Allen Burke

Fudan University, Shanghai, Shanghai Shi, China

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Publications (300)1745.26 Total impact

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    ABSTRACT: Objectives This study assessed grayscale intravascular ultrasound (IVUS) and near-infrared spectroscopy (NIRS) detection of a histological fibroatheroma (FA).Background NIRS-detected, lipid-rich plaques (LRPs) and IVUS-detected attenuated plaques are considered to be vulnerable.Methods IVUS-attenuated plaque and NIRS-LRP (yellow or tan block chemogram) were compared with histopathology in 1,943 sections of 103 coronary arteries from 56 autopsied hearts.Results IVUS-superficial attenuation and NIRS-LRP showed a similar high specificity of approximately 95%, whereas IVUS-superficial attenuation alone had a poor sensitivity (vs. NIRS-LRP) in detecting FAs (36% vs. 47%; p = 0.001). Compared with FA sections with superficial attenuation, FA sections without superficial attenuation had a smaller plaque burden (57.1% vs. 67.7%), a larger arc of calcium (79.7° vs. 16.8°), and a lower prevalence of a ≥20% histological necrotic core (28% vs. 50%) or late FA (14% vs. 37%; all p textless 0.05). Compared with FA sections with NIRS-LRP, FA sections without NIRS-LRP showed a smaller plaque burden (58.0% vs. 63.3%) and a lower prevalence of a ≥20% necrotic core (27% vs. 46%). Conversely, non-FAs with NIRS-LRP (vs. non-FAs without LRP) showed a larger plaque burden (55.1% vs. 46.3%), a greater prevalence of a ≥20% histological lipid pool (34% vs. 5%), and mostly pathological intimal thickening (50%) or fibrocalcific plaque (33%). When sections showed either IVUS attenuation or NIRS-LRP, the sensitivity for predicting a FA was significantly higher compared with IVUS attenuation alone (63% vs. 36%; p textless 0.001) or NIRS-LRP alone (63% vs. 47%; p textless 0.001). When sections showed both IVUS attenuation and NIRS-LRP, the positive predictive value improved compared with IVUS attenuation alone (84% vs. 66%; p textless 0.001) or NIRS-LRP alone (84% vs. 65%; p textless 0.001).Conclusions NIRS-LRP was more accurate than IVUS for predicting plaque containing a necrotic core or a large lipid pool, and the combination was more accurate than either alone.
    JACC Cardiovascular Imaging 01/2015; · 6.99 Impact Factor
  • Jennifer A. Collins, Yang Zhang, Allen P. Burke
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    ABSTRACT: Background There are few studies on the histologic findings in native infective endocarditis, especially regarding mimics of autoimmune valvulitis. Methods We prospectively studied 106 surgical specimens from 95 patients with a clinical diagnosis of infective endocarditis on native valves, and compared gross and histologic findings with culture results, underlying valve disease, risk factors and time interval from symptom onset to surgical intervention. Results There were 41 (39%) aortic, 33 (31%) mitral, 9 (9%) tricuspid, 1(.9%) pulmonic and 11 (10%) multiple valve replacements. Underlying valve disease was present in 26 (27%) patients (non-calcified bicuspid aortic valve, 10 (38%) cases; mitral valve prolapse, 5 (19%) cases; calcified trileaflet aortic valve, 5 (19%) cases; calcified bicuspid aortic valve, 2 (8%) cases; post-rheumatic mitral valve disease, 2 (8%) cases; hypertrophic cardiomyopathy-related mitral valve disease, 1 (4%) case, trileaflet aortic insufficiency 1 (4%) case) and associated with streptococcal infection (p=.001). Absence of underlying valve disease was associated with intravenous drug abuse (p=.01) and dialysis dependent renal disease (p=.006). Intravenous drug abuse was associated with staphylococcal infection (p=.03). Vegetations were present in 80 (75%) of cases, and on the nonflow surface of the valve in 65 (81%) of these. Gram-stain positivity and neutrophilic microabscesses were associated with staphylococcal infection (p=.03). Epithelioid macrophages with palisading features mimicking necrobiotic granulomas were seen in 42 (40%) valves and more frequently associated with streptococcal infection (p=.03). As expected, the presence of valve necrosis and acute inflammation decreased with an increase in time with respect to symptomatic onset. Conclusion Histologic findings mimicking autoimmune inflammation is frequent in infective endocarditis and associated with streptococcal infection. Risk factors for infective endocarditis include calcific valve disease.
