Microbial Epidemiology of Acute and Perforated Appendicitis: A Post-Hoc Analysis of an EAST Multicenter Study.

BACKGROUND: There are significant practice variations in antibiotic treatment for appendicitis, ranging from short-course narrow spectrum to long-course broad-spectrum. We sought to describe the modern microbial epidemiology of acute and perforated appendicitis in adults to help inform appropriate empiric coverage and support antibiotic stewardship initiatives. METHODS: This is a post-hoc secondary analysis of the Multicenter Study of the Treatment of Appendicitis in America: Acute, Perforated, and Gangrenous (MUSTANG) which prospectively enrolled adult patients (age ≥ 18 years) diagnosed with appendicitis between January 2017 and June 2018 across 28 centers in the United States. We included all subjects with positive microbiologic cultures during primary or secondary (rescue after medical failure) appendectomy or percutaneous drainage. Culture yield was compared between low- and high-grade appendicitis as per the AAST classification. RESULTS: A total of 3,471 patients were included: 230 (7%) had cultures performed, and 179/230 (78%) had positive results. Cultures were less likely to be positive in grade 1 compared to grades 3, 4, or 5 appendicitis with 2/18 (11%) vs 61/70 (87%) (p < .001). Only 1 subject had grade 2 appendicitis and culture results were negative. E. coli was the most common pathogen and cultured in 29 (46%) of primary appendectomy samples, 16 (50%) of secondary, and 44 (52%) of percutaneous drainage samples. CONCLUSION: Culturing low-grade appendicitis is low yield. E. coli is the most commonly cultured microbe in acute and perforated appendicitis. This data helps inform empiric coverage for both antibiotics alone and as an adjunct to operative or percutaneous intervention.

Narrow- versus Broad-Spectrum Antibiotics for Simple Acute Appendicitis Treated by Appendectomy: A Post Hoc Analysis of EAST MUSTANG Study.

BACKGROUND: We sought to compare the effectiveness of narrow- versus broad-spectrum antibiotics (abx) in preventing infectious complications in adults with acute appendicitis treated with appendectomy. METHODS: In this post hoc analysis of a prospective multicenter observational study of appendicitis in adults (≥18 y) conducted from January 2017 to June 2018, we included only patients with simple appendicitis. Subjects were grouped based on receipt of broad-spectrum or narrow-spectrum abx before and/or after appendectomy. Outcomes compared were surgical site infection, intra-abdominal abscess, secondary interventions (percutaneous drainage or operation), emergency department (ED) visits, 30-d readmission, and hospital length of stay. RESULTS: A total of 2336 subjects were analyzed. In comparing narrow (n = 778) versus broad (n = 1558) groups, there were no differences in male sex (53% versus 54%, P = 0.704), white blood cell (13.0 ± 3.9 versus 13.4 ± 4.5, P = 0.05), Alvarado score (6 [5-7] versus 6 [5-7], P = 0.25), or Charlson comorbidity index (0 [0-1] versus 0 [0-1], P = 0.09). A total of 688 (29%) received postoperative abx, [184 (24%) narrow and 504 (32%) broad, P < 0.001] for a median 5 [2-7] d [42 (23%) narrow and 235 (47%) broad, P < 0.001]. There were no significant differences between narrow and broad groups in surgical site infection, intra-abdominal abscess, secondary interventions, ED visits, or hospital readmissions. CONCLUSIONS: Significant practice variation in duration and spectrum of antibiotic adjunct for surgical treatment of simple acute appendicitis treatment is evident, and broad-spectrum abx did not offer clinical advantages over narrow-spectrum abx. Restriction of antibiotic spectrum should be considered, although randomized trials are required to overcome selection bias.

Complicated Appendicitis: Are Extended Antibiotics Necessary? A Post Hoc Analysis of the EAST Appendicitis "MUSTANG" Study.

