Diagnostic assays for identification of anaplastic lymphoma kinase‐positive non–small cell lung cancer

In series dominated by adenocarcinoma histology, approximately 5% of non–small cell lung cancers (NSCLCs) harbor an anaplastic lymphoma kinase (ALK) gene rearrangement. Crizotinib, a tyrosine kinase inhibitor with significant activity against ALK, has demonstrated high response rates and prolonged progression‐free survival in ALK‐positive patients enrolled in phase 1/2 clinical trials. In 2011, crizotinib received accelerated approval from the US Food and Drug Administration (FDA) for the treatment of proven ALK‐positive NSCLC using an FDA‐approved diagnostic test. Currently, only break‐apart fluorescence in situ hybridization testing is FDA approved as a companion diagnostic for crizotinib; however, many other assays are available or in development. In the current review, the authors summarize the diagnostic tests available, or likely to become available, that could be used to identify patients with ALK‐positive NSCLC, highlighting the pros and cons of each. Cancer 2013. © 2012 American Cancer Society.     

Mental disturbances and perceived complexity of nursing care in medical inpatients: results from a European study

AIMS AND OBJECTIVES: The relationship between mental disturbances - anxiety and depression, somatization and alcohol abuse - on admission to internal medicine units and perceived complexity of care as indicated by the nurse at discharge was studied. The goal was to study the utility of short screeners for mental disturbances to select patients for case-management on admission. DESIGN: The study had a cohort design: patients were included on admission and followed through their hospital stay until discharge. The study was conducted within the framework of the European Biomed 1 Risk Factor study. RESEARCH METHODS AND INSTRUMENTS: In the first 3 days of admission the patients were interviewed by a trained health care professional, who scored the SCL-8D, a somatization questionnaire based on the Whiteley-7 and the CAGE. At discharge, nurses rated the complexity of the patient's care. RESULTS: Patients with high scores on anxiety and depression (SCL-8D) and on somatization received higher ratings on perceived nursing complexity than those with low scores, with and without control for age, severity of illness and chronicity. The actual nursing intensity and medical care utilization, as measured daily by means of a checklist, could not explain these relations. No differences were found between patients with high or low scores on alcohol abuse. CONCLUSIONS: The study shows a potential use of screeners for mental disturbances to detect patients for whom nurses might need additional help. However, mental disturbance is not the sole criterion: functional status and other variables that predict medical and nursing care utilization should be included in a screening strategy for case-management programmes.     

Rapid‐onset hypogonadism secondary to crizotinib use in men with metastatic nonsmall cell lung cancer

BACKGROUND:

The objective of this study was to document the differences in testosterone (T) levels between crizotinib‐treated and noncrizotinib‐treated patients with metastatic nonsmall cell lung cancer (NSCLC).

METHODS:

Testosterone levels were measured in 19 men with metastatic NSCLC who received crizotinib and in 19 men with metastatic NSCLC who did not receive crizotinib. Clinical characteristics of the patients were compared, and additional hormone assays were performed as appropriate. Two patients who began crizotinib and 4 patients who had dose interruptions or who stopped crizotinib therapy had serial hormone measurements, permitting the documentation of dynamic hormone changes on and off crizotinib treatment.

RESULTS:

Total T levels were low (<241 ng/dL) in 19 of 19 (100%) crizotinib‐treated men and in 6 of 19 men (32%) with metastatic NSCLC who did not receive crizotinib (mean T levels, 131 ng/dL and 311 ng/dL, respectively; P = .0002). Only 1 in 5 patients who had anaplastic lymphoma kinase (ALK) gene rearrangements and had not yet received crizotinib had low T. The initiation of crizotinib in 2 patients who had previously normal T levels was associated with a rapid decreases in T and in luteinizing hormone and follicle stimulating hormone levels within 14 to 21 days. Discontinuation of crizotinib led to increases back to normal T levels.

CONCLUSIONS:

Crizotinib therapy caused rapid suppression of T levels in men. The current results indicated that the site of action must include a central (hypothalamic or pituitary) effect, but additional direct testicular effects could not be excluded. Further work is required to assess the correlation between low T levels and crizotinib side effects as well as the exact molecular mechanism and site of drug toxicity. Cancer 2012. © 2012 American Cancer Society.     

Ideomotor limb apraxia in Huntington's disease

Introduction Ideomotor limb apraxia is the disturbance of planning and of execution of motor activity,which is not caused by a dysfunction of the motor or sensory nervous system. Apraxia is a diagnostic criterion in dementialike Alzheimer's disease. However, this symptom may also occur in dementia with subcortical lesions like Huntington's disease (HD), a hereditary, devastating neurodegenerative disease leading to neurological and psychiatric dysfunction. The aim of our study is to determine the correlation between the occurrence of ideomotor limb apraxia and neuropsychological deficits in HD. Methods To assess the correlation between apraxia and neuropsychological abilities in HD, 41 patients with HD and 33 age- and sex-matched controls were examined. The De Renzi test for apraxia and an apraxia test battery containing tests of i) imitation of meaningless gestures of hands, ii) imitation of meaningless gestures of fingers, iii) performance of meaningful gestures on demand, and iv) pantomime of tool use were used to assess apraxia. Moreover, neuropsychological function was rated by the Mini Mental State Examination (MMSE), the Rey Complex Figure Memory Test, the Trail Making Test A and B, the California Verbal Learning Test (German version), the Stroop Color and Word Test, the Controlled Oral Word Association Test, and the Mehrfachwahl- Wortschatz-Intelligenztest for measuring verbal intelligence. Motor function was assessed in all HD patients by the Unified HD Rating Scale (UHDRS), rating oculomotor and orolingual function, fine motor tasks, parkinsonism, dystonia, chorea and statics and gait. Results Apraxic HD patients showed worse results than non-apraxic HD patients in three items of the Rey Complex Figure Memory Test (Organisation, short-term and longterm memory), but not in other assessed neuropsychological tests. In assessment of meaningful gestures on demand 39.3% of HD patients were apraxic, in assessment of pantomime of tool use 67.9% of HD patients showed apraxia. Patients with HD showed highly significant worse results than controls in the De Renzi test, in hands' and fingers' imitation, in performance of gestures on demand, in pantomime of tool use and every neuropsychological test except for the test measuring verbal intelligence. Apraxic HD patients showed worse results than non-apraxic HD patients in the UHDRS total motor score and the score for oculomotor function. Conclusion This is the largest study on apraxia in HD. Ideomotor limb apraxia is a common sign in HD patients, occurring in a high percentage. In contrast to the opinion of several authors, occurrence of apraxia in HD is independent from neuropsychological decline and the severity of most neurological symptoms.