First-line gemcitabine with cisplatin or epirubicin in advanced non-small-cell lung cancer: a phase III trial

The purpose of our study was to compare progression-free survival and quality of life (QOL) after cisplatin-gemcitabine (CG) or epirubicin-gemcitabine (EG) in chemotherapy-naive patients with unresectable non-small-cell lung cancer. Patients (n = 240) were randomised to receive gemcitabine 1125 mg m(-2) (days 1 and 8) plus either cisplatin 80 mg m(-2) (day 2) or epirubicin 100 mg m(-2) (day 1) every 3 weeks for a maximum of five cycles. Eligible patients had normal organ functions and Eastern Cooperative Oncology Group performance status less than or equal to2. QOL was measured with European Organisation for Research and Treatment of Cancer QLQ-C30 and LC13 questionnaires. There were no significant differences in median progression-free survival (CG 26 weeks, EG 23 weeks), median overall survival (CG 43 weeks, EG 36 weeks), or tumour response rates (CG 46%, EG 36%). Toxicity was mainly haematologic. In the EG arm granulocytopenia occurred more frequently, leading to more febrile neutropenia. Also, elevation of serum transaminases, mucositis, fever, and decline in LVEF were more common in the EG arm. In the CG arm, more patients experienced elevated serum creatinine levels, sensory neuropathy, nausea, and vomiting. Global QOL was not different in both arms. Progression-free survival, overall survival, response rate, and QOL were not different between both arms; however, overall toxicity was more severe in the EG arm

Depletion of Saccharomyces cerevisiae in psoriasis patients, restored by Dimethylfumarate therapy (DMF)

Background Psoriasis and inflammatory bowel disease (IBD) are chronic inflammatory diseases sharing similar pathogenic pathways. Intestinal microbial changes such as a decrease of bakers' yeast Saccharomyces cerevisiae have been reported in IBD, suggesting the presence of a gut-skin axis. Objective To investigate whether the S. cerevisiae abundance was altered in psoriasis patients versus healthy controls, and whether dimethylfumarate (DMF) interacted with this yeast. Methods Using qPCR, faecal samples were compared between psoriasis patients without DMF (n = 30), psoriasis patients with DMF (n = 28), and healthy controls (n = 32).Results Faecal S. cerevisiae abundance was decreased in psoriasis compared to healthy controls (p<0.001). Interestingly, DMF use raised S. cerevisiae levels (p<0.001). Gastrointestinal adverse-effects of DMF were correlated with a higher S. cerevisiae abundance (p = 0.010).In vitro, a direct effect of DMF on S. cerevisiae growth was observed. In addition, anti-Saccharomyces cerevisiae antibodies were not elevated in psoriasis. Conclusion The abundance of baker's yeast S. cerevisiae is decreased in psoriasis patients, but appears to b

Activity of high-dose epirubicin combined with gemcitabine in advanced non-small-cell lung cancer: a multicenter phase I and II study

The aim of the study was to evaluate efficacy and tolerance of epirubicin and gemcitabine as first-line chemotherapy in patients with advanced non-small-cell lung cancer. A phase I study was performed with the combination of escalating doses of epirubicin intravenously on day 1 and a fixed dose of gemcitabine on days 1 and 8 of a 21-day cycle. Eighteen patients were included in the phase I part of the study before the maximum tolerated dose was found. Dose-limiting toxicity was febrile neutropenia. The phase II part of the study was continued with epirubicin 100 mg m−2on day 1 and gemcitabine 1125 mg m−2on days 1 and 8 of a 21-day cycle. Forty-three chemotherapy-naive patients were included. The median age of the patients was 60 years (range 26–75). Most patients (74%) were in stage IV. Granulocytopenia CTC grade 4 occurred in 32.5% and thrombocytopenia grade 4 in 11.6% of cycles. Febrile neutropenia occurred in six patients. Non-haematological toxicity was mainly mucositis CTC grade 2 and 3 in 35% of patients. The tumour response rate was 49% (95% confidence interval (CI) 35–63%). The median survival time for the patients was 42 weeks (95% CI 13–69). © 2000 Cancer Research Campaig

