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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.Methods: In this randomized, double-blind controlled study, 122 consecutive patients undergoing elective surgery for aerodigestive tract cancer were included. Long-term alcohol use was defined as consuming at least 60 g of ethanol daily and fulfilling the Diagnostic and Statistical Manual of Mental Disorders IV criteria for either alcohol abuse or dependence. Nonalcoholic patients were included but only as a descriptive control. Perioperative intervention with low-dose ethanol (0.5 g/kg body weight per day), morphine (15 microg/kg body weight per hour), ketoconazole (200 mg four times daily), and placebo was started on the morning before surgery and continued for 3 d after surgery. Blood samples to analyze the neuroendocrine-immune axis were obtained on the morning before intervention and on Days 1, 3, and 7 after surgery.Measurements and Main Results: In long-term alcoholic patients, all interventions decreased postoperative hypercortisolism and prevented impairment of the cytotoxic T-lymphocyte type 1:type 2 ratio. All interventions decreased the pneumonia rate from 39% to a median of 5.7% and shortened intensive care unit stay by 9 d (median) compared with the placebo-treated long-term alcoholic patients.Conclusions: Intervention at the level of the HPA axis altered the immune response to surgical stress. This resulted in decreased postoperative pneumonia rates and shortened intensive care unit stay in long-term alcoholic patients. [ABSTRACT FROM AUTHOR]

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 ( n = 6,109) required emergency blood transfusion and were treated at the Charité - Universitätsmedizin Berlin between 2001 and 2015. Primary uncrossmatched O Rh(D)-positive or -negative RBC units were immediately transfused prior to complete regulatory serological testing including determination of ABO group, Rhesus antigens, antibody screening, and crossmatching., Results: Without any significant change in the protocol of emergency transfusion of RBCs, a total of 63,373 RBC units were transfused in 6,109 patients. Antibody screening was positive in 413 patients (6.8%), and 19 of these patients received RBC units against clinically significant alloantibodies. None of these patients appeared to have developed significant hemolysis, and only one patient with anti-D seems to have developed signs of insignificant hemolysis following the transfusion of three Rh(D)-positive units. One patient who had anti-Jk a received unselected units and did not develop a hemolytic transfusion reaction., Conclusion: Transfusion of uncrossmatched ABO-compatible RBCs against alloantibodies is highly safe in patients with life-threatening hemorrhage., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 by The Author(s). Published by S. Karger AG, Basel.)

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. Results revealed that the masking releases by those two cues are inversely related as a function of spatial separation, with a gender-specific difference of transition between the two types of masking release., (© 2021 Author(s).)

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. Sixty male and 60 female rats were randomized into single-sex groups to receive daily doses of pasireotide (0.3mg/kg/day, subcutaneously), osilodrostat (20mg/kg/day, orally), osilodrostat/pasireotide in combination (low dose, 1.5/0.03mg/kg/day; mid-dose, 5/0.1mg/kg/day; or high dose, 20/0.3mg/kg/day), or vehicle for 13weeks. Mean body-weight gains from baseline to Week 13 were significantly lower in the pasireotide-alone and combined-treatment groups compared to controls, and were significantly higher in female rats receiving osilodrostat monotherapy. Osilodrostat and pasireotide monotherapies were associated with significant changes in the histology and mean weights of the pituitary and adrenal glands, liver, and ovary/oviduct. Osilodrostat alone was associated with adrenocortical hypertrophy and hepatocellular hypertrophy. In combination, osilodrostat/pasireotide did not exacerbate any target organ changes and ameliorated the liver and adrenal gland changes observed with monotherapy. Cmax and AUC0-24h of osilodrostat and pasireotide increased in an approximately dose-proportional manner. In conclusion, the pasireotide and osilodrostat combination did not exacerbate changes in target organ weight or toxicity compared with either monotherapy, and had an acceptable safety profile; addition of pasireotide to the osilodrostat regimen may attenuate potential adrenal gland hyperactivation and hepatocellular hypertrophy, which are potential side effects of osilodrostat monotherapy., (Copyright © 2015. Published by Elsevier Inc.)

