Immunoglobulins in COVID-19 pneumonia: from the acute phase to the recovery phase.

BACKGROUND: COVID-19 pneumonia causes hyperinflammatory response that culminates in acute respiratory syndrome (ARDS) related to increased multiorgan dysfunction and mortality risk. Antiviral-neutralizing immunoglobulins production reflect the host humoral status and illness severity, and thus, immunoglobulin (Ig) circulating levels could be evidence of COVID-19 prognosis. METHODS: The relationship among circulating immunoglobulins (IgA, IgG, IgM) and COVID-19 pneumonia was evaluated using clinical information and blood samples in a COVID-19 cohort composed by 320 individuals recruited during the acute phase and followed up to 4 to 8 weeks (n = 252) from the Spanish first to fourth waves. RESULTS: COVID-19 pneumonia development depended on baseline Ig concentrations. Circulating IgA levels together with clinical features at acute phase was highly associated with COVID-19 pneumonia development. IgM was positively correlated with obesity (ρb = 0.156, P = 0.020), dyslipemia (ρb = 0.140, P = 0.029), COPD (ρb = 0.133, P = 0.037), cancer (ρb = 0.173, P = 0.007) and hypertension (ρb = 0.148, P = 0.020). Ig concentrations at recovery phase were related to COVID-19 treatments. CONCLUSIONS: Our results provide valuable information on the dynamics of immunoglobulins upon SARS-CoV-2 infection or other similar viruses.

Clinical and Microbiological Impact of Implementing a Decision Support Algorithm through Microbiologic Rapid Diagnosis in Critically Ill Patients: An Epidemiological Retrospective Pre-/Post-Intervention Study.

BACKGROUND: Data on the benefits of rapid microbiological testing on antimicrobial consumption (AC) and antimicrobial resistance patterns (ARPs) are scarce. We evaluated the impact of a protocol based on rapid techniques on AC and ARP in intensive care (ICU) patients. METHODS: A retrospective pre- (2018) and post-intervention (2019-2021) study was conducted in ICU patients. A rapid diagnostic algorithm was applied starting in 2019 in patients with a lower respiratory tract infection. The incidence of nosocomial infections, ARPs, and AC as DDDs (defined daily doses) were monitored. RESULTS: A total of 3635 patients were included: 987 in the pre-intervention group and 2648 in the post-intervention group. The median age was 60 years, the sample was 64% male, and the average APACHE II and SOFA scores were 19 points and 3 points. The overall ICU mortality was 17.2% without any differences between the groups. An increase in the number of infections was observed in the post-intervention group (44.5% vs. 17.9%, p < 0.01), especially due to an increase in the incidence of ventilator-associated pneumonia (44.6% vs. 25%, p < 0.001). AC decreased from 128.7 DDD in 2018 to 66.0 DDD in 2021 (rate ratio = 0.51). An increase in Pseudomonas aeruginosa susceptibility of 23% for Piperacillin/tazobactam and 31% for Meropenem was observed. CONCLUSION: The implementation of an algorithm based on rapid microbiological diagnostic techniques allowed for a significant reduction in AC and ARPs without affecting the prognosis of critically ill patients.

Mitochondrial dysfunction, lipids metabolism, and amino acid biosynthesis are key pathways for COVID-19 recovery.

The metabolic alterations caused by SARS-CoV-2 infection reflect disease progression. To analyze molecules involved in these metabolic changes, a multiomics study was performed using plasma from 103 patients with different degrees of COVID-19 severity during the evolution of the infection. With the increased severity of COVID-19, changes in circulating proteomic, metabolomic, and lipidomic profiles increased. Notably, the group of severe and critical patients with high HRG and ChoE (20:3) and low alpha-ketoglutaric acid levels had a high chance of unfavorable disease evolution (AUC = 0.925). Consequently, patients with the worst prognosis presented alterations in the TCA cycle (mitochondrial dysfunction), lipid metabolism, amino acid biosynthesis, and coagulation. Our findings increase knowledge regarding how SARS-CoV-2 infection affects different metabolic pathways and help in understanding the future consequences of COVID-19 to identify potential therapeutic targets.