    Pathology - Research and Practice 12/2014; · 1.56 Impact Factor
  • Paul Staats, Fabio Tavora, Allen P Burke
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    ABSTRACT: Aortic sarcomas are predominantly endoluminal tumours that are believed derived from the intima. Because of their rarity, relatively little is known about their pathological features. We report a series of 26 aortic and iliofemoral tumours with histopathological and clinical data.Of the 26 cases, there were 16 men (63.6 ± 13 years) and 10 women (58.6 ± 18 years). Tumours occurred in the abdominal aorta (13), descending thoracic aorta (8), iliac or femoral arteries (4) and ascending aorta (1). Presenting tumour manifestations included claudication or peripheral vascular disease (6), pain (5), pulsatile aneurysm (2) abdominal aortic aneurysm (AAA; 2), occluded graft (2), renal artery stenosis (1), pain from bone metastasis (1), aortic rupture (1), fever (1), weight loss (1), vasculitis (1) impotence (1), incidental finding (1) and bowel ischaemia (1). The diagnosis was not suspected clinically in any case. The tumours were sampled by endarterectomy (9), aortic resection (8), repair of aneurysm (5), and in four the diagnosis was made at autopsy. Histologically and immunohistochemically, 13 were categorised as poorly differentiated angiosarcomas, seven as undifferentiated sarcomas, three as osteosarcomas, two as myxofibrosarcomas, and one as myxoid sarcoma, not otherwise specified. The undifferentiated sarcomas and angiosarcomas were histologically similar to one another and were characterised by tumour cells within and overlying thrombus. The angiosarcomas were defined by diffuse CD31 expression with co-expression of pancytokeratin in 10 (77%). Undifferentiated sarcomas were composed of spindled and/or epithelioid cells and 71% expressed smooth muscle actin. Histological material from metastatic tumours was available in two osteosarcomas and two undifferentiated sarcomas, and showed undifferentiated pleomorphic sarcoma in all cases.In this series, half of aortic intimal sarcomas are histologically undifferentiated and express endothelial and epithelial markers (epithelioid angiosarcoma). The second largest group is undifferentiated sarcoma without immunohistochemical evidence of endothelial differentiation and frequent actin positivity. Rare types include myxofibrosarcoma and osteosarcoma.
    Pathology 12/2014; 46(7):596-603. · 2.62 Impact Factor
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    ABSTRACT: There are few studies addressing survival of diffuse peritoneal mesotheliomas (DPM).In this study, survival data were obtained retrospectively from 73 patients treated with intended cytoreductive surgery for DPM, with a mean follow-up of 42 months. Mesotheliomas were classified as well differentiated papillary (WDPM, n = 2), multicystic (MCM, n = 4), and epithelioid mesotheliomas were subclassified as tubulopapillary (TPM, n = 27), solid/deciduoid (S/DM, n = 34), and or biphasic mesothelioma (BPM, n = 6). Invasion was characterised as absent (grade 0), into stroma (grade 1), into fat (grade 2), and into adjacent structures (grade 3). Peritoneal cancer index (PCI) and completeness of cytoreduction (CCR) were assessed surgically.There were no deaths in the WDPM, MCM, and epithelioid DPM with ≤ grade 1 invasion. There was a stepwise decrease in overall survival from invasive TPM, S/DM, and BPM (p < 0.0001). By univariate analysis, advanced age (p = 0.01), incomplete CCR (p < 0.001), PCI (p = 0.004), mitotic count (p < 0.001), nuclear grade (p < 0.0001), stromal inflammation (p = 0.013), depth of invasion (p < 0.0001), necrosis (p = 0.002), and sarcomatoid growth (p < 0.0001) were associated with decreased overall survival. By multivariate analysis, only sarcomatoid growth (p = 0.0006), depth of invasion (p = 0.02), elevated CCR (CCR 2-3) (p = 0.02), and presence of inflammatory stroma (p = 0.04) were significant variables associated with decreased overall survival.DPM form a spectrum of indolent to highly aggressive tumours. Solid epithelioid/deciduoid tumours have a prognosis intermediate between biphasic mesotheliomas and invasive TPM. The presence and degree of invasion, sarcomatoid features, and inflammatory stroma are poor prognostic indicators.