BACKGROUND: The need for extended postoperative antibiotics (Abx) for complicated (gangrenous or perforated) appendicitis (CA) remains unclear. We hypothesize that giving ≤24 h of Abx for CA is not inferior to a longer duration in preventing infectious complications after appendectomy. METHODS: In this post hoc analysis of a prospective multicenter study, only patients with intraoperative diagnosis of CA were included. ANOVA and Chi-squared tests were used to compare length of stay, 30-day readmission rates, surgical site infection (SSI), and intra-abdominal abscess (IAA) between patients receiving ≥96 h and ≤24 h of Abx. RESULTS: Of 751 patients with CA, 704 met inclusion criteria. Mean age was 48 (±17) y; 391 (56%) were male. A total of 185 (26%) received Abx for ≤24 h and 100 (14% of overall) received no Abx. 85 (12%) patients were lost to follow-up at 30 d postop. Twenty-seven (4%) patients developed an SSI (≤24 h = 5 (3%), ≥96 h = 22 (5%), P = 0.502) and 82 (13%) developed IAA (≤24 h = 11 (7%), ≥96 h = 71 (15%), P = 0.008) within 30d postop. Sixty-six (11%) patients underwent a secondary intervention for infection within 30 d postop. 41% of SSIs (11/27) and 60% (49/82) of IAA occurred during the index hospitalization. On the multivariate analysis, there was not any evidence of an association between the duration of Abx and an increased rate of SSI (P = 0.539), IAA (P = 0.274), emergency department visits (P = 0.509), readmission (P = 0.911), or secondary interventions (P = 0.523). CONCLUSIONS: No evidence of an association between the duration of Abx (≤24 h versus ≥ 96 h) for complicated appendicitis and an increased rate of SSI was observed and ≤24 h duration was associated with shorter length of stay. Because of possible selection bias, adequately powered randomized trials are required to definitely prove noninferiority of shorter course Abx duration.

Blunt Trauma: What Is Behind the Widened Mediastinum on Chest X-Ray (CXR)?

BACKGROUND: It is commonly taught that a widened mediastinum (WM) on chest X-ray (CXR) is a marker for aortic injury (AI). We sought to describe the epidemiology of injuries for all patients with WM and compare their CXR to those of patients with confirmed AI. METHODS: Adults (age ≥ 18) sustaining blunt traumatic injuries from January 2017 to June 2017 with both CXR (supine, anterior-posterior) and chest CT were included. We excluded those whose CT preceded CXR and those with missing data. Basic demographics, injury characteristics, mediastinal width (MW), mediastinal-to-thoracic width ratio (MTR), and all thoracic imaging findings were analyzed. MW > 8 cm was considered WM. We also queried our registry for all AI patients over a 4-year period. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of WM on CXR for AI were calculated. Multivariate logistic regression was performed to identify factors associated with positive traumatic findings, controlling for body mass index (BMI), sex, high-energy mechanism, MTR, and mediastinal width. RESULTS: Of 749 included subjects, 502 (67%) had an MW > 8 cm: mean age was 48 ± 20 y, 381 (76%) were men, and BMI was 28 ± 5 kg/m2. Mechanism of injury was motor vehicle crash in 335 (67%); fall in 113 (23%); assault in 31 (6%); other (jet-ski accidents, etc.) in 17 (3%), and unknown in 6 (1%). Only 128 (26%) of patients with WM had positive findings on CT, with the most common [80 (16%)] being nontraumatic findings (pericardial infusion, lymph nodes, etc.), followed by hemomediastinum/pneumomediastinum [32 (6%)], sternal fractures [18 (4%)], multiple findings [15 (3%)], and vertebral fractures [6 (1%)]. Only 2 (1%) had AI. The sensitivity was 100%, specificity was 33%, PPV was 0.4%, NPV was 100%, and accuracy was 33%. From 2013 to 2017, 38 patients had AI: mean age was 46 ± 19 y, 26 (68%) were men, and BMI was 28 ± 4 kg/m2. Motor vehicle crash was the most common mechanism (89%), followed by "other" trauma mechanism (5%), fall (3%), and assault (3%). On univariate analysis, compared with all patients with WM, patients with AI had significantly greater MW (9.5 [8.8-10.4] versus 10.2 [9.1-11.1]; P = 0.042) and MTR (0.31 [0.28-0.34] versus 0.32 [0.31-0.37]; P = 0.001), although the actual differences were not clinically significant. The regression analysis did not identify any factors associated with traumatic CXR findings. CONCLUSIONS: Most bluntly injured adults have a WM, and the majority have either no findings or nontraumatic findings. The PPV of a WM for AI is <1%. WM on supine CXR is nonspecific and inaccurate for diagnosing traumatic injuries, especially AI.

