S. Kim Suvarna

A prospective randomised comparison of cardiotomy suction and cell saver for recycling shed blood during cardiac surgery

OBJECTIVEnPost-operative neuropsychological complications correlate with intra-operative microemboli in the middle cerebral artery. When severe neurological complications follow cardiac surgery, diffuse cerebral fat emboli are present at autopsy. Recycling shed blood with cardiotomy suction is an important source of cerebral fat microemboli. A cell saver may reduce this.nnnMETHODSnTwenty patients were prospectively randomised to assess the amount of fat in blood salvaged from the pericardium and returned to the patient with either cell saver or cardiotomy suction. Blood samples were taken before and after filtration in the cardiotomy suction group or cell saver processing in the cell saver group. After centrifuging samples, fat content was graded on a scale of 0-3 by a blinded independent observer. Fat content was also quantified by weight.nnnRESULTSnCompared with cardiotomy suction, cell saver removed significantly more fat from shed blood. Median fat grading after cell saver was 0 (0-1) compared with 1 (1-2) for cardiotomy suction (P=0.0001). Percentage reduction in fat weight achieved by cell saver or cardiotomy suction was 87% compared to 45% (P=0.007). There was no difference in the post-operative use of blood or blood products, haemoglobin, or bleeding between the two groups.nnnCONCLUSIONnUse of cell saver results in less fat being recycled during cardiopulmonary bypass.

Consensus statement on surgical pathology of the aorta from the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology: I. Inflammatory diseases

Inflammatory diseases of the aorta include routine atherosclerosis, aortitis, periaortitis, and atherosclerosis with excessive inflammatory responses, such as inflammatory atherosclerotic aneurysms. The nomenclature and histologic features of these disorders are reviewed and discussed. In addition, diagnostic criteria are provided to distinguish between these disorders in surgical pathology specimens. An initial classification scheme is provided for aortitis and periaortitis based on the pattern of the inflammatory infiltrate: granulomatous/giant cell pattern, lymphoplasmacytic pattern, mixed inflammatory pattern, and the suppurative pattern. These inflammatory patterns are discussed in relation to specific systemic diseases including giant cell arteritis, Takayasu arteritis, granulomatosis with polyangiitis (Wegeners), rheumatoid arthritis, sarcoidosis, ankylosing spondylitis, Cogan syndrome, Behçets disease, relapsing polychondritis, syphilitic aortitis, and bacterial and fungal infections.

Desensitisation of mast cell β2‐adrenoceptor‐mediated responses by salmeterol and formoterol

The long‐acting β2‐adrenoceptor agonist formoterol (10−10–10−6 M) inhibited the IgE‐dependent release of histamine from human lung mast cells in a concentration‐dependent manner. Formoterol was more potent and a full agonist relative to the nonselective β‐adrenoceptor agonist isoprenaline. By contrast, the long‐acting β2‐adrenoceptor agonist salmeterol (10−10–10−6 M) was about two‐thirds less efficacious than either formoterol or isoprenaline as an inhibitor of histamine release. Isoprenaline, formoterol and salmeterol (all at 10−5 M) increased total cell cAMP levels in mast cells over basal by 361±90 (P<0.05), 321±89 (P<0.05) and 64±24% (P>0.05), respectively. Long‐term (24 h) incubation of mast cells with formoterol (10−6 M) or salmeterol (10−6 M) essentially abolished the subsequent ability of isoprenaline to inhibit histamine release. Both formoterol and salmeterol were more effective at inducing the functional desensitisation than isoprenaline (10−6 M) or the short‐acting β2‐adrenoceptor agonist salbutamol (10−6 M). The desensitisation induced by long‐term treatments with salmeterol and formoterol was specific for β2‐adrenoceptor‐mediated inhibition of histamine release as the inhibitory effects of alternative cAMP‐elevating compounds, prostaglandin E2, a receptor‐mediated activator of adenylate cyclase, and forskolin, a direct activator of adenylate cyclase, were unaffected by desensitising treatments. Radioligand binding studies were performed to determine β2‐adrenoceptor density in cell membranes after pretreatment (24 h) of cells with agonists. Isoprenaline, formoterol and salmeterol (all at 10−6 M) reduced β2‐adrenoceptor density by 13±5 (P>0.05), 49±13 (P<0.05) and 35±17% (P>0.05), respectively. These data indicate that long‐term exposure of mast cells to both salmeterol and formoterol can cause substantial levels of desensitisation to β2‐adrenoceptor‐mediated responses in mast cells.