    Pathology 12/2014; 46(7):604-9. · 2.62 Impact Factor
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    ABSTRACT: Background There is little information comparing high-resolution computed tomography (HRCT) findings in UIP with different components that make up remodeling histologically. Design We compared histologic features with HRCT scans from 69 explants with UIP. The extent of 7 histologic features were semi-quantitated: respiratory-lined cysts, bronchiolectasis, pulmonary interstitial emphysema (PIE), lobular remodeling, areas resembling non-specific interstitial pneumonia (NSIP), desquamative interstitial pneumonia (DIP)-like pattern, and mucus pooling within cysts extending into surrounding parenchyma. Subpleural cystic spaces and areas of lobular remodeling were measured morphometrically. Histologic features were compared to three findings on HRCT: diagnostic pattern (UIP, probable UIP, or inconsistent with UIP pattern), degree of honeycombing, and degree of ground-glass opacities. Results Histologically, respiratory-lined cysts were observed in 78%, bronchiolectasis in 83%, interstitial emphysema in 22%, lobular remodeling in 96%, NSIP-like areas in 87%, DIP-like reaction in 10%, and mucin extravasation in 78%. Morphometrically, cysts of PIE measured 6.2 ± 2.9 mm, respiratory-lined cysts 3.5 ± 2.4 mm, and bronchiolectatic cysts 3.3 ± 1.5 mm. Remodeled lobules measured 3.6 ± 1.1 mm. UIP pattern on CT correlated strongly with histologic extent of bronchiolectasis (p = 0.001). HRCT honeycombing showed a positive correlation with histologic bronchiolectasis (p = 0.001) and respiratory-lined cysts (p = 0.001). GGO was positively associated with NSIP-like areas (p = 0.02) and extravasated mucus (p = 0.05). Conclusions HRCT findings typical of UIP and HRCT honeycombing correlate best with bronchiolectasis histologically. NSIP pattern is common, and is associated with CT finding of GGO.
    Pathology - Research and Practice 10/2014; · 1.56 Impact Factor
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    ABSTRACT: Background The histopathologic distinction between typical carcinoid (TC) and atypical carcinoid (AC) of the lung is based largely on mitotic index. Ki-67 may aid in separation of these tumors, as well as the distinction from large cell neuroendocrine carcinoma (LCNEC).Methods We identified 55 surgically resected primary neuroendocrine lung tumors (39 TC, 7 AC, 9 LCNEC) based on mitotic rate and histologic features. Ki-67 proliferative index based on automated image analysis, tumor necrosis, nodal metastases, local or distant recurrence, and survival were compared across groups.ResultsThe mean mitotic count and Ki-67 index for TC, AC, and LCNEC were 0.1 and 2.3%, 3.4 and 16.8%, and 56.1 and 81.3% respectively. The Ki-67 index did not overlap among groups, with ranges of 0¿6.7% for TC, 9.9-25.7% for AC, and 63.2-91.9% for LCNEC. Nodal metastases were identified in 4/39 (10%) TC, 2/7 (22%) AC, and 2/8 (25%) LCNEC. There was no survival difference between TC and AC, but there was a significant survival difference between LCNEC and TC and AC combined (p¿<¿0.001). There was a step-wise increase in disease free survival with tumor grade: no TC recurred, 2/7 AC recurred or progressed (median interval 35.5 months), and all LCNEC recurred or progressed (median interval 10.1 months). No patient with TC or AC died of disease, compared to 7/8 LCNEC with follow-up data.Conclusions We conclude that Ki-67 index is a useful diagnostic marker for neuroendocrine tumors, with 7% a divider between AC and TC, and 50% a divider between LCNEC and AC. LCNEC is biologically different from AC and TC, with a much more aggressive course, and a high Ki-67 index.Virtual SlidesThe virtual slide(s) for this article can be found here:
