Cyclodextrin-Induced Suppression of PEG Crystallization from the Melt in a PEG-Peptide Conjugate.

The influence of alpha-cyclodextrin (αCD) on PEG crystallization is examined for a peptide-PEG conjugate, YYKLVFF-PEG3k comprising an amyloid peptide YYKLVFF linked to PEG with molar mass 3 kg mol-1. Remarkably, differential scanning calorimetry (DSC) and simultaneous synchrotron small-angle/wide-angle X-ray scattering (SAXS/WAXS) show that crystallization of PEG is suppressed by αCD, provided that the cyclodextrin content is sufficient. A hexagonal mesophase is formed instead. The αCD threading reduces the conformational flexibility of PEG, and hence suppresses crystallization. These results show that addition of cyclodextrins can be used to tune the crystallization of peptide-polymer conjugates and potentially other polymer/biomolecular hybrids.

Homeotropic orientation of an ion-channel forming mesophase induced by nanotemplate wetting.

Anodic aluminum oxide (AAO) membranes were used as templates to control orientation of an ion-channel forming columnar mesophase obtained by self assembly of a wedge-shaped sulfonate molecule. Inside the AAO structure, the director vector of the mesophase is oriented parallel to the pore axis due to the confinement effect. The molecular arrangement induced by the spatial confinement within the pores is extended over several microns into the remnant film on the AAO surface. The homeotropic alignment of the channels promotes unidimensional ion conduction through the film plane, which is manifested by a considerable increase in conductivity relative to isotropic samples.

Stroke Prevention in Blunt Cerebrovascular Injury: Role of Aspirin 81 mg.

BACKGROUND: The stroke rate in blunt cerebrovascular injury (BCVI) varies from 25% without treatment to less than 8% with antithrombotic therapy. There is no consensus on the optimal management to prevent stroke BCVI. We investigated the efficacy and safety of oral Aspirin (ASA) 81 mg to prevent BCVI-related stroke compared to historically reported stroke rates with ASA 325 mg and heparin. METHODS: A single-center retrospective study included adult trauma patients who received oral ASA 81 mg for BCVI management between 2013 and 2022. Medical records were reviewed for demographic and injury characteristics, imaging findings, treatment-related complications, and outcomes. RESULTS: Eighty-four patients treated with ASA 81 mg for BCVI were identified. The mean age was 41.50 years, and 61.9% were male. The mean Injury Severity Score and Glasgow Coma Scale were 19.82 and 12.12, respectively. A total of 101 vessel injuries were identified, including vertebral artery injuries in 56.4% and carotid artery injuries in 44.6%. Traumatic brain injury was found in 42.9%, and 16.7% of patients had a solid organ injur. Biffl grade I (52.4%) injury was the most common, followed by grade II (37.6%) and grade III (4.9%). ASA 81 mg was started in the first 24 hours in 67.9% of patients, including 20 patients with traumatic brain injury and 8 with solid organ injuries. BCVI-related stroke occurred in 3 (3.5%) patients with Biffl grade II (n = 2) and III (n = 1). ASA-related complications were not identified in any patient. The mean length of stay in the hospital was 10.94 days, and 8 patients died during hospitalization due to complications of polytrauma. Follow-up with computed tomography angiography was performed in 8 (9.5%) patients, which showed improvement in 5 and a stable lesion in 3 at a mean time of 58 days after discharge. CONCLUSIONS: In the absence of clear guidelines regarding appropriate medication, BCVI management should be individualized case-by-case through a multidisciplinary approach. ASA 81 mg is a viable option for BCVI-related stroke prevention compared to the reported stroke rates (2%-8%) with commonly used antithrombotics like heparin and ASA 325 mg. Future prospective studies are needed to provide insight into the safety and efficacy of the current commonly used agent in managing BCVI.

Radiation damage and dose limits in serial synchrotron crystallography at cryo- and room temperatures.