Consensus statement on surgical pathology of the aorta from the Society for Cardiovascular Pathology and the Association for European Cardiovascular Pathology: II. Noninflammatory degenerative diseases - Nomenclature and diagnostic criteria

Surgical aortic specimens are usually examined in Pathology Departments as a result of treatment of aneurysms or dissections. A number of diseases, genetic syndromes (Marfan syndrome, Loeys-Dietz syndrome, etc.), and vasculopathic aging processes involved in vascular injury can cause both distinct and nonspecific histopathologic changes with degeneration of the media as a common denominator. Terminology for these changes has varied over time leading to confusion and inconsistencies. This consensus document has established a revised, unified nomenclature for the variety of noninflammatory degenerative aortic histopathologies seen in such specimens. Older terms such as cystic medial necrosis and medionecrosis are replaced by more technically accurate terms such as mucoid extracellular matrix accumulation (MEMA), elastic fiber fragmentation and/or loss, and smooth muscle cell nuclei loss. A straightforward system of grading is presented to gauge the extent of medial degeneration and synoptic reporting tables are provided. Herein we present a standardized nomenclature that is accessible to general pathologists and useful for future publications describing these entities.

Guidelines for autopsy investigation of sudden cardiac death: 2017 update from the Association for European Cardiovascular Pathology

Although sudden cardiac death (SCD) is one of the most important modes of death in Western countries, pathologists and public health physicians have not given this problem the attention it deserves. New methods of preventing potentially fatal arrhythmias have been developed and the accurate diagnosis of the causes of SCD is now of particular importance. Pathologists are responsible for determining the precise cause and mechanism of sudden death but there is still considerable variation in the way in which they approach this increasingly complex task. The Association for European Cardiovascular Pathology has developed these guidelines, which represent the minimum standard that is required in the routine autopsy practice for the adequate investigation of SCD. The present version is an update of our original article, published 10xa0years ago. This is necessary because of our increased understanding of the genetics of cardiovascular diseases, the availability of new diagnostic methods, and the experience we have gained from the routine use of the original guidelines. The updated guidelines include a detailed protocol for the examination of the heart and recommendations for the selection of histological blocks and appropriate material for toxicology, microbiology, biochemistry, and molecular investigation. Our recommendations apply to university medical centers, regionals hospitals, and all healthcare professionals practicing pathology and forensic medicine. We believe that their adoption throughout Europe will improve the standards of autopsy practice, allow meaningful comparisons between different communities and regions, and permit the identification of emerging patterns of diseases causing SCD. Finally, we recommend the development of regional multidisciplinary networks of cardiologists, geneticists, and pathologists. Their role will be to facilitate the identification of index cases with a genetic basis, to screen appropriate family members, and ensure that appropriate preventive strategies are implemented.

Administration of the stress protein gp96 prolongs rat cardiac allograft survival, modifies rejection-associated inflammatory events, and induces a state of peripheral T-cell hyporesponsiveness

Abstract High-dose gp96 has been shown to inhibit experimental autoimmune disease by a mechanism that appears to involve immunoregulatory CD4+ T cells. This study tested the hypothesis that high-dose gp96 administration modifies allograft rejection and associated inflammatory events. Wistar cardiac allografts were transplanted into Lewis recipient rats and graft function was monitored daily by palpation. Intradermal administration of gp96 purified from Wistar rat livers (100 μg) at the time of transplantation and 3 days later significantly prolonged allograft survival (14 vs 8 days in phosphate-buffered saline [PBS]-treated recipients; P = 0.009). Rejected allografts from gp96-treated animals were significantly less enlarged than allografts from their PBS-treated counterparts (2.8 vs 4.3 g; P < 0.004). Gp96 was also effective when administered on days 1 and 8 (13 vs 7 days), but not if it was derived from recipient (Lewis) liver tissue or administered on days 0, 3, and 6. In parallel studies, CD3+ T cells from gp96-treated untransplanted animals secreted less interleukin (IL)-4, IL-10, and interferon (IFN)-γ after in vitro polyclonal stimulation than CD3+ T cells from PBS-treated animals. Gp96 administration might therefore influence the induction of immunity to coencountered antigenic challenges and inflammatory events by inducing what appears to be a state of peripheral T-cell hyporesponsiveness.

Pulmonary Artery Denervation Reduces Pulmonary Artery Pressure and Induces Histological Changes in an Acute Porcine Model of Pulmonary Hypertension