    Diagnostic Pathology 10/2014; 9(1):174. · 2.41 Impact Factor
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    ABSTRACT: Mucinous tubular and spindle cell carcinoma (MTSCC) is a rare type of kidney tumor with relatively indolent behavior. Non-classic morphological variants have not been well studied and rarely been reported. We report a challenging case MTSCC with a peculiar morphology in a 42-year-old man, arising in a background of end-stage renal disease (ESRD). Predominant areas with extensive papillary architecture, psammoma bodies and stromal macrophageal aggregates, reminiscent of a papillary renal cell carcinoma (papillary RCC), were intermixed with foci that transitioned into a MTSCC-like morphology exhibiting elongated tubules and a low grade spindle cell component in a background of mucinous stroma. Immunuhostochemistry demonstrated diffuse positivity for P504s/AMACR and vimentin in tumor cells. Focal positivity for RCC, CD10 and CK7 was also noted. Kidney-specific cadherin, cytokeratin 34betaE12 and TFE3 stains were negative in the tumor. The major differential diagnostic considerations were papillary RCC, clear cell papillary RCC, and Xp11.2 translocation carcinoma. Negative FISH studies for trisomy 7 and 17 in both papillary and spindled components supported the diagnosis of MTSCC. The ultrastructrural profile was not entirely indicative of the cellular origin of the tumor. Cytogenetic analysis should be performed in atypical cases of MTSCC for precise diagnosis.
    Pathology - Research and Practice 07/2014; · 1.56 Impact Factor
  • The American journal of surgical pathology. 06/2014;
  • Lauren Xu, Jonathon Heath, Allen Burke
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    ABSTRACT: There are few single-institution clinicopathological series of aortitis. In this study, all ascending aneurysms were prospectively evaluated pathologically with ≥6 aortic sections over a 6-year period.Of 300 ascending aortic resections, there were 21 cases of aortitis (7%), in 11 women and 10 men (mean 67, range 41-88 years). There were 19 patients with aneurysms, and two patients with sclerosing periaortitis, clinically suspected to have intramural haematoma.Of the 19 patients with aneurysms (11 women), two had prior temporal arteritis, one ankylosing spondylitis, one IgA nephropathy, one undifferentiated autoimmune disease, one Lyme disease, and one fibromyalgia. In only two patients was aortitis suspected before surgery as the cause of aneurysm. Four patients developed distal aortic aneurysm requiring repeat surgery. Valve replacement or repair was necessary in nine patients, and two patients died after surgery. There were no significant differences between patients with and without autoimmune disease. The histological features were necrotising aortitis in 18 of 19 patients with aneurysmal aortitis, and there was one case of non-necrotising aortitis. One valve showed autoimmune valvulitis, congenitally bicuspid associated with ankylosing spondylitis. Necrotising aortitis was classified as acute (n = 5), healing (n = 9), and healed (n = 4). Acute necrotising aortitis was associated with need for valve replacement (p = 0.01) and younger age (p = 0.01). The healed phase had subtle histological features, sparse medial inflammation, marked medial attenuation, and chronic adventitial inflammation.Two patients with periaortitis demonstrated marked fibroinflammatory thickening of the adventitia with histological features typical of IgG4-related disease; neither had systemic symptoms.Ascending aortitis is histologically diverse, most frequently of the medial necrotising type, and is usually not suspected pre-operatively. Awareness of the histological spectrum is necessary for pathological diagnosis.
