Aberrant Oxygen Concentrations Induce Systemic Inflammation in a Murine Model.

INTRODUCTION: Hypoxia is a significant cause of secondary insult in the critically ill trauma or surgical patient. The cause of increased mortality following a brief period of hypoxia is not well understood. The aim of this study is to determine the effect of acute, isolated deviations in oxygen concentration on proinflammatory cytokine release and markers of endothelial stress in a murine model. METHODS: Mice were randomized to either control, hypoxia, or hyperoxia group. The control group was exposed to room air for 60 min, the hyperoxia group was exposed to 70% fraction of inspired oxygen, and the hypoxia group was exposed to 10% fraction of inspired oxygen for 60 min. Whole blood collection was completed via cardiac puncture. Serum concentrations of proinflammatory cytokines and endothelial stress markers were analyzed via enzyme-linked immunosorbent assay. RESULTS: Following exposure to hypoxic conditions, there was a significant increase in interleukin (IL)-1α (IL-1 α), IL-1 ß, IL-3, IL-4, IL-6, IL-10, tumor necrosis factor α . Following exposure to hyperoxic conditions, there was a significant increase in monocyte chemoattractant protein-1 and regulated upon activation normal T cell expressed and presumably secreted, as well as a significant decrease in IL-12, and IL-17. No clinically significant difference was noted in serum concentration of endothelial stress markers between the treatment groups. DISCUSSION: Exposure to oxygen extremes induces systemic inflammation as measured by proinflammatory cytokines in a murine model. Hyperoxia also demonstrates the ability to downregulate certain inflammatory pathways while inducing others. No effect on serum concentration of endothelial stress markers is observed following acute, isolated hypoxic or hyperoxic conditions.

Perceptions of the White Coat: Generational, Regional, and Gender Differences Among Surgeons.

INTRODUCTION: Recent studies have evaluated patient perception of physician attire; however, few studies have considered physician perceptions of workplace attire. This study aimed to assess current trends regarding attire preferences among surgeons. METHODS: A national, population-based survey was distributed via email and "X" (Twitter). Participants were asked to complete an online questionnaire regarding their perception of the white coat, preferred attire in clinical settings, and reasons for choice of attire. RESULTS: Of 481 participants, 172 (36%) were attendings, 164 (34%) were residents, 125 (26%) were medical students, and 20 (4%) were fellows. Those who practiced in the Midwest region were more likely to wear a white coat daily (35.1% versus 28.5% South, 23.5% Northeast, 20.0% West, P < 0.05). Late career surgeons (practicing >20 y) were more likely to wear a white coat in the hospital and wear it daily (56% versus 36% of middle-career surgeons, 34% early-career surgeons, and 26% in training, P < 0.05). Women surgeons more frequently wore a white coat in clinic (64% versus 54% men, P < 0.05), reported that wearing a white coat was influenced by their program's culture (61% versus 46% of men surgeons, P < 0.05), that they would stop wearing a white coat if other members of their department stopped (50% versus 35% of men, P < 0.05), and that they believe the white coat helps distinguish female doctors from nurses (61% versus 50% of men surgeons, P < 0.05). CONCLUSIONS: This study demonstrates generational, regional, and gender differences among surgeons in their perception of the white coat at a national level.

Weight loss after Roux-en-Y gastric bypass and single anastomosis duodenoileostomy following failed sleeve gastrectomy.

OBJECTIVE: While sleeve gastrectomy (SG) results in sustained weight loss for the majority of patients, some will experience inadequate weight loss or weight regain requiring revision. The objective of this study was to evaluate differences in weight loss over time between patients undergoing Roux-en-Y gastric bypass (RYGB) or single anastomosis duodenoileostomy (SADI) after SG. METHODS: We queried a single institution's bariatrics registry to identify patients who underwent RYGB or SADI after previous SG over a three-year period. Demographics, operative characteristics, and post-operative complications were evaluated. Interval total body weight loss (TBWL) and excess body weight loss (EBWL) were calculated from available follow-ups within 2 years. RESULTS: We identified 124 patients who underwent conversion to RYGB (n = 61) or SADI (n = 63) following previous SG. There were no differences in sex, age, or medical comorbidities between groups. The median initial BMI was higher in the SADI group (44.9 vs. 41.9 for RYGB, p = 0.03) with greater excess body weight (56.7 vs. 64.3 kg, p = 0.04). The SADI group had a shorter median operative duration (157 vs. 182 min for RYGB, p < 0.01) and lower readmission rates (0 vs. 14.75%, p < 0.01). There was no difference in post-operative complications or need for rehydration therapy between the groups. Among 122 patients (98.4%) that had follow-up weights available, there were no differences in TBWL between groups. RYGB patients had a higher EBWL at 2, 3, and 6 months (p < 0.05 for all comparisons), but there were no differences between RYGB and SADI at 1 or 2 years. CONCLUSIONS: Both RYGB and SADI conversions proved effective for further weight loss following failed SG at our academic center. While neither demonstrated clear superiority in long-term (> 1 year) weight loss, RYGB's restrictive gastric pouch may explain its early weight loss advantage.

