Factors that help sustain humanism in medical education and patient care (modified from Chou CM et al. [11]).
\\n\\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:null},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
\n'}],latestNews:[{slug:"intechopen-expands-to-all-global-amazon-channels-with-full-catalog-of-books-20210308",title:"IntechOpen Expands to All Global Amazon Channels with Full Catalog of Books"},{slug:"stanford-university-identifies-top-2-scientists-over-1-000-are-intechopen-authors-and-editors-20210122",title:"Stanford University Identifies Top 2% Scientists, Over 1,000 are IntechOpen Authors and Editors"},{slug:"intechopen-authors-included-in-the-highly-cited-researchers-list-for-2020-20210121",title:"IntechOpen Authors Included in the Highly Cited Researchers List for 2020"},{slug:"intechopen-maintains-position-as-the-world-s-largest-oa-book-publisher-20201218",title:"IntechOpen Maintains Position as the World’s Largest OA Book Publisher"},{slug:"all-intechopen-books-available-on-perlego-20201215",title:"All IntechOpen Books Available on Perlego"},{slug:"oiv-awards-recognizes-intechopen-s-editors-20201127",title:"OIV Awards Recognizes IntechOpen's Editors"},{slug:"intechopen-joins-crossref-s-initiative-for-open-abstracts-i4oa-to-boost-the-discovery-of-research-20201005",title:"IntechOpen joins Crossref's Initiative for Open Abstracts (I4OA) to Boost the Discovery of Research"},{slug:"intechopen-hits-milestone-5-000-open-access-books-published-20200908",title:"IntechOpen hits milestone: 5,000 Open Access books published!"}]},book:{item:{type:"book",id:"1897",leadTitle:null,fullTitle:"Metamaterial",title:"Metamaterial",subtitle:null,reviewType:"peer-reviewed",abstract:"In-depth analysis of the theory, properties and description of the most potential technological applications of metamaterials for the realization of novel devices such as subwavelength lenses, invisibility cloaks, dipole and reflector antennas, high frequency telecommunications, new designs of bandpass filters, absorbers and concentrators of EM waves etc. In order to create a new devices it is necessary to know the main electrodynamical characteristics of metamaterial structures on the basis of which the device is supposed to be created. The electromagnetic wave scattering surfaces built with metamaterials are primarily based on the ability of metamaterials to control the surrounded electromagnetic fields by varying their permeability and permittivity characteristics. The book covers some solutions for microwave wavelength scales as well as exploitation of nanoscale EM wavelength such as visible specter using recent advances of nanotechnology, for instance in the field of nanowires, nanopolymers, carbon nanotubes and graphene. Metamaterial is suitable for scholars from extremely large scientific domain and therefore given to engineers, scientists, graduates and other interested professionals from photonics to nanoscience and from material science to antenna engineering as a comprehensive reference on this artificial materials of tomorrow.",isbn:null,printIsbn:"978-953-51-0591-6",pdfIsbn:"978-953-51-6209-4",doi:"10.5772/2319",price:159,priceEur:175,priceUsd:205,slug:"metamaterial",numberOfPages:628,isOpenForSubmission:!1,isInWos:1,hash:"56517158cb186183585408e26e16cf8f",bookSignature:"Xun-Ya Jiang",publishedDate:"May 16th 2012",coverURL:"https://cdn.intechopen.com/books/images_new/1897.jpg",numberOfDownloads:63591,numberOfWosCitations:47,numberOfCrossrefCitations:22,numberOfDimensionsCitations:52,hasAltmetrics:0,numberOfTotalCitations:121,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"May 9th 2011",dateEndSecondStepPublish:"June 6th 2011",dateEndThirdStepPublish:"October 11th 2011",dateEndFourthStepPublish:"November 10th 2011",dateEndFifthStepPublish:"March 9th 2012",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6,7",editedByType:"Edited by",kuFlag:!1,editors:[{id:"103012",title:"Dr.",name:"Xun-Ya",middleName:null,surname:"Jiang",slug:"xun-ya-jiang",fullName:"Xun-Ya Jiang",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:"State Key Laboratory of Functional Materials for Informatics\nShanghai Institute of Microsystem and Information Technology\nCAS, Shanghai, China",institutionString:null,position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"1",institution:{name:"Chinese Academy of Sciences",institutionURL:null,country:{name:"China"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"929",title:"Electrostatics",slug:"materials-science-composite-materials-electrostatics"}],chapters:[{id:"37001",title:"Novel Electromagnetic Phenomena in Graphene and Subsequent Microwave Devices Enabled by Multi-Scale Metamaterials",doi:"10.5772/37691",slug:"novel-electromagnetic-phenomena-in-graphene-and-subsequent-microwave-devices-enabled-by-multi-scale-",totalDownloads:2784,totalCrossrefCites:0,totalDimensionsCites:0,signatures:"Dimitrios L. 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In METAVIR, only interface hepatitis and lobular necrosis determine the grade of activity, while in Ishak, portal infiltrate and confluent necrosis are included with the two previous parameters. Confluent necrosis is very rare in chronic hepatitis C, that in most patients the actual score limit is 12 instead of 18 (Ishak score), that mostly underscore the actual necroinflammation. Also, portal inflammatory infiltrate may reflect immunological response rather than necroinflammation. This may explain the discrepancy between enzyme elevation and necroinflammatory score as determined by Ishak score (modified HAI) in assessment of chronic hepatitis C biopsy specimens. On the other hand, no study has clearly tested such discrepancy in applying METAVIR.
