Biomedical subjects

Rolf Fimmers

Publications and source records attributed to Rolf Fimmers.

At least 37 records · Page 2Linked to original sources

PubMed2004

[Irritable bowel syndrome: colonoscopy painful and difficult?].

BACKGROUND AND PURPOSE: Hyperalgesia induced by pelvic colon distension has been demonstrated in patients with irritable bowel syndrome (IBS). In this study the authors analyzed whether colonoscopy of patients with IBS is more painful and technically more demanding as compared to non-IBS patients. PATIENTS AND METHODS: In a prospective study 639 patients (132 with IBS, 507 without IBS) who underwent colonoscopy were evaluated for sex, age, body mass index, administration of sedatives and analgesics, time for cecal intubation, intensity of pain during examination (intensity graduated 1-5), diagnosis and degree of diverticulosis, spasticity, loop formation, elongation and distortion, respectively. A statistical comparison of both patient groups was performed. RESULTS: Patients of the IBS group were significantly younger compared with patients in the control group (p < 0.001). In an age-matched comparison of both groups low pain (intensity 1) was noted in 29 (22%) of IBS patients and 82 patients (31%) in the control group. Severe pain (intensity 4 and 5) occurred in 17 (12.9%) and six (4.5%), respectively, of IBS patients and in 21 (8%) and five patients (2%), respectively, of the control group. The differences were statistically not significant (p = 0.1). Administration of analgesics occurred significantly more frequently in the IBS group (p = 0.01), however, only nine IBS patients (6.8%) and four patients without IBS (1.5%) received analgesics. All other parameters analyzed did not show significant differences between the groups. CONCLUSION: Regarding perception of procedure-related pain and technical problems in colonoscopy, patients with IBS do not show significant differences compared to patients without IBS.

Adult↗

PubMed2004

Norepinephrine transporter (NET) promoter and 5'-UTR polymorphisms: association analysis in panic disorder.

Several biochemical and pharmacological studies suggest that the catecholaminergic system involving the norepinephrine transporter (NET) is relevant for the pathogenesis of panic disorder. Three single nucleotide polymorphisms in the promoter or untranslated 5' region of the NET gene were investigated by means of RFLP analysis in a sample of 115 German patients with panic disorder and 115 matched controls. Statistical analysis failed to show association with the overall diagnosis of panic disorder. In the subgroup of patients with panic disorder without agoraphobia, however, two polymorphisms were found to be associated with the disease (G/C (rs2397771): p < 0.05; T/C (rs2242446): p < 0.01). While our data do not support a major function of the NET gene in the development of panic disorder, it may play a role in the subgroup of panic disorder without agoraphobia.

5' Untranslated Regions↗

PubMed2004

Supratentorial gangliogliomas: histopathologic grading and tumor recurrence in 184 patients with a median follow-up of 8 years.

BACKGROUND: Supratentorial gangliogliomas (GGs) are rare tumors of the central nervous system and are commonly associated with chronic seizures. To date, only case reports and small series of patients with short-term follow-up have been available for the assessment of the potential of GGs to recur and progress. METHODS: Data from 184 patients who underwent resection of GGs between 1988 and 2001 were available from the University of Bonn Epilepsy Surgery Center (Bonn, Germany). Analysis of factors that influenced tumor recurrence and patient survival, such as preoperative history, age at operation, tumor location, histopathologic findings (including immunohistochemical findings), extent of tumor resection, and recurrence evaluated on postoperative magnetic resonance imaging (MRI), was performed. RESULTS: The median follow-up period was 8 years (range, 1-14 years). One hundred seventy-eight patients (97%) presented with long-term seizures (> or = 2 years). The median age at surgery was 26 years (range, 2-65 years). Tumor location was temporal in 79% of patients and frontal in 12% of patients. Eleven tumors (6%) were classified as World Health Organization (WHO) Grade 2 lesions, and 2 tumors were classified as anaplastic WHO Grade 3 lesions. For 38 patients (21%), postoperative MRIs revealed residual tumors. Two years after surgery, 5 patients (3%) experienced tumor recurrence, which resulted in malignant progression in 3 patients (2%) and death in 2 patients (1%). Eighty-four percent of patients with epilepsy had complete and sustained seizure relief. The calculated 7.5-year recurrence-free survival rate was 97%. Lower rates of recurrence were found in patients with tumors classified as WHO Grade 1 lesions (P < 0.0001), patients with temporal lesions (P < 0.0001), patients who underwent complete tumor resection (P = 0.0278), and patients with long-standing epilepsy (P < 0.0001). CONCLUSIONS: Supratentorial GGs are benign tumors, and the surgical goal for patients with GG should be complete resection. Residual tumor masses, frontal tumor location, and WHO Grade 2 or 3 lesions are associated with a greater risk of recurrence or malignant progression. Patients with such characteristics should be considered for long-term clinical follow-up using MRI. .

