Association of biliary distention with a diagnosis of acute cholecystitis.

BACKGROUND: Gallbladder distention has been described in radiology literature but its value on point-of-care ultrasound (PoCUS) performed by emergency physicians is unclear. We sought to determine the test characteristics of gallbladder distention on PoCUS for cholecystitis (acute or chronic), and secondarily whether distention was associated with an obstructing stone-in-neck (SIN), acute cholecystitis on subsequent pathology report, and longer cholecystectomy operative times. METHODS: This was a dual-site retrospective cohort study of all Emergency Department (ED) patients that underwent diagnostic biliary PoCUS and were subsequently admitted from 11/1/2020 to 10/31/2022. Patients with pregnancy, liver failure, ascites, hepatobiliary cancer, prior cholecystectomy, or known cholecystitis were excluded. Gallbladder distention was defined as a width ≥4 cm or a length ≥10 cm. Saved ultrasound images were reviewed by three independent reviewers who obtained measurements during the review. Test characteristics, Cohen's kappa (κ), and strength of association between distention and our variables (acute cholecystitis on pathology report and SIN on PoCUS) were calculated using a Chi Square analysis, where intervention (cholecystectomy, percutaneous cholecystostomy, or intravenous antibiotics) was used as the reference standard for AC. A one-tail two sample t-test was calculated for mean operative times. RESULTS: Of 280 admitted patients who underwent ED biliary PoCUS, 53 were excluded, and 227 were analyzed. Of the 227 patients, 113 (49.8%) had cholecystitis according to our reference standard, and 68 (30.0%) had distention on PoCUS: 32 distended by both width and length, 16 distended by width alone, and 20 distended by length alone. Agreement between investigators was substantial for width (κ 0.630) and length (κ 0.676). Distention was 85.09% (95% CI 77.20-91.07%) specific and 45.1% (95% CI 35.8-54.8%) sensitive for cholecystitis. There was an association between distention and SIN; odds ratio (OR) 2.76 (95% CI 1.54-4.97). Distention of both length and width was associated with acute over chronic cholecystitis; OR 4.32 (95% CI 1.42-13.14). Among patients with acute cholecystitis, mean operative times were 114 min in patients with distention and 89 min in patients without distention (p = 0.03). CONCLUSION: Gallbladder distention on PoCUS was specific for cholecystitis (acute or chronic), and associated with SIN, acute cholecystitis on subsequent pathology report, and longer cholecystectomy operative times. Measurement of gallbladder dimensions as part of the assessment of cholecystitis may be advantageous.

Multi-color dual wavelength vat photopolymerization 3D printing via spatially controlled acidity.

Dual wavelength vat photopolymerization (DW-VP) has emerged as a powerful approach to create multimaterial objects. However, only a limited range of properties have been showcased. In this work, we report the 3D printing (3DP) of multi-color objects from a single resin vat using DW-VP. This was accomplished by concurrently curing resin with visible light and modulating local resin color with 365-nm ultraviolet (UV) light. The key advance was to use a photoacid generator (PAG) in combination with pH responsive dyes in the 3DP resins. The specific color is dictated by the extent of reaction, or local acidity in our case, and controlled by the light dosage and pattern of UV light applied. Multi-color object formation was implemented in two-step processes involving first 3DP to set the object structure, followed by UV exposure, as well as single processes that leveraged DW-VP to create a broad range of vibrant colors and patterns.

Bilateral nephrectomy impairs cardiovascular function and cerebral perfusion in a rat model of acute hemodilutional anemia.

