Empagliflozin and Dapagliflozin Reduce ROS Generation and Restore NO Bioavailability in Tumor Necrosis Factor α-Stimulated Human Coronary Arterial Endothelial Cells.

Background/aims: Heart failure is characterized by chronic low-grade vascular inflammation, which in itself can lead to endothelial dysfunction. Clinical trials showed reductions in heart failure-related hospitalizations of type 2 diabetic patients using sodium glucose co-transporter 2 inhibitors (SGLT2i's). Whether and how SGLT2i's directly affect the endothelium under inflammatory conditions is not completely understood.

Insights into postoperative respiration by using continuous wireless monitoring of respiratory rate on the postoperative ward: a cohort study.

Change of respiratory rate (RespR) is the most powerful predictor of clinical deterioration. Brady- (RespR ≤ 8) and tachypnea (RespR ≥ 31) are associated with serious adverse events. Simultaneously, RespR is the least accurately measured vital parameter.

Impact of Ca-Sensitive Potassium Channels in Levosimendan-Induced Postconditioning.

Purpose: Small and big conductance Ca-sensitive potassium (K) channels are involved in cardioprotective measures aiming at reducing myocardial reperfusion injury. For levosimendan, infarct size-reducing effects were shown. Whether activation of these channels is involved in levosimendan-induced postconditioning is unknown.

Volume incompliance and transfusion are essential for transfusion-associated circulatory overload: a novel animal model.

Background: Transfusion-associated circulatory overload (TACO) is the predominant complication of transfusion resulting in death. The pathophysiology is poorly understood, but inability to manage volume is associated with TACO, and observational data suggest it is different from simple cardiac overload due to fluids. We developed a two-hit TACO animal model to assess the role of volume incompliance ("first-hit") and studied whether volume overload ("second-hit") by red blood cell (RBC) transfusion is different compared to fluids (Ringer's lactate [RL]).

Timing of Preoperative Antibiotic Prophylaxis and Surgical Site Infection: TAPAS, An Observational Cohort Study.

Objective: To test the hypothesis that surgical site infection (SSI) risk differs, after administration of surgical antibiotic prophylaxis (SAP) within 60-30 or 30-0 minutes before incision.

Background: The importance of appropriate timing of SAP before surgery has long been recognized. However, available evidence is contradictive on the best timing within a 60-0 minutes time interval before incision.

Characteristics of Dexmedetomidine Postconditioning in the Field of Myocardial Ischemia-Reperfusion Injury.

Background: Timing and onset of myocardial ischemia are mostly unpredictable. Therefore, postconditioning could be an effective cardioprotective intervention. Because ischemic postconditioning is an invasive and not practicable treatment, pharmacological postconditioning would be a more suitable alternative cardioprotective measure.

High Pressure Stress Response: Involvement of NMDA Receptor Subtypes and Molecular Markers.

Professional divers who are exposed to high pressure (HP) above 1.1 MPa suffer from high pressure neurological syndrome (HPNS), which is characterized by reversible CNS hyperexcitability and cognitive and motor deficits. HPNS remains the final major constraints on deep diving at HP.

Use of a train-of-four ratio of 0.95 versus 0.9 for tracheal extubation: an exploratory analysis of POPULAR data.

Background: The prospective observational European multicentre cohort study (POPULAR) of postoperative pulmonary complications (NCT01865513) did not demonstrate that adherence to the recommended train-of-four ratio (TOFR) of 0.9 before extubation was associated with better pulmonary outcomes from the first postoperative day up to hospital discharge. We re-analysed the POPULAR data as to whether there existed a better threshold for TOFR recovery before extubation to reduce postoperative pulmonary complications in patients who had quantitative neuromuscular monitoring (87% acceleromyography).

The use of a machine-learning algorithm that predicts hypotension during surgery in combination with personalized treatment guidance: study protocol for a randomized clinical trial.

Background: Intraoperative hypotension is associated with increased morbidity and mortality. Current treatment is mostly reactive. The Hypotension Prediction Index (HPI) algorithm is able to predict hypotension minutes before the blood pressure actually decreases.

The relationship between patient factors and the refusal of analgesics in adult Emergency Department patients with extremity injuries, a case-control study.

Background and aims Previous studies have described the phenomenon of oligo-analgesia in Emergency Department patients with traumatic injuries, despite the high prevalence of pain among these patients. Besides aspects related to health care staff, patient related factors might also play a role in suboptimal pain treatment, however evidence is scarce. Therefore, the objective of the current study was to evaluate patient related factors in adult patients refusing offered analgesics during an Emergency Department presentation with extremity injuries.

Enhanced mGlu5 Signaling in Excitatory Neurons Promotes Rapid Antidepressant Effects via AMPA Receptor Activation.

Conventional antidepressants have limited efficacy and many side effects, highlighting the need for fast-acting and specific medications. Induction of the synaptic protein Homer1a mediates the effects of different antidepressant treatments, including the rapid action of ketamine and sleep deprivation (SD). We show here that mimicking Homer1a upregulation via intravenous injection of cell-membrane-permeable TAT-Homer1a elicits rapid antidepressant effects in various tests.

Isomerization of Asp7 in Beta-Amyloid Enhances Inhibition of the α7 Nicotinic Receptor and Promotes Neurotoxicity.

