Effectiveness of the Ad26.COV2.S vaccine in health-care workers in South Africa (the Sisonke study): results from a single-arm, open-label, phase 3B, implementation study.

BACKGROUND: We aimed to assess the effectiveness of a single dose of the Ad26.COV2.S vaccine (Johnson & Johnson) in health-care workers in South Africa during two waves of the South African COVID-19 epidemic. METHODS: In the single-arm, open-label, phase 3B implementation Sisonke study, health-care workers aged 18 years and older were invited for vaccination at one of 122 vaccination sites nationally. Participants received a single dose of 5 × 1010 viral particles of the Ad26.COV2.S vaccine. Vaccinated participants were linked with their person-level data from one of two national medical insurance schemes (scheme A and scheme B) and matched for COVID-19 risk with an unvaccinated member of the general population. The primary outcome was vaccine effectiveness against severe COVID-19, defined as COVID-19-related admission to hospital, hospitalisation requiring critical or intensive care, or death, in health-care workers compared with the general population, ascertained 28 days or more after vaccination or matching, up to data cutoff. This study is registered with the South African National Clinical Trial Registry, DOH-27-022021-6844, ClinicalTrials.gov, NCT04838795, and the Pan African Clinical Trials Registry, PACTR202102855526180, and is closed to accrual. FINDINGS: Between Feb 17 and May 17, 2021, 477 102 health-care workers were enrolled and vaccinated, of whom 357 401 (74·9%) were female and 119 701 (25·1%) were male, with a median age of 42·0 years (33·0-51·0). 215 813 vaccinated individuals were matched with 215 813 unvaccinated individuals. As of data cutoff (July 17, 2021), vaccine effectiveness derived from the total matched cohort was 83% (95% CI 75-89) to prevent COVID-19-related deaths, 75% (69-82) to prevent COVID-19-related hospital admissions requiring critical or intensive care, and 67% (62-71) to prevent COVID-19-related hospitalisations. The vaccine effectiveness for all three outcomes were consistent across scheme A and scheme B. The vaccine effectiveness was maintained in older health-care workers and those with comorbidities including HIV infection. During the course of the study, the beta (B.1.351) and then the delta (B.1.617.2) SARS-CoV-2 variants of concerns were dominant, and vaccine effectiveness remained consistent (for scheme A plus B vaccine effectiveness against COVID-19-related hospital admission during beta wave was 62% [95% CI 42-76] and during delta wave was 67% [62-71], and vaccine effectiveness against COVID-19-related death during beta wave was 86% [57-100] and during delta wave was 82% [74-89]). INTERPRETATION: The single-dose Ad26.COV2.S vaccine shows effectiveness against severe COVID-19 disease and COVID-19-related death after vaccination, and against both beta and delta variants, providing real-world evidence for its use globally. FUNDING: National Treasury of South Africa, the National Department of Health, Solidarity Response Fund NPC, The Michael & Susan Dell Foundation, The Elma Vaccines and Immunization Foundation, and the Bill & Melinda Gates Foundation.

Development of a New Referral Tool to Identify Psoriasis Patients with Concomitant Psoriatic Arthritis: Results of the Prospective DAPPER Cohort.

Patients with psoriasis are at risk of developing psoriatic arthritis, which can lead to joint damage. While screening questionnaires have been developed, their performance varies. The objective of this study was to develop a referral tool for dermatologists to identify psoriasis patients with concomitant psoriatic arthritis for rheumatological referral. This study used data from the DAPPER study, in which psoriasis patients were screened by a rheumatologist for the presence of concomitant psoriatic arthritis. Multivariable regression analysis was used to identify predictive variables for the presence of concomitant psoriatic arthritis: treatment history with conventional systemic drugs (odds ratio (OR) 2.97, 95% confidence interval (95% CI) 1.01-8.74, p = 0.04), treatment history with biologicals/small molecule inhibitors (OR 2.90, 95% CI 1.52-5.53, p = 0.01), patient-reported history of joint pain not caused by trauma (OR 4.23, 95% CI 1.21-14.79, p = 0.01), patient-reported history of swollen joints (OR 4.25, 95% CI 2.17-8.32, p < 0.001), and patient-reported history of sausage-like swollen digits (OR 2.38, 95% CI 1.25-4.55, p = 0.01). Based on these variables, a referral tool was created with an area under the curve of 0.82. This referral tool could be used to aid dermatologists to identify psoriasis patients with concomitant psoriatic arthritis, who may benefit from rheumatological referral.

