Stress shielding effect after total hip arthroplasty varies between combinations of stem design and stiffness-a comparing biomechanical finite element analysis.

PURPOSE: Total hip arthroplasty (THA) has become a highly frequent orthopaedic procedure. Multiple approaches have been made to design the femoral component for THA with a mechanical behaviour as close as possible to a natural femur. The aim of this study was to compare different combinations of design and biomechanical properties of THA prostheses and their impact on stress shielding of the periprosthetic bone. METHODS: Virtual implantation of different stem designs (straight standard stem, straight short stem, anatomical short stem) by finite element analysis based on in vivo data from computer tomography was performed. For each stem, three grades of stiffness were generated, followed by a strain analysis. RESULTS: Reduction of stem stiffness led to less stress shielding. Implantation of an anatomical short-stem prosthesis with low stiffness provided the most physiological strain-loading effect (p < 0.001). CONCLUSION: A combination of a short and an anatomically designed stem with a low stiffness might provide a more physiological strain transfer during THA. Biomechanical properties of the femoral component for THA should be considered as a multifactorial function of dimensions, design, and stiffness.

Biomechanical comparison of different implants for PIP arthrodesis.

BACKGROUND: Surgical correction of hammertoe deformities with arthrodesis of the proximal interphalangeal joint (PIP) is one of the most frequent forefoot procedures. Recently, new intramedullary fixation devices for PIP arthrodesis have been introduced. The aim of this study was to compare a newly developed absorbable intramedullary implant made of magnesium (mm.PIP), an already available intramedullary implant made of titanium (PipTree), and the classical Kirschner-wire (K-wire). METHODS: The three intramedullary devices (mm.PIP, PipTree, and K-wire) for PIP arthrodesis were compared. A classical arthrodesis of the PIP joint was performed on fifty-four composite synthetic bone pairs. After arthrodesis, torsional load, weight-bearing and cyclic load tests were performed, and stability of the synthetic bone pairs was analyzed. RESULTS: The mm.PIP was the most torsion resistant (mm.PIP vs. PipTree and K-wire, p < 0.001). The PipTree showed the best overall stability during cyclic weight-bearing simulation (PipTree vs. mm.PIP and K-wire, p < 0.001). K-wire demonstrated the highest breaking loads during bending tests (K-wire vs. mm-PIP and PipTree, p < 0.001). CONCLUSION: Biomechanical properties of two new intramedullar implants, the bioresorbable mm.PIP made of magnesium and the PipTree made of titanium, were found to be comparable to the biomechanical properties of a K-wire which is commonly used for this procedure. Future work should be directed towards a clinical assessment of the bioabsorbable fixation devices for hammertoe procedures.

The role of cell-free hemoglobin and haptoglobin in acute kidney injury in critically ill adults with ARDS and therapy with VV ECMO.

BACKGROUND: Increased plasma concentrations of circulating cell-free hemoglobin (CFH) are supposed to contribute to the multifactorial etiology of acute kidney injury (AKI) in critically ill patients while the CFH-scavenger haptoglobin might play a protective role. We evaluated the association of CFH and haptoglobin with AKI in patients with an acute respiratory distress syndrome (ARDS) requiring therapy with VV ECMO. METHODS: Patients with CFH and haptoglobin measurements before initiation of ECMO therapy were identified from a cohort of 1044 ARDS patients and grouped into three CFH concentration groups using a risk stratification. The primary objective was to assess the association of CFH and haptoglobin with KDIGO stage 3 AKI. Further objectives included the identification of a target haptoglobin concentration to protect from CFH-associated AKI. MEASUREMENTS AND MAIN RESULTS: Two hundred seventy-three patients fulfilled the inclusion criteria. Of those, 154 patients (56.4%) had AKI at ECMO initiation. The incidence of AKI increased stepwise with increasing concentrations of CFH reaching a plateau at 15 mg/dl. Compared to patients with low [< 5 mg/dl] CFH concentrations, patients with moderate [5-14 mg/dl] and high [≥ 15 mg/dl] CFH concentrations had a three- and five-fold increased risk for AKI (adjusted odds ratio [OR] moderate vs. low, 2.69 [95% CI, 1.25-5.95], P = 0.012; and OR high vs. low, 5.47 [2.00-15.9], P = 0.001). Among patients with increased CFH concentrations, haptoglobin plasma levels were lower in patients with AKI compared to patients without AKI. A haptoglobin concentration greater than 2.7 g/l in the moderate and 2.4 g/l in the high CFH group was identified as clinical cutoff value to protect from CFH-associated AKI (sensitivity 89.5% [95% CI, 83-96] and 90.2% [80-97], respectively). CONCLUSIONS: In critically ill patients with ARDS requiring therapy with VV ECMO, an increased plasma concentration of CFH was identified as independent risk factor for AKI. Among patients with increased CFH concentrations, higher plasma haptoglobin concentrations might protect from CFH-associated AKI and should be subject of future research.

