The search for complementary treatments in primary prevention of cardiovascular disease (CVD) is a high-priority challenge. Grape and wine polyphenol resveratrol confers CV benefits, in part by ...exerting anti-inflammatory effects. However, the evidence in human long-term clinical trials has yet to be established. We aimed to investigate the effects of a dietary resveratrol-rich grape supplement on the inflammatory and fibrinolytic status of subjects at high risk of CVD and treated according to current guidelines for primary prevention of CVD. Seventy-five patients undergoing primary prevention of CVD participated in this triple-blinded, randomized, parallel, dose–response, placebo-controlled, 1-year follow-up trial. Patients, allocated in 3 groups, consumed placebo (maltodextrin), a resveratrol-rich grape supplement (resveratrol 8 mg), or a conventional grape supplement lacking resveratrol, for the first 6 months and a double dose for the next 6 months. In contrast to placebo and conventional grape supplement, the resveratrol-rich grape supplement significantly decreased high-sensitivity C-reactive protein (−26%, p = 0.03), tumor necrosis factor-α (−19.8%, p = 0.01), plasminogen activator inhibitor type 1 (−16.8%, p = 0.03), and interleukin-6/interleukin-10 ratio (−24%, p = 0.04) and increased anti-inflammatory interleukin-10 (19.8%, p = 0.00). Adiponectin (6.5%, p = 0.07) and soluble intercellular adhesion molecule-1 (−5.7%, p = 0.06) tended to increase and decrease, respectively. No adverse effects were observed in any patient. In conclusion, 1-year consumption of a resveratrol-rich grape supplement improved the inflammatory and fibrinolytic status in patients who were on statins for primary prevention of CVD and at high CVD risk (i.e., with diabetes or hypercholesterolemia plus ≥1 other CV risk factor). Our results show for the first time that a dietary intervention with grape resveratrol could complement the gold standard therapy in the primary prevention of CVD.
Numerous studies have shown that resveratrol (RES) exerts anti-inflammatory effects but human trials evidencing these effects in vivo are limited. Furthermore, the molecular mechanisms triggered in ...humans following the oral intake of RES are not yet understood. Therefore, the purpose of this study was to investigate the molecular changes in peripheral blood mononuclear cells (PBMCs) associated to the one-year daily intake of a RES enriched (8mg) grape extract (GE-RES) in hypertensive male patients with type 2 diabetes mellitus (T2DM). We used microarrays and RT-PCR to analyze expression changes in genes and microRNAs (miRs) involved in the inflammatory response modulated by the consumption of GE-RES in comparison to a placebo and GE lacking RES. We also examined the changes in several serobiochemical variables, inflammatory and fibrinolytic markers. Our results showed that supplementation with GE or GE-RES did not affect body weight, blood pressure, glucose, HbA1c or lipids, beyond the values regulated by gold standard medication in these patients. We did not find either any significant change on serum inflammatory markers except for a significant reduction of ALP and IL-6 levels. The expression of the pro-inflammatory cytokines CCL3, IL-1β and TNF-α was significantly reduced and that of the transcriptional repressor LRRFIP-1 increased in PBMCs from patients taking the GE-RES extract. Also, a group of miRs involved in the regulation of the inflammatory response: miR-21, miR-181b, miR-663, miR-30c2, miR-155 and miR-34a were found to be highly correlated and altered in the group consuming the GE-RES for 12 months. Our results provide preliminary evidence that long-term supplementation with a grape extract containing RES downregulates the expression of key pro-inflammatory cytokines with the involvement of inflammation-related miRs in circulating immune cells of T2DM hypertensive medicated patients and support a beneficial immunomodulatory effect in these patients.
Scope
The cardioprotective role of resveratrol as part of the human diet is not yet clear. Our aim was to investigate the effect of a grape supplement containing 8 mg resveratrol in oxidized LDL ...(LDLox), apolipoprotein‐B (ApoB), and serum lipids on statin‐treated patients in primary cardiovascular disease prevention (PCP).