Defining the minimal important change (MIC) and meaningful change value (MCV) for the Psoriatic Arthritis Disease Activity Score (PASDAS) in a routine practice cohort of patients with psoriatic arthritis.

OBJECTIVE: The aim of the study was to determine the Minimal Important Change (MIC) values and Meaningful Change (MCV) values for the Psoriatic Arthritis Disease Activity Score (PASDAS) and the Standard Error of Measurement (s.e.m.) of the PASDAS. METHODS: The routine practice data for 544 patients with PsA was available for analysis. An anchor-based method using linear regression analyses was used to determine the MICs and MCVs for the PASDAS. With this anchor-based method, we compared changes in the PASDAS score with an external reference (anchor). The anchor question inquired whether the patient's well-being had changed since their previous visit. It consisted of a 7-point Likert scale (range: very much improved to very much deteriorated). Interperiod correlation matrix analysis was performed to determine the s.e.m. RESULTS: The overall MIC and MCV for the PASDAS were 0.67 (95% CI: 0.55, 0.79) and 1.34 (95% CI: 1.21, 1.46), respectively. Results for improvement and deterioration were 0.65 (95% CI: 0.46, 0.83) and 0.71 (95% CI: 0.49, 0.93) for the MIC, respectively, and 1.29 (95% CI: 1.11, 1.48) and 1.42 (95% CI: 1.19, 1.64) for the MCV, respectively. The s.e.m. was determined at 0.81. CONCLUSION: The MIC for the PASDAS is a tool for physicians treating patients with PsA enabling them to give context to the patient's perspective of disease activity, while the MCV might aid the use of the PASDAS in PsA clinical trials.

Being overweight is associated with not reaching low disease activity in women but not men with psoriatic arthritis.

OBJECTIVE: To assess sex differences in disease activity parameters and health-related quality of life in PsA, and to assess whether determinants associated with not reaching treatment target differed between men and women. METHODS: Routine practice data of 855 PsA patients, who were all tightly monitored and treated, was used. Sex differences including, but not limited to, PsA Disease Activity Score (PASDAS), skin/nail disease, SF-12 PCS/MCS, and inflammatory back pain (IBP) were assessed. Multivariate analyses were used to examine determinants associated with not reaching treatment target (PASDAS ≤ 3.2) in men and women. RESULTS: Women had worse scores for-among others-swollen and tender joints, CRP, enthesitis and function (all P < 0.001). Higher PASDAS scores were found for women [3.5 (1.5)] than men [2.7 (1.5), P < 0.001]. Likewise, women were more often not at PASDAS treatment target (OR = 2.03, P < 0.001). No difference in current medication use was found. Nail disease, IBP, number of DMARDs used (past and current), and BMI were associated with not reaching treatment target in the overall sample. For women, but not men, BMI was associated with not reaching PASDAS low disease activity (LDA) (OR between 2.41 and 3.43, P < 0.001). CONCLUSIONS: Women with PsA in a tightly monitored and treated setting have more severe disease than men. This is demonstrated by worse scores for women in both subjective and objective disease activity measures, in addition to women less often reaching the treatment target. Notably, being overweight is associated with higher disease activity in women, but not men.

Tumour necrosis factor inhibitor dose adaptation in psoriatic arthritis and axial spondyloarthritis (TAPAS): a retrospective cohort study.

