The COVID-19 pandemic and the associated lockdown can be regarded as a forced social experiment, the results of which show how to use energy under specific conditions. During this period, there was a ...reduction in electricity consumption at the level of the power system, but a different specificity distinguishes the group of household users. The article aims at presenting and analysing the identified issues concerning residential electricity users based on the experience from the COVID-19 pandemic lockdown. Data from energy meters from almost 7000 flats in Warsaw’s housing estates during the lockdown in 2020 and the analogous period before the pandemic were used. The analysis showed that, on average, residential users staying practically the whole day in their flats increased their energy consumption, but without increasing their average daily peak power, smoothing the profile in the morning hours to the level reaching the peak power that had occurred in the analogous period before the lockdown. The peak power of the sections feeding the different numbers of dwellings also remained practically unchanged during the lockdown compared to the pre-pandemic period. The pressure to work and educate remotely should contribute to an increase in the digital competence of society, which may result in an increased interest in new forms of activity and cooperation based on demand-side response and prosumption mechanisms, with digital settlements for energy exchange and services.
Natural killer (NK) cells are part of the cellular immune response. They target mainly cancer and virally infected cells. To a high extent cytotoxic activity of NK cells is regulated inter alia by ...signals from killer immunoglobulin-like receptors (KIR). The major histocompatibility complex (MHC) class I molecules are important ligands for KIR receptors. Binding of ligands (such as MHC I) to the KIR receptors has the important role in solid organ or hematopoietic cell transplantation. Of note, the understanding of the relationship between KIR and MHC receptors may contribute to the improvement of transplant results. Donor-recipient matching, which also includes the KIR typing, may improve monitoring, individualize the treatment and allow for predicting possible effects after transplantation, such as the graft-versus-leukemia effect (GvL) or viral re-infection. There are also less evident implications of KIR/MHC matching, such as with pregnancy and cancer. In this review, we present the most relevant literature reports on the importance of the KIR/MHC relationship on NK cell activity and hematopoietic stem cell transplantation (HSCT)/solid organ transplantation (SOT) effects, the risk of allograft rejection, protection against post-transplant cytomegalovirus (CMV) infection, pregnancy complications, cancer and adoptive therapy with NK cells.
Recipient’s high resolution HLA typing is required in allogeneic hematopoietic cell transplantation from unrelated donors, as well as for haploidentical family donors. For these purposes, ...Next-Generation Sequencing (NGS) methods are the gold standard.
We present a case of a patient with an incorrect HLA typing result caused by the population of circulating lymphoma cells. The first HLA examination was performed from peripheral blood (PB) using NGS in the active phase of diffuse large B-cell lymphoma with bone marrow involvement.
Because of rare and inconclusive results, confirmed twice for the A* locus (A*02:32N), real-time polymerase chain reaction (RT-PCR)was performed. With RT-PCR method, we obtained more expected results according to the population allele frequency: in HLA-A locus (A*02:01) but also in DQB1 (DQB1*03:01, not as in NGS – DQB1*03:10). For the final verification, we used swab material and we obtained unambiguous NGS result with expected, frequent HLA-A*02:01 and DQB1*03:01 alleles corresponding to the RT-PCR result from PB.
To conclude, we suspect that the discrepancies between NGS and RT-PCR results were caused by the presence of a significant amount of circulating lymphoma cells in the peripheral blood sample. Lymphomagenic mutations may involve the histocompatibility antigen coding region and affect HLA expressed on malignant cells. This finding may be relevant for the selection of test material in primary and confirmatory HLA testing in patients with active hematological malignancies because of the strong impact of incorrect HLA typing on the procedure of a donor selection.
Background
Sodium–glucose co‐transporter 2 (SGLT2) inhibitors have been shown to reduce the risk of incident heart failure hospitalization in individuals with type 2 diabetes who have, or are at high ...risk of, cardiovascular disease. Most patients in these trials did not have heart failure at baseline and the effect of SGLT2 inhibitors on outcomes in individuals with established heart failure (with or without diabetes) is unknown.
Design and methods
The Dapagliflozin And Prevention of Adverse‐outcomes in Heart Failure trial (DAPA‐HF) is an international, multicentre, parallel group, randomized, double‐blind, study in patients with chronic heart failure, evaluating the effect of dapagliflozin 10 mg, compared with placebo, given once daily, in addition to standard care, on the primary composite outcome of a worsening heart failure event (hospitalization or equivalent event, i.e. an urgent heart failure visit) or cardiovascular death. Patients with and without diabetes are eligible and must have a left ventricular ejection fraction ≤ 40%, a moderately elevated N‐terminal pro B‐type natriuretic peptide level, and an estimated glomerular filtration rate ≥ 30 mL/min/1.73 m2. The trial is event‐driven, with a target of 844 primary outcomes. Secondary outcomes include the composite of total heart failure hospitalizations (including repeat episodes), and cardiovascular death and patient‐reported outcomes. A total of 4744 patients have been randomized.
