Early Cold Stored Platelet Transfusion Following Severe Injury: A Randomized Clinical Trial.

OBJECTIVE: To determine the feasibility, efficacy, and safety of early cold stored platelet transfusion compared with standard care resuscitation in patients with hemorrhagic shock. BACKGROUND: Data demonstrating the safety and efficacy of early cold stored platelet transfusion are lacking following severe injury. METHODS: A phase 2, multicenter, randomized, open label, clinical trial was performed at 5 US trauma centers. Injured patients at risk of large volume blood transfusion and the need for hemorrhage control procedures were enrolled and randomized. The intervention was the early transfusion of a single apheresis cold stored platelet unit, stored for up to 14 days versus standard care resuscitation. The primary outcome was feasibility and the principal clinical outcome for efficacy and safety was 24-hour mortality. RESULTS: Mortality at 24 hours was 5.9% in patients who were randomized to early cold stored platelet transfusion compared with 10.2% in the standard care arm (difference, -4.3%; 95% CI, -12.8% to 3.5%; P =0.26). No significant differences were found for any of the prespecified ancillary outcomes. Rates of arterial and/or venous thromboembolism and adverse events did not differ across treatment groups. CONCLUSIONS AND RELEVANCE: In severely injured patients, early cold stored platelet transfusion is feasible, safe and did not result in a significant lower rate of 24-hour mortality. Early cold stored platelet transfusion did not result in a higher incidence of arterial and/or venous thrombotic complications or adverse events. The storage age of the cold stored platelet product was not associated with significant outcome differences. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT04667468.

Ideal timing of early cholecystectomy for acute cholecystitis: An ACS-NSQIP review.

BACKGROUND: Current guidelines fail to specify optimal timing of early cholecystectomy for acute cholecystitis. We hypothesized delaying operation past hospital day (HD) 2 would result in increased 30-day morbidity and mortality. METHODS: The ACS-NSQIP database was queried from 2012 to 2015 for all cholecystectomies for acute cholecystitis from HD 1-7. RESULTS: Delay in cholecystectomy to HD 3-7 was observed in 30% of patients with acute cholecystitis. Patients undergoing operation on HD 3-7 were older with higher rates of comorbidities (median 58yrs; 66%) than HD 1 (48yrs; 51%) or HD 2 (51yrs, p < 0.001; 55%, p < 0.001). Operations on HD 3-7 had increased 30-day mortality (1.0%) and morbidity (12%) in comparison to HD 1 (0.3%, 7%) or HD 2 (0.5%, p < 0.001; 8%, p < 0.001). On multivariable analysis, HD was an independent predictor of mortality (OR 1.15, 95% CI [1.04-1.26]). CONCLUSIONS: Acute cholecystitis should be treated with an urgent operation within 2 days of admission due to increased morbidity and mortality when delayed past HD 2.

Simultaneous lateral interbody fusion and pedicle screws (SLIPS) with CT-guided navigation.

OBJECTIVES: The advent of minimally invasive, percutaneous techniques for the placement of pedicle screws has led to the evolution of a popular treatment paradigm: anterior or lateral interbody fusions followed by posterior percutaneous pedicle screw placement. We present the operative technique for anterior-to-psoas lateral interbody fusion (ATP-LIF) with simultaneous posterior lumbar percutaneous pedicle screw fixation using intraoperative CT-guided navigation. PATIENTS AND METHODS: This technique capitalizes both on the more oblique approach used in the ATP-LIF procedure, as well as the anatomic clarity gleaned from intraoperative CT-guided navigation, to allow for simultaneous placement of pedicle screws in the lateral position without the need for guiding fluoroscopy. RESULTS: The parallel execution of both procedures, in the lateral position, reduces operative time, consolidates a two-stage procedure into one stage, and eliminates the need for prone re-positioning. The use of intraoperative CT-guided navigation reduces the need for fluoroscopy and overall radiation exposure while allowing for pedicle screw placement and the-LIF procedure in truly simultaneous fashion. In this pilot study, a total of 14 pedicle screws were placed with two lateral breaches (14%). CONCLUSION: Simultaneous Lateral Interbody and Pedicle Screws (SLIPS) represents a meaningful evolution of the newly reported single-position lateral interbody fusion with posterior percutaneous pedicle screw fixation.

Population-level outcomes of early versus delayed appendectomy for acute appendicitis using the American College of Surgeons National Surgical Quality Improvement Program.

