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Plasma levels of TNF-alpha and IL-6 are inversely related to cytochrome P450-dependent drug metabolism in patients with congestive heart failure.

BACKGROUND: Cytochrome P450 (CYP) enzymes are important mediators of drug metabolism, and activity of these enzymes is a major determinant of the duration and intensity of drug effect. Circulating plasma concentrations of pro-inflammatory cytokines (e.g., tumor necrosis factor [TNF]-alpha and interleukin [IL]-6) are elevated in patients with heart failure and these cytokines have been shown to down-regulate CYP enzyme activity. The purpose of this study was to evaluate the relationship between plasma cytokine concentrations and CYP enzyme activities in patients with heart failure. METHODS AND RESULTS: Sixteen patients with congestive heart failure (New York Heart Association classes II-IV) received a metabolic probe cocktail consisting of caffeine, mephenytoin, dextromethorphan, and chlorzoxazone to assess the activities of the CYP enzymes 1A2, 2C19, 2D6, and 2E1. Blood and urine samples were collected for drug and metabolite determinations by high-performance liquid chromatography (HPLC); cytokine concentrations were measured by enzyme-linked immunosorbent assay (ELISA). We found a striking inverse relationship between both TNF-alpha and IL-6 plasma concentrations and the activity of CYP2C19; metabolism of caffeine (CYP1A2) also had a negative association with IL-6 plasma concentrations. CONCLUSIONS: Cytokine-mediated decreases in drug metabolism may contribute to observed variability in drug response and augment the risk of adverse drug effects in CHF patients.

Adult↗

Serum amyloid A and transferrin in chicken. A preliminary investigation of using acute-phase variables to assess diseases in chickens.

The concentrations of serum amyloid A protein (SAA) and transferrin in blood samples from broilers in various stages of natural Staphylococcus aureus infection, from healthy counterparts, and from turpentine- or saline-injected pullets were measured using sodium dodecyl sulphate polyacrylamide gel electrophoresis (SDS-PAGE), immunoblotting, and densitometry. SAA was not detected in healthy chickens but was detected in turpentine-injected pullets and in S. aureus-infected broilers. Relative percentages of transferrin in turpentine- and saline-injected pullets were not different. Broilers with a S. aureus infection had a two-fold higher transferrin level than did their unaffected counterparts. There was also a difference between the transferrin levels of healthy broilers and healthy pullets, which indicates that other variables, such as breed or breeding conditions, may influence the transferrin level. This preliminary study showed that SAA is an acute-phase protein and a more reliable variable for diagnosing lesions in chickens than transferrin.

Animals↗

Mucin-secreting cellular ependymoma: a light and electron microscopy study.

Mucin accumulation in ependymomas is thought to be limited to the myxopapillary variant and represents an important diagnostic feature. Similarly, signet-ring cells in ependymomas have been shown by electron microscopy to represent microrosette instead of mucin secretion. This study describes an infratentorial ependymoma largely composed of mucinous areas and signet-ring cells. The ependymal nature of mucin-secreting cells was confirmed by ultrastructural analysis. This case widens the variable spectrum of ependymal morphology. The value of electron microscopy in differentiating central nervous system neoplasms showing mucous secretion is stressed.

Biomarkers, Tumor↗

Urinary biochemical markers of dietary intake in the INTERSALT study.

The INTERSALT Study, an international, collaborative, cross-sectional investigation of the relation between blood pressure and dietary and other factors, used quality-controlled, standardized procedures and assessment of multiple possible confounding factors to study 10,079 men and women in 52 population-based samples in 32 countries. In this study 24-h urinary excretion data were used as biochemical markers of intakes of sodium, potassium, and protein, with repeat examinations done in a randomly selected 8% of participants to asses reliability and correct for regression-dilution bias. INTERSALT showed that high salt intake, low potassium intake, excess alcohol consumption, and energy imbalance resulting in overweight are critically involved in the origins of the high blood pressure prevalent among a majority of adult populations. The findings also show that obtaining accurate estimates of associations between dietary intake and blood pressure requires large population-based samples, high-quality dietary information, control for multiple confounding variables, and modern multivariate methods of data analyses, including correction of observed associations for within-person variation in intake.

Adult↗

Immunoglobulins and complement factor C4 in adult rhinosinusitis.

