Effect of a Structured Teaching Module Including Intensive Prophylactic Measures on Reducing the Incidence of Capecitabine-Induced Hand-Foot Syndrome: Results of a Prospective Randomized Phase III Study

Lessons Learned

• A structured teaching module including intensive prophylactic measures to alleviate hand‐foot syndrome (HFS) during capecitabine therapy is feasible but ineffective at protecting patients from HFS.
• Pharmacologic therapeutic interventions should be investigated for the management of this complication.

BackgroundCapecitabine‐induced hand‐foot syndrome (HFS) has a detrimental effect on quality of life. The effect of a structured teaching module including intensive prophylactic measures was evaluated.MethodsThis non‐crossover phase III double‐blinded clinical trial randomized patients in a 1:1 ratio to either a control group or to a group administered a structured teaching model including intensive prophylactic measures on HFS administered by a trained oncology nurse at regular intervals (case) versus standard information on HFS care administered by treating clinician (control). The primary endpoint was comparison of fraction of patients in both arms developing at least grade 2 HFS.ResultsBetween June 15, 2016, and April 4, 2018, 280 patients (140 to case and 140 to control) were enrolled. The median number of capecitabine chemotherapy cycles was eight; 269 patients (96%) were evaluable for HFS, of whom 89 patients (33.08%) developed at least grade 2 HFS (grade 2 HFS, 73 patients [26.1%]; grade 3 HFS, 16 patients (5.7%}). There was no difference in at least grade 2 HFS between evaluable case and control arms of the study (control group, 45/135 [33.3%]; case, 44/134 [32.8%]; p = .93).ConclusionThe use of a structured teaching module including intensive prophylactic measures was feasible, but this did not reduce the incidence and severity of capecitabine‐induced HFS.     

HDAC and MAPK/ERK Inhibitors Cooperate To Reduce Viability and Stemness in Medulloblastoma

Journal of Molecular Neuroscience - Medulloblastoma (MB), which originates from embryonic neural stem cells (NSCs) or neural precursors in the developing cerebellum, is the most common malignant...     

Test–retest repeatability of [18F]Flortaucipir PET in Alzheimer’s disease and cognitively normal individuals

The aim of this study was to investigate the test–retest (TRT) repeatability of various parametric quantification methods for [¹⁸F]Flortaucipir positron emission tomography (PET). We included eight subjects with dementia or mild cognitive impairment due to Alzheimer’s disease and six cognitively normal subjects. All underwent two 130-min dynamic [¹⁸F]Flortaucipir PET scans within 3 ± 1 weeks. Data were analyzed using reference region models receptor parametric mapping (RPM), simplified reference tissue method 2 (SRTM2) and reference logan (RLogan), as well as standardized uptake value ratios (SUVr, time intervals 40–60, 80–100 and 110–130 min post-injection) with cerebellar gray matter as reference region. We obtained distribution volume ratio or SUVr, first for all brain regions and then in three tau-specific regions-of-interest (ROIs). TRT repeatability (%) was defined as |retest–test|/(average (test + retest)) × 100. For all methods and across ROIs, TRT repeatability ranged from (median (IQR)) 0.84% (0.68–2.15) to 6.84% (2.99–11.50). TRT repeatability was good for all reference methods used, although semi-quantitative models (i.e. SUVr) performed marginally worse than quantitative models, for instance TRT repeatability of RPM: 1.98% (0.78–3.58) vs. SUVr_80–100: 3.05% (1.28–5.52), p < 0.001. Furthermore, for SUVr_80–100 and SUVr_110–130, with higher average SUVr, more variation was observed. In conclusion, while TRT repeatability was good for all models used, quantitative methods performed slightly better than semi-quantitative methods.     

Atherosclerotic pseudoaneurysm of the ascending aorta.

Pseudoaneurysms in the ascending aorta most commonly occur as a complication of surgical procedures at this site. They have also been reported in association with trauma, infection, aortitis, and other disorders. Pseudoaneurysm formation in the descending aorta or arch may occur as a result of penetrating ulcers in the presence of severe atherosclerotic plaque. Pseudoaneurysm as a result of atherosclerotic disease has only rarely been noted in the ascending aorta, where complex plaque is less common. We report here the finding with transesophageal echocardiography of a pseudoaneurysm in the ascending aorta as a result of atherosclerotic disease and penetrating ulcer.     

Novel polymorphisms in mec genes and a new mec complex type in methicillin-resistant Staphylococcus aureus isolates obtained in rural Wisconsin

We determined allelic polymorphisms in the mec complexes of 524 methicillin-resistant Staphylococcus aureus isolates by partial or complete sequencing of three mec genes, mecA, mecI, and mecR1. The isolates had been collected over a 10-year period from patients living in rural Wisconsin, where the use of antibiotics was expected to be lower than in the bigger cities. Of the 18 mutation types identified, 16 had not been described previously. The five most common mutations were a mutation 7 nucleotides (nt) upstream from the start site (G-->T) in the mecA promoter (34.7%), an E246G change encoded by mecA (2.2%), a cytosine insertion at codon 257 in mecA (13.2%), an N121K change encoded by mecI (7.8%), and a major mecI-mecR1 deletion designated as a class B1 mec complex deletion type (25.4%). There was a high degree of conservation of the amino acid sequence of MecR1. Strains with the same mutations had variable resistance to oxacillin, and the median MIC for isolates that harbored the 7-nt-upstream mutation was lower than that for strains harboring other mutations. Our data suggest that the mecA promoter mutation plays a more important role in determining methicillin resistance than mutations in mecI and mecA do. Eighty-five percent of the tested isolates (n = 148) with the mecA promoter mutation and the class B1 mec complex deletion belonged to the same major clonal group, identified as MCG-2, and harbored the type IV staphylococcal cassette chromosome mec DNA. There was also a wide range of oxacillin MICs for strains with wild-type mecA, mecI, and mecR1 sequences, suggesting that the genetic backgrounds of clinical strains are significant in determining susceptibility to methicillin.