Exosomal proteins as prognostic biomarkers in non-small cell lung cancer.

BACKGROUND: Use of exosomes as biomarkers in non-small cell lung cancer (NSCLC) is an intriguing approach in the liquid-biopsy era. Exosomes are nano-sized vesicles with membrane-bound proteins that reflect their originating cell. Prognostic biomarkers are needed to improve patient selection for optimal treatment. We here evaluate exosomes by protein phenotyping as a prognostic biomarker in NSCLC. METHODS: Exosomes from plasma of 276 NSCLC patients were phenotyped using the Extracellular Vesicle Array; 49 antibodies captured the proteins on the exosomes, and a cocktail of biotin-conjugated antibodies binding the general exosome markers CD9, CD81 and CD63 was used to visualise the captured exosomes. For each individual membrane-bound protein, results were analysed based on presence, in a concentration-dependent manner, and correlated to overall survival (OS). RESULTS: The 49 proteins attached to the exosomal membrane were evaluated. NY-ESO-1, EGFR, PLAP, EpCam and Alix had a significant concentration-dependent impact on inferior OS. Due to multiple testing, NY-ESO-1 was the only marker that maintained a significant impact on inferior survival (hazard rate (HR) 1.78 95% (1.78-2.44); p = 0.0001) after Bonferroni correction. Results were adjusted for clinico-pathological characteristics, stage, histology, age, sex and performance status. CONCLUSION: We illustrate the promising aspects associated with the use of exosomal membrane-bound proteins as a biomarker and demonstrate that they are a strong prognostic biomarker in NSCLC.

[Nosocomial infections with penicillin-resistant Streptococcus pneumoniae. Four clusters with pneumococci serotype 9V]. / Nosokomielle infektioner med penicillinresistent Streptococcus pneumoniae. Fire ophobninger med pneumokokker serotype 9V.

INTRODUCTION: The objective was to alert Danish hospital physicians to the risk of nosocomial spread of penicillin-resistant Streptococcus pneumoniae (PRP). MATERIALS AND METHODS: The study was conducted in the County of Northern Jutland during the 3-year period 1996-1998. Data on isolates of PRP were retrieved retrospectively from a computerised laboratory information system, and additional information was obtained from patients' charts and notes by infection control nurses. RESULTS: Four incidents of likely nosocomial spread of PRP, serotype 9V, were identified in departments of medicine or pulmonary diseases. Clusters included two to four patients. The eleven patients were 53 to 92 years of age, and all but one had severe underlying pulmonary disease or a malignant disorder. During the same period, we found that among pneumococcal bacteraemias of definite origin 8.9% (95% confidence limits 5.9-12.9%) was nosocomial. CONCLUSION: The risk of nosocomial spread of pneumococci, including PRP, should be acknowledged. A policy of isolation should be implemented for patients with PRP; isolation precautions should also be considered for patients with a previous isolate of PRP if readmitted, as such patients may become chronic carriers.

Collagenous colitis: a long-term follow-up study.

OBJECTIVE: Collagenous colitis was first described in 1976. It is a rare disorder and the long-term course and prognosis of the disease are unknown. The aim of this study was to evaluate the course of the disease more than 5 years after the diagnosis. DESIGN: A retrospective follow-up of patients with collagenous colitis diagnosed during the period 1979-1990. METHODS: All examinations performed at the time of diagnosis were reviewed and the clinical courses of the patients were determined by evaluation of the medical records. At a follow-up visit in 1996 complete histories were obtained and conventional laboratory tests were performed. RESULTS: Two men and 22 women aged 20-82 years with collagenous colitis were identified. At the time of diagnosis, extensive investigation did not reveal other gastrointestinal diseases. At the time of follow-up, six patients had died from diseases unrelated to collagenous colitis, 10 patients suffered from chronic or intermittent diarrhoea, and four patients had been without gastrointestinal symptoms for the last 2-10 years. None of the patients developed colorectal cancer or chronic inflammatory bowel disease. Four patients were lost to follow-up. CONCLUSION: Collagenous colitis is a benign disease, most often with a chronic course. No association with other gastrointestinal diseases was found.

[General practitioners' handling of patients with dyspepsia]. / Praktiserende laegers håndtering af patienter med dyspepsi.

The handling of patients with dyspepsia by 102 general practitioners was investigated prospectively using a standardised application form for gastroscopy followed by a questionnaire to the practitioners. A mean of 5.3 indications were stated among 16 performed referral possibilities in 143 applications. Referral because of long-standing symptoms, ineffective treatment trial and atypical dyspepsia were more often stated than certain important risk factors (high age, NSAID-ingestion etc.). In 23% of cases no specific suspicion of organic disease was stated. The questionnaire was answered by 85%. More than 90% of doctors would use a treatment trial before further investigation of dyspeptic patients with first time consultation. A wide variation of medical empirical treatment was indicated. The practitioners wished to retain the open access model for referring, but a great majority desired practical guidelines for the handling of dyspeptic patients. This study confirms the relevance of such guidelines to improve present practice.