| 1. |
- Barbosa, Pedro, et al.
(författare)
-
CD8+Treg cells play a role in the obesity-associated insulin resistance
- 2024
-
Ingår i: Life Sciences. - : Elsevier. - 0024-3205 .- 1879-0631. ; 336
-
Tidskriftsartikel (refereegranskat)abstract
- Obesity-related chronic low-grade inflammation may trigger insulin resistance and type 2 diabetes (T2D) development. Cells with regulatory phenotype have been shown to be reduced during obesity, especially CD4+ Treg cells. However, little is known about the CD8+ Treg cells. Therefore, we aim to characterize the CD8+ Treg cells in human peripheral blood and adipose tissue, specifically, to address the effect of obesity and insulin resistance in this regulatory immune cell population. A group of 42 participants with obesity (OB group) were recruited. Fourteen of them were evaluated pre-and post-bariatric surgery. A group of age-and sex-matched healthy volunteers (n = 12) was also recruited (nOB group). CD8+ Treg cell quantification and phenotype were evaluated by flow cytometry, in peripheral blood (PB), subcutaneous (SAT), and visceral adipose tissues (VAT). The OB group displayed a higher percentage of CD8+ Treg cells in PB, compared to the nOB. In addition, they were preferentially polarized into Tc1-and Tc1/17-like CD8+ Treg cells, compared to nOB. Moreover, SAT displayed the highest content of CD8+ Tregs infiltrated, compared to PB or VAT, while CD8+ Tregs infiltrating VAT displayed a higher percentage of cells with Tc1-like phenotype. Participants with pre-diabetes displayed a reduced percentage of TIM-3+CD8+ Tregs in circulation, and PD-1+CD8+ Tregs infiltrated in the VAT. An in-crease in the percentage of circulating Tc1-like CD8+ Treg cells expressing PD-1 was observed post-surgery. In conclusion, obesity induces significant alterations in CD8+ Treg cells, affecting their percentage and phenotype, as well as the expression of important immune regulatory molecules.
|
|
| 2. |
- De Bus, Liesbet, et al.
(författare)
-
Antimicrobial de-escalation in the critically ill patient and assessment of clinical cure : the DIANA study
- 2020
-
Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 46:7, s. 1404-1417
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSE: The DIANA study aimed to evaluate how often antimicrobial de-escalation (ADE) of empirical treatment is performed in the intensive care unit (ICU) and to estimate the effect of ADE on clinical cure on day 7 following treatment initiation.METHODS: Adult ICU patients receiving empirical antimicrobial therapy for bacterial infection were studied in a prospective observational study from October 2016 until May 2018. ADE was defined as (1) discontinuation of an antimicrobial in case of empirical combination therapy or (2) replacement of an antimicrobial with the intention to narrow the antimicrobial spectrum, within the first 3 days of therapy. Inverse probability (IP) weighting was used to account for time-varying confounding when estimating the effect of ADE on clinical cure.RESULTS: Overall, 1495 patients from 152 ICUs in 28 countries were studied. Combination therapy was prescribed in 50%, and carbapenems were prescribed in 26% of patients. Empirical therapy underwent ADE, no change and change other than ADE within the first 3 days in 16%, 63% and 22%, respectively. Unadjusted mortality at day 28 was 15.8% in the ADE cohort and 19.4% in patients with no change [p = 0.27; RR 0.83 (95% CI 0.60-1.14)]. The IP-weighted relative risk estimate for clinical cure comparing ADE with no-ADE patients (no change or change other than ADE) was 1.37 (95% CI 1.14-1.64).CONCLUSION: ADE was infrequently applied in critically ill-infected patients. The observational effect estimate on clinical cure suggested no deleterious impact of ADE compared to no-ADE. However, residual confounding is likely.
|
|
| 3. |
- Sartelli, Massimo, et al.
(författare)
-
Ten golden rules for optimal antibiotic use in hospital settings: the WARNING call to action
- 2023
-
Ingår i: WORLD JOURNAL OF EMERGENCY SURGERY. - 1749-7922. ; 18:1
-
Forskningsöversikt (refereegranskat)abstract
- Antibiotics are recognized widely for their benefits when used appropriately. However, they are often used inappropriately despite the importance of responsible use within good clinical practice. Effective antibiotic treatment is an essential component of universal healthcare, and it is a global responsibility to ensure appropriate use. Currently, pharmaceutical companies have little incentive to develop new antibiotics due to scientific, regulatory, and financial barriers, further emphasizing the importance of appropriate antibiotic use. To address this issue, the Global Alliance for Infections in Surgery established an international multidisciplinary task force of 295 experts from 115 countries with different backgrounds. The task force developed a position statement called WARNING (Worldwide Antimicrobial Resistance National/International Network Group) aimed at raising awareness of antimicrobial resistance and improving antibiotic prescribing practices worldwide. The statement outlined is 10 axioms, or "golden rules," for the appropriate use of antibiotics that all healthcare workers should consistently adhere in clinical practice.
|
|
| 4. |
- Barbosa, Pedro, et al.
