Proceedings of the conference Terminology and Artificial Intelligence 2015 (Granada, Spain) 107 The time factor as an associative concept relation in modelling post-liver transplant management complications Paul Sambre Cornelia Wermuth Hendrik J. Kockaert MIDI MIDI QLVL Multimodality, interaction Multimodality, interaction and Quantitative lexicology and and discourse discourse variational linguistics University of Leuven, Bel- University of Leuven, Bel- University of Leuven, Bel- gium gium gium & University of The paul.sambre@ku- cornelia.wermuth@ku- Free State, South-Africa leuven.be leuven.be hendrik.kockaert@ku- leuven.be medical complications, more specifically those Abstract occurring in post-liver-transplant management (PLTM). In the area of liver transplantation, ter- We propose a first termontological analysis montology improves understanding of conceptual of temporal parameters and relations applied structures based on the lexico-grammatical struc- to the case of medical complications in post- tures retrieved from scientific literature about liver transplant management (PLTM). Medi- complications following transplantation. So far, cal complications contribute to different de- medical complications have not been the subject grees of morbidity and mortality in the process of medical follow-up after transplant of much analysis in terminological or applied on- surgery. Understanding the full ontological tology. Yet, they represent a rich resource for in- and conceptual complexity of such complex vestigating cause-effect relations that constitute a spanning (SPAN) time events time is a cen- specific subcase of causal events. In a broader tral issue in drawing an implementable se- sense, a complication is any adverse, undesired mantic map of the potential causes of early and unintentional result of disease management. and long term complications, their diagnosis More technically, medical complications are iat- and the potential effects due to medical treat- rogenic (i.e. disease-related) subsets of cause-ef- ment. The analysis is usage-based and relies fect relations and refer to the (negative, adverse) on linguistic utterances for complications in morbid consequence of a disease or disorder re- a concise medical review article. sulting from unsuccessful disease management. Complications, occasionally known as subopti- 1 Intro: medical complications and asso- mal (negative) outcome, are not to be confused ciative relations in termontology with sequelae of previous acute medical condi- This paper deals with medical complications and tions and therapies. Negative outcomes can be their termontological description. Termontology subdivided into failure to cure (pre-existing con- (Roche, 2007) combines insights from terminol- ditions that remain unchanged after the transplan- ogy and applied ontology, combining them with a tation procedure), negative sequel and linguistic dimension: whereas terminology is ba- complication (Clavien et al., 2006). Complica- sically interested in complex tree representations tions differ from the commonly expected sequelae between terms and their normalized definitions, resulting from an anterior acute medical condition applied ontology models (visual) representations and therapy. Understanding and dealing effi- of complex concept systems, including semantic ciently with postsurgical medical complications is relations that dynamically connect static entities a crucial issue for the improvement of healthcare in a terminological database. This paper combines quality, since complications require longer and both preoccupations, starting from descriptions of more expensive treatment, and, more importantly, Proceedings of the conference Terminology and Artificial Intelligence 2015 (Granada, Spain) 108 will negatively affect patient prognosis. In ex- example taken from a specialized journal on trans- treme cases, they may lead to severe co-morbidity plantation in medicine should help to illustrate our and even death. objective. The example discusses a complication Concept relations are a key concept in knowledge in PLTM, i.e. hepatic artery thrombosis (HAT): representation, because they interconnect the dif- “[…] hepatic artery thrombosis (HAT) is the sec- ferent concepts or entities in a given knowledge ond main cause of liver graft failure. Moreover, domain. Despite extensive work on concept rela- HAT is the most common vascular complication tions (e.g. Khoo and Jin-Cheon, 2006), a descrip- in orthotopic liver transplantation (OLT). It is as- tive, usage-based account of associative relations sociated with a marked increase in morbidity, be- is lacking to date (Sambre and Wermuth, 2010). ing the leading cause of graft loss (53%) and In the termontological approach, the focus has mortality (33%) during the immediate postopera- been on (static) hierarchical concept relations tive period. […] the consensus definition for early such as type-token and/or meronymic relations. HAT was an arterial thrombosis detected during Biomedical terminology uses these vertical re- the first month after OLT. Late HAT was also de- lations for unique designations of medical con- fined as the event detected ≥ 1 month after OLT. cepts and their