BACKGROUND: The optimal timing of appendectomy for acute appendicitis has been analyzed with mixed results. We hypothesized that delayed appendectomy would be associated with increased 30-d morbidity and mortality. MATERIALS AND METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was queried for all patients undergoing nonelective appendectomy from 2012 to 2015 with a postoperative diagnosis of appendicitis. Patients were grouped based on hospital day (HD) of operation. Primary outcomes included 30-d mortality and major complications. Logistic regression was performed to determine predictors of major morbidity and mortality. RESULTS: From 2012 to 2015, 112,122 patients underwent appendectomy for acute appendicitis. Appendectomies performed on HD 3 had significantly worse outcomes as demonstrated by increased 30-d mortality (0.6%) and all major postoperative complications (8%) in comparison with operations taking place on HD 1 (0.1%; 3.4%) or HD 2 (0.1%, P < 0.001; 3.6%, P < 0.001). In subgroup analysis, open operations had significantly higher mortality and major postoperative complications, including organ/space surgical site infections (4.6% open versus 2.1% laparoscopic; P < 0.001). Patients with decreased baseline physical status by the American Society of Anesthesiologists Physical Status class had the worst outcomes (1.5% mortality; 14% major complications) when operation was delayed to HD 3. Logistic regression revealed higher American Society of Anesthesiologists Physical Status class and open operations as predictors of major complications; however, HD was not (P = 0.2). CONCLUSIONS: Data from the American College of Surgeons National Surgical Quality Improvement Program demonstrate similar outcomes of appendectomy for acute appendicitis when the operation is performed on HD 1 or 2; however, outcomes are significantly worse for appendectomies delayed until HD 3. Increased complications in this group are likely not attributable to HD of operation, but rather decreased baseline health status and procedure type.

Surgical rescue: The next pillar of acute care surgery.

BACKGROUND: The evolving field of acute care surgery (ACS) traditionally includes trauma, emergency general surgery, and critical care. However, the critical role of ACS in the rescue of patients with a surgical complication has not been explored. We here describe the role of "surgical rescue" in the practice of ACS. METHODS: A prospective, electronic medical record-based ACS registry spanning January 2013 to May 2014 at a large urban academic medical center was screened by ICD-9 codes for acute surgical complications of an operative or interventional procedure. Long-term outcomes were derived from the Social Security Death Index. RESULTS: Of 2,410 ACS patients, 320 (13%) required "surgical rescue": most commonly, from wound complications (32%), uncontrolled sepsis (19%), and acute obstruction (15%). The majority of complications (85%) were related to an operation; 15% were related to interventional procedures. The most common rescue interventions required were bowel resection (23%), wound debridement (18%), and source control of infection (17%); 63% of patients required operative intervention, and 22% required surgical critical care. Thirty-six percent of complications occurred in ACS primary patients ("local"), whereas 38% were referred from another surgical service ("institutional") and 26% referred from another institution ("regional"). Hospital length of stay was longer, and in-hospital and 1-year mortalities were higher in rescue patients compared with those without a complication. Outcomes were equivalent between "local" and "institutional" patients, but hospital length of stay and discharge to home were significantly worse in "institutional" referrals. CONCLUSION: We here describe the distinct role of the acute care surgeon in the surgical management of complications; this is an additional pillar of ACS. In this vital role, the acute care surgeon provides crucial support to other providers as well as direct patient care in the "surgical rescue" of surgical and procedural complications. LEVEL OF EVIDENCE: Epidemiological study, level III; therapeutic/care management study, level IV.

Computed tomography abbreviated assessment of sarcopenia following trauma: The CAAST measurement predicts 6-month mortality in older adult trauma patients.