Microvesicles from stored red blood cells induce P-selectin and von Willebrand factor release from endothelial cells via a protein kinase C-dependent mechanism.

INTRODUCTION: The use of packed red blood cells (pRBCs) for resuscitation is limited by the red blood cell storage lesion, a series of biochemical and physiological changes that occur during the storage and aging of blood. Microvesicles (MVs) shed from pRBCs during this process are one component of the red blood cell storage lesion and lead to acute lung injury and pulmonary vascular microthrombi. We hypothesized that MVs from stored pRBCs lead to the release of P-selectin and von Willebrand factor (vWF) from endothelial cells and that this mechanism is mediated via activation of protein kinase C (PKC) or protein kinase A (PKA). METHODS: Leukoreduced, platelet-poor murine pRBCs were isolated from C57BL/6 8-12 week-old male mice via cardiac puncture, prepared via centrifugation using a Ficoll gradient, and stored for up to 14 days, the equivalent of 42 days of storage in humans. MVs were isolated from the stored pRBC units via sequential high-speed centrifugation. Murine lung endothelial cells (MLECs) were cultured and grown to confluence, then treated with MVs and either calphostin C, a PKC inhibitor (10 µg/mL), or PKI 14-22 amide, a PKA inhibitor (10 µM). The supernatant was collected after 1 h. P-selectin and vWF A2 concentrations were quantified via ELISA. Immunofluorescent staining for vWF was performed on MLECs. Statistical analysis was performed via unpaired t-test or ANOVA as indicated and reported as mean ± SD. Concentration is reported as pg/mL. RESULTS: MLECs treated with MVs isolated from stored pRBCs demonstrated increased release of P-selectin and vWF A2 in a dose-dependent fashion. MLECs treated with MVs prepared from stored as compared to fresh pRBCs demonstrated increased release of P-selectin (3751 ± 726 vs 359 ± 64 pg/mL, p < 0.0001) and vWF A2 (3141 ± 355 vs 977 ± 75 pg/mL, p < 0.0001) with increasing duration of storage. The treatment of MVs with calphostin C decreased the amount of P-selectin (1471 ± 444 vs 3751 ± 726 pg/mL, p < 0.0001) and VWF A2 (2401 ± 289 vs 3141 ± 355 pg/mL, p = 0.0017) released into the supernatant by MLECs compared to MVs alone. The treatment of MVs with PKI 14-22 increased the amount of P-selectin released compared to MVs alone (1999 ± 67 vs 1601 ± 135 pg/mL, p = 0.0018). CONCLUSIONS: MVs from stored pRBCs stimulate the release of P-selectin and VWF A2 from endothelial cells. The effect of MVs increases with both dose of MVs and age of stored pRBCs from which they are formed. This mechanism is dependent on activation of PKC and inhibition of this enzyme represents a potentially significant strategy to modulate the inflammatory response to resuscitation with stored pRBCs.

Whole blood storage duration alters fibrinogen levels and thrombin formation.

INTRODUCTION: Whole blood resuscitation for hemorrhagic shock in trauma represents an opportunity to correct coagulopathy in trauma while also supplying red blood cells. The production of microvesicles in stored whole blood and their effect on its hemostatic parameters have not been described in previous literature. We hypothesized that microvesicles in aged stored whole blood are procoagulant and increase thrombin production via phosphatidylserine. METHODS: Whole blood was obtained from male C57BL/6 male mice and stored in anticoagulant solution for up to 10 days. At intervals, stored whole blood underwent examination with rotational thromboelastography, and platelet-poor plasma was prepared for analysis of thrombin generation. Microvesicles were prepared from 10-day-old whole blood aliquots and added to fresh whole blood or platelet-poor plasma to assess changes in coagulation and thrombin generation. Microvesicles were treated with recombinant mouse lactadherin prior to addition to plasma to inhibit phosphatidylserine's role in thrombin generation. RESULTS: Aged murine whole blood had decreased fibrin clot formation compared with fresh samples with decreased plasma fibrinogen levels. Thrombin generation in plasma from aged blood increased over time of storage. The addition of microvesicles to fresh plasma resulted in increased thrombin generation compared with controls. When phosphatidylserine on microvesicles was blocked with lactadherin, there was no difference in the endogenous thrombin potential, but the generation of thrombin was blunted with lower peak thrombin levels. CONCLUSION: Cold storage of murine whole blood results in decreased fibrinogen levels and fibrin clot formation. Aged whole blood demonstrates increased thrombin generation, and this is due in part to microvesicle production in stored whole blood. One mechanism by which microvesicles are procoagulant is by phosphatidylserine expression on their membranes.