terminological variants that result […] The true incidence of early HAT is unknown, in a compendium of several controlled vocabular- but it varies between 0% and 42%. […] improve- ies such as the Unified Medical Language System ments in postoperative care have led to a marked (UMLS) and the controlled thesaurus of Medical reduction in its incidence.” (Pareja et al., 2010) Subject Headings (MeSH) (Grabar et al., 2012). As can be seen from the example, there is clear These classifications display conceptual and so- linguistic evidence of both hierarchical and asso- called static snap shots of medical events. Bio- ciative relations. The following observations can medical ontologies, conversely, aim to explore be made: snap shot relations against a dynamic background 1. The linguistic expression (italics) designating of temporal unfolding, which results in so-called the most common vascular complication, the SPAN (or spanning time) relations. This approach hepatic arterial thrombosis, refers to a hierar- reflects the true conditions as medical concepts chical type of thrombosis (kind_of relation). simultaneously express both hierarchical and as- 2. Causal information is provided by the linguis- sociative (i.e. time-based) relations. The dy- tic expressions cause of liver graft failure, namicity of medical concepts is a phenomenon cause of graft loss and mortality. that deserves further study. In this paper, we 3. Implicit instrumental reference is made to the therefore investigate in greater detail dynamic as- medical treatment in (complex) nouns such as sociative relations, focusing on the temporal un- liver transplantation, graft failure and post- derpinnings of causality in medical complications operative care. in post-liver transplant management (PLTM). The 4. Temporal relations are set up between the rationale is that causes, by definition, precede ef- medical treatment and the post-surgery ad- fects both from a logical and experiential perspec- verse effect by means of prepositions express- tive. Thus, the medical complications under ing a relation of time such as during the investigation can be assumed to entail both causal immediate postoperative period, during the and time-related relations. Our primary objective first month after OLT, or ≥ 1 month after OLT. is to set out temporal parameters to be used in a From the above we can conclude that in medical conceptual model and to inventory specific asso- discourse recurrent, grammatically complex lin- ciative time elements inherent to the concept of guistic patterns are used in order to connect (1) the medical complication in PLTM. entities and types, (2) the causes and (unintended) effects of health care, as well as (3) the instrumen- 2 Time in the conceptual map of medical tal treatment administered by medical doctors complications against a sequential background of (4) time. The interplay between these four kinds of relations Time, in our view, is the underlying conceptual may serve as a lexico-grammatical starting point basis or background against which causality of for drawing up a conceptual map of the medical (un)intentional medical events occur, as these subdomain under investigation. events are or are not triggered by instrumental ac- Such conceptual maps are fundamental for im- tions performed by medical teams. The following proving general procedures (in English) regarding Proceedings of the conference Terminology and Artificial Intelligence 2015 (Granada, Spain) 109 complications for medical care in multidiscipli- 3.1 Peri- and post-operative time nary medical treatment. PLTM occurs in hospital A first important time factor is the distinction be- teams, where physicians and nurses specialized in tween treatment peripheral to the central (intra- complementary fields of haematology, radiology, operative) transplant intervention that can have a internal medicine, surgery and intensive care etc., direct impact on the reduction of post-surgical collaborate in order to improve survival rates and complications (Junttila et al., 2005), and the time reduce the impact of complications. Patient-cen- lapse proper to the complication itself (the so- tered healthcare implies collaborative settings that called post-operative time). Peri-operative time call for efficient IT support systems to monitor pa- has to do with non-problematic follow up of sur- tient status and share information on the needs of gery, before, during and after surgery. The differ- patients. These maps are to be shared between the ence between this peri- and post-operative time is healthcare team’s actors, providing the scenarios minimal, given the fact that some complications they share and the input of each team section or such as infections may arise due to improperly member based on their individual knowledge lev- performed medical actions: els, their educational training, and the different (1) The prophylaxis of bacterial infection in- services and platforms these persons work in. cludes the following strategies: a) selective intestinal decontamination; b) administration 3 A usage-based account of the concep- of systemic antibiotics peri-operatively, c) tual structure of time antibiotic prophylaxis before invasive explo- Our goal