Safety of Uncrossmatched ABO-Compatible RBCs in Alloimmunized Patients with Bleeding: Data from Two Decades: Results of a Systematic Analysis in 6,109 Patients.

Introduction: Uncrossmatched ABO-compatible red blood cells (RBCs) are generally recommended in patients with life-threatening massive bleeding. There is little data regarding RBC transfusion when patients are transfused against clinically significant alloantibodies because compatible RBCs are not immediately available.

Methods/patients: All patients reviewed in this study ( = 6,109) required emergency blood transfusion and were treated at the Charité - Universitätsmedizin Berlin between 2001 and 2015.

Preclinical Characterization and Phase I Study of an Anti-HER2-TLR7 Immune-Stimulator Antibody Conjugate in Patients with HER2+ Malignancies.

Immune-stimulator antibody conjugates (ISAC) combining tumor-targeting monoclonal antibodies with immunostimulatory agents allow targeted delivery of immune activators into tumors. NJH395 is a novel, first-in-class ISAC comprising a Toll-like receptor 7 (TLR7) agonist conjugated to an anti-HER2 antibody via a noncleavable linker payload. Preclinical characterization showed ISAC-mediated activation of myeloid cells in the presence of antigen-expressing cancer cells, with antigen targeting and TLR7 agonism contributing to antitumor activity.

Interaction between voice-gender difference and spatial separation in release from masking in multi-talker listening environments.

Voice-gender difference and spatial separation between talkers are important cues for speech segregation in multi-talker listening environments. The goal of this study was to investigate the interactions of these two cues to explore how they influence masking release in normal hearing listeners. Speech recognition thresholds in competing speech were measured, and masking release benefits by either voice-gender difference or spatial separation cues were calculated.

The effect of angiotensin receptor neprilysin inhibitor, sacubitril/valsartan, on central nervous system amyloid-β concentrations and clearance in the cynomolgus monkey.

Sacubitril/valsartan (LCZ696) is the first angiotensin receptor neprilysin inhibitor approved to reduce cardiovascular mortality and hospitalization in patients with heart failure with reduced ejection fraction. As neprilysin (NEP) is one of several enzymes known to degrade amyloid-β (Aβ), there is a theoretical risk of Aβ accumulation following long-term NEP inhibition. The primary objective of this study was to evaluate the potential effects of sacubitril/valsartan on central nervous system clearance of Aβ isoforms in cynomolgus monkeys using the sensitive Stable Isotope Labeling Kinetics (SILK™)-Aβ methodology.

Osilodrostat (LCI699), a potent 11β-hydroxylase inhibitor, administered in combination with the multireceptor-targeted somatostatin analog pasireotide: A 13-week study in rats.

The somatostatin analog pasireotide and the 11β-hydroxylase inhibitor osilodrostat (LCI699) reduce cortisol levels by distinct mechanisms of action. There exists a scientific rationale to investigate the clinical efficacy of these two agents in combination. This manuscript reports the results of a toxicology study in rats, evaluating different doses of osilodrostat and pasireotide alone and in combination.

Red blood cell storage duration is associated with various clinical outcomes in pediatric cardiac surgery.

Background: Recommendations on the use of fresh red blood cells (RBCs) in pediatric patients undergoing cardiac surgery are based on limited information. Furthermore, the RBC storage time cut-off of fresh units remains unknown.

Methods: Data from 139 pediatric patients who underwent cardiac surgery and received RBCs from a single unit within 14 days of storage were analyzed.

Vascular origin of vildagliptin-induced skin effects in Cynomolgus monkeys: pathomechanistic role of peripheral sympathetic system and neuropeptide Y.

The purpose of this article is to characterize skin lesions in cynomolgus monkeys following vildagliptin (dipeptidyl peptidase-4 inhibitor) treatment. Oral vildagliptin administration caused dose-dependent and reversible blister formation, peeling and flaking skin, erosions, ulcerations, scabs, and sores involving the extremities at ≥5 mg/kg/day and necrosis of the tail and the pinnae at ≥80 mg/kg/day after 3 weeks of treatment. At the affected sites, the media and the endothelium of dermal arterioles showed hypertrophy/hyperplasia.

Blood transfusion determines postoperative morbidity in pediatric cardiac surgery applying a comprehensive blood-sparing approach.

