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Transcatheter pulmonary valve implantation (TPVI) is indicated for use in the management of failing pulmonary valves in humans. We report here the long-term follow-up of the first documented transcatheter pulmonary valve implanted in a client-owned dog. A one-year-old Beagle dog with severe congenital type A valvular pulmonic stenosis first underwent percutaneous balloon pulmonary valvuloplasty, leading two years later to severe pulmonary regurgitation. A TPVI using a Melody™ bioprosthetic valve was then successfully performed, with normalization of the right heart cavities. Repeated two- and three-dimensional transthoracic echocardiographic examinations combined with Doppler modes confirmed the appropriate position and function of the valve for four years. Mitral myxomatous valvular degeneration led to refractory left-sided congestive heart failure, and the dog was humanely euthanized. After postmortem examination, X-ray imaging and histopathological evaluation of the stent and the valve were performed. Ex-vivo imaging of the implanted valve using a Faxitron® Path radiography system and microscopic evaluation of the implanted stent and bioprosthetic leaflets did not show any relevant leaflet or stent alterations. This case provides a proof of concept in interventional veterinary cardiology, showing that TPVI can be performed in dogs with subsequent long-term maintaining normal pulmonary valve function. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Tissue engineering is an attractive alternative to conventional esophageal replacement techniques using intra-abdominal organs which are associated with a substantial morbidity. The objective was to evaluate the feasibility of esophageal replacement by an allogenic decellularized esophagus in a porcine model. Secondary objectives were to evaluate the benefit of decellularized esophagus recellularization with autologous bone marrow mesenchymal stromal cells and omental maturation of the decellularized esophagus. Eighteen pigs divided into 4 experimental groups according to mesenchymal stromal cells recellularization and omental maturation underwent a 5-cm long circumferential replacement of the thoracic esophagus. Turbo green florescent protein labelling was used for in vivo mesenchymal stromal cells tracking. The graft area was covered by a stent for 3 months. Clinical and histologic outcomes were analyzed over a 6-month period. The median follow-up was 112 days [5; 205]. Two animals died during the first postoperative month, 2 experienced an anastomotic leakage, 13 experienced a graft area stenosis following stent migration of which 3 were sacrificed as initially planned after successful endoscopic treatment. The stent could be removed in 2 animals: the graft area showed a continuous mucosa without stenosis. After 3 months, the graft area showed a tissue specific regeneration with a mature epithelium and muscular cells. Clinical and histologic results were similar across experimental groups. Circumferential esophageal replacement by a decellularized esophagus was feasible and allowed tissue remodeling toward an esophageal phenotype. We could not demonstrate any benefit provided by the omental maturation of the decellularized esophagus nor its recellularization with mesenchymal stromal cells. [ABSTRACT FROM AUTHOR]

Tissue-based gene expression approaches have been developed as a companion tool of routine pathology to refine the diagnosis of cardiac rejection. Whole-transcriptome profiling was used to define molecular phenotypes of rejection but its clinical application remains limited by several hurdles. The Banff Human Organ Transplant (BHOT) panel is a consensus list of 770 genes developed to facilitate cost-effective and reproducible expression analysis of solid organ allografts. We aimed at validating in-silico the targeted panel as a proxy to whole-transcriptome analysis. To assess the BHOT panel reliability in detecting gene expression pattern associated with antibody-mediated rejection (AMR), we performed in silico analysis and projected the BHOT panel on already published microarray data of 141 heart transplant biopsies We compared the targeted and whole-transcriptome molecular profiles in AMR-biopsies (n = 71) and non-AMR matched-control (non-rejection or acute cellular rejection, n = 71) by performing differential expression, pathway, and network analyses. Out of the 30 most differentially expressed genes between AMR and non-AMR identified in whole-transcriptome analysis, two-thirds (n = 19) were included in the BHOT panel (Figure 1). These genes covered major immune pathways and key cells involved in the physiology of AMR. Overall, differential gene expression, pathway and network analyses showed that the targeted gene expression analysis was able to detect biologically and clinically relevant genes (IFNG-inducible, NK-cells, injury, monocytes-macrophage, B-cells), pathways (interleukin and interferon signaling, neutrophil degranulation, immunoregulatory interactions) and networks reflecting the pathophysiological mechanisms associated with AMR previously identified in whole-transcriptome analysis. The targeted molecular signature of AMR based on the B-HOT panel detected relevant AMR-related genes and pathways. The targeted panel can be used as a proxy to whole-transcriptome to analyze the molecular profile of heart allograft rejection. [ABSTRACT FROM AUTHOR]

Clinical and post-mortem examination of an adult neutered male cat with immune-mediated haemolytic anaemia revealed suspected nodules of tumour tissue in the cortex of the right kidney. Cytology and histopathology indicated a malignant renal tumour of undetermined type. Immunohistochemistry confirmed renin production by a proportion of the tumour cells. The lesion may represent a renal adenocarcinoma producing renin or a tumour of juxtaglomerular cells ('reninoma'). [ABSTRACT FROM AUTHOR]

Objective Various animal models of critical limb ischemia have been developed in the past. However, there is no animal model that can undergo endovascular treatment, while providing reproducible true critical limb ischemia with arterial ulcers and rest pain. We evaluated the efficacy of a new model of rabbit hindlimb ischemia created through a percutaneous approach using embolization with calibrated particles. Methods Through a percutaneous transauricular artery approach and selective catheterization of the superficial femoral artery, embolization of distal limb vessels was performed using a mixture of 300- to 500-μm calibrated microparticles (Embosphere, Merit Medical, Salt Lake City, Utah), saline solution, and iodine contrast. Clinical and ultrasound imaging-based blood flow evaluation was performed before embolization and during follow-up. Histologic evaluation was performed at humane killing 14 days after the procedure. Results The model was successfully created in 10 rabbits (10 limbs). One rabbit died of sudden death at 8 days after the procedure. The nine surviving rabbits developed hind ulcers. All rabbits had a higher pain score in the follow-up compared to baseline value ( P < .0001). Blood flow in the saphenous artery decreased significantly after the procedure and later at 14 days follow-up (baseline value 63.4 ± 31.3 μL per cardiac cycle vs 32.0 ± 28.4 μL per cardiac cycle postprocedure [ P = .0013] and 32.0 ± 28.4 μL per cardiac cycle at 14 days [ P = .0015]). Pathology showed signs of severe limb ischemia in all rabbits with subacute and chronic injury patterns. Conclusions A rabbit hind limb ischemia model created by percutaneous transauricular distal femoral artery embolization with calibrated particles may overcome some of the limitations of existing animal models. As such, this model could prove useful for assessing therapies designed to improve arterial perfusion and collateral growth. [ABSTRACT FROM AUTHOR]