Large Animal Models for Simulating Physiology of Transfusion of Red Cell Concentrates-A Scoping Review of The Literature.

Background and Objectives: Transfusion of red cell concentrates is a key component of medical therapy. To investigate the complex transfusion-associated biochemical and physiological processes as well as potential risks for human recipients, animal models are of particular importance. This scoping review summarizes existing large animal transfusion models for their ability to model the physiology associated with the storage of erythrocyte concentrates. Materials and Methods: The electronic databases PubMed, EMBASE, and Web of Science were systematically searched for original studies providing information on the intravenous application of erythrocyte concentrates in porcine, ovine, and canine animal models. Results: A total of 36 studies were included in the analysis. The majority of porcine studies evaluated hemorrhagic shock conditions. Pig models showed high physiological similarities with regard to red cell physiology during early storage. Ovine and canine studies were found to model typical aspects of human red cell storage at 42 days. Only four studies provided data on 24 h in vivo survival of red cells. Conclusions: While ovine and canine models can mimic typical human erythrocyte storage for up to 42 days, porcine models stand out for reliably simulating double-hit pathologies such as hemorrhagic shock. Large animal models remain an important area of translational research since they have an impact on testing new pharmacological or biophysical interventions to attenuate storage-related adverse effects and allow, in a controlled environment, to study background and interventions in dynamic and severe disease conditions.

Tert-butylhydroquinone augments Nrf2-dependent resilience against oxidative stress and improves survival of ventilator-induced lung injury in mice.

Oxidative stress caused by mechanical ventilation contributes to the pathophysiology of ventilator-induced lung injury (VILI). A key mechanism maintaining redox balance is the upregulation of nuclear factor-erythroid-2-related factor 2 (Nrf2)-dependent antioxidant gene expression. We tested whether pretreatment with an Nrf2-antioxidant response element (ARE) pathway activator tert-butylhydroquinone (tBHQ) protects against VILI. Male C57BL/6J mice were pretreated with an intraperitoneal injection of tBHQ (n = 10), an equivalent volume of 3% ethanol (EtOH3%, vehicle, n = 13), or phosphate-buffered saline (controls, n = 10) and were then subjected to high tidal volume (HVT) ventilation for a maximum of 4 h. HVT ventilation severely impaired arterial oxygenation ([Formula: see text] = 49 ± 7 mmHg, means ± SD) and respiratory system compliance, resulting in a 100% mortality among controls. Compared with controls, tBHQ improved arterial oxygenation ([Formula: see text] = 90 ± 41 mmHg) and respiratory system compliance after HVT ventilation. In addition, tBHQ attenuated the HVT ventilation-induced development of lung edema and proinflammatory response, evidenced by lower concentrations of protein and proinflammatory cytokines (IL-1ß and TNF-α) in the bronchoalveolar lavage fluid, respectively. Moreover, tBHQ enhanced the pulmonary redox capacity, indicated by enhanced Nrf2-depentent gene expression at baseline and by the highest total glutathione concentration after HVT ventilation among all groups. Overall, tBHQ pretreatment resulted in 60% survival (P < 0.001 vs. controls). Interestingly, compared with controls, EtOH3% reduced the proinflammatory response to HVT ventilation in the lung, resulting in 38.5% survival (P = 0.0054 vs. controls). In this murine model of VILI, tBHQ increases the pulmonary redox capacity by activating the Nrf2-ARE pathway and protects against VILI. These findings support the efficacy of pharmacological Nrf2-ARE pathway activation to increase resilience against oxidative stress during injurious mechanical ventilation.