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. Skin lesion formation was prevented by elevating ambient temperature. Vildagliptin treatment also produced an increase in blood pressure and heart rate likely via increased sympathetic tone. Following treatment with vildagliptin at 80 mg/kg/day, the recovery time after lowering the temperature in the feet of monkeys and inducing cold stress was prolonged. Ex vivo investigations showed that small digital arteries from skin biopsies of vildagliptin-treated monkeys exhibited an increase in neuropeptide Y-induced vasoconstriction. This finding correlated with a specific increase in NPY and in NPY1 receptors observed in the skin of vildagliptin-treated monkeys. Present data provide evidence that skin effects in monkeys are of vascular origin and that the effects on the NPY system in combination with increased peripheral sympathetic tone play an important pathomechanistic role in the pathogenesis of cutaneous toxicity., (© 2014 by The Author(s).)

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. To identify the optimal cut-off storage time of RBCs for transfusion, multiple multivariate analyses aimed at different outcome parameters were performed., Results: 26 patients received RBC units stored for ≤3 days, while 126 patients received RBCs that were stored for 4-14 days. The latter group required more RBC transfusions and fresh frozen plasma (FFP) than the former group (19 vs. 25 ml/kg, p = 0.003 and 73% vs. 35%, p = 0.0006, respectively). In addition, the odds for the administration of FFP increased with the transfusion of RBCs stored for more than 4 days. The optimal cut-off for post-operative morbidity was observed with a storage time of ≤6 days for length of ventilation (p = 0.02) and peak of C-reactive protein (CRP; p = 0.008)., Conclusions: The obtained results indicate that the hazard of blood transfusion increased with increasing storage time of RBCs. The results of this study suggest that transfusion of fresh RBCs with a storage time of ≤2 or 4 days (concerning transfusion requirements) or ≤6 days (concerning postoperative morbidity) may be beneficial in pediatric patients undergoing cardiac surgery. However, further prospective randomized studies are required in order to draw any final conclusions.

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. To assess whether transfusion independently determined the length of mechanical ventilation and length of intensive care unit stay, a multivariate model was applied. Additionally, in the subgroup of transfused infants, the effect of the applied volume of packed red blood cells was assessed., Results: The median length of mechanical ventilation was 11 hours (interquartile range, 9-18 hours), 33 hours (interquartile range, 18-80 hours), and 93 hours (interquartile range, 34-161 hours) in the no transfusion, postoperative transfusion only, and intraoperative transfusion groups, respectively (P < .00001). The corresponding median lengths of intensive care unit stay were 1 day (interquartile range, 1-2 days), 3.5 days (interquartile range, 2-5 days), and 8 days (interquartile range, 3-9 days; P < .00001). The multivariate hazard ratio for early extubation was 0.24 (95% confidence interval, 0.16-0.35) and 0.37 (95% confidence interval, 0.25-0.55) for the intraoperative transfusion and postoperative transfusion only groups, respectively (P < .00001). In addition, the cardiopulmonary time, body weight, need for reoperation, and hemoglobin during cardiopulmonary bypass affected the length of mechanical ventilation. Similar results were obtained for the length of intensive care unit stay. In the subgroup of transfused infants, the volume of packed red blood cells also independently affected both the length of mechanical ventilation and the length of intensive care unit stay., Conclusions: The incidence and volume of blood transfusion markedly affects postoperative morbidity in pediatric cardiac surgery. These results, although obtained by retrospective analysis, might stimulate attending physicians to establish stringent blood-sparing approaches in their institutions., (Copyright © 2013 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

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., Methods: A total of 288 children with body weights between 1.7 and 15.9 kg were included and divided into 3 groups: No transfusion, postoperative transfusion only, and intraoperative and postoperative transfusion. Groups were compared by analysis of variance or analysis of variance on ranks. Risk factors predisposing for transfusion were identified by multivariate logistic regression., Results: Of the infants, 24.7% required no transfusion, 23.6% received postoperative transfusion only and 51.7% received intraoperative and postoperative transfusion. Groups differed by age, body weight, and size and by duration of surgery, CPB, and aortic crossclamp (P<.00001). Body weight (P<.00001), CPB duration (P<.00001), and persisting cyanosis (P=.03) were predictors of intraoperative and postoperative transfusion, whereas body weight (P=.00095), reoperations (P=.0051), and cyanotic heart defects (P=.035) were associated with postoperative transfusion only., Conclusions: Our blood-sparing approach allows for transfusion-free surgery in a substantial number of infants. The strongest predictors of transfusion requirement, body weight and complexity of surgery as reflected by CPB duration, are not amenable to further improvements. Better preservation of the coagulatory system might allow for reduction of postoperative transfusion requirements., (Copyright © 2012 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