Objective: Recently we suggested a comprehensive blood-sparing approach in pediatric cardiac surgery that resulted in no transfusion in 71 infants (25%), postoperative transfusion only in 68 (24%), and intraoperative transfusion in 149 (52%). We analyzed the effects of transfusion on postoperative morbidity and mortality in the same cohort of patients.

Methods: The effect of transfusion on the length of mechanical ventilation and intensive care unit stay was assessed using Kaplan-Meier curves.

Thawed solvent/detergent-treated plasma: too precious to be wasted after 6 hours?

Background: Coagulopathy associated with trauma and bleeding requires early administration of haemostatic agents. Solvent/detergent-treated plasma (S/D-plasma) requires thawing and its availability for clinical use is, therefore, delayed. The long-term stability of clotting factors in thawed S/D-plasma has not been thoroughly investigated.

Effects of a comprehensive blood-sparing approach using body weight-adjusted miniaturized cardiopulmonary bypass circuits on transfusion requirements in pediatric cardiac surgery.

Objectives: Transfusion-free pediatric cardiac surgery remains a challenge, mainly owing to the mismatch between the cardiopulmonary bypass (CPB) priming volume and the infants' blood volume. Within a comprehensive blood-sparing approach, we developed body weight-adjusted miniaturized CPB circuits with priming volumes of 95, 110, and 200 mL for, respectively, infants weighing less than 3 kg, 3 to 5 kg and 5 to 16 kg. We analyzed the effects of this approach on transfusion requirements and risk factors predisposing for blood transfusion.

Minimizing intraoperative hemodilution by use of a very low priming volume cardiopulmonary bypass in neonates with transposition of the great arteries.

Objective: Owing to the mismatch between cardiopulomary bypass priming volume and infants' blood volume, pediatric cardiac surgery is often associated with transfusion of homologous blood, which may increase the risk of perioperative complications. Here we report the impact of a very low volume (95-110 mL) cardiopulmonary bypass circuit during arterial switch operations in neonates with transposition of the great arteries on blood requirements, tissue oxygenation, and patient outcome.

Methods: Twenty-three consecutively treated neonates aged 2 to 17 days were treated with the blood-sparing approach.

Separation of fast from slow anabolism by site-specific PEGylation of insulin-like growth factor I (IGF-I).

Insulin-like growth factor I (IGF-I) has important anabolic and homeostatic functions in tissues like skeletal muscle, and a decline in circulating levels is linked with catabolic conditions. Whereas IGF-I therapies for musculoskeletal disorders have been postulated, dosing issues and disruptions of the homeostasis have so far precluded clinical application. We have developed a novel IGF-I variant by site-specific addition of polyethylene glycol (PEG) to lysine 68 (PEG-IGF-I).

Lyophilised plasma: evaluation of clotting factor activity over 6 days after reconstitution for transfusion.

Aims: Little is known about long-term stability of clotting factors in dissolved human lyophilised plasma. This study evaluated clotting factor and inhibitor activity in reconstituted lyophilised plasma after storage for up to 6 days at 4 degrees C.

Methods: Five samples from different lots of pooled lyophilised plasma (LyoPlas; German Red Cross Blood Transfusion Service West) were reconstituted.

The perioperative von Willebrand factor activity and factor VIII levels among alcohol use disorder patients undergoing total knee or hip replacement.

Alcohol use disorder patients have a five-fold higher risk of postoperative bleeding complications. We measured the perioperative von Willebrand factor and factor VIII levels in consecutive patients with alcohol use disorder. In one university hospital, 105 patients scheduled for arthroplasty were screened, and 25 fulfilled inclusion criteria.

Validation of a hospital-laboratory workstation for immunohematologic methods.

Background: The FREELYS Nano system (Diagast) is a manual workstation for ABO/D grouping, Rh phenotyping, K typing, and antibody screening (ABS) for immunoglobulin G (IgG) antibodies only and works with the erythrocyte-magnetized technology (EMT). The principle of EMT is based on magnetization of red blood cells and avoids centrifugation and washing steps.

Study Design And Methods: A total of 304 samples were tested with our routine blood bank methods, 100 samples for ABO/D grouping, 196 samples (100 at first evaluation, 96 at second evaluation) for Rh phenotyping and K typing (PK7200, Olympus), and 108 samples for ABS (DiaMed).