Background—Pulmonary arterial hypertension is a devastating disease with high morbidity and mortality and limited treatment options. Recent studies have shown that pulmonary artery denervation improves pulmonary hemodynamics in an experimental model and in an early clinical trial. We aimed to evaluate the nerve distribution around the pulmonary artery, to determine the effect of radiofrequency pulmonary artery denervation on acute pulmonary hypertension induced by vasoconstriction, and to demonstrate denervation of the pulmonary artery at a histological level. Methods and Results—Histological evaluation identified a circumferential distribution of nerves around the proximal pulmonary arteries. Nerves were smaller in diameter, greater in number, and located in closer proximity to the luminal aspect of the pulmonary arterial wall beyond the pulmonary artery bifurcation. To determine the effect of pulmonary arterial denervation acute pulmonary hypertension was induced in 8 pigs by intravenous infusion of thromboxane A2 analogue. Animals were assigned to either pulmonary artery denervation, using a prototype radiofrequency catheter and generator, or a sham procedure. Pulmonary artery denervation resulted in reduced mean pulmonary artery pressure and pulmonary vascular resistance and increased cardiac output. Ablation lesions on the luminal surface of the pulmonary artery were accompanied by histological and biochemical alteration in adventitial nerves and correlated with improved hemodynamic parameters. Conclusions—Pulmonary artery denervation offers the possibility of a new treatment option for patients with pulmonary arterial hypertension. Further work is required to determine the long-term efficacy and safety.

Oral presentation of malignant mesothelioma

We report a case of metastatic mesothelioma presenting as an oral metastasis in a 46-year-old patient. The patient presented with 2 polypoid lesions that appeared to be benign on the dorsum of the tongue. Excisional biopsy showed the presence of metastatic carcinoma that on further investigation proved to be mesothelioma. The initial presentation of mesothelioma as an oral metastasis is not previously reported. This article highlights the importance of biopsy and histopathological diagnosis in presumed benign lesions and the role of the general dental practitioner in screening for oral neoplasms.

Multi-elemental analysis of human lung samples using inductively coupled plasma mass spectrometry

The aim of this study was to establish concentrations of a wide range of elements in human lung samples to allow better identification of potential exposures in subsequent cases. This study reports concentrations of 48 elements (Al, As, Au, B, Ba, Be, Bi, Br, Cd, Ce, Co, Cr, Cs, Cu, Fe, Ga, Gd, Ge, Hf, Hg, In, Li, Mn, Mo, Nb, Ni, Os, Pb, Pd, Pt, Rb, Re, Ru, Sb, Se, Sm, Sn, Sr, Ta, Te, Ti, Tl, Tm, V, W, Y, Zn and Zr) in fresh lung tissue samples from 54 hospital patients, of which 93% exhibited various forms of neoplasia. The lung samples were taken from unaffected, background tissue. The samples were stored as fresh tissue in alcohol, dried and microwave digested before analysis by inductively coupled mass spectrometry (ICP-MS). It was possible to establish 95th percentiles for all elements except for rhenium and for 40 elements mixed effects modelling was undertaken. Overall, the levels reported are commensurate with ranges for those elements that had been reported previously. The data were examined for gender, smoking and occupational exposures to metals. The results show that males have higher lung concentrations of Ni, Cr, Gd, Au and Be than females, but significantly lower lung concentrations of Co, Sn, W and In. Cadmium lung concentrations were significantly higher in smokers. Platinum lung concentrations were higher in those who had undergone chemotherapy and gadolinium concentrations were predictably high in those who had undergone imaging scans. More essential elements such as Cu, Br, Fe and also Ge varied the least within lung samples from individuals whilst Be, Hf and Pt had the greatest variances. Between individuals V and Li lung concentrations varied the most, whilst Cu varied least. Analysis of the data for those who reported as having previously worked with metals showed 24 of the 48 elements determined were higher than those from those who had not reported working with metals.

Evaluation of the anti-inflammatory effects of β-adrenoceptor agonists on human lung macrophages.

The principal mechanism by which bronchodilator β-adrenoceptor agonists act is to relax airways smooth muscle although they may also be anti-inflammatory. However, the extent of anti-inflammatory activity and the cell types affected by these agonists are uncertain. The purpose of this study was to evaluate whether β-adrenoceptor agonists prevent pro-inflammatory cytokine generation from activated human lung macrophages. Macrophages were isolated and purified from human lung. The cells were pre-treated with both short-acting (isoprenaline, salbutamol, terbutaline) and long-acting (formoterol, salmeterol, indacaterol) β-agonists before activation with lipopolysaccharide (LPS) to induce cytokine (TNFα, IL-6, IL-8 and IL-10) generation. The experiments showed that short-acting β-agonists were poor inhibitors of cytokine generation. Of the long-acting β-agonists studied, formoterol was also a weak inhibitor of cytokine generation whereas only indacaterol and salmeterol showed moderate inhibitory activity. Further experiments using the β2-adrenoceptor antagonist ICI-118,551 suggested that the effects of indacaterol were likely to be mediated by β2-adrenoceptors whereas those of salmeterol were not. These findings were corroborated by functional desensitization studies in which the inhibitory effects of indacaterol appeared to be receptor-mediated whereas those of salmeterol were not. Taken together, the data indicate that the anti-inflammatory effects of β-adrenoceptor agonists on human lung macrophages are modest.