Anemia and renal failure are independent risk factors for perioperative stroke, prompting us to assess the combined impact of acute hemodilutional anemia and bilateral nephrectomy (2Nx) on microvascular brain Po2 (PBro2) in a rat model. Changes in PBro2 (phosphorescence quenching) and cardiac output (CO, echocardiography) were measured in different groups of anesthetized Sprague-Dawley rats (1.5% isoflurane, n = 5-8/group) randomized to Sham 2Nx or 2Nx and subsequently exposed to acute hemodilutional anemia (50% estimated blood volume exchange with 6% hydroxyethyl starch) or time-based controls (no hemodilution). Outcomes were assessed by ANOVA with significance assigned at P < 0.05. At baseline, 2Nx rats demonstrated reduced CO (49.9 ± 9.4 vs. 66.3 ± 19.3 mL/min; P = 0.014) and PBro2 (21.1 ± 2.9 vs. 32.4 ± 3.1 mmHg; P < 0.001) relative to Sham 2Nx rats. Following hemodilution, 2Nx rats demonstrated a further decrease in PBro2 (15.0 ± 6.3 mmHg, P = 0.022). Hemodiluted 2Nx rats did not demonstrate a comparable increase in CO after hemodilution compared with Sham 2Nx (74.8 ± 22.4 vs. 108.9 ± 18.8 mL/min, P = 0.003) that likely contributed to the observed reduction in PBro2. This impaired CO response was associated with reduced fractional shortening (33 ± 9 vs. 51 ± 5%) and increased left ventricular end-systolic volume (156 ± 51 vs. 72 ± 15 µL, P < 0.001) suggestive of systolic dysfunction. By contrast, hemodiluted Sham 2Nx animals demonstrated a robust increase in CO and preserved PBro2. These data support the hypothesis that the kidney plays a central role in maintaining cerebral perfusion and initiating the adaptive increase in CO required to optimize PBro2 during acute anemia.NEW & NOTEWORTHY This study has demonstrated that bilateral nephrectomy acutely impaired cardiac output (CO) and microvascular brain Po2 (PBro2), at baseline. Following acute hemodilution, nephrectomy prevented the adaptive increase in CO associated with acute hemodilution leading to a further reduction in PBro2, accentuating the degree of cerebral tissue hypoxia. These data support a role for the kidney in maintaining PBro2 and initiating the increase in CO that optimized brain perfusion during acute anemia.

Transfusion thresholds in acute coronary syndromes.

PURPOSE OF REVIEW: Anemia is prevalent in patients with acute coronary syndromes. In this setting, there is uncertainty and controversy surrounding the optimal transfusion strategy for managing anemia. The goal of this review is to summarize the current clinical evidence, guidelines, and future directions for managing transfusion in acute coronary syndromes. RECENT FINDINGS: There is limited evidence from randomized trials evaluating restrictive versus liberal transfusion in patients hospitalized with and/or for acute coronary syndromes. The results from these studies suggest clinical equipoise between transfusion strategies for short term outcomes, and a trend toward favoring a liberal strategy for long term major adverse cardiac events. There is inconsistency across clinical practice guidelines with respect to the optimal strategy for managing anemia and transfusion in acute coronary syndromes due to insufficient evidence. SUMMARY: More evidence is urgently needed to conclusively establish the optimal strategy for transfusion management in the setting of acute coronary syndromes. These data will directly inform harmonization of clinical practice guidelines. Future investigations should explore alternative strategies to hemoglobin for quantifying the degree of anemic stress for personalizing transfusion therapy, the effects on functional outcomes, and managing anemia following hospital discharge.

Importance of assessing biomarkers and physiological parameters of anemia-induced tissue hypoxia in the perioperative period

Abstract Anemia is associated with increased risk of Acute Kidney Injury (AKI), stroke and mortality in perioperative patients. We sought to understand the mechanism(s) by assessing the integrative physiological responses to anemia (kidney, brain), the degrees of anemia-induced tissue hypoxia, and associated biomarkers and physiological parameters. Experimental measurements demonstrate a linear relationship between blood Oxygen Content (CaO2) and renal microvascular PO2 (y = 0.30x + 6.9, r2= 0.75), demonstrating that renal hypoxia is proportional to the degree of anemia. This defines the kidney as a potential oxygen sensor during anemia. Further evidence of renal oxygen sensing is demonstrated by proportional increase in serum Erythropoietin (EPO) during anemia (y = 93.806*10−0.02, r2= 0.82). This data implicates systemic EPO levels as a biomarker of anemia-induced renal tissue hypoxia. By contrast, cerebral Oxygen Delivery (DO2) is defended by a profound proportional increase in Cerebral Blood Flow (CBF), minimizing tissue hypoxia in the brain, until more severe levels of anemia occur. We hypothesize that the kidney experiences profound early anemia-induced tissue hypoxia which contributes to adaptive mechanisms to preserve cerebral perfusion. At severe levels of anemia, renal hypoxia intensifies, and cerebral hypoxia occurs, possibly contributing to the mechanism(s) of AKI and stroke when adaptive mechanisms to preserve organ perfusion are overwhelmed. Clinical methods to detect renal tissue hypoxia (an early warning signal) and cerebral hypoxia (a later consequence of severe anemia) may inform clinical practice and support the assessment of clinical biomarkers (i.e., EPO) and physiological parameters (i.e., urinary PO2) of anemia-induced tissue hypoxia. This information may direct targeted treatment strategies to prevent adverse outcomes associated with anemia.