Hemolysis in patients with Extracorporeal Membrane Oxygenation therapy for severe Acute Respiratory Distress Syndrome - a systematic review of the literature.

The Acute Respiratory Distress Syndrome (ARDS) is common in patients on the Intensive Care Unit and associated with significant mortality rates. In situations of severe respiratory insufficiency and failure of all possible conservative therapeutic approaches, veno-venous extracorporeal membrane oxygenation (VV ECMO) is used as a final option for temporary replacement of pulmonary function. ARDS as well as sepsis and VV ECMO treatment are all associated with intravascular hemolysis. The extent and relevance of intravascular hemolysis in the context of ARDS therapy is unclear. This systematic review aims to summarize the current evidence on the incidence and associated complications of intravascular hemolysis in adult patients with ARDS and treatment with VV ECMO. The databases MEDLINE, EMBASE and Web of Science were systematically searched and 19 publications fulfilled inclusion criteria. The incidence of hemolysis in patients with ARDS and treatment with VV ECMO ranged from 0 to 41% with survivors showing lower incidences and less severe hemolysis. A pump head thrombosis and high blood flows (≥3 l/min) as well as use of dual-lumen cannulas but not different pump models were associated with increased hemolysis. In conclusion, intravascular hemolysis in patients with ARDS and treatment with VV ECMO is a common and relevant complication that appears associated with increased mortality. Apart from ECMO hardware-settings, no additional possible causes for increased red cell breakdown such as disease severity, duration of ECMO therapy, or number and quality of red blood cell transfusions were investigated. Further research is needed to determine the origin and relevance of intravascular hemolysis in patients with ARDS and treatment with VV ECMO.

End-of-Life Decision-Making in Intensive Care Ten Years after a Law on Advance Directives in Germany.

Background and Objectives: Mortality on Intensive Care Units (ICUs) is high and death frequently occurs after decisions to limit life-sustaining therapies. An advance directive is a tool meant to preserve patient autonomy by guiding anticipated future treatment decisions once decision-making capacity is lost. Since September 2009, advance directives are legally binding for the caregiver team and the patients' surrogate decision-maker in Germany. The change in frequencies of end-of-life decisions (EOLDs) and completed advance directives among deceased ICU patients ten years after the enactment of a law on advance directives in Germany is unknown. Materials and Methods: Retrospective analysis on all deceased patients of surgical ICUs of a German university medical center from 08/2008 to 09/2009 and from 01/2019 to 09/2019. Frequency of EOLDs and advance directives and the process of EOLDs were compared between patients admitted before and after the change in legislation. (No. of ethical approval EA2/308/20) Results: Significantly more EOLDs occurred in the 2019 cohort compared to the 2009 cohort (85.8% vs. 70.7% of deceased patients, p = 0.006). The number of patients possessing an advance directive to express a living or therapeutic will was higher in the 2019 cohort compared to the 2009 cohort (26.4% vs. 8.9%; difference: 17.5%, p < 0.001). Participation of the patients' family in the EOLD process (74.7% vs. 60.9%; difference: 13.8%, p = 0.048) and the frequency of documentation of EOLD-relevant information (50.0% vs. 18.7%; difference: 31.3%, p < 0.001) increased from 2009 to 2019. Discussion: During a ten-year period from 2009 to 2019, the frequency of EOLDs and the completion rate of advance directives have increased considerably. In addition, EOLD-associated communication and documentation have further improved.