Age above all: The impact of storage duration in mice resuscitated with whole blood or packed red blood cells and plasma in a hemorrhagic shock model.

BACKGROUND: The use of whole blood compared with a balanced ratio of components in trauma resuscitation remains an area of ongoing investigation. One factor that may affect outcomes is the age of the blood product transfused. We used a murine model of blood banking and hemorrhagic shock resuscitation to compare the effect of storage duration in whole blood and packed red blood cells on the recipient inflammatory response. METHODS: Murine whole blood or packed red blood cells were evaluated for the red blood cells storage lesion up to 14 days. Mice underwent hemorrhagic shock followed by resuscitation with whole blood or packed red blood cells combined with equal volume of thawed plasma (1:1) stored for 1, 7, or 14 days. Serum and lung cytokine/chemokine levels were measured and leukocyte infiltration determined via immunohistochemistry. RESULTS: Both whole blood and packed red blood cells develop a blood storage lesion. Four hours after resuscitation, mice resuscitated with either day 14 whole blood or 1:1 demonstrated increased inflammatory cytokines and chemokines with similar findings within lung tissue compared with mice resuscitated with whole blood and 1:1 products stored for 1 or 7 days. CONCLUSIONS: Resuscitation with murine packed red blood cells or whole blood stored for 14 days produces a pronounced recipient inflammatory response compared with those units stored for lesser durations. Given the shorter storage duration of human whole blood to packed RBCs, resuscitation with whole blood within current storage limits may represent an advantageous resuscitation strategy compared with older packed red blood cells.

Does using artificial intelligence take the person out of personal statements? We can't tell.

BACKGROUND: Use of artificial intelligence to generate personal statements for residency is currently not permitted but is difficult to monitor. This study sought to evaluate the ability of surgical residency application reviewers to identify artificial intelligence-generated personal statements and to understand perceptions of this practice. METHODS: Three personal statements were generated using ChatGPT, and 3 were written by medical students who previously matched into surgery residency. Blinded participants at a single institution were instructed to read all personal statements and identify which were generated by artificial intelligence; they then completed a survey exploring their opinions regarding artificial intelligence use. RESULTS: Of the 30 participants, 50% were faculty (n = 15) and 50% were residents (n = 15). Overall, experience ranged from 0 to 20 years (median, 2 years; interquartile range, 1-6.25 years). Artificial intelligence-derived personal statements were identified correctly only 59% of the time, with 3 (10%) participants identifying all the artificial intelligence-derived personal statements correctly. Artificial intelligence-generated personal statements were labeled as the best 60% of the time and the worst 43.3% of the time. When asked whether artificial intelligence use should be allowed in personal statements writing, 66.7% (n = 20) said no and 30% (n = 9) said yes. When asked if the use of artificial intelligence would impact their opinion of an applicant, 80% (n = 24) said yes, and 20% (n = 6) said no. When survey questions and ability to identify artificial intelligence-generated personal statements were evaluated by faculty/resident status and experience, no differences were noted (P > .05). CONCLUSION: This study shows that surgical faculty and residents cannot reliably identify artificial intelligence-generated personal statements and that concerns exist regarding the impact of artificial intelligence on the application process.

Direct red blood cell effect on thrombosis is dependent on the interaction of tissue factor and calcium with membrane phosphatidylserine.