Some of the terminologies applied in METAVIR are in need of revision or declaration. For example; the term “septa” is used to mean actual fibrous bridges, while in Ishak score both terms; septa and bridges; are applied by different meaning. Ishak et al, 1995, in their system, applied both terminologies (septa & bridges), however in completely different meaning. Septa, means expansion of portal tract edges without formation of bridges or actual connection between portal areas or portal area and central vein (1). On the other hand, the term bridge was applied to actual fibrous connection between two portal areas or portal area and central vein. Because of this confusion, some studies comparing both scoring systems have committed some mistakes.
Some studies have compared both Ishak and METAVIR systems, but they included small number of patients or included hepatitis B and hepatitis C. Therefore, the objectives of this chapter are:
Revision of histological grading and staging in chronic hepatitis C.
Clarification of the METAVIR terminology for future applications.
Establishing an Ishak to METAVIR fibrosis score conversion table.
The new approach to classify chronic hepatitis C involves three separate considerations. The first is a comment on etiology. Frequently, this cannot be determined on the basis of histological appearance alone, and the diagnosis is made on the basis of other laboratory investigations. The second assessment relates to the severity and distribution of necroinflammatory activity (histological “grade”). Thirdly, an attempt should be made to assess the degree of fibrosis (histological “stage”) (2).
Inflammatory activity in the liver can be divided into two main components. The first involves portal tracts (portal hepatitis) with variable extension into the adjacent periportal regions (periportal hepatitis). The second involves liver parenchyma (lobular hepatitis). These different patterns of inflammation are probably related to the different pathways whereby circulating inflammatory cells can gain access to the liver (3).
Inflammatory cells migrating across the endothelium of portal vessels pass into portal connective tissue which is rich in antigen presenting dendritic cells. A predominantly portal inflammatory infiltrate is one of the characteristic histological features of chronic hepatitis. However it should kept in mind that portal hepatitis by itself does not necessarily indicate a diagnosis of chronic hepatitis. Mild portal inflammatory changes, indistinguishable from low-grade chronic viral hepatitis, can be seen in a variety of conditions including systemic illness, nearby space-occupying lesion and even in some livers, which otherwise would be considered as normal. Furthermore, a predominantly portal inflammatory infiltrate is sometimes present in cases of acute viral hepatitis, without any implication of chronicity (4).
Considerable attention has focused on the extension of portal inflammatory cells into the adjacent liver parenchyma associated with destruction of the limiting plate and damage to periportal hepatocytes (interface hepatitis) (5).
Inflammatory cells migrating across the endothelium of hepatic sinusoids can gain direct access to the liver parenchyma causing lobular inflammation. Typically this presents as “spotty” inflammation dispersed randomly throughout the liver parenchyma. In some cases inflammatory changes are more pronounced in perivenular (acinar zone 3) region and are associated with areas of confluent necrosis. When areas of zone 3 necrosis link vascular structures, in particular portal tracts to hepatic venules, the term “bridging necrosis” is used. Rarely in severe cases, there may be complete destruction of hepatocytes in one or more acini (panacinar necrosis or multiacinar necrosis) (6).
The main purpose in identifying different patterns of necroinflammatory activity is that these may have different functional and prognostic significance in terms of progression to fibrosis and ultimately cirrhosis.
Interface hepatitis has long been considered as an important lesion in the evolution of chronic hepatitis to cirrhosis. In the original classification proposed by De Groote et al, 1968 (7), chronic persistent hepatitis (portal inflammation without piecemeal necrosis) was thought to have a favorable prognosis, whereas chronic active hepatitis (portal inflammation with piecemeal necrosis) was regarded as having substantial risk for progression to cirrhosis. Interface hepatitis with associated periportal liver cell loss and collapse of the reticulin framework can readily be visualized as a mechanism for the development of periportal fibrosis (2).
There have been few attempts to validate this lesion as a prognostic feature in serial biopsies. One study showed that the presence of interface hepatitis in initial biopsies from patients with chronic hepatitis correlate with subsequent development of cirrhosis (8). Two other studies have demonstrated an association between the severities of necroinflammatory activity (including interface hepatitis as a major component) in an initial biopsy and the development of fibrosis or cirrhosis in follow up biopsies (9).
Bursts of lobular inflammatory activity are thought to be particularly important in pathogenesis of chronic hepatitis C infection, where progression to cirrhosis is common despite the lack of interface activity (10). For these reasons it has been suggested that the pattern and severity of lobular inflammation should be taken in account in assessing the outcome in cases of chronic hepatitis (11).