Point-of-Care diagnostics of coagulation in the management of bleeding and transfusion in trauma patients.

PURPOSE OF REVIEW: Trauma-associated bleeding and coagulopathy require timely identification, prevention, and effective treatment. The present review summarizes the recent literature around point-of-care (POC) coagulation tests, their usefulness in the management of trauma-induced coagulopathy (TIC), their impact on trauma patient outcomes, and the requirement of quality assurance. RECENT FINDINGS: Best practice algorithms to manage TIC have been compiled in the 2019 European Guideline on the management of major bleeding and coagulopathy after trauma. Evidence supports the use of goal-directed approaches to manage TIC. POC coagulation tests can accelerate and tailor individualized therapies. Recent findings emphasize: the time sparing of POC tests in prehospital settings and the validity of POC measurements in extreme environments; the potential scalability of POC-guided TIC algorithms in burn injuries and the pediatric population; the need for careful considerations of strategies to monitor and reverse the effects of direct oral anticoagulants in major trauma. SUMMARY: In contrast to an abundance of reviews and practical approaches to POC coagulation management in trauma patients, there is a scarcity of research in the field and large-scale clinical trials are urgently needed. The paneuropean multicenter trial Implementing Treatment Algorithms for the Correction of Trauma Induced Coagulopathy (iTACTIC) will inform on the potential of viscoelastic tests to augment transfusion protocols for better patient outcomes.

Risk perception of blood transfusions - a comparison of patients and allied healthcare professionals.

BACKGROUND: Due to an increasing demand in health care services plans to substitute selective physician-conducted medical activities have become attractive. Because administration of a blood transfusion is a highly standardized procedure, it might be evaluated if obtaining a patient's consent for a blood transfusion can be delegated to allied healthcare professionals. Physicians and patients perceive risks of transfusions differently. However, it is unknown how allied healthcare professionals perceive risks of transfusion-associated adverse events. METHODS: Patients (n = 506) and allied healthcare professionals (n = 185) of an academic teaching hospital were asked to quantify their concerns about transfusions including five predefined transfusion-associated risks and their incidences. RESULTS: Blood transfusions were considered to be generally harmful by 10.9% of patients and 14.6% of caregivers (P = 0.180). Among all surveyed patients, 36.8% were worried about infection-transmissions (caregivers: 27.6%; P = 0.024). Compared to 5.4% of caregivers, 13.6% of patients believed infection-transmission was a frequent complication (P = 0.003). Caregivers ranked the risks of receiving an AB0-mismatch transfusion (caregivers: 29.7% vs. PATIENTS: 19.2%, P = 0.003) or a transfusion-associated allergic reaction (caregivers: 17.3% vs. PATIENTS: 11.1%, P = 0.030) significantly higher than patients and were aware of the high incidence of transfusion-associated fever (caregivers: 17.8% vs. PATIENTS: 8.3%, P < 0.001). CONCLUSION: A significant part of interviewees perceived transfusions as a general health hazard. Patients perceived infection-transmissions as the most frequent and greatest transfusion-associated threat while caregivers focused on fatal AB0-mismatch transfusions and allergic reactions. Understanding the patients' main concerns about blood transfusions and considering that these concerns might differ from the view of healthcare professionals might improve the process of shared decision making.

[The Relevance of Hemolysis in Anesthesia and Intensive Care Medicine]. / Die Bedeutung der Hämolyse in Anästhesie und Intensivmedizin.

Hemolysis leads to an increase of circulating intravascular cell-free hemoglobin. Increased plasma concentrations of cell-free hemoglobin are relevant in critically ill patients because cell-free hemoglobin causes vasoconstriction by depletion of endothelial nitric oxide, oxidative stress, and inflammation. Furthermore, cell-free hemoglobin contributes to tissue injuries such as renal failure and intestinal mucosa damage after cardiac surgery. High concentrations of cell-free hemoglobin are associated with an increased mortality in patients with sepsis. Currently, it is unclear if hemolysis associated with transfusion of packed red blood cells that have been stored for prolonged periods of time is relevant for the clinical outcome. However, humans possess plasma proteins haptoglobin and hemopexin which bind to plasma hemoglobin and cell-free heme, respectively. The haptoglobin-hemoglobin and hemopexin-heme complexes are then eliminated from the plasma by hepatic or splenic uptake.

