Palbociclib in highly pretreated metastatic ER-positive HER2-negative breast cancer.

PURPOSE: We aimed to investigate the role of palbociclib, a first-in-class cyclin-dependent kinase 4 and 6 inhibitor, in postmenopausal women with highly pretreated endocrine therapy-resistant metastatic breast cancer (MBC). METHODS: Between 28 September 2015 and 14 March 2017, a compassionate use program was established in the University Hospitals Leuven in which 82 postmenopausal women with estrogen receptor-positive, HER2-negative MBC were included after at least four lines of systemic treatment. The efficacy and safety analysis was performed in 82 patients who had received at least one dose of palbociclib and who had at least 6-month follow-up at the data cut-off point. The primary objective was the evaluation of efficacy of the combination of palbociclib and endocrine therapy with clinical benefit as primary endpoint, defined as the absence of progressive disease and being on treatment for at least 6 months. Secondary objectives were the evaluation of toxicity and the identification of potential predictors for clinical benefit. RESULTS: The median age of the patients was 67.1 years (range 34.8-85.9) at the time of inclusion. The average duration of treatment was 5.6 months (range 1-19), with a median progression-free survival of 3.17 (95% CI 2.76-4.70) months. At the data cut-off point, 10 patients were still on treatment with palbociclib. In this highly pretreated setting, 34 patients experienced no progressive disease within 6 months, resulting in an overall clinical benefit rate (CBR) of 41.5%. 20.7% (17/82) showed stable disease for ≥ 9 months and 13.4% for ≥ 12 months. None of the investigated predicting factors were significantly associated with clinical benefit at 6 months. For 43.9% of the patients, treatment delay or dose reduction was indicated. CONCLUSIONS: Palbociclib in combination with endocrine therapy shows an unexpectedly high CBR and favorable safety profile in heavily pretreated endocrine-resistant estrogen receptor-positive, HER2-negative MBC patients.

Pain inhibition and postexertional malaise in myalgic encephalomyelitis/chronic fatigue syndrome: an experimental study.

OBJECTIVES: To examine the efficacy of the pain inhibitory systems in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) during two different types of exercise and to examine whether the (mal)functioning of pain inhibitory systems is associated with symptom increases following exercise. DESIGN: A controlled experimental study. SETTING AND SUBJECTS: Twenty-two women with ME/CFS and 22 healthy sedentary controls were studied at the Department of Human Physiology, Vrije Universiteit Brussel. INTERVENTIONS: All subjects performed a submaximal exercise test and a self-paced, physiologically limited exercise test on a cycle ergometer. The exercise tests were undertaken with continuous cardiorespiratory monitoring. Before and after the exercise bouts, subjects filled out questionnaires to assess health status, and underwent pressure pain threshold measurements. Throughout the study, subjects' activity levels were assessed using accelerometry. RESULTS: In patients with ME/CFS, pain thresholds decreased following both types of exercise, whereas they increased in healthy subjects. This was accompanied by a worsening of the ME/CFS symptom complex post-exercise. Decreased pressure thresholds during submaximal exercise were associated with postexertional fatigue in the ME/CFS group (r = 0.454; P = 0.034). CONCLUSIONS: These observations indicate the presence of abnormal central pain processing during exercise in patients with ME/CFS and demonstrate that both submaximal exercise and self-paced, physiologically limited exercise trigger postexertional malaise in these patients. Further study is required to identify specific modes and intensity of exercise that can be performed in people with ME/CFS without exacerbating symptoms.

Delta, theta, alpha and beta power spectrum of sleep electroencephalogram in infants aged two to eleven months.

Automatic sleep EEG analysis was performed on infants from 2 to 11 months of age. Partial power spectra of delta, theta, alpha, and beta 1 bands were studied as function of sleep stages, age, and time of the night. beta 1, alpha, and delta power spectra are significantly lower in paradoxical sleep (PS) than in quiet sleep (QS) whatever the age; but theta is lower in PS than in QS only after 5 months of age. delta, theta, and alpha power increase with age in QS. Only delta and theta are greater in the first half of the night than in the second half. beta 1 power does not differ significantly in stages 2 and 3 of QS, during the course of the night or as a function of age. Thus delta, theta, alpha may be the best spectral parameters for the maturation of quiet sleep EEGs during the first year of life.

[First results given by a sleep automatic analysis for 2- to 12-months-old infants (author's transl)]. / Premiers résultats d'une méthode d'analyse automatique de sommeil du nourrisson.

A sleep automatic analysis program was performed for infants older than 2 months. It used spectral analysis of the EEG and polygraphic parameters. Three EEG parameters and three polygraphic parameters are considered to be sufficient to stage babies' sleep with computers. Automatic detection was satisfactory for babies older than 4 1/2 months: agreement was better than 0.8 between automatic and human observation. Results are less satisfactory for the younger infants where there is only between .50 and .60 agreement between machine and human observers. These preliminary results confirm that decision criteria must be age related.