In the majority of cases fibrosis begins as expansion of portal tracts occurring in association of interface hepatitis. As fibrosis progresses, there is formation of septa with the development of portal-portal linkage. Eventually hepatocyte nodules are completely surrounded by fibrous tissue. Development of established cirrhosis usually takes several years. However, in some situations (e.g. viral hepatitis recurring following liver transplantation) cirrhosis can develop much more quickly. Parenchymal fibrosis can also occur in presence of lobular inflammation, particularly in areas of bridging necrosis (12). This may be responsible of for formation of portal-central septa, which have been regarded as more significant in the development of cirrhosis than portal-portal linkages (13).
The work of the two decades preceding the Knodell HAI provided the foundation for our current understanding of the histopathology of chronic hepatitis. Early descriptions and classifications focused on differentiating acute and chronic hepatitis and on lesions that predicted disease progression. The first histological classification, which was published by De Groote in 1968 (7), codified the terminology, chronic persistent and chronic\n\t\t\t\taggressive hepatitis. Both conditions involved portal inflammation, but were distinguished by the severity of piecemeal necrosis, inflammation, and structural remodeling of the liver. Inflammatory activity was graded as moderate or severe, but exact criteria were not given. The classification system also incorporated the concept that chronic persistent hepatitis had a generally good prognosis whereas chronic aggressive hepatitis could evolve to cirrhosis (7).
Popper and Schaffner (1971) (14) affirmed the value of liver biopsy for diagnosis and prognosis and recommended use of “topographic” descriptors for hepatitis, that is, chronic lobular, chronic portal, or chronic periportal hepatitis. The last of these, synonymous with chronic aggressive hepatitis, was believed to progress, whereas chronic portal hepatitis, synonymous with chronic persistent hepatitis, was considered a non-progressive process. Chronic lobular hepatitis was a term for histological findings similar to those of acute hepatitis, but with a clinical duration of more than 3 months. It was thought to be non-progressive except when seen in combination with chronic periportal hepatitis.
The explosion of scientific information on viral and non-viral hepatitis in the last decades of the 20th century led pathologists to question the conventional nomenclature of chronic persistent and chronic active (aggressive) hepatitis because of a growing understanding that etiology may be more significant than morphological classification in predicting the natural history of liver disease. This shift in thinking was driven largely by the apparent dissociation between the mild histology of non A-non B hepatitis (hepatitis C) and its progressive clinical course. It was found that, in many cases, the lesions of this form of viral hepatitis fell between those described as chronic persistent and chronic active hepatitis and could not be clearly categorized (15).
The lack of severe piecemeal necrosis and confluent lobular necrosis resulted in the diagnosis of chronic persistent hepatitis, implying a benign course. At the same time, the lobular component was being recognized as more significant than portal lesions with respect to disease progression. Also, confluent necrosis, which when present in severe autoimmune hepatitis and hepatitis B confers an ominous prognosis, is uncommon in hepatitis C, and yet progression to fibrosis or cirrhosis occurs in all 3 diseases (2).
For a system to be effective in every day diagnostic practice, it must be simple to understand, simple to apply, communicate effectively to the treating clinician, and clinically relevant (16). The system that is most appropriate for clinical practice may not be the most informative for investigative work (17).
This scheme represents an extension of the original Knodell system, with a number of minor modifications. Firstly, a continuous scale is used for scoring each of the features assessed. Secondly, necroinflammatory activity and fibrosis are considered as separate categories. Thirdly, confluent necrosis is separated from periportal hepatitis and is included as a separate category of necroinflammatory activity. The term interface hepatitis was used in place of ‘‘piecemeal necrosis,’’ to reflect the growing evidence that apoptosis, not necrosis, occurs at the limiting plate.
The first category (piecemeal necrosis) scores are defined as follows: 0, no piecemeal necrosis; 1, focal piecemeal necrosis in few portal areas; 2, focal piecemeal necrosis in most portal areas; 3, continuous piecemeal necrosis around <50% of tracts or septa; 4, continuous piecemeal necrosis around >50% of tracts or septa.
The second category (Confluent Necrosis) scores are defined as follows: 0, no confluent necrosis; 1, focal confluent necrosis; 2, zone 3 necrosis in some areas; 3, zone 3 necrosis in most areas; 4, zone 3 necrosis and occasional portal-central (P-C) bridging; 5, zone 3 necrosis and multiple (P-C) bridging; 6, panacinar or multiacinar necrosis.
The third category (focal lytic necrosis, apoptosis, and focal inflammation) scores are defined as follows: 0, No focal necrosis; 1, one focus or less per 10x objective; 2, two to four foci per 10x objective; 3, five to ten foci per 10x objective; 4, more than ten foci per 10x objective.