Circulating pyruvate is a potent prognostic marker for critical COVID-19 outcomes.

Background: Coronavirus-19 (COVID-19) disease is driven by an unchecked immune response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus which alters host mitochondrial-associated mechanisms. Compromised mitochondrial health results in abnormal reprogramming of glucose metabolism, which can disrupt extracellular signalling. We hypothesized that examining mitochondrial energy-related signalling metabolites implicated in host immune response to SARS-CoV-2 infection would provide potential biomarkers for predicting the risk of severe COVID-19 illness. Methods: We used a semi-targeted serum metabolomics approach in 273 patients with different severity grades of COVID-19 recruited at the acute phase of the infection to determine the relative abundance of tricarboxylic acid (Krebs) cycle-related metabolites with known extracellular signaling properties (pyruvate, lactate, succinate and α-ketoglutarate). Abundance levels of energy-related metabolites were evaluated in a validation cohort (n=398) using quantitative fluorimetric assays. Results: Increased levels of four energy-related metabolites (pyruvate, lactate, a-ketoglutarate and succinate) were found in critically ill COVID-19 patients using semi-targeted and targeted approaches (p<0.05). The combined strategy proposed herein enabled us to establish that circulating pyruvate levels (p<0.001) together with body mass index (p=0.025), C-reactive protein (p=0.039), D-Dimer (p<0.001) and creatinine (p=0.043) levels, are independent predictors of critical COVID-19. Furthermore, classification and regression tree (CART) analysis provided a cut-off value of pyruvate in serum (24.54 µM; p<0.001) as an early criterion to accurately classify patients with critical outcomes. Conclusion: Our findings support the link between COVID-19 pathogenesis and immunometabolic dysregulation, and show that fluorometric quantification of circulating pyruvate is a cost-effective clinical decision support tool to improve patient stratification and prognosis prediction.

Lipoprotein Profile in Immunological Non-Responders PLHIV after Antiretroviral Therapy Initiation.

Nuclear magnetic resonance (NMR)-based advanced lipoprotein tests have demonstrated that LDL and HDL particle numbers (LDL-P and HDL-P) are more powerful cardiovascular (CV) risk biomarkers than conventional cholesterol markers. Of interest, in people living with HIV (PLHIV), predictors of preclinical atherosclerosis and vascular dysfunction may be associated with impaired immune function. We previously stated that immunological non-responders (INR) were at higher CV risk than immunological responders (IR) before starting antiretroviral therapy (ART). Using Liposcale® tests, we characterized the lipoprotein profile from the same cohort of PLHIV at month 12 and month 36 after starting ART, intending to explore what happened with these indicators of CV risk during viral suppression. ART initiation dissipates the differences in lipoprotein-based CV risk markers between INR and IR, and only an increase in the number of HDL-P was found in INR + IR when compared to controls (p = 0.047). Interestingly, CD4+ T-cell counts negatively correlated with medium HDL-P concentrations at month 12 in all individuals (ρ = -0.335, p = 0.003). Longitudinal analyses showed an important increase in LDL-P and HDL-P at month 36 when compared to baseline values in both IR and INR. A proper balance between a proatherogenic and atherogenic environment may be related to the reconstitution of CD4+ T-cell count in PLHIV.

Elevated α-Ketoglutaric Acid Concentrations and a Lipid-Balanced Signature Are the Key Factors in Long-Term HIV Control.