We assessed whether complement and its factor C4 or abnormal immunoglobulin levels are associated with chronic or recurrent rhinosinusitis. We used multiple patient and control groups to obtain clinically meaningful data. Adult chronic or recurrent rhinosinusitis and acute purulent rhinosinusitis patients were compared with unselected adults and controls without previous rhinosinusitis. Associated clinical factors were reviewed. Levels of immunoglobulins, plasma C3, C4 and classical pathway haemolytic activity were analysed. C4 immunophenotyping was used to detect C4A and C4B deficiencies as null alleles. Complement was up-regulated in rhinosinusitis. C4A nulls and low IgA, IgG, IgG1, IgG2, IgG3 and IgG4 levels were all more common in chronic or recurrent rhinosinusitis patients than in unselected and healthy controls. We searched for relevant differences between the patient groups. According to stepwise logistic regression analysis, nasal polyposis [odds ratio (OR) 10.64, 95% confidence interval (CI) 2.5-45.7, P = 0.001], bronchial asthma (OR 8.87, 95% CI 2.3-34.9, P = 0.002), C4A null alleles (OR 5.84, 95% CI 1.4-24.9, P = 0.017) and low levels of IgG4 together with either IgG1 or IgG2 (OR 15.25, 95% CI 1.4-166.8, P = 0.026) were more common in chronic or recurrent rhinosinusitis than in acute rhinosinusitis patients. Isolated low IgG subclasses had limited value in patient assessment. C4A null alleles are associated with chronic or recurrent rhinosinusitis, potentially through their effect on immune defence and inflammation control. Multiple clinical and immunological parameters may need to be evaluated when searching for prognostic variables.

Adult↗

Prognostic comparative study of S-phase fraction and Ki-67 index in breast carcinoma.

AIMS: To investigate the prognostic value of recently proposed flow cytometric S-phase fraction (SPF) variables (average SPF and SPF tertiles) compared with conventional SPF, and to compare the one with the best predictive value with the immunohistochemical Ki-67 index in breast carcinoma. METHODS: A short term follow up study (median, 39.6 months) of a large series of patients (n = 306) was conducted. DNA ploidy was analysed on fresh/frozen tumour samples by flow cytometry, and the SPF was calculated from the DNA histogram using an algorithm. The Ki-67 index was assessed on paraffin wax embedded material by immunohistochemistry (cut off point, 10%). The two methods were compared by means of kappa statistics, and the prognostic significance of both in relation to disease free survival (DFS) and overall survival (OS) was determined. RESULTS: SPF and Ki-67 analysis was performed on 234 (76.5%) and 295 (96.4%) tumours, respectively. The two assessments were simultaneously available in 230 cases. All SPF variables analysed in the whole series significantly correlated with disease evolution, with the conventional median SPF (cut off point, 6.1%) showing the highest predictive value in relation to both DFS (p = 0.0001) and OS (p = 0.0003). SPF tertiles and median SPF evaluated according to DNA ploidy status had no prognostic significance. The Ki-67 index showed a trend in relation to DFS (p = 0.086) that did not reach significance, and no correlation with OS was found (p = 0.264). The comparative analysis of SPF and Ki-67 revealed some agreement between the two methods (agreement, 69.13%; kappa statistic, 0.3844; p < 0.001), especially in the subgroup of diploid tumours. CONCLUSIONS: Flow cytometric SPF is a better prognosticator than the Ki-67 index, but only SPF variables applied in the whole series show potential clinical usefulness.

Adult↗

Cytologic diagnosis of anaplastic large cell lymphoma.

OBJECTIVE: To identify characteristic cytomorphologic and immunocytochemical features of anaplastic large cell lymphoma (ALCL). STUDY DESIGN: We reviewed all positive cytology cases from patients with histologically confirmed ALCL at the National Institutes of Health/National Cancer Institute for patient demographics, cytologic appearance and, when available, immunocytochemical staining pattern with markers for CD30, CD3, L26, CD15, leukocyte common antigen and epithelial membrane antigen (EMA). RESULTS: Twenty-one cases were reviewed from seven patients (four males and three females) aged 2-83 years; 2 were human immunodeficiency virus positive. Specimens included exfoliative (cerebrospinal fluid, pleural fluid) and aspirated material (lymph node, lung, soft tissue). Commonly noted morphologic features included a smear pattern of largely dispersed cells with focal aggregates; variability in cell size with smaller and larger multinucleated giant forms (average cell size 42 microm); eccentric, round to oval nuclei; prominent nucleoli; a "ropy" chromatin pattern; and deeply basophilic, variably vacuolated cytoplasm. Necrosis was frequent. A proteinaceous background was prominent in cellular samples. Lymphoglandular bodies and lymphoid tangles were not prominent. Of cases evaluated immunocytochemically, 100% were positive for CD30, and 75% showed EMA positivity. Expression of other markers was variable. CONCLUSION: ALCL has a distinct cytomorphologic appearance and immunocytochemical staining pattern such that a reliable diagnosis can be made on cytologic material.

