Implementation of an anaemia walk-in clinic: Feasibility and preliminary data from the Orthopedic University Hospital.

BACKGROUND: Approximately one in three patients suffers from preoperative anaemia. Even though haemoglobin is measured before surgery, anaemia management is not implemented in every hospital. OBJECTIVE: Here, we demonstrate the implementation of an anaemia walk-in clinic at an Orthopedic University Hospital. To improve the diagnosis of iron deficiency (ID), we examined whether reticulocyte haemoglobin (Ret-He) could be a useful additional parameter. MATERIAL AND METHODS: In August 2019, an anaemia walk-in clinic was established. Between September and December 2019, major orthopaedic surgical patients were screened for preoperative anaemia. The primary endpoint was the incidence of preoperative anaemia. Secondary endpoints included Ret-He level, red blood cell (RBC) transfusion rate, in-hospital length of stay and anaemia at hospital discharge. RESULTS: A total of 104 patients were screened for anaemia. Preoperative anaemia rate was 20.6%. Intravenous iron was supplemented in 23 patients. Transfusion of RBC units per patient (1.7 ± 1.2 vs. 0.2 ± 0.9; p = 0.004) and hospital length of stay (13.1 ± 4.8 days vs. 10.6 ± 5.1 days; p = 0.068) was increased in anaemic patients compared to non-anaemic patients. Ret-He values were significantly lower in patients with ID anaemia (33.3 pg [28.6-40.2 pg]) compared to patients with ID (35.3 pg [28.9-38.6 pg]; p = 0.015) or patients without anaemia (35.4 pg [30.2-39.4 pg]; p = 0.001). CONCLUSION: Preoperative anaemia is common in orthopaedic patients. Our results proved the feasibility of an anaemia walk-in clinic to manage preoperative anaemia. Furthermore, our analysis supports the use of Ret-He as an additional parameter for the diagnosis of ID in surgical patients.

The Emerging Therapeutic Potential of Nitro Fatty Acids and Other Michael Acceptor-Containing Drugs for the Treatment of Inflammation and Cancer.

Nitro fatty acids (NFAs) are endogenously generated lipid mediators deriving from reactions of unsaturated electrophilic fatty acids with reactive nitrogen species. Furthermore, Mediterranean diets can be a source of NFA. These highly electrophilic fatty acids can undergo Michael addition reaction with cysteine residues, leading to post-translational modifications (PTM) of selected regulatory proteins. Such modifications are capable of changing target protein function during cell signaling or in biosynthetic pathways. NFA target proteins include the peroxisome proliferator-activated receptor γ (PPAR-γ), the pro-inflammatory and tumorigenic nuclear factor-κB (NF-κB) signaling pathway, the pro-inflammatory 5-lipoxygenases (5-LO) biosynthesis pathway as well as soluble epoxide hydrolase (sEH), which is essentially involved in the regulation of vascular tone. In several animal models of inflammation and cancer, the therapeutic efficacy of well-tolerated NFA has been demonstrated. This has already led to clinical phase II studies investigating possible therapeutic effects of NFA in subjects with pulmonary arterial hypertension. Albeit Michael acceptors feature a broad spectrum of bioactivity, they have for a rather long time been avoided as drug candidates owing to their presumed unselective reactivity and toxicity. However, targeted covalent modification of regulatory proteins by Michael acceptors became recognized as a promising approach to drug discovery with the recent FDA approvals of the cancer therapeutics, afatanib (2013), ibrutinib (2013), and osimertinib (2015). Furthermore, the Michael acceptor, neratinib, a dual inhibitor of the human epidermal growth factor receptor 2 and epidermal growth factor receptor, was recently approved by the FDA (2017) and by the EMA (2018) for the treatment of breast cancer. Finally, a number of further Michael acceptor drug candidates are currently under clinical investigation for pharmacotherapy of inflammation and cancer. In this review, we focus on the pharmacology of NFA and other Michael acceptor drugs, summarizing their potential as an emerging class of future antiphlogistics and adjuvant in tumor therapeutics.