The fourth category (portal inflammation) scores are defined as follows: 0, no portal inflammation; 1, mild in some or all portal areas; 2, moderate in some or all portal areas; 3, moderate to marked, all portal areas; 4, marked in all portal areas. By combining scores for each of the four individual necroinflammatory categories, histological grading scores ranging from 0-18 can now be achieved. The overall activity scores are defined as follows: 1-3, minimal; 4-8, mild; 9-12, moderate; 13-18, severe (1).
Ishak Modified HAI (1995) (1).
The fibrosis scores are defined as follows: 0, no fibrosis; 1, fibrous expansion of some portal areas, with or without short fibrous septa; 2, fibrous expansion of most portal areas, with or without short fibrous septa; 3, fibrous expansion of most portal areas with occasional portal to portal bridging; 4, fibrous expansion of most portal areas with marked bridging (portal to portal as well as portal to central); 5, marked bridging with occasional nodules (incomplete cirrhosis); 6, cirrhosis, probable or definite (1).
Difficulties with the Ishak system have been noted. Use of the X10 objective for the evaluation of necroinflammatory foci raises concerns of reproducibility, because the size of the field may vary among microscopes. In addition, definitions of a “focus” of lymphocytic aggregates, apoptotic hepatocytes, or confluent necrosis may vary among pathologists (18).
The French METAVIR Cooperative Study Group stated that another possible approach for grading the necroinflammatory activity is to consider that periportal and intra-lobular necroinflammatory lesions are related to the same pathologic mechanism and that they must be globally assessed. A panel decided to define activity according to its potential predictive value for the occurrence of liver fibrosis. They chose to include in algorithm only two features (piecemeal necrosis and lobular necrosis) (19).
Portal inflammation was excluded from the algorithm, because this feature is a prerequisite for the definition of chronic hepatitis even without activity. Furthermore they observed a strong correlation with piecemeal necrosis, making these two features redundant criteria.
Piecemeal necrosis was chosen as the first decision criterion because of its proven potential value in other types of chronic hepatitis. It was then suspected that another feature, lobular necrosis, was of major importance in the prediction of liver fibrosis. It is believed that aggravation of chronic hepatitis C occurs through a burst of lobular necrosis, a lesion that is frequently present in chronic hepatitis C. The two lesions were therefore combined to propose a simple algorithm that defined activity.
In several existing classifications, the degree of piecemeal and lobular necrosis was independently assessed and their scores then added, thus giving each of these two lesions the same weight in the definition of activity. The METAVIR system included both piecemeal necrosis and lobular necrosis in the definition of activity, but with different values. The rationale for overweighting the piecemeal necrosis item by comparison with lobular necrosis is that piecemeal necrosis is the major discriminating factor used to grade activity, as shown by stepwise discriminate analysis.
The first criterion (piecemeal necrosis) scores are defined as follows: 0, absent; 1, focal alteration of the periportal plate in some portal tracts; 2, diffuse alteration of the periportal plate in some portal tracts or focal lesion around all portal tracts; 3, diffuse alteration of the periportal plate in all portal tracts.
The second criterion (focal lobular necrosis) scores are defined as follows: 0, less than one necroinflammatory foci per lobule; 1, at least one necroinflammatory foci per lobule; 2, several necroinflammatory foci per lobule or confluent or bridging necrosis. The overall activity scores are defined as follows: 0, No activity; 1, mild; 2, moderate; 3, severe (20).
The fibrosis scores are defined as follows: F0, no fibrosis; F1, portal fibrosis without septa; F2, portal fibrosis with rare septa; F3 numerous septa without cirrhosis; F4, cirrhosis (19).
The METAVIR system has the advantage of simplicity, reproducibility and application to a large number of biopsies (20). This score is composed of a two-letter and two-number coding system: A= histological activity and F= fibrosis (Table 2).
The METAVIR System.
There are a number of problems which apply to all the scoring systems currently in use.
Lack of scientific validation:
A fundamental problem with histological “scoring” is that the numbers which are generated do not represent measurement of continuous variable. Instead, they simply represent different categories of severity. This contrasts with biochemical measurements, for example, serum transaminases, for which a true numerical progression can be more readily justified (21).
Observer variation:
There are problems in obtaining reproducible results, even when scoring system is applied by experts in the field of liver pathology. In general, better reproducibility has been obtained for scoring fibrosis than for scoring inflammatory activity. This is probably due to imprecise terminology which is used in individual histological features. Terms such as “occasional”, “some”, or “mild’, “moderate and “severe” are used without defining precisely what these mean (22).
Sampling Variation:
Much of the knowledge regarding this problem has come from the examination of hepatectomy specimens obtained at liver transplantation. Sampling variation exist, both for the grade of necroinflammatory activity and for the stage of fibrosis. For example, small areas of multiacinar necrosis can often be found in a liver which otherwise show a relatively inactive cirrhosis. These areas are typically subcapsular in location but may be also present elsewhere. If a needle biopsy is taken from one of these areas, a “falsely high” inflammatory score may be obtained. Chronic viral hepatitis may affect the liver uniformly, but considerable variation in the severity of fibrosis can be seen when whole liver are available for examination (2).