Acute neuropsychiatry:a confused patient and a puzzled doctor

BACKGROUND: Anti-NMDA-receptor-encephalitis is a progressive autoimmune disease with significant mortality if left untreated.CASE DESCRIPTION: A 58-year-old man without previous psychiatric or neurologic history presented at the emergency department after brief loss of consciousness at work. Within a few hours, the patient developed acute neuropsychiatric symptoms, including altered levels of consciousness, aggression, incoherence, change in behaviour, and psychomotor agitation. Initially, additional blood, cerebrospinal fluid and EEG tests showed no abnormalities. Over the course of the following days, catatonia, orofacial dyskinesia and autonomic-function disorder developed, eventually with respiratory insufficiency, necessitating transfer to the intensive-care unit. At this stage, the EEG did show abnormalities, and cerebrospinal fluid analysis showed marginal pleocytosis. The patient was treated with intravenous methylprednisolone and immunoglobins. Anti-NMDA-receptor antibodies were present in the blood and cerebrospinal fluid. Screening for malignancy identified small-cell lung carcinoma, for which the patient was treated with cytostatic agents.CONCLUSION: Acute neuropsychiatric symptoms in a middle-aged patient with no psychiatric medical history are suggestive of an underlying somatic cause. Timely recognition and treatment of anti-NMDA-receptor encephalitis is essential to improve the prognosis.</p

Effect of Metformin Treatment on Lipoprotein Subfractions in Non-Diabetic Patients with Acute Myocardial Infarction:A Glycometabolic Intervention as Adjunct to Primary Coronary Intervention in ST Elevation Myocardial Infarction (GIPS-III) Trial

OBJECTIVE:Metformin affects low density lipoprotein (LDL) and high density (HDL) subfractions in the context of impaired glucose tolerance, but its effects in the setting of acute myocardial infarction (MI) are unknown. We determined whether metformin administration affects lipoprotein subfractions 4 months after ST-segment elevation MI (STEMI). Second, we assessed associations of lipoprotein subfractions with left ventricular ejection fraction (LVEF) and infarct size 4 months after STEMI. METHODS:371 participants without known diabetes participating in the GIPS-III trial, a placebo controlled, double-blind randomized trial studying the effect of metformin (500 mg bid) during 4 months after primary percutaneous coronary intervention for STEMI were included of whom 317 completed follow-up (clinicaltrial.gov Identifier: NCT01217307). Lipoprotein subfractions were measured using nuclear magnetic resonance spectroscopy at presentation, 24 hours and 4 months after STEMI. (Apo)lipoprotein measures were obtained during acute STEMI and 4 months post-STEMI. LVEF and infarct size were measured by cardiac magnetic resonance imaging. RESULTS:Metformin treatment slightly decreased LDL cholesterol levels (adjusted P = 0.01), whereas apoB remained unchanged. Large LDL particles and LDL size were also decreased after metformin treatment (adjusted P<0.001). After adjustment for covariates, increased small HDL particles at 24 hours after STEMI predicted higher LVEF (P = 0.005). In addition, increased medium-sized VLDL particles at the same time point predicted a smaller infarct size (P<0.001). CONCLUSION:LDL cholesterol and large LDL particles were decreased during 4 months treatment with metformin started early after MI. Higher small HDL and medium VLDL particle concentrations are associated with favorable LVEF and infarct size

Multi-modal volumetric concept activation to explain detection and classification of metastatic prostate cancer on PSMA-PET/CT

Explainable artificial intelligence (XAI) is increasingly used to analyze the behavior of neural networks. Concept activation uses human-interpretable concepts to explain neural network behavior. This study aimed at assessing the feasibility of regression concept activation to explain detection and classification of multi-modal volumetric data. Proof-of-concept was demonstrated in metastatic prostate cancer patients imaged with positron emission tomography/computed tomography (PET/CT). Multi-modal volumetric concept activation was used to provide global and local explanations. Sensitivity was 80% at 1.78 false positive per patient. Global explanations showed that detection focused on CT for anatomical location and on PET for its confidence in the detection. Local explanations showed promise to aid in distinguishing true positives from false positives. Hence, this study demonstrated feasibility to explain detection and classification of multi-modal volumetric data using regression concept activation.Comment: Accepted as: Kraaijveld, R.C.J., Philippens, M.E.P., Eppinga, W.S.C., J\"urgenliemk-Schulz, I.M., Gilhuijs, K.G.A., Kroon, P.S., van der Velden, B.H.M. "Multi-modal volumetric concept activation to explain detection and classification of metastatic prostate cancer on PSMA-PET/CT." MICCAI workshop on Interpretability of Machine Intelligence in Medical Image Computing (iMIMIC), 202