Adolescent↗

PubMed2004

Association of the functional V158M catechol-O-methyl-transferase polymorphism with panic disorder in women.

Panic disorder is an anxiety disorder with an estimated heritability of up to 48%. Pharmacological and genetic studies suggest that genes coding for proteins involved in the catecholaminergic system might be relevant for the pathogenesis of the disease. In the present study, we genotyped a single nucleotide polymorphism (472G/A=V158M) in the coding region of the catechol-O-methyl-transferase (COMT) gene in 115 patients with panic disorder and age- and sex-matched controls. Association analysis revealed a significant excess of the more active COMT allele (472G=V158) in patients with panic disorder (p=0.04), particularly in female patients (p=0.01), but not in male patients (p=1.0). The assessment of a possible interaction of the COMT polymorphism with a previously reported functional 30-bp VNTR in the monoamine oxidase A promoter (MAOALPR) in female patients did not yield significant results. Our data support a role of the 472G/A (V158M) COMT polymorphism or a nearby locus in the pathogenesis of panic disorder in women.

Adult↗

PubMed2004

Association of a functional 1019C>G 5-HT1A receptor gene polymorphism with panic disorder with agoraphobia.

Panic disorder is a common anxiety disorder which frequently co-occurs with agoraphobia. A functional promoter polymorphism in the serotonin receptor 1A (5-HT1A) gene has been found to be associated with major depression as well as anxiety- and depression-related personality traits. We investigated a possible association between this 5-HT1A gene promoter polymorphism and panic disorder by genotyping the 1019C>G single nucleotide polymorphism in 134 panic-disorder patients with and without agoraphobia and matched 134 controls. In our sample no significant evidence of allelic association in the combined panic-disorder group was found. However, our results show a significant association with the G allele in patients with panic disorder with agoraphobia (p=0.03, n=101). In conclusion, our findings do not support a major contribution of this polymorphism to the pathogenesis of panic disorder, but provide evidence for a possible role in the subgroup with agoraphobia.

Adult↗

PubMed2004

Ethnic differences in the association of factor V Leiden mutation and the C677T methylenetetrahydrofolate reductase gene polymorphism with preeclampsia.

OBJECTIVE: This case-control study evaluates the association of the factor V Leiden mutation with preeclampsia and potential synergistic effects of the MTHFR-677T and factor V Leiden mutations with regard to disease risk in two different ethnic populations. STUDY DESIGN: 198 women and their 143 newborns from Germany/Croatia and Indonesia with normal pregnancy or preeclampsia participated in the study. The factor V Leiden mutation was determined by direct sequencing and the MTHFR genotype by a PCR-based RFLP method. RESULTS: The factor V Leiden mutation is rare in Indonesians. In Germans/Croatians, the frequency of the mutation was significantly increased in mothers with preeclampsia compared to controls. No disease association was found for combined factor V Leiden/MTHFR-677T genotypes on the maternal and fetal level. CONCLUSIONS: Our results underline the need for a clear distinction of ethnicity in association studies of functional gene polymorphisms. They further support the concept of preeclampsia as a complex disease with variable contributions of disease genes in different ethnic groups.

Asian People↗

PubMed2004

Prediction of necrosis after chemotherapy of advanced germ cell tumors: results of a prospective multicenter trial of the German Testicular Cancer Study Group.