Etiological considerations:
The scoring systems currently in common use incorporate histological features which may be seen in all types of chronic hepatitis. However, different types of chronic hepatitis have marked differences in natural history and response to therapy. These differences in behavior may be reflected by different patterns of histological damage. For example, ballooning, rosetting, and giant cell transformation may be regarded as signs of severe damage in cases of autoimmune hepatitis, even in the absence of conspicuous inflammatory activity. Direct cytopathic damage (e.g. ballooning or fatty change) may be important in the pathogenesis of fibrosis in chronic hepatitis C infection (2).
Terminology in METAVIR as regard fibrosis stage assessment is not clear and confusing; with narrow range (F0-F4). F3 indicates numerous septa, however, in practical application early (developing) cirrhosis is included too, irrespective of being not described in the score details. On the other hand, Ishak fibrosis score is wider (0-6), more sensitive, as well clearly separate incomplete (developing, early) cirrhosis from established cirrhosis (1,20,23).
Rozario and Ramakrishna, 2003(24) have built their analysis, tables and comparison on the inaccurate idea that F2 of METAVIR (rare septa) is equal to stage 2 of Ishak. However, the correct is that, F1 stage of METAVIR is equal to stages 1&2 of Ishak, and F2 of METAVIR is equal to stage 3 of Ishak (occasional bridging fibrosis). This resulted in a defect that may affect the idea and the conclusion (4).
Applying semi-quantitative terminology reflecting grades of necroinflammatory injury as recorded by Ishak may underestimate the severity of these changes. In Ishak scoring, 6 points out of the 18 are related to confluent necrosis, which is a rare event in chronic hepatitis C.
Elzbieta and Marek, 2005 (25) reported that, the comparison of three histological scoring systems used to evaluate chronic hepatitis (Batts and Ludwig, Ishak et al. and METAVIR scoring systems) revealed a high coefficient of positive correlation between the respective scales. Thus, the systems seem comparable in the estimation of the inflammation grade and stage of fibrosis. Table 2 may be advised for converting fibrosis score from Ishak to METAVIR.
Goodman in his review 2007(26), considered Ishak stage 5 (incomplete cirrhosis) to be included in METAVIR F4 stage, that is different from the opinion of Bedossa and others of METAVIR group. This is a pitfall that may affect the results of some research studies.
In assessment of regression of fibrosis after autoimmune hepatitis treatment, Abdalla et al, 2009 have reported higher sensitivity of Ishak compared with METAVIR in detection of fibrosis regression (27). They also found statistically higher sensitivity for quantitative assessment of fibrosis by analysis of digitalized pictures of sirus red. Czaja and Carpente 2004, reported a sensitivity of Ishak in assessment of fibrosis regression (28). Esmat et al, 2007 (applying Ishak fibrosis score) have demonstrated a correlation between fibrosis score and hyaluronic acid level (29). Tsochatzis1 et al 2011, in their meta-analysis of diagnostic accuracy of elastography for the diagnosis of severity of fibrosis in chronic liver disease, the different stages of fibrosis (scoring systems) were converted to comparable stages in METAVIR (30). Goodman 2007, suggested application of METAVIR in routine work, and Ishak score in clinical trials, because of higher sensitivity in fibrosis assessment (28). Lefkowitch 2007 and Guido et al, 2011, suggested application of any of the scoring systems, that is not home made, and the clinicians with whom they work prefer (31,32).
Although liver biopsy has long been regarded as a gold standard procedure, it has obvious limitations. It represents an approximation of liver fibrosis for the whole liver and is, therefore, not the gold standard for fibrosis assessment. Nevertheless, it is the best procedure currently available (33). Germani et al 2010 recommend liver pathologists to perform computer-assisted digital analysis of Sirius red-stained histological sections in addition to the scoring system established to describe the stage of the liver disease (34).
Regarding fibrosis:
Ishak and METAVIR are nearly identical; however, Ishak is of a wider scale.
The term “Septa” in METAVIR is equal to “bridging fibrosis” in Ishak.
F3 stage in METAVIR score includes incomplete (developing) cirrhosis.
Regarding necroinflammatory injury
METAVIR is more sensitive to severe activity and more reproducible. However, without numerical scoring that let it less effective for monitoring minor changes.
Ishak modified HAI has a wider scale. However, 6 points of it (confluent necrosis) are nearly out of the chronic hepatitis C scope. This minimizes the actual scoring to 12 points instead of 18 in practical application.
The proposed table is advised for unidirectional converting fibrosis scores from Ishak to METAVIR.
METAVIR F3 stage may better be subdivided into F3a: Marked bridging fibrosis and F3b: incomplete (early cirrhosis) (developing cirrhosis).
More work is needed in:
Assessing the validity of the current scoring systems in post-liver transplant patients with recurrent HCV especially those with a back ground of graft pathologies such as rejection and those with associated HBV or cytomegalovirus and HIV infections.