Adult↗

Time domain heart rate variability analysis in patients with thalassaemia major.

OBJECTIVE: Cardiac complication is one of the major causes of death in patients with thalassaemia major. Heart rate variability is a non-invasive index of neuronal modulation of heart rate. In this study, autonomic functions of the heart in a preclinical stage of heart disease were evaluated in 48 thalassaemic patients with time domain heart rate variability analysis; the control group consisted of 45 healthy subjects. METHODS AND RESULTS: Mean RR time in the study and control group was 0.73 +/- 0.1, and 0.82 +/- 0.1 ms respectively (p < 0.001). In the study group; SDNN, SDNN-i, SDANN-i, RMSSD, and PNN50 were found to be 167.4 +/- 86.2 ms, 153.9 +/- 108.1 ms, 111.4 +/- 60.4 ms, 108.9 +/- 86.7 ms, and 14.5 +/- 13.4%, respectively. Time domain parameters were significantly lower in the study group than the control group (p < 0.00 1). There was a significant positive correlation between the mean RR time and SDNN, SDNN-i, SDANN-i, RMSSD, and PNN50 (for the RMSSD p < 0.05, r = 0.31; for the others p = 0.000, and r values were 0.65, 0.65, 0.38, 0.37 for the SDNN, SDNN-i, SDANN-i, and PNN50, respectively). CONCLUSION: The analysis of heart rate variability might be helpful to detect cardiac complications in the preclinical stage of the cardiac involvement.

Adolescent↗

Psychiatric disorder and metabolic control among youths with IDDM. A longitudinal study.

OBJECTIVE: To investigate the longitudinal relationship between psychiatric diagnostic variables and metabolic control among youths with IDDM. RESEARCH DESIGN AND METHODS: A group of 88 youths, 8 to 13 years old at onset of IDDM, were evaluated repeatedly during a 9-year follow-up period, on average, using a standardized psychiatric protocol. Levels of HbA1 were also assessed repeatedly. Psychiatric diagnoses were derived independently of HbA1 values. RESULTS: In univariate longitudinal analyses, the psychiatric diagnosis of noncompliance with medical treatment was significantly related to HbA1 level. There was a trend of an association between any major psychiatric disorder, as well as nondepressive disorder, and HbA1. Interaction terms between IDDM duration (or age) and psychiatric variables were also significantly related to metabolic control. According to the final multivariate model of repeatedly assessed HbA1, noncompliance with medical treatment (irrespective of IDDM duration) and the interaction between nondepressive psychiatric disorder and IDDM duration contributed to worse metabolic control. CONCLUSIONS: We found some support for the hypothesis that psychiatric morbidity negatively affects blood glucose regulation and that its consequences are more marked the longer young patients have had IDDM. We did not confirm the hypothesis that depressive illness has particularly deleterious consequences on metabolic control. Noncompliance with medical treatment and having had nondepressive psychiatric illness in interaction with IDDM duration account for a statistically significant but clinically modest amount of variability in HbA1 over time. The weak relationship among these variables may explain the inconsistent findings in the literature regarding psychiatric morbidity and metabolic control.

Adolescent↗

[Oxidative stress in critically ill patients].

