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Chest 01/2012; 141(1):259-64. · 5.25 Impact Factor
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ABSTRACT: A 38-year-old woman with clinical T3N1M0 esophageal adenocarcinoma received an institutional protocol of induction chemotherapy, esophagectomy, and consolidation chemoradiotherapy. Three months after treatment, she had an acute mental status change develop and grand mal seizures. Intracranial imaging demonstrated massive cerebral air emboli, and a rapidly fatal neurologic deterioration ensued. At autopsy, a nonmalignant 0.5-cm gastric conduit to the left atrial fistula was identified. This case illustrates a rare, but fatal, late benign complication of aggressive therapy for locally advanced esophageal cancer.
The Annals of thoracic surgery 11/2011; 92(5):1901-3. · 3.74 Impact Factor
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ABSTRACT: The purpose of this study was to examine the prevalence and histopathologic correlates of pericardial delayed hyperenhancement (DHE) seen with cardiac magnetic resonance imaging (CMR) among patients with constrictive pericarditis (CP) undergoing pericardiectomy.
Constrictive pericarditis patients studied by CMR will occasionally demonstrate pericardial DHE following gadolinium contrast administration.
We identified 25 CP patients who underwent pericardiectomy following CMR-gadolinium study. We also assessed 10 control subjects with no evidence of pericardial disease referred for cardiac viability imaging. A novel 14-segment pericardial model was used to determine pericardial DHE score and thickness score. Histopathology of pericardial specimens was reviewed and evaluated semiquantitatively on a 4-point scale for the extent of calcification, fibrosis, inflammation, and neovascularization.
DHE was present in 12 (48%) CP patients (DHE+ group), and absent in 13 CP patients (DHE- group) and all control patients. The DHE+ group had greater fibroblastic proliferation and neovascularization, as well as more prominent chronic inflammation and granulation tissue. Fibroblastic proliferation and chronic inflammation correlated with DHE presence quantitated by DHE score (Spearman r = 0.578, p < 0.002, and r = 0.590, p < 0.002, respectively), but not with pericardial thickness. Segmental analysis demonstrated no significant difference in the percentage of patients with different pericardial segmental thickness; however, overall, in each segment, the DHE+ group tended to have greater pericardial thickness.
The presence of pericardial DHE on CMR is common in patients with CP, and its presence is associated with histological features of organizing pericarditis, which may be a target for future focused pharmacological interventions. Patients with CP without pericardial DHE had more pericardial fibrosis and calcification, as well as lesser degrees of pericardial thickening.
JACC. Cardiovascular imaging 11/2011; 4(11):1180-91. · 14.29 Impact Factor
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ABSTRACT: We use the BD GeneOhm StaphSR Assay (BD Diagnostics, Oakville, Canada) to screen for Staphylococcus aureus nasal colonization and sought to evaluate this assay for the assessment of valve specimens from patients with endocarditis. We examined 23 paired fresh and formalin-fixed, paraffin-embedded cardiac valve tissue samples, 12 of which had S aureus endocarditis, using the BD GeneOhm StaphSR Assay for the detection and differentiation of methicillin-susceptible and methicillin-resistant S aureus. This assay appropriately characterized all specimens with respect to the presence or absence of S aureus. There was an 87.5% correlation between the presence or absence of the mecA gene and the oxacillin susceptibility results for the S aureus isolates studied. The GeneOhm StaphSR assay accurately detected S aureus in cardiac valve tissue samples. Rare discordances were observed between oxacillin susceptibility status and mecA gene detection by this assay.
American Journal of Clinical Pathology 11/2011; 136(5):686-9. · 2.60 Impact Factor
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Circulation 09/2011; 124(10):1180-1. · 14.74 Impact Factor
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ABSTRACT: The host response and remodeling of ECM scaffolds are believed to be critical determinants of success or failure in repair or reconstructive procedures. Host response has been investigated in subcutaneous or abdominal wall implantation models. The extent to which evaluation of the host response to ECM intended for tendon or ligament repair should be performed in an orthotopic site is not known. This study compared the host response to human-derived fascia lata ECM among various implantation sites in the rat model. Results showed that a xenograft in the rat shoulder does not exhibit a different host response at 7 days from xenograft in the body wall, suggesting that either site may be appropriate to study the early host response to biologic grafts as well as the effect of various treatments aimed to modify the early host response. By 28 days, a xenograft in the rat shoulder does elicit a unique host response from that seen in the body wall. Therefore, it may be more appropriate to use an orthotopic shoulder model for investigating the long-term host response and remodeling of biologic grafts to be used for rotator cuff repair.
