Anda Baicus

Utility of Routine Hematological and Inflammation Parameters for the Diagnosis of Cancer in Involuntary Weight Loss

Introduction A quarter of patients with involuntary weight loss (IWL) have cancer. Inflammation and anemia are associated with cancer, and recent studies showed that red blood cell distribution width (RDW) is a predictor of mortality, including cancer-related death. The aim of this study was to assess the ability of routine hematological and inflammation parameters to diagnose cancer in patients with IWL. Materials and Methods A total of 253 consecutive patients with IWL admitted in a secondary care university hospital were included. Routine hematological and inflammatory parameters (hemoglobin level, mean corpuscular volume, RDW, serum iron level, erythrocyte sedimentation rate, C-reactive protein level, and ferritin level) were recorded for all patients. The investigative workup was not standardized, but the patients were followed up for 6 months to avoid misclassification concerning the final diagnosis. Results All parameters, excepting mean cellular volume, were statistically associated with cancer. The areas under the curve were 0.708 (95% confidence interval [CI], 0.627-0.790) for C-reactive protein level, 0.690 (95% CI: 0.620-0.760) for erythrocyte sedimentation rate, 0.651 (95% CI, 0.566-0.735) for serum iron level, 0.607 (95% CI, 0.526-0.687) for hemoglobin level, 0.598 (95% CI, 0.518-0.679) for ferritin level, 0.594 (95% CI, 0.517-0.671) for RDW, and 0.561 (95% CI, 0.474-0.649) for mean cellular volume. In the multivariable analysis, only erythrocyte sedimentation rate remained associated with cancer. Conclusions In patients with IWL, the hematological and inflammation parameters were statistically different in patients with cancer and in those without cancer. However, in clinical practice, they were modest diagnostic tests for cancer.

Carbapenemase-Producing Klebsiella pneumoniae in Romania: A Six-Month Survey.

This study presents the first characterization of carbapenem-non-susceptible Klebsiella pneumoniae isolates by means of a structured six-month survey performed in Romania as part of an Europe-wide investigation. Klebsiella pneumoniae clinical isolates from different anatomical sites were tested for antibiotic susceptibility by phenotypic methods and confirmed by PCR for the presence of four carbapenemase genes. Genome macrorestriction fingerprinting with XbaI was used to analyze the relatedness of carbapenemase-producing Klebsiella pneumoniae isolates collected from eight hospitals. Among 75 non-susceptible isolates, 65 were carbapenemase producers. The most frequently identified genotype was OXA-48 (n = 51 isolates), eight isolates were positive for bla NDM-1 gene, four had the bla KPC-2 gene, whereas two were positive for bla VIM-1. The analysis of PFGE profiles of OXA-48 and NDM-1 producing K. pneumoniae suggests inter-hospitals and regional transmission of epidemic clones. This study presents the first description of K. pneumoniae strains harbouring bla KPC-2 and bla VIM-1 genes in Romania. The results of this study highlight the urgent need for the strengthening of hospital infection control measures in Romania in order to curb the further spread of the antibiotic resistance.

Fever of unknown origin-predictors of outcome. A prospective multicenter study on 164 patients.

BACKGROUND: To date, the studies that have been done on fever of unknown origin have mostly been descriptive. Therefore, we know the etiogical spectrum and how it has changed since 1966 for many regions of the world. However, we do not know if there are clinical or laboratory predictors of severe outcome. Being able to estimate the severity of the disease early on would allow one to determine how intensive the diagnostic work-up should be. METHODS: A multicenter cohort study was carried out on 164 consecutive patients who met the classic, modified criteria of fever of unknown origin. The study lasted 2 years (1997-1998) and included a follow-up period of another 2 years. The main outcome measured was the final diagnosis established at the end of follow-up. RESULTS: When the white cell count was abnormal, the relative risk for a serious disease was 1.49 (CI: 1.15-1.94; p=0.004), when anemia was present, the relative risk was 1.55 (CI: 1.21-1.98; p=0.003), and for high alanine aminotransferase (ALAT), bilirubin, or lactate dehydrogenase (LDH), the relative risks were 1.57 (CI: 1.21-2.02; p=0.010), 1.57 (CI: 1.18-2.08; p=0.007), and 3.43 (CI: 1.81-6.48; p=0.0002), respectively. In multivariate analysis, the odds ratios for serious diseases were 2.7 (CI: 1.17-6.4; p=0.02) for abnormal white cell count, 2.8 (CI: 1.14-7.16; p=0.02) for anemia, 4.3 (CI: 1.6-11.5; p=0.003) for high serum bilirubin, and 5.3 (1.5-18.6; p=0.009) for high serum ALAT. CONCLUSIONS: In patients having a fever of unknown origin, anemia, abnormal white cell count, and high ALAT and bilirubin are independent predictors of severe outcome.