Additive Manufacturing by Heating at a Patterned Photothermal Interface.

Direct additive manufacturing (AM) of commercial silicones is an unmet need with high demand. We report a new technology, heating at a patterned photothermal interface (HAPPI), which achieves AM of commercial thermoset resins without any chemical modifications. HAPPI integrates desirable aspects of stereolithography with the thermally driven chemical modalities of commercial silicone formulations. In this way, HAPPI combines the geometric advantages of vat photopolymerization with the materials properties of, for example, injection molded silicones. We describe the realization of the new technology, HAPPI printing using a commercial Sylgard 184 polydimethylsiloxane resin, comparative analyses of material properties, and demonstration of HAPPI in targeted applications.

Importance of assessing biomarkers and physiological parameters of anemia-induced tissue hypoxia in the perioperative period.

Anemia is associated with increased risk of Acute Kidney Injury (AKI), stroke and mortality in perioperative patients. We sought to understand the mechanism(s) by assessing the integrative physiological responses to anemia (kidney, brain), the degrees of anemia-induced tissue hypoxia, and associated biomarkers and physiological parameters. Experimental measurements demonstrate a linear relationship between blood Oxygen Content (CaO2) and renal microvascular PO2 (y = 0.30x + 6.9, r2 = 0.75), demonstrating that renal hypoxia is proportional to the degree of anemia. This defines the kidney as a potential oxygen sensor during anemia. Further evidence of renal oxygen sensing is demonstrated by proportional increase in serum Erythropoietin (EPO) during anemia (y = 93.806*10-0.02, r2 = 0.82). This data implicates systemic EPO levels as a biomarker of anemia-induced renal tissue hypoxia. By contrast, cerebral Oxygen Delivery (DO2) is defended by a profound proportional increase in Cerebral Blood Flow (CBF), minimizing tissue hypoxia in the brain, until more severe levels of anemia occur. We hypothesize that the kidney experiences profound early anemia-induced tissue hypoxia which contributes to adaptive mechanisms to preserve cerebral perfusion. At severe levels of anemia, renal hypoxia intensifies, and cerebral hypoxia occurs, possibly contributing to the mechanism(s) of AKI and stroke when adaptive mechanisms to preserve organ perfusion are overwhelmed. Clinical methods to detect renal tissue hypoxia (an early warning signal) and cerebral hypoxia (a later consequence of severe anemia) may inform clinical practice and support the assessment of clinical biomarkers (i.e., EPO) and physiological parameters (i.e., urinary PO2) of anemia-induced tissue hypoxia. This information may direct targeted treatment strategies to prevent adverse outcomes associated with anemia.

Multifactorial Causes of Paranoid Schizophrenia With Auditory-Visual Hallucinations in a 31-Year-Old Male With History of Traumatic Brain Injury and Substance Abuse.

Schizophrenia is a chronic psychiatric disorder that classically presents with distortions of thought, behavior, and perceptions that are often misdiagnosed. One difficulty in diagnosing schizophrenia is due to its phenotypically heterogeneous condition that can be precipitated by a combination of genetic, epigenetic, and environmental factors. The prevalence of schizophrenia is roughly 1%, but it is often misdiagnosed. Possible differential diagnoses include depression or bipolar disorder with psychosis, psychosis due to a medical condition, schizotypal and schizoid personality disorders, and neurocognitive disorders.  In this case report, a 31-year-old male presents with thoughts of suicide following a recent exacerbation of his hallucinations. On presentation, the patient presented with a historical diagnosis of "paranoid schizophrenia" as well as a history of traumatic brain injury (TBI), poly-substance use disorder, and a family history of schizophrenia. This case serves to highlight the difficulties of making an accurate diagnosis and providing evidenced-based treatment.

