Homicide Manner-of-Death Classification in Arrest-Related Death.

ABSTRACT: Multiple studies have documented various factors that influence or determine forensic pathologist classification of manner of death. There do not appear to be any published studies on manner of death classification specifically regarding arrest-related deaths (ARDs). The goal of this study was to consider a large body of cases of nonfirearm ARDs to analyze the homicide classification with regards to numerous decedent and practitioner (medical examiner/coroner [ME/C]) variables. We analyzed 1145 US autopsy reports from the years 2006-2020, inclusive, and considered decedent variables of age, ethnicity, height, weight, body mass index, toxicology, and mention of a conducted electrical weapon and ME/C influence variables of gender, country region, and year. We found that the homicide classification likelihood increased by a factor of 1.04-1.05 per year, 1.34-1.37 for a female medical examiner, and 1.4-1.5 going from Southern states to Western states. There is an increasing trend for ME/C to label nonfirearm ARDs as homicides in the United States. The homicide classification is more common in Western states and less common in Southern states, and it was more common with a female ME/C.

Perceived Hospital Stress, Severe Acute Respiratory Syndrome Coronavirus 2 Activity, and Care Process Temporal Variance During the COVID-19 Pandemic.

OBJECTIVES: The COVID-19 pandemic threatened standard hospital operations. We sought to understand how this stress was perceived and manifested within individual hospitals and in relation to local viral activity. DESIGN: Prospective weekly hospital stress survey, November 2020-June 2022. SETTING: Society of Critical Care Medicine's Discovery Severe Acute Respiratory Infection-Preparedness multicenter cohort study. SUBJECTS: Thirteen hospitals across seven U.S. health systems. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed 839 hospital-weeks of data over 85 pandemic weeks and five viral surges. Perceived overall hospital, ICU, and emergency department (ED) stress due to severe acute respiratory infection patients during the pandemic were reported by a mean of 43% ( sd , 36%), 32% (30%), and 14% (22%) of hospitals per week, respectively, and perceived care deviations in a mean of 36% (33%). Overall hospital stress was highly correlated with ICU stress (ρ = 0.82; p < 0.0001) but only moderately correlated with ED stress (ρ = 0.52; p < 0.0001). A county increase in 10 severe acute respiratory syndrome coronavirus 2 cases per 100,000 residents was associated with an increase in the odds of overall hospital, ICU, and ED stress by 9% (95% CI, 5-12%), 7% (3-10%), and 4% (2-6%), respectively. During the Delta variant surge, overall hospital stress persisted for a median of 11.5 weeks (interquartile range, 9-14 wk) after local case peak. ICU stress had a similar pattern of resolution (median 11 wk [6-14 wk] after local case peak; p = 0.59) while the resolution of ED stress (median 6 wk [5-6 wk] after local case peak; p = 0.003) was earlier. There was a similar but attenuated pattern during the Omicron BA.1 subvariant surge. CONCLUSIONS: During the COVID-19 pandemic, perceived care deviations were common and potentially avoidable patient harm was rare. Perceived hospital stress persisted for weeks after surges peaked.

Centers for Disease Control (CDC) Wound Classification is Prognostic of 30-Day Readmission Following Surgery.

BACKGROUND: The goal of this study was to investigate factors associated with 30-day readmission in a multivariate model, including the CDC wound classes "clean," "clean/contaminated," "contaminated," and "dirty/infected." METHODS: The 2017-2020 American College of Surgeons-National Surgical Quality Improvement Program (ACS-NSQIP) database was queried for all patients undergoing total hip replacement, coronary artery bypass grafting, Ivor Lewis esophagectomy, pancreaticoduodenectomy, distal pancreatectomy, pneumonectomy, and colectomies. ACS-defined wound classes were concordant with CDC definitions. Multivariate linear mixed regression was used to determine risk factors for readmission while adjusting for type of surgery as a random intercept. RESULTS: 477,964 cases were identified, with 38,734 (8.1%) patients having experienced readmission within 30 days of surgery. There were 181,243 (37.9%) cases classified as wound class "clean", 215,729 (45.1%) cases classified as "clean/contaminated", 40,684 cases (8.5%) classified as "contaminated", and 40,308 (8.4%) cases classified as "dirty/infected". In the multivariate generalized mixed linear model adjusting for type of surgery, sex, body mass index, race, American Society of Anesthesiologists class, presence of comorbidity, length of stay, urgency of surgery, and discharge destination, "clean/contaminated" (p < .001), "contaminated" (p < .001), and "dirty/infected" (p < .001) wound classes (when compared to "clean") were significantly associated with 30-day readmission. Organ/space surgical site infection and sepsis were among the most common reasons for readmission in all wound classes. CONCLUSIONS: Wound classification was strongly prognostic for readmission in multivariable models, suggesting that it may serve as a marker of readmissions. Surgical procedures that are "non-clean" are at significantly greater risk for 30-day readmission. Readmissions may be due to infectious complications; optimizing antibiotic use or source control to prevent readmission are areas of future study.