Long-term elite controllers (LTECs) are a fascinating small subset of HIV individuals with viral and immunological HIV control in the long term that have been designated as models of an HIV functional cure. However, data on the LTEC phenotype are still scarce, and hence, the metabolomics and lipidomics signatures in the LTEC-extreme phenotype, LTECs with more than 10 years of viral and immunological HIV control, could be pivotal to finding the keys for functional HIV remission. Metabolomics and lipidomics analyses were performed using high-resolution mass spectrometry (ultra-high-performance liquid chromatography-electrospray ionization-quadrupole time of flight [UHPLC-(ESI) qTOF] in plasma samples of 13 patients defined as LTEC-extreme, a group of 20 LTECs that lost viral and/or immunological control during the follow-up study (LTEC-losing) and 9 EC patients with short-term viral and immunological control (less than 5 years; no-LTEC patients). Long-term viral and immunological HIV-1 control was found to be strongly associated with elevated tricarboxylic acid (TCA) cycle function. Interestingly, of the nine metabolites identified in the TCA cycle, α-ketoglutaric acid (p = 0.004), a metabolite implicated in the activation of the mTOR complex, a modulator of HIV latency and regulator of several biological processes, was found to be a key metabolite in the persistent control. On the other hand, a lipidomics panel combining 45 lipid species showed an optimal percentage of separation and an ability to differentiate LTEC-extreme from LTEC-losing, revealing that an elevated lipidomics plasma profile could be a predictive factor for the reignition of viral replication in LTEC individuals.

Adipokines as New Biomarkers of Immune Recovery: Apelin Receptor, RBP4 and ZAG Are Related to CD4+ T-Cell Reconstitution in PLHIV on Suppressive Antiretroviral Therapy.

A significant proportion of people living with HIV (PLHIV) who successfully achieve virological suppression fail to recover CD4+ T-cell counts. Since adipose tissue has been discovered as a key immune organ, this study aimed to assess the role of adipokines in the HIV immunodiscordant response. This is a multicenter prospective study including 221 PLHIV starting the first antiretroviral therapy (ART) and classified according to baseline CD4+ T-cell counts/µL (controls > 200 cells/µL and cases ≤ 200 cells/µL). Immune failure recovery was considered when cases did not reach more than 250 CD4+ T cells/µL at 144 weeks (immunological nonresponders, INR). Circulating adipokine concentrations were longitudinally measured using enzyme-linked immunosorbent assays. At baseline, apelin receptor (APLNR) and zinc-alpha-2-glycoprotein (ZAG) concentrations were significantly lower in INRs than in immunological responders (p = 0.043 and p = 0.034), and they remained lower during all ART follow-up visits (p = 0.044 and p = 0.028 for APLNR, p = 0.038 and p = 0.010 for ZAG, at 48 and 144 weeks, respectively). ZAG levels positively correlated with retinol-binding protein 4 (RBP4) levels (p < 0.01), and low circulating RBP4 concentrations were related to a low CD4+ T-cell gain (p = 0.018 and p = 0.039 at 48 and 144 weeks, respectively). Multiple regression adjusted for clinical variables and adipokine concentrations confirmed both low APLNR and RBP4 as independent predictors for CD4+ T cells at 144 weeks (p < 0.001). In conclusion, low APLNR and RBP4 concentrations were associated with poor immune recovery in treated PLHIV and could be considered predictive biomarkers of a discordant immunological response.

Impact of random safety analyses on structure, process and outcome indicators: multicentre study.

BACKGROUND: To assess the impact of a real-time random safety tool on structure, process and outcome indicators. METHODS: Prospective study conducted over a period of 12 months in two adult patient intensive care units. Safety rounds were conducted three days a week ascertaining 37 safety measures (grouped into 10 blocks). In each round, 50% of the patients and 50% of the measures were randomized. The impact of this safety tool was analysed on indicators of structure (safety culture, healthcare protocols), process (improvement proportion related to tool application, IPR) and outcome (mortality, average stay, rate of catheter-related bacteraemias and rate of ventilator-associated pneumonia, VAP). RESULTS: A total of 1214 patient-days were analysed. Structure indicators: the use of the safety tool was associated with an increase in the safety climate and the creation/modification of healthcare protocols (sedation/analgesia and weaning). Process indicators: Twelve of the 37 measures had an IPR > 10%; six showed a progressive decrease in the IPR over the study period. Nursing workloads and patient severity on the day of analysis were independently associated with a higher IPR in half of the blocks of variables. Outcome indicators: A significant decrease in the rate of VAP was observed. CONCLUSIONS: The real-time random safety tool improved the care process and adherence to clinical practice guidelines and was associated with an improvement in structure, process and outcome indicators.