Opioid prescribing and utilization patterns in patients having elective hip and knee arthroplasty: association between prescription patterns and opioid consumption.

PURPOSE: Although guidelines can reduce postoperative opioid prescription, the problem of unused opioids persists. We assessed the pattern of opioid prescription and utilization after total hip arthroplasty (THA) and total knee arthroplasty (TKA). We hypothesized that opioid prescription patterns can influence opioid utilization. METHODS: With institutional ethics approval, patients undergoing THA and TKA were enrolled prospectively. Surveys on opioid use were completed at two, six, and 12 weeks after surgery. Patients' age, sex, American Society of Anesthesiologists' Physical Status score, first 24-hr opioid consumption, quantity of opioid prescribed, and quantity of opioid utilized were analyzed to evaluate their effect on opioid consumption, unused opioid, and patient satisfaction. RESULTS: Patients received prescriptions ranging from 200 morphine milligram equivalents (MME) to 800 MME. Three hundred and thirty THA and 230 TKA patients completed the surveys. Opioid utilization was influenced by the amount of prescribed opioids for both THA and TKA. The percentage of prescribed opioids used (~55% in THA and ~75% in TKA) and the proportion of patients using all prescribed opioids (~22% in THA and ~50% in TKA) were higher after TKA vs THA (P < 0.001 for both). Patients who used opioids for two days or less accounted for most (~50%) of the unused opioid. Patient satisfaction remained high and was not influenced by the amount of prescribed opioid. CONCLUSION: This study showed that larger prescriptions are associated with higher opioid consumption. A wide variation in opioid consumption requires approaches to minimize the initial opioid prescription and to provide additional prescriptions for patients that require higher levels of analgesia.

RéSUMé: OBJECTIF: Bien que les lignes directrices puissent réduire la prescription d'opioïdes postopératoires, le problème des opioïdes inutilisés persiste. Nous avons évalué les schémas de prescription et d'utilisation d'opioïdes après une arthroplastie totale de la hanche (ATH) et une arthroplastie totale du genou (ATG). Nous avons émis l'hypothèse que les schémas de prescription d'opioïdes pouvaient influencer l'utilisation des opioïdes. MéTHODE: Avec l'approbation du comité d'éthique de notre établissement, les patients bénéficiant d'une ATH et une ATG ont été recrutés de manière prospective. Les questionnaires sur la consommation d'opioïdes ont été complétés deux, six et 12 semaines après la chirurgie. L'âge, le sexe et le score de statut physique selon l'American Society of Anesthesiologists des patients, ainsi que la consommation d'opioïdes au cours des premières 24 heures postopératoires, la quantité d'opioïdes prescrits et la quantité d'opioïdes utilisés ont été analysés pour évaluer leur effet sur la consommation d'opioïdes, les opioïdes inutilisés et la satisfaction des patients. RéSULTATS: Les patients ont reçu des ordonnances allant de 200 équivalents de morphine en milligrammes (EMM) à 800 EMM. Trois cent trente patients bénéficiant d'une ATH et 230 patients d'une ATG ont répondu aux questionnaires. L'utilisation des opioïdes a été influencée par la quantité d'opioïdes prescrits pour l'ATH et l'ATG. Le pourcentage d'opioïdes prescrits utilisés (~55 % dans l'ATH et ~75 % dans l'ATG) et la proportion de patients utilisant tous les opioïdes prescrits (~22 % dans l'ATH et ~50 % dans l'ATG) étaient plus élevés après l'ATG vs l'ATH (P < 0,001 pour les deux). Les patients qui ont utilisé des opioïdes pendant deux jours ou moins étaient à l'origine de la plupart (~ 50%) des opioïdes inutilisés. La satisfaction des patients est demeurée élevée et n'a pas été influencée par la quantité d'opioïdes prescrits. CONCLUSION: Cette étude a démontré que les ordonnances plus élevées sont associées à une consommation plus élevée d'opioïdes. Une grande variation dans la consommation d'opioïdes nécessite des approches visant à minimiser la prescription initiale d'opioïdes et à fournir des ordonnances supplémentaires aux patients qui nécessitent des niveaux plus élevés d'analgésie.

