Ferritin above 100 mcg/L could rule out colon cancer, but not gastric or rectal cancer in patients with involuntary weight loss

BACKGROUND: A tenth of patients with involuntary weight loss (IWL) have gastrointestinal cancer. Ferritin is the first parameter to be modified during the process leading to iron deficiency anaemia, therefore it should be the most sensitive. The aim of this study was to assess the ability of ferritin to rule out gastrointestinal cancer in patients with involuntary weight loss. METHODS: All consecutive patients with IWL admitted in a secondary care university hospital were prospectively studied. Ferritin, haemoglobin with erythrocyte indices and serum iron were recorded for all patients. The reference standard was bidirectional endoscopy and/or 6 months follow-up. RESULTS: 290 patients were included, a quarter had cancer, of which 22 (7.6%) had gastrointestinal cancer (8 gastric cancer, 1 ileum cancer, 13 colorectal cancer). Ferritin had the best area under the curve (AUC), both for gastrointestinal cancer (0.746, CI: 0.691-0.794), and colorectal cancer (0.765, CI: 0.713-0.813), compared to the other parameters of iron deficiency. In the diagnosis of colorectal cancer, ferritin with a cut-off value of 100 mcg/L had a sensitivity of 93% (CI: 69-100%), and negative likelihood ratio of 0.13, with a negative predictive value of 99% (96-100%), while for gastrointestinal cancer, the sensitivity was lower (89%, CI: 67-95%), with a negative likelihood ratio of 0.24. There were three false negative patients, two with gastric cancer, and one with rectal cancer. CONCLUSION: In patients with involuntary weight loss, a ferritin above 100mcg/L could rule out colon cancer, but not gastric or rectal cancer

Interleukin-17 -association to silent lupus nephritis and disease activity

ABSTRACT Background: Systemic lupus erythematosus is a multiorganic, chronic immune disease and lupus nephritis, a severe manifestation, represents the strongest predictor of a poor outcome of this pathology. Cytokines play an important role in lupus nephritis and consequently, their use as biomarkers of active systemic lupus erythematosus disease is of particular interest. The purpose of this work was to study the pro-inflammatory role of interleukin-17 in renal involvement in patients with systemic lupus erythematosus (SLE). Methods: We performed a retrospective study of 87 patients diagnosed with SLE according to the Systemic Lupus International Collaborating Clinics 2012 diagnosis criteria. In this study, we determined the serum levels of interleukin-17 by ELISA. Results: It was observed that 49 patients in the study group presented with positive values of interleukin-17, range (1.12 -23.66) pg/ml. There was a positive correlation of interleukin-17 with active SLE as assessed by the Systemic Lupus Erythematous Disease Activity Index. No association was found between serum interleukin-17 level and renal pathology at the inclusion or in the clinical history of the patients. Patients with leukocyturia and hematuria presented higher values of serum interleukin-17 than those without these manifestations. In the linear regression model, after adjusting for age, gender and treatment we found an independent association between serum IL-17 levels and leukocyturia presence with OR=2.06, 95% CI range (1.22-2.89). Conclusions: A positive correlation has been observed between serum IL-17 and the SLE disease activity as assessed by the SLEDAI score computed without anti-DNA antibodies. Also, the IL-17 levels was strongly associated with the presence of leukocyturia and hematuria, even in patients with no clinical evidence of renal disease that might have silent lupus nephritis usually associated with a benign renal outcome

Criteria and Non-Criteria Antiphospholipid Antibodies and Cancer in Patients with Involuntary Weight Loss