Haptoglobin or Hemopexin Therapy Prevents Acute Adverse Effects of Resuscitation After Prolonged Storage of Red Cells.

BACKGROUND: Extracellular hemoglobin and cell-free heme are toxic breakdown products of hemolyzed erythrocytes. Mammals synthesize the scavenger proteins haptoglobin and hemopexin, which bind extracellular hemoglobin and heme, respectively. Transfusion of packed red blood cells is a lifesaving therapy for patients with hemorrhagic shock. Because erythrocytes undergo progressive deleterious morphological and biochemical changes during storage, transfusion of packed red blood cells that have been stored for prolonged intervals (SRBCs; stored for 35-40 days in humans or 14 days in mice) increases plasma levels of cell-free hemoglobin and heme. Therefore, in patients with hemorrhagic shock, perfusion-sensitive organs such as the kidneys are challenged not only by hypoperfusion but also by the high concentrations of plasma hemoglobin and heme that are associated with the transfusion of SRBCs. METHODS: To test whether treatment with exogenous human haptoglobin or hemopexin can ameliorate adverse effects of resuscitation with SRBCs after 2 hours of hemorrhagic shock, mice that received SRBCs were given a coinfusion of haptoglobin, hemopexin, or albumin. RESULTS: Treatment with haptoglobin or hemopexin but not albumin improved the survival rate and attenuated SRBC-induced inflammation. Treatment with haptoglobin retained free hemoglobin in the plasma and prevented SRBC-induced hemoglobinuria and kidney injury. In mice resuscitated with fresh packed red blood cells, treatment with haptoglobin, hemopexin, or albumin did not cause harmful effects. CONCLUSIONS: In mice, the adverse effects of transfusion with SRBCs after hemorrhagic shock are ameliorated by treatment with either haptoglobin or hemopexin. Haptoglobin infusion prevents kidney injury associated with high plasma hemoglobin concentrations after resuscitation with SRBCs. Treatment with the naturally occurring human plasma proteins haptoglobin or hemopexin may have beneficial effects in conditions of severe hemolysis after prolonged hypotension.

Endothelial dysfunction inhibits the ability of haptoglobin to prevent hemoglobin-induced hypertension.

Intravascular hemolysis produces injury in a variety of human diseases including hemoglobinopathies, malaria, and sepsis. The adverse effects of increased plasma hemoglobin are partly mediated by depletion of nitric oxide (NO) and result in vasoconstriction. Circulating plasma proteins haptoglobin and hemopexin scavenge extracellular hemoglobin and cell-free heme, respectively. The ability of human haptoglobin or hemopexin to inhibit the adverse effects of NO scavenging by circulating murine hemoglobin was tested in C57Bl/6 mice. In healthy awake mice, the systemic hemodynamic effects of intravenous coinfusion of cell-free hemoglobin and exogenous haptoglobin or of cell-free hemoglobin and hemopexin were compared with the hemodynamic effects of infusion of cell-free hemoglobin or control protein (albumin) alone. We also studied the hemodynamic effects of infusing hemoglobin and haptoglobin as well as injecting either hemoglobin or albumin alone in mice fed a high-fat diet (HFD) and in diabetic (db/db) mice. Coinfusion of a 1:1 weight ratio of haptoglobin but not hemopexin with cell-free hemoglobin prevented hemoglobin-induced systemic hypertension in healthy awake mice. In mice fed a HFD and in diabetic mice, coinfusion of haptoglobin mixed with an equal mass of cell-free hemoglobin did not reverse hemoglobin-induced hypertension. Haptoglobin retained cell-free hemoglobin in plasma, but neither haptoglobin nor hemopexin affected the ability of hemoglobin to scavenge NO ex vivo. In conclusion, in healthy C57Bl/6 mice with normal endothelium, coadministration of haptoglobin but not hemopexin with cell-free hemoglobin prevents acute hemoglobin-induced systemic hypertension by compartmentalizing cell-free hemoglobin in plasma. In murine diseases associated with endothelial dysfunction, haptoglobin therapy appears to be insufficient to prevent hemoglobin-induced vasoconstriction.NEW & NOTEWORTHY Coadministraton of haptoglobin but not hemopexin with cell-free hemoglobin prevents hemoglobin-induced systemic hypertension in mice with a normal endothelium. In contrast, treatment with the same amount of haptoglobin is unable to prevent hemoglobin-induced vasoconstriction in mice with hyperlipidemia or diabetes mellitus, disorders that are associated with endothelial dysfunction.