Journal of Orthopaedic Research 08/2011; 30(3):461-7. · 2.81 Impact Factor
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Journal of Materials Science Materials in Medicine 06/2011; · 2.32 Impact Factor
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Gerald J Berry,
Annalisa Angelini,
Margaret M Burke,
Patrick Bruneval,
Michael C Fishbein,
Elizabeth Hammond,
Dylan Miller,
Desley Neil,
Monica P Revelo, E Rene Rodriguez,
Susan Stewart,
Carmela D Tan,
Gayle L Winters,
Jon Kobashigawa,
Mandeep R Mehra
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 06/2011; 30(6):601-11. · 3.54 Impact Factor
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ABSTRACT: Naturally-occurring biomaterial scaffolds derived from extracellular matrix (ECM) have been previously investigated for soft tissue repair. We propose to enrich fascia ECM with high molecular weight tyramine substituted-hyaluronan (TS-HA) to modulate inflammation associated with implantation and enhance fibroblast infiltration. As critical determinants of constructive remodeling, the host inflammatory response and macrophage polarization to TS-HA enriched fascia were characterized in a rat abdominal wall model. TS-HA treated fascia with cross-linking had a similar lymphocyte (P = 0.11) and plasma cell (P = 0.13) densities, greater macrophage (P = 0.001) and giant cell (P < 0.0001) densities, and a lower density of fibroblast-like cells (P < 0.0001) than water treated controls. Treated fascia, with or without cross-linking, exhibited a predominantly M2 pro-remodeling macrophage profile similar to water controls (P = 0.82), which is suggestive of constructive tissue remodeling. Our findings demonstrated that HA augmentation can alter the host response to an ECM, but the appropriate concentration and molecular weight needed to minimize chronic inflammation within the scaffold remains to be determined.
Journal of Materials Science Materials in Medicine 06/2011; 22(6):1465-77. · 2.32 Impact Factor
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Jon Kobashigawa,
Maria G Crespo-Leiro,
Stephan M Ensminger,
Hermann Reichenspurner,
Annalisa Angelini,
Gerald Berry,
Margaret Burke,
Lawrence Czer,
Nicola Hiemann,
Abdallah G Kfoury, [......],
Marlene L Rose,
Stuart D Russell,
Randy Starling,
Nicole Suciu-Foca,
Jose Tallaj,
David O Taylor,
Adrian Van Bakel,
Lori West,
Adriana Zeevi,
Andreas Zuckermann
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ABSTRACT: The problem of AMR remains unsolved because standardized schemes for diagnosis and treatment remains contentious. Therefore, a consensus conference was organized to discuss the current status of antibody-mediated rejection (AMR) in heart transplantation.
The conference included 83 participants (transplant cardiologists, surgeons, immunologists and pathologists) representing 67 heart transplant centers from North America, Europe, and Asia who all participated in smaller break-out sessions to discuss the various topics of AMR and attempt to achieve consensus.
A tentative pathology diagnosis of AMR was established, however, the pathologist felt that further discussion was needed prior to a formal recommendation for AMR diagnosis. One of the most important outcomes of this conference was that a clinical definition for AMR (cardiac dysfunction and/or circulating donor-specific antibody) was no longer believed to be required due to recent publications demonstrating that asymptomatic (no cardiac dysfunction) biopsy-proven AMR is associated with subsequent greater mortality and greater development of cardiac allograft vasculopathy. It was also noted that donor-specific antibody is not always detected during AMR episodes as the antibody may be adhered to the donor heart. Finally, recommendations were made for the timing for specific staining of endomyocardial biopsy specimens and the frequency by which circulating antibodies should be assessed. Recommendations for management and future clinical trials were also provided.
The AMR Consensus Conference brought together clinicians, pathologists and immunologists to further the understanding of AMR. Progress was made toward a pathology AMR grading scale and consensus was accomplished regarding several clinical issues.
The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 03/2011; 30(3):252-69. · 3.54 Impact Factor
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ABSTRACT: Lymphocytic myocarditis is a clinically important condition that is difficult to diagnose and distinguish. We hypothesized that the transcriptome obtained from an endomyocardial biopsy would yield clinically relevant and accurate molecular signatures.