(författare)
-
Bariatric Surgery Induces Alterations in the Immune Profile of Peripheral Blood T Cells
- 2024
-
Ingår i: Biomolecules. - : MDPI. - 2218-273X. ; 14:2
-
Tidskriftsartikel (refereegranskat)abstract
- Low-grade inflammation is closely linked to obesity and obesity-related comorbidities; therefore, immune cells have become an important topic in obesity research. Here, we performed a deep phenotypic characterization of circulating T cells in people with obesity, using flow cytometry. Forty-one individuals with obesity (OB) and clinical criteria for bariatric surgery were enrolled in this study. We identified and quantified 44 different circulating T cell subsets and assessed their activation status and the expression of immune-checkpoint molecules, immediately before (T1) and 7-18 months after (T2) the bariatric surgery. Twelve age- and sex-matched healthy individuals (nOB) were also recruited. The OB participants showed higher leukocyte counts and a higher percentage of neutrophils. The percentage of circulating Th1 cells were negatively correlated to HbA1c and insulin levels. OB Th1 cells displayed a higher activation status and lower PD-1 expression. The percentage of Th17 and Th1/17 cells were increased in OB, whereas the CD4+ Tregs' percentage was decreased. Interestingly, a higher proportion of OB CD4+ Tregs were polarized toward Th1- and Th1/17-like cells and expressed higher levels of CCR5. Bariatric surgery induced the recovery of CD4+ Treg cell levels and the expansion and activation of Tfh and B cells. Our results show alterations in the distribution and phenotype of circulating T cells from OB people, including activation markers and immune-checkpoint proteins, demonstrating that different metabolic profiles are associated to distinct immune profiles, and both are modulated by bariatric surgery.
|
|
| 5. |
- Leone, Marc, et al.
(författare)
-
Update in antibiotic therapy in intensive care unit : report from the 2019 Nîmes International Symposium
- 2019
-
Ingår i: Anaesthesia Critical Care & Pain Medicine. - : Elsevier BV. - 2352-5568. ; 38:6, s. 647-656
-
Forskningsöversikt (refereegranskat)abstract
- The 2019 Nîmes International Symposium in Antibiotic Therapy Optimisation aimed at determining the best approaches of a number of the antibiotic management strategies for critically ill patients. Experts reviewed the latest literature relating to requirements for an optimal antibiotic stewardship program, risks of sub-therapeutic dosing of antibiotics in critically ill patients, persisting issues about efficiency of combination therapy and the value of de-escalation, new perspectives of pharmacokinetics, drug toxicities including collateral damages-associated with antibiotics, the place of nebulisation of antibiotics, management of patients receiving extracorporeal therapies and the place of new antibiotics. In this paper, each of these issues is discussed with key messages presented after a brief review of evidence.
|
|
| 6. |
- Ricci, Fabrizio, et al.
(författare)
-
Pulmonary blood volume index as a quantitative biomarker of haemodynamic congestion in hypertrophic cardiomyopathy
- 2019
-
Ingår i: European Heart Journal Cardiovascular Imaging. - : Oxford University Press (OUP). - 2047-2412 .- 2047-2404. ; 20:12, s. 1368-1376
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS : The non-invasive assessment of left ventricular (LV) diastolic function and filling pressure in hypertrophic cardiomyopathy (HCM) is still an open issue. Pulmonary blood volume index (PBVI) by cardiovascular magnetic resonance (CMR) has been proposed as a quantitative biomarker of haemodynamic congestion. We aimed to assess the diagnostic accuracy of PBVI for left atrial pressure (LAP) estimation in patients with HCM. METHODS AND RESULTS : We retrospectively identified 69 consecutive HCM outpatients (age 58 ± 11 years; 83% men) who underwent both transthoracic echocardiography (TTE) and CMR. Guideline-based detection of LV diastolic dysfunction was assessed by TTE, blinded to CMR results. PBVI was calculated as the product of right ventricular stroke volume index and the number of cardiac cycles for a bolus of gadolinium to pass through the pulmonary circulation as assessed by first-pass perfusion imaging. Compared to patients with normal LAP, patients with increased LAP showed significantly larger PBVI (463 ± 127 vs. 310 ± 86 mL/m2, P < 0.001). PBVI increased progressively with worsening New York Heart Association functional class and echocardiographic stages of diastolic dysfunction (P < 0.001 for both). At the best cut-off point of 413 mL/m2, PBVI yielded good diagnostic accuracy for the diagnosis of LV diastolic dysfunction with increased LAP [C-statistic = 0.83; 95% confidence interval (CI): 0.73-0.94]. At multivariable logistic regression analysis, PBVI was an independent predictor of increased LAP (odds ratio per 10% increase: 1.97, 95% CI: 1.06-3.68; P = 0.03). CONCLUSION : PBVI is a promising CMR application for assessment of diastolic function and LAP in patients with HCM and may serve as a quantitative marker for detection, grading, and monitoring of haemodynamic congestion.
|
|