Convertibility of the results of these scoring systems and image pattern of contrast enhanced ultrasound of the liver.
Modified and reprinted (19).
The METAVIR Fibrosis staging system. F0 is normal liver (no fibrosis). F1 = portal fibrosis. F2 = few septa. F3 = many septa. F4 = cirrhosis.
Portal tract expansion by fibrosis, Masson trichrom stain.
Bridging fibrosis, Masson trichrom stain.
Multiple portal-portal bridges,, Masson trichrom stain.
Regenerating nodules rimmed by fibrosis, Masson trichrom stain.
Regenerating nodules rimmed by dense fibrosis, Masson trichrom stain.
Interface hepatitis, H&E stain.
Evident interface hepatitis with apoptosis, H&E stain.
Confluent necrosis, reticulin collapse, sirus red stain. [1]
Patient-centered care means organizing health care to serve the patients. In this context, and in order to respond to the new demands of society for the reliability of doctors in the 21st century and seeking greater adaptation and development of professionals, Competence Based Training (CBT) was developed [1]. Humanism in medicine, a central aspect of professionalism, combines scientific knowledge and skills with respectful, compassionate care that is sensitive to the values, autonomy, beliefs and cultural backgrounds of patients and their families.
\nAccording to Jean-Paul Sartre, “humanism is a theory which upholds man as the end-in-itself and as the supreme value”. Man is the point-of-care, the thing-of-focus, and the centerpiece of our attention. Medical humanism, or humanistic medicine, is an interdisciplinary field which aims to address problems in health care. According to The Arnold P. Gold Foundation, it is “characterized by a respectful and compassionate relationship between physicians and their patients” centered on several ideals, including integrity, excellence, compassion, altruism, respect, empathy, and service [2].
\nHumanism represents the basis of medicine throughout history, beginning from the time of Hippocrates and the development of the Hippocratic Oath. Medicine has been regarded as a moral profession and carried out in accordance with a set of morals and ethics [3]. The first conference concerned with humanism, was held at Chicago University in 1933, recommended considering humanistic science as the basis of morality and decision-making in medical practice.
\nThe past four decades showed great advances in medical knowledge and new technological devices have been extensively incorporated into medical practice. Physicians emphasized on the disease, use of technology, laboratory investigations, treatment and physical recovery. They ignore patient psychological status, ethical and social cultures. These events abolished medical humanistic spirit. Such dehumanized medicine appears to have no past, no cultural language and no philosophy.
\nSir William Osler (1837–1901), considered as the father of modern medicine, advised ¨Listen to the patient. He is telling you the diagnosis¨. Sir Osler also stated that (it is much more important to know what sort of person has a disease, than to know what sort of disease a person has) [3]. Marañón’s words provide us with the following reflection “… a mere diagnostic system, deduced exclusively from analytical data, dehumanized, independent of direct and endearing observation of the patient, carries the fundamental error of forgetting the personality, which is so important in etiologies and to stipulate the prognosis of the patient and teach us, doctors, what we can do to alleviate his sufferings” [4].
\nHumanism is an essential component of the art of Neurosurgery that allows the science of Neurosurgery to prosper. Without humanism, medicine is no longer; without medical science, medical humanism has no vehicle. The practice of Neurosurgery is both a science and an art. Contemporary Neurosurgery is based on scientific rigor but good medical practice should be ‘an art that uses science as one of its tools’. It is the art of Neurosurgery that facilitates teamworking, communication, partnership with patients and maintenance of trust—key elements of professional guidance on good medical practice—whereas science upholds evidence-supported practice.
\nThe young resident begins the residency full of dreams and desires to take care of patients, full of idealism; and by a process that has not been explained sufficiently ends up becoming indifferent to human suffering, gets used to the disease, unleashes the sufferer and becomes “dehumanized”. The question is: what skills and qualities do neurosurgeons need to practice a humanistic patient-centered care?
\nKnowing how to care for the sick in all their human dimensions is the main challenge facing medical education today. This is the construction of a new medical humanism capable of harmonizing the care that the patient needs. A training programme was conducted to teach medical humanism core values through lectures, role modeling, and training in interpersonal skills, literature and humanities study. Improvements in medical humanism attitudes and behaviors were attained after successfully completing the course through lectures, role modeling, and training in interpersonal skills, literature and humanities study. A humanistic neurosurgeon provides a skilled, compassionate, and empathic care to her/his patients, and demonstrates respect for their values, autonomy, and cultural backgrounds. Neurosurgery is an apprenticeship profession, where medical humanism can be taught and behaviors associated with humanism can be learned.
\nA set of 10 humanistic values that can help residents and practicing physicians to maintain humanism behaviors in their practice are presented here [5]. A proposal of a new model of medical humanism in neurosurgery, resulting from harmony that perfectly combines the science of modern neurosurgery with the art of care, which involves understanding the sick as a person, focusing on the patient.