Evaluation of immunohematologic routine methods using the new erythrocyte-magnetized technology on the QWALYS 2 system.

Background: QWALYS 2 is a fully automated system for ABO/D grouping, Rh phenotyping, K typing, and antibody screening (ABS). Its new erythrocyte-magnetized technology (EMT) is based on the use of magnetic nanoparticles and avoids centrifugation and washing steps.

Study Design And Methods: Overall 499 blood samples were tested with our routine blood bank methods for ABO/D grouping, 313 samples for Rh phenotyping and K typing (microtiter plates; Olympus PK 7200), and 478 samples for ABS (gel centrifugation technique, DiaMed).

Self-regulation strategies of children with emotional disturbance.

Children with emotional disturbance frequently have difficulty regulating their classroom behaviors. Many have co-occurrence of other disabilities, such as sensory processing problems, which compound difficulties in school participation. This exploratory project evaluated the 8-week-long use of the Alert Program within the classroom setting for seven children with emotional disturbance.

Unobserved heterogeneity in trauma patients' desire for autonomy in medical decision making in an emergency department.

Background: To evaluate unobserved heterogeneity in trauma patients' desire for autonomy in medical decision making (DAD).

Material/methods: This cross-sectional study at an inner-city emergency department screened 1009 patients for DAD (using the Decision Making Preference Scale of the Autonomy Preference Index), education level, and substance use. To investigate unobserved heterogeneity, a covariate adjusted finite mixture model was established.

Socioeconomic factors, hazardous alcohol consumption, and smoking in patients with minor trauma in an inner-city emergency department.

Emergency Department (ED) patients show a high prevalence of hazardous alcohol consumption and smoking. The objective of this study was to determine if socioeconomic factors and smoking status help to optimize screening for hazardous alcohol consumption (HAC) in patients with minor trauma. A survey was conducted in an ED in an inner-city university hospital.

The effect of stress-reducing, low-dose ethanol infusion on frequency of bleeding complications in long-term alcoholic patients undergoing major surgery.

Perioperative low-dose ethanol infusion is a feasible option for stress reduction and prophylaxis of alcoholism-associated complications. Because alcohol has inhibitory effects on hemostasis, our study focused on the effect of perioperative low-dose ethanol infusion on bleeding complications, defined as transfused blood units and reoperations, in alcoholic patients undergoing major surgery. We included 44 long-term alcoholic patients scheduled for tumor resection of the aerodigestive and gastrointestinal tract.

Predictors of loss to follow-up in young patients with minor trauma after screening and written intervention for alcohol in an urban emergency department.

Objective: In health promotion studies, young age, male gender, low education, and substance use have been found to be relevant predictors of loss to follow-up. The purpose of this study was to assess factors of loss to follow-up after screening and tailored brief advice for alcohol problems in an emergency department setting.

Method: A randomized controlled intervention study was conducted and followed up at 12 months.

Peri-operative decreased cAMP levels in long-term alcoholic patients.

Long-term alcoholic patients have a five-fold higher risk of post-operative bleeding complications compared with nonalcoholic individuals. Serotonin increases and cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) decrease platelet aggregation. We examined the platelet-rich plasma levels of these substances and agonist-induced platelet aggregation in long-term alcoholic patients before and after surgery.

Cryopreservation of platelets at the end of their conventional shelf life leads to severely impaired in vitro function.

Storage time for platelet concentrates (PCs) is limited to five days due to 'aging' of the platelets and an increasing risk of bacterial proliferation. Storage time can be prolonged by cryopreservation. We investigated in vitro function of six consecutive PCs at the end of their conventional shelf life followed by cryopreservation for 24 hours.

Intervention at the level of the neuroendocrine-immune axis and postoperative pneumonia rate in long-term alcoholics.

Rationale: Postoperative pneumonia is three to four times more frequent in patients with alcohol use disorders followed by prolonged intensive care unit (ICU) stay. Long-term alcohol use leads to an altered perioperative hypothalamus-pituitary-adrenal (HPA) axis and immunity.

Objectives: The aim of this study was to evaluate HPA intervention with low-dose ethanol, morphine, or ketoconazole on the neuroendocrine-immune axis and development of postoperative pneumonia in long-term alcoholic patients.