Objective Aortitis is an exceedingly rare manifestation of tuberculosis. We describe 11 patients with tuberculous aortitis (TA). Methods Multicenter medical charts of patients hospitalized between 2003 and 2015 with TA in Paris, France, were reviewed. Demographic, medical history, laboratory, imaging, pathologic findings, treatment, and follow-up data were extracted from medical records. TA was considered when aortitis was diagnosed in a patient with active tuberculosis. Results Eleven patients (8 women; median age, 44.6 years) with TA were identified during this 12-year period. No patient had human immunodeficiency virus infection. Tuberculosis was active in all cases, with a median delay of 18 months between the first symptoms and diagnosis. At disease onset, vascular signs were mainly claudication, asymmetric blood pressure, and diminished distal pulses. Constitutional symptoms or extravascular signs were present in all patients at some point. Aortic pseudoaneurysm was the most frequent lesion, but three patients had isolated inflammatory aortic stenosis. TA appeared as extension from a contiguous infection in only three cases. Tuberculosis was considered because of clinical features, tuberculin skin or QuantiFERON-TB Gold (Quest Diagnostics, Madison, NJ) test results, pathologic findings, and improvement on antituberculosis therapy. A definite Mycobacterium tuberculosis identification was made in only three cases. All patients received antituberculosis therapy for 6 to 12 months. Surgery including Bentall procedures, aortic bypass, and open abdominal aneurysm repair was performed at diagnosis in eight patients. Seven patients received steroids as an adjunct therapy. All patients clinically improved under treatment. No patients died for a median follow-up duration of 4 years. Conclusions TA may result in aneurysms contiguous to regional adenitis but also in isolated inflammatory aortic stenosis. Steroids may be associated with antituberculosis therapy for inflammatory stenotic lesions. Surgery is indicated for aneurysms and in case of worsening stenotic lesions despite anti-inflammatory drugs. No patient died after such combined treatment strategy. [ABSTRACT FROM AUTHOR]

Whether Barlow disease (BD) and fibroelastic deficiency (FED), the main causes of mitral valve prolapse (MVP), should be considered 2 distinct diseases remains unknown. Mitral valves from patients who required surgery for severe mitral regurgitation due to degenerative nonsyndromic MVP were analyzed. Intraoperative diagnosis of BD or FED was based on leaflet redundancy and thickness, number of segments involved, and annular dimension. The removed medial scallop of the posterior leaflet and attached chordae were used for histopathological and immunohistological assessment. Histologically, compared to normal controls (n = 3), BD (n = 14), and FED (n = 9) leaflets demonstrated an altered architecture and increased thickness. Leaflet thickness was greater and chordae thickness lower in BD than FED (P < 0.0001). In BD, increased thickness was owing to spongiosa expansion (proteoglycan accumulation) and intimal thickening on fibrosa and atrialis; in FED, local thickening was predominant on the fibrosa side, with accumulation of proteoglycan-like material around the chordae. Collagen accumulation was observed in FED leaflets and chords and decreased in BD. Fragmented elastin fibers were present in BD and FED; elastin decreased in BD but increased in FED leaflets and around chordae. Activated myofibroblasts accumulate in both diseased leaflets and chords, but more abundantly in FED chordae (P < 0.0001), independently of age, suggesting a role of these cells in chordal rupture. There were more CD34-positive cells in BD leaflets and in FED chordae (P < 0.01). In BD leaflets (but not chordae) proliferative Ki67-positive cells were more abundant (P < 0.01) and matrix metalloproteinase 2 levels were increased (P < 0.01) indicating tissue remodeling. Upregulation of transforming growth factor beta and pERK signaling pathways was evident in both diseases but more prominent in FED leaflets (continued on next page)(P < 0.001), with pERK upregulation in FED chordae (P < 0.0001). Most cellular and signaling markers were negligible in control valves. Quantitative immunohistopathological analyses demonstrated distinct changes between BD and FED valves: predominant matrix degradation in BD and increased profibrotic signaling pathways in FED, indicating that BD and FED are 2 different entities. These results may pave the way for genetic studies of MVP and development of preventive drug therapies. [ABSTRACT FROM AUTHOR]

Summary Tissue engineering, which consists of the combination and in vivo implantation of elements required for tissue remodeling toward a specific organ phenotype, could be an alternative for classical techniques of esophageal replacement. The current hybrid approach entails creation of an esophageal substitute composed of an acellular matrix and autologous epithelial and muscle cells provides the most successful results. Current research is based on the use of mesenchymal stem cells, whose potential for differentiation and proangioogenic, immune-modulator and anti-inflammatory properties are important assets. In the near future, esophageal substitutes could be constructed from acellular “intelligent matrices” that contain the molecules necessary for tissue regeneration; this should allow circumvention of the implantation step and still obtain standardized in vivo biological responses. At present, tissue engineering applications to esophageal replacement are limited to enlargement plasties with absorbable, non-cellular matrices. Nevertheless, the application of existing clinical techniques for replacement of other organs by tissue engineering in combination with a multiplication of translational research protocols for esophageal replacement in large animals should soon pave the way for health agencies to authorize clinical trials. [ABSTRACT FROM AUTHOR]

The pathology-based diagnosis of antibody-mediated rejection (AMR) following heart transplantation relies on the 2013 Working Formulation in which microvascular inflammation (MVI) is considered as present or absent regardless of its extent. This work assessed the biological and clinical value of a semiquantitative evaluation of the extent of MVI in endomyocardial biopsies (EMB). We retrospectively graded the extent of MVI in 291 EMB from 291 patients according to a 4-point scale where MVI scores of 0, 1, 2 and 3 represented 0%, 1–10%, 11–50% and > 50% of the myocardial area, respectively. We analyzed the association between the MVI score and tissue rejection molecular activity assessed by micro-arrays or reverse transcriptase multiplex ligation-dependent probe amplification, current pathology classification (pAMR), circulating anti-HLA donor-specific antibodies (DSA) and graft dysfunction. Overall, 172 (59.1%), 33 (11.4%), 42 (14.4%) and 44 (15.1%) EMB were given MVI scores of 0, 1, 2 and 3, respectively. pAMR1(H+) and pAMR2/3 categories were found to be heterogenous in terms of MVI score. Acute cellular rejection grades did not influence the MVI score. In both molecular approaches, we observed a stepwise increase in the expression of AMR-related transcripts with increasing MVI scores, independently of the C4d or CD68 status (Fig. 1, P < 0.001). Both the frequency and mean fluorescence intensity of DSA gradually increased with the MVI score (P < 0.001). Acute graft dysfunction was more frequent in MVI score 3 (P < 0.001). The intensity of MVI in EMB, based on a semiquantitative evaluation of its extent, has biological and clinical importance. [ABSTRACT FROM AUTHOR]

Summary Indoleamine 2,3-dioxygenase 1 (Ido1) is a rate-limiting enzyme that catalizes the degradation of tryptophan along the kynurenine pathway. Here, we show that Ido1 activity sustains an immunostimulatory potential through inhibition of interleukin (Il)10. In atherosclerosis, Ido1-dependent inhibition of Il10 translates into disease exacerbation. The resistance of Ido1-deficient mice to enhanced immune activation is broken in Ido1/Il10 double-deficient mice, which show exaggerated immune responses and develop severe spontaneous colitis. We demonstrate that Ido1 activity is required for the regulation of Il10 and that kynurenic acid (Kna), an Ido1-derived metabolite, is responsible for reduced Il10 production through activation of a cAMP-dependent pathway and inhibition of Erk1/2 phosphorylation. Resupplementation of Ido1-deficient mice with Kna limits Il10 expression and promotes atherosclerosis. In human atherosclerotic lesions, increased levels of Kna are associated with an unstable plaque phenotype, and its blood levels predict death and recurrent myocardial infarction in patients with coronary artery disease. [ABSTRACT FROM AUTHOR]