Conclusions
DAPA‐HF will determine the efficacy and safety of the SGLT2 inhibitor dapagliflozin, added to conventional therapy, in a broad spectrum of patients with heart failure and reduced ejection fraction.
IMPORTANCE: Additional treatments are needed for heart failure with reduced ejection fraction (HFrEF). Sodium-glucose cotransporter 2 (SGLT2) inhibitors may be an effective treatment for patients ...with HFrEF, even those without diabetes. OBJECTIVE: To evaluate the effects of dapagliflozin in patients with HFrEF with and without diabetes. DESIGN, SETTING, AND PARTICIPANTS: Exploratory analysis of a phase 3 randomized trial conducted at 410 sites in 20 countries. Patients with New York Heart Association classification II to IV with an ejection fraction less than or equal to 40% and elevated plasma N-terminal pro B-type natriuretic peptide were enrolled between February 15, 2017, and August 17, 2018, with final follow-up on June 6, 2019. INTERVENTIONS: Addition of once-daily 10 mg of dapagliflozin or placebo to recommended therapy. MAIN OUTCOMES AND MEASURES: The primary outcome was the composite of an episode of worsening heart failure or cardiovascular death. This outcome was analyzed by baseline diabetes status and, in patients without diabetes, by glycated hemoglobin level less than 5.7% vs greater than or equal to 5.7%. RESULTS: Among 4744 patients randomized (mean age, 66 years; 1109 23% women; 2605 55% without diabetes), 4742 completed the trial. Among participants without diabetes, the primary outcome occurred in 171 of 1298 (13.2%) in the dapagliflozin group and 231 of 1307 (17.7%) in the placebo group (hazard ratio, 0.73 95% CI, 0.60-0.88). In patients with diabetes, the primary outcome occurred in 215 of 1075 (20.0%) in the dapagliflozin group and 271 of 1064 (25.5%) in the placebo group (hazard ratio, 0.75 95% CI, 0.63-0.90) (P value for interaction = .80). Among patients without diabetes and a glycated hemoglobin level less than 5.7%, the primary outcome occurred in 53 of 438 patients (12.1%) in the dapagliflozin group and 71 of 419 (16.9%) in the placebo group (hazard ratio, 0.67 95% CI, 0.47-0.96). In patients with a glycated hemoglobin of at least 5.7%, the primary outcome occurred in 118 of 860 patients (13.7%) in the dapagliflozin group and 160 of 888 (18.0%) in the placebo group (hazard ratio, 0.74 95% CI, 0.59-0.94) (P value for interaction = .72). Volume depletion was reported as an adverse event in 7.3% of patients in the dapagliflozin group and 6.1% in the placebo group among patients without diabetes and in 7.8% of patients in the dapagliflozin group and 7.8% in the placebo group among patients with diabetes. A kidney adverse event was reported in 4.8% of patients in the dapagliflozin group and 6.0% in the placebo group among patients without diabetes and in 8.5% of patients in the dapagliflozin group and 8.7% in the placebo group among patients with diabetes. CONCLUSIONS AND RELEVANCE: In this exploratory analysis of a randomized trial of patients with HFrEF, dapagliflozin compared with placebo, when added to recommended therapy, significantly reduced the risk of worsening heart failure or cardiovascular death independently of diabetes status. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03036124
Abstract
Aims
Concern about hypotension often leads to withholding of beneficial therapy in patients with heart failure and reduced ejection fraction (HFrEF). We evaluated the efficacy and safety of ...dapagliflozin, which lowers systolic blood pressure (SBP),according to baseline SBP in Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure trial (DAPA-HF).