Appendectomy versus nonoperative management of simple appendicitis: A post hoc analysis of an Eastern Association for the Surgery of Trauma multicenter study using a hierarchical ordinal scale.

BACKGROUND: Controversy exists about the preferred initial treatment of appendicitis. We sought to compare the two treatments for initial management of simple appendicitis. METHODS: In this post hoc analysis of the Multicenter Study for the Treatment of Appendicitis in America: Acute, Perforated, and Gangrenous database, subjects were divided into appendectomy or nonoperative management (NOM; antibiotics only or percutaneous drainage) cohorts. A novel topic-specific hierarchical ordinal scale was created with eight mutually exclusive categories: mortality, reoperation, other secondary interventions, readmission, emergency department visit, wound complication, surgical site infection, and no complication. Pairwise comparisons of American Association for the Surgery of Trauma Imaging Severity Grade 1 (simple appendicitis) patients were compared using win-lose-tie scoring and the sums of appendectomy/NOM groups were compared. RESULTS: A total 3,591 subjects were included: 3,262 appendectomy and 329 NOM, with significant differences in baseline characteristics between groups. Across 28 sites, the rate of NOM ranged from 0% to 48%, and the loss to follow-up rate was significantly higher for NOM compared with appendectomy (16.5% vs. 8.7%, p = 0.024). In the simple appendicitis hierarchical ordinal scale analysis, 2,319 subjects resulted in 8,714,304 pairwise comparisons; 75% of comparisons resulted in ties. The median (interquartile range) sums for the two groups are as follows: surgical, 400 (400-400), and NOM, 400 (-2,427 to 400) (p < 0.001). A larger proportion of appendectomy subjects (88.1%) had an outcome that was equivalent (or better) than at least half of the subjects compared with NOM subjects (NOM, 70.5%; OR [95% confidence interval], 0.3 [0.2-0.4]). CONCLUSION: In contemporary American practice, appendectomy (compared with NOM) for simple appendicitis is associated with lower odds of developing clinically important unfavorable outcomes in the first year after illness. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level III.

Early hypermetabolism is uncommon in trauma intensive care unit patients.

BACKGROUND: Classic experiments demonstrating hypermetabolism after major trauma were performed in a different era of critical care. We aim to describe the modern posttraumatic metabolic response in the trauma intensive care unit (TICU). METHODS: This prospective observational study enrolled TICU mechanically ventilated adults (aged ≥18) from 3/2018-2/2019. Multiple, daily resting energy expenditure (REE) measurements were recorded. Basal energy expenditure (BEE) was calculated by the Harris-Benedict equation. Hypometabolism was defined as average daily REE < 0.85*BEE and hypermetabolism defined as average daily REE > 1.15*BEE. Demographics, interventions, and clinical outcomes were abstracted. Descriptive statistics and multivariable logistical regression models evaluating demographics with the outcome variable of hypermetabolism for the first 3 days ("sustained hypermetabolism") were performed, along with group-based trajectory modeling (GBTM). RESULTS: Fifty-five patients were analyzed: median age was 38 (28-56) years; 38 (69%) were male; body mass index (kg/m2 ) was 28 (26-32); and Injury Severity Score was 27 (19-34), with (38 [71%] blunt, 8 [15%] penetrating, 7 [13%] burn) injury mechanism. Overall, 19 (35%) had hypermetabolism on day 1 ("immediate hypermetabolism"), and 11 (21%) had sustained hypermetabolism for the first 3 days. Logistic regression analysis identified penetrating mechanism (adjusted odds ratio [AOR], 16.4; 95% CI, 1.9-199.6; p = .015), burn mechanism (AOR, 11.1; 95% CI, 1.3-116.8; p =.029), and maximum temperature (AOR, 4.2; 95% CI, 1.3-20.3; p= .041) as independent predictors of sustained hypermetabolism. GBTM identified 4 nutrition phenotypes, with 2 hyperconsumptive phenotypes associated with increased risk of malnutrition at discharge. CONCLUSION: Only a minority of injured patients is hypermetabolic in the first week after injury. Elevated temperature, penetrating mechanism, and burn mechanism are independently associated with sustained hypermetabolism. Hyperconsumptive phenotype patients are more likely to develop malnutrition during hospitalization.