Background Esophageal replacement by the colon or the stomach for malignant and nonmalignant esophageal diseases exposes to significant morbidity and mortality. In this setting, tissue engineering seems to be a seductive alternative. Methods In a porcine model, we performed a 5-cm-long circumferential replacement of the cervical esophagus by a tubulized acellular matrix (small intestinal submucosa) cellularized with autologous skeletal myoblasts and covered by a human amniotic membrane seeded with autologous oral epithelial cells. The substitute was grown for 2 weeks in the great omentum before esophageal replacement. Eighteen minipigs (divided into 3 groups: group A [substitute with esophageal endoprothesis; n = 6], group B [substitute alone; n = 6], and group C [endoprothesis alone; n = 6]) were included. The esophageal endoprothesis was removed at 6 months. Animals were killed sequentially over a 12 month-period. Clinical, endoscopic, radiologic and histologic outcomes were analyzed. Results All animals except 1 of in groups B and C died during the first 2 months owing to refractory esophageal stenosis or endoprothesis extrusion. Nutritional autonomy without endoprothesis was observed in all animals of group A with a follow-up of >6 months ( n = 3). A phenotype similar to that of native esophagus, consisting of a mature epithelium, submucosal glands, and a circular muscular layer, was observed after 9 months. Conclusion In this model, the circumferential replacement of the cervical esophagus by a tube-shaped tissue-engineered substitute under the temporary cover of an esophageal endoprothesis allowed nutritional autonomy and tissue remodeling toward an esophageal phenotype. [ABSTRACT FROM AUTHOR]

Copyright of Archives of Cardiovascular Diseases is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Revue Francophone des Laboratoires is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Esophageal replacement by biological graft is associated with a high risk of anastomotic leak–related mediastinitis. Objective: To determine whether a self-expanding plastic stent can help avoid anastomotic leak after full-thickness replacement of the esophagus in a porcine model. Design: Experimental feasibility study in a porcine model. Subjects: Twelve pigs were analyzed in the study. Interventions: Replacement of a 2-cm-long segment of the cervical esophagus by an aortic allograft was performed in 12 pigs, with 6 pigs used as graft donors. Animals were divided into 2 groups depending on whether a self-expanding removable plastic stent protecting the 2 aortoesophageal anastomoses was inserted (n = 7) or not (n = 5), and were allowed to eat 24 hours postoperatively. Main Outcome Measurements: The relative occurrence of mediastinitis caused by anastomotic leakage in stented and nonstented groups was assessed; endoscopic evaluation and histological analysis of the graft area were performed 1 month after esophageal replacement. Results: All animals (n = 5) without stent insertion died of anastomotic leakage within 20 days of surgery. Two of the 7 stented animals died at day 2, and 5 survived 1 month in good clinical condition. Two stent migrations were noted. Stent extraction was followed by the development of a fibrous stricture. Conclusions: The use of a self-expanding plastic stent seems to allow leak-free healing after circumferential replacement of the esophagus by a biological graft in a porcine model. [Copyright &y& Elsevier]

Background: Pneumonectomy is well known for a high risk of postoperative death. The alternative, sleeve lobectomy, is sometimes technically inaccessible, and is associated with locoregional recurrence. In certain situations, the use of a bronchial substitute would allow longer bronchial resections with better security margins. Previous experiments demonstrated that aortic grafts are valuable tracheal and carinal substitutes. The present study evaluated bronchial replacement with arterial allografts. Methods: Fifteen female sheep underwent a left bilobectomy with replacement of the bronchus intermedius with arterial allografts: 5 received a fresh graft (group 1) and 10 received cryopreserved (group 2). A bronchial silicone stent was used to confer rigidity. Evaluation was conducted on clinical and histologic criteria at regular intervals up to 18 months. Results: There were no perioperative deaths. Atelectasis, the only early postoperative complication (n = 2), was successfully treated by fiberscopic aspiration. The late postoperative period was uneventful in 12 sheep. Complications included 1 bronchopneumonia, 1 pulmonary abscess, and 1 distortion of the bronchial stent. Fiberscopic examination revealed 3 sheep with granuloma formation. The bronchial stent was removed in 3 sheep, 1 at 9 months and 2 at 12 months, without clinical complications or stenosis of the graft. Histologic analysis showed regeneration of new bronchial tissue, comprising epithelium and cartilage. Conclusions: This study confirmed that an arterial allograft could be a valuable bronchial substitute. The use of a bronchial substitute offers new perspectives in surgical resection of lung cancer because it would avoid pneumonectomy in some patients. [Copyright &y& Elsevier]

Background: Esophageal replacement is a challenging problem requiring complex reconstruction. In response to the recent success of tracheal replacement by fresh allogenic aorta in humans, we assessed in a pig model the feasibility of circumferential segmental esophageal replacement by a fresh aortic allograft. Methods: A 4-cm long aortic allograft was interposed after a circumferential 2-cm long resection of the cervical esophagus in 18 minipigs. Anastomoses were protected temporarily by self-expanding polyester-silicone stents (Polyflex®; Boston Scientific, Montigny-le-Bretonneux, France). No immunosuppression was given. When stenosis occurred after stent removal or migration, a new stent was inserted. After clinical and endoscopic evaluation, pigs were killed sequentially at 1, 3, 6 and 12 months for analysis. Results: Mortality during the first month was 33%. Four animals died from stent migration during the entire follow-up. Maintenance of a lumen through the graft area by a stent was necessary for 6 months, in order to avoid stenosis occurrence. After the sixth postoperative month, esophageal lumen remained patent until the twelfth month, allowing an apparently normal feeding and weight gain. Gradual contraction of the graft area was observed with time. Sequential histologic analysis showed an inflammatory reaction that decreased with time and a progressive epithelialization of the graft area which became similar to native esophageal epithelium. After 12 months, islets of smooth muscle organized as fascicules or in bundles were visible within the fibrotic tissue. Conclusion: Short esophageal replacement by fresh aortic allograft, under the cover of a temporary maintenance of the lumen of the graft area by an esophageal stent, allows the restitution of a patent esophageal lumen and nutritional autonomy. [Copyright &y& Elsevier]

Background & Aims: Colorectal cancer is a complex disease involving immune defense mechanisms within the tumor. Herein, we used data integration and biomolecular network reconstruction to generate hypotheses about the mechanisms underlying immune responses in colorectal cancer that are relevant to tumor recurrence. Methods: Mechanistic hypotheses were formulated on the basis of data from 108 patients and tested using different assays (gene expression, phenome mapping, tissue-microarrays, T-cell receptor [TCR] repertoire). Results: This integrative approach revealed that chemoattraction and adhesion play important roles in determining the density of intratumoral immune cells. The presence of specific chemokines (CX3CL1, CXCL10, CXCL9) and adhesion molecules (ICAM1, VCAM1, MADCAM1) correlated with different subsets of immune cells and with high densities of T-cell subpopulations within specific tumor regions. High expression of these molecules correlated with prolonged disease-free survival. Moreover, the expression of certain chemokines associated with particular TCR repertoire and specific TCR use predicted patient survival. Conclusions: Data integration and biomolecular network reconstruction is a powerful approach to uncover molecular mechanisms. This study shows the utility of this approach for the investigation of malignant tumors and other diseases. In colorectal cancer, the expression of specific chemokines and adhesion molecules were found as being critical for high densities of T-cell subsets within the tumor and associated with particular TCR repertoire. Intratumoral-specific TCR use correlated with the prognosis of the patients. [Copyright &y& Elsevier]