Microarray analysis was performed on samples from patients with histologically proven lymphocytic myocarditis (n=16) and idiopathic dilated cardiomyopathy (n=32) to develop accurate diagnostic transcriptome-based biomarkers using multiple classification algorithms. We identified 9878 differentially expressed genes in lymphocytic myocarditis versus idiopathic dilated cardiomyopathy (fold change >1.2; false discovery rate <5%) from which a transcriptome-based biomarker containing 62 genes was identified that distinguished myocarditis with 100% sensitivity (95% confidence interval, 46 to 100) and 100% specificity (95% confidence interval, 66 to 100) and was generalizable to a broad range of secondary cardiomyopathies associated with inflammation (n=27), ischemic cardiomyopathy (n=8), and the normal heart (n=11). Multiple classification algorithms and quantitative real-time reverse-transcription polymerase chain reaction analysis further reduced this subset to a highly robust molecular signature of 13 genes, which still performed with 100% accuracy.
Together, these findings demonstrate that transcriptomic biomarkers from a single endomyocardial biopsy can improve the clinical detection of patients with inflammatory diseases of the heart. This approach advances the clinical management and treatment of cardiac disorders with highly variable outcome.
Circulation 03/2011; 123(11):1174-84. · 14.74 Impact Factor
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ABSTRACT: Autosomal dominant retinocerebral vasculopathy with cerebral leukodystrophy (RVCL) is a rare neurovascular syndrome causing retinal and central nervous system vasculopathy often recognized as contrast-enhancing white matter changes or pseudotumors on imaging. Heterozygous frameshift mutations in the 3-prime repair exonuclease 1 gene have been identified in families affected by RVCL. Variable light microscopic findings and a characteristic ultrastructural appearance of the vasculature in the brain have been reported. Description of the ophthalmic histopathology is exceedingly rare. Here, we report previously undescribed bilateral eye findings in a patient diagnosed with RVCL. The ophthalmic pathology includes thickening and reduplication of the retinal capillary basal lamina demonstrated by electron microscopy. These findings expand what is known about this disease and help further delineate its phenotype.
Journal of neuro-ophthalmology: the official journal of the North American Neuro-Ophthalmology Society 03/2011; 31(1):20-4. · 1.09 Impact Factor
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The Journal of heart and lung transplantation: the official publication of the International Society for Heart Transplantation 11/2010; 30(2):136-8. · 3.54 Impact Factor
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ABSTRACT: PURPOSE OF REVIEW: Currently clinical antibody-mediated rejection (AMR) requires demonstration of histopathologic changes, presence of donor-specific allo-antibodies and allograft dysfunction to establish the diagnosis. Pathology practice patterns in the immunopathologic evaluation and interpretation of cardiac transplant biopsies vary. Specific recommendations for post-transplant allo-antibody monitoring are lacking. Recently, the occurrence of surveillance biopsies being positive for immunopathologic markers of AMR without concomitant graft dysfunction is increasingly recognized. This review focuses on issues of standardization in the diagnosis of AMR and the need for updated criteria. RECENT FINDINGS: Concomitant use of C4d and C3d proved to be strongly predictive of the presence of circulating allo-antibodies and allograft dysfunction in heart transplant recipients. Asymptomatic patients with histopathologic evidence of AMR in their biopsies appear to have increased risk for cardiac allograft vasculopathy and cardiovascular mortality. The role of nonhuman leukocyte antigen antibodies in AMR has not been adequately addressed. SUMMARY: A consensus on the frequency of AMR screening, antibody panels, interpretation and reporting of stains will enhance standardization of the diagnosis of AMR. Further studies are needed to define asymptomatic or subclinical AMR and to determine the long-term outcome of pathologic evidence of complement activation without allograft dysfunction.
Current opinion in organ transplantation 09/2010; · 1.22 Impact Factor
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Circulation Cardiovascular Interventions 12/2009; 2(6):565-73. · 6.06 Impact Factor
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ABSTRACT: We sought to assess the diagnostic accuracy and incremental prognostic value of delayed hyper-enhancement cardiac magnetic resonance (DHE-CMR) compared with electrocardiographic and transthoracic echocardiographic (TTE) parameters in such patients.
Utility of DHE-CMR in the diagnosis of patients with suspected cardiac amyloidosis (CA) has recently been demonstrated, but its incremental prognostic utility is unclear.
Forty-seven consecutive patients (mean age 63 years, 70% men, 55% New York Heart Association functional class >II) with suspected CA who underwent electrocardiography (ECG), TTE, DHE-CMR, and biopsy (38 endomyocardial, 9 extracardiac) were studied. Low voltage on ECG was defined as S-wave in lead V(1) + R-wave in lead V(5) or V(6) <15 mm. TTE parameters, including deceleration time, E/E' ratio, and diastolic grade were recorded. CMR was considered positive with diffuse DHE of the subendocardium extending to adjacent myocardium. All-cause mortality was ascertained.