Antibiotics after Simple (Acute) Appendicitis are not Associated with Better Clinical Outcomes: A Post-Hoc Analysis of an EAST Multi-Center Study.

Background: The post-operative management of simple (acute) appendicitis differs throughout the United States. Guidelines regarding post-operative antibiotic usage remain unclear, and treatment generally is dictated by surgeon preference. We hypothesize that post-operative antibiotic use for simple appendicitis is not associated with lower post-operative complication rates. Methods: In a post-hoc analysis in a large multi-center observational study, only patients with an intra-operative diagnosis of AAST EGS Grade I were included. Subjects were classified into those receiving post-operative antibiotics (POST) and those given pre-operative antibiotics only (NONE). Clinical outcomes examined were length of stay (LOS), 30-day emergency department (ED) visits and hospital re-admissions, secondary interventions, surgical site infection (SSI), and intra-abdominal abscess (IAA). Results: A total of 2,191 subjects were included, of whom 612 (28%) received post-operative antibiotics. Compared with the NONE group, POST patients were older (age 37 [range 26-50] versus 33 [26-46] years; p < 0.001), weighed more (82 [70-96] versus 79 [68-93] kg (p = 0.038), and had higher white blood cell counts (13.5 ± 4.2 versus 13.1 ± 4.4/103/mcL (p = 0.046), Alvarado Scores (6 [5-7] versus 6 [5-7]; p < 0.001), and Charlson Comorbidity Indices (median score 0 in both cohorts; p < 0.001). The POST patients had a longer LOS (1 [1-2] versus 1 [1-1] days; p < 0.001). There were no differences in the number who had ED visits within 30 days (9% versus 8%; p = 0.435), hospital re-admission (4% versus 2%; p = 0.165), an index hospitalization SSI (0.2% for both cohorts; p = 0.69), an SSI within 30 days (4% versus 2%; p = 0.165), index hospitalization IAA rate (0.3% versus 0.1%; p = 0.190), 30-day IAA (2% versus 1%; p = 0.71), index hospitalization interventions (0.5% versus 0.1%; p = 0.137) or 30-day secondary interventions (2% versus 1%; p = 0.155). Conclusions: Post-operative antibiotic use after appendectomy for simple appendicitis is not associated with better post-operative clinical outcomes at index hospitalization or at 30 days after discharge.

Prophylactic Drainage after Appendectomy for Perforated Appendicitis in Adults: A Post Hoc Analysis of an EAST Multi-Center Study.

Background: We sought to assess the efficacy of prophylactic abdominal drainage to prevent complications after appendectomy for perforated appendicitis. Methods: In this post hoc analysis of a prospective multi-center study of appendicitis in adults (≥ 18 years), we included patients with perforated appendicitis diagnosed intra-operatively. The 634 subjects were divided into groups on the basis of receipt of prophylactic drains. The demographics and outcomes analyzed were surgical site infection (SSI), intra-abdominal abscess (IAA), Clavien-Dindo complications, secondary interventions, and hospital length of stay (LOS). Multivariable logistic regression for the cumulative 30-day incidence of IAA was performed controlling for age, Charlson Comorbidity Index (CCI), antibiotic duration, presence of drains, and Operative American Association for the Surgery of Trauma (AAST) Grade. Results: In comparing the Drain (n = 159) versus No-Drain (n = 475) groups, there was no difference in the frequency of male gender (61% versus 55%; p = 0.168), weight (87.9 ± 27.9 versus 83.8 ± 23.4 kg; p = 0.071), Alvarado score (7 [6-8] versus 7 [6-8]; p = 0.591), white blood cell (WBC) count (14.8 ± 4.8 versus 14.9 ± 4.5; p = 0.867), or CCI (1 [0-3] versus 1 [0-2]; p = 0.113). The Drain group was significantly older (51 ± 16 versus 48 ± 17 years; p = 0.017). Drain use increased as AAST EGS Appendicitis Operative Severity Grade increased: Grade 3 (62/311; 20%), Grade 4 (46/168; 27%), and Grade 5 (51/155; 33%); p = 0.007. For index hospitalization, the Drain group had a higher complication rate (43% versus 28%; p = 0.001) and longer LOS (4 [3-7] versus 3 [1-5] days; p < 0.001). We could not detect a difference between the groups in the incidence of SSI, IAA, or secondary interventions. There was no difference in 30-day emergency department visits, re-admissions, or secondary interventions. Multi-variable logistic regression showed that only AAST Grade (odds ratio 2.7; 95% confidence interval7 1.5-4.7; p = 0.001) was predictive of the cumulative 30-day incidence of IAA. Conclusions: Prophylactic drainage after appendectomy for perforated appendicitis in adults is not associated with fewer intra-abdominal abscesses but is associated with longer hospital LOS. Increasing AAST EGS Appendicitis Operative Grade is a strong predictor of intra-abdominal abscess.

