Proteomics to predict the response to tumour necrosis factor-α inhibitors in rheumatoid arthritis using a supervised cluster-analysis based protein score.

OBJECTIVE: In rheumatoid arthritis (RA), it is of major importance to identify non-responders to tumour necrosis factor-α inhibitors (TNFi) before starting treatment, to prevent a delay in effective treatment. We developed a protein score for the response to TNFi treatment in RA and investigated its predictive value. METHOD: In RA patients eligible for biological treatment included in the BiOCURA registry, 53 inflammatory proteins were measured using xMAP® technology. A supervised cluster analysis method, partial least squares (PLS), was used to select the best combination of proteins. Using logistic regression, a predictive model containing readily available clinical parameters was developed and the potential of this model with and without the protein score to predict European League Against Rheumatism (EULAR) response was assessed using the area under the receiving operating characteristics curve (AUC-ROC) and the net reclassification index (NRI). RESULTS: For the development step (n = 65 patient), PLS revealed 12 important proteins: CCL3 (macrophage inflammatory protein, MIP1a), CCL17 (thymus and activation-regulated chemokine), CCL19 (MIP3b), CCL22 (macrophage-derived chemokine), interleukin-4 (IL-4), IL-6, IL-7, IL-15, soluble cluster of differentiation 14 (sCD14), sCD74 (macrophage migration inhibitory factor), soluble IL-1 receptor I, and soluble tumour necrosis factor receptor II. The protein score scarcely improved the AUC-ROC (0.72 to 0.77) and the ability to improve classification and reclassification (NRI = 0.05). In validation (n = 185), the model including protein score did not improve the AUC-ROC (0.71 to 0.67) or the reclassification (NRI = -0.11). CONCLUSION: No proteomic predictors were identified that were more suitable than clinical parameters in distinguishing TNFi non-responders from responders before the start of treatment. As the results of previous studies and this study are disparate, we currently have no proteomic predictors for the response to TNFi.

A comparison of amodiaquine and sulfadoxine-pyrimethamine as first-line treatment of falciparum malaria in Kenya.

A randomized 14-day study in vivo compared the response of Plasmodium falciparum malaria to amodiaquine (35 mg/kg) and sulfadoxine-pyrimethamine (sulfadoxine, 25 mg/kg) in symptomatic outpatients at 2 sites in northern and western Kenya during 1993. Of the 239 patients recruited, 181 (76%) completed the study [84 (46%) on amodiaquine and 97 (54%) on sulfadoxine-pyrimethamine]. There were no significant differences in the parasitological, clinical or haematological responses between the 2 drug groups in both areas, with 18.5% resistance to amodiaquine versus 9.5% for sulfadoxine-pyrimethamine in the north and 35.1% against amodiaquine versus 34.5% for sulfadoxine-pyrimethamine in the west. In both sites defervescence was significantly more rapid with amodiaquine (P < 0.05) and true clinical failure (symptomatic illness with recurrent parasitaemia) was unusual (9%). As high-level resistance to chloroquine is widespread, both drugs are valuable alternatives. However, the significantly higher levels of resistance in the west may be a sign of the increased drug pressure in this holoendemic area and send an important warning concerning resistance to sulfadoxine-pyrimethamine.

Gynaecomastia: is one cause enough?

Gynaecomastia can be detected in between one-third and two-thirds of men. A wide variety of causes of gynaecomastia, some physiological, some very serious, have been identified. We present a case in which the cause of the gynaecomastia seemed obvious after history taking and physical examination but we finally ended up with a more complex combination of diagnoses. This case stresses the importance of combining history taking and physical examination with additional laboratory testing for the assessment of gynaecomastia.