Among critically ill patients, several physio-pathological processes such as global and local hypo-perfusion, hypoxia, endothelial injury and acidosis have been associated with the production and release of large amounts of reactive oxygen species (ROS) in a non regulated fashion. Although in physiologic conditions ROS influence intracellular processes and participate in the defense against infectious organism, in critically ill conditions they are associated with potential oxidative damage over cellular structures and with persistent activation of the inflammatory response. Mechanisms associated with oxidative damage are activation of the macrophage-monocyte system and neutrophils, ischemia-reperfusion events and intracellular ROS production. Endogenous compounds, mainly enzymes, and dietary components act as antioxidant. Several studies show that in critically ill patients increase levels of ROS or reduction of antioxidant levels are related to disease severity. In animal models of critical diseases, antioxidant therapy has shown to reduce mortality. Nevertheless, there are few studies in humans that only show improvements in hemodynamic variables, reduction in inflammatory mediators levels, decreases in oxidized compounds and that suggest a lower incidence of multiple organ failure.

Antioxidants↗

Increased inflammatory status and higher prevalence of three-vessel coronary artery disease in patients with concomitant coronary and peripheral atherosclerosis.

The aim of this study was to determine whether patients with coronary artery disease (CAD) and concomitant peripheral arterial disease (PAD) have a greater inflammatory status than those with CAD alone. To this aim, we evaluated PAD (ankle/brachial pressure index <0.9), and measured plasma levels of C-reactive protein (CRP), interleukin-6 (IL-6) and the soluble forms of intercellular adhesion molecule-1 (sICAM-1) and vascular cell adhesion molecule-1 (sVCAM-1) in 234 patients who underwent coronary angiography. Median levels of CRP, IL-6 and sICAM-1 were higher in the CAD without PAD (n=134) and CAD+PAD (n=40) groups than in 60 patients without either disease ("controls"). Median CRP values were higher in patients with CAD+PAD than in patients with CAD alone (4.7 mg/L [1.5; 7.6] vs 2.4 mg/L [0.9; 3.8], p < 0.01).Three-vessel CAD was diagnosed in 60% of CAD+PAD patients and in 21% (p< 0.01) of CAD only patients. After adjustment for confounding factors, only PAD was independently associated with three-vessel CAD (p<0.001). This association was maintained after adjustment for IL-6, the only inflammatory parameter significantly associated with three-vessel CAD at univariate analysis (p<0.01). In conclusion, in CAD the coexistence of PAD is associated with a greater inflammatory status and more widespread coronary atherosclerosis. These results could help to explain the high cardiovascular risk of patients with concomitant CAD and PAD and suggest that PAD be included among the variables used to identify CAD patients for further diagnostic evaluation.

Aged↗

Correlation of steroid receptors with histopathologic characteristics in breast carcinoma.

Estrogen and progesterone receptors were correlated to histologic variables in 288 breast cancer patients from western India. The progesterone receptors (PR) were significantly elevated as compared to estrogen receptors (ER) amongst primary pre- and peri-menopausal breast carcinomas. ER positivity was correlated significantly to nuclear grade. Lymphatic invasion and vascular permeation were not found to be linked to ER, while PR positivity could be linked to lymphatic invasion and inversely to vascular permeation. Higher frequency of ER positivity was observed in lobular carcinomas. PR concentrations of the tumor had better correlations with histologic variables as compared to ER.

Adult↗

The pathology of low-grade adenosquamous carcinoma of the breast. An immunohistochemical study.

Low-grade adenosquamous carcinoma of the breast is a variant of metaplastic mammary carcinoma characterized by a locally invasive growth pattern and a low risk for metastases. In this study none of the carcinomas exhibited greater than 5 percent nuclear immunoreactivity for estrogen or progesterone receptors, and as a result they were classified as negative for these receptors. Reactivity for cathepsin D was found in 39 percent of the tumors, largely limited to areas of epidermoid differentiation. Membrane immunoreactivity for HER-2/neu oncogenes was present in glandular components of 46 percent of the carcinomas. Immunoreactivity for p53 (greater than 10 percent of nuclei) was present in 13 percent of the tumors, also in glandular elements. Six different patterns of coexpression of p53, HER-2/neu and cathepsin D were found, the most frequent being the following: HER-2/neu(+), p53(-), cathepsin D(-) (9 cases, 39%); cathepsin D(+), p53(-), HER-2/neu(-) (5 cases, 22%); and the three markers negative (5 cases, 22 percent). Coexpression of the two oncogenes was found in only one tumor which was also positive for cathepsin D. These results indicate that the expression of various immunohistochemical prognostic markers may be heterogeneous and that there may not be a specific pattern of marker coexpression within a carefully defined histologic subtype of mammary carcinoma. Furthermore, characteristics reported to be associated with an unfavorable prognosis (negative hormone receptors, presence of cathepsin D, and expression of oncogenes such as HER-2/neu) may be found in a substantial proportion of tumors that comprise this clinically and histologically low-grade variant of mammary carcinoma. This disassociation between expected prognosis based on expression of current prognostic markers and observed prognosis occurs in other forms of mammary carcinoma. Medullary carcinoma, when diagnosed on the basis of rigorously defined criteria, has an excellent prognosis despite the fact that these tumors are characterized by absence of estrogen and progesterone receptors and a high proliferative rate. The histological classification of mammary carcinomas is itself an important prognostic variable that may take precedence over selected biochemical markers.