Radiation damage limits the accuracy of macromolecular structures in X-ray crystallography. Cryogenic (cryo-) cooling reduces the global radiation damage rate and, therefore, became the method of choice over the past decades. The recent advent of serial crystallography, which spreads the absorbed energy over many crystals, thereby reducing damage, has rendered room temperature (RT) data collection more practical and also extendable to microcrystals, both enabling and requiring the study of specific and global radiation damage at RT. Here, we performed sequential serial raster-scanning crystallography using a microfocused synchrotron beam that allowed for the collection of two series of 40 and 90 full datasets at 2- and 1.9-Å resolution at a dose rate of 40.3 MGy/s on hen egg white lysozyme (HEWL) crystals at RT and cryotemperature, respectively. The diffraction intensity halved its initial value at average doses (D1/2) of 0.57 and 15.3 MGy at RT and 100 K, respectively. Specific radiation damage at RT was observed at disulfide bonds but not at acidic residues, increasing and then apparently reversing, a peculiar behavior that can be modeled by accounting for differential diffraction intensity decay due to the nonuniform illumination by the X-ray beam. Specific damage to disulfide bonds is evident early on at RT and proceeds at a fivefold higher rate than global damage. The decay modeling suggests it is advisable not to exceed a dose of 0.38 MGy per dataset in static and time-resolved synchrotron crystallography experiments at RT. This rough yardstick might change for proteins other than HEWL and at resolutions other than 2 Å.

Improved perioperative mortality after secondary aortoenteric fistula repair and lessons learned from a 20-year experience.

BACKGROUND: Secondary aortoenteric fistulas (SAEFs) are rare but represent one of the most challenging and devastating problems for vascular surgeons. Several issues surrounding SAEF treatment remain unresolved, including optimal surgical reconstruction and conduit choice. We performed an audit of our experience with SAEFs and highlight aspects of care that have affected outcomes over time with the intent to identify factors associated with best outcomes. METHODS: We performed a single center, retrospective review of all consecutive SAEF repairs (1999-2019), defined as presence of a false communication between an enteric structure and pre-existing aortic graft. The primary endpoint was 30-day mortality. Secondary endpoints included incidence of complications and overall survival. Time-dependent outcome comparison was performed. Cox proportional hazards modeling and life-table analysis estimated risk and freedom from endpoints. RESULTS: A total of 57 patients (63% male; n = 36) presented with SAEF (median age, 69 years; interquartile range [IQR], 61-74 years). Median follow-up time was 10 months (interquartile range, 3-21 months. The most common presenting symptoms were gastrointestinal bleeding (60%; n = 34) and abdominal pain (56%; n= 3 2). For the overall cohort, 30% (n = 17) underwent extra-anatomic bypass with aortic ligation, 30% (n = 17) rifampin-soaked Dacron graft, 26% (n = 15) femoral vein (eg, neoaortoiliac system), and 14% (n = 8) cryopreserved aortic allograft. The enteric communication involved the duodenum in 85% (n = 48), and a double-layer hand-sewn primary repair was most commonly employed (61%; n = 35). Thirty-day mortality was 35% (n = 20) with no significant difference between 90 days (39%; n = 22) and 180 days (42%; n = 24). Morbidity was 70% (n = 40), with gastrointestinal (30%; n = 17; leak [9%]), pulmonary (25%; n = 14), and renal (21%) complications being most common. Incidence of reoperation for any vascular and/or gastrointestinal-related complication was 56% (n = 32). One-year and 3-year survival was 54% ± 6% and 48% ± 8%, respectively. Over time, 30- and 90-day mortality improved (odds ratio, 0.1; 95% confidence interval, 0.4-0.5; P = .002) despite no change in patient factors, operative strategy, conduit choice, or morbidity rate. Prehospital history of gastrointestinal bleeding was associated with worse survival (hazard ratio, 2.0; 95% confidence interval, 1.0-3.9; P = .06); however, reconstruction strategy (in-situ vs extra-anatomic bypass), postoperative gastrointestinal and/or vascular complication, omental flap use, and preoperative endovascular aneurysm repair history were not associated with outcome. CONCLUSIONS: In conclusion, we observed improved short-term mortality despite no significant change in patient presentation or postoperative complications. This highlights increasing institutional experience in selecting the optimal surgical strategy and improved ability to rescue patients experiencing adverse postoperative events. An individualized approach to reconstruction and conduit choice can lead to best outcomes after SAEF management when patients are treated at a high-volume aortic surgery center.