Iron Loading Exaggerates the Inflammatory Response to the Toll-like Receptor 4 Ligand Lipopolysaccharide by Altering Mitochondrial Homeostasis.

BACKGROUND: Perioperative and critically ill patients are often exposed to iron (in the form of parenteral-iron administration or blood transfusion) and inflammatory stimuli, but the effects of iron loading on the inflammatory response are unclear. Recent data suggest that mitochondrial reactive oxygen species have an important role in the innate immune response and that increased mitochondrial reactive oxygen species production is a result of dysfunctional mitochondria. We tested the hypothesis that increased intracellular iron potentiates lipopolysaccharide-induced inflammation by increasing mitochondrial reactive oxygen species levels. METHODS: Murine macrophage cells were incubated with iron and then stimulated with lipopolysaccharide. C57BL/6 wild-type mice were intraperitoneally injected with iron and then with lipopolysaccharide. Markers of inflammation and mitochondrial superoxide production were examined. Mitochondrial homeostasis (the balance between mitochondrial biogenesis and destruction) was assessed, as were mitochondrial mass and the proportion of nonfunctional to total mitochondria. RESULTS: Iron loading of mice and cells potentiated the inflammatory response to lipopolysaccharide. Iron loading increased mitochondrial superoxide production. Treatment with MitoTEMPO, a mitochondria-specific antioxidant, blunted the proinflammatory effects of iron loading. Iron loading increased mitochondrial mass in cells treated with lipopolysaccharide and increased the proportion of nonfunctional mitochondria. Iron loading also altered mitochondrial homeostasis to favor increased production of mitochondria. CONCLUSIONS: Acute iron loading potentiates the inflammatory response to lipopolysaccharide, at least in part by disrupting mitochondrial homeostasis and increasing the production of mitochondrial superoxide. Improved understanding of iron homeostasis in the context of acute inflammation may yield innovative therapeutic approaches in perioperative and critically ill patients.

Sensitivity to Sevoflurane anesthesia is decreased in mice with a congenital deletion of Guanylyl Cyclase-1 alpha.