is to pinpoint the major dimensions of rations of the biliary tract, and d) personnel time in the description of complications in PLMT. hand washing together with strict asepsis in For reasons of concision, we base our depiction all invasive procedures. on an often-quoted review article about PLTM The following observations can be made about ex- (Moreno and Berenguer, 2006), a common genre ample (1): strategies a), b) and c) in the example in the medical scholar tradition, that summarizes refer to such perioperative precautions. As a part available data for a given medical phenomenon. of medical prevention, peri-operative treatment The article under investigation provides an over- contributes to building the temporal barrier ab quo view of allograft dysfunctions and surgical com- the time sequence of complication starts to run. plications following liver-transplant and discusses Preventive, pre-operative treatment is an im- the state-of-the art concerning their medical fol- portant time issue that should be taken into ac- low-up. Strikingly, the article conceptually op- count in modelling medical complications: a poses immediate and long-term complications. distinction is needed between pre-symptomatic These complications are of a different nature: they (example 2) and post-symptomatic treatment of can be strictly medical (think of respiratory complications. Prophylaxis aims at non-invasive changes, renal dysfunction or hemodynamic com- avoidance of complication outbreak (example 3) plications), or technical (complications due to and therefore reduces medical cost (example 4). h(a)emorrhage or vascular complications result- (2) Another form of prevention, mainly targeted ing, for example, in infections or draft dysfunc- to avoiding the development of clinically tions (major complications in this particular case manifest CMV disease, is the treatment of in- are acute cellular rejection or recurrent viral hep- fection in the pre-symptomatic stage. [81; atitis)). Both short and long-term complications note of the authors: CMV refers to cytomeg- are rather heterogeneous as well, due to the fact alovirus, the most frequent micro-organism that the liver interacts with very different subsys- in liver transplantation] tems of the organism, whereby any dysfunction (3) Universal prophylaxis is useful mainly in may cause diseases such as chronic rejection, ar- high-risk patients […] and can be done effec- terial hypertension, obesity or bone complica- tively and safely with oral drugs […]. [81] tions, just to name a few. Our investigation is (4) Anticipated treatment is also an effective and limited to the temporal aspects of the different probably most cost-effective strategy. complications, leaving aside other conceptual as- The distinction between peri- and post-operative pects such as anatomical location or severity. time as classification parameter is a central issue in the temporal (when do problems occur?), causal (what effects are produced?) and instru- Proceedings of the conference Terminology and Artificial Intelligence 2015 (Granada, Spain) 110 mental (what therapy positively affects such ef- during this early post-transplant period are hemo- fects?) format of medical decision-making. In dynamic alterations, and respiratory, renal and medical discourse, peri-operative techniques are neurological complications. explicitly juxtaposed to post-operative care, as the A global distinction is the one between early and following example shows. late complications, or more correctly, between (5) The results of liver transplantation have im- immediate and long-term complications. Late proved due to advances in perioperative tech- complications are gaining importance as survival nique, a better understanding of the course rates during the early-postoperative period in- and prognosis of several [sic] liver disease creases. The distinction between complication improved immunosuppressive therapy and subtypes is based on the point of their occurrence more effective postoperative care. [77] in time: In fact, knowledge about postoperative complica- (9) The complications occur either immediately tions is actively used in optimal peri-operative post-transplantation or in the long-term. The treatment. main complications in the immediate postop- A second time factor at the interface between erative period are related to the function of peri-operative management and post-operative the graft (dysfunction and rejection), the sur- complications is the moment of detection of gical technique, infections (bacterial, fungal, (early) complication symptoms. Detection and di- and viral), and systemic problems (pulmo- agnosis of new symptoms clearly marks the dis- nary, renal, or neurological). In the long tinction between prophylaxis and post-operative term, the complications are typically a con- care. The following excerpt illustrates this distinc- sequence of the prolonged immunosuppres- tion: sive therapy, and include diabetes mellitus, (6) Thus, knowledge of complications that systemic arterial hypertension, de novo neo- emerge during follow up period, early and plasia, and organ toxicities, particularly ne- accurate establishment of diagnosis, and phrotoxicity. prompt institution