Collapsing glomerulopathy is an aggressive kidney disease with rapid progression toward end-stage renal disease. Rare cases of de novo collapsing glomerulopathy have been reported during the post-transplant course and, in some instances, have been associated with renal graft vascular lesions. This finding raises the important question of whether ischemia could induce podocyte transdifferentiation, a hypothesis supported by evidence of hypoxia-inducible factor-dependent podocyte proliferation in HIV-associated nephropathy. We describe here 3 HIV-negative kidney transplant recipients in whom early graft biopsy performed in the vicinity of segmental graft infarction disclosed the typical features of glomerular collapse. Podocyte transdifferentiation was characterized by hallmark lesions, such as loss of mature podocyte phenotype, podocyte proliferation, and acquisition of a macrophage-like phenotype. Together, these data suggest that acute glomerular ischemia may lead to glomerular collapse in kidney transplants. [ABSTRACT FROM AUTHOR]

Background: Seven years of experimental research provided a valuable tracheal substitute, the aortic allograft, which can promote the regeneration of epithelium and cartilage. In human application, both fresh and preserved aortic allografts could be used. The optimal method of aortic allograft preservation remains to be evaluated. This study assessed the use of cryopreserved, decellularized, or glutaraldehyde-treated aortic allografts as tracheal substitutes. Methods: Twenty-two sheep underwent tracheal replacement using cryopreserved (n = 10), decellularized (n = 7) or glutaraldehyde-treated (n = 5) allografts, supported by a temporary stent to prevent airway collapse. Aortic segments were retrieved at regular intervals up to 12 months after implantation to analyze the regenerative process. Results: All animals survived the operation. Major complications such as infection, stent migration, or obstruction were predominantly encountered in the decellularized group. The lack of major inflammatory response within the aortic graft observed in the glutaraldehyde group was associated with the absence of tracheal regeneration. Histologic examinations showed a progressive transformation of the aorta into a tracheal tissue comprising respiratory epithelium and cartilage only in the cryopreserved group. Conclusions: This study demonstrated that regeneration of a functional tissue could be obtained after tracheal replacement with a cryopreserved aortic allograft. The regenerative process followed the same pattern as previously described for fresh allografts. Cryopreserved aortic allografts present major advantages: availability in tissue banks, permanent storage, and no need for immunosuppression. This offers a new field of perspectives for clinical application in patients with extensive tracheal cancer. [Copyright &y& Elsevier]

Juvenile hyaline fibromatosis is a rare disorder characterized by an extracellular accumulation of hyaline deposit. In the extremities, lesions may remain quiescent or gradually increase in size, eventually resulting in skin ulceration. There is no curative treatment. Surgery may allow some recovery of function, but recurrence is possible. We report a case of juvenile hyaline fibromatosis in both hands of a 25-year-old man who required multiple surgical procedures to address problems with function, pain, and appearance. [ABSTRACT FROM AUTHOR]

Takayasu arteritis (TAK) is a large vessel vasculitis resulting in artery wall remodeling with segmental stenosis and/or aneurysm formation. Mast cells (MCs) are instrumental in bridging cell injury and inflammatory response. This study sought to investigate the contribution of MCs on vessel permeability, angiogenesis, and fibrosis in patients with TAK. MC activation and their tissue expression were assessed in sera and in aorta from patients with TAK and from healthy donors (HDs). In vivo permeability was assessed using a modified Miles assay. Subconfluent cultured human umbilic vein endothelial cells and fibroblasts were used in vitro to investigate the effects of MC mediators on angiogenesis and fibrogenesis. This study found increased levels of MC activation markers (histamine and indoleamine 2,3-dioxygenase) in sera of patients with TAK compared with in sera of HDs. Marked expression of MCs was shown in aortic lesions of patients with TAK compared with in those of noninflammatory aorta controls. Using Miles assay, this study showed that sera of patients with TAK significantly increased vascular permeability in vivo as compared with that of HDs. Vessel permeability was abrogated in MC-deficient mice. MCs stimulated by sera of patients with TAK supported neoangiogenesis (increased human umbilic vein endothelial cell proliferation and branches) and fibrosis by inducing increased production of fibronectin, type 1 collagen, and α-smooth muscle actin by fibroblasts as compared to MCs stimulated by sera of HD. MCs are a key regulator of vascular lesions in patients with TAK and may represent a new therapeutic target in large vessel vasculitis. [ABSTRACT FROM AUTHOR]

Objective: Cardiac stem cell transplantation as a potential means of regenerating infarcted myocardium is currently receiving a great deal of interest. However, data on these endogenous cardiac precursors are primarily derived from animal studies, and their clinical relevance still remains elusive. Methods: We prospectively screened 32 endomyocardial biopsies harvested from heart transplant recipients (off rejection episodes) and 18 right appendage biopsies collected during coronary artery bypass surgery, and processed the tissue specimens for the immunohistochemical detection of markers of stemness (c-kit, MDR-1, Isl-1), hematopoietic origin (CD45), mast cells (tryptase), endothelial cells (CD105), and cardiac lineage (Nkx2.5). Confocal microscopy was used for colocalization experiments. Three right appendage biopsies were also cultured for 2 to 3 weeks, at the completion of which c-kit–positive cells were sorted by flow cytometry. Results: In endomyocardial biopsies, a median number of 2.7 (1.8–4) c-kit–positive cells/mm2 were found, and this number was even significantly smaller in right appendage biopsies (1 [0.5–1.8] c-kit–positive cell/mm2, P = .01). All of these c-kit–positive cells co-stained for CD45 and were more specifically identified as mast cells by their positive staining for the specific tryptase marker. However, none of the c-kit–positive cells expressed the markers of stemness MDR-1 and Isl-1 or colocalized with CD105. Flow cytometry confirmed the small number of c-kit–positive cells in cultured right atrial appendages. Conclusion: These data raise a cautionary note on the therapeutic exploitation of cardiac stem cells in patients with ischemic cardiomyopathy, who may be the elective candidates for regenerative therapy. [Copyright &y& Elsevier]

Summary: Juxtaglomerular cell tumor (JGCT), first described in 1967, is a rare tumor of the kidney that derived from specialized smooth muscle cells of the wall of the glomerular afferent arteriole. Less than 100 cases have been published, mainly as isolated case reports or small series. JGCTs are considered benign, but the clinical follow-up is short in most reported cases. Only 1 metastatic case has been reported to date, raising the question of tumors of uncertain malignant potential rather than clearly benign neoplasms. Genomic features have been studied in only 2 cases that showed gain of chromosome 10 as well as loss of chromosomes 9, 11q, and X. The present work studied the genomic characteristics of 2 additional cases of JGCT by comparative genomic hybridization. Similarly to the 2 previously reported cases, these 2 tumors showed loss of chromosomes 9 and 11, suggesting recurrent chromosomal imbalances. In addition, 1 case showed gain and loss of entire chromosomes, similar to a previous case studied by karyotyping. Such an aneuploid karyotype may reflect a potential for malignancy as previously reported. Thus, JGCT might be better considered as a tumor of uncertain malignant potential and then necessitates a prolonged follow-up. Future clinicopathologic and genomic studies of large retrospective and prospective series may help to better understand the biology of this fascinating entity. [Copyright &y& Elsevier]