Adult↗

Incidence, target antigens, and clinical implications of antineutrophil cytoplasmic antibodies in rheumatoid arthritis.

OBJECTIVE: To determine the incidence of antineutrophil cytoplasmic antibodies (ANCA) in rheumatoid arthritis (RA), to detect the target antigens of ANCA, and to compare clinical and laboratory data of ANCA+ with ANCA- patients with RA. METHODS: 385 sera of patients with RA were screened for ANCA by indirect immunofluorescence. ANCA+ sera were further analyzed for target antigens by ELISA: The ANCA+ patients were compared to randomly selected ANCA- patients with RA with respect to serological and radiological variables and extraarticular involvement. RESULTS: ANCA were found in 16% of patients with RA (61/385 sera). All sera showed a perinuclear (pANCA) pattern. Antibodies directed against proteinase 3 were not observed. The analysis of ANCA+ and ANCA- patients revealed that the pANCA+ group exhibited significantly higher serological markers of inflammation (p < 0.005) and a higher incidence of rheumatoid factor (p < 0.005). Furthermore, vasculitic involvement was found at a higher frequency (p < 0.05) in the pANCA+ group. Five patients in the pANCA+ group had pulmonary involvement, but none in the pANCA- group. CONCLUSION: pANCA in RA may be a marker for a more aggressive course of disease in respect to serological variables and extraarticular manifestations including rheumatoid vasculitis and lung involvement.

Aged↗

Influence of maximal ergometric exercise on endothelin concentrations in relation to molecular markers of the hemostatic system.

The effects of moderate 30 min cycle ergometer exercise (aerobic metabolism; 0.85-3.71 mmol.1(-1) lactate) followed by short-term exercise at maximal capacity (anaerobic metabolism; 5.09 to 17.75 mmol.1(-1) lactate) on endothelin (ET) and hemostatic variables (tissue plasminogen activator [t-PA] antigen, prothrombin fragments [F1,2], thrombin-antithrombin III complex [TAT], prothrombin time and partial thromboplastin time) were investigated in 15 male healthy subjects of varying fitness levels. Endothelin was measured twice before and immediately after maximal cycle exercise. The results show an increase in endothelin concentration [10.0 pg.ml-1 (baseline) + 6.1 pg.ml-1 (increase post exercise)]. ET did not increase under control conditions. Moderate 30 min exercise caused an increase in t-PA antigen concentration (3.66 + 3.15 ng.ml-1) and short-term maximal exercise produced a markedly higher elevation in this variable (+10.6 ng.ml-1). F1,2 increased (810 + 40 pmol.l-1) under moderate and by 150 pmol.l-1 under anaerobic exercise. TAT increased only at maximal exercise levels (1.01 + 0.32 ng.l-1). No changes were found in any of these variables under control conditions. No correlation of endothelin and the hemostatic variables was found. It is concluded that endothelin and hemostatic markers increase independently during moderate and maximal exercise.

Adult↗

Urinary progesterone and pregnanediol. Use for monitoring progesterone treatment.