Methods and results
A triple‐blind, randomized, placebo‐controlled trial was conducted. Seventy‐five patients (three parallel arms) consumed one capsule (350 mg) daily for 6 months containing resveratrol‐enriched grape extract (GE‐RES, Stilvid®), grape extract (GE, similar polyphenolic content but no resveratrol), or placebo (maltodextrin). After 6 months, no changes were observed in the placebo group and only LDL cholesterol (LDLc) decreased by 2.9% (p = 0.013) in the GE group. In contrast, LDLc (−4.5%, p = 0.04), ApoB (−9.8%, p = 0.014), LDLox (−20%, p = 0.001), and LDLox/ApoB (−12.5%, p = 0.000) decreased in the Stilvid® group, whereas the ratio non‐HDLc (total atherogenic cholesterol load)/ApoB increased (8.5%, p = 0.046). No changes were observed in hepatic, thyroid, and renal function. No adverse effects were observed in any of the patients.
Conclusion
This GE‐RES reduced atherogenic markers and might exert additional cardioprotection beyond the gold‐standard medication in patients from PCP. The presence of resveratrol in the GE was necessary to achieve these effects.
Primary prevention of cardiovascular disease (CVD) aims to avoid a first event in subjects that are at risk but have not yet been diagnosed with heart disease. Secondary prevention of CVD aims to ...avoid new events in patients with established heart disease. Both approaches involve clinical intervention and implementation of healthy lifestyles. The grape and wine polyphenol resveratrol (3,5,4′‐trihydroxy‐trans‐stilbene) has shown cardioprotective benefits in humans. Most of these approaches deal with rather high doses and short follow‐ups, and do not address the issue of long‐term resveratrol consumption safety, especially in medicated individuals. Here, we review the trials conducted with resveratrol in patients at risk for or with established CVD, focusing on the two longest human clinical trials reported so far (1‐year follow‐up). We also discuss the expectations for resveratrol from a dietary and clinical perspective in relation to CVD. However, statistically significant changes in CVD‐risk markers do not necessarily equal clinical significance in the daily care of patients.
Purpose
The grape and wine polyphenol resveratrol exerts cardiovascular benefits but evidence from randomized human clinical trials is very limited. We investigated dose-depending effects of a ...resveratrol-containing grape supplement on stable patients with coronary artery disease (CAD) treated according to currently accepted guidelines for secondary prevention of cardiovascular disease.
Methods
In a triple-blind, randomized, placebo-controlled, one-year follow-up, 3-arm pilot clinical trial, 75 stable-CAD patients received 350 mg/day of placebo, resveratrol-containing grape extract (grape phenolics plus 8 mg resveratrol) or conventional grape extract lacking resveratrol during 6 months, and a double dose for the following 6 months. Changes in circulating inflammatory and fibrinolytic biomarkers were analyzed. Moreover, the transcriptional profiling of inflammatory genes in peripheral blood mononuclear cells (PBMCs) was explored using microarrays and functional gene expression analysis.
Results
After 1 year, in contrast to the placebo and conventional grape extract groups, the resveratrol-containing grape extract group showed an increase of the anti-inflammatory serum adiponectin (9.6 %,
p
= 0.01) and a decrease of the thrombogenic plasminogen activator inhibitor type 1 (PAI-1) (−18.6 %,
p =
0.05). In addition, 6 key inflammation-related transcription factors were predicted to be significantly activated or inhibited, with 27 extracellular-space acting genes involved in inflammation, cell migration and T-cell interaction signals presenting downregulation (
p <
0.05) in PBMCs. No adverse effects were detected in relation to the study products.
Conclusions
Chronic daily consumption of a resveratrol-containing grape nutraceutical could exert cardiovascular benefits in stable-CAD patients treated according to current evidence-based standards, by increasing serum adiponectin, preventing PAI-1 increase and inhibiting atherothrombotic signals in PBMCs.
•PCV10 and PCV13 protect similarly against invasive disease due to vaccine serotypes.•PCV13 provides direct protection against serotype 3 and vaccine-related serotype 6C.•PCV10 does not provide ...significant protection against vaccine-related serotypes 19A and 6C.•PCV13 effectiveness declined with time after booster, in particular for serotypes 3 and 19A.•Multinational networks are crucial for the evaluation of PCV15/ PCV20 that may be introduced.