Non-syndromic Abdominal Aortic Aneurysm (AAA) is one of the leading causes of cardiovascular death in elderly men. AAA is characterized by extracellular matrix degradation, smooth muscle cell apoptosis and infiltration of inflammatory cells in the aortic wall. TREM (Triggering Receptor Expressed on Myeloid cells)-1, a receptor expressed by myeloid cells, is a key regulator of innate immune cell activity, and we hypothesized that it might be involved in AAA development. We aim to decipher the role of TREM-1 in the immuno-inflammatory response associated with AAA development and rupture. To study the role of TREM-1 in AAA development, we used an experimental model of Angiotensin-II-induced AAA in ApoE-/-Trem-1-/- and ApoE-/-Trem-1+/+ mice. At day 0, 3, 7 and 28, we analyzed monocyte trafficking (flow cytometry), inflammatory cell infiltration within the aortic wall (immunostaining, qPCR), aortic wall remodeling (histology) and finally AAA development. Angiotensin II infusion increased TREM-1 expression on both classical and non-classical monocytes. TREM-1 deficiency limits Angiotensin II-induced monocytosis at day 3 and limits macrophage infiltration in the aorta at day 7. Trem-1 genetic deletion limits pro-inflammatory response and metalloprotease activity in the aortic wall and protects against elastin degradation. Finally, TREM-1 deficiency significantly reduced AAA rupture and severity. We showed that TREM-1 deficiency reduced AAA development and rupture in an Angiotensin II-induced experimental mouse model. [ABSTRACT FROM AUTHOR]

Post thrombotic syndrome is a frequent complication of deep venous thrombosis, associated with high morbidity. Treatments currently available are invasive. Pulsed cavitational ultrasound therapy (PCUT) is a new technique to destroy remotely soft tissue. We demonstrated that PCUT was able to recanalize non-invasively in in-vitro model of human blood clot. We aim to test the safety and efficacy of venous recanalization by non-invasive PCUT in vivo swine model of acute venous thrombosis. All the experiments were performed on White large X Landrace swine. We induced an acute femoral deep venous thrombosis by using endovascular approach combined with local injection of thrombin. A 3 cm length occlusive thrombosis was obtained after 2 hours. Swine were divided in three groups: one with PCUT without follow-up (n = 11), one with PCUT and follow-up at 14 days (n = 8), and a control group also followed for 14 days (n = 5). Acutely and during follow up all swine received curative anticoagulation. To achieve PCUT, a 2.25 MHz transducer (Imasonic©) centered by a linear probe was used and cavitation was obtained in the centre of the vein. Effectiveness of recanalization was evaluated by echo-Doppler and phlebography. Safety was assessed by Doppler ultrasound and by histological analysis of vein, artery and lungs. Among the 24 swine, we obtained 22 occlusive venous thromboses and 2 partials. The median length of the thrombus was 26 ± 4.4 mm. Acutely, thrombosis recanalization was obtained among the 19 swine with PCUT with median treatment duration of 33 min. After a 14-day follow-up, 75% of recanalisation remains permeable vs. 0% of vein permeable in the no therapy group (P = 0.008). Residual diameter was 2.6 ± 1.2 mm, 50% of the venous diameter. No embolism or pulmonary infarction was observed in all pigs (Fig. 1). We have demonstrated in vivo the safety and the efficacy of PCUT for non-invasive venous recanalization, persistent after 2 weeks. [ABSTRACT FROM AUTHOR]

Background: Carinal replacement after extensive resection remains a tremendous challenge in thoracic surgery. In previous studies, we demonstrated that an aortic graft could be a valuable tracheal substitute. The goal of this new study was to evaluate the reconstruction of the carina using a stent supported bifurcated aortic allograft. Methods: In 15 sheep the replacement of the tracheobronchial bifurcation with an aortic allograft was performed under cardiopulmonary bypass. A temporary stent prevented airway collapse. No immunosuppression was used. Aortic segments were retrieved at regular intervals up to 24 months after implantation. Results: All animals survived the initial aortic allograft operation. Six animals died postoperatively (1 of graft necrosis, 2 of pneumonia, and 3 of bronchial fistula). The remaining 9 animals were in good condition until they were euthanized. Stent removal was tolerated after 9 months in 3 animals. Progressive transformation of the arterial graft initially into extensive inflammatory tissue, and after 3 to 6 months into a tracheal tissue comprising a well-differentiated epithelium and cartilage was confirmed by histology. Conclusions: This study showed that regeneration of a functional tissue can be obtained after replacement of the carina with an aortic allograft. The origin and mechanisms of this regenerative process remains to be discovered. These results represent an important hope for the reconstruction of the carina after extensive resection, especially for cancer lesions. In human application, the systemic use of omentoplasty or myoplasty should further reduce its risk of complication. [Copyright &y& Elsevier]

Objective: Early cell death remains a major limitation of skeletal myoblast transplantation. Because the poor vascularization of the target scars contributes to cell loss, we assessed the effects of combining skeletal myoblast transplantation with administration of hypoxia-inducible factor 1α, a master gene that controls the expression of a wide array of angiogenic factors. Methods: A myocardial infarction was created in 56 rats by means of coronary artery ligation. Eight days later, rats were randomly allocated to receive in-scar injections of culture medium (control animals, n = 11), skeletal myoblasts (5 × 106, n = 13), adenovirus-encoded hypoxia-inducible factor 1α (1.0 × 1010 pfu/mL, n = 7), or skeletal myoblasts (5 × 106) in combination with an empty vector (n = 3) or active hypoxia-inducible factor 1α (1.0 × 1010 pfu/mL, n = 13). A fifth group (n = 9) underwent a staged approach in which hypoxia-inducible factor 1α (1.0 × 1010 pfu/mL) was injected at the time of infarction, followed 8 days later by skeletal myoblasts (5 × 106). Left ventricular function was assessed echocardiographically before transplantation and 1 month thereafter. Explanted hearts were then processed for the immunohistochemical detection of myotubes, quantification of angiogenesis, myoblast engraftment, and cell survival. Results: Baseline ejection fractions were not significantly different among groups (35%–40%). One month later, ejection fraction had decreased from baseline in control hearts and in those injected with hypoxia-inducible factor 1α. In contrast, it did not deteriorate after injections of skeletal myoblasts alone or combined with either the empty vector or active hypoxia-inducible factor 1α administered sequentially. The most striking change occurred in the skeletal myoblast plus hypoxia-inducible factor 1α combined group in which ejection fraction increased dramatically (by 27%) above baseline levels and was thus markedly higher than in all other groups (P = .0001 and P = .001 vs control animals and animals receiving hypoxia-inducible factor 1α, respectively). Compared with skeletal myoblasts alone, the coadministration of hypoxia-inducible factor 1α resulted in a significantly greater degree of angiogenesis, cell engraftment, and cell survival. Conclusion: Induction of angiogenesis is an effective means of potentiating the functional benefits of myoblast transplantation, and hypoxia-inducible factor 1α can successfully achieve this goal. [Copyright &y& Elsevier]

