Introduction
Dynamic predictors of fluid responsiveness have shown good performance in mechanically ventilated patients at tidal volumes (Vt) > 8 mL kg
−1
. Nevertheless, most critically ill ...conditions demand lower Vt. We sought to evaluate the operative performance of several predictors of fluid responsiveness at Vt ≤ 8 mL kg
−1
by using meta-regression and subgroup analyses.
Methods
A sensitive search was conducted in the Embase and MEDLINE databases. We searched for studies prospectively assessing the operative performance of pulse pressure variation (PPV), stroke volume variation (SVV), end-expiratory occlusion test (EEOT), passive leg raising (PLR), inferior vena cava respiratory variability (Δ-IVC), mini-fluid challenge (m-FC), and tidal volume challenge (VtC), to predict fluid responsiveness in adult patients mechanically ventilated at Vt ≤ 8 ml kg
−1
, without respiratory effort and arrhythmias, published between 1999 and 2020. Operative performance was assessed using hierarchical and bivariate analyses, while subgroup analysis was used to evaluate variations in their operative performance and sources of heterogeneity. A sensitivity analysis based on the methodological quality of the studies included (QUADAS-2) was also performed.
Results
A total of 33 studies involving 1,352 patients were included for analysis. Areas under the curve (AUC) values for predictors of fluid responsiveness were: for PPV = 0.82, Δ-IVC = 0.86, SVV = 0.90, m-FC = 0.84, PLR = 0.84, EEOT = 0.92, and VtC = 0.92. According to subgroup analyses, variations in methods to measure cardiac output and in turn, to classify patients as responders or non-responders significantly influence the performance of PPV and SVV (
p
< 0.05). Operative performance of PPV was also significantly affected by the compliance of the respiratory system (
p
= 0.05), while type of patient (
p
< 0.01) and thresholds used to determine responsiveness significantly affected the predictability of SVV (
p
= 0.05). Similarly, volume of fluids infused to determine variation in cardiac output, significantly affected the performance of SVV (
p
= 0.01) and PLR (
p
< 0.01). Sensitivity analysis showed no variations in operative performance of PPV (
p
= 0.39), SVV (
p
= 0.23) and EEOT (
p
= 0.15).
Conclusion
Most predictors of fluid responsiveness reliably predict the response of cardiac output to volume expansion in adult patients mechanically ventilated at tidal volumes ≤ 8 ml kg
−1
. Nevertheless, technical and clinical variables might clearly influence on their operative performance
HLA-G is a non-classical HLA class I molecule with immunomodulatory properties. It was initially described at the maternal-fetal interface, and it was later found that this molecule was ...constitutively expressed on certain immuneprivileged tissues, such as cornea, endothelial and erythroid precursors, and thymus. The immunosuppressive effect of HLA-G is exerted through the interaction with its cognate receptors, expressed on immunocompetent cells, like ILT2, expressed on NK, B, T cells and APCs; ILT4, on APCs; KIR, found on the surface of NK cells; and finally, the co-receptor CD8. Because of these immunomodulatory functions, HLA-G has been involved in several processes, amongst which organ transplantation, viral infections, cancer progression, and autoimmunity. HLA-G neo-expression on tumors has been recently described in several types of malignancies. In fact, tumor progression is tightly linked to the presence of the molecule, as it exerts its tolerogenic function, inhibiting the cells of the immune system and favoring tumor escape. Several polymorphisms in the 3'UTR region condition changes in HLA-G expression (14bp and +3142C/G, among others), which have been associated with both the development and outcome of patients with different tumor types. Also, in recent years, several studies have shown that HLA-G plays an important role in the control of autoimmune diseases. The ability of HLA-G to limit the progression of these diseases has been confirmed and, in fact, levels of the molecule and several of its polymorphisms have been associated with increased susceptibility to the development of autoimmune diseases, as well as increased disease severity. Thus, modulating HLA-G expression in target tissues of oncology patients or patients with autoimmune diseases may be potential therapeutic approaches to treat these pathological conditions.
Abstract
Introduction
Prediction of fluid responsiveness in acutely ill patients might be influenced by a number of clinical and technical factors. We aim to identify variables potentially modifying ...the operative performance of fluid responsiveness predictors commonly used in clinical practice.
Methods
A sensitive strategy was conducted in the Medline and Embase databases to search for prospective studies assessing the operative performance of pulse pressure variation, stroke volume variation, passive leg raising (PLR), end-expiratory occlusion test (EEOT), mini-fluid challenge, and tidal volume challenge to predict fluid responsiveness in critically ill and acutely ill surgical patients published between January 1999 and February 2023. Adjusted diagnostic odds ratios (DORs) were calculated by subgroup analyses (inverse variance method) and meta-regression (test of moderators). Variables potentially modifying the operative performance of such predictor tests were classified as technical and clinical.