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. The purpose of this study was to evaluate stability of clotting factors and inhibitors in thawed S/D-plasma stored at 4 °C for 6 days., Materials and Methods: Clotting factor levels and bacterial contamination were investigated using 20 units of S/D-plasma. Fibrinogen, factor (F) II, FV, FVII, FVIII, FIX, FX, FXI, FXII, FXIII, antithrombin, von Willebrand antigen (VWF-Ag), plasmin inhibitor, protein C and free protein S were analysed over time., Results: After 6 days of storage the results were as follows: fibrinogen 270 mg/dL (-10 mg/dL, p=0.0204), FII 75% (-5%, p<0.0001), FV 88% (-14%, p<0.0001), FVII 81% (-24%, p<0.0001), FVIII 70% (-16%, p<0.0001), FIX 96% (-8, p<0.0001), FX 92% (-1%, p<0.0001), FXI 119% (-4%, p=0.3666), FXII 94% (-2%, p=0.3602), FXIII 89% (-1%, p 0.0019), free protein S 76% (-4%, p<0.0001), protein C 96% (+1%, p=0.0371), antithrombin 92% (-3%, p<0.0001), plasmin inhibitor 29% (-4%, p<0.0299), VWF-Ag 137% (+2%, p=0.2205). FVII and FVIII showed a critical drop of more than 20% or approached the lower quality assurance threshold after storage for more than 24 hours. No S/D-plasma showed bacterial contamination., Conclusion: All clotting factors in thawed S/D plasma remained stable for up to 24 hours when stored at 4 °C. Storage of thawed S/D plasma may improve the availability of this product in emergency situations.

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. Asanguineous priming was used in all cases and packed red blood cells were added when hemoglobin concentration decreased below 7 g/dL. Cerebral and lower body tissue oxygenation was monitored by near-infrared spectroscopy. Intraoperative and postoperative transfusion, duration of ventilation and intensive care unit stay, wound infection, and 30-day mortality were assessed for patient outcome., Results: Intraoperative blood transfusion was necessary in 6 of 23 neonates. An additional 11 neonates received postoperative blood transfusions on the intensive care unit, leaving 6 infants who received no blood at all. Preoperative hemoglobin concentration was the only predictor for intraoperative transfusion requirement (11.6 ± 0.9 and 13.3 ± 0.4 g/dL in infants with and without intraoperative transfusion, respectively). Despite marked differences in hemoglobin concentrations between infants with and without transfusion, regional tissue oxygenation increased in both groups during cardiopulmonary bypass and returned to baseline at the end of surgery. In-hospital patient outcome was similar in both groups., Conclusions: Transfusion-free complex cardiac surgery can be achieved even in neonates without jeopardizing tissue oxygenation or patient safety., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

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. A total of 2562 patients with minor trauma were screened for HAC (≥ 8 points in men and ≥ 5 points in women on the Alcohol Use Disorders Identification Test), smoking status, and socioeconomic factors. The median age of participants was 32 years, with 62.1% being male. A total of 84.2% of patients had an Injury Severity Score of 1, indicating minor trauma. Overall, 23.5% of patients showed a pattern of HAC, whereas 46.2% were current smokers. Compared to patients without HAC, those with HAC were characterized by lower incomes, no partnership, living in a single-household, and being unemployed. The strongest discriminative variable for HAC for patients aged ≤ 53 years was smoking status. Gender differences played a role only in patients older than 53 years. Although socioeconomic factors showed a non-equal distribution in patients with respectively without HAC, solely age, gender, and smoking status may provide a successful stratification for alcohol screening and intervention in these patients., (Copyright © 2010 Elsevier Inc. All rights reserved.)

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 activity of fibrinogen, factor II (FII), FV, FVII, FVIII, FIX, FX, FXI, FXII, FXIII, antithrombin, plasmin inhibitor, von Willebrand factor antigen, free protein S and protein C were determined immediately and at 2, 4, 6, 24, 48, 72, 96, 120 and 144 h after reconstitution. Tests for bacterial contamination were performed after 12, 72 and 144 h from each plasma bottle., Results: Storage at 4 degrees C for 6 h led to a decrease in the activity of FVIII (Delta -14.9%), FIX (Delta -6.9%) and FXI (Delta -6.3%), and an increase in the activity of plasmin inhibitor (Delta +10.2%). Storage for up to 6 days resulted in a further decrease in activity of FVIII (Delta -24.3%), FIX (Delta -13.4%) and FXI (Delta -22.9%), and, additionally, a decrease in the activity of FV (Delta -15.0%), fibrinogen (Delta -6.9%) and plasmin inhibitor (Delta -17.5%). Other factors and inhibitors, with exception of protein C (Delta +8.2%), remained almost unchanged over time. Blood cultures were sterile and showed no bacterial growth., Conclusions: The activity of all measured coagulation factors and inhibitors in a time course of up to 6 days met required quality standards. Further in vivo testing is required to demonstrate safety and efficacy of extended clinical use of refrigerated reconstituted lyophilised plasma.