Nutritional impact of omega 3 fatty acids and metabolites in acute and chronic critical illness.

PURPOSE OF REVIEW: Lipids have been utilized historically as a calorie dense means to ensure delivery of essential fatty acids (FA). Since the development of mixed lipid emulsion and investigation of immunomodulatory formulas, there has been an awakening that not all lipids are created equal. This narrative review focuses on contemporary evidence in the utilization of lipids (namely omega 3 fatty acids) in both acute and chronic critical illness. RECENT FINDINGS: Though randomized control trials and meta-analyses provide little guidance regarding clinical practice for patients suffering from chronic critical illness, available literature suggests the potential to use lipid formulas to decrease the inflammatory cycle that drives catabolism. Additionally, this review will address the expanding evidence that specialized pro-resolving mediators (SPMs) may be the future of immunomodulating inflammation in acute and chronic critical illness and the persistent inflammation, immunosuppression, and catabolic syndrome (PICS). SUMMARY: Although societal guidelines, expert consensus, and literature support the use of omega 3 fatty acids in the acute critically ill population, more research is needed regarding omega 3 fatty acids for chronic critical illness and PICS.

Obesity and critical care nutrition: current practice gaps and directions for future research.

BACKGROUND: This review has been developed following a panel discussion with an international group of experts in the care of patients with obesity in the critical care setting and focuses on current best practices in malnutrition screening and assessment, estimation of energy needs for patients with obesity, the risks and management of sarcopenic obesity, the value of tailored nutrition recommendations, and the emerging role of immunonutrition. Patients admitted to the intensive care unit (ICU) increasingly present with overweight and obesity that require individualized nutrition considerations due to underlying comorbidities, immunological factors such as inflammation, and changes in energy expenditure and other aspects of metabolism. While research continues to accumulate, important knowledge gaps persist in recognizing and managing the complex nutritional needs in ICU patients with obesity. Available malnutrition screening and assessment tools are limited in patients with obesity due to a lack of validation and heterogeneous factors impacting nutrition status in this population. Estimations of energy and protein demands are also complex in patients with obesity and may include estimations based upon ideal, actual, or adjusted body weight. Evidence is still sparse on the role of immunonutrition in patients with obesity, but the presence of inflammation that impacts immune function may suggest a role for these nutrients in hemodynamically stable ICU patients. Educational efforts are needed for all clinicians who care for complex cases of critically ill patients with obesity, with a focus on strategies for optimal nutrition and the consideration of issues such as weight stigma and bias impacting the delivery of care. CONCLUSIONS: Current nutritional strategies for these patients should be undertaken with a focus on individualized care that considers the whole person, including the possibility of preexisting comorbidities, altered metabolism, and chronic stigma, which may impact the provision of nutritional care. Additional research should focus on the applicability of current guidelines and evidence for nutrition therapy in populations with obesity, especially in the setting of critical illness.

Cuticle - Designed by nature for the sake of the hair.