Reduced circulating levels of TWEAK are associated with gestational diabetes mellitus.

BACKGROUND: To evaluate the inflammatory axis mediated by tumour necrosis factor-like weak inducer of apoptosis (TWEAK) and its scavenger receptor CD163 during pregnancy and their influence on insulin sensitivity in normal pregnancy and in gestational diabetes mellitus (GDM). MATERIALS AND METHODS: One hundred and thirty seven women with one singleton pregnancy, 71 with normal glucose tolerance (NGT) and 66 with GDM were studied. Glucose metabolism was assessed by oral glucose tolerance test. Serum concentrations of soluble TWEAK (sTWEAK) and CD163 (sCD163) and insulin resistance (HOMA-IR index) were determined in maternal blood drawn at recruitment, in the early third trimester. Offspring weight and height were assessed at birth. RESULTS: Women with GDM had lower circulating sTWEAK concentrations than control NGT group (237·8 (192·1-301·0) pg/mL vs. 277·2 (206·4-355·7) pg/mL; P = 0·013). sTWEAK was negatively associated with the presence of GDM (r = -0·212; P = 0·013), HOMA-IR index (r = -0·197; P = 0·021) and ponderal index of the newborn (r = -0·196; P = 0·025), but positively with HDL cholesterol (r = 0·283; P = 0·001). In multiple regression analysis, sTWEAK concentration emerged as one of the main predictors of insulin resistance, along with BMI, triglycerides and low concentrations of HDL cholesterol (R(2)  = 0·486; P < 0·001). No relationship was found between HOMA-IR index and sCD163 or sCD163/sTWEAK ratio. CONCLUSIONS: sTWEAK concentrations are lower in patients with GDM compared with healthy pregnant women, and low concentrations of sTWEAK are associated with insulin resistance. These findings suggest that insulin resistance during pregnancy is closely linked to inflammatory imbalance and sTWEAK may represent a new candidate associated with GDM.

Involvement of the LPS-LPB-CD14-MD2-TLR4 inflammation pathway in HIV-1/HAART-associated lipodystrophy syndrome (HALS).

OBJECTIVES: A relationship between obesity and intestinal bacterial translocation has been reported. Very little information is available with respect to the involvement of the bacterial translocation mechanistic pathway in HIV-1/highly active antiretroviral therapy (HAART)-associated lipodystrophy syndrome (HALS). We determined whether lipopolysaccharide (LPS)-binding protein (LBP), cluster of differentiation 14 (CD14), myeloid differentiation protein 2 (MD2) and toll-like receptor 4 (TLR4) single-nucleotide polymorphisms and LPS, LBP and soluble CD14 (sCD14) plasma levels are involved in HALS. PATIENTS AND METHODS: This cross-sectional multicentre study involved 558 treated HIV-1-infected patients, 240 with overt HALS and 318 without HALS. Anthropometric, clinical, immunovirological and metabolic variables were determined. Polymorphisms were assessed by genotyping. Plasma levels were determined by ELISA in 163 patients (81 with HALS and 82 without HALS) whose stored plasma samples were available. Student's t-test, one-way ANOVA, two-way repeated measures ANOVA, the χ(2) test and Pearson and Spearman correlation analyses were carried out for statistical analysis. RESULTS: LBP rs2232582 T→C polymorphism was significantly associated with HALS (P = 0.01 and P = 0.048 for genotype and allele analyses, respectively). Plasma levels of LPS (P = 0.009) and LBP (P < 0.001) were significantly higher and sCD14 significantly lower (P < 0.001) in patients with HALS compared with subjects without HALS. LPS levels were independently predicted by triglycerides (P < 0.001) and hepatitis C virus (P = 0.038), LBP levels by HALS (P < 0.001) and sCD14 levels by age (P = 0.008), current HIV-1 viral load (P = 0.001) and protease inhibitor use (P = 0.018). CONCLUSIONS: HALS is associated with LBP polymorphism and with higher bacterial translocation.

