How has the Affordable Care Act changed outcomes in emergency general surgery?

INTRODUCTION: Lack of insurance coverage increases complications and mortality from surgical procedures. The 2014 Affordable Care Act (ACA) Open Enrollment (OE) insured more Americans, but it is unknown if this improved outcomes from emergency general surgery (EGS) procedures. This study seeks to determine how ACA OE coverage changes outcomes in EGS. METHODS: This is a retrospective review using the Nationwide Inpatient Sample database from 2012 to 2014. Patients aged 18 to 64 years undergoing EGS procedures were identified by International Classification of Diseases, Ninth Revision, codes. Medicare patients were excluded. Patient demographics, hospital characteristics, and Charlson comorbidity index were obtained. Outcomes were measured by mortality, complications, and calculated costs. Univariate and difference-in-differences multivariate analyses were performed to determine the effect of the ACA OE on EGS outcomes. RESULTS: A total of 304,110 EGS cases were identified. After Medicare patients were excluded, there were 275,425 cases. In 2014, Medicaid admissions increased 18.2% from 18,495 to 22,615 (p < 0.001) and self-pay admissions decreased 33% from 14,938 to 10,630 (p < 0.001). Mortality significantly increased for self-pay patients in 2014 from 0.81% to 1.22% (p < 0.001). Difference-in-differences analysis indicated that, after risk adjustment, the ACA OE was associated with a small reduction in mortality for insured patients (-0.12%, p = 0.034), increased complications (1.4%, p = 0.009), and increased wage-index adjusted mean costs (4.6%, p < 0.001). There was a significant increase in Medicare (+26.5%) and private (+12.2%, p < 0.001) insurance admissions in teaching hospitals, while nonteaching hospitals had fewer EGS admissions with a greater reduction in uninsured EGS admissions. CONCLUSIONS: The ACA OE created a significant reduction in uninsured EGS admissions but did not reduce EGS mortality. Mortality decreased in insured patients but increased in uninsured patients, indicating that the ACA OE primarily insured lower-risk patients. The ACA OE did increase cost and complications in insured admissions. Teaching hospitals saw the majority of the increase in Medicaid and private insurance EGS admissions. A national registry would improve future study of insurance policy on EGS outcomes. LEVEL OF EVIDENCE: Economic analysis, level IV.

Abdominal vascular trauma.

Abdominal vascular trauma, primarily due to penetrating mechanisms, is uncommon. However, when it does occur, it can be quite lethal, with mortality ranging from 20% to 60%. Increased early mortality has been associated with shock, acidosis, hypothermia, coagulopathy, free intraperitoneal bleeding and advanced American Association for the Surgery of Trauma Organ Injury Scale grade. These patients often arrive at medical centers in extremis and require rapid surgical control of bleeding and aggressive resuscitation including massive transfusion protocols. The most important factor in survival is surgical control of hemorrhage and restoration of appropriate perfusion to the abdominal contents and lower extremities. These surgical approaches and the techniques of definitive vascular repair can be quite challenging, particularly to the inexperienced surgeon. This review hopes to describe the most common abdominal vascular injuries, their presentation, outcomes, and surgical techniques to control and repair such injuries.

Multimodal signaling by the ADAMTSs (a disintegrin and metalloproteinase with thrombospondin motifs) promotes neurite extension.

Aggregating proteoglycans (PG) bearing chondroitin sulfate (CS) side chains associate with hyaluronan and various secreted proteins to form a complex of extracellular matrix (ECM) that inhibits neural plasticity in the central nervous system (CNS). Chondroitinase treatment depletes PGs of their CS side chains and enhances neurite extension. Increasing evidence from in vivo models indicates that proteolytic cleavage of the PG core protein by members of the ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) family of glutamyl-endopeptidases also promotes neural plasticity. The purpose of this study was to determine whether proteolytic action of the ADAMTSs influences neurite outgrowth in cultured neurons. Transfection of primary rat neurons with ADAMTS4 cDNA induced longer neurites, whether the neurons were grown on a monolayer of astrocytes that secrete inhibitory PGs or on laminin/poly-L-lysine substrate alone. Similar results were found when neurons were transfected with a construct encoding a proteolytically inactive, point mutant of ADAMTS4. Addition of recombinant ADAMTS4 or ADAMTS5 protein to immature neuronal cultures also enhanced neurite extension in a dose-dependent manner, an effect demonstrated to be dependent on the activation of MAP ERK1/2 kinase. These results suggest that ADAMTS4 enhances neurite outgrowth via a mechanism that does not require proteolysis but is dependent on activation of the MAP kinase cascade. Thus a model to illustrate multimodal ADAMTS activity would entail proteolysis of CS-bearing PGs to create a loosened matrix environment more favorable for neurite outgrowth, and enhanced neurite outgrowth directly stimulated by ADAMTS signaling at the cell surface.

Discordant localization of WFA reactivity and brevican/ADAMTS-derived fragment in rodent brain.