Use of an extended KDIGO definition to diagnose acute kidney injury in patients with COVID-19: A multinational study using the ISARIC-WHO clinical characterisation protocol.

BACKGROUND: Acute kidney injury (AKI) is one of the most common and significant problems in patients with Coronavirus Disease 2019 (COVID-19). However, little is known about the incidence and impact of AKI occurring in the community or early in the hospital admission. The traditional Kidney Disease Improving Global Outcomes (KDIGO) definition can fail to identify patients for whom hospitalisation coincides with recovery of AKI as manifested by a decrease in serum creatinine (sCr). We hypothesised that an extended KDIGO (eKDIGO) definition, adapted from the International Society of Nephrology (ISN) 0by25 studies, would identify more cases of AKI in patients with COVID-19 and that these may correspond to community-acquired AKI (CA-AKI) with similarly poor outcomes as previously reported in this population. METHODS AND FINDINGS: All individuals recruited using the International Severe Acute Respiratory and Emerging Infection Consortium (ISARIC)-World Health Organization (WHO) Clinical Characterisation Protocol (CCP) and admitted to 1,609 hospitals in 54 countries with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection from February 15, 2020 to February 1, 2021 were included in the study. Data were collected and analysed for the duration of a patient's admission. Incidence, staging, and timing of AKI were evaluated using a traditional and eKDIGO definition, which incorporated a commensurate decrease in sCr. Patients within eKDIGO diagnosed with AKI by a decrease in sCr were labelled as deKDIGO. Clinical characteristics and outcomes-intensive care unit (ICU) admission, invasive mechanical ventilation, and in-hospital death-were compared for all 3 groups of patients. The relationship between eKDIGO AKI and in-hospital death was assessed using survival curves and logistic regression, adjusting for disease severity and AKI susceptibility. A total of 75,670 patients were included in the final analysis cohort. Median length of admission was 12 days (interquartile range [IQR] 7, 20). There were twice as many patients with AKI identified by eKDIGO than KDIGO (31.7% versus 16.8%). Those in the eKDIGO group had a greater proportion of stage 1 AKI (58% versus 36% in KDIGO patients). Peak AKI occurred early in the admission more frequently among eKDIGO than KDIGO patients. Compared to those without AKI, patients in the eKDIGO group had worse renal function on admission, more in-hospital complications, higher rates of ICU admission (54% versus 23%) invasive ventilation (45% versus 15%), and increased mortality (38% versus 19%). Patients in the eKDIGO group had a higher risk of in-hospital death than those without AKI (adjusted odds ratio: 1.78, 95% confidence interval: 1.71 to 1.80, p-value < 0.001). Mortality and rate of ICU admission were lower among deKDIGO than KDIGO patients (25% versus 50% death and 35% versus 70% ICU admission) but significantly higher when compared to patients with no AKI (25% versus 19% death and 35% versus 23% ICU admission) (all p-values <5 × 10-5). Limitations include ad hoc sCr sampling, exclusion of patients with less than two sCr measurements, and limited availability of sCr measurements prior to initiation of acute dialysis. CONCLUSIONS: An extended KDIGO definition of AKI resulted in a significantly higher detection rate in this population. These additional cases of AKI occurred early in the hospital admission and were associated with worse outcomes compared to patients without AKI.

The compartmental distribution of knee osteoarthritis - a systematic review and meta-analysis.