OBJECTIVE: The cuticle of human hair has been examined, via a range of analytical methods, in order to reveal previously unknown information about its structure and to deepen understanding of its contribution to fibre properties. METHODS: Cross-sections of hair fibre have been examined with X-ray microdiffraction oriented perpendicular to the surface of the cross-sections. AFM investigations were carried out for further investigating and deciphering the structure of the cuticle. Moisture sorption analytics of cuticle separated from fibre and mechanical tests of decuticled fibres against virgin fibres were used for understanding the role of the cuticle in the economy of hair fibre. RESULTS: Previously unknown swelling behaviour of the hair cuticle during moisture sorption has been revealed, as has an increased significance of the cuticle's role in moisture management at higher values of relative humidity. Through AFM investigation, the reaction of hair cuticles with chlorine water has further strengthened the idea that the Allwörden membrane does not exist, and is actually an artefact of the delamination of the A-layer and exocuticle from the underlying endocuticle. Using decuticled fibres for stress-strain tests, and by comparing the results with those of virgin fibres, the effect of the cuticle on the post-yield area of the hair fibre stress-strain diagram has also been demonstrated. Finally, X-ray microdiffraction and AFM investigations suggest that the cuticle possesses a small-scale ordered structure, based on possibly not fully crystalline and irregularly arranged α-helices oriented almost perpendicular to the growth axis of the fibre and enhancing the general description of cuticle as the protective layer of the fibre. CONCLUSION: The role of the cuticle for the hair fibre is more complex than previously thought. The cuticle is demonstrated not only to possess a hidden rod-matrix structure, that supports its protective nature, but also to play specific roles in the fibre's response to moisture, and in fibre mechanical behaviour.

OBJECTIF : la cuticule des cheveux humains a été examinée à l'aide d'un ensemble de méthodes analytiques, afin de révéler des informations jusqu'alors inconnues sur sa structure et d'approfondir la compréhension de son rôle dans les propriétés de la fibre. MÉTHODES : des coupes transversales de fibres capillaires ont été examinées par microdiffraction radiographique orientée perpendiculairement à la surface des coupes. Des expérimentations par AFM ont été réalisées pour approfondir les recherches et découvrir la structure de la cuticule. Des analyses d'absorption de l'humidité de la cuticule séparée de la fibre et des tests mécaniques des fibres décuticulées par rapport aux fibres vierges ont été utilisés pour comprendre le rôle de la cuticule dans la préservation de la fibre capillaire. RÉSULTATS : un comportement de gonflement jusqu'alors inconnu de la cuticule des cheveux durant l'absorption de l'humidité a été révélé, de même qu'une importance accrue du rôle de la cuticule dans la gestion de l'humidité à des valeurs plus élevées d'humidité relative. À l'aide des expérimentations par AFM, la réaction de la cuticule des cheveux avec de l'eau chlorée a à nouveau renforcé l'idée selon laquelle la membrane d'Allwörden n'existe pas et est en réalité un artéfact de délaminage de la couche A et de l'exocuticule provenant de l'endocuticule sous-jacente. L'utilisation de fibres décuticulées pour des tests de contrainte et la comparaison des résultats avec ceux de fibres vierges ont également démontré l'effet de la cuticule sur la zone post-rendement du diagramme de contrainte de la fibre capillaire. Enfin, les expérimentations par microdiffraction radiographique et AFM suggèrent que la cuticule possède une structure ordonnée à petite échelle, basée sur des hélices alpha potentiellement non entièrement cristallines et disposées de manière irrégulière, orientées presque perpendiculairement à l'axe de croissance de la fibre, améliorant la description générale de la cuticule comme couche protectrice de la fibre. CONCLUSION : le rôle de la cuticule pour la fibre capillaire est plus complexe qu'on ne le pensait. Il a été démontré que la cuticule possède non seulement une structure rod-matrix cachée, qui maintient sa nature protectrice, mais joue également des rôles spécifiques dans la réponse de la fibre à l'humidité et dans son comportement mécanique.

Abdominal Wall Thickness Predicts Surgical Site Infection in Emergency Colon Operations.