PURPOSE: We evaluated the prognostic parameters of necrotic residual tumors after chemotherapy of advanced germ cell tumors to improve on the current indications for surgery. MATERIALS AND METHODS: Between January 1996 and January 2000, in 8 centers of the German Testicular Cancer Study Group, preoperative parameters were assessed to predict necrosis in the residual tumors of 261 patients with retroperitoneal residual tumor resection after first (92%) and second line (8%) chemotherapy. RESULTS: Of 232 evaluable patients 39 had pure seminoma and 5 had viable cancer (1 with seminoma) in the residual tumor. Of the remaining 193 patients with nonseminoma 35% had necrosis, 34% teratoma and 31% had viable carcinoma in the residual tumor. After multivariate analysis and exclusion of patients with seminoma, the 3 parameters independently predictive of necrosis were alpha-fetoprotein before chemotherapy less than 20 ng/ml, and tumor volume before and after chemotherapy. A mathematical model to predict necrosis yielded a test accuracy of 75%, a sensitivity to predict necrosis of 52% and a specificity of 87%. CONCLUSIONS: Patients with pure seminoma should not undergo residual tumor resection because 97% of patients who received adequate chemotherapy were found to have no residual seminoma. In cases of nonseminoma alpha-fetoprotein values before chemotherapy less than 20 ng/ml and a high percentage of shrinkage during chemotherapy reliably predicted only 19% of cases of necrosis. Therefore, this model is clinically irrelevant and patients with minimal residual disease should undergo surgery. New methods are necessary to improve the preoperative selection of patients after chemotherapy.

Germinoma↗

PubMed2004

Oligodendroglial tumors: refinement of candidate regions on chromosome arm 1p and correlation of 1p/19q status with survival.

Loss of heterozygosity (LOH) on the chromosome arms 1p and 19q is frequent in oligodendroglial tumors and has been correlated with chemosensitivity and good prognosis in anaplastic oligodendrogliomas. The oligodendroglioma-associated tumor suppressor genes on 1p and 19q are as yet unknown. To narrow down candidate regions on 1p, we investigated oligodendroglial tumors from 89 patients for LOH at up to 30 polymorphic loci on 1p. In addition, all tumors were studied for LOH at 7 loci on 19q. Combined LOH on 1p and 19q was detected in 20 (83%) of 24 oligodendrogliomas, 15(63%) of 24 anaplastic oligodendrogliomas, 10 (56%) of 18 oligoastrocytomas, and 12 (52%) of 23 anaplastic oligoastrocytomas. Five tumors demonstrated partial deletions on 1p, which allowed to define 3 distinct candidate regions at 1p36.31-pter distal to D1S2633, 1p36.22-p36.31 between D1S489 and D1S2642, and 1p34.2-p36.1 between D1S2743 and D1S482, respectively. No partial deletions were detected on 19q. Combined LOH on 1p and 19q was associated with prolonged time to progression (TTP), longer overall survival (OS), and a higher 5-year survival rate. Depending on the presence or absence of combined LOH on 1p and 19q, patients with anaplastic oligodendroglial tumors treated with adjuvant radio- and/or chemotherapy showed a median TTP of 86 months versus 39 months, a median OS of 91 months versus 46 months, and a 5-year survival rate of 80% versus 36%, respectively. Similarly, LOH on 1p and 19q was associated with longer survival in patients with low-grade oligodendroglial tumors (TTP: 57 months versus 47 months; OS: 172 months versus 105 months; 5-year survival rate: 92% versus 70%). Thus, our results refine the location of putative oligodendroglioma suppressor genes on 1p and support the significance of LOH on 1p and 19q as a favorable prognostic marker.

Adolescent↗

PubMed2003

Primary central nervous system lymphoma: results of a pilot and phase II study of systemic and intraventricular chemotherapy with deferred radiotherapy.