OBJECTIVES: We investigated the effect of disease activity-guided dose optimization (DAGDO) of TNF inhibitor (TNFi) on disease activity and TNFi dose in PsA and axial spondyloarthritis (axSpA) patients with low disease activity (LDA). METHODS: A retrospective cohort study was conducted in PsA and axSpA patients doing well on TNFi and eligible for TNFi DAGDO. Three different treatment periods were defined: (i) full dose continuation period, (ii) TNFi DAGDO period, and (iii) period with stable TNFi dose after DAGDO. A mixed-model analysis was used to estimate mean Disease Activity Score 28-joint count CRP (DAS28-CRP) and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) during these periods, and a mean percentage of the daily defined dose (%DDD) was calculated as secondary outcome. RESULTS: Three hundred and twenty-four patients (153 PsA and 171 axSpA) were included, with a mean of 6.5 DAS28-CRP and 6.4 BASDAI measurements and a median follow-up duration of 46 and 44 months, respectively. A corrected difference of 0.06 (95% CI: -0.09, 0.21) in mean DAS28-CRP was found for the TNFi DAGDO period and 0.03 (95% CI: -0.14, 0.20) for the period with stable TNFi dose, compared with full dose continuation period. Differences for BASDAI were 0.03 (95% CI: -0.21, 0.27) and 0.05 (95% CI: -0.24, 0.34), respectively. The mean %DDD for the three treatment periods was for PsA 108%, 62% and 78%, and for axSpA 108%, 62% and 72%, respectively. CONCLUSION: DAGDO of TNFi reduces drug exposure and has no negative effects on disease activity in PsA and axSpA patients compared with full dose continuation.

Telemedicine During COVID-19 Pandemic: Endocrine Surgery Patient Perspective.

INTRODUCTION: In response to the COVID-19 pandemic, many medical providers have turned to telemedicine as an alternative method to provide ambulatory patient care. Perspectives of endocrine surgery patients regarding this mode of healthcare delivery remains unclear. The purpose of this study is to evaluate the opinions and perspectives of endocrine surgery patients regarding telemedicine. METHODS: The first 100 adult patients who had their initial telemedicine appointment with two endocrine surgeons were contacted at the conclusion of their visit. The survey administered assessed satisfaction with telemedicine, the provider, and whether attire or video background played a role in their perception of the quality of care received using a 5-point Likert scale. Differences in responses between new and returning patients were also evaluated. RESULTS: Telemedicine endocrine surgery patients stated excellent satisfaction with their visit (4.89 out of 5) and their provider (4.96 out of 5). Although there was less consensus that telemedicine was equivalent to in-person or face-to-face clinic visits (4.15 out of 5), patients would recommend a telemedicine visit to others and most agreed that this modality made it easier to obtain healthcare (4.7 out of 5). Attire of the provider and video background did not influence patient opinion in regard to the quality of care they received. Returning patients were more likely to be satisfied with this modality (4.94 versus 4.73, P = 0.02) compared to new patients. CONCLUSIONS: This study shows that telemedicine does not compromise patient satisfaction or healthcare delivery for patients and is a viable clinic option for endocrine surgery.

Discovery of Psoriatic Arthritis in Psoriasis Patients for Early Rheumatological Referral (DAPPER) Study: A Prospective Observational Cohort.

Patients with psoriasis are at risk of developing psoriatic arthritis, which can lead to irreversible joint damage. However, a proportion of patients with psoriasis and concomitant psoriatic arthritis remain undiscovered in practice. The aims of this study were: to prospectively determine prevalence, characteristics, and disease burden of psoriatic arthritis in a psoriasis population; and to determine the prevalence and characteristics of patients with active psoriatic arthritis, who were not under rheumatological care. Patients with psoriasis were screened by a rheumatologist at the dermatology outpatient clinic for psoriatic arthritis. Patients with suspected active psoriatic arthritis who were not seeing a rheumatologist were referred to a rheumatologist for confirmation. The total prevalence of psoriatic arthritis in this observational, prospective cohort (n = 303) was 24%. Patients with psoriasis with concomitant psoriatic arthritis had longer duration of skin disease and more often a treatment history with systemic therapies. In this academic, specialized, setting, 2.3% of patients (n = 7), were not receiving rheumatological care despite having active psoriatic arthritis. These patients were characterized by a combination of low (perceived) disease burden and low yield of screening questionnaires, making it difficult for dermatologists to discover psoriatic arthritis in these patients. Thus, screening for more subtle active arthritis in patients with psoriasis in a dermatology setting could be improved.