    Pathology 05/2014; · 2.62 Impact Factor
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    ABSTRACT: Restenosis after stenting occurs secondary to the neointima formation. Neovessels have been found in the neointima within stents. However, there are few studies correlating neointimal angiogenesis and in-stent restenosis in humans. We analyzed 65 post-mortem stented arteries from 33 patients with duration >3 months. Cause of death was determined incidental to the coronary findings in every case. Stented segments were embedded in paraffin and stained immunohistochemically for CD68 (macrophages), and endothelial marker PECAM-1 (CD31). Computerized morphometry was performed to quantitate neovessel density for CD31, macrophage infiltrates, as well as plaque and neointimal area. In-stent restenosis was defined as luminal narrowing ≥75% cross-section of the stented area. Underlying plaque morphology was classified as fibrous or atheromatous. Neovessels were present in the neointima of 57 stented segments (88%). Mean neovessel density was greater in restenotic vs. non-restenotic neointimas (p=0.009) and macrophage density was also greater (p=0.006). Neointimal area correlated positively with density of neointimal vessels (p=0.002), as well as neointimal macrophage density (p=0.006), but not type of stent, underlying plaque type, or underlying plaque macrophage score. We conclude that in-stent restenosis is associated with neointimal angiogenesis which is accompanied by macrophage inflammation. The relevance of these findings to treatment and prevention of in-stent restenosis needs to be further explored.
    Pathology - Research and Practice 04/2014; · 1.56 Impact Factor
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    ABSTRACT: Antibody mediated rejection (AMR) is characterized histologically by intracapillary macrophages. Macrophage density may be an alternative method of determining inflammatory changes in AMR. We identified 118 heart transplant patients with serologic testing for HLA alloantibodies. Macrophage density was graded as 1+ (< 45 / mm(2) ), 2+ (46-90 / mm(2) ), and 3+ (>90 / mm(2) ). Maximal macrophage density and complement staining over multiple biopsies were correlated with peak panel reactive antibodies (PRA), donor specific antibodies (DSA) and the clinical diagnosis of AMR. The presence of PRA correlated with macrophage score (p=.001). Macrophage density correlated with any DSA (p<.0001), class I DSA (p<.0001), class II DSA (p<.0001), and class II DQ (p<.0001). Nine patients had clinical AMR. Among patients with AMR, 89% had a biopsy over the period of AMR with ≥ 3+ macrophage density (89% sensitivity); among patients without AMR, 93% of patients had no biopsy at any time with ≥ 3+ macrophage density (specificity). There was perfect concordance between the scores of C4d positivity and macrophage density in 61% and only partial concordance in 20%, with complete discordance in 19% in biopsies taken during clinical episodes of AMR. Macrophage density in allograft endomyocardial biopsies is frequently elevated during clinical episodes of AMR and correlates well with alloantibodies. This article is protected by copyright. All rights reserved.
    Clinical Transplantation 03/2014; · 1.49 Impact Factor
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    ABSTRACT: Restenosis after stenting occurs secondary to the neointima formation. Neovessels have been found in the neointima within stents. However, there are few studies correlating neointimal angiogenesis and in-stent restenosis in humans.We analyzed 65 post-mortem stented arteries from 33 patients with duration > 3 months. Cause of death was determined incidental to the coronary findings in every case. Stented segments were embedded in paraffin and stained immunohistochemically for CD68 (macrophages), and endothelial marker PECAM-1(CD31). Computerized morphometry was performed to quantitate neovessel density for CD31, macrophage infiltrates, as well as plaque and neointimal area. In-stent restenosis was defined as luminal narrowing ≥ 75% cross-section of the stented area. Underlying plaque morphology was classified as fibrous or atheromatous. Neovessels were present in the neointima of 57 stented segments (88%). Mean neovessel density was greater in restenotic vs. non-restenotic neointimas (p = 0.009). and macrophage density was also greater (p = 0.006). Neointimal area correlated positively with density of neointimal vessels (p = 0.002), as well as neointimal macrophage density (p = 0.006), but not type of stent, underlying plaque type, or underlying plaque macrophage score. We conclude that in-stent restenosis is associated with neointimal angiogenesis which is accompanied by macrophage inflammation. The relevance of these findings to treatment and prevention of in-stent restenosis needs to be further explored.