Objective: Beyond the first 2 months of life, pulmonary artery banding is warranted before two-stage arterial switch operation. The aim of this study was to explore whether myogenic cell transplantation could contribute to right ventricular function during pulmonary artery constriction in an ovine model. Methods: Sixteen rams were assigned to one of the following groups: group 1, simple pulmonary artery banding (n = 5); group 2, pulmonary artery banding and cell implantation in the right ventricle (n = 7); and group 3, pulmonary artery banding and placebo injection in the right ventricle (n = 4). Hemodynamic assessment with pressure-volume loops was performed on days 0 and 60. The pulmonary artery banding and the injections were achieved through a left fourth intercostal thoracotomy. Autologous myogenic cell implantation was carried out with a noncultured cell preparation, as previously described by our group. Implanted sites were processed with monoclonal antibodies to a fast skeletal-specific isoform of myosin heavy chain (MY32). Results: Skeletal myosin heavy chain expression was detected at 2 months after noncultured cell implantation in all grafted animals. Right ventricular training resulted in statistically significant increased signs of contractility in all three groups. There was no observed difference, however, between the cell therapy group and the other two groups with respect to signs of cardiac function. Conclusion: Successful engraftment of noncultured cells into right ventricular myocardium did not translate into a functional benefit that we could demonstrate in our ovine model. Cellular therapy thus is probably not useful to strengthen a left ventricle being retrained through pulmonary artery banding before arterial switch operation. However, cell transplantation may affect the outcome of right ventricular failure long term after atrial switch operation. Although preliminary, this investigation paves the way for further research into cellular cardiomyoplasty, right ventricular failure, and congenital heart disease. [Copyright &y& Elsevier]

Endocarditis due to Legionella spp. is uncommon but presumably underestimated given the prevalence of Legionellae in the environment. We report a first and unusual case of chronic native valve endocarditis due to L. anisa and advocate that the diagnosis of endocarditis be made collaboratively between the cardiologist, surgeon, microbiologist and pathologist. [ABSTRACT FROM AUTHOR]

Ultrafast Ultrasound Imaging (UUI) provides an estimation of carotid plaque stiffness by shear wave elastography (SWE) and the quantification of wall shear stress (WSS) by ultrafast Doppler. We aimed to evaluate the combined criteria of plaque stiffness and WSS applied on the plaque as potential biomarkers of plaque vulnerability assessed by histology. We included patients for whom carotid endarterectomy had been decided by a multidisciplinary team. UUI was performed within 48 hours before surgery, and acquisitions were obtained on a carotid longitudinal view. After endarterectomy, gross examination and histological analysis were performed on each removed plaque. Forty-six plaques with SWE data and 29 with WSS data were analysed. Histological analysis revealed 29 vulnerable and 17 stable plaques. Gray Scale Median analysis by B mode, mean and standard deviation of stiffness by SWE did not differ between vulnerable and stable plaques. SWE analysis revealed that the percentage of stiffness range of [3–5] m/s was significantly increased in vulnerable plaques (P = 0.048). WSS alone showed no difference between stable and vulnerable plaques regardless of the segment of the plaque which was analysed. A multiparametric score using maximal WSS at the peak of the plaque associated with SWE texture analysis parameters was calculated by stepwise regression, leading to a score with a sensitivity of 80% and a specificity of 78%. Area under the Receiver Operating Characteristics curve was 0.85. A multiparameter scoring system including plaque stiffness and flow analysis using UUI allows to effectively identify histologically vulnerable carotid plaques. [ABSTRACT FROM AUTHOR]

Sudden cardiac death (SCD) is a major contributor to the rate of mortality after heart transplantation. However, little is known about the incidence of SCD in heart recipients. To assess the incidence of SCD after heart transplantation. We enrolled consecutive patients transplanted between 2004 and 2017 in two French referral centers. We defined 7 main groups of causes of deaths: SCD, cardiovascular (including Cardiac allograft vasculopathy), infection, primary graft dysfunction, graft failure (including late graft dysfunction, rejection), malignancy and others. Causes of deaths were independently adjudicated by two senior cardiologists based on the analysis of death certificates and medical records. Discrepancies were resolved by discussion until a consensus was made. SCD was defined as an unexpected out-of-hospital cardiac arrest without obvious non-cardiac cause, in the first hour after initiation of symptoms. A total of 1,363 patients were included. The median follow-up post-transplant was 3.99 years (IQR = 0.49–7.49). A total of 450 patients (33%) deceased during the first year. The leading cumulative causes of death in the first year after transplantation were infection, primary graft failure, multiple organ failure during the period in intensive car unit. Beyond the post-operative high-risk period of the first year, the leading cumulative cause of death was SCD: among the 213 deaths that occurred beyond the first year, 44 patients (21%) died from SCD. In this period, the incidence rate of SCD reached 0,82 per 100 person-year (95% CI: 0.51–2.05) (Fig. 1). In a large multicentric and highly phenotyped cohort of heart transplant recipients, the leading cumulative cause of death beyond the first-year post transplant was sudden cardiac death. Our results open discussion on management of heart recipient, such as the implementation of cardioverter-defibrillators. [ABSTRACT FROM AUTHOR]

The diagnosis of cardiac allograft rejection is based on the histological analysis of a myocardial tissue sample obtained by endomyocardial biopsy (EMB), an invasive procedure at risk of complications. Our aim is to enable the shift from a protocol biopsy approach, to a precision medicine approach, in which the need for EMB is tailored to each patient's individual risk. To analyze the incidence and the risk factors for biopsy-proven rejections following heart transplantation in a large cohort of highly phenotyped heart-transplant recipients. We performed a multicenter, retrospective, observational study (Pitié-Salpêtrière, HEGP, 2004–2016). We included all patients with ≥ 1 EMB during the first year (n = 1050 patients, 13677 EMB). All EMB performed before 2012 were retrospectively reviewed and graded according to ISHLT guidelines. Rejections were defined as acute cellular rejection (ACR) ≥ 1R1B and/or antibody-mediated rejections (AMR) ≥ pAMR1. Pre-formed DSA were evaluated using Luminex Single Antigen Assay (MFI ≥ 500). Risk factors for rejection were identified using Cox proportional hazard model. Biopsy-proven rejections were diagnosed in 489 patients (46.4%) representing 1009 EMB (7.3%, mostly low-grade rejections: ACR 1R1B or 1R2: n = 724, see Fig. 1). Risk factors for rejection included recipient's age (HR = 0.988 per 1-year increment, P = 0.002), type of transplantation (combined heart-kidney and heart-liver compared to isolated heart: HR = 0.336 and 0.204 respectively, P < 0.001), pre-formed DSA (HR = 1.422, P < 0.001), HLA A-B-DR mismatches (HR = 1.129 per 1-mismatch increment, P = 0.02) and the type of induction (basiliximab compared to anti-thymocyte globulins: HR = 1.725, P = 0.008). We identified five independent risk factors for biopsy-proven rejection during the first-year post-heart transplantation. Our findings might help clinicians to customize post-transplant endomyocardial biopsies monitoring. [ABSTRACT FROM AUTHOR]