Measuring disease activity in psoriatic arthritis: PASDAS implementation in a tightly monitored cohort reveals residual disease burden.

OBJECTIVES: We aimed to investigate the disease activity and overall disease burden of (subgroups of) patients with PsA using the Psoriatic Arthritis Disease Activity Score (PASDAS) in an already tightly monitored cohort. METHODS: This is a cross-sectional study evaluating data from the first visit of 855 PsA patients after implementation of the PASDAS in our tightly monitored cohort [e.g. DAS 28 (DAS28) was provided as an anchor]. Differences in clinical outcomes between subgroups of patients using established cut-offs for disease activity status [i.e. very low (VLDA), low (LDA), moderate (MDA), and high disease activity (HDA)] were examined. RESULTS: Based on the PASDAS, 53.1% of patients were in VLDA/LDA. 29.5% of patients had ≥1 swollen joint, 20.6% had ≥1 enthesitis index point and 3.0% had active dactylitis. Based on DAS28, 77.5% of the patients were in VLDA/LDA. Patients reaching both DAS28 VLDA/LDA status and PASDAS VLDA/LDA status [N = 445 (52.0%)] were compared with patients reaching only DAS28 VLDA/LDA status [N = 218 (25.5%)]. For these latter patients, significantly worse scores on separate parameters were found in measures used for PASDAS/DAS28 calculation (e.g. swollen and tender joint count and patient's visual analogue scale global disease activity) as well as other disease measures (e.g. function and inflammatory back pain). This result remained, even when the stricter VLDA cut-off was used for the DAS28. CONCLUSION: PASDAS implementation uncovered relevant residual disease activity in a quarter of patients previously assessed as being in DAS28 VLDA/LDA, underscoring the potential value of PASDAS measurements in PsA clinical care.

Blood-Based Immune Profiling Combined with Machine Learning Discriminates Psoriatic Arthritis from Psoriasis Patients.

Psoriasis (Pso) is a chronic inflammatory skin disease, and up to 30% of Pso patients develop psoriatic arthritis (PsA), which can lead to irreversible joint damage. Early detection of PsA in Pso patients is crucial for timely treatment but difficult for dermatologists to implement. We, therefore, aimed to find disease-specific immune profiles, discriminating Pso from PsA patients, possibly facilitating the correct identification of Pso patients in need of referral to a rheumatology clinic. The phenotypes of peripheral blood immune cells of consecutive Pso and PsA patients were analyzed, and disease-specific immune profiles were identified via a machine learning approach. This approach resulted in a random forest classification model capable of distinguishing PsA from Pso (mean AUC = 0.95). Key PsA-classifying cell subsets selected included increased proportions of differentiated CD4+CD196+CD183-CD194+ and CD4+CD196-CD183-CD194+ T-cells and reduced proportions of CD196+ and CD197+ monocytes, memory CD4+ and CD8+ T-cell subsets and CD4+ regulatory T-cells. Within PsA, joint scores showed an association with memory CD8+CD45RA-CD197- effector T-cells and CD197+ monocytes. To conclude, through the integration of in-depth flow cytometry and machine learning, we identified an immune cell profile discriminating PsA from Pso. This immune profile may aid in timely diagnosing PsA in Pso.

GRAPPA Trainee Symposium 2020: A Summary of Oral and Poster Presentations.

The Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) held a trainee symposium at its 2020 virtual meeting. Dermatology and rheumatology trainees presented their work on psoriasis and psoriatic arthritis. This report briefly reviews the 5 oral presentations and 25 posters presented at the event.

