Trained immunity in organ transplantation

Consistent induction of donor‐specific unresponsiveness in the absence of continuous immunosuppressive therapy and toxic effects remains a difficult task in clinical organ transplantation. Transplant immunologists have developed numerous experimental treatments that target antigen‐presentation (signal 1), costimulation (signal 2), and cytokine production (signal 3) to establish transplantation tolerance. While promising results have been obtained using therapeutic approaches that predominantly target the adaptive immune response, the long‐term graft survival rates remain suboptimal. This suggests the existence of unrecognized allograft rejection mechanisms that contribute to organ failure. We postulate that trained immunity stimulatory pathways are critical to the immune response that mediates graft loss. Trained immunity is a recently discovered functional program of the innate immune system, which is characterized by nonpermanent epigenetic and metabolic reprogramming of macrophages. Since trained macrophages upregulate costimulatory molecules (signal 2) and produce pro‐inflammatory cytokines (signal 3), they contribute to potent graft reactive immune responses and organ transplant rejection. In this review, we summarize the detrimental effects of trained immunity in the context of organ transplantation and describe pathways that induce macrophage training associated with graft rejection.     

Inpatient Physicians and Nurses With Dual Diagnosis: An Exploratory Study

Objective: This study explored the clinical features of physicians and nurses with dual diagnosis.

 Methods: We conducted a retrospective review of 150 medical records of physicians (n = 120) and nurses (n = 30) admitted from February 2008 to February 2011 to the Barcelona Psychiatric Inpatient Unit for Health Professionals. Routine intake included the Spanish version of the Psychiatric Research Interview for Substance and Mental Disorders (PRISM-IV) and a clinical interview.

 Results: The mean age of participants was 48.59 (SD = 8.9) years and 57.3% were male. Patients experienced substance dependence with alcohol (n = 112, 74.7%), sedatives (n = 59, 39.3%), cocaine (n = 24, 16%), other stimulants (n = 15, 10%), and opiates other than heroin (n = 16, 10.7%). About 41% (n = 61) also met criteria for a mental health disorder, mainly major depressive disorder (n = 42, 28%), while 8% (n = 12) had attention deficit hyperactivity disorder. A high proportion of physicians (n = 95, 79.2%) and nurses (n = 25, 83.3%) had nicotine dependence. The most common comorbidity was alcohol dependence and major depressive disorder. No differences were found between groups in the prevalence of substance use disorders, mental health disorders, and dual diagnosis.

 Conclusions: Dual diagnosis is a common condition among inpatient physicians and nurses with substance use disorders and its clinical presentation may be similar in both groups.     

Beneficial dose conversion after switching from higher doses of shorter-acting erythropoiesis-stimulating agents to C.E.R.A in CKD patients in clinical practice: MINERVA Study

Purpose

To assess whether the correction dose recommended by the summary of product characteristics was adequate and to confirm the adequacy of the recommended conversion dosing strategies from shorter-acting erythropoiesis-stimulating agents (ESAs) to continuous erythropoietin receptor activator (C.E.R.A) in anaemic chronic kidney disease (CKD) patients in the clinical setting.

Methods

This was a 12-month, multicenter, prospective, observational study in anaemic CKD patients on haemodialysis and not on dialysis receiving C.E.R.A (at least one dose).

Results

A total of 227 patients were included (not on dialysis; n = 142; haemodialysis: n = 85). The present analysis was conducted on ESA-naïve patients (not on dialysis: n = 31) and patients switched from other ESA (not on dialysis: n = 63; haemodialysis: n = 57). Both on and not on dialysis patients switched from other ESA received lower starting C.E.R.A doses than those recommended, and remained stable during the 12-month period. The higher the previous ESA dose was, the more beneficial the C.E.R.A dose conversion factor was. The proportion of patients with stable haemoglobin within the target range (11–13 g/dL) did not vary during the 12-month period both in nondialysis CKD patients and in those undergoing dialysis [baseline: 42 (66.7 %) and 34 (59.6 %); month 6: 21 (55.3 %) and 26 (50.0 %); month 12: 20 (64.5 %) and 25 (69.4 %), respectively]. In naïve patients, the mean weight-adjusted C.E.R.A dose during the study (1.19 ± 0.49 µg/kg/month) was similar to the recommended one. C.E.R.A was well tolerated.