OBJECTIVE: To compare progesterone (P) and pregnanediol glucuronide (PDG) levels in urine with respect to their potential use for monitoring luteal activity and P treatment. STUDY DESIGN: Two different experiments were carried out. In the first experiment, each of seven normal, ovulatory women collected first morning urines daily throughout an entire menstrual cycle. The day of ovulation was determined by transvaginal ultrasound scanning. P, PDG, estrone glucuronide, luteinizing hormone and creatinine were measured in each urine specimen. In the second experiment, each of three normal, ovulatory women was given a single oral dose of 200 mg of micronized P and, 2 days later, a single intramuscular injection of 25 mg of P during days 2-5 of the cycle. Blood and urine were collected prior to each treatment and 1, 4, 8, 12 and 24 hours after treatment. P was measured in both serum and urine; PDG was quantified only in urine. RESULTS: The mean initial rises and peak days, as well as the patterns of urinary excretion of P and PDG during the menstrual cycles, were similar; however, the variability of PDG was much greater. Concentrations of PDG were 1,000-4,000 times greater than those of P. A significant correlation was observed between urinary P and PDG. Following either intramuscular or oral P treatment, serum P levels rose rapidly and reached peak levels (7.0-11.8 ng/mL) by one hour. In contrast, both urinary P and PDG peaked considerably later (4-12 hours). Twenty-four hours after intramuscular treatment, serum and urinary P and urinary PDG were still elevated. Following oral treatment the levels of these compounds decreased after peaking and were 10- to 20- fold lower at 24 hours. Also, after oral P treatment, urinary PDG levels were considerably higher and more variable as compared to urinary P levels. CONCLUSION: Urinary P appears to be as good a clinical marker of luteal activity and therapeutic P administration as PDG and may be measured in place of this metabolite. There appears to be greater variability in urinary PDG as compared to urinary P when P is administered.

Adult↗

The effect of very-low-dose warfarin on markers of hypercoagulation in metastatic breast cancer: results from a randomized trial.

Malignancy is a risk factor for thromboembolism and anti-cancer chemotherapy can increase this risk. Prophylaxis of thrombosis with very-low-dose warfarin given concurrently with chemotherapy has a significantly reduced rate of thromboembolism in a randomized trial in women with stage IV breast cancer. In a group of 32 patients randomized in one center (16 subjects on warfarin and 16 on placebo), we have prospectively studied the plasma levels of: 1. Markers of 'in vivo' clotting activation (thrombin-antithrombin complex [TAT], prothrombin fragment 1+2 [F1+2] and D-dimer), 2. Factor VII (FVII), and 3. Natural anticoagulants (protein C [PC] and antithrombin [AT]). The aims of this study were: 1. to examine whether laboratory tests predicted those patients who developed thrombosis, and 2. to evaluate the effect of very-low-dose warfarin on hemostatic variables. The patients' hemostatic parameters were evaluated before entry into the study and after starting chemotherapy +/- prophylaxis, before each course for nine courses. Before-treatment results were compared to those of a sex and age-matched non-cancer control group. There was a significant elevation of plasma levels of TAT (p <0.001), F1+2 (p <0.001), D-dimer (p <0.0001) and FVIIa (p <0.05), as well as an increase of FVII proteolysis (p <0.05), whereas plasma PC and AT concentrations were not different from controls. After starting chemotherapy, markers of clotting activation were progressively lower in the group receiving warfarin prophylaxis compared to the group on placebo. Differences between the groups became statistically significant (p <0.01) after the 4th course of chemotherapy. Deep vein thrombosis occurred in two patients in the placebo arm. The results of this study indicate that before therapy, an hypercoagulable state is present in stage IV breast cancer, and after starting chemotherapy, abnormalities of hypercoagulation markers persist, however they are reduced by very-low-dose-warfarin. None of the laboratory variables could predict thrombosis in the single patient.

Adult↗

Prognostic significance of different biomarkers in non-small cell lung cancer.

The purpose of our study was to examine the prognostic significance of different biomarkers [DNA content, proliferating cell nuclear antigen labeling index (PCNA-LI), p53 mutation and apoptosis], in 152 surgically resected non-small cell lung cancer (NSCLC). The ploidy was carried out by densitometry; PCNA-LI, p53 and apoptosis were determined with immunohistochemistry. The results were correlated to histology, stage and patient survival. A considerable variability of the PCNA indices, ranging from 0 to 33.5% with a mean value of 7.0%, was found. DNA evaluation showed a prevalence of aneuploid tumors (62%) with a DNA index >1. Overexpression of p53 protein and apoptotic positivity were observed in low percentages of cases (16% and 32% respectively). Only stage and PCNA-LI were found to be significant prognostic factors on multivariate analysis. PCNA was superior to stage in predicting shortened survival of patients with NSCLC. PCNA immunostaining can be applied on a routine basis in formalin-fixed, paraffin-embedded samples of NSCLC to predict patient prognosis and thus to identify patients in need of additional postoperative therapies.

Adult↗