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

BackgroundA 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.MethodsAll 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.Results290 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.ConclusionIn patients with involuntary weight loss, a ferritin above 100mcg/L could rule out colon cancer, but not gastric or rectal cancer.

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.

Fever of unknown origin—predictors of outcome

Abstract Background: To date, the studies that have been done on fever of unknown origin have mostly been descriptive. Therefore, we know the etiogical spectrum and how it has changed since 1966 for many regions of the world. However, we do not know if there are clinical or laboratory predictors of severe outcome. Being able to estimate the severity of the disease early on would allow one to determine how intensive the diagnostic work-up should be. Methods: A multicenter cohort study was carried out on 164 consecutive patients who met the classic, modified criteria of fever of unknown origin. The study lasted 2 years (1997–1998) and included a follow-up period of another 2 years. The main outcome measured was the final diagnosis established at the end of follow-up. Results: When the white cell count was abnormal, the relative risk for a serious disease was 1.49 (CI: 1.15–1.94; p =0.004), when anemia was present, the relative risk was 1.55 (CI: 1.21–1.98; p =0.003), and for high alanine aminotransferase (ALAT), bilirubin, or lactate dehydrogenase (LDH), the relative risks were 1.57 (CI: 1.21–2.02; p =0.010), 1.57 (CI: 1.18–2.08; p =0.007), and 3.43 (CI: 1.81–6.48; p =0.0002), respectively. In multivariate analysis, the odds ratios for serious diseases were 2.7 (CI: 1.17–6.4; p =0.02) for abnormal white cell count, 2.8 (CI: 1.14–7.16; p =0.02) for anemia, 4.3 (CI: 1.6–11.5; p =0.003) for high serum bilirubin, and 5.3 (1.5–18.6; p =0.009) for high serum ALAT. Conclusions: In patients having a fever of unknown origin, anemia, abnormal white cell count, and high ALAT and bilirubin are independent predictors of severe outcome.

Serum Cytokines and Cancer in Involuntary Weight Loss

Background Tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and IL-6 may be associated with involuntary weight loss in patients with and without cancer. However, results of previous studies have been conflicting. We evaluated patients who had involuntary weight loss to determine cytokine levels and the correlation of these cytokines with weight loss, the association with inflammation, and the potential for use in cancer diagnosis. Materials and Methods In 290 consecutive patients with involuntary weight loss (74 patients [26%] with cancer and 216 patients [74%] without cancer), erythrocyte sedimentation rate (ESR), and serum levels of C-reactive protein, TNF-α, IL-1β, and IL-6 were determined. Results Higher ESR and levels of C-reactive protein, TNF-α, IL-1β, and IL-6 were associated with cancer. The levels of TNF-α, IL-1β, and IL-6 did not correlate with the amount of weight loss. In multivariable analysis, only ESR was associated with cancer. Conclusions In patients with involuntary weight loss, TNF-α, IL-1β, and IL-6 were associated with cancer but were not weight loss mediators.

Impaired ankle-brachial index in antiphospholipid syndrome: Beyond the traditional risk factors

The patients with antiphospholipid syndrome (APS) associate an increased risk of atherosclerosis.

Extended Antiphospholipid Antibodies Screening in Systemic Lupus Erythematosus Patients