OBJECTIVES: For a population with knee osteoarthritis (OA), determine: 1) the prevalence of single compartmental, bicompartmental and tricompartmental OA, 2) the prevalence of isolated medial tibiofemoral, lateral tibiofemoral, or patellofemoral OA, and combinations thereof. METHODS: PubMed and Web of Science databases, and reference lists of identified studies, were searched to find studies which reported on the compartmental distribution and prevalence of knee OA. Two independent reviewers assessed studies against pre-defined inclusion criteria and prevalence data were extracted along with subject characteristics. The methodological quality of each included study was assessed. A random-effects model meta-analysis was performed for each OA category to estimate the relative prevalence of OA in the knee compartments amongst people with knee OA. RESULTS: 16 studies (3,786 knees) met the inclusion criteria. High heterogeneity was measured. Normalised for knees with OA, estimated prevalence rates (95% CI) were: single compartmental 50% (31.5-58.3%), bicompartmental 33% (23.1-37.2%) and tricompartmental only 17% (8.8-24.8%). Isolated medial tibiofemoral OA, isolated patellofemoral OA, and combined medial tibiofemoral and patellofemoral OA were more common than tricompartmental disease, occurring in 27% (15.2-31.1%), 18% (9.9-22.7%) and 23% (14.1-27.3%) of people respectively. Single/bicompartmental patterns of disease involving the lateral tibiofemoral compartment were less common, summing to 15% (8.5-18.7%). CONCLUSION: Three-quarters of people with knee OA do not have tricompartmental disease. This is not reflected in the frequency with which partial and combined partial knee arthroplasties are currently used. TRIAL REGISTRATION NUMBER: PROSPERO systematic review protocol (CRD42019140345).

Clinical Data Extraction During Public Health Emergencies: A Blockchain Technology Assessment.

OBJECTIVE: We sought to explore the technical and legal readiness of healthcare institutions for novel data-sharing methods that allow clinical information to be extracted from electronic health records (EHRs) and submitted securely to the Food and Drug Administration's (FDA's) blockchain through a secure data broker (SDB). MATERIALS AND METHODS: This assessment was divided into four sections: an institutional EHR readiness assessment, legal consultation, institutional review board application submission, and a test of healthcare data transmission over a blockchain infrastructure. RESULTS: All participating institutions reported the ability to electronically extract data from EHRs for research. Formal legal agreements were deemed unnecessary to the project but would be needed in future tests of real patient data exchange. Data transmission to the FDA blockchain met the success criteria of data connection from within the four institutions' firewalls, externally to the FDA blockchain via a SDB. DISCUSSION: The readiness survey indicated advanced analytic capability in hospital institutions and highlighted inconsistency in Fast Healthcare Interoperability Resources format utilitzation across institutions, despite requirements of the 21st Century Cures Act. Further testing across more institutions and annual exercises leveraging the application of data exchange over a blockchain infrastructure are recommended actions for determining the feasibility of this approach during a public health emergency and broaden the understanding of technical requirements for multisite data extraction. CONCLUSION: The FDA's RAPID (Real-Time Application for Portable Interactive Devices) program, in collaboration with Discovery, the Critical Care Research Network's PREP (Program for Resilience and Emergency Preparedness), identified the technical and legal challenges and requirements for rapid data exchange to a government entity using the FDA blockchain infrastructure.

Examining the effect of social distancing on the compound growth rate of COVID-19 at the county level (United States) using statistical analyses and a random forest machine learning model.

OBJECTIVES: The goal of the present work is to investigate trends among US counties and coronavirus disease 2019 (COVID-19) growth rates in relation to the existence of shelter-in-place (SIP) orders in that county. STUDY DESIGN: This is a prospective cohort study. METHODS: Compound growth rates were calculated using cumulative confirmed COVID-19 cases from January 21, 2020, to March 31, 2020, in all 3139 US counties. Compound growth was chosen as it gives a single number that can be used in machine learning to represent the speed of virus spread during defined time intervals. Statistical analyses and a random forest machine learning model were used to analyze the data for differences in counties with and without SIP orders. RESULTS: Statistical analyses revealed that the March 16 presidential recommendation (limiting gatherings to ≤10 people) lowered the compound growth rate of COVID-19 for all counties in the US by 6.6%, and the counties that implemented SIP after March 16 had a further reduction of 7.8% compared with the counties that did not implement SIP after March 16. A random forest machine learning model was built to predict compound growth rate after a SIP order and was found to have an accuracy of 92.3%. The random forest found that population, longitude, and population per square mile were the most important features when predicting the effect of SIP. CONCLUSIONS: SIP orders were found to be effective at reducing the growth rate of COVID-19 cases in the US. Counties with a large population or a high population density were found to benefit the most from a SIP order.