BACKGROUND: Older adult trauma patients are at increased risk of poor outcome, both immediately after injury and beyond hospital discharge. Identifying patients early in the hospital stay who are at increased risk of death after discharge can be challenging. METHODS: Retrospective analysis was performed using our trauma registry linked with the social security death index from 2010 to 2014. Age was categorized as 18 to 64 and 65 years or older. We calculated mortality rates by age category then selected elderly patients with mechanism of injury being a fall for further analysis. Computed Tomography Abbreviated Assessment of Sarcopenia for Trauma (CAAST) was obtained by measuring psoas muscle cross-sectional area adjusted for height and weight. Kaplan-Meier survival analysis was performed, and proportional hazards regression modeling was used to determine independent risk factors for in-hospital and out-of-hospital mortality. RESULTS: A total of 23,622 patients were analyzed (16,748, aged 18-64 years; and 6,874, aged 65 or older). In-hospital mortality was 1.96% for ages 18 to 64 and 7.19% for age 65 or older (p < 0.001); postdischarge 6-month mortality was 1.1% for ages 18 to 64 and 12.86% for age 65 or older (p < 0.001). Predictors of in-hospital and postdischarge mortality for ages 18 to 64 and in-hospital mortality for ages 65 or older group included injury characteristics such as ISS, admission vitals, and head injury. Predictors of postdischarge mortality for age 65or older included skilled nursing before admission, disposition, and mechanism of injury being a fall. A total of 57.5% (n = 256) of older patients who sustained a fall met criteria for sarcopenia. Sarcopenia was the strongest predictor of out-of-hospital mortality in this cohort with a hazard ratio of 4.77 (95% confidence interval, 2.71-8.40; p < 0.001). CONCLUSION: Out of hospital does not assure out of danger for the elderly. Sarcopenia is a strong predictor of 6-month postdischarge mortality for older adults. The CAAST measurement is an efficient and inexpensive measure that can allow clinicians to target older trauma patients at risk of poor outcome for early intervention and/or palliative care services. LEVEL OF EVIDENCE: Prognostic and epidemiologic study, level III.

Selective roles for toll-like receptors 2, 4, and 9 in systemic inflammation and immune dysfunction following peripheral tissue injury.

BACKGROUND: Toll-like receptors (TLRs) detect endogenous ligands released after trauma and contribute to the proinflammatory response to injury. Posttraumatic mortality correlates with the extent of the immunoinflammatory response to injury that is composed of a complex regulation of innate and adaptive immune responses. Although TLRs are known to modulate innate immune responses, their role in the suppression of lymphocyte responses following traumatic tissue injury is unclear. METHODS: This study used a murine model of severe peripheral tissue injury, involving muscle crush injury and injection of fracture components, to evaluate the roles of TLR2, TLR4, and TLR9 in the early and delayed immunoinflammatory phenotype. Posttraumatic immune dysfunction was measured in our trauma model using the following parameters: ex vivo splenocyte proliferation, TH1 cytokine release, and iNOS (inducible nitric oxide synthase) induction within splenic myeloid-derived suppressor cells. Systemic inflammation and liver damage were determined by circulating interleukin 6 levels and hepatocellular injury. RESULTS: Suppression of splenocyte responses after injury was dependent on TLR4 and TLR9 signaling as was posttraumatic iNOS upregulation in splenic myeloid-derived suppressor cells. TLR2 was found to have only a partial role through contribution to inhibition of splenocyte proliferation. This study also reveals the involvement of TLR2 and TLR4 in the initial systemic inflammatory response to traumatic tissue injury; however, this response was found to be TLR9 independent. CONCLUSION: These findings demonstrate the previously unidentified role of TLR2, TLR4, and TLR9 in the T cell-associated immune dysfunction following traumatic tissue injury. Importantly, this study also illustrates that TLRs play differing and selective roles in both the initial proinflammatory response and adaptive immune response after trauma. Furthermore, results in TLR9-deficient mice establish that the upregulation of early proinflammatory markers do not always correlate with the extent of sustained immune dysfunction. This suggests potential for targeted therapies that could limit immune dysfunction through selective inhibition of receptor function following injury.

Inducible nitric oxide synthase contributes to immune dysfunction following trauma.

Trauma results in a persistent depression in adaptive immunity, which contributes to patient morbidity and mortality. This state of immune paralysis following trauma is characterized by a change in cell-mediated immunity, specifically a depression in T-cell function and a shift toward TH2 T-cell phenotype. Upregulation of inducible nitric oxide synthase (iNOS) is well recognized after injury and contributes to the inflammatory response and organ damage early after trauma. However, it is unknown whether iNOS plays a role in adaptive immune dysfunction after trauma. This study utilized a murine model of severe peripheral tissue injury to show that iNOS is rapidly upregulated in macrophages and a (Gr-1-CD11b) myeloid-derived suppressor cell subpopulation in the spleen. Through the use of iNOS knockout mice, a specific iNOS inhibitor, and a nitric oxide (NO) scavenger, this study demonstrates that iNOS-derived NO is required for the depression in T-lymphocyte proliferation, interferon γ, and interleukin 2 production within the spleen at 48 h after trauma. These findings support the hypothesis that iNOS regulates immune suppression following trauma and suggest that targeting the sustained production of NO by iNOS may attenuate posttraumatic immune depression.

Crystalloid to packed red blood cell transfusion ratio in the massively transfused patient: when a little goes a long way.

