•Why carry out this study?•Does sex matter? The importance of sex inequalities in solid organ transplantation.•There is limited evidence assessing the impact of sex on transplant recipient ...outcomes.•What was learned from the study?•Females account for 1/3 of the solid organ transplant recipient's cohort and have higher survival than males after liver and kidney transplant.•Allograft dysfunction was influenced by combination of donor-recipient sex and age.•Consider sex as a factor to optimize the management of transplant patients.
Sex disparities are related to biological differences, which may have significant impact on patient and allograft outcomes. The aim was to investigate the impact of sex on clinical and safety outcomes after solid organ transplantation (SOT).
A systematic review and meta-analysis was performed. Observational studies comparing females vs. males after SOT were considered for inclusion after a systematic search of the Pubmed, Cochrane Library, and Web of Science databases conducted from 2016 to 2021. Primary outcome was mortality. PROSPERO register number: CRD42021282615.
After retrieving 1103 studies, 22 observational studies (1,045,380 subjects) were finally deemed eligible for inclusion. Females accounted 36.3% of SOT recipients, but presented significantly lower mortality (odds ratio (OR): 0.87, 95% confidence interval (CI): 0.83–0.92, I2=78%). In subgroup analyses, mortality was significantly lower in females undergoing liver (OR: 0.89 95%CI: 0.86–0.92, I2=0%) or kidney transplantation (OR: 0.82 95%CI: 0.76–0.89, I2=72%). Male sex was consistently reported as a protective factor against hospital readmission. Among the outcomes, allograft dysfunction was influenced by a combination of donor-recipient sex and age. Data on overall infections were inconclusive. Several reports suggest a higher risk of malignancy among males.
Females represent one-third of SOT recipients but have higher survival rates than males after liver and kidney transplantation. The impact on graft dysfunction was heterogeneous. While further research is warranted, our findings should encourage clinicians and researchers to consider sex as a factor when taking decisions regarding SOT management.
•IA use in stable NCFB had microbiologic benefit with 10% reduction of exacerbations.•IA therapy in NCFB increased antimicrobial resistance, with NNT of 6.•Minimal benefit in terms of ...patient-centered outcomes was documented.•Further research is required in high inflammatory phenotypes and alternative strategies.
Inhaled antibiotics (IA) in non-cystic fibrosis bronchiectasis (NCFB) are recommended by some clinical practice guidelines for prevention or treatment of NCFB exacerbations.
We performed a systematic review and meta-analysis to evaluate the efficacy and safety of IA use for treatment of adults with NCFB and Pseudomonas aeruginosa chronic bronchial infection. The search was performed in the Cochrane Library, PubMed, and Web of Science databases from 2000 to 2019. Studies of IA for treatment of stable or exacerbated NCFB adults (≥18 years) with P. aeruginosa infection were considered eligible. PROSPERO Registration number: CRD42019136154.
Twelve trials (2476 participants) were included. IA therapy increased P. aeruginosa eradication from sputum in patients with exacerbations (OR: 3.19, 95%CI: 1.70–5.99) with similar effects on stable patients (OR: 7.22, 95%CI: 2.81–18.59), and a trend to reduced emergence of new respiratory pathogens (OR: 0.58, 95%CI: 0.28–1.18). IA achieved significant reduced exacerbation rates (RR: 0.90; 95%CI: 0.82–0.98) in stable patients, with a number needed to treat (NNT) of 59, but no significant changes in FEV1, mortality, hospitalizations or quality of life were identified. In stable patients, IA use increased antimicrobial resistance (RR: 2.10, 95%CI: 1.35–3.27) at the end of therapy, with a number needed to treat of 6.
IA therapy achieved a statistically significant eradication of P. aeruginosa from sputum, with a 10% reduction of exacerbations in stable patients. This effect has to be balanced with significant increases in antimicrobial resistance. Our meta-analysis failed to show a significant benefit in terms of patient-centered outcomes.