Impact of sodium glucose linked cotransporter-2 inhibition on renal microvascular oxygen tension in a rodent model of diabetes mellitus.

BACKGROUND: The mechanisms whereby inhibitors of sodium-glucose linked cotransporter-2 (SGLT2) exert their nephroprotective effects in patients with diabetes are incompletely understood but have been hypothesized to include improved tissue oxygen tension within the renal cortex. The impact of SGLT2 inhibition is likely complex and region specific within the kidney. We hypothesize that SGLT2 inhibitors have differential effects on renal tissue oxygen delivery and consumption in specific regions of the diabetic kidney, including the superficial cortex, containing SGLT2-rich components of proximal tubules, versus the deeper cortex and outer medulla, containing predominantly SGLT1 receptors. METHODS: We measured glomerular filtration rate (GFR), microvascular kidney oxygen tension (Pk O2 ), erythropoietin (EPO) mRNA, and reticulocyte count in diabetic rats (streptozotocin) treated with the SGLT2 inhibitor, dapagliflozin. Utilizing phosphorescence quenching by oxygen and an intravascular oxygen sensitive probe (Oxyphor PdG4); we explored the effects of SGLT2 inhibition on Pk O2 in a region-specific manner, in vivo, in diabetic and non-diabetic rats. Superficial renal cortical or deeper cortical and outer medullary Pk O2 were measured utilizing excitations with blue and red light wavelengths, respectively. RESULTS: In diabetic rats treated with dapagliflozin, measurement within the superficial cortex (blue light) demonstrated no change in Pk O2 . By contrast, measurements in the deeper cortex and outer medulla (red light) demonstrated a significant reduction in Pk O2 in dapagliflozin treated diabetic rats (p = 0.014). Consistent with these findings, GFR was decreased, hypoxia-responsive EPO mRNA levels were elevated and reticulocyte counts were increased with SGLT2 inhibition in diabetic rats (p < 0.05 for all). CONCLUSIONS: These findings indicate that microvascular kidney oxygen tension is maintained in the superficial cortex but reduced in deeper cortical and outer medullary tissue, possibly due to the regional impact of SGLT-2 inhibition on tissue metabolism. This reduction in deeper Pk O2 had biological impact as demonstrated by increased renal EPO mRNA levels and circulating reticulocyte count.

Renal microvascular oxygen tension during hyperoxia and acute hemodilution assessed by phosphorescence quenching and excitation with blue and red light.

PURPOSE: The kidney plays a central physiologic role as an oxygen sensor. Nevertheless, the direct mechanism by which this occurs is incompletely understood. We measured renal microvascular partial pressure of oxygen (PkO2) to determine the impact of clinically relevant conditions that acutely change PkO2 including hyperoxia and hemodilution. METHODS: We utilized two-wavelength excitation (red and blue spectrum) of the intravascular phosphorescent oxygen sensitive probe Oxyphor PdG4 to measure renal tissue PO2 in anesthetized rats (2% isoflurane, n = 6) under two conditions of altered arterial blood oxygen content (CaO2): 1) hyperoxia (fractional inspired oxygen 21%, 30%, and 50%) and 2) acute hemodilutional anemia (baseline, 25% and 50% acute hemodilution). The mean arterial blood pressure (MAP), rectal temperature, arterial blood gases (ABGs), and chemistry (radiometer) were measured under each condition. Blue and red light enabled measurement of PkO2 in the superficial renal cortex and deeper cortical and medullary tissue, respectively. RESULTS: PkO2 was higher in the superficial renal cortex (~ 60 mmHg, blue light) relative to the deeper renal cortex and outer medulla (~ 45 mmHg, red light). Hyperoxia resulted in a proportional increase in PkO2 values while hemodilution decreased microvascular PkO2 in a linear manner in both superficial and deeper regions of the kidney. In both cases (blue and red light), PkO2 correlated with CaO2 but not with MAP. CONCLUSION: The observed linear relationship between CaO2 and PkO2 shows the biological function of the kidney as a quantitative sensor of anemic hypoxia and hyperoxia. A better understanding of the impact of changes in PkO2 may inform clinical practices to improve renal oxygen delivery and prevent acute kidney injury.