Pneumococcal conjugate vaccines covering 10 (PCV10) and 13 (PCV13) serotypes have been introduced in the infant immunization schedule of most European countries in 2010–11. To provide additional real-life data, we measured the effectiveness of PCV10 and PCV13 against invasive pneumococcal disease (IPD) in children of 12 European sites (SpIDnet).
We compared the vaccination status of PCV10 and PCV13 serotype IPD (cases) to that of nonPCV13 serotype IPD (controls) reported in 2012–2018. We calculated pooled effectiveness as (1-vaccination odds ratio)*100, and measured effectiveness over time since booster dose.
The PCV13 and PCV10 studies included 2522 IPD cases from ten sites and 486 cases from four sites, respectively. The effectiveness of ≥ 1 PCV13 dose was 84.2% (95 %CI: 79.0–88.1) against PCV13 serotypes (n = 2353) and decreased from 93.1% (87.8–96.1) < 12 months to 85.1% (72.0–92.1) ≥ 24 months after booster dose. PCV13 effectiveness of ≥ 1 dose was 84.7% (55.7–94.7) against fatal PCV13 IPD, 64.5% (43.7–77.6), 83.2% (73.7–89.3) and 85.1% (67.6–93.1) against top serotypes 3, 19A and 1, respectively, and 85.4% (62.3–94.4) against 6C. Serotype 3 and 19A effectiveness declined more rapidly. PCV10 effectiveness of ≥ 1 dose was 84.8% (69.4–92.5) against PCV10 serotypes (n = 370), 27.2% (-187.6 to 81.6) and 85.3% (35.2–96.7) against top serotypes 1 and 7F, 32.5% (-28.3 to 64.5) and −14.4% (-526.5 to 79.1) against vaccine-related serotypes 19A and 6C, respectively.
PCV10 and PCV13 provide similar protection against IPD due to the respective vaccine serotype groups but serotype-specific effectiveness varies by serotype and vaccine. PCV13 provided individual protection against serotype 3 and vaccine-related serotype 6C IPD. PCV10 effectiveness was not significant against vaccine-related serotypes 19A and 6C. PCV13 effectiveness declined with time after booster vaccination. This multinational study enabled measuring serotype-specific vaccine effectiveness with a precision rarely possible at the national level. Such large networks are crucial for the post-licensure evaluation of vaccines.
Over 5 million stillbirths and neonatal deaths occur annually. Limited and imprecise information on the cause of these deaths hampers progress in achieving global health targets. Complete diagnostic ...autopsies (CDAs)-the gold standard for cause of death determination-are difficult to perform in most high-burden settings. Therefore, validation of simpler and more feasible methods is needed.
In this observational study, the validity of a minimally invasive autopsy (MIA) method in determining the cause of death was assessed in 18 stillbirths and 41 neonatal deaths by comparing the results of the MIA with those of the CDA. Concordance between the categories of diseases obtained by the 2 methods was assessed by the Kappa statistic, and the sensitivity, specificity, positive, and negative predictive values of the MIA diagnoses were calculated. A cause of death was identified in 16/18 (89%) and 15/18 (83%) stillborn babies in the CDA and the MIA, respectively. Fetal growth restriction accounted for 39%, infectious diseases for 22%, intrapartum hypoxia for 17%, and intrauterine hypoxia for 11% of stillborn babies. Overall, the MIA showed in this group a substantial concordance with the CDA (Kappa = 0.78, 95% CI 0.56-0.99). A cause of death was identified in all (100%) and 35/41 (85%) neonatal deaths in the CDA and the MIA, respectively. In this group, the majority of deaths were due to infectious diseases (66%). The overall concordance of the MIA with the CDA in neonates was moderate (Kappa = 0.40, 95% CI 0.18-0.63). A high percentage of accuracy was observed for the MIA in all the diagnostic categories in both stillbirths and neonates (>75%). The main limitation of this study is that some degree of subjective interpretation is inherent to cause-of-death attribution in both the MIA and the CDA; this is especially so in stillbirths and in relation to fetal growth restriction.