Since a large proportion of patients resuscitated from out-of-hospital sudden cardiac arrest (SCA) die in the intensive care unit (ICU), early systematic investigation towards identifying etiology may be crucial to ensure appropriate future prevention among relatives, especially when the index case is young. We hypothesized that etiologic investigations were not initiated in a timely manner in a significant proportion of young SCA patients prior to death. In this prospective ongoing multicenter, population-based registry (6.7 million inhabitants), data from all SCA over a 5-year period were analyzed with a specific focus on young patients (< 45 year-old) alive at hospital admission and who eventually died in ICU. Investigations and diagnoses arrived at were analyzed from the medical records by two cardiologists for each case. Of the 18,622 out-of-hospital cardiac arrests from May 2011 to May 2016, 3,028 were admitted alive to ICU. Among them, 2,190 (72.3%) died in ICU, including 367 (16.8%) young cases (< 45 y.o.). Among the young patients, while 163 cases (44.4%) had a specific diagnosis established, 204 (55.6%) remained unexplained. Coronary angiograms (18.3%), CT scan (brain and chest) (24.5%), and transthoracic echocardiography (29.1%) were all underutilized. Main SCA causes were acute coronary syndrome (44.5%), followed by structural non-ischemic heart disease (25.5%), pulmonary embolism (13.6%), chronic CAD (10%), non-structural heart disease (1.8%) and miscellaneous (4.6%). The proportion of autopsy (10.9%), as well as blood sample collection for further genetic testing (1.4%) was low. Information on family screening was rarely provided in the ICU. More than half of young SCA cases who died in ICU remained unexplained. Efforts to promote early systematic investigation through better collaboration between intensivist and cardiologist may improve future targeted preventive strategies for family members. [ABSTRACT FROM AUTHOR]

Macrophages play a critical role in the initiation and progression of abdominal aortic aneurysm (AAA) and are classically distinguished into M1 "proinflammatory" and M2 "anti-inflammatory" macrophages. Topical application of elastase associated with transforming growth factor β (TGF-β) systemic neutralization reproduces the main pathologic features of human AAA, offering a new model to investigate their role. The aim of this study was to investigate whether macrophages contribute to the expression of canonical M1/M2 markers in the aorta in the AAA model induced by elastase and systemic blockade of TGF-β and whether blocking of TGF-β activity affects macrophage phenotype and the expression of the M2 marker arginase 1 (ARG1). C57Bl/6J male mice (6-8 weeks old) were randomly assigned to three experimental groups: mice that had local application of heat-inactivated elastase or elastase and mice that had elastase application and received injection of anti-TGF-β (elastase + anti-TGF-β group). Monocyte-macrophage depletion was achieved in the elastase + anti-TGF-β group using liposome clodronate. Macrophage phenotype was characterized by quantitative polymerase chain reaction, flow cytometry, and immunohistochemistry. Human infrarenal AAA tissues (n = 10) were obtained to analyze ARG1 expression. Analysis of gene expression in the infrarenal aortic wall revealed that after 14 days, no significant difference for the expression of CCL2, NOS2, and Ym1/2 was observed in the elastase group compared with the elastase + anti-TGF-β group, whereas the expression of ARG1, interleukin (IL) 1β, and IL-6 was significantly increased. Macrophage depletion in the elastase + anti-TGF-β group led to a significant decrease of IL-1β, IL-6, ARG1, and Ym1/2 gene expression. Immunofluorescent staining confirmed that TGF-β neutralization significantly enhanced ARG1 protein expression in the aneurysmal tissue. Flow cytometry analysis revealed an increase of macrophages expressing ARG1 in the aorta of mice treated with elastase + anti-TGF-β compared with the elastase group, and their proportion increased with aneurysmal dilation. In humans, ARG1 protein expression was increased in aneurysmal tissues compared with controls, and positive cells were mainly found in the adventitia. TGF-β neutralization finely tunes macrophage phenotype in elastase-induced AAA and leads to an increase in ARG1 gene and protein expression in the aortic wall. Even if further studies are required to elucidate its role in AAA development, ARG1 could represent a new prognostic or therapeutic target in aneurysmal disease. Abdominal aortic aneurysm is associated with an infiltration of inflammatory cells including macrophages. However, their role in the disease is not fully understood, and they could represent an interesting therapeutic target. This study characterized macrophage phenotype and explored the expression of arginase 1, a marker of "anti-inflammatory" macrophages during abdominal aortic aneurysm initiation and progression. Arginase 1 expression was increased in the aneurysmal wall in both animal and human samples, suggesting its potential interest as a new prognostic or therapeutic target in aneurysmal disease. [ABSTRACT FROM AUTHOR]

Contexte Le papillomavirus humain (HPV) semble être impliqué dans la carcinogenèse de certains carcinomes épidermoïdes de la région tête et cou, notamment à localisation oropharyngée. Cependant, le rôle de ce virus est plus débattu dans d’autres localisations. Comme la plupart des études sont conduites en Amérique du Nord ou l’Europe du Nord, peu de données sont disponibles concernant la distribution de l’HPV en France. Les buts de cette étude sont d’évaluer, dans un seul centre pendant un an, la prévalence de l’HPV dans les carcinomes épidermoïdes de la région tête et cou et de déterminer si les immunomarquages par p16, pRB et Cycline D1 ainsi que l’hybridation in situ HPV améliorent l’exactitude diagnostique dans la prise en charge dans la pratique quotidienne de ces tumeurs en comparaison à la détection par PCR. Matériels et méthodes 165 cas de carcinomes épidermoïdes de la région tête et cou nouvellement diagnostiqués, la même année, étaient étudiés par immunohistochimie par les anticorps anti-p16, anti-pRb et anti-cyclineD1 et par hybridation in situ chromogènique (CISH) pour HPV à haut risque. L’ADN des cellules tumorales a été extrait et soumis à un typage HPV à large spectre (INNO-Lipa). L’expression de p16, pRb et la cycline D1 a été évaluée semi-quantitativement par deux pathologistes indépendants. Concernant p16, l’immunomarquage a été signalé comme suit : positif, hétérogène, ou négatif. Le marquage cytoplasmique faible, ou le marquage fort dans < 5 % des cellules ont été interprétés comme négatifs. Le marquage intense et diffus a été considéré comme positif. Les marquages hétérogènes de p16 ont été également rapportés. La positivité pour pRb a été retenue en cas de présence d’un marquage nucléaire modérée d›au moins 10 % des cellules tumorales. L’immunomarquage par la cycline D1 a été classé comme suit : 0 : pas de marquage, 1 : marquage nucléaire de moins de 10 % de cellules tumorales, 2 : marquage nucléaire de 10–50 % des cellules tumorales 3 : marquage nucléaire de plus de 50 % des cellules tumorales. Résultats p16 était positif dans 33,8 %, 11,8 % et 20,8 % des cas dans l’oropharynx et la cavité buccale, le larynx et l’hypopharynx respectivement. L’expression de p16 était corrélée avec la positivité par la PCR (p < 0,0001). Douze pour cent des carcinomes épidermoides étaient HPV CISH +, avec une corrélation excellente avec la PCR (p < 0,0001). L’ADN de l’HPV a été détecté dans 33 cas (20,6 %). Le sous-type HPV 16 a été principalement identifié (82 % des cas). Une perte d’expression pRb a été observée dans 59 % des cas. Aucune corrélation entre pRb et l’expression p16 n’a été trouvée. La cycline D1 était positivement exprimée (2 + ou 3 +) dans 58 % des cas, sans relation significative avec p16. En comparaison avec la PCR HPV, l’immunohistochimie par p16 a montré une sensibilité de 67,7 % et une spécificité de 90 %, tandis que l’hybridation in situ a montré une sensibilité de 53 % et une spécificité de 88 %. Conclusion Comme attendu, la plupart des carcinomes épidermoïdes HPV positifs sont situés dans la cavité buccale ou dans l’oropharynx. Dans d’autres localisations, l’HPV était rarement retrouvé, soulevant des questions concernant [ABSTRACT FROM AUTHOR]