Methods and results
Key inclusion criteria were: New York Heart Association Class II−IV, left ventricular ejection fraction ≤ 40%, elevated N-terminal pro-B-type natriuretic peptide level, and SBP ≥95 mmHg. The primary outcome was a composite of worsening heart failure or cardiovascular death. The efficacy and safety of dapagliflozin were examined using SBP as both a categorical and continuous variable. A total of 1205 patients had a baseline SBP <110 mmHg; 981 ≥ 110 < 120; 1149 ≥ 120 < 130; and 1409 ≥ 130 mmHg. The placebo-corrected reduction in SBP from baseline to 2 weeks with dapagliflozin was −2.54 (−3.33 to −1.76) mmHg (P < 0.001), with a smaller between-treatment difference in patients in the lowest compared to highest SBP category. Patients in the lowest SBP category had a much higher rate (per 100 person-years) of the primary outcome 20.6, 95% confidence interval (95% CI) 17.6–24.2 than those in the highest SBP category (13.8, 11.7–16.4). The benefit and safety of dapagliflozin was consistent across the range of SBP; hazard ratio (95% CI) in each SBP group, lowest to highest: 0.76 (0.60–0.97), 0.76 (0.57–1.02), 0.81 (0.61–1.08), and 0.67 (0.51–0.87), P interaction = 0.78. Study drug discontinuation did not differ between dapagliflozin and placebo across the SBP categories examined.
Conclusion
Dapagliflozin had a small effect on SBP in patients with HFrEF and was superior to placebo in improving outcomes, and well tolerated, across the range of SBP included in DAPA-HF.
Clinical Trial Registration:
ClinicalTrials.gov NCT03036124.
Graphical Abstract
Corneal transplantations (CTXs) are a vision-saving procedure. Routinely, while CTXs' survival rates remain high, the risk of graft failure increases significantly for repeated CTXs. The reason is an ...alloimmunization following previous CTXs and development of memory T (Tm) and B (Bm) cells.
We characterized populations of cells present in explanted human corneas from patients receiving the first CTX and marked as a primary CTX (PCTX) or the second or more CTXs and marked as a repeated CTX (RCTX). Cells extracted from resected corneas and from peripheral blood mononuclear cells (PBMCs) were analyzed by the flow cytometry method using multiple surface and intracellular markers.
Overall, the number of cells was similar in PCTX and RCTX patients. Extracted infiltrates from PCTXs and RCTXs contained similar numbers of T cell subsets, namely CD4+, CD8+, CD4+ Tm, CD8+ Tm, CD4+Foxp3+ T regulatory (Tregs), CD8+ Treg cells, while very few B cells (all p = NS). However, when compared to peripheral blood, PCTX and RCTX corneas contained significantly higher percentages of effector memory CD4+ and CD8+ T cells (both p < 0,05). In comparison to PCTX, RCTX group had the highest levels of Foxp3 in T CD4+ Tregs (p = 0,04) but decreased percentage of Helios-positive CD4+ Tregs.
PCTXs and especially RCTXs are rejected mainly by local T cells. The accumulation of effector CD4+ and CD8+ T cells, as well as CD4+ and CD8+ Tm cells is associated with the final rejection. Furthermore, local CD4+ and CD8+ Tregs expressing Foxp3 and Helios are probably insufficient to impose the acceptance of CTX.
•Various subsets of T cells infiltrate rejected grafts and autologous corneas before transplantation.•T regulatory cells in rejected corneas have high expression of Foxp3 and low expression of Helios.•Among T cells in corneal infiltrates, effector memory subset is the most prevalent.
The sodium-glucose cotransporter 2 inhibitor dapagliflozin reduced the risk of cardiovascular mortality and worsening heart failure in the Dapagliflozin and Prevention of Adverse Outcomes in Heart ...Failure (DAPA-HF) trial. This report explores the effect of dapagliflozin on incident type 2 diabetes (T2D) in the cohort without diabetes enrolled in the trial.
The subgroup of 2,605 patients with heart failure and reduced ejection fraction (HFrEF), no prior history of diabetes, and an HbA
of <6.5% at baseline was randomized to dapagliflozin 10 mg daily or placebo. In this exploratory analysis, surveillance for new-onset diabetes was accomplished through periodic HbA
testing as part of the study protocol and comparison between the treatment groups assessed through a Cox proportional hazards model.
At baseline, the mean HbA
was 5.8%. At 8 months, there were minimal changes, with a placebo-adjusted change in the dapagliflozin group of -0.04%. Over a median follow-up of 18 months, diabetes developed in 93 of 1,307 patients (7.1%) in the placebo group and 64 of 1,298 (4.9%) in the dapagliflozin group. Dapagliflozin led to a 32% reduction in diabetes incidence (hazard ratio 0.68, 95% CI 0.50-0.94;
= 0.019). More than 95% of the participants who developed T2D had prediabetes at baseline (HbA
5.7-6.4%). Participants who developed diabetes in DAPA-HF had a higher subsequent mortality than those who did not.
In this exploratory analysis among patients with HFrEF, treatment with dapagliflozin reduced the incidence of new diabetes. This potential benefit needs confirmation in trials of longer duration and in people without heart failure.
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