Intensive care to facilitate organ donation (ICOD) has been defined as the initiation or continuation of intensive care measures in patients with a devastating brain injury (DBI) in whom treatment ...for curative purposes is deemed futile, and who are considered possible organ donors, with the aim of offering donation after brain death (DBD) inside their end-of-life care plans. We describe the effect on the donation and transplantation activity of the implementation of ICOD protocol at a university hospital.
Retrospective analysis (2015-2018) of demographics and outcomes of all patients with a DBI, in whom ICOD was considered as part of their end-of-life care in Vall d’Hebron University Hospital, Barcelona.
Of the 983 possible donors evaluated, ICOD was considered in 206 (21%), of whom 115 (55.8%) were medically unsuitable for donation. Family consent was obtained for 69 (76%) of the remaining patients. Refusal rate was twice as high when nontherapeutic ventilation was required for organ donation (34%) vs patients previously ventilated (13.6%) (P = .02). Patients subject to ICOD died in a median of 2 days (1-3 d) and 88.4% became actual donors (39 after brain death; 22 after circulatory death). Nine (17.6%) donors were finally not utilized. ICOD contributed to 29% (ranging from 27.7% in 2015 to 31.6% in 2018) of the 208 actual donors and 26% of the 603 organs transplanted.
ICOD is well-accepted by families and offers the donation option to an increasing number of patients at our hospital. It provides an important and sustained increment of the organ pool for transplantation.
•New technologies can help detect and refer possible donors outside the intensive care unit (ICU).•Intensive care to facilitate organ donation (ICOD) is as well accepted by families as other standard scenarios in organ donation.•Nontherapeutic ventilation is the cornerstone in the consent for ICOD.•ICOD permits organ donation to increase by up to one third.•ICOD represents less than 1% of ICU admissions with a median stay of only 2 days.
Background
The aim was to identify the causing organisms and assess the association of procalcitonin (PCT) with bacterial pneumonia within 24 hours of intensive care unit admission (ICU‐A) among lung ...transplant (LT) adult recipients.
Methods
Secondary analysis from a prospective cohort study. All LT adults admitted to ICU for acute respiratory failure (ARF) over 5 years were included. Patients were followed until hospital discharge or death.
Results
Fifty‐eight consecutive LT patients were enrolled. The most important cause of ICU‐A due to ARF was pneumonia 29 (50%) followed by acute rejection 3 (5.2%) and bronchiolitis obliterans syndrome exacerbation 3 (5.2%). Microorganisms were isolated from 22/29 cases with pneumonia (75.9%): 17 (77.2%) bacterial, 4 (18.2%) viral, 1 (4.5%) Aspergillus fumigates, with Pseudomonas aeruginosa being the most common cause (45.5%) of pneumonia, with 10 patients presenting chronic colonization by P aeruginosa. Median Interquartile range (IQR) PCT levels within 24 hours after admission were higher in pneumonia (1.5 µg/L; IQR:0.3‐22.0), than in non‐pneumonia cases (0.2 µg/L; IQR:0.1‐0.7) (P = .019) and PCT levels within 24 hours helped to discriminate bacterial pneumonia (8.2 µg/L; IQR:0.2‐43.0) from viral pneumonia and non‐pneumonia cases (0.2 µg/L; IQR:0.1‐0.7). The overall negative predictive value for bacterial pneumonia was 85.1%, increasing to 91.6% among episodes after 6 months of LT.
Conclusions
Causes of severe pneumonia in LT are changing, with predominant role of P aeruginosa and respiratory viruses. PCT ≤ 0.5 μg/L within 24 hours helps to exclude bacterial pneumonia diagnosis in LT adults requiring ICU‐A. A negative PCT test allows antimicrobial de‐escalation and requires an alternative diagnostic to bacterial pneumonia.
Autoimmune thyroid diseases are the most common types of autoimmune diseases, but their physiopathology is still relatively unexplored. Genotype-tissue expression (GTEx) is a publicly available ...repository containing RNAseq data, including profiles from thyroid. Approximately 14.8% of these glands were affected by focal lymphocytic thyroiditis and 6.3% were annotated as Hashimoto. We interrogated these data to improve the characterization of infiltrating cells and to identify new molecular pathways active in autoimmune thyroiditis.