    Pathology - Research and Practice 01/2014; · 1.56 Impact Factor
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    ABSTRACT: Objectives Three intravascular ultrasound (IVUS) signatures have been associated with coronary artery disease instability: echo-attenuation, intraplaque echolucent zone, and spotty calcification. We sought to investigate the substrates responsible for these IVUS signatures in a relatively large series of postmortem human coronary samples. Background The exact mechanisms and pathologic correlates underlying echo-attenuation, an intraplaque echolucent zone, and spotty calcification remain poorly understood. Methods IVUS was compared to near-infrared spectroscopy (NIRS) detection of lipid core plaque (LCP) and histopathology in 2294 vessel segments from 151 coronary specimens from 62 patients at necropsy using the modified American Heart Association classification. Results IVUS detected echo-attenuated plaques in 18.3% segments, echolucent plaques in 10.5% segments, and spotty calcification in 14.4% segments. Histopathologically, 91.4% echo-attenuated plaques corresponded to either a fibroatheroma with a necrotic core or pathologic intimal thickening with a lipid pool; almost all segments with superficial echo-attenuation indicated the presence of a fibroatheroma with an advanced necrotic core. Echolucent plaques indicated the presence of a relatively smaller lipid/necrotic core compared to echo-attenuated plaques (thickness: 0.51 [interquartile range (IQR): 0.35-0.64] vs. 0.70 [IQR: 0.54-0.92] mm, p<0.001; arc: 74.5° [IQR: 59.0°-101.0°] vs. 90° [IQR: 70.0°-112.0°], p<0.001), although 82.8% of superficial echolucent zones indicated a necrotic core-containing fibroatheroma. IVUS spotty calcification, especially superficial in location (72.6%), was often associated with a fibroatheroma with calcium deposits and had smaller arcs of calcium in the setting of fibroatheroma versus fibrocalcific plaques (37.5° [IQR, 23.0°-53.0°] vs. 59.0° [IQR, 46.0°-69.0°], p<0.001). Comparisons between IVUS and NIRS revealed that echo-attenuated plaques contained the highest probability of NIRS-derived LCP followed by echolucent plaques and spotty calcifications. Conclusions This study demonstrated that echo-attenuated plaque, especially superficial echo-attenuation, was the most reliable IVUS signature for identifying a high-risk plaque, ie, a fibroatheroma containing a large necrotic core.
    Journal of the American College of Cardiology 01/2014; · 15.34 Impact Factor
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    ABSTRACT: There are few histologic studies of intracoronary stents found at autopsy. We studied histologic findings of 87 intracoronary stents from 45 autopsy hearts. There were 40 patients with chronically implanted stents and five shorter than 30 days. Of five patients with recent stent placement, the cause of death was related to the stent (in-stent thrombosis) in one case. Of the 40 patients with chronic stents, there were 16 sudden coronary deaths and 24 noncoronary deaths (controls). There were no late stent thromboses in the coronary deaths. In the coronary deaths, 26% of stents showed restenosis versus 11% in controls (p = 0.1). The rate of healed infarcts and cardiomegaly was similar in the coronary and noncoronary groups, and acute thrombi in native arteries were seen only in three hearts in the coronary group. We conclude that the cause of death is rarely impacted by in-stent findings at autopsy, especially in chronically implanted stents.
    Journal of Forensic Sciences 11/2013; 58(6):1542-8. · 1.31 Impact Factor
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    ABSTRACT: We report a case of a 30-year-old woman who suddenly collapsed after having a physical altercation with her husband. Despite immediate resuscitation, she died on arrival at the hospital. The victim's parents requested an autopsy because they believed that their daughter was killed by her husband. Postmortem examination revealed that the victim had a diffusely enlarged thyroid gland and cardiomegaly with left ventricular hypertrophy. There was no evidence of significant trauma on the body. Further postmortem thyroid function tests and review of her medical history indicated that her death was due to Graves' disease. To the best of our knowledge, this is the first case reported of sudden death due to cardiac arrhythmia from Graves' disease induced by physical and emotional stress associated with the criminal activity of another person. The autopsy findings are described. In addition, the literature is reviewed and the significance of postmortem evaluation of thyroid hormones in the cases of sudden death is discussed.