The utmost important rule in Medicine: Aeger Primo, “The Patient First” [5]. The patient-centered perspective suggests physician-patient relationship, communication and relational skills and techniques are a core professional competence to be used by clinicians. Placing patients first adds important dimensions to how we judge the success and failure as neurosurgeons.
Every patient is a unique human being: In patient-centered medicine, the patient has to be understood as a unique human being. “Treat the patient, not the disease”. The biopsychosocial model challenges the neurosurgeon to address both the biological as well as psychosocial dimensions of illness; care the needs of the patient [6]. The practice of neurosurgery that reflects humanism values involves physician– patient interactions during which the patient is seen as a unique individual who should be treated with dignity and respect.
The practice of Neurosurgery is both a science and an art. Carefully planning the surgical procedure is accomplished by a thorough preoperative assessment and a comprehensive treatment plan, review the anatomy and follow a careful and aseptic technique, the most basic principle of surgery. The supreme rule of the Greek medical ethics (Hippocrates): opheléein ê mê bláptein, “first to be useful, then do no harm”.
Some neurosurgical conditions have no satisfactory solutions: To be honest but not brutal, to offer hope always and if we cannot cure, we can help, are some useful principles in guiding patients through their process when faced with catastrophic disease that has no satisfactory solution [7]. Some diseases are incurable; it’s attributed to Hippocrates that in Medicine we are called “to cure sometimes, to relieve often, and to comfort always”. The neurosurgeon must remember that any outcome estimates are statistical probabilities based on large groups of patients and do not predict how any given individual patient will respond.
Neurosurgery, as much as Medicine, is a service profession and the commitment to serve our patients is a hallmark of humanistic physicians. The Gold Foundation defines service as “the sharing of one’s talent, time, and resources with those in need; giving beyond what is required” [8].
The humanistic neurosurgeon demonstrates the following attributes: Integrity, clinical excellence, compassion and collaboration, altruism, respect and resilience, empathy and service to her/his patients.
To participate in biomedical research and the advancement of neurosurgery and medicine. We, as a community of learners and knowledge builders, can and must develop meaningful methods of learning and improvement in practice [9]. We must find ways to make continuous learning and improvement an integral part of our workday, just as much as our neurosurgical procedures themselves.
To maintain an open, flexible and life-long learning-oriented mentality. Carl Rogers, a humanist psychologist, stated the goal of modern education: The only man who is educated is the man who has learned how to adapt and change—the man who has realized that no knowledge is secure and that only the process of seeking knowledge gives a basis for security. The goal of education, if we are to survive, is the facilitation of change and (life-long) learning.
To be skeptical: scientific knowledge, the methods and results must be continuously scrutinized for possible errors. It is difficult for the medical literature to exceed 50% (17–85%) of correction, on average. Understanding of the methodology and application of evidence-based medicine (\nFigure 1\n) is needed to correctly interpret the literature on causation, prognosis, diagnostic tests and treatment strategies.
Neurosurgery is a teamwork: preparation, effective communication and respect are essential elements that affect both patient outcomes and the work environment. Good leadership knowledge and skills are crucial to team success and, more important, patient outcomes.
The 5 steps of evidence-based medicine process (5 A’s) based upon the Sackett et al. model [10]. Integrating the best available evidence with clinical expertise (proficiency and judgment) and patient values, beliefs and preferences.
The humanities incorporated in the academic training process are an important resource that allows developing the human dimension of the physician. In coexistence with these realities, the humanities help and, above all, they educate. Educating is much more than training skills: involves creating a thoughtful attitude and a continuing desire to learn.
\nTeaching medical humanism today implies facing the challenge of promoting a true philosophical reconstruction of the physician, which is the anthropological position. And thus building “bifocal” neurosurgeons, who are capable of caring to their patients with a professional, technical and humanistic competence, in harmony, taking advantage of the best that progress offers them, to serve them in their physiological and human needs (\nTable 1\n).
\n\n
| \nHumility Curiosity Standard of behavior Humanism as medically important for the patient. Humanism as important for the physician. Role of physician as treating more than just the disease. | \n
\n
| \nSelf-reflection Seeking connection with patients Teaching/role modeling humanism Striving to achieve balance Mindfulness and spiritual practices | \n
\n
| \n\n |
Factors that help sustain humanism in medical education and patient care (modified from Chou CM et al. [11]).
Humanism and professionalism, to some authors, identify two different ethos of physician practice and emerge from divergent visions for the physician–patient relationship (\nTable 2\n) [12].
\nCharacteristic | \nHumanism | \nProfessionalism | \n
---|---|---|
Types of values | \nUniversal (Apply to all humans equally) | \nLocal (A socially constructed, local phenomenon) | \n
Sources of learning | \nHuman experience | \nSocialization into profession | \n
Motivation | \nHuman welfare | \nStrengthening of professional identity | \n
Primary duty | \nTo other humans; to society | \nTo the professional group | \n
Cognitive basis | \n“Postconventional thinking”: Judging behavior through deliberation about universal values. | \n“Conventional thinking”: Judging behavior by comparison with the accepted social norms of a specific group. | \n
Humanism and professionalism characteristics (modified from Goldberg JL [12]).