Heterogeneous combinatorial expression of Hoxd genes in single cells during limb development.

BACKGROUND: Global analyses of gene expression during development reveal specific transcription patterns associated with the emergence of various cell types, tissues, and organs. These heterogeneous patterns are instrumental to ensure the proper formation of the different parts of our body, as shown by the phenotypic effects generated by functional genetic approaches. However, variations at the cellular level can be observed within each structure or organ. In the developing mammalian limbs, expression of Hox genes from the HoxD cluster is differentially controlled in space and time, in cells that will pattern the digits and the forearms. While the Hoxd genes broadly share a common regulatory landscape and large-scale analyses have suggested a homogenous Hox gene transcriptional program, it has not previously been clear whether Hoxd genes are expressed together at the same levels in the same cells. RESULTS: We report a high degree of heterogeneity in the expression of the Hoxd11 and Hoxd13 genes. We analyzed single-limb bud cell transcriptomes and show that Hox genes are expressed in specific combinations that appear to match particular cell types. In cells giving rise to digits, we find that the expression of the five relevant Hoxd genes (Hoxd9 to Hoxd13) is unbalanced, despite their control by known global enhancers. We also report that specific combinatorial expression follows a pseudo-time sequence, which is established based on the transcriptional diversity of limb progenitors. CONCLUSIONS: Our observations reveal the existence of distinct combinations of Hoxd genes at the single-cell level during limb development. In addition, we document that the increasing combinatorial expression of Hoxd genes in this developing structure is associated with specific transcriptional signatures and that these signatures illustrate a temporal progression in the differentiation of these cells.

Do patient-specific instruments (PSI) for UKA allow non-expert surgeons to achieve the same saw cut accuracy as expert surgeons?

INTRODUCTION: High-volume unicompartmental knee arthroplasty (UKA) surgeons have lower revision rates, in part due to improved intra-operative component alignment. This study set out to determine whether PSI might allow non-expert surgeons to achieve the same level of accuracy as expert surgeons. MATERIALS AND METHODS: Thirty-four surgical trainees with no prior experience of UKA, and four high-volume UKA surgeons were asked to perform the tibial saw cuts for a medial UKA in a sawbone model using both conventional and patient-specific instrumentation (PSI) with the aim of achieving a specified pre-operative plan. Half the participants in each group started with conventional instrumentation, and half with PSI. CT scans of the 76 cut sawbones were then segmented and reliably orientated in space, before saw cut position in the sagittal, coronal and axial planes was measured, and compared to the pre-operative plan. RESULTS: The compound error (absolute error in the coronal, sagittal and axial planes combined) for experts using conventional instruments was significantly less than that of the trainees (11.6°±4.0° v 7.7° ±2.3º, p = 0.029). PSI improved trainee accuracy to the same level as experts using conventional instruments (compound error 5.5° ±3.4º v 7.7° ±2.3º, p = 0.396) and patient-specific instruments (compound error 5.5° ±3.4º v 7.3° ±4.1º, p = 0.3). PSI did not improve the accuracy of high-volume surgeons (p = 0.3). CONCLUSIONS: In a sawbone model, PSI allowed inexperienced surgeons to achieve more accurate saw cuts, equivalent to expert surgeons, and thus has the potential to reduce revision rates. The next test will be to determine whether these results can be replicated in a clinical trial.

Fine-mapping the MHC locus in juvenile idiopathic arthritis (JIA) reveals genetic heterogeneity corresponding to distinct adult inflammatory arthritic diseases.