Solicitud de sangre preoperatoria en cirugía programada de colon: ¿necesidad o rutina? / Preoperative blood ordering in elective colon surgery: Requirement or routine?

INTRODUCCIÓN: La solicitud de sangre preoperatoria en cirugía programada de colon es una norma frecuente, incluso en aquellos procedimientos con escasa probabilidad de transfusión. El objetivo de este estudio es evaluar la proporción de pacientes que reciben transfusión peroperatoria y determinar sus factores asociados. Métodos Estudio retrospectivo de pacientes consecutivos en cirugía electiva de colon en el periodo 2007-2012. Se analizan variables clinicopatológicas, quirúrgicas y se calculan la ratio sangre «en reserva»/sangre transfundida (ratio C/T), la probabilidad de transfusión y el índice transfusional. Los pacientes se dividen en 2 grupos en función de haber recibido o no transfusión peroperatoria. RESULTADOS: Se contabilizan 457 pacientes, transfundiéndose 171 unidades sanguíneas en 74 pacientes, siendo la probabilidad de transfusión del 16,2%, la ratio C/T de 5,34 y el índice transfusional de 0,18. Las variables que se han asociado significativamente a recibir transfusión sanguínea tras el análisis multivariable son: la cifra preoperatoria de hemoglobina inferior a 10 g/dl (OR: 309,8; IC 95%: 52,7-985,2), enfermedad pulmonar obstructiva crónica (OR: 3,7; IC 95%: 1,3-10,7), anticoagulación oral (OR: 5,7; IC 95%: 1,7-19,4) y tiempo quirúrgico superior a 120 min (OR: 10,7; IC 95%: 4,7-24,1).Conclusiones La probabilidad de necesidad de transfusión en pacientes a los que se les realiza cirugía electiva de colon es baja. Entre los factores asociados, la cifra de hemoglobina preoperatoria inferior a 10 g/dl es el que presenta una mayor fuerza de asociación. Los pacientes con dichas cifras de hemoglobina preoperatoria no deberían ser intervenidos en cirugía electiva de colon hasta haber recibido tratamiento apropiado

BACKGROUND: Preoperative blood ordering is frequently in elective colon surgery, even for procedures that rarely require blood transfusion. Most often this procedure is performed without proper analysis of the real needs. The aim of this study was to evaluate the patients who receive transfusion and determining their associated factors. METHODS: Retrospective study of all consecutive patients scheduled for elective colon surgery was carried out at 2007-2012. Several clinico-pathological and surgical variables were analyzed and predictive blood transfusion indices such as the cross-matched/transfusion ratio (C/T ratio), transfusion index and transfusion probability were calculated. Patients were divided in 2 groups according have received perioperative surgical transfusion or not. RESULTS: There were 457 surgery patients. A total of 171 blood units, in a 74 patients were perioperative transfused. Overall cross-matched transfused ratio was 5.34, the transfusion probability 162%, and the transfusion index 0.18. Variables that were significantly associated with receiving blood transfusion in a multivariable analysis were a preoperative haemoglobin level less than 10 g/dl (OR: 309.8; 95% CI: 52.7-985.2), chronic pulmonary obstructive disease (OR: 3.7; 95% CI: 1.3-10.7), oral anticoagulant therapy (OR: 5.7; 95% CI: 1.7-19.4) and surgical time over 120 min (OR: 10.7; 95% CI: 4.7-24.1). CONCLUSIONS: Likelihood of receiving perioperative transfusion in elective colon surgery is very low. Among their associated factors, the haemoglobin level less than 10 g/dl is the one with strongest association. Those patients with such low preoperative haemoglobin level should not be scheduled for elective colon surgery until they received specific treatment

[Preoperative blood ordering in elective colon surgery: requirement or routine?]. / Solicitud de sangre preoperatoria en cirugía programada de colon: ¿necesidad o rutina?