    Journal of Forensic Sciences 08/2013; · 1.31 Impact Factor
  • The Brazilian journal of infectious diseases: an official publication of the Brazilian Society of Infectious Diseases 08/2013; · 1.04 Impact Factor
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    ABSTRACT: There are few autopsy studies of patients dying suddenly with obstructive sleep apnea (OSA). Twenty-five forensic autopsies of unexpected sudden death in individuals with OSA were reviewed. The causes of death were as follows: cardiomyopathy (n = 11); sudden unexpected death without morphologic findings (SUDNA, n = 6); and other cardiovascular diseases not related to OSA (n = 8). The cardiomyopathy group comprised five hearts with concentric left ventricular hypertrophy without dilatation and six with left ventricular diameter >4 cm (dilated cardiomyopathy). Four of six hearts in the SUDNA group showed right ventricular dilatation compared with seven of 11 showed cardiomyopathy and one of eight miscellaneous. The degree of obesity was greatest in the dilated cardiomyopathy group (10 of 11 obese) followed by the SUDNA group (four of six obese). The cardiac findings in patients dying suddenly and unexpectedly with OSA include nonspecific cardiomyopathy, other cardiac conditions, and hearts without a morphologic cause of death, which show frequent right ventricular dilatation as the only finding.
    Journal of Forensic Sciences 07/2013; · 1.31 Impact Factor
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    ABSTRACT: Diffuse peritoneal mesothelioma (DPM) forms a spectrum of indolent surface tumours to malignant invasive cancers. There are few pathological series that span well and poorly differentiated lesions that show diffuse peritoneal spread. Sixty-four DPM treated by initial cytoreductive therapy were retrospectively reviewed. Tumours were classified by surface and invasive growth pattern and correlated with risk factors, peritoneal cancer index (PCI) and completeness of cytoreduction (CCR). Degree of invasion was quantitated as absent (0), into stroma (I), into fat (II), and into adjacent structures (III) and was correlated with cytological features. Selected immunohistochemical stains were performed. There were three well differentiated papillary mesotheliomas (WDPM; type A), four multicystic mesothelioma (type B), 22 tubulopapillary epithelioid mesotheliomas (type C), and 35 poorly differentiated epithelioid mesotheliomas with solid or sarcomatoid growth (Type D). Seven type D tumours had prominent sarcomatoid areas, 12 deciduoid areas, and four lymphohistiocytoid features. Risk factors were present in all groups except type A, and included prior abdominal surgery (n = 24), asbestos exposure (n = 5) and radiation (n = 2). Extra-pleural mesothelioma was present in all groups except type B (total n = 7, 11%). Two type A and eight type C tumours lacked invasion; only type D showed level III invasion. The invasive portion of one type A tumour and two type B tumours showed adenomatoid features. PCI and CCR were greater in type D compared to the other groups (p = 0.02), as well as mitotic rate, degree of necrosis, and nuclear pleomorphism (p < 0.001). Degree of invasion was strongly correlated with CCR (p = 0.007), necrosis (p < 0.0001), nuclear grade (p < 0.0001), and mitotic rate (p = 0.001), but not PCI (p = 0.1). Immunohistochemical results were similar across groups, with frequent positivity for CA125 (94%), EGFR (94%) and calretinin (93%), followed by p16 (85%), cytokeratin 5,6 (76%), D2-40 (71%) and WT-1 (47%). PAX-8 was negative in all tumours, except one type A tumour that showed diffuse nuclear positivity. Diffuse peritoneal mesotheliomas can be classified into four groups that reflect invasive potential, degree of adverse histological features, and amenability for CCR. Non-invasive tumours include both type A and type C tumours.
    Pathology 07/2013; · 2.62 Impact Factor
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    ABSTRACT: The mechanisms of interstitial lung disease (ILD) remain incompletely understood, though recent observations have suggested an important contribution by interleukin (IL)-33. Substantial elevation in IL-33 expression was found in the lungs of patients with idiopathic pulmonary fibrosis and scleroderma lung disease as well as in the bleomycin injury mouse model. Most of the observed IL-33 expression was intracellular and intranuclear, suggesting involvement of the full-length (fl) protein but not the proteolytically processed mature IL-33 cytokine. The effects of flIL-33 on mouse lungs were assessed independently and in combination with bleomycin injury using recombinant adenovirus-mediated gene delivery. Bleomycin-induced changes were not affected by gene deficiency of the IL-33 receptor T1/ST2. Combined flIL-33 expression and bleomycin injury had a synergistic effect on pulmonary lymphocyte and collagen accumulation, which could be explained by synergistic regulation of the cytokines TGF-β, IL-6, MCP-1, MIP-1α, and TNF-α. By contrast, there was no increase in the levels of the Th2 cytokines IL-4, IL-5, or IL-13. Also, flIL-33 was found to significantly increase expression of several heat shock proteins, particularly HSP70, which is known to be associated with ILD. Thus, full-length IL-33 is a synergistic proinflammatory and profibrotic regulator that acts by stimulating expression of several non-Th2 cytokines and activates expression of HSP70.