PURPOSE: To evaluate response rate, response duration, overall survival (OS), and toxicity in primary CNS lymphoma (PCNSL) after systemic and intraventricular chemotherapy with deferred radiotherapy. PATIENTS AND METHODS: From September 1995 to July 2001, 65 consecutive patients with PCNSL (median age, 62 years) were enrolled onto a pilot and phase II study evaluating chemotherapy without radiotherapy. A high-dose methotrexate (MTX; cycles 1, 2, 4, and 5) and cytarabine (ARA-C; cycles 3 and 6)-based systemic therapy (including dexamethasone, vinca-alkaloids, ifosfamide, and cyclophosphamide) was combined with intraventricular MTX, prednisolone, and ARA-C. RESULTS: Sixty-one of 65 patients were assessable for response. Of these, 37 patients (61%) achieved complete response, six (10%) achieved partial response, and 12 (19%) progressed under therapy. Six (9%) of 65 patients died because of treatment-related complications. Follow-up is 0 to 87 months (median, 26 months). The Kaplan-Meier estimates for median time to treatment failure (TTF) and median OS were 21 months and 50 months, respectively. For patients older than 60 years, median survival was 34 months, and the median TTF was 15 months. In patients younger than 61 years, median survival and median TTF have not been reached yet; the 5-year survival fraction is 75%. Systemic toxicity was mainly hematologic. Ommaya reservoir infection occurred in 12 patients (19%), and permanent cognitive dysfunction possibly as a result of treatment occurred in only two patients (3%). CONCLUSION: Primary chemotherapy based on high-dose MTX and ARA-C is highly efficient in PCNSL. Response rate and response duration in this series are comparable to the response rates and durations reported after combined radiotherapy and chemotherapy. Neurotoxicity was infrequent.

Adult↗

PubMed2003

Mitochondrial DNA control region diversity in hairs and body fluids of monozygotic triplets.

Length heteroplasmy of the homopolymeric cytosine stretch in the hypervariable region II of the mitochondrial D-loop was investigated in blood, buccal cells and hair shafts of monozygotic triplets. The proportions of length heteroplasmy were determined by cloning and sequencing of multiple independent clones. Blood and buccal cells showed an accumulation of molecules with one and two insertions of cytosine residues in relation to the Cambridge Reference Sequence (CRS). The results did not show statistically significant differences between blood and buccal cells of one and the same individual and also not between the three monozygotic brothers. In the hair samples a loss of cytosine residues was established in all three monozygotic individuals compared to blood and buccal cells, suggesting that this must be a regular process. Furthermore, the hair shaft samples showed significant differences between the frequencies of 7, 8 or 9 Cs in the poly C region comparing the three individuals (p<0.008) and in addition there were highly significant differences (p<0.0001) when comparing the results for six different hairs of each individual separately. From these results it can be assumed that besides a common genetic bottleneck during embryonic development, a post-embryonic bottleneck seems to exist in each hair follicle.

Adult↗

PubMed2003

Repeated bone-targeted therapy for hormone-refractory prostate carcinoma: tandomized phase II trial with the new, high-energy radiopharmaceutical rhenium-188 hydroxyethylidenediphosphonate.

PURPOSE: We investigated the effect of repeated bone-targeted therapy with rhenium-188 hydroxyethylidenediphosphonate (HEDP) in patients with progressive, hormone-resistant prostate carcinoma and bone pain. The aim of this study was to determine the pain palliation and the antitumor effect of rhenium-188 HEDP treatments. PATIENTS AND METHODS: Sixty-four patients were randomly assigned to one of two groups for radionuclide therapy with rhenium-188 HEDP; patients of group A received a single injection, patients of group B received two injections (interval, 8 weeks). After therapy, patients were followed-up by assessment of pain palliation and clinical outcome until death. RESULTS: In both groups, toxicity was low, with moderate thrombopenia and leukopenia (maximum common toxicity criteria grade of 2). The effectiveness of rhenium-188 HEDP for pain palliation was better in the repeated treatment group (group B), with a response rate and time of response of 92% and 5.66 months, respectively (P =.006 and P =.001). In group B, 11 (39%) of 28 patients had a prostate-specific antigen decrease of more than 50% for at least 8 weeks, compared with two (7%) of 30 patients in the single-injection group (group A). The median times to progression of group A and group B were 2.3 months (range, 0 to 12.2 months) and 7.0 months (range, 0 to 24.1 months), respectively (P =.0013), and the median overall survival times were 7.0 months (range, 1.3 to 36.7 months) and 12.7 months (range, 4.1 to 32.2 months), respectively (P =.043). CONCLUSION: Compared with single-injection therapy, repeated bone-targeted therapy with rhenium-188 HEDP administered to patients with advanced progressive hormone-refractory prostate carcinoma enhanced pain palliation and improved progression-free and overall survival. Larger studies are justified to further evaluate the use of rhenium-188 HEDP.

