The Value of Outsourcing Selected Cases in a Medical Examiner Population: A 10-Year Experience.

Due to increasing caseloads and inadequate staffing, the burden on Coroner/Medical Examiner Offices to comply with recommended autopsy limits for forensic pathologists (FPs) has been difficult. Since 2006, pathologists at the University of Alabama at Birmingham have performed select autopsies for the Alabama Department of Forensic Sciences. Each case was reviewed by a state FP and scene investigator to determine appropriateness for referral. All referred cases received full postmortem examination including microscopic examination and collection of toxicological samples, and toxicology was ordered by the referring FP as appropriate. The final cause and manner of death were determined by the referring state FP after review of all findings. A majority of the 421 cases were ruled accidental deaths (233), most due to drug toxicity. Of the 178 natural deaths, 118 were attributed to cardiovascular disease. Outsourcing select forensic cases can be educational and an effective tool to manage workflow without compromising quality.

Anterior gradient protein-2 is a regulator of cellular adhesion in prostate cancer.

Anterior Gradient Protein (AGR-2) is reported to be over-expressed in many epithelial cancers and promotes metastasis. A clear-cut mechanism for its observed function(s) has not been previously identified. We found significant upregulation of AGR-2 expression in a bone metastatic prostate cancer cell line, PC3, following culturing in bone marrow-conditioned medium. Substantial AGR-2 expression was also confirmed in prostate cancer tissue specimens in patients with bone lesions. By developing stable clones of PC3 cells with varying levels of AGR-2 expression, we identified that abrogation of AGR-2 significantly reduced cellular attachment to fibronectin, collagen I, collagen IV, laminin I and fibrinogen. Loss of cellular adhesion was associated with sharp decrease in the expression of α4, α5, αV, ß3 and ß4 integrins. Failure to undergo apoptosis following detachment is a hallmark of epithelial cancer metastasis. The AGR-2-silenced PC3 cells showed higher resistance to Tumor necrosis factor-related apoptosis- inducing ligand (TRAIL) induced apoptosis in vitro. This observation was also supported by significantly reduced Caspase-3 expression in AGR-2-silenced PC3 cells, which is a key effector of both extrinsic and intrinsic death signaling pathways. These data suggest that AGR-2 influence prostate cancer metastasis by regulation of cellular adhesion and apoptosis.

Histological characteristics of the fetal inflammatory response associated with neurodevelopmental impairment and death in extremely preterm infants.

OBJECTIVE: To test the hypothesis that increasing severity of the fetal inflammatory response (FIR) would have a dose-dependent relationship with severe neurodevelopmental impairment or death in extremely preterm infants. STUDY DESIGN: We report 347 infants of 23-28 weeks gestational age admitted to a tertiary neonatal intensive care unit between 2006 and 2008. The primary outcome was death or neurodevelopmental impairment at the 18- to 22-month follow-up. Exposure status was defined by increasing stage of funisitis (stage 1, phlebitis; stage 2, arteritis with or without phlebitis; stage 3, subacute necrotizing funisitis) and severity of chorionic plate vasculitis (inflammation with or without thrombosis). RESULTS: A FIR was detected in 110 placentas (32%). The rate of severe neurodevelopmental impairment/death was higher in infants with subacute necrotizing funisitis compared with infants without placental/umbilical cord inflammation (60% vs 35%; P < .05). Among infants with stage 1 or 2 funisitis, the presence of any chorionic vasculitis was associated with a higher rate of severe neurodevelopmental impairment/death (47% vs 23%; P < .05). After adjustment for confounding factors, only subacute necrotizing funisitis (risk ratio, 1.87; 95% CI, 1.04-3.35; P = .04) and chorionic plate vasculitis with thrombosis (risk ratio, 2.21; 95% CI, 1.10-4.46; P = .03) were associated with severe neurodevelopmental impairment/death. CONCLUSION: Severe FIR, characterized by subacute necrotizing funisitis and severe chorionic plate vasculitis with thrombosis, is associated with severe neurodevelopmental impairment/death in preterm infants.

Incremental value of live/real time three-dimensional transesophageal echocardiography over the two-dimensional technique in the assessment of sinus of valsalva aneurysm rupture.

We present an adult patient with rupture of the right sinus of Valsalva aneurysm in whom the two-dimensional transesophageal echocardiogram failed to show the rupture. On the other hand, live/real time three-dimensional transesophageal echocardiography clearly delineated the site of rupture into the pericardium and mediastinum.

Clostridium septicum aortitis causing aortic dissection in a 22-year-old man.

Clostridium septicum infection is a rare cause of aortic dissection, and the mortality rate for the condition is high. Only 26 cases of C. septicum aortitis have been reported; all of those patients were elderly, and 20 of them had an associated colonic neoplasm. Herein, we present the case of a 22-year-old man whose C. septicum aortitis resulted in aortic dissection that involved the entire length of the aorta. Upon autopsy, no neoplasm or other predisposing condition was identified in this patient. To the best of our knowledge, this is the 1st report of C. septicum aortitis, fatal or otherwise, in a young individual.

Statins improve human coronary atherosclerotic plaque morphology.

Statin treatment markedly reduces the incidence of acute coronary events in patients with coronary atherosclerosis. Although imaging studies have indirectly shown the beneficial effects of statins on plaque morphology, there has to our knowledge been no reported histologic comparison of the morphology of coronary plaque in statin-treated versus untreated patients who had substantial coronary artery atherosclerosis. We retrospectively studied arterial sections from the native hearts of patients who had experienced end-stage ischemic heart disease and subsequent cardiac transplantation. Of 44 qualified patients, 33 study patients had received pre-transplantation statin therapy, and 11 control patients had not. Pathologic examination of each explanted heart confirmed coronary artery disease and previous myocardial infarction in all patients. Diabetes mellitus was more prevalent in the study group. The groups were similar in levels of total and low-density lipoprotein cholesterol, and in the available number of arterial cross-sections per patient. All patients had plaques. High-grade lesions were found in 66.3% of cross-sections in the control group, and in 34.6% in the study group (P=0.011). Conversely, the degree of inflammation was markedly lower in the study group: low-grade fibrous plaques occurred in 45.7% of cross-sections in the study group, versus 11.3% in the control group (P=0.006). The study group had significantly fewer high-grade plaques and more fibrous plaques than did the control group at the time of transplantation. Our findings show that statin therapy substantially enhances plaque stabilization. We further suggest that reduction of plaque inflammation is an important aspect of this stabilization.