The MIA could be a useful tool for cause-of-death determination in stillbirths and neonatal deaths. These findings may help to accelerate progress towards meeting global health targets by obtaining more accurate information on the causes of death in these age groups, which is essential in guiding the design of new interventions and increasing the effectiveness of those already implemented.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The risk of suffering from some infectious diseases can be related to specific microbiota profiles. Specifically, the nasopharyngeal microbiota could play a role as a risk or protective factor in the ...development of invasive disease caused by
.
We analyzed the nasopharyngeal microbiota of children with invasive pneumococcal disease (IPD) and that of healthy controls matched by age, sex, and seasonality from Catalonia, Spain. Epidemiological, microbiological and clinical variables were considered to compare microbiota profiles, analyzed by sequencing the V1-V4 region of the 16S rRNA gene.
Twenty-eight children with IPD (median age 43 months) and 28 controls (42.6 months) were included in the study. IPD children presented a significantly higher bacterial diversity and richness (
< 0.001). Principal coordinate analysis revealed three different microbiota profiles: microbiota A, dominated by the genus
(44.3%); Microbiota B, mostly represented by
(36.9%) and
(21.3%) and a high diversity of anaerobic genera including
and
; and Microbiota C, mainly containing
(52.1%) and
(31.4%). The only explanatory factor for the three microbiotas was the classification of children into disease or healthy controls (
= 0.006). A significant negative correlation was found between
vs.
(
= 0.029), suggesting a potential antagonistic effect against pneumococcal pathogens.
The higher bacterial diversity and richness in children with IPD could suggest an impaired immune response. This lack of immune competence could be aggravated by breastfeeding <6 months and by the presence of keystone pathogens such as
, a bacterium which has been shown to be able to manipulate the immune response, and that could favor the overgrowth of many proteolytic anaerobic organisms giving rise to a dramatic dysbiosis. From an applied viewpoint, we found suggestive microbiota profiles associated to IPD or asymptomatic colonization that could be used as disease biomarkers or to pave the way for characterizing health-associated inhabitants of the respiratory tract. The identification of beneficial bacteria could be useful to prevent pneumococcal infections by integrating those microorganisms in a probiotic formula. The present study suggests not only respiratory tract samples, but also breast milk, as a potential source of those beneficial bacteria.
Objective: Our objective was to determine and describe the opinion and attitudes of patients and their families regarding the limitation of therapeutic effort and advanced directives in critical ...patients and whether end-of-life planning occurs. Religious affiliation, education level, and pre-admission quality of life were also evaluated to determine whether they may influence decisions regarding appropriate therapeutic effort. Methods: A prospective, observational and descriptive study, approved by the center’s ethical committee, was carried out with 257 participants (94 patients and 163 family members) in the intensive care unit (ICU). A questionnaire regarding the opinions of patients and relatives about situations of therapeutic appropriateness in case of poor prognosis or poor quality of life was used. The questionnaire had three sections. In the first section, sociodemographic features were investigated. In the second section, information was collected on the quality of life and functional situation before ICU admission (taking as a reference the situation one month before admission) assessed by the Karnofsky scale, Barthel index, and the PAEEC scale (Project for the Epidemiological Analysis of Critical Care Patients). The third section aimed to determine whether the family knew the patient’s opinion regarding his/her end of life. Results: Of those interviewed, 62.2% would agree to limit treatment in case of poor prognosis or poor quality of future life. In contrast, 37.7% considered that they should fight for life, even if it is irretrievable. Only 1.6% had advanced directives registered, 43.9% of the participants admitted deterioration in their quality of life before ICU admission, 18.2% with moderate-severe deterioration. Our study shows that the higher the educational level, the lower the desire to fight for life when it is irretrievable and the greater the agreement to limit treatment. Besides, those participants not affiliated with a religion were significantly less likely to fight for life, including when irretrievable, than Catholics and were more likely to agree to limit treatment. Conclusions: More than half of the participants would agree to limit treatment in the case of a poor prognosis. Our results indicate that patients do not prepare for the dying process well in advance. Religion and educational level were determining factors for the choice of procedures at the end of life, both for patients and their families.
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