Cancer patients have higher prevalences of antiphospholipid antibodies (aPLs), occasionally associated with thrombotic events. A cross-sectional study regarding the presence of criteria (IgG/IgM anti-cardiolipin-aCL, anti-β2 glycoprotein I-aβ2GPI) and non-criteria (IgG/IgM anti-phosphatidylserine-aPS, anti-phosphatidylethanolamine-aPE, anti-prothrombin-aPT) aPLs in 146 patients with involuntary weight loss was performed. None of the patients had thrombotic events during the study. Out of the 36 cancer patients, 33 had non-hematologic malignancies. In the cancer subgroup, 60% of the patients had at least one positive aPL, with significantly more patients being positive for aβ2GPI IgG compared with the non-cancer subgroup—p = 0.03, OR = 2.23 (1.02–4.88). When evaluating the titres, aCL IgG/IgM, aβ2GPI IgG, aPE IgG, and aPS IgG had significantly higher values in cancer patients, the best cancer predictor being aβ2GPI IgG—AUC 0.642 (0.542–0.742). Gastrointestinal cancer patients were studied separately, and aCL IgM positivity was significantly higher—p = 0.008, OR = 6.69 (1.35–33.02). Both the titres of aCL IgM (p = 0.006) and aPS IgM (p = 0.03) were higher in the gastrointestinal cancer subgroup, with aCL IgM being the best predictor for gastrointestinal cancer development—AUC 0.808 (0.685–0.932). Despite criteria and non-criteria aPLs being frequent in cancer, their connection with thrombosis in these patients is probably dependent on other important risk factors and needs further research

Editorial Effect measure for quantitative endpoints: Statistical versus clinical significance, or "how large the scale is?" EJINME-01683; No of Pages 2

Keywords: Effect measure Statistical significance Clinical importance Minimal important difference Chronic obstructive pulmonary disease Osteoarthritis Whenever a study finds a statistical significance for the difference between treatment and placebo, we must always ask ourselves if the difference is clinically important, too. In order to do this, we need to know at least how large the scale is, and to compare the size of the scale with the size of the effect. Sometimes, the effect of placebo is greater than the intrinsic effect of the drug. The results of these studies are expressed as averages of effects on patients who respond to treatments and patients who do not, so in our daily practice we must distinguish these categories, treating only the first. © 2008 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved. Frequently when a study finds a statistical significance for the difference between treatment and placebo, the scientific society of the respective specialty introduces this new treatment in its guidelines To demonstrate the difference between statistical and clinical significance we will choose a few examples. The first is a study concerning the effect of the locally applied diclofenac in knee osteoarthritis, published in CMAJ [2] in 2004 and reviewed in Evidence Based Medicine with the title "Topical diclofenac improved pain and physical function with no systemic side effects in primary osteoarthritis of the knee" In order to assess the magnitude of the effect and the clinical significance, we must find out what the WOMAC scale means, and searching on the Internet (by Google search), we find that this scale assigns 50 points for pain, 170 points for physical function and 20 points for stiffness. Comparing the size of the scale with the size of the effect, we have the right to think: on a 50 points scale, is a 1.4 points reduction of the pain clinically important? The same, on a 170 points scale, is a 5.9 points improvement of the physical function clinically significant? Moreover, one can observe another phenomenon: the intrinsic effect of the active substance (the difference between the total effect and the placebo effect) is lesser than the placebo effect (1.4 points against 2.5 obtained with placebo for pain, 4.5 points against 7.1 obtained with placebo for the improvement of the physical function, 0.2 points against 0.6 obtained with placebo for the pain in walking). In this situation, a philosophical dilemma emerges: how much attention deserves a drug which intrinsic effect is lesser than the placebo effect? The answer depends on how clinically important is this effect in a view of potential side effects. Another stud

Cancer and involuntary weight loss: failure to validate a prediction score.