Results
A total of 149 studies were included in the analysis. The volume used during fluid loading, the method used to assess variations in macrovascular flow (cardiac output, stroke volume, aortic blood flow, volume‒time integral, etc.) in response to PLR/EEOT, and the apneic time selected during the EEOT were identified as technical variables modifying the operative performance of such fluid responsiveness predictor tests (
p
< 0.05 for all adjusted vs. unadjusted DORs). In addition, the operative performance of fluid responsiveness predictors was also influenced by clinical variables such as the positive end-expiratory pressure (in the case of EEOT) and the dose of norepinephrine used during the fluid responsiveness assessment for PLR and EEOT (for all adjusted vs. unadjusted DORs).
Conclusion
Prediction of fluid responsiveness in critically and acutely ill patients is strongly influenced by a number of technical and clinical aspects. Such factors should be considered for individual intervention decisions.
Classical
HLA
(Human Leukocyte Antigen) is the Major Histocompatibility Complex (MHC) in man. HLA genes and disease association has been studied at least since 1967 and no firm pathogenic mechanisms ...have been established yet.
HLA-G
immune modulation gene (and also
-E
and
-F
) are starting the same arduous way: statistics and allele association are the trending subjects with the same few results obtained by
HLA
classical genes, i.e., no pathogenesis may be discovered after many years of a great amount of researchers’ effort. Thus, we believe that it is necessary to follow different research methodologies: (1) to approach this problem, based on how evolution has worked maintaining together a cluster of immune-related genes (the MHC) in a relatively short chromosome area since amniotes to human at least, i.e., immune regulatory genes (MHC-G, -E and -F), adaptive immune classical class I and II genes, non-adaptive immune genes like (C2, C4 and Bf) (2); in addition to using new in vitro models which explain pathogenetics of
HLA
and disease associations. In fact, this evolution may be quite reliably studied during about 40 million years by analyzing the evolution of
MHC-G, -E, -F
, and their receptors (KIR—killer-cell immunoglobulin-like receptor, NKG2—natural killer group 2-, or TCR-T-cell receptor—among others) in the primate evolutionary lineage, where orthology of these molecules is apparently established, although cladistic studies show that
MHC-G
and
MHC-B
genes are the ancestral class I genes, and that New World apes
MHC-G
is paralogous and not orthologous to all other apes and man
MHC-G
genes. In the present review, we outline past and possible future research topics: co-evolution of adaptive
MHC
classical (class I and II), non-adaptive (i.e., complement) and modulation (i.e., non-classical class I) immune genes may imply that the study of full or part of MHC haplotypes involving several loci/alleles instead of single alleles is important for uncovering HLA and disease pathogenesis. It would mainly apply to starting research on HLA-G extended haplotypes and disease association and not only using single HLA-G genetic markers.
HLA‐G in Mayas from Yucatan: An evolutionary approach Arnaiz‐Villena, Antonio; Suárez‐Trujillo, Fabio; Palacio‐Gruber, José ...
International journal of immunogenetics,
October 2021, 2021-Oct, 2021-10-00, 20211001, Volume:
48, Issue:
5
Journal Article
Peer reviewed
HLA‐G allele frequencies were studied in Yucatán (Mexico) Maya Amerindians by a direct exon DNA sequencing technique. It is described that Mayas are probably one of the first populations together ...with Olmecs that populated Meso America and that important HLA genetic differences between Mexican and Guatemalan Mayas support that Maya languages were imposed to several neighbouring Amerindian groups. HLA‐G*01:01:02, HLA‐G*01:01:01 and HLA‐G*01:04:01 are the most frequent alleles in this population. It is remarkable that HLA‐G*01:05N allele was not found in the population in accordance with similar results found in another Amerindians. Also, protein allele HLA‐G*01:04 frequency is found not to differ to those found in another far or close living Amerindians in contrast to other World populations. It seems that while high HLA‐G*01:05N frequency is found in Iran and Middle East populations, probably where this allele appeared within an ancestral HLA‐A*19 group of alleles haplotype and it is maintained by unknown evolutionary forces, Amerindians do not have a high frequency because a founder effect or because required natural evolutionary forces do not exist in America. Finally, we believe useful to study HLA‐G evolution for its physiopathology understanding in addition to the many papers on statistics on HLA‐G and in vitro models that are yearly published.
Summary The traditional trial paradigm is often criticized as being slow, inefficient, and costly. Statistical approaches that leverage external trial data have emerged to make trials more efficient ...by augmenting the sample size. However, these approaches assume that external data are from previously conducted trials, leaving a rich source of untapped real-world data (RWD) that cannot yet be effectively leveraged. We propose a semi-supervised mixture (SS-MIX) multisource exchangeability model (MEM); a flexible, two-step Bayesian approach for incorporating RWD into randomized controlled trial analyses. The first step is a SS-MIX model on a modified propensity score and the second step is a MEM. The first step targets a representative subgroup of individuals from the trial population and the second step avoids borrowing when there are substantial differences in outcomes among the trial sample and the representative observational sample. When comparing the proposed approach to competing borrowing approaches in a simulation study, we find that our approach borrows efficiently when the trial and RWD are consistent, while mitigating bias when the trial and external data differ on either measured or unmeasured covariates. We illustrate the proposed approach with an application to a randomized controlled trial investigating intravenous hyperimmune immunoglobulin in hospitalized patients with influenza, while leveraging data from an external observational study to supplement a subgroup analysis by influenza subtype.