Aged↗

PubMed2003

Risk factors for relapse in clinical stage I nonseminomatous testicular germ cell tumors: results of the German Testicular Cancer Study Group Trial.

PURPOSE: To prospectively assess potential risk factors for relapse in clinical stage I nonseminomatous germ cell tumors of the testis (CS I NSGCT). PATIENTS AND METHODS: From September 1996 to May 2002, 200 patients with CS I NSGCT were prospectively assigned to retroperitoneal lymph node dissection (RPLND), and risk factor assessment was performed within a multicenter protocol. One hundred sixty-five patients had an adequate minimum follow-up of 12 months (mean, 34.5 months) or had pathologic stage II. RESULTS: Pathologic stage II disease was found in 27.9% of patients. Only 0.6% of patients relapsed in the retroperitoneum after confirmation of pathologic stage I disease. With reference pathology, vascular invasion (VI) was most predictive of stage in multifactorial analysis (accuracy, 65.1%). However, the positive predictive value (PPV) of VI to predict patients who have metastatic disease or relapse during follow-up was only 52.7%. With absent VI, low-risk patients had a negative predictive value (NPV) of 76.9%. With a combination of several risk factors, the PPV increased to 63.6% and the negative predictive value increased to 86.5%. CONCLUSION: Even with an optimal combination of prognostic factors and reference pathology, more than one third of patients predicted to have pathologic stage II or relapse during follow-up will not harbor metastatic disease and, therefore, would be overtreated with adjuvant therapy. However, patients at low risk may be predicted at an 86.5% level, and thus, surveillance in highly compliant patients would be a valuable option. For high-risk patients, further reduction of adjuvant treatment is necessary.

Adult↗

PubMed2003

Silent and apparent cerebral embolism after retrograde catheterisation of the aortic valve in valvular stenosis: a prospective, randomised study.

BACKGROUND: In most patients, severity of valvular aortic stenosis can be accurately assessed non-invasively by echocardiography. However, retrograde catheterisation of the aortic valve is often undertaken. This procedure has a potential risk of neurological complications, with an unknown incidence of clinically silent embolism. We aimed to establish the frequency of clinically apparent and silent cerebral embolism after this procedure. METHODS: We prospectively randomised 152 consecutive patients with valvular aortic stenosis at a German university hospital to receive either cardiac catheterisation with (n=101) or without (n=51) passage through the aortic valve. Patients underwent cranial MRI and neurological assessment within 48 h before and after the procedure to assess cerebral embolism. Controls were 32 patients without valvular aortic stenosis who underwent coronary angiography and laevocardiography. FINDINGS: 22 of 101 patients (22%) who underwent retrograde catheterisation of the aortic valve had focal diffusion-imaging abnormalities in a pattern consistent with acute cerebral embolic events after the procedure; three of these patients (3%) had clinically apparent neurological deficits. By contrast, none of the patients without passage of the valve, or any of the controls, had evidence of cerebral embolism as assessed by MRI. INTERPRETATION: Patients with valvular aortic stenosis who undergo retrograde catheterisation of the aortic valve have a substantial risk of clinically apparent cerebral embolism, and frequently have silent ischaemic brain lesions. Patients should be informed about these risks, and this procedure should be used only in patients with unclear echocardiographical findings when additional information is necessary for clinical management.

Aortic Valve↗

PubMed2003

Transit time flow measurement in on-pump and off-pump coronary artery surgery.

