patients with renal disease PWV is increased, but not the AIx. We believe that the AIx is not a reliable measure of arterial stiffness in hypertensive patients with kidney disease.

Biomarkers improve mortality prediction by prognostic scales in community-acquired pneumonia.

BACKGROUND: Prognostic scales provide a useful tool to predict mortality in community-acquired pneumonia (CAP). However, the inflammatory response of the host, crucial in resolution and outcome, is not included in the prognostic scales. METHODS: The aim of this study was to investigate whether information about the initial inflammatory cytokine profile and markers increases the accuracy of prognostic scales to predict 30-day mortality. To this aim, a prospective cohort study in two tertiary care hospitals was designed. Procalcitonin (PCT), C-reactive protein (CRP) and the systemic cytokines tumour necrosis factor alpha (TNFalpha) and interleukins IL6, IL8 and IL10 were measured at admission. Initial severity was assessed by PSI (Pneumonia Severity Index), CURB65 (Confusion, Urea nitrogen, Respiratory rate, Blood pressure, > or = 65 years of age) and CRB65 (Confusion, Respiratory rate, Blood pressure, > or = 65 years of age) scales. A total of 453 hospitalised CAP patients were included. RESULTS: The 36 patients who died (7.8%) had significantly increased levels of IL6, IL8, PCT and CRP. In regression logistic analyses, high levels of CRP and IL6 showed an independent predictive value for predicting 30-day mortality, after adjustment for prognostic scales. Adding CRP to PSI significantly increased the area under the receiver operating characteristic curve (AUC) from 0.80 to 0.85, that of CURB65 from 0.82 to 0.85 and that of CRB65 from 0.79 to 0.85. Adding IL6 or PCT values to CRP did not significantly increase the AUC of any scale. When using two scales (PSI and CURB65/CRB65) and CRP simultaneously the AUC was 0.88. CONCLUSIONS: Adding CRP levels to PSI, CURB65 and CRB65 scales improves the 30-day mortality prediction. The highest predictive value is reached with a combination of two scales and CRP. Further validation of that improvement is needed.