of appropriate interven- An important note is that the underlying pathol- tions are essential for optimal patient and ogy causing the transplantation is not considered graft outcome [77] a complication, though the causal trigger may per- An important part of the state-of-the-art consists sist (or reemerge at some later point in time). in describing so-called early detection methods The definition or discursive description of such as in the following example: complications typically contains the designation (7) Methods for early detection of viral infec- of the medical phenomenon, a general characteri- tion, in the case of cytomegalovirus, are pe- zation in terms of immediate or late occurrence, riodic determination of CMV antigenemia in followed by a more precise time label for the time peripheral blood leukocytes and PCR tech- span within which complications arise (in terms niques to detect the blood viral genome. of hours, as in (10), days, or, in the case of late Defining medical states is a central issue in liver complications, months). transplant surgery. The literature defines the nor- (10) A hemorrhage in the immediate postopera- mal state in the intensive care unit, after transplan- tive period is another potential complication tation that shows increasing degrees of recovery […].It is typically diagnosed within the first as illustrated in the following example by the dif- 48 hours post-transplantation (hemorrhagic ferent modified verbal and nominal phrases: abdominal drainages, hemodynamic instabil- (8) When the transplant evolves favorably, the ity, serial determination of the hematocrit/he- patient is awake, hemodynamically stable, moglobin). with spontaneous respiration, preserved re- In the above example, the time label is followed nal function, and with progressively improv- by a summary of medical actions performed dur- ing liver activity. ing this time lapse. Modelling complications then may entail two different time lines: one for occur- 3.2 Time of occurrence: immediate and rence of complications as such (snap and span, no- long-term tions defined in the introduction of this paper), Complications are possible alterations to the de- and one mapping the full (linear or cyclical) sce- sired optimal condition. The most frequent in nario of common medical actions associated with PLTM are complications that can be expected postoperative care. Proceedings of the conference Terminology and Artificial Intelligence 2015 (Granada, Spain) 111 The review article also mentions a shift in the 3.3 Timing of occurrence and diagnosis historical evolution of PLTM complications: as An interesting issue is the fact that even within the surgical techniques and immunosuppressive treat- subgroup of immediate complications, both the ment improve, prognosis and survival chances in- nature of the complication and its treatment de- crease, correspondingly extending the time span pend on the moment of discovery: similar sets of of (late) medical post-surgical follow-up (cfr. (11) symptoms may cause different kinds of pathol- and (12)). ogy. This is the case, for example, for the most (11) The main barriers to overcome in the first pe- frequent complication in pediatric cases: riod were immediate post-surgical survival (18) Symptoms are highly variable and depend on together with prevention of acute rejection. the timing of development and diagnosis. (12) With greater survival of patients, new prob- (19) When the thrombosis occurs at an early lems have arose that basically affect trans- stage, it typically leads to ischemia/necrosis plant recipients with long-term follow up of the graft; in contrast, when it occurs at a Long-term complications are rather flexible con- later time point, it generally leads to biliary ceptual notions. Their emergence is connected complications (intrahepatic biliomas and bil- with the specific complication (such as chronic re- iary stenosis) but with preservation of the nal failure, systemic arterial hypertension, diabe- graft function. tes mellitus, etc.), but at the same time differs This evolutionary, dynamic nature of medical accordingly. Generic time information is com- conditions needs to be taken explicitly into ac- monly expressed as occurring at a random mo- count in concept modelling of complications. In ment (13), or by means of unspecified post- its earlier or later diagnostic establishment, a com- operative time (14). plication takes up different forms and therefore re- (13) […] malignant tumors can appear at any time quires different treatment types. Consequently, in after transplantation […]. the case of thrombosis mentioned in the previous (14) A variable percentage of patients, 4-20% ac- example, the therapy in the acute or late form con- cording to the series, will develop diabetes sists of different medical actions: mellitus following transplantation (de novo (20) In the acute form, thrombolysis can be ac- DM). complished by surgical radiology. Arterial Apart from these general time labels, also differ- thrombectomy may be an alternative that can ent discursive strategies are used for indicating a be done either by interventional radiology or precise moment in time, specifically in late com- surgical