BACKGROUND: Many patients who have involuntary weight loss have cancer. The Hernandez prediction rule includes 5 variables (elevated levels of alkaline phosphatase and lactate dehydrogenase, low albumin, high white blood cell count, and age >80 years). The purpose of this study was to evaluate the validity of the prediction rule. METHODS: We prospectively evaluated 290 consecutive inpatients and outpatients who had involuntary weight loss. Clinical, hematologic, and biochemical parameters were determined. There were 259 patients who had follow-up at 6 months to determine the cause of involuntary weight loss, and 31 other patients were lost to follow-up. The 5 variables were introduced into a regression logistic model with cancer as a dependent variable. RESULTS: Cancer was diagnosed in 72 of the 290 patients (25%) who had involuntary weight loss. Bivariate analysis showed that serum albumin, C-reactive protein, erythrocyte sedimentation rate, alkaline phosphatase, iron, lactate dehydrogenase, white blood cell count, hemoglobin, and ferritin levels were associated with cancer (range of area under the receiver operating characteristic curve, 0.589 to 0.688). Multivariate analysis showed that albumin, erythrocyte sedimentation rate, iron, white blood cell count, and lactate dehydrogenase levels were associated with cancer. When dichotomized, only low albumin (odds ratio, 2.6, CI [1.3-5.2]) and high alkaline phosphatase (odds ratio, 2.3, CI [1.7-4.7]) were associated with cancer. The area under the receiver operating characteristic curve of the 5-variable prediction rule was only 0.70 (95% confidence interval, 0.61-0.78). The negative predictive value of this model with 3 variables (age >60 y, alkaline phosphatase, and albumin level) increased from 85% to 95% when all tests were negative. CONCLUSIONS: In patients who had involuntary weight loss, those who have cancer are likely to have ≥1 abnormal laboratory test. The 5-variable prediction rule had a significantly lower accuracy than originally reported. Further evaluation of the 3-variable modification of the prediction rule may be useful

Cancer and Involuntary Weight Loss: Failure to Validate a Prediction Score

<div><p>Background</p><p>Many patients who have involuntary weight loss have cancer. The Hernandez prediction rule includes 5 variables (elevated levels of alkaline phosphatase and lactate dehydrogenase, low albumin, high white blood cell count, and age >80 years). The purpose of this study was to evaluate the validity of the prediction rule.</p><p>Methods</p><p>We prospectively evaluated 290 consecutive inpatients and outpatients who had involuntary weight loss. Clinical, hematologic, and biochemical parameters were determined. There were 259 patients who had follow-up at 6 months to determine the cause of involuntary weight loss, and 31 other patients were lost to follow-up. The 5 variables were introduced into a regression logistic model with cancer as a dependent variable.</p><p>Results</p><p>Cancer was diagnosed in 72 of the 290 patients (25%) who had involuntary weight loss. Bivariate analysis showed that serum albumin, C-reactive protein, erythrocyte sedimentation rate, alkaline phosphatase, iron, lactate dehydrogenase, white blood cell count, hemoglobin, and ferritin levels were associated with cancer (range of area under the receiver operating characteristic curve, 0.589 to 0.688). Multivariate analysis showed that albumin, erythrocyte sedimentation rate, iron, white blood cell count, and lactate dehydrogenase levels were associated with cancer. When dichotomized, only low albumin (odds ratio, 2.6, CI [1.3–5.2]) and high alkaline phosphatase (odds ratio, 2.3, CI [1.7–4.7]) were associated with cancer. The area under the receiver operating characteristic curve of the 5-variable prediction rule was only 0.70 (95% confidence interval, 0.61–0.78). The negative predictive value of this model with 3 variables (age >60 y, alkaline phosphatase, and albumin level) increased from 85% to 95% when all tests were negative.</p><p>Conclusions</p><p>In patients who had involuntary weight loss, those who have cancer are likely to have ≥1 abnormal laboratory test. The 5-variable prediction rule had a significantly lower accuracy than originally reported. Further evaluation of the 3-variable modification of the prediction rule may be useful.</p></div

Multivariable Analysis in Patients Who Had Involuntary Weight Loss^*.

<p>*N = 290 patients. Age cutoff, 60 years. Area under the receiver operating characteristic curve for the logistic regression model in the entire patient group: 0.74; 95% confidence interval, 0.66–0.81.</p