Continuous Indirect Calorimetry in Critically Injured Patients Reveals Significant Daily Variability and Delayed, Sustained Hypermetabolism.

BACKGROUND: Previous studies have used using Indirect Calorimetry (IC) with solitary or sparse measurements of resting energy expenditure (REE). This "snapshot" may not capture the dynamic nature of metabolic requirements. Using continuous IC, we describe the variation of REE during the first days in the intensive care unit. METHODS: Injured adults (≥18 years) requiring mechanical ventilation from March 2018 to September 2018 were enrolled. IC was initiated within 4 days of admission and continuous REE recorded until 14 days, extubation, or death. Multiple 10-minute periods collected during steady state were used to calculate daily REE maximum, minimum, average, and variability [(REEmax - REEmin/2)/average REE]. RESULTS: We included 55 patients. Median age was 38 [27-58] years, 38 (69%) were male, body mass index was 28 [25-33] kg/m2 , and Acute Physiology and Chronic Health Evaluation II was 17 [14-24]. Mechanism of injury was: blunt (n = 38, 69%), penetrating (n = 9, 16%), and burn (n = 8, 15%). Average REE increased gradually from 1,663 kcal [1,435-2,143] to a maximum of 2,080 [1,701-2,336] on day 7, a relative 25% increase, which was sustained through day 14. REE variability ranged 8%-13% and was not reliably predicted by fever, tachycardia, elevated intracranial pressures, hypertension, or hypotension. CONCLUSION: In critically injured patients, steady-state REE measurements display fluctuations over a 24-hour period and demonstrate a gradual rise over the first few days after injury. Continuous REE, if available, is recommended for more precise matching of energy delivery to metabolic requirements.

Use of Predictive Equations for Energy Prescription Results in Inaccurate Estimation in Trauma Patients.

BACKGROUND: Overfeeding and underfeeding are associated with poor clinical outcomes. In the absence of indirect calorimetry (IC), the Society of Critical Care Medicine/ASPEN recommend prescribing 25-30 kcal/kg. The Harris-Benedict equation (HBE) multiplied by a stress factor is commonly applied in critically ill patients. We describe the difference between estimated and actual energy needs in critically injured patients. METHODS: From March to November 2018, we collected demographics and energy needs determined by continuous IC (started within 4 days) in intubated adults. Ideal or adjusted body weight was used for 25-30 kcal/kg, and HBE was multiplied by a 1.3 stress factor (1.3HBE). Daily requirements up to 14 days, extubation, or death were calculated using all 3 methods and compared with IC. RESULTS: Fifty-five subjects were included. Median age was 38 [27-58] years, 38 (69%) were male, body mass index was 28 [25-33] kg/m2 , and Acute Physiology and Chronic Health Evaluation II score was 17 [14-24] Mechanism of injury was blunt (38, 69%), penetrating (9, 16%), and burn (8, 15%). By day 14, compared with measured energy requirements by IC, the other methods could result in a cumulative 1827-kcal (+7%) surplus (1.3HBE), a 1313-kcal (-5%) deficit (25 kcal/kg), or a 3950-kcal (+14%) surplus (30 kcal/kg) per patient over a median 9 days. CONCLUSION: In critically injured patients, predictive equations for energy needs do not account for dynamic metabolic changes over time and could result in underfeeding or overfeeding. Adjusting daily prescription based on continuous IC may result in better individualized treatment.