intervention. In patients where these plications. Here, different scenarios may occur. In options fail, urgent re-transplantation may be the first one a precise numeric cut-off point after required. In the late form, treatment is mainly transplantation is expressed (not until, not before): focused to prevent/treat biliary complica- (15) Chronic rejection is usually not evident until tions derived from the thrombosis. at least 6 months after transplant. The patho- Note that in the late form, treatment does not genesis is still unclear. zoom in on the primary complication, but on the In the second scenario, the complication is associ- derived one. This example clearly shows that one ated with a risk decreasing in time, without men- complication may trigger another one. The same tioning an endpoint: complication may be connected with or caused by (16) Arterial hypertension (AHT) is a frequent different intentional operations, leading to these complication in liver transplant recipients. Its unintended side effects at different stages in post- prevalence varies between 50-70% in the operative care: first post-transplantation months but de- (21) Biliary fistula can occur initially in the first creases thereafter probably due to the reduc- month in relation to anastomotic dehiscence tion of the immunosuppressive doses. secondary to technical errors or biliary tract In the third scenario, the full span of time is ex- ischemia. It is also a common complication pressed (e.g. a one-year period) during which the in the third month when the T-tube is with- complication is most pronounced: drawn. (17) Obesity is a very frequent complication in A central issue in this dynamic picture is the no- transplanted patients […] one year after tion of lead time to diagnosis: given the fact that transplantation, the period when the greatest complications constantly evolve, this time factor weight gain is seen. Proceedings of the conference Terminology and Artificial Intelligence 2015 (Granada, Spain) 112 contributes to variable medical decisions, taking irreversible way. Hyperacute rejection is humoral, transplantation as a starting point: whereas acute rejection has a cellular origin. This (22) The clinical picture is variable and depends is the primary difference with acute rejection, for on the time of development, lead time to di- which drugs are available. The primary difference agnosis, and existence of a T-tube. with the third subtype is that We finish this part of our investigation with two (26) […] Chronic rejection generally occurs over specific subcases of timing. First, some complica- a span of months, can be unresponsive to cur- tions can occur both early, or emerge only late, rent therapy, and contributes to be a source after a so-called normal postoperative course. The of graft loss. following example refers to liver graft dysfunc- An interesting, yet unsolved issue is the difference tion: between chronic and repeated acute rejection. (23) Dysfunction of the graft may occur in the im- Some studies report that acute rejection generally mediate postoperative period (early dysfunc- occurs in the first few weeks following transplan- tion) or late during the follow-up of the tation, whereas chronic rejection “typically occurs patient {typically related to the recurrence of several months to a year posttransplantation” the original disease (viral hepatitis, primary (Batts, 1999) and requires additional more histo- biliary disease, sclerosing cholangitis, alco- logical fine-tuning by means of liver biopsy. hol or autoimmune liver disease) or chronic Determining correct diagnosis for each of rejection}. these complications is a highly complex issue, be- This later complication’s manifestation has a very cause of the many clinical parameters shared by distinct causal origin: it is overtly tied to the orig- different complications. inal disease, which urged for liver transplantation. Second, different complications (as the neurolog- 3.5 Frequency and prevalence ical states) sometimes occur simultaneously: the Frequency and prevalence are commonly used first complication is continuous (disorientation), terms when describing the epidemiological status and then punctuated by episodes of the second one of a complication (Greenberg et al., 2005, chapter (agitation and confusion). 2). Whereas incidence refers to the number of new (24) The most frequent neurological alterations cases occurring in a given period of time, preva- are disorientation with episodes of agitation lence indicates the actual number of cases alive and confusion. either during a period or at some point in time. A very specific feature of generic late compli- The prevalence can be addressed in different cations such as malignant tumor is the correlation ways: on average and based on variation (either between duration (of immunosuppression) and within the different complications of a subtype or specific cancer subtypes (Kaposi’s sarcoma, skin as a sample within the complication population). tumors, carcinomas of vulva and perineum): The following three examples illustrate this char- (25) Although malignant tumors can appear at acterization in three progressive steps. any time after transplantation, Kaposi’s