Chronic Lymphocytic Thyroiditis May Lower Accuracy of AUS/FLUS Cytopathology in Surgical Patients.

BACKGROUND: Chronic lymphocytic thyroiditis (CLT) increases cytologic atypia on fine-needle aspiration of thyroid nodules, and its effect on rate of malignancy in atypia of undetermined significance (AUS)/follicular lesions of undetermined significance (FLUS) thyroid nodules remains unclear. This study evaluates the effect of concomitant CLT on malignancy rates of AUS/FLUS thyroid nodules in surgical patients. METHODS: Retrospective review of 1061 patients who underwent thyroidectomy for a dominant thyroid nodule from a single institution was performed. Fine-needle aspiration was classified according to the Bethesda System for Reporting Thyroid Cytopathology. Patients with AUS/FLUS cytopathology were classified into two cohorts: AUS/FLUS with CLT and AUS/FLUS without CLT. Final pathology was reviewed, and the cohorts were further stratified into benign and malignant subgroups. When applicable, patients with gene expression classifier (GEC) testing were reviewed and the positive predictive value (PPV) was calculated. RESULTS: Of the entire surgical series, 293 (28%) patients had AUS/FLUS cytopathology with a rate of malignancy of 56% (163/293) on final pathology. Seventy-three (25%) patients had AUS/FLUS with CLT, of which 44% (n = 32) were malignant by final pathology. The remaining 75% (n = 220) had AUS/FLUS without CLT, 60% (n = 131) of which were malignant. GEC testing was performed in 36 of the AUS/FLUS with CLT patients, where of the 33 suspicious results, 17 were malignant on final pathology, yielding a PPV of 52%. CONCLUSIONS: The rate of malignancy for AUS/FLUS thyroid nodules is lower with coexisting CLT, and similar to previous studies, the PPV of GEC testing is approximately 50%. Cytologic atypia due to CLT may increase more AUS/FLUS results in thyroid nodules, which may lead to overestimation of malignancy rates in this patient population.

High Rates of Underlying Thyroid Cancer in Patients Undergoing Thyroidectomy for Hyperthyroidism.

BACKGROUND: The rate of thyroid cancer in patients with hyperthyroidism is reported to be rare, and patients with toxic thyroid nodules do not routinely undergo fine-needle aspiration (FNA) to evaluate for malignancy. However, higher rates of malignancy in hyperthyroid patients may exist than previously reported. This study examines the rate of malignancy in patients with hyperthyroidism who have undergone thyroidectomy. METHODS: A retrospective review of prospectively collected data of 138 patients with hyperthyroidism who underwent thyroidectomy at a single institution was performed. Patients were divided into three groups: Graves' disease (n = 80), toxic multinodular goiter (n = 46), and toxic solitary nodule (n = 12). Patients with previous thyroid surgery were excluded from the study. All patients had biochemical confirmation of hyperthyroidism with thyroid-stimulating hormone <0.1 mIU/L and clinical diagnosis by a referring physician. RESULTS: Of 138 patients, 22% (31/138) were found to have malignancy on final pathology. The breakdown of malignancy by hyperthyroid condition was as follows: 16% in Graves' disease, 24% in toxic multinodular goiter patients, and 50% in toxic solitary nodule patients. CONCLUSIONS: There is a clinically significant rate of malignancy seen in patients who undergo thyroidectomy for hyperthyroidism. Patients with distinct thyroid nodules in the presence of hyperthyroidism may have the highest rates of malignancy and should undergo appropriate workup with ultrasound and FNA to exclude underlying malignancy. In cases with suspicious ultrasound features and/or FNA cytopathology, surgical treatment should be considered as initial management.

A Significant Proportion of Small Bowel Obstructions Require >48 Hours to Resolve After Gastrografin.