BACKGROUND: Volatile anesthetics increase levels of the neurotransmitter nitric oxide (NO) and the secondary messenger molecule cyclic guanosine monophosphate (cGMP) in the brain. NO activates the enzyme guanylyl cyclase (GC) to produce cGMP. We hypothesized that the NO-GC-cGMP pathway contributes to anesthesia-induced unconsciousness. METHODS: Sevoflurane-induced loss and return of righting reflex (LORR and RORR, respectively) were studied in wild-type mice (WT) and in mice congenitally deficient in the GC-1α subunit (GC-1-/- mice). Spatial distributions of GC-1α and the GC-2α subunit in the brain were visualized by in situ hybridization. Brain cGMP levels were measured in WT and GC-1-/- mice after inhaling oxygen with or without 1.2% sevoflurane for 20 min. RESULTS: Higher concentrations of sevoflurane were required to induce LORR in GC-1-/- mice than in WT mice (1.5 ± 0.1 vs. 1.1 ± 0.2%, respectively, n = 14 and 14, P < 0.0001). Similarly, RORR occurred at higher concentrations of sevoflurane in GC-1-/- mice than in WT mice (1.0 ± 0.1 vs. 0.8 ± 0.1%, respectively, n = 14 and 14, P < 0.0001). Abundant GC-1α and GC-2α mRNA expression was detected in the cerebral cortex, medial habenula, hippocampus, and cerebellum. Inhaling 1.2% sevoflurane for 20 min increased cGMP levels in the brains of WT mice from 2.6 ± 2.0 to 5.5 ± 3.7 pmol/mg protein (n = 13 and 10, respectively, P = 0.0355) but not in GC-1-/- mice. CONCLUSION: Congenital deficiency of GC-1α abolished the ability of sevoflurane anesthesia to increase cGMP levels in the whole brain, and increased the concentration of sevoflurane required to induce LORR. Impaired NO-cGMP signaling raises the threshold for producing sevoflurane-induced unconsciousness in mice.

Exposure of Stored Packed Erythrocytes to Nitric Oxide Prevents Transfusion-associated Pulmonary Hypertension.

BACKGROUND: Transfusion of packed erythrocytes stored for a long duration is associated with increased pulmonary arterial pressure and vascular resistance. Prolonged storage decreases erythrocyte deformability, and older erythrocytes are rapidly removed from the circulation after transfusion. The authors studied whether treating stored packed ovine erythrocytes with NO before transfusion could prevent pulmonary vasoconstriction, enhance erythrocyte deformability, and prolong erythrocyte survival after transfusion. METHODS: Ovine leukoreduced packed erythrocytes were treated before transfusion with either NO gas or a short-lived NO donor. Sheep were transfused with autologous packed erythrocytes, which were stored at 4°C for either 2 ("fresh blood") or 40 days ("stored blood"). Pulmonary and systemic hemodynamic parameters were monitored before, during, and after transfusion. Transfused erythrocytes were labeled with biotin to measure their circulating lifespan. Erythrocyte deformability was assessed before and after NO treatment using a microfluidic device. RESULTS: NO treatment improved the deformability of stored erythrocytes and increased the number of stored erythrocytes circulating at 1 and 24 h after transfusion. NO treatment prevented transfusion-associated pulmonary hypertension (mean pulmonary arterial pressure at 30 min of 21 ± 1 vs. 15 ± 1 mmHg in control and NO-treated packed erythrocytes, P < 0.0001). Washing stored packed erythrocytes before transfusion did not prevent pulmonary hypertension. CONCLUSIONS: NO treatment of stored packed erythrocytes before transfusion oxidizes cell-free oxyhemoglobin to methemoglobin, prevents subsequent NO scavenging in the pulmonary vasculature, and limits pulmonary hypertension. NO treatment increases erythrocyte deformability and erythrocyte survival after transfusion. NO treatment might provide a promising therapeutic approach to prevent pulmonary hypertension and extend erythrocyte survival.

End-of-life decisions in surgical intensive care medicine - the relevance of blood transfusions.

BACKGROUND: End-of-life decisions (EOLDs) are common in the intensive care unit (ICU). EOLDs underlie a dynamic process and limitation of ICU-therapies is often done sequentially. Questionnaire-based and observational studies on medical ICUs and in palliative care reveal blood transfusions as the first therapy physicians withhold as an EOLD. METHODS: To test whether this practice also applies to surgical ICU-patients, in an observational study, all deceased patients (n = 303) admitted to an academic surgical ICU in a three-year period were analyzed for the process of limiting ICU-therapies. RESULTS: Restriction of further surgery (85.4%) and limiting doses of vasopressors (75.8%) were the most frequent forms of limitations in surgical ICU therapies. Surgical patients, who had blood transfusions withheld (44.6%), had more ICU-therapies withheld or withdrawn simultaneously than patients who had transfusions maintained (5 ± 2 vs. 2 ± 1, p < 0.001). Secondary EOLDs and subsequent limitations occurred less frequently in patients who had transfusions withheld with their first EOLD (17.1% vs. 35.6%, p < 0.05). CONCLUSION: Limitation orders for blood transfusions are not a prioritized decision in EOLDs of surgical ICU patients. Withholding blood transfusions correlates with discontinuation of further significant life-support therapies. This suggests that EOLDs to withhold blood transfusions are part of the most advanced limitations of therapy on the surgical ICU.