BACKGROUND: Massive transfusion (MT) protocols have emphasized the importance of ratio-based transfusion of plasma and platelets relative to packed red blood cells (PRBCs); however, the risks attributable to crystalloid resuscitation in patients requiring MT remain largely unexplored. We hypothesized that an increased crystalloid:PRBC (C:PRBC) ratio would be associated with increased morbidity and poor outcome after MT. METHODS: Data were obtained from a multicenter prospective cohort study evaluating outcomes in blunt injured adults with hemorrhagic shock. Patients requiring MT (≥ 10 units PRBCs in first 24 hours) were analyzed. The C:PRBC ratio was computed by the ratio of crystalloid infused in liters (L) to the units of PRBCs transfused in the first 24 hours postinjury. Logistic regression modeling was used to characterize the independent risks associated with the 24-hour C:PRBC ratio, after controlling for important confounders and other blood component transfusion requirements. RESULTS: Logistic regression revealed that the 24-hour C:PRBC ratio was significantly associated with a greater independent risk of multiple organ failure (MOF), acute respiratory distress syndrome (ARDS), and abdominal compartment syndrome (ACS). No association with mortality or nosocomial infection was found. A dose-response analysis revealed that patients with a C:PRBC ratio >1.5:1 had over a 70% higher independent risk of MOF and over a twofold higher risk of ARDS and ACS. CONCLUSION: In patients requiring MT, crystalloid resuscitation in a ratio greater than 1.5:1 per unit of PRBCs transfused was independently associated with a higher risk of MOF, ARDS, and ACS. These results suggest overly aggressive crystalloid resuscitation should be minimized in these severely injured patients. Further research is required to determine whether incorporation of the C:PRBC ratio into MT protocols improves outcome.

Preoperative weight loss in high-risk superobese bariatric patients: a computed tomography-based analysis.

BACKGROUND: Superobesity, through organomegaly, excessive adiposity, and associated severe co-morbidities, is a recognized risk factor for bariatric surgery. Our study examined the utility of preoperative weight loss with a liquid low-calorie diet (LCD) as a method of risk reduction. METHODS: All patients with a body mass index (BMI) >50 kg/m(2) were instructed to consume a LCD (800 kcal/d) with the goal of losing ≥10% of their body weight. The co-morbidities were monitored. The abdominal wall depth and cross-sectional areas of subcutaneous adipose tissue (SAT) at 12 and 20 cm below the costal margin, visceral adipose tissue (VAT), and liver volume were measured, using computed tomography, at baseline and after completion of the LCD. Laparoscopic gastric bypass was performed in all patients. RESULTS: The study included 30 patients (27 men and 3 women) with a mean age of 53 years (range 34-53). The mean BMI was reduced from 56 kg/m(2) (range 50-69) at baseline to 49 kg/m(2) (range 43-60) after an average of 9 weeks of the LCD. The VAT decreased from a mean of 388 cm(2) to 342 cm(2). The abdominal wall depth decreased from 3.6 to 3.2 cm at 12 cm below the costal margin and from 3.7 to 3.4 cm at 20 cm. The mean SAT at both 12 and 20 cm below the costal margin had decreased from 577 cm(2) and 687 cm(2) to 509 cm(2) and 614 cm(2), respectively. The liver volume was reduced by 18%. All co-morbidities were well controlled at LCD completion. No patient died, and 2 minor complications occurred postoperatively. CONCLUSION: The results of our study have shown that preoperative LCD is a safe and effective tool leading to a significant decrease in liver volume and abdominal wall depth, as well as a reduction in both VAT and SAT. Its use might contribute to improved short-term surgical outcomes in high-risk superobese patients.

Central blockade of IL-1 does not impair taste-LPS associative learning.

After saccharin intake is associated with the consequences of peripheral lipopolysaccharide (LPS) administration, rats develop a strong conditioned avoidance behavior against this gustatory stimulus. To investigate the role of central interleukin-1 (IL-1) as a key signal during taste-LPS engram formation, rats were chronically infused with IL-1 receptor antagonist into the lateral ventricle of the brain before, during and after a single association trial. The results indicate that a stable taste-LPS engram can be formed even under the chronic blockade of central IL-1 signaling during engram formation and consolidation. More importantly, our data show that animals which did not experience a fever response during association phase (due to the LPS encounter) were unable to elicit hyperthermia as part of the conditioned response. These data indicate that pairing a relevant taste stimulus with an immune challenge, such as LPS, might result in the formation of multiple engrams, specifically codifying independent information.