RéSUMé: OBJECTIF: Les reins jouent un rôle physiologique central en tant que détecteurs d'oxygène. Cependant, le mécanisme direct de ce rôle n'est pas complètement compris. Nous avons mesuré la pression partielle d'oxygène microvasculaire rénal (PkO2) afin de déterminer l'impact de conditions pertinentes d'un point de vue clinique qui modifient de façon aiguë la PkO2, y compris l'hyperoxie et l'hémodilution. MéTHODE: Nous avons utilisé l'excitation à deux longueurs d'onde (spectres rouge et bleu) de la sonde phosphorescente, sensible à l'oxygène, intravasculaire Oxyphor PdG4 afin de mesurer la PO2 dans le tissu rénal de rats sous anesthésie (isoflurane 2 %, n = 6) dans deux conditions de contenu en oxygène du sang artériel (CaO2) altéré : 1) hyperoxie (fraction d'oxygène inspiré 21 %, 30 % et 50 %) et 2) anémie par hémodilution aiguë (valeurs de base, hémodilution aiguë 25 % et 50 %). La tension artérielle moyenne (TAM), la température rectale, les gaz sanguins artériels et la chimie (radiomètre) ont été mesurés dans chacune des conditions. Les lumières bleue et rouge ont permis de mesurer la PkO2 dans le cortex rénal superficiel et les tissus cortical et médullaire plus profonds, respectivement. RéSULTATS: La PkO2 était plus élevée dans le cortex rénal superficiel (~ 60 mmHg, lumière bleue) comparativement au cortex rénal plus profond et à la zone médullaire extérieure (~ 45 mmHg, lumière rouge). L'hyperoxie a entraîné une augmentation proportionnelle des valeurs de PkO2, alors que l'hémodilution a diminué la PkO2 microvasculaire de façon linéaire tant dans les régions rénales superficielles que plus profondes. Dans les deux cas (lumières bleue et rouge), la PkO2 était corrélée au CaO2 mais pas à la TAM. CONCLUSION: La relation linéaire observée entre le CaO2 et la PkO2 montre la fonction biologique du rein en tant que détecteur quantitatif de l'hypoxie anémique et de l'hyperoxie. Une meilleure compréhension de l'impact des changements de la PkO2 pourrait guider les pratiques cliniques afin d'améliorer la distribution d'oxygène aux reins et prévenir l'insuffisance rénale aiguë.

When to transfuse your acute care patient? A narrative review of the risk of anemia and red blood cell transfusion based on clinical trial outcomes.

This narrative review critically evaluates the evidence for risk of anemia and red blood cell (RBC) transfusion. For this purpose, it assesses large prospective randomized-controlled trials (RCTs) in medical, surgical, and critical care patient populations in which the impact of specific hemoglobin transfusion thresholds are compared. In these trials, the risks of anemia relative to those of RBC transfusion are assessed. The results of published systematic reviews and meta-analyses are also discussed. Lastly, recommendations for patient blood management and treatment of anemia are explored. The main conclusion of this review emphasizes that the decision to transfuse RBCs is complex and depends on the interaction between multiple factors including the balance between the risk of anemia and the risk of RBC transfusion, existing patient comorbidities, and medical and surgical exposures. The transfusion thresholds recommended by current guidelines vary for medical and surgical patient populations. Guidelines suggesting specific transfusion thresholds for different patient populations should be viewed as a starting point for making an informed decision about RBC transfusion. Alternatives to transfusion (i.e., patient blood management), biomarkers of anemia-induced tissue hypoxia, and transfusion alternatives should continue to be evaluated in large RCTs, with the goal of improving event-free survival in critically ill and perioperative patients.