BACKGROUND: Gastrografin (GG)-based nonoperative approach is both diagnostic and therapeutic for partial small bowel obstruction (SBO). Absence of X-ray evidence of GG in the colon after 8 h is predictive of the need for operation, and a recent trial used 48 h to prompt operation. We hypothesize that a significant number of patients receiving the GG challenge require >48 h before an effect is seen. METHODS: A post hoc analysis of an Eastern Association for the Surgery of Trauma multi-institutional SBO database was performed including only those receiving GG challenge. Successful nonoperative management (NOM) was defined as passage of flatus or nasogastric tube (NGT) removal. NOM was considered a failure if operative intervention was required. Multiple logistic regression was performed to identify predictors of delayed (>48 h) GG challenge effect and expressed as odds ratios with 95% confidence intervals. RESULTS: Of 286 patients receiving GG, 208 patients (73%) were successfully managed nonoperatively. A total of 60 (29%) NOM patients had NGT decompression for >48 h (n = 54) or required >48 h to pass flatus (n = 34), with some requiring both (n = 28). Prior abdominal operations and SBO admission were protective of delayed GG effect (0.411 [0.169-1.00], P < 0.05; 0.478 [0.240-0.952], P < 0.036). CONCLUSIONS: A significant proportion of patients at 48 h (29%) "failed" the GG challenge as they had yet to pass flatus or still required NGT but were nonetheless successfully managed nonoperatively. Extending the GG challenge beyond 48 h may help avoid unnecessary operations. LEVEL OF EVIDENCE: Level II.

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.

Risk Factors and Clinical Outcomes Associated With Augmented Renal Clearance in Trauma Patients.

BACKGROUND: Augmented renal clearance (ARC; i.e., creatinine clearance [CLCr] ≥ 130 mL/min) has an incidence of 14%-80% in critically ill patients and has been associated with therapy failures for renally cleared drugs. However, the clinical implications of ARC are poorly defined. We hypothesize that modifiable risk factors that contribute to ARC can be identified in severely injured trauma patients and that these risk factors influence clinical outcome. METHODS: In 207 trauma intensive care unit patients, 24-h CLCr was correlated with clinical estimates of glomerular filtration rate (by Cockroft-Gault, modification of diet in renal disease, or chronic kidney disease epidemiology), and clinical outcomes (infection, venous thromboembolism [VTE], length of stay, and mortality). RESULTS: The population was 45 ± 20 y, 68% male, 77% blunt injury with injury severity score of 24 (17-30). Admission serum creatinine was 1.02 ± 0.35 mg/dL, CLCr was 154 ± 77 mL/min, VTE incidence was 15%, ARC incidence was 57%, and mortality was 11%. Clinical estimates of glomerular filtration rate by Cockroft-Gault, modification of diet in renal disease, chronic kidney disease epidemiology underestimated actual CLCr by 20%, 22%, or 15% (all P < 0.01). CLCr was higher in males and those who survived, and lower in those with hypertension, diabetes, positive cultures, receiving transfusions, or pressors (all P < 0.05). On multivariate analysis, male gender (odds ratio [OR] 2.9 [1.4-6.1]), age (OR 0.97 [0.95-0.99]), and packed red blood cells transfusion (OR 0.31 [0.15-0.66]) were the only independent predictors of ARC. CONCLUSIONS: ARC occurs in more than half of all high-risk trauma intensive care unit patients and is underestimated by standard clinical equations. ARC was not associated with increased incidence of VTE or infection but rather is associated with younger healthier males and reduced mortality. ARC seems to be a beneficial compensatory response to trauma.

Outcomes of Pediatric Pelvic Fractures: A Level I Trauma Center's 20-Year Experience.