BACKGROUND: Body mass index (BMI) does not reliably predict Surgical site infections (SSI). We hypothesize that abdominal wall thickness (AWT) would serve as a better predictor of SSI for patients undergoing emergency colon operations. METHODS: We retrospectively evaluated our Emergency Surgery Database (2007-2018). Emergency colon operations for any indication were included. AWT was measured by pre-operative CT scans at 5 locations. Only superficial and deep SSIs were considered as SSI in the analysis. Univariate then multivariable analyses were used to determine predictors of SSI. RESULTS: 236 patients met inclusion criteria. The incidence of post-operative SSI was 25.8% and the median BMI was 25.8kg/m2 [22.5-30.1]. The median AWT between patients with and without SSI was significantly different (2.1cm [1.4, 2.8] and 1.8cm [1.2, 2.5], respectively). A higher BMI trended toward increased rates of SSI, but this was not statistically significant. In overweight (BMI 25-29.9kg/m2) and obese (BMI ≥30kg/m2) patients, SSI versus no SSI rates were (50.0% versus 41.9% and 47.4% versus 36.4%, P = 0.365 and 0.230) respectively. The incidence of SSI in patients with an average AWT < 1.8cm was 20% and 30% for patients with average AWT ≥1.8cm. On multivariable analysis, AWT ≥1.8cm at 2cm inferior to umbilicus was an independent predictor of SSI (OR 2.98, 95%CI 1.34-6.63, P = 0.007). CONCLUSIONS: AWT is a better predictor of SSI than BMI. Preoperative imaging of AWT may direct intraoperative decisions regarding wound management. Future clinical outcomes research in emergency surgery should include abdominal wall thickness as an important patient variable.

Direct Oral Anticoagulants Are a Potential Alternative to Low-Molecular-Weight Heparin for Thromboprophylaxis in Trauma Patients Sustaining Lower Extremity Fractures.

BACKGROUND: Trauma patients are at a significant risk of venous thromboembolism (VTE), with lower extremity fractures (LEF) being independent risk factors. Use of direct oral anticoagusants (DOACs) for VTE prophylaxis is effective in elective orthopedic surgery, but currently not approved for trauma patients. The primary objective of this study was to compare the effectiveness and safety of thromboprophylaxis of DOACs with low-molecular-weight heparin (LMWH) in trauma patients sustaining LEF. MATERIALS AND METHODS: We included adult trauma patients admitted to trauma quality improvement program participating trauma centers (between 2013 and 2016), who sustained LEF and were started on DOACs or LMWH for thromboprophylaxis after admission. Propensity score matching was performed to compare symptomatic VTE and bleeding control interventions between the groups. RESULTS: Of 1,009,922 patients in trauma quality improvement program, 167,640 met inclusion criteria (165,009 received LMWH and 2631 received DOACs). After propensity score matching, 2280 predominantly elderly (median age: 67 y) isolated femur fracture patients (median ISS: 10) were included in each group (4560 patients in total). Symptomatic VTE occurred in 1.4% of patients in both matched groups (P = 0.992). Bleeding control interventions occurred less often in the DOAC group, albeit statistically insignificant (5.8% versus 6.0%, P = 0.772). CONCLUSIONS: This study found similar rates of VTE and bleeding control measures for thromboprophylaxis with DOACs or LMWH in matched trauma patients with LEF. Further prospective research is warranted to consolidate the safety of DOAC thromboprophylaxis in trauma patients with LEF. Favorable oral administration and likely increased adherence could benefit this high-risk population.

Nanobeam X-ray fluorescence and diffraction computed tomography on human bone with a resolution better than 120 nm.

Studying nanostructured hierarchical materials such as the biomineralized bone is challenging due to their complex 3D structures that call for high spatial resolution. One route to study such materials is X-ray powder diffraction computed tomography (XRD-CT) that reveals the 3D distribution of crystalline phases and X-ray fluorescence computed tomography (XRF-CT) that provides element distributions. However, the spatial resolution of XRD-CT has thus far been limited. Here we demonstrate better than 120 nm 3D resolution on human bone in XRD-CT and XRF-CT measured simultaneously using X-ray nanobeams. The results pave the way for nanoscale 3D characterization of nanocrystalline composites like bone at unprecedented detail.

Omega-3 fatty acid-containing parenteral nutrition in ICU patients: systematic review with meta-analysis and cost-effectiveness analysis.