Histological GTEx images of 336 thyroid samples were classified into three categories, that is, non-infiltrated thyroid, small focal infiltrated thyroid, and extensive lymphoid infiltrated thyroid. Differentially expressed genes among these categories were identified and subjected to
pathway enrichment analysis accordingly. CIBERSORTx deconvolution was used to characterize infiltrating cells.
As expected, most of the transcriptional changes were dependent on tissue infiltration. Upregulated genes in tissues include-in addition to lineage-specific B and T cell genes-a broad representation of inhibitory immune checkpoint receptors expressed by B and T lymphocytes. CIBERSORTx analysis identified 22 types of infiltrating cells showed that T cells predominate 3:1 over B cells in glands with small infiltrates, only by 1.7:1 in those with large infiltrates. Follicular helper and memory CD4 T cells were significantly more abundant in glands with large infiltrates (
< 0.0001), but the most prominent finding in these glands was an almost sixfold increase in the number of naive B cells (
< 0.0001). A predominance of M2 macrophages over M1 and M0 macrophages was observed in the three gland categories (
< 0.001).
Analysis of transcriptomic RNA-seq profiles constitutes a rich source of information for the analysis of autoimmune tissues. High-resolution transcriptomic data analysis of thyroid glands indicates the following: (a) in all infiltrated glands, active autoimmune response coexists with suppressor counteracting mechanisms involving several inhibitory checkpoint receptor pairs, (b) glands with small infiltrates contain an unexpected relatively high proportion of B lymphocytes, and (c) in highly infiltrated glands, there is a distinct transcriptomic signature of active tertiary lymphoid organs. These results support the concept that the autoimmune response is amplified in the thyroid tissue.
Intensive Care to facilitate Organ Donation (ICOD) consists of the initiation or continuation of intensive care measures in patients with a devastating brain injury (DBI) in whom curative treatment ...is deemed futile and death by neurological criteria (DNC) is foreseen, to incorporate organ donation into their end-of-life plans. In this study we evaluate the outcomes of patients subject to ICOD and identify radiological and clinical factors associated with progression to DNC. In this first prospective multicenter study we tested by multivariate regression the association of clinical and radiological severity features with progression to DNC. Of the 194 patients, 144 (74.2%) patients fulfilled DNC after a median of 25 h (95% IQR: 17-44) from ICOD onset. Two patients (1%) shifted from ICOD to curative treatment, both were alive at discharge. Factors associated with progression to DNC included: age below 70 years, clinical score consistent with severe brain injury, instability, intracranial hemorrhage, midline shift ≥5 mm and certain types of brain herniation. Overall 151 (77.8%) patients progressed to organ donation. Based on these results, we conclude that ICOD is a beneficial and efficient practice that can contribute to the pool of deceased donors.
The study of the immune response in thyroid autoimmunity has been mostly focused on the autoantibodies and lymphocytes, but there are indications that intrinsic features of thyroid tissue cells may ...play a role in disrupting tolerance that needs further investigation. The overexpression of HLA and adhesion molecules by thyroid follicular cells (TFC) and our recent demonstration that PD-L1 is also moderately expressed by TFCs in autoimmune thyroid indicates that TFCs they may activate but also inhibit the autoimmune response. Intriguingly, we have recently found that in vitro cultured TFCs are able to suppress the proliferation of autologous lymphocyte T in a contact-dependent manner which is independent of the PD-1/PD-L1 signaling pathway.
To get a more comprehensive picture of TFC activating and inhibitory molecules/pathways driving the autoimmune response in the thyroid glands, preparations of TFCs and stromal cells from five Graves’ disease (GD) and four control thyroid glands were compared by scRNA-seq. The results confirmed the previously described interferon type I and type II signatures in GD TFCs and showed unequivocally that they express the full array of genes that intervene in the processing and presentation of endogenous and exogeneous antigens. GD TFCs lack however expression of costimulatory molecules CD80 and CD86 required for priming T cells. A moderate overexpression of CD40 by TFCs was confirmed. GD Fibroblasts showed widespread upregulation of cytokine genes.