Patient blood management implementation strategies and their effect on physicians' risk perception, clinical knowledge and perioperative practice - the frankfurt experience.

INTRODUCTION: A multicomponent, evidence-based and interdisciplinary Patient Blood Management (PBM) program was introduced at the University Hospital Frankfurt in July 2013. The implementation strategy included practical and tactical components aimed to increase knowledge on the risks of preoperative anemia, to standardize hemotherapy, and to facilitate PBM components. METHODS: This article analyzes barriers to PBM implementation and outlines a strategy to introduce and manifest PBM. The effects in Frankfurt were measured in a before and after questionnaire study distributed among groups of physicians immediately before and 1 year after PBM implementation. RESULTS: 142 clinicians completed the questionnaire in July 2013 and 101 clinicians in August 2014. Absolute certainty that the treatment of preoperative anemia favorably influences morbidity and mortality rose from 25 to 37%. Transfusion behavior seems to have been affected: In 2014, 56% of clinicians stated that they clinically reassess the patient and analyze hemoglobin following each single red blood cell unit compared to only 38% stating this in 2013. CONCLUSION: These results show that our implementation strategy was effective in changing physicians' risk perception, attitude, and knowledge on PBM principles. Our experience highlights key success factors for the implementation of a comprehensive PBM program.

Mild hypothermia alone or in combination with anesthetic post-conditioning reduces expression of inflammatory cytokines in the cerebral cortex of pigs after cardiopulmonary resuscitation.

INTRODUCTION: Hypothermia improves survival and neurological recovery after cardiac arrest. Pro-inflammatory cytokines have been implicated in focal cerebral ischemia/reperfusion injury. It is unknown whether cardiac arrest also triggers the release of cerebral inflammatory molecules, and whether therapeutic hypothermia alters this inflammatory response. This study sought to examine whether hypothermia or the combination of hypothermia with anesthetic post-conditioning with sevoflurane affect cerebral inflammatory response after cardiopulmonary resuscitation. METHODS: Thirty pigs (28 to 34 kg) were subjected to cardiac arrest following temporary coronary artery occlusion. After seven minutes of ventricular fibrillation and two minutes of basic life support, advanced cardiac life support was started according to the current American Heart Association guidelines. Return of spontaneous circulation was achieved in 21 animals who were randomized to either normothermia at 38 degrees C, hypothermia at 33 degrees C or hypothermia at 33 degrees C combined with sevoflurane (each group: n = 7) for 24 hours. The effects of hypothermia and the combination of hypothermia with sevoflurane on cerebral inflammatory response after cardiopulmonary resuscitation were studied using tissue samples from the cerebral cortex of pigs euthanized after 24 hours and employing quantitative RT-PCR and ELISA techniques. RESULTS: Global cerebral ischemia following resuscitation resulted in significant upregulation of cerebral tissue inflammatory cytokine mRNA expression (mean +/- SD; interleukin (IL)-1beta 8.7 +/- 4.0, IL-6 4.3 +/- 2.6, IL-10 2.5 +/- 1.6, tumor necrosis factor (TNF)alpha 2.8 +/- 1.8, intercellular adhesion molecule-1 (ICAM-1) 4.0 +/- 1.9-fold compared with sham control) and IL-1beta protein concentration (1.9 +/- 0.6-fold compared with sham control). Hypothermia was associated with a significant (P < 0.05 versus normothermia) reduction in cerebral inflammatory cytokine mRNA expression (IL-1beta 1.7 +/- 1.0, IL-6 2.2 +/- 1.1, IL-10 0.8 +/- 0.4, TNFalpha 1.1 +/- 0.6, ICAM-1 1.9 +/- 0.7-fold compared with sham control). These results were also confirmed for IL-1beta on protein level. Experimental settings employing hypothermia in combination with sevoflurane showed that the volatile anesthetic did not confer additional anti-inflammatory effects compared with hypothermia alone. CONCLUSIONS: Mild therapeutic hypothermia resulted in decreased expression of typical cerebral inflammatory mediators after cardiopulmonary resuscitation. This may confer, at least in part, neuroprotection following global cerebral ischemia and resuscitation.