BACKGROUND: Omega-3 (ω-3) fatty acid (FA)-containing parenteral nutrition (PN) is associated with significant improvements in patient outcomes compared with standard PN regimens without ω-3 FA lipid emulsions. Here, we evaluate the impact of ω-3 FA-containing PN versus standard PN on clinical outcomes and costs in adult intensive care unit (ICU) patients using a meta-analysis and subsequent cost-effectiveness analysis from the perspective of a hospital operating in five European countries (France, Germany, Italy, Spain, UK) and the US. METHODS: We present a pharmacoeconomic simulation based on a systematic literature review with meta-analysis. Clinical outcomes and costs comparing ω-3 FA-containing PN with standard PN were evaluated in adult ICU patients eligible to receive PN covering at least 70% of their total energy requirements and in the subgroup of critically ill ICU patients (mean ICU stay > 48 h). The meta-analysis with the co-primary outcomes of infection rate and mortality rate was based on randomized controlled trial data retrieved via a systematic literature review; resulting efficacy data were subsequently employed in country-specific cost-effectiveness analyses. RESULTS: In adult ICU patients, ω-3 FA-containing PN versus standard PN was associated with significant reductions in the relative risk (RR) of infection (RR 0.62; 95% CI 0.45, 0.86; p = 0.004), hospital length of stay (HLOS) (- 3.05 days; 95% CI - 5.03, - 1.07; p = 0.003) and ICU length of stay (LOS) (- 1.89 days; 95% CI - 3.33, - 0.45; p = 0.01). In critically ill ICU patients, ω-3 FA-containing PN was associated with similar reductions in infection rates (RR 0.65; 95% CI 0.46, 0.94; p = 0.02), HLOS (- 3.98 days; 95% CI - 6.90, - 1.06; p = 0.008) and ICU LOS (- 2.14 days; 95% CI - 3.89, - 0.40; p = 0.02). Overall hospital episode costs were reduced in all six countries using ω-3 FA-containing PN compared to standard PN, ranging from €-3156 ± 1404 in Spain to €-9586 ± 4157 in the US. CONCLUSION: These analyses demonstrate that ω-3 FA-containing PN is associated with statistically and clinically significant improvement in patient outcomes. Its use is also predicted to yield cost savings compared to standard PN, rendering ω-3 FA-containing PN an attractive cost-saving alternative across different health care systems. STUDY REGISTRATION: PROSPERO CRD42019129311.

The Impact of Prior Laparotomy and Intra-abdominal Adhesions on Bowel and Mesenteric Injury Following Blunt Abdominal Trauma.

BACKGROUND: Early recognition of bowel and mesenteric injury following blunt abdominal trauma remains difficult. We hypothesized that patients with intra-abdominal adhesions from prior laparotomy would be subjected to visceral sheering deceleration forces and increased risk for bowel and mesenteric injury following blunt abdominal trauma. METHODS: We performed a multicenter retrospective cohort analysis of 267 consecutive adult trauma patients who underwent operative exploration following moderate-critical (abdominal injury score 2-5) blunt abdominal trauma, comparing patients with prior laparotomy (n = 31) to patients with no prior laparotomy (n = 236). Multivariable regression was performed to identify predictors of bowel or mesenteric injury. RESULTS: There were no significant differences between groups for injury severity scores or findings on abdominal ultrasound, diagnostic peritoneal aspirate/lavage, pelvic radiography, or preoperative CT scan. The prior laparotomy cohort had greater incidence of full thickness bowel injury (26 vs. 9%, p = 0.010) and mesenteric injury (61 vs. 31%, p = 0.001). The proportion of bowel and mesenteric injuries occurring at the ligament of Treitz or ileocecal region was greater in the no prior laparotomy group (52 vs. 25%, p = 0.003). Prior laparotomy was an independent predictor of bowel or mesenteric injury (OR 5.1, 95% CI 1.6-16.8) along with prior abdominal inflammation and free fluid without solid organ injury (model AUC: 0.81, 95% CI 0.74-0.88). CONCLUSIONS: Patients with a prior laparotomy are at increased risk for bowel and mesenteric injury following blunt abdominal trauma. The distribution of bowel and mesenteric injuries among patients with no prior laparotomy favors embryologic transition points tethering free intraperitoneal structures to the retroperitoneum.