BACKGROUND: Preoperative blood ordering is frequently in elective colon surgery, even for procedures that rarely require blood transfusion. Most often this procedure is performed without proper analysis of the real needs. The aim of this study was to evaluate the patients who receive transfusion and determining their associated factors. METHODS: Retrospective study of all consecutive patients scheduled for elective colon surgery was carried out at 2007-2012. Several clinico-pathological and surgical variables were analyzed and predictive blood transfusion indices such as the cross-matched/transfusion ratio (C/T ratio), transfusion index and transfusion probability were calculated. Patients were divided in 2 groups according have received perioperative surgical transfusion or not. RESULTS: There were 457 surgery patients. A total of 171 blood units, in a 74 patients were perioperative transfused. Overall cross-matched transfused ratio was 5.34, the transfusion probability 162%, and the transfusion index 0.18. Variables that were significantly associated with receiving blood transfusion in a multivariable analysis were a preoperative haemoglobin level less than 10 g/dl (OR: 309.8; 95% CI: 52.7-985.2), chronic pulmonary obstructive disease (OR: 3.7; 95% CI: 1.3-10.7), oral anticoagulant therapy (OR: 5.7; 95% CI: 1.7-19.4) and surgical time over 120 min (OR: 10.7; 95% CI: 4.7-24.1). CONCLUSIONS: Likelihood of receiving perioperative transfusion in elective colon surgery is very low. Among their associated factors, the haemoglobin level less than 10 g/dl is the one with strongest association. Those patients with such low preoperative haemoglobin level should not be scheduled for elective colon surgery until they received specific treatment.

Prevalence of nosocomial infections in acute care hospitals in Catalonia (VINCat Program).

The first objective of the Catalonian Nosocomial Infection Surveillance Program (VINCat) is to monitor the prevalence (%) of patients with nosocomial infections (NI), patients undergoing urinary catheterization with closed circuit drainage (%) and patients undergoing antibiotic treatment (%). We present the results for the period 2008-2010. Comprehensive and point annual prevalence surveys were conducted that included conventionally hospitalized patients in acute care hospitals belonging to the VINCat Program. The number of participating hospitals was 46 (2008), 48 (2009) and 61 (2010), most belonging to the Network of Public Use Hospitals of Servei Català de la Salut. The results are presented globally and by hospital size (<200 beds, 200-500 beds, >500 beds). The prevalence of patients with active NI acquired during the current or the previous hospitalization (global NI/P%) was 7.6 (2008), 6.2 (2009) and 6.3 (2010). The prevalence of patients with active NI acquired during the current (actual NI/P%) was 6.2 (2008), 4.7 (2009) and 4.6 (2010).The results by hospital size shows that the variation occurred mainly in <200 beds hospitals. The proportion of closed circuit urinary catheterization use was 90.2%. The use of antibiotics varied between 34.6% and 37.6%, with no differences due to hospital size. The global prevalence of NI provides information on the burden of NI at the institutional and regional level. Between 17.3% and 26.9% of patients with NI at the time of the study had acquired it in a previous hospitalization at the same institution.

Epidemiology of surgical site infections after total hip and knee joint replacement during 2007-2009: a report from the VINCat Program.

The VINCat Program is a system for epidemiological surveillance of healthcare-related infections in which the majority of Catalan hospitals participate. It has a specific module for surgical site infections (SSI) surveillance. Primary hip and knee arthroplasties are basic indicators of the program due to their high frequency and the important morbidity of SSI of these sites. Results are presented for surgical site infection (SSI) surveillance of primary hip and knee arthroplasties for the first three years of the VINCat Program. The program requires SSI surveillance to be performed in a standardized, prospective and continuous manner by an infection control team from the centers. With primary arthroplasties, as with all procedures involving implants, the surveillance is maintained for 1 year after the intervention. The VINCat Program uses the SSI definitions of the Centers for Disease Control (CDC) and patients are stratified by surgical risk, following the classification of the National Healthcare Safety Network (NHSN). During the period 2007-2009, 51 Catalan hospitals participated in the SSI surveillance of prosthetic orthopedic surgery. The overall SSI rate in the interventions for total primary hip prosthesis (7,804 procedures) was 3.0% (IC 95%: 2.6-3.4) and for total primary knee prosthesis (16,781 procedures) was 3.3% (IC95%: 3.0-3.6). During the period 2007-2009, the overall SSI rates for total primary hip and knee arthroplasty were higher than those published by some surveillance systems in our environment. There were significant differences in the infection rates by procedure and in those adjusted by risk among the different hospitals.