OBJECTIVE: Transit time flow measurement is frequently used during coronary artery bypass with and without cardiopulmonary bypass to detect graft dysfunction resulting from technical errors. METHODS: Intraoperative transit time flow measurement measurements of 896 patients requiring surgery for double- or triple-vessel disease were reviewed retrospectively. Six-hundred and ninety-five patients were operated on-pump (Group A: coronary artery bypass with cardiopulmonary bypass), and 201 patients off-pump (Group B: coronary artery bypass without cardiopulmonary bypass). Transit time flow measurement measurements were analyzed for mean flow (mL/min). In total, measurements of 2247 grafts were analyzed. RESULTS: Transit time flow measurement flows were lower in coronary artery bypass without cardiopulmonary bypass patients (left internal thoracic artery to left anterior descending artery: Group A, 37 [31, 40] mL/min vs Group B, 24 [20, 26] mL/min; saphenous vein graft to left anterior descending artery: Group A, 46.5 [40, 56] mL/min vs Group B, 21 [14, 57] mL/min. Troponin I release was reduced in the coronary artery bypass without cardiopulmonary bypass patients, with median values of 7.8 [7.0, 8.3] microg/L in Group A and 1.2 [0.9, 2.3] microg/L in Group B. CONCLUSION: Evaluation of transit time flow measurement is valuable in determining coronary graft patency after coronary artery bypass with cardiopulmonary bypass and coronary artery bypass without cardiopulmonary bypass. Decreased troponin I release suggests a myocardial benefit of coronary artery bypass without cardiopulmonary bypass compared to coronary artery bypass with cardiopulmonary bypass, although the intraoperative transit time flow measurement flow measurements are markedly lower.

Aged↗

PubMed2003

The spectrum of long-term epilepsy-associated tumors: long-term seizure and tumor outcome and neurosurgical aspects.

PURPOSE: To describe the histologic spectrum and clinical characteristics of patients with neuroepithelial tumors and drug-resistant epilepsy and to analyze clinical data and treatment related to seizure outcome and survival. METHODS: Data were analyzed from 207 consecutive patients with intractable epilepsy (aged 2-54 years), who between 1988 and 1999 had >or=50% resection of supratentorial, neuroepithelial tumors. Extent of resection was assessed on postoperative magnetic resonance imaging (MRI); seizure outcome was classified according to Engel's outcome scale; and follow-up data were prospectively updated. RESULTS: Median follow-up was eight years (range, 2-14 years). Histologic examination revealed 154 classic epilepsy-associated tumors (ganglioglioma, dysembryoplastic neuroepithelial tumor, pleomorphic xanthoastrocytoma, and pilocytic astrocytomas) and 53 others (astrocytomas and oligodendrogliomas). Four World Health Organization (WHO) grade III tumors were found (astrocytoma, n = 3; ganglioglioma, n = 1). After surgery, 82% of the patients were seizure free (class I). The following factors were associated with improved seizure outcome: Short duration of epilepsy before surgery, single EEG focus, absence of additional hippocampal sclerosis or cortical dysplasia, transsylvian approach, other than astrocytomas, and complete tumor resection. After 5 years, only nine (4%) patients had tumor recurrence, four (2%) with malignant transformation and death. None of the four patients with anaplastic tumors died. Even patients with astrocytomas of WHO grade II or III showed 10-year recurrence of only 25% and 10-year survival of 90%. CONCLUSIONS: Tumors associated with long-term epilepsy should be removed early for two different reasons: high rate of seizure freedom and rare but potential risk of malignant tumor progression. The unexpected long survival of these astrocytomas should be investigated by using immunohistochemistry and molecular biology.

Adolescent↗

PubMed2003

An independent evaluation of modern prognostic scores in a central European cohort of 120 patients with hepatocellular carcinoma.