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. Postoperatively, we found significantly decreased von Willebrand factor ristocetin cofactor values over time among alcohol use disorder patients and significantly different time courses of factor VIII levels between patients with and without a diagnosed alcohol use disorder. Blood loss was significantly increased among alcohol use disorder patients on their first postoperative day.

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). All samples were tested in parallel with the FREELYS Nano., Results: We found a 100% concordance between the observed (FREELYS Nano) and the expected (Olympus PK7200) results for ABO/D grouping in all 100 samples. For Rh phenotyping and K tests, in 24 of 100 samples false-positive reactions were observed in the first evaluation by the FREELYS Nano. After changing the test kit batch for Rh phenotyping by the manufacturer, a complete concordance in Rh phenotyping and K tests was observed in a second evaluation. For ABS, the FREELYS Nano showed in 4 of 108 samples (3.7%) false-negative reactions for IgG antibodies (two anti-K, one anti-E, one anti-C(w)), and one (0.9%) false-positive reaction., Conclusions: The FREELYS Nano is reliably suited to ABO/D grouping, Rh phenotyping, and K testing. The rate of false-negative reactions for IgG antibodies should be reduced.

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). All samples were tested in parallel with the EMT., Results: In 496 of 499 samples (99.4%), a complete concordance between the observed (QWALYS 2) and the expected results for ABO/D grouping was found. One sample with a weak A in an AB blood group and 2 samples with a weak D were not detected by the QWALYS system. Rh phenotyping and K tests revealed a 100% concordance. In the two ABS techniques, 427 samples were negative in both and 15 samples showed the same antibody specificity in both. Three immunoglobulin M antibodies were as expected negative in EMT and positive by DiaMed. In 32 cases (6.7%), false-positive reactions were observed by EMT due to 22 unspecific reactions (4.6%) and 10 lipemic or fibrinic plasmas (2.1%). One autoantibody was found by EMT only., Conclusion: The EMT is reliably suited to ABO/D grouping, Rh phenotyping, and K testing and is suitable to detect immunoglobulin G red blood cell alloantibodies as well. The rate of false-positive reactions in ABS due to lipemic and fibrinic samples needs to be reduced.

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. Model fit was evaluated with the Bayesian Information Criterion., Results: The median age of participants was 32 years (range, 18-84 years) and 62% were male. Unobserved heterogeneity explained more variance in DAD than did sex, age, or substance use, but less variance than level of education. The best overall model fit was found with 3 latent subpopulations: 53.3% of patients with low DAD, 35.6% of patients with medium DAD, and 11.1% of patients with high DAD. Female sex and level of education showed a positive association; higher age and substance use showed a negative association with patients' DAD., Conclusions: Apart from a negative association with substance use and the known associations with sex and level of education, trauma patients' DAD showed substantial variability between individuals, and this variability could not be explained by these factors.

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. Patients were randomly assigned to the ethanol or control group. Ethanol infusion (0.5 g ethanol/kg body weight/24 hours) started before surgery and was continued until the postoperative Day 3. Regarding all patients, there was no statistically significant difference in the amount of transfused blood between the ethanol and control groups. However, the effect of ethanol infusion on bleeding complications depended on the site of surgery. Ethanol infusion resulted in an increased number of transfused blood units in gastrointestinal patients and a decreased number of transfused units in patients undergoing tumor resection of the aerodigestive tract. In conclusion, perioperative ethanol infusion in long-term alcoholic patients with tumor resections of the aerodigestive tract is an option for stress reduction without increased risk for blood transfusion. In contrast, ethanol infusion in patients with tumor resections in the gastrointestinal tract could increase the risk for bleeding complications.