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases, comprising seven categories. Genetic data could potentially be used to help redefine JIA categories and improve the current classification system. The human leucocyte antigen (HLA) region is strongly associated with JIA. Fine-mapping of the region was performed to look for similarities and differences in HLA associations between the JIA categories and define correspondences with adult inflammatory arthritides. METHODS: Dense genotype data from the HLA region, from the Immunochip array for 5043 JIA cases and 14 390 controls, were used to impute single-nucleotide polymorphisms, HLA classical alleles and amino acids. Bivariate analysis was performed to investigate genetic correlation between the JIA categories. Conditional analysis was used to identify additional effects within the region. Comparison of the findings with those in adult inflammatory arthritic diseases was performed. RESULTS: We identified category-specific associations and have demonstrated for the first time that rheumatoid factor (RF)-negative polyarticular JIA and oligoarticular JIA are genetically similar in their HLA associations. We also observe that each JIA category potentially has an adult counterpart. The RF-positive polyarthritis association at HLA-DRB1 amino acid at position 13 mirrors the association in adult seropositive rheumatoid arthritis (RA). Interestingly, the combined oligoarthritis and RF-negative polyarthritis dataset shares the same association with adult seronegative RA. CONCLUSIONS: The findings suggest the value of using genetic data in helping to classify the categories of this heterogeneous disease. Mapping JIA categories to adult counterparts could enable shared knowledge of disease pathogenesis and aetiology and facilitate transition from paediatric to adult services.

Adjuvant psychological therapy in long-term endocrine conditions.

Consideration of psychological distress in long-term endocrine conditions is of vital importance given the prevalence of anxiety and depression in such disorders. Poor mental health can lead to compromised self-care, higher utilization of health services, lower rates of adherence, reduced quality of life and ultimately poorer outcomes. Adjuvant psychological therapy offers an effective resource to reduce distress in endocrine conditions. While the vast majority of work in this area has focused on psychological screening and intervention in diabetes, identification and recognition of psychological distress are equally important in other endocrinological conditions, with supportive evidence in polycystic ovary syndrome and Addison's disease. Referral pathways and recommendations set out by UK guidelines and the Department of Health mandate requires greater attention across a wider range of long-term endocrine conditions to facilitate improved quality of life and health outcome.

Genomic responses in mouse models poorly mimic human inflammatory diseases.

A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R(2) between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases.

The acute psychobiological impact of the intensive care experience on relatives.

There is a growing awareness amongst critical care practitioners that the impact of intensive care medicine extends beyond the patient to include the psychological impact on close family members. Several studies have addressed the needs of relatives within the intensive care context but the psychobiological impact of the experience has largely been ignored. Such impact is important in respect to health and well-being of the relative, with potential to influence patient recovery. The current feasibility study aimed to examine the acute psychobiological impact of the intensive care experience on relatives. Using a mixed methods approach, quantitative and qualitative data were collected simultaneously. Six relatives of patients admitted to the intensive care unit (ICU) of a District General Hospital, were assessed within 48 h of admission. Qualitative data were provided from semi-structured interviews analysed using interpretative phenomenological analysis. Quantitative data were collected using a range of standardised self-report questionnaires measuring coping responses, emotion, trauma symptoms and social support, and through sampling of diurnal salivary cortisol as a biomarker of stress. Four themes were identified from interview: the ICU environment, emotional responses, family relationships and support. Questionnaires identified high levels of anxiety, depression and trauma symptoms; the most commonly utilised coping techniques were acceptance, seeking support through advice and information, and substance use. Social support emerged as a key factor with focused inner circle support relating to family and ICU staff. Depressed mood and avoidance were linked to greater mean cortisol levels across the day. Greater social network and coping via self-distraction were related to lower evening cortisol, indicating them as protective factors in the ICU context. The experience of ICU has a psychological and physiological impact on relatives, suggesting the importance of identifying cost-effective interventions with evaluations of health benefits to both relatives and patients.

Development of a Core Clinical Dataset to Characterize Serious Illness, Injuries, and Resource Requirements for Acute Medical Responses to Public Health Emergencies.