Intermittent versus continuous feeding in critically ill adults.

PURPOSE OF REVIEW: Early enteral nutrition is recommended in critically ill adult patients. The optimal method of administering enteral nutrition remains unknown. Continuous enteral nutrition administration in critically ill patients remains the most common practice worldwide; however, its practice has recently been called into question in favor of intermittent enteral nutrition administration, where volume is infused multiple times per day. This review will outline the key differences between continuous and intermittent enteral nutrition, describe the metabolic responses to continuous and intermittent enteral nutrition administration and outline recent studies comparing continuous with intermittent enteral nutrition administration on outcomes in critically ill adults. RECENT FINDINGS: In separate studies, healthy humans and critically ill patients receiving intermittent nutrition (infused over 3 h) had improved whole body protein balance from negative to positive. These studies did not have an isonitrogenous control group. A randomized controlled trial of intermittent bolus versus continuous enteral nutrition in healthy humans found that intermittent bolus feeding increased mesenteric arterial blood flow, increased insulin and peptide YY and reduced blood glucose concentration. A randomized controlled trial comparing intermittent bolus to continuous enteral nutrition in critically ill patients did not demonstrate clinically relevant differences in glycemic variability, insulin use or tube feeding volume or caloric intake between the two groups. SUMMARY: Studies in healthy humans suggest that intermittent nutrient administration, as opposed to continuous, improves whole body protein synthesis. Unfortunately, similarly designed studies are lacking for critically ill patients. Future studies evaluating the impact of intermittent versus continuous nutrition administration on critical care outcomes should take into account factors such as protein quantity, protein quality and delivery route (enteral and/or parenteral). Until further studies are conducted in critically ill patients, a recommendation for or against intermittent nutrition delivery cannot be made.

The effects of beta blockade and clonidine on persistent injury-associated anemia.

BACKGROUND: Nonselective beta blockade (BB) and clonidine may abrogate catecholamine-mediated persistent injury-associated anemia. We hypothesized that critically ill trauma patients who received BB or clonidine would have favorable hemoglobin (Hb) trends when adjusting for operative blood loss (OBL), phlebotomy blood loss (PBL), and red blood cell (RBC) transfusion volumes, and that the effect would be greatest among the elderly, who have higher catecholamine levels. METHODS: We performed a 4-y retrospective cohort analysis of 280 consecutive trauma patients with ICU stay ≥48 h and moderate/severe anemia. Patients who received BB or clonidine for ≥25% of their hospital stay were grouped as the BB/clonidine cohort (n = 84); all other patients served as controls (n = 196). Admission and discharge Hb were used to calculate ΔHb. OBL, PBL, and RBC volume were used to calculate adjusted ΔHb assuming 300 mL RBC = 1 g/dL Hb. RESULTS: BB/clonidine and control patients had similar age, injury severity, comorbid illness, and admission Hb. BB/clonidine patients received fewer RBCs despite greater OBL, though neither association was statistically significant. BB/clonidine patients had higher discharge Hb (9.9 versus 9.5, P = 0.029) and adjusted ΔHb (+1.0 versus -0.8, P = 0.003). Hb curves separated after hospital day 10. The difference in adjusted ΔHb between groups increased with advanced age (all patients: 1.7, ≥50 y: 1.8, ≥60 y: 2.4, ≥70 y: 3.7). CONCLUSIONS: Critically ill trauma patients receiving BB or clonidine had favorable Hb trends when accounting for OBL, PBL, and RBC transfusions. These findings support the hypothesis that BB and clonidine alleviate persistent injury-associated anemia, with strongest effects among the elderly.

Autophagy: should it play a role in ICU management?