Leptin and adiponectin, but not IL18, are related with insulin resistance in treated HIV-1-infected patients with lipodystrophy.

Leptin, adiponectin and IL18 are adipokines related with obesity, insulin resistance and dyslipidemia in the general population. Treated HIV-1-infected patients with lipodystrophy may develop insulin resistance and proatherogenic dyslipidemia. We assessed the relationship between plasma adipokine levels, adipokine genetics, lipodystrophy and metabolic disturbances. Plasma leptin, adiponectin and IL18 levels were assessed in 446 individuals: 282 HIV-1-infected patients treated with antiretroviral drugs (132 with lipodystrophy and 150 without) and 164 uninfected controls (UC). The LEP2410A>G, LEPRQ223R, ADIPQ276G>T, ADIPOR2-Intron5A>G and IL18-607C>A polymorphisms were validated by sequencing. Leptin levels were higher in UC than in HIV-1-infected, either with or without lipodystrophy (p<0.001 for both comparisons) and were lower in patients with lipodystrophy compared with those without lipodystrophy (p=0.006). In patients with lipodystrophy, leptin had a positive correlation with insulin and with HOMA-IR. Adiponectin levels were non-significantly different in UC and HIV-1-infected patients. Patients with lipodystrophy had lower adiponectin levels than non-lipodystrophy subjects (p<0.001). In patients with lipodystrophy, adiponectin was negatively correlated with insulin, HOMA-IR and triglycerides. Plasma IL18 levels were higher in HIV-1-infected patients compared with UC (p<0.001), and no differences were found according to the presence of lipodystrophy. In patients with lipodystrophy there was a negative correlation between IL18 levels and LDLc. Genetic analyses indicated no significant associations with lipodystrophy nor with insulin resistance or with lipid abnormalities. In conclusion, HIV-1-infected patients have reduced plasma leptin levels. This reduction is magnified in patients with lipodystrophy whose adiponectin levels were lower than that of non-lipodystrophy subjects. Plasma IL18 levels are increased in infected patients irrespective of the presence of lipodystrophy. The polymorphisms assessed are not associated with lipodystrophy or metabolic disturbances in treated HIV-1-infected patients.

Zinc alpha-2 glycoprotein is implicated in dyslipidaemia in HIV-1-infected patients treated with antiretroviral drugs.

OBJECTIVES: Treated HIV-1-infected patients with lipodystrophy often develop insulin resistance and proatherogenic dyslipidaemia. Zinc alpha-2 glycoprotein (ZAG) is a recently characterized adipokine which has been shown to be involved in the development of obesity and metabolic syndrome in uninfected subjects. We assessed the relationship between circulating ZAG levels and metabolic derangements in HIV-1-infected patients receiving antiretroviral drugs. METHODS: Plasma ZAG levels were assessed in 222 individuals: 166 HIV-1-infected patients treated with antiretroviral drugs (77 with lipodystrophy and 89 without lipodystrophy) and 56 uninfected controls. Plasma ZAG levels were assessed by enzyme-linked immunosorbent assay (ELISA) and were correlated with fat distribution abnormalities and metabolic parameters. RESULTS: HIV-1-infected patients had lower plasma ZAG levels compared with uninfected controls (P < 0.001). No differences were found in ZAG plasma levels according to the presence of lipodystrophy, components of the metabolic syndrome or type of antiretroviral treatment regimen. Circulating ZAG levels were strongly determined by high-density lipoprotein cholesterol (HDLc) in men (B = 0.644; P < 0.001) and showed a positive correlation with total cholesterol (r = 0.312; P < 0.001) and HDLc (r = 0.216; P = 0.005). CONCLUSIONS: HIV-1-infected patients have lower plasma ZAG levels than uninfected controls. In infected patients, plasma ZAG levels are in close relationship with total cholesterol and HDLc.