RéSUMé: Ce compte rendu narratif évalue de façon critique les données probantes concernant le risque de l'anémie et de la transfusion d'érythrocytes. Pour ce faire, nous avons évalué des études randomisées contrôlées (ERC) prospectives de grande envergure réalisées auprès de populations de patients médicaux, chirurgicaux et de soins intensifs dans lesquelles l'impact de seuils spécifiques de transfusion d'hémoglobine est comparé. Dans ces études, les risques de l'anémie sont comparés aux risques de la transfusion d'érythrocytes. Les résultats des comptes rendus systématiques et méta-analyses publiés sont également présentés. Enfin, les recommandations concernant la gestion du sang des patients et le traitement de l'anémie sont explorées. La conclusion principale de ce compte rendu souligne que la décision de transfuser des érythrocytes est complexe et dépend de l'interaction de plusieurs facteurs, notamment de l'équilibre entre le risque de l'anémie et le risque de la transfusion d'érythrocytes, les comorbidités existantes du patient, et les risques médicaux et chirurgicaux. Les seuils de transfusion recommandés par les directives actuelles sont différents pour les populations de patients médicaux et chirurgicaux. Les directives proposant des seuils de transfusion spécifiques en fonction des différentes populations de patients devraient être considérées comme point de départ pour prendre une décision informée concernant la transfusion d'érythrocytes. Les alternatives à la transfusion (c.-à-d. la gestion du sang des patients), les biomarqueurs d'une hypoxie tissulaire induite par l'anémie et les alternatives à la transfusion devraient continuer à être évalués dans des ERC d'envergure, avec pour but l'amélioration de la survie sans complication des patients en état critique et périopératoires.

Renal tissue Po2 sensing during acute hemodilution is dependent on the diluent.

Sensing changes in blood oxygen content ([Formula: see text]) is an important physiological role of the kidney; however, the mechanism(s) by which the kidneys sense and respond to changes in [Formula: see text] are incompletely understood. Accurate measurements of kidney tissue oxygen tension ([Formula: see text]) may increase our understanding of renal oxygen-sensing mechanisms and could inform decisions regarding the optimal fluid for intravascular volume resuscitation to maintain renal perfusion. In some clinical settings, starch solution may be nephrotoxic, possibly due to inadequacy of tissue oxygen delivery. We hypothesized that hemodilution with starch colloid solutions would reduce [Formula: see text] to a more severe degree than other diluents. Anesthetized Sprague-Dawley rats (n = 77) were randomized to undergo hemodilution with either colloid (6% hydroxyethyl starch or 5% albumin), crystalloid (0.9% saline), or a sham procedure (control) (n = 13-18 rats/group). Data were analyzed by ANOVA with significance assigned at P < 0.05. After hemodilution, mean arterial pressure (MAP) decreased marginally in all groups, while hemoglobin (Hb) and [Formula: see text] decreased in proportion to the degree of hemodilution. Cardiac output was maintained in all groups after hemodilution. [Formula: see text] decreased in proportion to the reduction in Hb in all treatment groups. At comparably reduced Hb, and maintained arterial oxygen values, hemodilution with starch resulted in larger decreases in [Formula: see text] relative to animals hemodiluted with albumin or saline (P < 0.008). Renal medullary erythropoietin (EPO) mRNA levels increased more prominently, relative to other hypoxia-regulated molecules (GLUT-1, GAPDH, and VEGF). Our data demonstrate that the kidney acts as a biosensor of reduced [Formula: see text] following hemodilution and that [Formula: see text] may provide a quantitative signal for renal cellular responsiveness to acute anemia. Evidence of a more severe reduction in [Formula: see text] following hemodilution with starch colloid solution suggests that tissue hypoxia may contribute to starch induced renal toxicity.

Emerging investigator series: primary emissions, ozone reactivity, and byproduct emissions from building insulation materials.