Abstract Background. The antiphospholipid syndrome (APS) is one of the most encountered autoimmunity in systemic lupus erythematosus (SLE) patients and pathogenesis of these two seems to be intricate. Aim. To investigate the association of antiphospholipid antibodies (APLAs) titer with the presence of secondary APS diagnosis in SLE patients. Methods. 65 patients fulfilling the 2012 Systemic Lupus Collaborating International Clinics (SLICC) SLE’s criteria were included. The APS diagnosis was sustained according to the 2006 Sydney APS’s criteria. Three groups of patients were defined: SLE patients with secondary APS, SLE with history of positive “criteria” APLAs but without APS clinical features, respectively SLE patients without positive APLAs or clinical APS criteria. An extended APLAs panel was searched in all cases: both IgM and IgG of anticardiolipin antibodies (aCL), anti-β2 glycoprotein I antibodies (aβ2GPI), antiphosphatidylethanolamine antibodies (aPE), antiphosphatidylserine antibodies (aPS), respectively antiprothrombin antibodies (aPT). Results. Only the aβ2GPI, both IgM and IgG serotypes, had significantly higher titers in patients with SLE and secondary APS compared to no APS (with/without positive APLAs): median (min; max) 7.0 (0.0-300.0) vs. 1.0 (0.0-28.0) vs. 1.0 (0.0-12.0), respectively 3.0 (0.0-79.0) vs. 1.0 (0.0-3.0) vs. 1.0 (0.0-12.0) (p<0.001, Kruskal-Wallis test)]. Also, in regression logistic models, only the aβ2 GPI (IgG and IgM) were identified as risk factors for secondary APS diagnosis in the SLE patients: OR(95%CI) 5.9 (2.2-15.7), respectively 1.3 (1.1-1.5). In regard with the SLE markers, the IgG serotypes of the “non-criteria” APLAs analyzed (aPS, aPT, aPE) were correlated with the antiDNA titers while the IgM serotypes inversely associated with the complement C3 levels. Conclusions. IgG aβ2 GPI are accompanied by almost 6-fold increase risk of secondary APS when screening SLE patients. On the contrary, the “non-criteria” APLAs do not seem associated with the APS diagnosis in SLE patients. Some correlates of the “non-criteria” APLAs with the antiDNA and complement C3 levels were also observed.

AB0159 Osteoprotegerin – a Possible Link Between Antiphospholipid Antibodies and Atherosclerosis

Background The antiphospholipid syndrome (APS) and systemic lupus erythematosus (SLE) are known to be associated with increased risk of cardiovascular disease (CVD). However, there are few data regarding the osteoprotegerin (OPG), one of the validated markers of the CVD risk, in patients with APS or SLE. Objectives The aim of this study was to evaluate the correlations between the OPG and antiphospholipid antibodies (APLA). Methods Patients with APS (primary and secondary to SLE) were successively included. The diagnosis was sustained according to the 2006 Sydney APSs criteria, respectively to the 2012 SLICC SLEs criteria. Laboratory workup included the “diagnostic” APLA [IgG and IgM anticardiolipin (aCL), IgG and IgM anti-β2 glycoprotein I (aβ2GPI)] and also the “non-diagnostic” APLA [IgG and IgM antiphosphatidylserine (aPS), IgG and IgM anti phosphatidylethanolamine (aPE), respectively IgG and IgM antiprothrombin (aPT)]. We assessed the SCORE and Framingham risk as the widely used score of CVD risk in general population. We divided the study group in two subgroups: A - patients with low OPG (≤1.5 pg/ml), and B - patients with high OPG (>1.5 pg/ml). Results For the 40 patients included, the mean age at inclusion (SD) was 43.7±10.7 years. OPG values were higher in patients with history of stroke vs patients without stroke (3.44±2.24 vs 2.15±1.5, p=0.02). We did not found differences of OPG values in patients with or without history of stable angina, myocardial infarction or peripheral artery disease. Values of SCORE risk (1.19±1.81 vs 0.43±0.75, p=0.03) and Framingham risk (6.56±6.41 vs 3.9±2.73, p=0.02) were significantly higher in group B comparing with group A. Moreover, in patients associating SLE, the SLEDAI score was higher in group B vs group A (4.47±3.51 vs 4.00±6.21, p=0.04). Also, for the SLE patients, we found a higher prevalence for the anti-DNA and anti-Sm in patients with high OPG (2/5 vs 13/0; p=0.042, respectively 0/7 vs 6/7; p=0.032). OPG values were positively correlates only with the values of IgM aPT (0.35, p=0.02). When we performed the ROC curve analysis, we found that the titers of IgM aPT, IgG aβ2GPI, and IgG aPE were the best predictors of an OPG values>1.5 [AUC (CI) 0.604 (0.418-0.791), 0.578 (0.392-0.795), respectively 0.536 (0.342-0.730)]. For the patients with APS secondary to SLE, IgM aPT and IgG aPE [AUC (CI) 0.632 (0.348-0.915), respectively 0.549 (0.289-0.810)] were the best predictors of high OPG levels. Conclusions OPG levels might be related with CVD risk in patients with APS. The OPG levels were correlated with “non-diagnostic” APLA, raising the hypothesis of “non-diagnostic” APLA involvement in the pathogenesis of CVD risk in patients with APS. Moreover, the anti-DNA and anti-Sm might be to be related with the OPG levels in patients with APS secondary to SLE. This is an interesting finding especially as we do not have yet a clear explanation for the increased CVD risk in SLE. Acknowledgements This paper is supported by the POSDRU/159/1.5/S/137390. Disclosure of Interest None declared