OBJECTIVES: In developed countries, public health systems have become adept at rapidly identifying the etiology and impact of public health emergencies. However, within the time course of clinical responses, shortfalls in readily analyzable patient-level data limit capabilities to understand clinical course, predict outcomes, ensure resource availability, and evaluate the effectiveness of diagnostic and therapeutic strategies for seriously ill and injured patients. To be useful in the timeline of a public health emergency, multi-institutional clinical investigation systems must be in place to rapidly collect, analyze, and disseminate detailed clinical information regarding patients across prehospital, emergency department, and acute care hospital settings, including ICUs. As an initial step to near real-time clinical learning during public health emergencies, we sought to develop an "all-hazards" core dataset to characterize serious illness and injuries and the resource requirements for acute medical response across the care continuum. SUBJECTS: A multidisciplinary panel of clinicians, public health professionals, and researchers with expertise in public health emergencies. DESIGN: Group consensus process. INTERVENTIONS: The consensus process included regularly scheduled conference calls, electronic communications, and an in-person meeting to generate candidate variables. Candidate variables were then reviewed by the group to meet the competing criteria of utility and feasibility resulting in the core dataset. MEASUREMENTS AND MAIN RESULTS: The 40-member panel generated 215 candidate variables for potential dataset inclusion. The final dataset includes 140 patient-level variables in the domains of demographics and anthropometrics (7), prehospital (11), emergency department (13), diagnosis (8), severity of illness (54), medications and interventions (38), and outcomes (9). CONCLUSIONS: The resulting all-hazard core dataset for seriously ill and injured persons provides a foundation to facilitate rapid collection, analyses, and dissemination of information necessary for clinicians, public health officials, and policymakers to optimize public health emergency response. Further work is needed to validate the effectiveness of the dataset in a variety of emergency settings.

Genome-wide data reveal novel genes for methotrexate response in a large cohort of juvenile idiopathic arthritis cases.

Clinical response to methotrexate (MTX) treatment for children with juvenile idiopathic arthritis (JIA) displays considerable heterogeneity. Currently, there are no reliable predictors to identify non-responders: earlier identification could lead to a targeted treatment. We genotyped 759 JIA cases from the UK, the Netherlands and Czech Republic. Clinical variables were measured at baseline and 6 months after start of the treatment. In Phase I analysis, samples were analysed for the association with MTX response using ordinal regression of ACR-pedi categories and linear regression of change in clinical variables, and identified 31 genetic regions (P<0.001). Phase II analysis increased SNP density in the most strongly associated regions, identifying 14 regions (P<1 × 10(-5)): three contain genes of particular biological interest (ZMIZ1, TGIF1 and CFTR). These data suggest a role for novel pathways in MTX response and further investigations within associated regions will help to reach our goal of predicting response to MTX in JIA.

Smooth muscle cells from abdominal aortic aneurysms are unique and can independently and synergistically degrade insoluble elastin.

BACKGROUND: The purpose of this study was to further elucidate the role of the vascular smooth muscle cells (SMCs) in abdominal aortic aneurysm (AAA) disease. We hypothesized that that AAA SMCs are unique and actively participate in the process of degrading the aortic matrix. METHODS: Whole-genome expression profiles of SMCs from AAAs, nondilated abdominal aorta (NAA), and carotid endarterectomy (CEA) were compared. We quantified elastolytic activity by culturing SMCs in [(3)H]elastin-coated plates and measuring solubilized tritium in the media after 7 days. Matrix metalloproteinase (MMP)-2 and MMP-9 production was assessed using real-time polymerase chain reaction, zymography, and Western blotting. RESULTS: Each SMC type exhibited a unique gene expression pattern. AAA SMCs had greater elastolytic activity than NAA-SMCs (+68%; P < .001) and CEA-SMCs (+45%; P < .001). Zymography showed an increase of active MMP-2 (62 kD) in media from AAA SMCs. AAA SMCs demonstrated twofold greater expression of MMP-2 messenger (m)RNA (P < .05) and 7.3-fold greater MMP-9 expression (P < .01) than NAA-SMCs. Culture with U937 monocytes caused a synergistic increase of elastolysis by AAA SMCs (41%; P < .001) but not NAA-SMCs or CEA-SMCs (P = .99). Coculture with U937 caused a large increase in MMP-9 mRNA in AAA-SMCs and NAA-SMCs (P < .001). MMP-2 mRNA expression was not affected. Western blots of culture media showed a fourfold increase of MMP-9 (92 kD) protein only in AAA-SMCs/U937 but not in NAA-SMCs/U937 (P < .001) and a large increase in active-MMP2 (62 kD), which was less apparent in NAA-SMCs/U937 media (P < .01). CONCLUSIONS: AAA-SMCs have a unique gene expression profile and a proelastolytic phenotype that is augmented by macrophages. This may occur by a failure of post-transcriptional control of MMP-9 synthesis.