Building insulation materials can affect indoor air by (i) releasing primary volatile organic compounds (VOCs) from building enclosure cavities to the interior space, (ii) mitigating exposure to outdoor pollutants through reactive deposition (of oxidants, e.g., ozone) or filtration (of particles) in infiltration air, and (iii) generating secondary VOCs and other gas-phase byproducts resulting from oxidant reactions. This study reports primary VOC emission fluxes, ozone (O3) reaction probabilities (γ), and O3 reaction byproduct yields for eight common, commercially available insulation materials. Fluxes of primary VOCs from the materials, measured in a continuous flow reactor using proton transfer reaction-time of flight-mass spectrometry, ranged from 3 (polystyrene with thermal backing) to 61 (cellulose) µmol m-2 h-1 (with total VOC mass emission rates estimated to be between ∼0.3 and ∼3.3 mg m-2 h-1). Major primary VOC fluxes from cellulose were tentatively identified as compounds likely associated with cellulose chemical and thermal decomposition products. Ozone-material γ ranged from ∼1 × 10-6 to ∼30 × 10-6. Polystyrene with thermal backing and polyisocyanurate had the lowest γ, while cellulose and fiberglass had the highest. In the presence of O3, total observed volatile byproduct yields ranged from 0.25 (polystyrene) to 0.85 (recycled denim) moles of VOCs produced per mole of O3 consumed, or equivalent to secondary fluxes that range from 0.71 (polystyrene) to 10 (recycled denim) µmol m-2 h-1. Major emitted products in the presence of O3 were generally different from primary emissions and were characterized by yields of aldehydes and acetone. This work provides new data that can be used to evaluate and eventually model the impact of "hidden" materials (i.e., those present inside wall cavities) on indoor air quality. The data may also guide building enclosure material selection, especially for buildings in areas of high outdoor O3.

Disruption of the nuclear p53-GAPDH complex protects against ischemia-induced neuronal damage.

Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) is conventionally considered a critical enzyme that involves in glycolysis for energy production. Recent previous studies have suggested that GAPDH is important in glutamate-induced neuronal excitotoxicity, while accumulated evidence also demonstrated that GAPDH nuclear translocation plays a critical role in cell death. However, the molecular mechanisms underlying this process remain largely unknown. In this study, we showed that GAPDH translocates to the nucleus in a Siah1-dependent manner upon glutamate stimulation. The nuclear GAPDH forms a protein complex with p53 and enhances p53 expression and phosphorylation. Disruption of the GAPDH-p53 interaction with an interfering peptide blocks glutamate-induced cell death and GAPDH-mediated up-regulation of p53 expression and phosphorylation. Furthermore, administration of the interfering peptide in vivo protects against ischemia-induced cell death in rats subjected to tMCAo. Our data suggest that the nuclear p53-GAPDH complex is important in regulating glutamate-mediated neuronal death and could serve as a potential therapeutic target for ischemic stroke treatment.

Disruption of the GluR2/GAPDH complex protects against ischemia-induced neuronal damage.

BACKGROUND: Excitotoxicity and neuronal death following ischemia involve AMPA (α-amino-3hydroxy-5-methylisoxazole-4-propionic acid) glutamate receptors. We have recently reported that the GluR2 subunit of AMPA receptors (AMPARs) forms a protein complex with GAPDH (glyceraldehyde-3-phosphate dehydrogenase). The GluR2/GAPDH complex co-internalizes upon activation of AMPA receptors. Disruption of the GluR2/GAPDH interaction with an interfering peptide protects cells against AMPAR-mediated excitotoxicity and protects against damage induced by oxygen-glucose deprivation (OGD), an in vitro model of brain ischemia. OBJECTIVE: We sought to test the hypothesis that disruption of the GluR2/GAPDH interaction with an interfering peptide would protect against ischemia-induced neuronal damage in vivo. METHOD: The rat 4-vessel occlusion (4-VO) model was used to investigate whether the GluR2/GAPDH interaction was enhanced in the hippocampus, and if our newly developed interfering peptide could protect against neuronal death in the ischemic brain area. The transient rat middle cerebral artery occlusion (tMCAo) model was used to determine whether our peptide could reduce infarction volume and improve neurological function. Finally, GAPDH lentiviral shRNA was injected into the brain to reduce GAPDH expression one week prior to tMCAo, to confirm the role of GAPDH in the pathophysiology of brain ischemia. RESULTS: The GluR2/GAPDH interaction is upregulated in the hippocampus of rats subjected to transient global ischemia. Administration of an interfering peptide that is able to disrupt the GluR2/GAPDH interaction in vivo protects against ischemia-induced cell death in rat models of global ischemia and decreases the infarct volume as well as neurological score in a rat model focal ischemia. Consistent with these observations, decreased GAPDH expression also protects against ischemia-induced cell death in an animal model of focal ischemia. CONCLUSION: Disruption of the GluR2/GAPDH interaction protects against ischemia-induced neuronal damage in vivo. The GluR2/GAPDH interaction may be a novel therapeutic target for development of treatment for ischemic stroke.