Conclusions

Conversion from shorter-acting ESAs to C.E.R.A doses lower than those recommended can efficiently maintain target haemoglobin levels both in nondialysis and haemodialysis CKD patients, particularly when switching from higher ESA doses. A monthly C.E.R.A dose of 1.2 µg/Kg seems adequate for anaemia correction.     

One-Stage Revision Arthroplasty Using Cementless Stem for Infected Hip Arthroplasties

The objective of this retrospective study was to evaluate our results with one-stage revision using cementless femoral stem for infected hip arthroplasties. Twenty-four patients were included in the study. The acetabular component was cemented in 9 cases. In 2 patients a structured bone allograft was necessary to fill an acetabular defect. After a mean follow-up of 44.6 months, 23 patients showed no signs of infection (95.8%), the mean functional response according to the Merle d’Aubigné scale was 13.8 and the mean Harris Hip Score was 65.4. One-stage revision hip arthroplasty using cementless femoral stem was associated with a high success rate.     

Highly reactive 2-deoxy-2-iodo-d-allo and d-gulo pyranosyl sulfoxide donors ensure β-stereoselective glycosylations with steroidal aglycones

The preparation of well-defined d-xylo and d-ribo glycosides represents a synthetic challenge due to the limited configurational availability of starting materials and the laborious synthesis of homogeneous 2-deoxy-β-glycosidic linkages, in particular that of the sugar-steroid motif, which represents the “stereoselective determining step” of the overall synthesis. Herein we describe the use of 2-deoxy-2-iodo-glycopyranosyl sulfoxides accessible from widely available d-xylose and d-ribose monosaccharides as privileged glycosyl donors that permit activation at very low temperature. This ensures a precise kinetic control for a complete 1,2-trans stereoselective glycosylation of particularly challenging steroidal aglycones.

Highly stereoselective synthesis of challenging steroidal 2-deoxy-β-glycosides with d-xylo and d-ribo configurations enabled by low temperature activation of 2-deoxy-2-iodoglycopyranosyl sulfoxides.     

Maturity Assessment model for Patient Blood Management to assist hospitals in improving patients’ safety and outcomes. The MAPBM project

BackgroundPatient blood management (PBM) is an evidence-based care bundle with proven ability to improve patients’ outcomes by managing and preserving the patient’s own blood. Since 2010, the World Health Organisation has urged member states to implement PBM. However, there has been limited progress in developing PBM programmes in hospitals due to the implicit challenges of implementing them. To address these challenges, we developed a Maturity Assessment Model (MAPBM) to assist healthcare organisations to measure, benchmark, assess in PBM, and communicate the results of their PBM programmes. We describe the MAPBM model, its benchmarking programme, and the feasibility of implementing it nationwide in Spain.Materials and methodsThe MAPBM considers the three dimensions of a transformation effort (structure, process and outcomes) and grades these within a maturity scale matrix. Each dimension includes the various drivers of a PBM programme, and their corresponding measures and key performance indicators. The structure measures are qualitative, and obtained using a survey and structured self-assessment checklist. The key performance indicators for process and outcomes are quantitative, and based on clinical data from the hospitals’ electronic medical records. Key performance indicators for process address major clinical recommendations in each PBM pillar, and are applied to six common procedures characterised by significant blood loss.ResultsIn its first 5 years, the MAPBM was deployed in 59 hospitals and used to analyse 181,826 hospital episodes, which proves the feasibility of implementing a sustainable model to measure and compare PBM clinical practice and outcomes across hospitals in Spain.ConclusionThe MAPBM initiative aims to become a useful tool for healthcare organisations to implement PBM programmes and improve patients’ safety and outcomes.