Cardiotoxicity during long-term trastuzumab use in patients with HER2-positive metastatic breast cancer: who needs cardiac monitoring?

PURPOSE: Patients with HER2-positive metastatic breast cancer (MBC) usually receive many years of trastuzumab treatment. It is unknown whether these patients require continuous left ventricular ejection fraction (LVEF) monitoring. We studied a real-world cohort to identify risk factors for cardiotoxicity to select patients in whom LVEF monitoring could be omitted. METHODS: We included patients with HER2-positive MBC who received > 1 cycle of trastuzumab-based therapy in eight Dutch hospitals between 2000 and 2014. Cardiotoxicity was defined as LVEF < 50% that declined > 10%-points and was categorized into non-severe cardiotoxicity (LVEF 40-50%) and severe cardiotoxicity (LVEF < 40%). Multivariable Cox and mixed model analyses were performed to identify risk factors associated with cardiotoxicity. Additionally, we explored the reversibility of cardiotoxicity in patients who continued trastuzumab. RESULTS: In total, 429 patients were included. Median follow-up for cardiotoxicity was 15 months (interquartile range 8-31 months). The yearly incidence of non-severe + severe cardiotoxicity in the first and second year was 11.7% and 9.1%, respectively, which decreased thereafter. The yearly incidence of severe cardiotoxicity was low (2.8%) and stable over time. In non-smoking patients with baseline LVEF > 60% and no cardiotoxicity during prior neoadjuvant/adjuvant treatment, the cumulative incidence of severe cardiotoxicity was 3.1% after 4 years of trastuzumab. Despite continuing trastuzumab, LVEF decline was reversible in 56% of patients with non-severe cardiotoxicity and in 33% with severe cardiotoxicity. CONCLUSIONS: Serial cardiac monitoring can be safely omitted in non-smoking patients with baseline LVEF > 60% and without cardiotoxicity during prior neoadjuvant/adjuvant treatment.

Effect of various rinsing protocols after use of amine fluoride/stannous fluoride toothpaste on the bacterial composition of dental plaque.

This clinical study evaluated the effect of different oral hygiene protocols on the bacterial composition of dental plaque. After a 2-week period of using fluoride-free toothpaste, 30 participants followed three 1-week experimental protocols, each followed by 2-week fluoride-free washout periods in a randomized crossover examiner-blind controlled trial. The 1-week experimental protocols comprised the use of AmF/SnF(2) toothpaste twice daily, after which participants either (1) rinsed with tap water, (2) did not rinse but only spat out the toothpaste, or (3) rinsed with an AmF/SnF(2) mouthwash. In the fluoride-free washout periods, the participants brushed their teeth with fluoride-free toothpaste without further instructions. Six hours after the last brushing (+/- rinsing) of each period, buccal plaque samples in the upper molar region were taken. The microbiota composition of the plaque samples was analyzed by checkerboard DNA:DNA hybridization. A statistically significant reduction was found in the total amount of DNA of the 39 major plaque species measured, and in the proportions of some acid-producing bacterial strains after the period having used the AmF/SnF(2) toothpaste + AmF/SnF(2) mouthrinsing. The results indicate that using the AmF/SnF(2) toothpaste and rinse combination could result in plaque of lower cariogenicity.

Health-related quality of life in patients treated for enterocutaneous fistula.

BACKGROUND: Patients with enterocutaneous fistulas undergo long intensive treatment. The aim of this study was to investigate the long-term health-related quality of life (HRQL) of these patients. METHODS: Consecutive patients treated for enterocutaneous fistula between 1990 and 2005 were eligible for this retrospective study. The Karnofsky Performance Scale (KPS), Short Form 36 (SF-36) and the Inflammatory Bowel Disease Questionnaire were used to measure HRQL. The SF-36 was matched with results from healthy controls. Patients also gave information on concurrent medical illnesses. RESULTS: Of 135 patients, 44 died, 14 were lost to follow-up and 12 refused to participate; of the remaining 65, 62 participated (response rate 81 per cent). HRQL was independent of patient characteristics during treatment. Scores for SF-36 domains were lower than in their matched controls (P < 0.050). Concurrent medical illness (cancer, depression and gastrointestinal disease) significantly reduced HRQL (for example with a 40 per cent reduction in vitality). The median KPS score was 80, indicating that activities could be performed with effort and patients had some signs of disease. CONCLUSION: HRQL is lower in patients treated for enterocutaneous fistula than in matched controls, particularly in those with concurrent medical illnesses. Patients treated successfully have normal independence in daily functioning.

Synchrony-dependent autocorrelation in eighth-nerve-fiber response to rippled noise.

Autocorrelograms and interval and delay histograms of the eighth-nerve-fiber response in cats to cosine noise were recorded. A good detectability level for the delay oscillations in the autocorrelograms was always found, when the fiber had a high value of the synchronization index at characteristic frequency (CF). In order to study their relationship, autocorrelograms for cosine noise stimulation were computed by the substitution of synchronization indices in the Poisson distribution formulas for higher-order intervals. The approach was made possible through a further exploration of Johnson's synchronization theory [D. H. Johnson, "The response of single auditory-nerve fibers in the cat to single tones: synchrony and average discharge rate," Ph. D. thesis, MIT, Cambridge, MA (1974)]. It was shown that computed autocorrelograms somewhat resembled experimental ones. The differences between them concerned the envelopes of the "onset" and "delay" oscillations, viz., in their constrictions and amplitudes. These constrictions were shown to be significant only in recordings at delays greater than or equal to 4/CF, corresponding to the dominant region for human repetition pitch.