New adipokines vaspin and omentin. Circulating levels and gene expression in adipose tissue from morbidly obese women.

BACKGROUND: Vaspin and omentin are recently described molecules that belong to the adipokine family and seem to be related to metabolic risk factors. The objectives of this study were twofold: to evaluate vaspin and omentin circulating levels and mRNA expression in subcutaneous and visceral adipose tissues in non-diabetic morbidly obese women; and to assess the relationship of vaspin and omentin with anthropometric and metabolic parameters, and other adipo/cytokines. DESIGN: We analysed vaspin and omentin circulating levels in 71 women of European descent (40 morbidly obese [BMI≥40 kg/m2] and 31 lean [BMI≤25]). We assessed vaspin and omentin gene expression in paired samples of visceral and subcutaneous abdominal adipose tissue from 46 women: 40 morbidly obese and 6 lean. We determined serum vaspin and plasma omentin levels with an Enzyme-Linked Immunosorbent Assay and adipose tissue mRNA expression by real time RT-PCR. RESULTS: Serum vaspin levels in the morbidly obese were not significantly different from those in controls. They correlated inversely with levels of lipocalin 2 and interleukin 6. Vaspin mRNA expression was significantly higher in the morbidly obese, in both subcutaneous and visceral adipose tissue.Plasma omentin levels were significantly lower in the morbidly obese and they correlated inversely with glucidic metabolism parameters. Omentin circulating levels, then, correlated inversely with the metabolic syndrome (MS). Omentin expression in visceral adipose tissue was significantly lower in morbidly obese women than in controls. CONCLUSIONS: The present study indicates that vaspin may have a compensatory role in the underlying inflammation of obesity. Decreased omentin circulating levels have a close association with MS in morbidly obese women.

Lipodystrophy and insulin resistance in combination antiretroviral treated HIV-1-infected patients: implication of resistin.

BACKGROUND: Little information is available with respect to the involvement of resistin in lipodystrophy and metabolic disturbances in HIV-1-infected patients treated with combination antiretroviral therapy (cART). We determined whether the resistin (rest) -420C>G single-nucleotide polymorphism and plasma resistin are associated with the development of lipodystrophy and metabolic disturbances in HIV-1-infected patients treated with cART. METHODS: The study group comprised 299 HIV-1-infected patients treated with a stable cART for at least 1 year (143 with lipodystrophy and 156 without) and 175 uninfected controls. Anthropometric, clinical, and metabolic variables were determined. Homeostasis model assessment for insulin resistance was used to evaluate insulin resistance. Plasma resistin levels were determined by enzyme-linked immunosorbent assay. The rest -420C>G was assessed using restriction fragment length polymorphism. Student t test, 1-way and 2-way analysis of variance, χ2 test, and Pearson and Spearman correlations were performed for statistical analysis. RESULTS: Genotypes containing the rest -420G variant allele were significantly more common in HIV-1-infected patients without lipodystrophy compared with those with lipodystrophy (P = 0.037). Infected patients had significantly greater plasma resistin levels than uninfected controls (P < 0.001). Among infected patients, plasma resistin levels were significantly lower in patients with lipodystrophy with respect to those without (P = 0.034). In infected patients, plasma resistin levels had a significant positive correlation with insulin and homeostasis model assessment for insulin resistance: P < 0.001 and P = 0.002 in the lipodystrophy subset and P = 0.002 and P = 0.03 in the nonlipodystrophy subset, respectively. CONCLUSIONS: In our cohort of white Spaniards, the rest -420C>G single-nucleotide polymorphism may be associated with cART-related lipodystrophy. Plasma resistin correlates with insulin resistance in infected patients with and without lipodystrophy.