End-of-life decisions in intensive care medicine-shared decision-making and intensive care unit length of stay.

BACKGROUND: Most deaths on the intensive care unit (ICU) occur after end-of-life decisions (EOLD) have been made. During the decision-making process, responsibility is often shared within the caregiver team and with the patients' surrogates. The intensive care unit length of stay (ICU-LOS) of surgical ICU-patients depends on the primary illness as well as on the past medical history. Whether an increasing ICU-LOS affects the process of EOLD making is unknown. METHODS: A retrospective analysis was conducted on all deceased patients (n = 303) in a 22-bed surgical ICU of a German university medical center. Patient characteristics were compared between surgical patients with an ICU-LOS up to 1 week and those with an ICU-LOS of more than 7 days. RESULTS: Deceased patients with a long ICU-LOS received more often an EOLD (83.2% vs. 63.6%, p = 0.001). Groups did not differ in urgency of admission. Attending intensivists participated in every EOLD. Participation of surgeons was significantly higher in patients with a short ICU-LOS (24.1%, p = 0.003), whereas nurses and the patients' surrogates were involved more frequently in patients with a long ICU-LOS (18.8%, p = 0.021 and 18.9%, p = 0.018, respectively). CONCLUSION: EOLDs of surgical ICU-patients are associated with the ICU-LOS. Reversal of the primary illness leads the early ICU course, while in prolonged ICU-LOS, the patients' predicted will and the expected post-ICU-quality of life gain interest. Nurses and the patients' surrogates participate more frequently in EOLDs with prolonged ICU-LOS. To improve EOLD making on surgical ICUs, the ICU-LOS associated participation of the different decision makers needs further prospective analysis.

Chronic Alcohol Consumption Leads to a Tissue Specific Expression of Uncoupling Protein-2.

Uncoupling proteins (UCPs) are anion channels that can decouple the mitochondrial respiratory chain. "Mild uncoupling" of internal respiration reduces free radical production and oxidative cell stress. Chronic alcohol consumption is a potent inducer of oxidative stress in multiple tissues and regulates UCP-2 and -4 expression in the brain. To analyse the impact of chronic alcohol intake on UCP-2 expression in tissues with high endogenous UCP-2 contents, male Wistar rats (n=34) were treated with a 12-week 5% alcohol diet. In the lungs and the spleen of rats with a chronic alcohol diet cytochrome c release from mitochondria was significantly increased. Both organs did not show any altered gene and protein expression of UCP-2. Different to cerebral tissue chronic alcohol consumption has no regulatory effect on UCP-2 gene and protein expression in organs with a high endogenous UCP-2 content. Therefore, chronic alcohol consumption leads to a tissue specific expression of UCP-2.

Use of a silver-coated plate to treat a postoperative infection after high tibial osteotomy - a case report.

Unilateral osteoarthritis of the knee can be treated by osteotomy. In case of postoperative infection after high tibial osteotomy, treatment can be challenging and often requires implant removal with the risk of loss of reduction. In the presented case, a 47-year old patient suffered postoperative infection after high tibial osteotomy using an angular stable plate with the need for multiple revision surgeries and anti-infective therapy. Implant exchange to a silver-coated angular plate led to infection control with undisturbed wound healing and further bone consolidation. Full bone consolidation could be achieved radiographically 12 months after the last revision surgery. One-step implant exchange using silver-coated implants could be a promising approach to address postoperative infections after high tibial osteotomy.