Autologous skeletal myoblast transplantation might improve postinfarction ventricular function, but graft viability and differentiation (ie, proof of concept) has not been shown. A 72-year-old man had autologous cultured myoblasts from his vastus lateralis injected to an area of transmural inferior myocardial infarction in non-reperfused scar tissue. He showed improvement in symptoms and left-ventricular ejection fraction. When he died 17·5 months after the procedure, the grafted post-infarction scar showed well developed skeletal myotubes with a preserved contractile apparatus. 65% of myotubes expressed the slow myosin isoform and 33% coexpressed the slow and fast isoforms (vs 44% and 0·6%, respectively, in skeletal muscle). Myoblast grafts can survive and show a switch to slow-twitch fibres, which might allow sustained improvement in cardiac function. [Copyright &y& Elsevier]

Syphilitic cardiovascular disease has been described since the 19th century, mainly on autopsy series. Major clinical manifestations are aortic aneurysm, aortic insufficiency, and coronary ostial stenosis. The diagnosis of syphilitic cardiovascular disease is based mainly on positive serologic tests and overt clinical manifestations. We present here a rare and unusual clinical presentation of a tertiary syphilis with recurrent tamponade and type B aortic dissection, whose positive diagnosis was made by polymerase chain reaction on pericardial fluid analysis. [Copyright &y& Elsevier]

Objectives: Recent advances in airway transplantation have shown the ability of ex vivo or in vivo tracheal regeneration with bioengineered conduits or biological substitutes, respectively. Previously, we established a process of in vivo–guided tracheal regeneration using vascular allografts as a biological scaffold. We theorized that tracheal healing was the consequence of a mixed phenomenon associating tracheal contraction and regeneration. The aim of the present study was to determine the role that bone marrow stem cells play in that regenerative process. Methods: Three groups of 12 rabbits underwent a gender-mismatched aortic graft transplantation after tracheal resection. The first group received no cells (control group), the second group had previously received autologous green fluorescent protein–labeled mesenchymal stem cell transplantation, and the third group received 3 labeled mesenchymal stem cell injections on postoperative days 0, 10, and 21. Results: The clinical results were impaired by stent complications (obstruction or migration), but no anastomotic leakage, dehiscence, or stenosis was observed. The rabbits were killed, and the trachea was excised for analysis at 1 to 18 months after tracheal replacement. In all 3 groups, microscopic examination showed an integrated aortic graft lined by metaplastic epithelium. By 12 months, immature cartilage was detected among disorganized elastic fibers. Positive SRY gene detection served as evidence for engraftment of cells derived from the male recipient. EF-green fluorescent protein detection showed bone marrow–derived mesenchymal stem cell involvement. Conclusions: The results of the present study imply a role for bone marrow stem cells in tracheal regeneration after aortic allografting. Studies are necessary to identify the local and systemic factors stimulating that regenerative process. [Copyright &y& Elsevier]

Purpose: It remains unknown whether heart rate reduction by the I f current inhibitor ivabradine (IVA) improves left ventricular (LV) function of the infarcted and reperfused myocardium. Accordingly, our goal was to investigate the effect of IVA on global and regional LV function following myocardial infarction and long term reperfusion in rabbits. Methods: Myocardial systolic function was assessed before a 20 min coronary artery occlusion and during the subsequent 3 weeks of reperfusion by echocardiography and tissue tracking imaging. Throughout reperfusion, rabbits received either IVA (10 mg/kg/day, n=9) or vehicle (Control, n=8) using implanted osmotic pumps. At 3 weeks reperfusion, LV remodeling was investigated by histology and expression of several proteins (SERCA2a, RyR2-P, phospholamban, FKBP12) involved in calcium handling. Results: After 3 weeks, IVA induced a significant decrease in heart rate by ≈20% as compared to Control (214±9 vs 266±14 bpm, respectively). In Control rabbits, ejection fraction and regional systolic displacement were significantly decreased as compared to baseline values (43±4% vs 63±2% and 1.4±0.2 vs 2.8±0.2 mm, respectively) and were associated with LV enlargement and interstitial fibrosis within the reperfused zone (risk zone: 30±2% of LV and infarct size: 8% of LV). Chronic administration of IVA prevented the reduction in ejection fraction (58±3% vs 66±3% in baseline) and the decrease in regional systolic displacement (1.9±0.3 vs 2.6±0.3 mm). This improvement was not related to a difference in infarct size and interstitial fibrosis. Interestingly, this was associated with a significant increase in FKBP12 expression in the reperfused area without any changes in SERCA2a, RyR2-P and phospholamban. Conclusion: Heart rate reduction with IVA significantly improves systolic function after 3 weeks of reperfusion. This beneficial effect might result from an adaptation of calcium handling as suggested by the increase in FKBP12 expression. [Copyright &y& Elsevier]

Purpose: Heart rate reduction by the selective If current inhibitor ivabradine improves systolic cardiac function in experimental congestive heart failure. Here, we investigated whether its administration would be also beneficial in early post-infarction remodelling following ischemia-reperfusion and particularly at the level of the contractile function of the viable reperfused area. Methods: Rabbits were submitted to 20min of coronary artery occlusion (CAO). Throughout the subsequent 3 weeks of reperfusion, they received continuous infusion of either ivabradine (10mg/kg/day, n=8) or vehicle (control, n=9) using implanted osmotic pumps. Global and regional systolic functions were assessed by echocardiography and tissue tracking imaging (TTI) (Vingmed System 7), respectively, at baseline (1 week before CAO) and throughout the 3 weeks of reperfusion. TTI was performed in the left ventricular (LV) free wall within the territory subjected to ischemia-reperfusion. Results: Throughout the 3 weeks of reperfusion, ivabradine significantly and constantly reduced heart rate (∼-20 %) (Table). Ejection fraction and regional systolic displacement assessed by TTI were significantly improved in ivabradine vs vehicle groups (e.g. +35 % and +36 % at Day 21, respectively). Post-mortem analyses revealed that the area subjected to ischemia was similar in both groups (29±2 and 29±3 % of LV, respectively). This area consisted into a thin infarcted scar (7±1 and 9±2 % of LV, respectively) surrounded by salvaged myocardium and fibrosis. Conclusion: Heart rate reduction induced by ivabradine improves global systolic function in the post-infarction period and moreover improves the regional contractility of the remodelled myocardium salvaged by reperfusion. These benefits suggest the potential interest of ivabradine in the management of post-infarcted myocardial dysfunction. Display Omitted [Copyright &y& Elsevier]

A letter to the editor is presented in response to article on a single specimen of transplant nephrectomy for recurrent idiopathic focal segmental glomerulosclerosis.