BACKGROUND: Prior literature has implicated red blood cells (RBCs) in the initiation of thrombosis and suggests that posttransfusion hypercoagulability may occur secondary to the effects of RBCs. Elevated serum tissue factor is a known sequelae of acute trauma. Phosphatidylserine (PS) is a prothrombotic phospholipid present within the RBC cell membrane. We hypothesized that RBC aggregation is dependent on the interaction between RBC membrane bound (exposed) PS, extracellular calcium, and tissue factor. METHODS: Human whole blood (WB) was separated into components, including RBCs and platelet-rich plasma (PRP). Whole blood, PRP, and RBCs underwent impedance aggregometry utilizing arachidonic acid (AA), ADP, collagen, calcium, and tissue factor (TF)-based agonists. Red blood cells then underwent impedance aggregometry utilizing combined calcium and TF agonists. Red blood cells were pretreated with Annexin V, a known PS blocking agent, and underwent impedance aggregometry with combined calcium and TF agonists to determine if the mechanism of calcium/TF-induced RBC aggregability is dependent on PS. Red blood cells treated with calcium, TF, calcium+TF, and pre-treated with Annexin V followed by calcium+TF were perfused through an in vitro model of pulmonary microcirculatory flow. RESULTS: Red blood cell aggregation was significantly higher than that of WB and PRP when utilizing a TF agonist, an effect unique to TF. The combination of calcium and TF demonstrated significantly higher RBC aggregation than either agonist alone. Pretreatment with Annexin V resulted in a significantly reduced aggregability of RBC following treatment with TF + calcium. Red blood cells aged to 42 days did not exhibit significant change in aggregation. Exposure to calcium and TF significantly reduced time to thrombosis of RBCs perfused through a pulmonary microcirculatory model. CONCLUSION: Treatment with both TF and calcium synergistically induces RBC aggregation. Phosphatidylserine appears to play an integral role in the TF/calcium-based, age-independent RBC aggregation response. Red blood cells treated with TF + calcium exhibit more rapid thrombus formation in an in vitro model of pulmonary microcirculatory perfusion.

Long-term follow-up of temporary abdominal closure in complex abdomens during liver transplant.

BACKGROUND: Temporary abdominal closure is commonly employed in liver transplantation when patient factors make primary fascial closure challenging. However, there is minimal data evaluating long-term survival and patient outcomes after temporary abdominal closure. METHODS: A single-center, retrospective review of patients undergoing liver transplantation from January 2013 through December 2017 was performed with a 5-year follow-up. Patients were characterized as either requiring temporary abdominal closure or immediate primary fascial closure at the time of liver transplantation. RESULTS: Of 422 patients who underwent 436 liver transplantations, 17.2% (n = 75) required temporary abdominal closure, whereas 82.8% (n = 361) underwent primary fascial closure. Patients requiring temporary abdominal closure had higher Model for End-Stage Liver Disease scores preoperatively (27 [22-36] vs 23 [20-28], P = .0002), had higher rates of dialysis preoperatively (28.0% vs 12.5%, P = .0007), and were more likely to be hospitalized within 90 days of liver transplantation (64.0% vs 47.5%, P = .0093). On univariable analysis, survival at 1 year was different between the groups (90.9% surviving at 1 year for primary fascial closure versus 82.7% for temporary abdominal closure, P = .0356); however, there was no significant difference in survival at 5 years (83.7% vs 76.0%, P = .11). On multivariable analysis, there was no difference in survival after adjusting for multiple factors. Patients requiring temporary abdominal closure were more likely to have longer hospital stays (median 16 days [9.75-29.5] vs 8 days [6-14], P < .0001), more likely to be readmitted within 30 days (45.3% vs 32.2%, P = .03), and less likely to be discharged home (36.5% vs 74.2%, P < .0001). CONCLUSIONS: Temporary abdominal closure after liver transplantation appears safe and has similar outcomes to primary fascial closure, though it is used more commonly in complex patients.

Literacy Promotion Strategies Within Reach Out and Read: An Exploratory Study.

Literacy promotion (LP) is an essential component of primary care. This study explored different LP strategies in 2 cohorts of children aged 6 months to 6 years coming for routine care. In cohort 1 (N = 24), LP consisted mainly of advice. In cohort 2 (C2, N = 21), LP prioritized observing parent-child dyads reading aloud and giving feedback. Parents were interviewed 1 to 2 weeks later. LP took longer in C2 (138 ± 66 seconds vs 73 ± 50, P < .001), and parents were more likely to recall having learned about reading aloud (48% vs 8%, P < .001), even after controlling for time spent. More parents in C2 reported uncertainty about their reading aloud skills (73% vs 22%, P < .002) and a desire to learn more about reading aloud (100% vs 17%, P < .001). Observation and feedback may make LP more memorable to parents and is more likely to motivate parents to improve their skills in this area.