PURPOSE OF REVIEW: This review is to discuss the role of autophagy in the critically ill patient population. As the understanding of autophagy continues to expand and evolve, there are certain controversies surrounding whether intensivist should allow the benefit of autophagy to supersede gold standard of insulin therapy or early nutritional support. RECENT FINDINGS: The review is relevant as the current literature seems to support under-feeding patients, and perhaps the reason these studies were positive could be prescribed to the mechanisms of autophagy. It is well understood that autophagy is a physiologic response to stress and starvation, and that the inducible form could help patients with end-organ dysfunction return to homeostasis. SUMMARY: The jury is still out as to how autophagy will play into clinical practice as we review several gold standard therapies for the critically ill.

Can Specialized Pro-resolving Mediators Deliver Benefit Originally Expected from Fish Oil?

PURPOSE OF THE REVIEW: Fish oil (FO) supplementation has historically been used by individuals suffering from cardiovascular disease and other inflammatory processes. However, a meta-analysis of several large randomized control trials (RCTs) suggested FO conferred no benefit in reducing cardiovascular risk. Skeptics surmised that the lack of benefit was related to FO dose or drug interactions; therefore, the widely accepted practice of FO consumption was brought into question. RECENT FINDINGS: Thereafter, Serhan et al. identified specialized pro-resolving mediators (SPMs) to be one of the bioactive components and mechanisms of action of FO. SPMs are thought to enhance resolution of inflammation, as opposed to classic anti-inflammatory agents which inhibit inflammatory pathways. Numerous diseases, including persistent Inflammation, immunosuppression, and catabolic syndrome (PICS), are rooted in a burden of chronic inflammation. SPMs are gaining traction as potential therapeutic agents used to resolve inflammation in cardiovascular disorders, inflammatory bowel disease, sepsis, pancreatitis, and acute respiratory distress syndrome (ARDS). This narrative reviews the history of FO and the various studies that made the health benefits of FO inconclusive, as well as an overview of SPMs and their use in specific disease states.

Effect of Time to Operation on Value of Care in Acute Care Surgery.

BACKGROUND: As reimbursement models evolve, there is increasing emphasis on maximizing value-based care for inpatient conditions. We hypothesized that longer intervals between admission and surgery would be associated with worse outcomes and increased costs for acute care surgery patients, and that these associations would be strongest among patients with high-risk conditions. METHODS: We performed a 5-year retrospective analysis of three risk cohorts: appendectomy (low-risk for morbidity and mortality, n = 618), urgent hernia repair (intermediate-risk, n = 80), and laparotomy for intra-abdominal sepsis with temporary abdominal closure (sTAC; high-risk, n = 102). Associations between the interval from admission to surgery and outcomes including infectious complications, mortality, length of stay, and hospital charges were assessed by regression modeling. RESULTS: Median intervals between admission and surgery for appendectomy, hernia repair, and sTAC were 9.3, 13.5, and 8.1 h, respectively, and did not significantly impact infectious complications or mortality. For appendectomy, each 1 h increase from admission to surgery was associated with increased hospital LOS by 1.1 h (p = 0.002) and increased intensive care unit (ICU) LOS by 0.3 h (p = 0.011). For hernia repair, each 1 h increase from admission to surgery was associated with increased antibiotic duration by 1.6 h (p = 0.007), increased hospital LOS by 3.3 h (p = 0.002), increased ICU LOS by 1.5 h (p = 0.001), and increased hospital charges by $1918 (p < 0.001). For sTAC, each 1 h increase from admission to surgery was associated with increased antibiotic duration by 5.0 h (p = 0.006), increased hospital LOS by 3.9 h (p = 0.046), increased ICU LOS by 3.5 h (p = 0.040), and increased hospital charges by $3919 (p = 0.002). CONCLUSIONS: Longer intervals from admission to surgery were associated with prolonged antibiotic administration, longer hospital and ICU length of stay, and increased hospital charges, with strongest effects among high-risk patients. To improve value of care for acute care surgery patients, operations should proceed as soon as resuscitation is complete.