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. At baseline (T0), 2,562 consecutive trauma patients (62.1% male) were screened for substance use (smoking, alcohol consumption, and illicit drug use) and for socioeconomic factors (income, relationship status, and education). Patients with five points or more in the Alcohol Use Disorders Identification Test randomly received tailored brief advice on alcohol and were followed up at 3 (T3), 6 (T6), 9 (T9), and 12 months (T12)., Results: At baseline, median age was 32 years (range: 18-89). There was a loss of 950 participants (37.1%) from T0 to T12. Loss to follow-up was strongly dependent on social factors. In participants with a high school diploma, only smoking was predictive of loss to follow-up (odds ratio [OR] = 1.81, 95% confidence interval [CI] = 1.43-2.29). In participants with no high school diploma, alcohol problems alone predicted loss to follow-up (medium level of alcohol problems, OR = 1.57, 95% CI = 1.09-2.27; high level of alcohol problems, OR = 1.62, 95% CI = 0.96-2.76; p = .017). Smoking (OR = 1.35, 95% CI = 0.97-1.89) and, for smokers, age 18-31 years (OR = 1.65, 95% CI = 0.98-2.78) showed a tendency toward an increased risk of loss to follow-up., Conclusions: After screening and a brief intervention in an emergency department, substance use and differences in education level predicted loss to follow-up. Patients with alcohol problems and no high school diploma are at increased risk of becoming lost to follow-up.

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. Thirty-three consecutive patients (13 long-term alcoholics and 20 non-alcoholics) scheduled for tumour resections of the upper digestive tract were included in the study. The levels of cAMP were significantly decreased before and after surgery in long-term alcoholic patients, but there were no significant differences in cGMP and serotonin levels in alcoholic compared with non-alcoholic patients. In contrast to previous studies, no significantly altered aggregation responses in long-term alcoholics were found. A possible explanation is decreased inhibition through diminished cAMP levels; cGMP and serotonin do not seem to influence peri-operative haemostasis.

Recent studies suggest a potential for activity-dependent reconstruction in the adult mammalian brainstem that exceeds previous expectations. We found that a unilateral cochlear lesion led within 1 week to a rise of choline acetyltransferase (ChAT) immunoreactivity in the ventral cochlear nucleus of the affected side, matching the lesion-induced expression of growth-associated protein 43 (GAP-43) previously described. The rise of both ChAT and GAP-43 immunoreactivity was reflected in the average density of the staining. Moreover, the number of light-microscopically identifiable boutons increased in both stains. GAP-43-positive boutons could, by distinct ultrastructural features, regularly be identified as presynaptic endings. However, GAP-43 immunoreactivity was not only found in presynaptic endings with a classical morphology, but also in profiles that suggest morphological dynamic structures by showing filopodia, assemblages of pleomorphic vesicles, large vesicles (diameter up to 200 nm) fusing with the presynaptic plasma membrane close to synaptic contacts, small dense-core vesicles (diameter about 80 nm) and presynaptic ribosomes. Moreover, we observed perforated synapses as well as GAP-43 immunoreactivity condensed in rafts, both indicative of growing or changing neuronal connections. Classical and untypical ultrastructural profiles that contained GAP-43 also contained ChAT. We conclude that there is extensive deafness-induced GAP-43-mediated synaptic plasticity in the cochlear nucleus, and that this plasticity is predominantly, if not exclusively, based on cholinergic afferents.

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. Spontaneous, adenosine diphosphate (ADP)-induced and collagen-induced activation before and after cryopreservation were determined by flow cytometry. Additionally, ADP- and collagen-induced aggregation was measured. After cryopreservation two-thirds of the platelets were spontaneously activated, twice as many as before the procedure (p < 0.001). ADP-induced activation was significantly reduced (p = 0.014). Collagen-induced activation was unchanged. Aggregation stimulated by ADP and collagen was significantly reduced (p = 0.005 and p = 0.009, respectively). Our results show severely impaired in vitro function of platelets after storage at 22 degrees C for five days followed by cryopreservation. Cryopreservation of PCs after a storage time of five days cannot be recommended.

Volume-reduced platelet concentrates (PCs) can be a useful option for transfusing a high number of platelets in the smallest possible plasma volume, especially in neonatal and other pediatric patients. In addition to decreasing the risk of circulatory overload, volume-reduced PCs contain less plasma, which may reduce the likelihood of adverse plasma-related transfusion reactions. Volume reduction can be achieved either during collection and processing of apheresis PCs (primary volume reduction) or, subsequently, by recentrifugation of stored PCs (secondary volume reduction). There is no standard method for preparing volume-reduced PCs. Although in vitro data suggest impaired platelet function with some methods of volume-reducing PCs, in vivo studies show acceptable hemostatic function, posttransfusion recovery, and platelet count increments for both primary and secondary volume-reduced PCs. This review presents an overview of recent studies on functional characteristics of different types of volume-reduced PCs.