The results from this first single transcriptomic profiling of TFC and thyroid stromal cells provides a more granular view of the events occurring in GD. The new data point at an important contribution of stromal cells and prompt a major re-interpretation of the role of MHC over-expression by TFC, from deleterious to protective. Most importantly this re-interpretation could also apply to other tissues, like pancreatic beta cells, where MHC over-expression has been detected in diabetic pancreas.
•Thyroid transcriptional changes are driven by IFN II response signature.•Proinflammatory cytokines and chemokines are expressed in control thyroids.•Thyrocytes in autoimmune expressed HLA genes but no costimulatory molecules.•Immunoregulatory genes are expressed by control and autoimmune thyrocytes.•Wound healing and structural signaling pathways are enhanced in autoimmunity.
Brain death triggers a systemic inflammatory response. Whether systemic inflammation is different in lung donors after brain- (DBD) or circulatory-death (DCD) is unknown, but this may potentially ...increase the incidence of primary graft dysfunction (PGD) after lung transplantation. We compared the plasma levels of interleukin (IL)-6, IL-8, IL-10 and TNF-α in BDB and DCD and their respective recipients, as well as their relationship with PGD and mortality after LT. A prospective, observational, multicenter, comparative, cohort-nested study that included 40 DBD and 40 DCD lung donors matched and their respective recipients. Relevant clinical information and blood samples were collected before/during lung retrieval in donors and before/during/after (24, 48 and 72 h) LT in recipients. Incidence of PGD and short-term mortality after LT was recorded. Plasma levels of all determined cytokines were numerically higher in DBD than in DCD donors and reached statistical significance for IL-6, IL-10 and IL-8. In recipients with PGD the donor’s plasma levels of TNF-α were higher. The post-operative mortality rate was very low and similar in both groups. DBD is associated with higher systemic inflammation than DCD donors, and higher TNF-α plasma levels in donors are associated with a higher incidence of PGD.
Immune Checkpoint Receptors include a number of inhibitory receptors that limit tissue damage during immune responses; blocking PD-1/PD-L1 checkpoint receptor axis led to a paradigm shift in cancer ...immunotherapy but also to autoimmune adverse effects, prominently thyroid autoimmunity. Although PD-L1 is known to be expressed on thyroid follicular cells (TFCs) of autoimmune glands the role on PD-1/PD-L1 in the interaction between T cells and thyroid cells in the tissue has not been investigated. Here we report that autologous primary TFCs, but not transformed TFCs, inhibit CD4 and CD8 T cell proliferation but no cytokine production. This effect is not, however, mediated by PD-1/PD-L1 nor locally produced cytokines. Beta galactosidase analysis excluded culture-induced senescence as an explanation. High resolution flow cytometry demonstrated that autologous TFC/T cells co-culture induced the expansion of several clusters of double negative (DN) T cells characterized by high expression of activation markers and negative immune checkpoints. Single cell transcriptomic profiling demonstrated that dissociated TFC express numerous candidate molecules for mediating this suppressive activity, including CD40, E-Cadherin and TIGIT ligands. These ligands directly or through the generation of a suppressor population of DN T cells, and not the PD-1/PD-L1 axis, are most likely the responsible of TFC immunosuppressive activity. These results contribute to reveal the complex network of inhibitory mechanism that operate at the tissue level to restrain autoimmunity but also point to pathways, other that PD-1/PD-L1, that can contribute to tumor evasion.
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•Cultured primary thyroid follicular cells (TFCs) spontaneously express PD-L1.•Autologous primary thyrocytes reduce T cell proliferation in vitro.•Proliferation inhibition is contact dependent, but is not mediated by PD-L1.•scRNA-seq allowed identification of candidate inhibitory molecules.
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