In the study population, 59% had low voltage on ECG, 30% had abnormal deceleration time < OR = 150 ms, 38% had E/E' ratio >15, and 47% had advanced (pseudonormal or restrictive) diastology.The diagnostic accuracy of DHE-CMR in patients undergoing endomyocardial biopsy was as follows: sensitivity 88%, specificity 90%, positive predictive value 88%, and negative predictive value 90%. On multivariable logistic regression testing of the diagnostic ability of various noninvasive imaging parameters, only DHE-CMR was significant (Wald chi-square statistic 9.6, p < 0.01). At 1-year post-biopsy, there were 9 (19%) deaths. On Cox proportional hazards analysis, only positive DHE-CMR was a predictor of 1-year mortality (Wald chi-square statistic 4.91, p = 0.03).
A characteristic DHE-CMR pattern is more accurate for diagnosis and is a stronger predictor of 1-year mortality in patients with suspected CA as compared with other noninvasive parameters.
JACC. Cardiovascular imaging 12/2009; 2(12):1369-77. · 14.29 Impact Factor
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Circulation Heart Failure 11/2009; 2(6):707-8. · 6.29 Impact Factor
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ABSTRACT: In the last decade, two advances have shifted attention from cellular rejection to antibody-mediated rejection (AMR) of cardiac transplants. First, more sensitive diagnostic tests for detection of AMR have been developed. Second, improvements in immunosuppression have made severe acute cellular rejection uncommon, but have had less effect on AMR.
Antibodies can contribute to graft rejection by activation of complement, by activation of vascular endothelial and smooth muscle cells, and by activation of neutrophils, macrophages or natural killer cells. Because acute rejection is a risk factor for chronic rejection in all types of organ transplants, it is has been proposed that AMR can cause chronic rejection.
Small animal models need to be developed to gain further insights into AMR and the role of antibodies in chronic graft arteriopathy. This article reviews the current clinical data and existing mouse models for AMR.
Journal of Clinical Immunology 10/2009; 29(6):722-9. · 3.08 Impact Factor
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Tetsuya Horai,
Hideyuki Fumoto,
Diyar Saeed,
Roula Zahr,
Tomohiro Anzai,
Yoko Arakawa,
Shanaz Shalli,
Chiyo Ootaki,
Jacquelyn Catanese,
Masatoshi Akiyama,
Carmela D Tan, E Rene Rodriguez,
James B Young,
Kiyotaka Fukamachi
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ABSTRACT: Allograft rejection remains the nemesis of solid organ transplantation. Soul Mate is a novel implantable wireless data transmission system that analyzes 9 intramyocardial electrogram parameters recorded from 4 or 6 configurations of 2 or 3 epicardial leads to detect allograft rejection. This study determined the ability of the Soul Mate to detect early rejection of transplanted hearts.
Five dogs underwent heterotopic cervical heart transplantation and simultaneous implantation of the Soul Mate's Cardiac Rejection Monitoring Device. Dogs were initially immunosuppressed, but subsequent drug discontinuation allowed allograft rejection to appear. Allograft biopsies were performed at regular intervals to determine rejection grade, which was compared to a calculated rejection score determined as percent change from baseline of values for each intramyocardial electrogram. There was significant correlation between the biopsy results and the evolution of 5 parameters. The strongest correlation (r=0.939; P<0.001) was obtained using the "general median" parameter from 4 configurations, assessed 1 day before the biopsy, with a sensitivity of 85.7% and a specificity of 100% compared to the myocardial biopsy results.
The Soul Mate allograft rejection monitoring system accurately detected transplanted heart rejection in a canine model noninvasively with continuous sampling. This proof-of-concept study suggests that the Soul Mate could be used to more intensely and more frequently monitor cardiac allografts for rejection.
Circulation 09/2009; 120(11 Suppl):S185-90. · 14.74 Impact Factor
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ABSTRACT: Fistulas between the aorta and tracheobronchial tree are rare fatal complications that occur in patients treated with external and endobronchial radiation for carcinomas of the upper and lower respiratory tract. The etiopathogenesis can be multifactorial. We report the case of a patient with irradiated tracheal carcinoma who died of massive hemoptysis 25 months after completing therapy. Autopsy revealed a fistula between the trachea and arch of the aorta. Multiple colonies of cocci and bacilli were demonstrated within the media at the site of rupture and were absent in other areas of the aorta. The development of an aortotracheal fistula in this patient was most probably related to infection in an area of tracheal and vascular wall previously damaged by exposure to high doses of radiation.
Archives of pathology & laboratory medicine 07/2009; 133(6):983-6. · 2.58 Impact Factor