BACKGROUND: Proteoglycan (PG) in the extracellular matrix (ECM) of the central nervous system (CNS) may act as a barrier for neurite elongation in a growth tract, and regulate other characteristics collectively defined as structural neural plasticity. Proteolytic cleavage of PGs appears to alter the environment to one favoring plasticity and growth. Brevican belongs to the lectican family of aggregating, chondroitin sulfate (CS)-bearing PGs, and it modulates neurite outgrowth and synaptogenesis. Several ADAMTSs (a disintegrin and metalloproteinase with thrombospondin motifs) are glutamyl-endopeptidases that proteolytically cleave brevican. The purpose of this study was to localize regions of adult CNS that contain a proteolytic-derived fragment of brevican which bears the ADAMTS-cleaved neoepitope sequence. These regions were compared to areas of Wisteria floribunda agglutin (WFA) reactivity, a common reagent used to detect "perineuronal nets" (PNNs) of intact matrix and a marker which is thought to label regions of relative neural stability. RESULTS: WFA reactivity was found primarily as PNNs, whereas brevican and the ADAMTS-cleaved fragment of brevican were more broadly distributed in neuropil, and in particular regions localized to PNNs. One example is hippocampus where the ADAMTS-cleaved brevican fragment is found surrounding pyramidal neurons, in neuropil of stratum oriens/radiatum and the lacunosum moleculare. The fragment was less abundant in the molecular layer of the dentate gyrus. Mostly PNNs of scattered interneurons along the pyramidal layer were identified by WFA. In lateral thalamus, the reticular thalamic nucleus stained abundantly with WFA whereas ventral posterior nuclei were markedly immunopositive for ADAMTS-cleaved brevican. Using Western blotting techniques, no common species were reactive for brevican and WFA. CONCLUSION: In general, a marked discordance was observed in the regional localization between WFA and brevican or the ADAMTS-derived N-terminal fragment of brevican. Functionally, this difference may correspond to regions with varied prevalence for neural stability/plasticity.

Evidence for proteolytic cleavage of brevican by the ADAMTSs in the dentate gyrus after excitotoxic lesion of the mouse entorhinal cortex.

BACKGROUND: Brevican is a member of the lectican family of aggregating extracellular matrix (ECM) proteoglycans that bear chondroitin sulfate (CS) chains. It is highly expressed in the central nervous system (CNS) and is thought to stabilize synapses and inhibit neural plasticity and as such, neuritic or synaptic remodeling would be less likely to occur in regions with intact and abundant, lectican-containing, ECM complexes. Neural plasticity may occur more readily when these ECM complexes are broken down by endogenous proteases, the ADAMTSs (adisintegrin and metalloproteinase with thrombospondin motifs), that selectively cleave the lecticans. The purpose of these experiments was to determine whether the production of brevican or the ADAMTS-cleaved fragments of brevican were altered after deafferentation and reinnervation of the dentate gyrus via entorhinal cortex lesion (ECL). RESULTS: In the C57Bl6J mouse, synaptic density in the molecular layer of the dentate gyrus, as measured by synaptophysin levels in ELISA, was significantly attenuated 2 days (nearly 50% of contralateral) and 7 days after lesion and returned to levels not different from the contralateral region at 30 days. Immunoreactive brevican in immunoblot was elevated 2 days after lesion, whereas there was a significant increase in the proteolytic product at 7, but not 30 days post-lesion. ADAMTS activity, estimated using the ratio of the specific ADAMTS-derived brevican fragment and intact brevican levels was increased at 7 days, but was not different from the contralateral side at 2 or 30 days after deafferentation. CONCLUSION: These findings indicate that ADAMTS activity in the dentate outer molecular layer (OML) is elevated during the initial synaptic reinnervation period (7 days after lesion). Therefore, proteolytic processing of brevican appears to be a significant extracellular event in the remodeling of the dentate after EC lesion, and may modulate the process of sprouting and/or synaptogenesis.

Altered production and proteolytic processing of brevican by transforming growth factor beta in cultured astrocytes.

Brevican, a proteoglycan of the lectican family, inhibits neurite outgrowth and may also stabilize synapses. Little is known about its expression or function in vitro. This study seeks to determine whether a brevican-containing matrix is present in neural cultures, and if so, how the production of brevican may be modulated. To accomplish this, the content of brevican and its proteolytic fragments were measured in primary cultures of neurons, astrocytes and microglia after treatment with cytokines. These experiments revealed that astrocytes and neurons express several isoforms of brevican, whereas microglia do not produce this proteoglycan. Cleavage fragments of brevican were found primarily in neuronal and astrocyte culture medium. ADAMTS4 (a disintegrin and metalloproteinase with thrombospondin motifs), a protease that selectively cleaves lecticans, was detected in cultures of neurons, astrocytes and microglia. When astrocytes were challenged with various cytokines, it was found that treatment with transforming growth factor beta (TGFbeta) resulted in a marked increase in intact brevican in the culture medium that was accompanied by a trend for a decrease in ADAMTS-generated fragments of brevican and apparent ADAMTS activity. Thus, TGFbeta may play a role in neuronal plasticity through its regulation of brevican and the activity of the ADAMTSs.