sar- (27) The prevalence of technical complications is coma followed by lymphoproliferative disor- on average 26%. ders are the earliest that usually develop. The (28) Arterial complications, particularly the later ones are skin tumors and carcinomas of thrombosis of the hepatic artery (prevalence the vulva and perineum. ranging from 1.5 to 25%) are the most fre- quent ones. 3.4 Duration of complication: rejection from (29) Hepatic artery thrombosis is a complication (hyper-) acute to chronic that develops more frequently in the pediatric Some complications occur either early or late. A population. specific case is graft rejection. An interesting time Apart from overall values (27-28) for the popula- distinction in this respect is the one between hy- tion, samples typically address age, such as chil- peracute and acute. There is not only a difference dren (29), specific pre-surgical diseases triggering in terms of time itself (hyperacute rejection occur- grafting (30), and retransplant patients (31): ring within minutes or hours), but also in terms of (30) Portal vein thrombosis is an infrequent com- the complications’ nature. The prefix hyper- re- plication with an overall prevalence of 2-3%. fers as well to the severity of the rejection reaction (31) Globally, 20-40% of liver transplant recipi- and the fact that antibodies reject the graft in an ents present atraumatic bone fractures; this Proceedings of the conference Terminology and Artificial Intelligence 2015 (Granada, Spain) 113 prevalence rises to 65% in patients trans- moment of grafting (38) and stage of drug devel- planted due to cholestatic disease and in re- opment. transplant patients. (37) The natural history of malignant tumors in Typical long-term spans include mention of the transplant patient tends to be different one and five year periods. from that of the normal population; they ap- (32) Currently though, survival rates of over 90- pear at an earlier age, tend to be in a more 95% and 70% at one year and five years post- advanced stage when diagnosed, and their transplantation, respectively are expected. evolution is more aggressive, causing high Prevalence spans reach from 100% to values mortality directly related to the tumor. as close as 1.5%, as in (33) and (28). (38) Some data suggest that in patients undergo- (33) Pleural leakage, predominantly on the right, ing liver transplantation in recent years, there is the most frequent complication with a is a higher incidence of hematological neo- prevalence reported to be as high as 100% in plasms with de novo internal neoplasms de- some series. veloping at earlier time-points than in those Different diagnostic criteria are used to character- transplanted years ago. ize a (chronic) complication. Variable prevalence A relevant measure and objective of PLTM man- is therefore a common measure: agement is the reduction of frequency of compli- (34) The prevalence is variable, depending on the cations to values for the general population, as in criterion used to define it and to the method the case of bacterial infections: used to assess renal function. Indeed, serum (39) After the sixth month, with the transplanted creatinine measurement may underestimate organ functioning normally and minimum the presence of renal failure. immunosuppressive doses, the frequency of Particularly in late complications, an im- bacterial infections is reduced to figures sim- portant comment on the relation between time and ilar to those of the general population and the treatment has to be made: a complication may dis- causes are pathogenic bacteria of the com- play decreasing prevalence over time. As men- munity. tioned before, complications are sometimes Liver transplantation entails serious risks. Preva- caused by immunosuppressive drugs. Since drug lence therefore is not only coined in terms of mor- administration may be decreased over time, this bidity, but also of (decreasing) global mortality. has an impact on its frequency. Conceptually, (40) The global mortality in this early posttrans- there is again a correlation (or even causal rela- plantation period is approximately 5-10%. tion) between treatment method and time, inde- Particularly in retransplantation, mortality rises. pendent of a specific complication, as the two Retransplantation entails two subsequent time se- following examples (concerning hypertension and quences: the management of the first graft, lead- diabetes, respectively) show. ing to an incurable complication (such as graft (35) Arterial hypertension (AHT) is a frequent rejection mentioned before) within the first 48 complication in liver transplant recipients. Its hours following surgery, and a second one, with prevalence varies between 50-70% in the reduced survival prognosis. first post-transplantation months but de- (41) However, if regression of the clinical situa- creases thereafter probably due to the reduc- tion is not observed after 24-48 hours, re- tion of the immunosuppressive doses. transplantation must be considered as soon as (36) A variable percentage of patients, 4-20% ac- possible to avoid the development of multi- cording to the series, will develop diabetes organ failure, in which case the mortality as- mellitus