HLA-G is a non-classical class I HLA molecule that induces tolerance by acting on receptors of both innate and adaptive immune cells. When overexpressed in tumors, limits surveillance by the immune ...system. The
gene shows several polymorphisms involved in mRNA and protein levels. We decided to study the implication of two polymorphisms (rs371194629; 14bp INS/DEL and rs1063320; +3142 C/G) in paired tissue samples (tumoral and non-tumoral) from 107 Spanish patients with gastric adenocarcinoma and 58 healthy control individuals, to assess the possible association of the
gene with gastric adenocarcinoma susceptibility, disease progression and survival. The presence of somatic mutations involving these polymorphisms was also analyzed. The frequency of the 14bp DEL allele was increased in patients (70.0%) compared to controls (57.0%, p=0.025). In addition, the haplotype formed by the combination of the 14bp DEL/+3142 C variants is also increased in patients (54.1%
44.4%, p=0.034, OR=1.74 CI95% 1.05-2.89). Kaplan-Meier analysis revealed that 14bp DEL/DEL patients showed lower 5-year life-expectancy than INS/DEL or INS/INS (p=0.041). Adjusting for TNM staging (Cox regression analysis) disclosed a significant difference in death risk (p=0.03) with an expected hazard 2.6 times higher. Finally, no somatic mutations were found when comparing these polymorphisms in tumoral
non-tumoral tissues, which indicates that this is a preexisting condition in patients and not a
, tumor-restricted, event. In conclusion, the variants predominant in patients were those increasing HLA-G mRNA stability and HLA-G expression, clearly involving this molecule in gastric adenocarcinoma susceptibility, disease progression and survival and making it a potential target for immunotherapeutic approaches.
Problem
Natural killer (NK, CD3−
CD56+/CD16+) and NKT‐like cells (CD3+
CD56+/CD16+) activity is considered among the key factors for reproductive success. In the absence of immunological screening, ...beneficial effects of intravenous immunoglobulin (IVIG) in preventing recurrent reproductive failure (RRF) have not been reported. Here, we analyse the IVIG influence on pregnancy success in women with RRF and circulating NK or/and NKT‐like cells expansion.
Method of study
One hundred fifty‐seven women with previous recurrent miscarriage and/or recurrent implantation failure after in vitro fertilization were consecutively studied. Sixty‐four patients with CD56+ cell expansion, no apparent underlying disease and who maintained their desire to conceive were selected. Forty of them received IVIG during pregnancy.
Results
Overall, the clinical pregnancy rate for the women under IVIG therapy was 92.5% and the live birth rate was 82.5%. Significantly lower pregnancy and live birth rates (25% and 12.5%, respectively) were observed for the patients with recurrent pregnancy loss and NK/NKT‐like cells expansion without IVIG. After three cycles of IVIG, NK cell percentages decreased significantly and these values persisted throughout gestation.
Conclusion
Intravenous immunoglobulin therapy for women with RRF and NK or NKT‐like cell expansion was a safe and beneficial therapeutic strategy that associated with high clinical pregnancy and live birth rates.
Accountability policies through standardized testing are widespread in diverse educational systems. Based on an ethnographic research study, we sought to understand how a learning assessment policy, ...used for over three decades in primary and lower secondary education, is lived and interpreted in daily school life in Chile. This article analyzes how learning assessment policies are re-contextualized (translated and interpreted) in three elementary and high schools located in poor neighborhoods with different performance categorization according to students’ test results. We conducted interviews and observations with teachers and school leadership team members. Results show that school actors experience the effects of testing both as a menace and as a pressure despite their different school categorization performance. They consider the tests a decontextualized and unjust measurement and therefore respond with similar strategies that seek to avoid these negative consequences. This study contributes to understanding the effects of tight accountability systems that attempt to place different levels of pressure through categorization.
Problem
Recurrent reproductive failure (RRF) has been associated with expansion of circulating NK cells, key cells for maternal tolerance, decidual vasculogenesis and embryo growth. This study ...reports our experience in intravenous immunoglobulin (IVIg) therapy of a large cohort of women with RRF with expanded circulating NK and/or NKT‐like cells (blood NKT cells are a heterogeneous subset of T cells that share properties of both T cells and NK cells).
Method of study
Observational study of RRF women with NK or NKT‐like expansion (>12% or 10% cutoff levels of total lymphocytes, respectively), treated with IVIg for the next gestation.
Results
By multivariant logistic regression analysis after adjusting for age, NK cells subsets and other therapies, IVIg significantly improved the live birth rate to 96.3% in women with recurrent miscarriage (RM) compared with 30.6% in case not receiving IVIg (P < 0.0001). In women with recurrent implantation failure (RIF), in comparison with women not receiving IVIg, treatment increased the pregnancy rate from 26.2 to 93.8% (P ≤ 0.0001) and the live birth rate from 17.9 to 80.0% in RIF (P ≤ 0.0001).
Conclusions
Immunomodulation with IVIg in our selected group of RRF patients with immunologic alterations enhanced clinical pregnancy and live birth rates. Our results may facilitate the design of future clinical trials of IVIg in this pathology.
PDF
