Surgical management of acute cholecystitis at a tertiary care center in the modern era

HYPOTHESIS: The advent of laparoscopy has changed the paradigm of surgical training and care delivery for the treatment of patients with acute cholecystitis (AC). DESIGN: Retrospective data collection and analysis. SETTING: Hospital admissions with a primary diagnosis of AC at a tertiary care center from January 1, 2002, to January 1, 2007. PATIENTS: During the study period, 923 patients were admitted with a primary diagnosis of AC. One hundred fourteen patients were excluded from the study because of missing data, medical management, incomplete operative notes or documents, or metastatic gastrointestinal cancer. MAIN OUTCOME MEASURES: Patient demographics, preoperative morbidity, procedures (medical and surgical), and postoperative outcomes were statistically analyzed using chi(2) test, t test, and analysis of variance. RESULTS: Eight hundred nine patients (87.6%) with a primary diagnosis of AC underwent surgery by 44 surgeons. Procedures included 663 laparoscopic cholecystectomies (LCs) (82.0%), 9 open cholecystectomies (1.1%), 51 conversions from LC to open cholecystectomy (6.3%), and 86 cholecystostomy tube placements (10.6%). During the study period, cholecystostomy tube placements increased, while open cholecystectomies and conversions from LC to open cholecystectomy decreased (P \u3c .05). Laparoscopic cholecystectomy was associated with significantly better outcomes, including shorter postsurgical stay (2.2 vs 6.3 days for other modalities) and fewer complications (8.5% vs 17.0%). CONCLUSIONS: Based on 5-year results from a tertiary care center, LC was performed with a low conversion rate to open surgery and was associated with decreased morbidity and mortality compared with other surgical modalities to treat AC. Our data confirm the benefits and widespread use of LC in the modern era, reflecting changes in the training paradigm and learning curve for laparoscopy

Loss of SR-A and CD36 activity reduces atherosclerotic lesion complexity without abrogating foam cell formation in hyperlipidemic mice

The scavenger receptors SR-A and CD36 have been implicated in macrophage foam cell formation during atherogenesis and in the regulation of inflammatory signaling pathways, including those leading to lesional macrophage apoptosis and plaque necrosis. To test the impact of deleting these receptors, we generated Apoe(-/-) mice lacking both SR-A and CD36 and fed them a Western diet for 12 weeks. We analyzed atheroma in mice, assessing lesion size, foam cell formation, inflammatory gene expression, apoptosis, and necrotic core formation. Aortic root atherosclerosis in Apoe(-/-)Cd36(-/-)Msr1(-/-) mice, as assessed by morphometry, electron microscopy, and immunohistochemistry, showed no decrease in lesion area or in vivo foam cell formation when compared to Apoe(-/-) mice. However, Apoe(-/-)Cd36(-/-)Msr1(-/-) lesions showed reduced expression of inflammatory genes and morphological analysis revealed a approximately 30% decrease in macrophage apoptosis and a striking approximately 50% decrease in plaque necrosis in aortic root lesions of these mice. Although targeted deletion of SR-A and CD36 does not abrogate macrophage foam cell formation or substantially reduce atherosclerotic lesion area in Apoe(-/-) mice, loss of these pathways does reduce progression to more advanced necrotic lesions. These data suggest that targeted inhibition of these pathways in vivo may reduce lesional inflammation and promote plaque stabilit

Elevated neuronal expression of CD200 protects Wlds mice from inflammation-mediated neurodegeneration.

Axonal damage secondary to inflammation is likely the substrate of chronic disability in multiple sclerosis and is found in the animal model of experimental autoimmune encephalomyelitis (EAE). Wld(s) mice have a triplication of the fusion gene Ube4b/Nmnat and a phenotype of axon protection. Wld(s) mice develop an attenuated disease course of EAE, with decreased demyelination, reduced axonal pathology, and decreased central nervous system (CNS) macrophage and microglial accumulation. We show that attenuated disease in Wld(s) mice was associated with robust constitutive expression of the nonsignaling CD200 molecule on neurons in the CNS compared with control mice. CD200 interacts with its signaling receptor CD200R, which we found to be expressed on microglia, astrocytes, and oligodendrocytes at similar levels in control and Wld(s) mice. Administration of blocking anti-CD200 antibody to Wld(s) mice abrogated disease attenuation and was associated with increased CNS inflammation and neurodegeneration. In vitro, Wld(s) neuronal cultures were protected from microglial-induced neurotoxicity compared with control cultures, but protection was abrogated by anti-CD200 antibody. The CD200-CD200R pathway plays a critical role in attenuating EAE and reducing inflammation-mediated damage in the CNS. Strategies that up-regulate the expression of CD200 in the CNS or molecules that ligate the CD200R may be relevant as neuroprotective strategies in multiple sclerosis