Cholinergic dysfunction in Alzheimer's disease (AD) can be mediated by the neuronal α7 nicotinic acetylcholine receptor (α7nAChR). Beta-amyloid peptide (Aβ) binds to the α7nAChR, disrupting the receptor's function and causing neurotoxicity. In vivo not only Aβ but also its modified forms can drive AD pathogenesis.

Use of a high platelet-to-RBC ratio of 2:1 is more effective in correcting trauma-induced coagulopathy than a ratio of 1:1 in a rat multiple trauma transfusion model.

Background: Platelet dysfunction importantly contributes to trauma-induced coagulopathy (TIC). Our aim was to examine the impact of transfusing platelets (PLTs) in a 2:1 PLT-to-red blood cell (RBC) ratio versus the standard 1:1 ratio on transfusion requirements, correction of TIC, and organ damage in a rat multiple trauma transfusion model.

Methods: Mechanically ventilated male Sprague Dawley rats were traumatized by crush injury to the small intestine and liver and a fracture of the femur, followed by exsanguination until a mean arterial pressure (MAP) of 40 mmHg.

Molecular mechanisms of action of systemic lidocaine in acute and chronic pain: a narrative review.

Systemic administration of the local anaesthetic lidocaine is antinociceptive in both acute and chronic pain states, especially in acute postoperative and chronic neuropathic pain. These effects cannot be explained by its voltage-gated sodium channel blocking properties alone, but the responsible mechanisms are still elusive. This narrative review focuses on available experimental evidence of the molecular mechanisms by which systemic lidocaine exerts its clinically documented analgesic effects.

Patient blood management in the cardiac surgical setting: An updated overview.

In cardiac surgical patients it is a complex challenge to find the ideal balance between anticoagulation and hemostasis. Preoperative anemia and perioperative higher transfusion rates are related to increased morbidity and mortality. Patient blood management (PBM) is an evidence based patient specific individualized protocol used in the perioperative setting in order to reduce perioperative bleeding and transfusion rates and to improve patient outcomes.

MiR-34a is differentially expressed in dorsal root ganglia in a rat model of chronic neuropathic pain.

Introduction: Recent evidence shows that numerous microRNAs (miRNAs) regulate pain-related genes in chronic pain. The aim of the present study was to further explore the regulation of miRNAs and their effect on the expression of pain-associated target genes in experimental neuropathic pain.

Methods: Male Wistar rats underwent chronic constriction injury (CCI) of the sciatic nerve or Sham procedure.

Opiophobia in Cancer Biology- Justified? - The Role of Perioperative Use of Opioids in Cancer Recurrence.

Opioids remain the standard of care in the provision of analgesia in the patient undergoing cancer surgery preoperatively. The effects of opioids on tumor growth and metastasis have been discussed for many years. In recent years their use as part of the perioperative pain management bundle in the patients undergoing cancer surgery has been thought to promote cancer recurrence and metastasis.

Shedding Light into the Subcutis: A Mass Spectrometry Based Immunocapture Assay Enabling Full Characterization of Therapeutic Antibodies after Injection in Vivo.

An understanding of what happens to therapeutic antibodies in vivo after subcutaneous injection is of high interest. Therefore, we applied the open flow microperfusion technique to extract interstitial fluid from the subcutaneous tissue. In order to analyze those biological samples, a specific and sensitive workflow was required.

Haemotherapy with Fibrinogen for Perioperative Bleeding Prevention-A View on Arterial Thrombogenesis and Myocardial Infarction in the Rat In Vivo.

Major blood loss during cardiac surgery is associated with increased morbidity and mortality. Clinical pilot studies indicated that preoperative fibrinogen supplementation reduces postoperative blood loss without increasing thrombotic complications. However, an increase in fibrinogen concentration might rather aggravate pre-existing thrombosis than increase the incidence of thrombotic events.

Paracetamol versus other analgesia in adult patients with minor musculoskeletal injuries: a systematic review.

Objectives: Pain treatment in acute musculoskeletal injuries usually consists of paracetamol, non-steroidal antiinflammatory drugs (NSAIDs) or opioids. It would be beneficial to determine whether paracetamol is as effective as other analgesics. The objective of this study was to evaluate available evidence regarding efficacy of paracetamol in these patients.

How incremental video training did not guarantee implementation due to fluctuating population prevalence.

Patients with stroke admitted at the neurology/neurosurgery ward of the Academic Medical Centre in Amsterdam, The Netherlands, may experience problems in communication, such as aphasia, severe confusion/delirium or severe language barriers. This may prevent self-reported pain assessment; therefore, pain behaviour observation scales are needed. In this project, we therefore aimed to implement the Rotterdam Elderly Pain Observation Scale (REPOS) by video training.

Changes in ventilator settings and ventilation-induced lung injury in burn patients-A systematic review.

Objective: Ventilation strategies aiming at prevention of ventilator-induced lung injury (VILI), including low tidal volumes (V) and use of positive end-expiratory pressures (PEEP) are increasingly used in critically ill patients. It is uncertain whether ventilation practices changed in a similar way in burn patients. Our objective was to describe applied ventilator settings and their relation to development of VILI in burn patients.