Connecting professionalism to humanism: nurture the humanistic dimension to promote professionalism.
Humanism conveys a deep respect to humans individually, and to humanity collectively, and concern for their general welfare and flourishing. The hallmarks of humanism are its universality, its egalitarianism, and its scope. Its concerns, on the one hand, and obligations, on the other, apply to all humans equally; its training ground, for the most part, is experience—as a human and with humanity; and its ultimate vision is for human welfare, as broadly conceived as possible.
\nProfessionalism, in contrast, is a socially constructed, local phenomenon. Professionalism raises expectations for professional behavior to the level of ideology, encouraging all members to embrace the traditions of the profession and to be as “professional” as they can. However, promoting professionalism -competence and excellence- does not mean to train technicians. No profession will be exercised competently if technical skills are not subordinate to a broader cultural training that encourages cultivating the spirit, the humanistic dimension. So, it is necessary to incorporate the humanistic dimension in the teaching of professionalism.
\nNurturing the humanistic predispositions of residents seems to be the key to ensuring that future neurosurgeons manifest the attributes of professionalism, as professionalism and humanism share common values and that each can enrich the other [13, 14]. The teaching of humanism values is recognized as an essential component of medical education and continuing professional development of physicians [15]. The application of humanism values in medical care can benefit residents, clinicians and patients [16]. The study of humanism values has a solid research base. Research has demonstrated that behaviors that are associated with humanism values improve practice and patient outcomes. The teaching of humanism values can be integrated into formal learning experiences and clinical settings, incorporating empathy, nurturing dignity, respect and confidentiality and fostering role modeling [5, 17].
\nThe fast scientific advances require, to maintain the equilibrium, an expansion of the scope of the medical humanism, that is, a medical humanism at the height of scientific advancement. And it would be this extension of humanism, adapted to the present day, in a modern version, which would lack the process of medical education. If this humanistic update is not made, it would fall into a disproportion that would be reflected in neurosurgeons technically trained, but with serious humanistic deficiencies. We will have deformed physicians, with hypertrophy of technical knowledge, without balance, which naturally does not conquer the confidence of the patient who expects a balanced doctor. Therefore, the function of the University and the training institutions would be to expand the humanist concept in modern views, opening horizons and new prospects. And, to achieve this, the methodology and the systematic learning how to do things, when these things are many and they are wrapped in high technology and commanded by a fast scientific progress. Thus building “bifocal” neurosurgeons, who are able to care for their patients with professional, technical and humanistic competence, in harmony, taking advantage of the best that progress offers, to serve them in their physiological and human needs and beliefs.
\nHumanism is, therefore, a source of knowledge that the neurosurgeon uses for his/her profession. A knowledge as important - neither more nor less - such as those acquired by other ways that help him in his desire to take care of the human being who is sick. They are different routes that find in the person –the realm of medical care- their common goal and allow, with mutual coexistence presided over by respect, the union of forces, synergy in the active will to heal. Humanism in Neurosurgery it is not a temperamental issue, an individual taste, not even an interesting complement. All that would be to place “humanistic attitudes” in the balance, to compensate for the excesses of science. Humanism is, for the neurosurgeon, a true work tool, not a cultural appendix; it is a scientific attitude, weighting, the result of a conscious effort of learning and a method. It is necessary for the neurosurgeon to have a correct balance, a bifocal perspective, that manages to combine in an artistic symbiosis the attention to the disease – with all the technical evolution – and to the patient who feels sick - with the vital understanding that requires. This is, in practice, the person-centered medical care, the most accurate synthesis of the physician practicing science and art simultaneously.
\nTherefore, it is not enough to recommend training in medical humanism, but rather it is necessary to find a formal curricular space, that is, it is necessary to dedicate time and resources. Acknowledge and address the hidden curriculum, while sustaining a vision that incorporates humanism values. Nurturing the development of humanistic values in neurosurgery residents requires individual and institutional appreciation, recognition and commitment. A successful training programme turns residents into professionals prepared for the exercise of the art and science of Neurosurgery, by means of an active learning, where the patient is the focus of health care. A humanistic neurosurgeon provides a skilled, compassionate, and empathic care to her/his patients, and demonstrates respect for their values, autonomy, beliefs and cultural backgrounds. Neurosurgery is an apprenticeship profession, where humanism values can be taught and behaviors associated with humanism can be learned. We present a set of 10 medical humanism core values that can help residents and practicing physicians to maintain humanism behaviors in their practice. A proposal of a new model of medical humanism in neurosurgery, resulting from harmony that perfectly combines the science of modern neurosurgery with the art of care, which involves understanding the sick as a person, focusing on the patient.
\nIn conclusion, to train a neurosurgeon who treats patients rather than diseases, and who lives the values of humanism.
\nThe author declares no conflict of interest.
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