Appendicitis in Pregnancy: A Post-Hoc Analysis of an EAST Multicenter Study.

Objective: To compare the presentation, management, and outcomes of appendicitis in pregnant and non-pregnant females of childbearing age (18-45 years). Methods: This was a post-hoc analysis of a prospectively collected database (January 2017-June 2018) from 28 centers in America. We compared pregnant and non-pregnant females' demographics, clinical presentation, laboratory data, imaging findings, management, and clinical outcomes. Results: Of the 3,597 subjects, 1,010 (28%) were of childbearing age, and 41 were pregnant: The mean age of the pregnant subjects was 30 ± 8 years at a median gestational age of 15 (range 10-23) weeks. The two groups had similar demographics and clinical presentation, but there were differences in management and outcomes. For example, in pregnant subjects, abdominal ultrasound scans (US) plus magnetic resonance imaging (MRI) was the most frequently used imaging method (41%) followed by MRI alone (29%), US alone (22%), computed tomography (CT) (5%), and no imaging (2%). Despite similar American Association for the Surgery of Trauma Emergency General Surgery Clinical and Imaging Grade at presentation, pregnant subjects were more likely to be treated with antibiotics alone (15% versus 4%; p = 0.008). Pregnant subjects were less likely to have simple appendicitis and were more likely to have complicated (perforated or gangrenous) appendicitis or a normal appendix. With the exception of index hospital length of stay, there were no significant differences between the groups in clinical outcomes at index hospitalization or at 30 days. Conclusion: Almost 1 in 20 women of childbearing age presenting with appendicitis is pregnant. Appendicitis most commonly affects women in early to mid-pregnancy. Compared with non-pregnant women of childbearing age, pregnant women presenting with appendicitis undergo non-operative management more often and are less likely to have simple appendicitis. Compared with non-pregnant patients, they have similar clinical outcomes at both index hospitalization and 30 days after discharge.

Validation of the American Association for the Surgery of Trauma emergency general surgery score for acute appendicitis-an EAST multicenter study.

BACKGROUND: The American Association for the Surgery of Trauma (AAST) has proposed a grading system for anatomic severity of 16 Emergency General Surgery conditions, including appendicitis. This is the first prospective, multicenter clinical study evaluating the AAST Appendicitis grading scale. METHODS: The EAST Appendicitis study utilized data collected prospectively from 27 centers, between January 2017 to June 2018. An overall grade was assigned as the highest grade of the subscales: clinical, radiographic, operative, and pathologic. Grade 1-3 of the clinical subscale was assigned as Grade 1. Patients with a final diagnosis other than appendicitis were excluded. The cohort was divided into two groups: simple appendicitis (Grades 1 and 2), and complicated appendicitis (Grades 3, 4, and 5).Fisher's exact and Kruskal-Wallis tests were used to determine association between the overall AAST grade and the following outcomes: infectious complications, Clavien-Dindo complications, hospital length of stay (LOS), 30-day emergency department visits, readmissions, and secondary interventions. RESULTS: A total of 2,909 cases were analyzed: 1,656 (57%) were Grade 1; 181 (6%), Grade 2; 399 (14%) Grade 4; and 549 (19%) Grade 5; 94% of patients underwent appendectomy. Index hospitalization LOS increased significantly with increasing grade: 1, [1,1], 1 [1,2], 1 [1,2], 2 [1,3], and 32,5 (p < 0.001). Infectious complications, Clavien-Dindo complications, hospital LOS, and secondary interventions were significantly associated with increasing AAST severity grade during index hospitalization. For 30-day outcomes, similar trends were noted for readmission, 30-day infections complications, 30-day cumulative infectious complications, 30-day Clavien-Dindo complications, 30-day cumulative Clavien-Dindo complications, 30-day secondary interventions, and 30-day cumulative secondary interventions. CONCLUSION: The AAST emergency general surgery grade for appendicitis is a valid predictor of clinical outcomes such as infectious complications, overall complications, and the need for secondary intervention. LEVEL OF EVIDENCE: Prognostic, level III.