    American Journal of Respiratory Cell and Molecular Biology 07/2013; · 4.15 Impact Factor
  • Lauren Xu, Allen Burke
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    ABSTRACT: BACKGROUND:: The histologic reaction in the adventitia to aortic dissections may be relevant to dating the onset of symptoms and to providing insight into pathogenesis. DESIGN:: We prospectively studied 43 surgically excised acute ascending aortic dissections before false-lumen rupture, with emphasis on inflammatory reaction in the false-lumen wall in relation to duration of symptoms. RESULTS:: A total of 31 men and 13 women were included in the study. Duration of symptoms was <12 hours (n=9), 12 to 24 hours (n=12), 1 to 2 days (n=8), 2 to 7 days (n=11), and >1 week (n=3). Medial inflammation was predominantly lymphohistiocytic and was marked in 3 cases but limited to the region adjacent to the dissection plane, unlike aortitis. Adventitial neutrophils occurred before 12 hours, peaked between 12 and 24 hours, and were rare after 2 days. Eosinophils occurred after 1 day, peaked between 2 and 7 days, and were predominant between 2 and 4 days. Macrophages were present after 1 day and peaked between 2 and 7 days. Mesothelial reaction occurred only after 1 day. Apoptosis and mitotic figures involving stromal cells occurred after 12 hours and peaked between 1 and 2 days; mitotic figures persisted up to 7 days. CONCLUSIONS:: Adventitial inflammation is prominent soon after intimal injury in aortic dissections before rupture of the false lumen. The pattern of inflammation is distinct from aortitis and can be used to date early aortic dissections.
    The American journal of surgical pathology 06/2013; · 4.59 Impact Factor

Publication Stats

16k Citations
1,745.26 Total Impact Points


  • 2011–2014
    • Fudan University
      • Department of Forensic Medicine
      Shanghai, Shanghai Shi, China
  • 2007–2014
    • University of Maryland Medical Center
      • Department of Pathology
      Baltimore, Maryland, United States
  • 2005–2014
    • University of Maryland, Baltimore
      • • Department of Pathology
      • • Department of Medicine
      Baltimore, Maryland, United States
    • Mayo Clinic - Rochester
      Rochester, Minnesota, United States
  • 2012
    • Universidade Federal de São Paulo
      San Paulo, São Paulo, Brazil
    • American Institute for Radiologic Pathology
      Silver Spring, Maryland, United States
  • 2010
    • Loyola University Maryland
      Baltimore, Maryland, United States
  • 1989–2010
    • Armed Forces Institute of Pathology
      Ralalpindi, Punjab, Pakistan
    • Uniformed Services University of the Health Sciences
      • Department of Radiobiology
      Maryland, United States
  • 2008
    • Shady Grove Adventist Hospital
      Maryland, United States
    • Johns Hopkins University
      Baltimore, Maryland, United States
    • Infraredx, Inc.
      Burlington, Massachusetts, United States
  • 2006–2008
    • CVPath Institute
      Maryland, United States
  • 2002
    • University of South Alabama
      • Department of Pathology
      Mobile, AL, United States
  • 2000
    • New England Baptist Hospital
      Boston, Massachusetts, United States
  • 1999
    • Walter Reed Army Institute of Research
      Silver Spring, Maryland, United States
    • Policlinico San Matteo Pavia Fondazione IRCCS
      Ticinum, Lombardy, Italy
  • 1994
    • Iwate Medical University
      Morioka, Iwate, Japan