BACKGROUND AND OBJECTIVES: Hepatocellular carcinoma (HCC) is a common cancer worldwide. As prognosis of HCC patients depends not only on tumour extension but also on liver function, TNM staging of HCC is of limited value. The Okuda score incorporating the variables of liver function and tumour extension is used widely. However, among patients with an intermediate Okuda score, survival varies considerably. Several newer scores promise to perform better than the Okuda score in stratifying HCC patients. We therefore tested the ability of several newer scores to predict survival in comparison to the Okuda score in a European cohort of HCC patients. PATIENTS AND METHODS: A total of 120 patients with sufficient follow-up data were identified retrospectively among the 130 patients with HCC first seen between 1997 and 2000 in our department. Child-Pugh score, Okuda score, Vienna survival model for HCC (VISUM-HCC) score, Chevret score, Barcelona clinic liver cancer (BCLC) classification and cancer of the liver Italian programme (CLIP) score were calculated. Survival analysis was performed for all eligible patients stratified according to each scoring system. Receiver operating characteristics analysis was performed using six months survival as the outcome measure. Univariate and stepwise logistic regression analyses were performed to identify prognostic factors. RESULTS: Survival times of HCC patients grouped according to all scores were significantly different. All scores performed similarly to the Okuda score in the receiver operating characteristic analysis. Prognostic factors for survival were albumin concentration and the presence of portal obstruction. CONCLUSION: In our central European cohort, there was no advantage of using the newer scores instead of the Okuda score.

Adult↗

PubMed2003

Comparison of MELD, Child-Pugh, and Emory model for the prediction of survival in patients undergoing transjugular intrahepatic portosystemic shunting.

OBJECTIVES: Recently, new prognostic models (Model for End-Stage Liver Disease [MELD model] and Emory score) were proposed for the prediction of survival in transjugular intrahepatic portosystemic shunt (TIPS) patients. Although the MELD model is considered to be superior and has consecutively been applied to priority listing for liver transplantation, these models have never been directly compared in terms of long-term prognosis. We therefore compared the prognostic accuracy of the different models, including the Child-Pugh score, in an unselected cohort of TIPS patients followed long-term. METHODS: Baseline risk scores for 162 unselected consecutive TIPS patients followed until death (n = 81), liver transplantation, or end of observation (n = 81) (mean follow-up 30.7 +/- 26.4 months) were calculated, and respective concordance- (c-)statistics for the predictive accuracy of 3-, 12-, and 36-month survival for the three models were compared statistically. RESULTS: All three models predicted short-term (3-month) survival with similar accuracy. The MELD model generated the best c-statistics for both 12-month (c-statistic 0.73, 95% CI = 0.64-0.82) and 36-month survival (c-statistic 0.74, 95% CI = 0.64-0.84). The predictive accuracy of the Emory score was significantly lower (c-statistic for 12-month survival: 0.60, 95% CI = 0.52-0.68, p = 0.012 vs MELD). In the statistical comparison of the MELD and the Child-Pugh model, only a trend favoring MELD for the prediction of 1-yr survival in patients with intestinal bleeding could be observed (MELD: c-statistic 0.78, 95% CI = 0.67-0.89; Child-Pugh: c-statistic 0.67, 95% CI = 0.55-0.80, p = 0.059). CONCLUSIONS: The MELD model is superior to the Emory score but only slightly superior to the Child-Pugh classification for the prediction of long-term survival in TIPS patients.

Evaluation Studies as Topic↗

PubMed2003

How to model a complex trait. 1. General considerations and suggestions.

Usually, when complex traits are at issue, not only are the loci of the responsible genes a priori unknown; the same also holds for the mode of inheritance of the trait, and sometimes even for the phenotype definition. The term mode of inheritance relates to both the genetic mechanism, i.e., the number of loci implicated in the etiology of the disease, and the genotype-phenotype relation, which describes the influence of these loci on the trait. Having an idea of the genetic model can crucially facilitate the mapping process. This holds especially in the context of linkage analysis, where an appropriate parametric model or a suitable nonparametric allele sharing statistic may accordingly be selected. Here, we review the difficulties with parametric and nonparametric linkage analysis when applied to multifactorial diseases. We address the question why it is necessary to adequately model a genetically complex trait in a linkage study, and elucidate the steps to do so. Furthermore, we discuss the value of including unaffected individuals into the analysis, as well as of looking at larger pedigrees, both with parametric and nonparametric methods. Our considerations and suggestions aim at guiding researchers to genotyping individuals at a trait locus as accurately as possible.

Chromosome Mapping↗