following transplantation (de novo sociated with retransplantation is very high. DM). The prevalence depends on the time elapsed since transplantation and particularly 4 Conclusion on the immunosuppressive drugs. In the ini- tial post-transplantation period, DM is very This paper proposes a first sketch of time factors frequent, probably due to the use of high CNI as an associative relation relevant for modelling and steroid doses. the temporal unfolding of PLTM complications. Typically, measures for prevalence and risk We list the time factors useful for a model of time. may compare patients with complications to the 1. A boundary separates peri-operative care and healthy population (37), taking into account the management of complications. Prophylaxis is Proceedings of the conference Terminology and Artificial Intelligence 2015 (Granada, Spain) 114 a peri-operative issue in avoiding complica- drugs, surgical techniques, are used in order to tions [3.1], and should be integrated in the time prevent, block or reduce what kind of complica- model. tions?). 2. Early complications are tested and detected against normal states. References 3. These complications are temporally decom- Batts, K.P. 1999. Acute and chronic hepatic allograft posed in immediate and late complications rejection: pathology and classification. Liver Trans- [3.2]; complications, however, do not belong plantation and Surgery 5(44 Suppl 1): S21-9. unequivocally to one of these. Clavien, Pierre.-Alain, Carlos A. Camargo, Ruth Crox- 4. Relevant time notions are the cut-off point for ford, Bernard Langer, Gary A. Levy & Paul D. Greig. 2006. Definition and classification of nega- occurrence and tive outcomes in solid organ transplantation. Appli- 5. the time span of (early) complications. cation in liver transplantation. Annals of Surgery 6. A distinction is needed between underlying 220(2): 109-120. pathologies not affected by transplantation Dindo, Daniel, Nicolas Demartines & Pierre-Alain [see section 3.1], and diseases that may affect Clavien. 2004. Classification of Surgical Complica- complications and patient prognosis. tions. A New Proposal with Evaluation in a Cohort 7. There is a variable correlation between the of 6336 Patients and Results of a Survey. Annals of snap/span time (Munn and Smith, 2008) line Surgery 240(2): 205-213 of complication occurrence and associated Grabar, N., Hamon, T., Bodenreider, O. 2012. Ontolo- medical diagnostic and therapeutic actions gies and terminologies: continuum or dichotomy? Applied Ontology 7(4): 375-386. [see section 3.3]. Greenberg, Raymond, S., Stephen R. Daniels, W. Dana 8. Complications take different symptomatic Flanders, John William Eley & John R. Boring III forms causing different pathologies and there- (eds.). 2005. Medical Epidemiology. New York: fore require various diagnostic tools. McGraw-Hill. 9. Lead time to diagnosis is an important time Junttila, K., S. Salantera & M. Hupli. 2005. Develop- dimension in this respect. ing terminology for documenting perioperative 10. A distinction is needed for duration in graft nursing interventions. International Journal of rejection, between a (hyper-) acute and Medical Informatics. 74(6): 461-471. chronic disease status (without treatment op- Khoo, C. & N. Jin-Cheon. 2006. Semantic Relations in tions or not) [see section 3.4]. Information Science. Annual Review of Information 11. Complications involve some measures [3.5] Science and Technology 40: 157–228. Moreno, R. & M. Berenguer. 2006. Post-liver trans- such as prevalence of morbidity and mortal- plantation medical complications. Annals of Hepa- ity. tology 5(2): 77-85. 12. Prevalence may decrease based on the reduc- Munn, Katherine & Barry Smith. 2008. Applied ontol- tion of immunosuppressive drugs in the long ogy. An Introduction. Frankfurt and Paris: Ontos. run. Pareja, E., M. Cortes, R. Navarro, F. Sanjuan, Future work will develop in three directions, R. López & J. Mir. 2010. Vascular complications The two first steps expand the corpus, taking into after orthotopic liver transplantation: hepatic artery account, first the most quoted review articles on thrombosis. Transplantation Proceedings 42: 2970- PLTM complications after 2006 and second, for 2972. specifying such time relations, in specialized re- Roche, Christophe. 2007. Terme et concept: fonde- ments pour une ontoterminologie. Proceedings search articles. The final goal is to transform this TOTh 2007 Terminologie & Ontologie: Théories et descriptive conceptual research into a logical en- Applications. Annecy, 1-22. tity-relation model, which can be useful in the Sambre, Paul & Cornelia Wermuth. 2010. Causal clinical decision-making process. Describing framing for medical instrumentality: applied ontol- such a model is clearly beyond this exploratory ogy and frame-based construction grammar. Bel- paper. Time in PLTM provides the conceptual ba- gian Journal of Linguistics 24: 163–191. sis for modelling subsequent associative relations: causal relations (what is the consequence of which (un)intended aspects of transplantation manage- ment, against which kinds of complications and/or sets of symptoms,?), as well as instrumental rela- tions (what therapeutic tools, such as devices,