BACKGROUND: Pediatric pelvic fractures are rare. The contribution of pelvic fracture pattern, risk factors for associated injuries, and mortality are poorly defined in this population. METHODS: Patients aged 0-17 with pelvic fractures at a level I trauma center over a 20-y period were reviewed. Fracture patterns were classified according to the Young-Burgess classification when applicable. Fractures were analyzed for location, pubic symphysis or sacroiliac widening, and contrast extravasation. RESULTS: There were 163 pelvic fractures in 8758 admissions (incidence 2%). The most common associated injures were extremity fractures (60%, n = 98), abdominal solid organ (55%, n = 89), and chest (48%, n = 78), with the majority (61%, n = 99) sustaining injuries to multiple organs. Unstable fractures were associated with injures to the thorax (70% versus 40%), heart (15% versus 2%), and spleen (40% versus 18%), all P < 0.05. Nonpelvic operative interventions were required in 45% (n = 73) and were more common in unstable fractures (36% versus 19%), contrast extravasation (63% versus 26%), sacroiliac widening (36% versus 20%), and sacral fractures (39% versus 13%), all P < 0.05. Mortality was 13% and higher in males versus females (18% versus 5%), contrast extravasation (50% versus 3%), or sacroiliac/pubic symphysis widening (13% versus 2%) (all P < 0.05). Male gender (OR 6.03), brain injury (OR 6.18), spine injury (OR 5.06), and cardiac injury (OR 35.0) were independently associated with mortality (all P < 0.05). CONCLUSIONS: Pediatric pelvic fractures are rare but critical injuries associated with significant morbidity and need for interventions. Increasing fracture severity corresponds to injuries to other body systems and increased mortality.

Hypercoagulability After Resection of Thoracic Malignancy: A Prospective Evaluation.

BACKGROUND: Rates of venous thromboembolism are increased in thoracic malignancy; however, coagulation patterns are not established. We hypothesize that patients with esophageal and lung malignancy have similar hypercoagulable pre- and postoperative profiles as defined by rotational thromboelastometry (ROTEM). METHODS: Prospective study was conducted in 47 patients with esophageal and lung cancer undergoing surgical resection. ROTEM evaluated pre/postoperative coagulation status. RESULTS: Patients with thoracic malignancy were hypercoagulable by ROTEM, but not by conventional coagulation tests. Preoperative hypercoagulability was higher in lung versus esophageal cancer (64 vs. 16%, p = 0.001). Lung cancer patients that were hypercoagulable preoperatively demonstrated decreased maximum clot firmness (MCF) (p = 0.044) and increased clot time (p = 0.049) after surgical resection, suggesting reversal of hypercoagulability. Resection of esophageal cancer increased hypercoagulability (16 vs. 56%, p = 0.002) via elevated MCF (reflecting platelet activity). Hypercoagulability remained at follow-up clinic for both lung and esophageal cancer patients. CONCLUSIONS: Hypercoagulability in patients with lung malignancies reversed following complete surgical resection, whereas hypercoagulability occurred only postoperatively in those with esophageal malignancies. In both, hypercoagulability was associated with fibrin and platelet function.

Low dietary iron intake restrains the intestinal inflammatory response and pathology of enteric infection by food-borne bacterial pathogens.

Orally administrated iron is suspected to increase susceptibility to enteric infections among children in infection endemic regions. Here we investigated the effect of dietary iron on the pathology and local immune responses in intestinal infection models. Mice were held on iron-deficient, normal iron, or high iron diets and after 2 weeks they were orally challenged with the pathogen Citrobacter rodentium. Microbiome analysis by pyrosequencing revealed profound iron- and infection-induced shifts in microbiota composition. Fecal levels of the innate defensive molecules and markers of inflammation lipocalin-2 and calprotectin were not influenced by dietary iron intervention alone, but were markedly lower in mice on the iron-deficient diet after infection. Next, mice on the iron-deficient diet tended to gain more weight and to have a lower grade of colon pathology. Furthermore, survival of the nematode Caenorhabditis elegans infected with Salmonella enterica serovar Typhimurium was prolonged after iron deprivation. Together, these data show that iron limitation restricts disease pathology upon bacterial infection. However, our data also showed decreased intestinal inflammatory responses of mice fed on high iron diets. Thus additionally, our study indicates that the effects of iron on processes at the intestinal host-pathogen interface may highly depend on host iron status, immune status, and gut microbiota composition.