Genomic and clinical characterization of a familial GIST kindred intolerant to imatinib.

Familial gastrointestinal stromal tumors (GIST) are rare. We present a kindred with multiple family members affected with multifocal GIST who underwent whole genome sequencing of the germline and tumor. Affected individuals with GIST harbored a germline variant found within exon 13 of the KIT gene (c.1965T>G; p.Asn655Lys, p.N655K) and a variant in the MSR1 gene (c.877 C > T; p.Arg293*, pR293X). Multifocal GISTs in the proband and her mother were treated with preoperative imatinib, which resulted in severe intolerance. The clinical features of multifocal GIST, cutaneous mastocytosis, allergies, and gut motility disorders seen in the affected individuals may represent manifestations of the multifunctional roles of KIT in interstitial cells of Cajal or mast cells and/or may be suggestive of additional molecular pathways which can contribute to tumorigenesis.

Systemic therapy in pediatric-type soft-tissue sarcoma.

Soft-tissue sarcoma (sts) is rare and represents approximately 7% of cancers in children and in adolescents less than 20 years of age. Rhabdomyosarcoma (rms) is most prevalent in children less than 10 years of age and peaks again during adolescence (16-19 years of age). Multi-agent chemotherapy constitutes the mainstay of treatment for rms. In other non-rhabdomyosarcoma soft-tissue tumours, such as synovial sarcoma, evidence for routine use of chemotherapy is less robust, and alternative treatment options, including targeted agents and immunotherapy, are being explored. In this review, we focus on chemotherapy for pediatric-type rms and discuss the advances and challenges in systemic treatment for select non-rhabdomyosarcoma soft-tissue tumours in children and adolescents. We support an increasingly cooperative approach for treating pediatric and adult sts.

Uptake of self-management strategies in a heart failure management programme.

BACKGROUND: Multidisciplinary heart failure programs including patient education and self-management strategies such as daily recording of body weight and use of a patient diary decrease hospital readmissions and improve quality of life. However, the degree of uptake of individual components of these programs and their contribution to patient benefit are uncertain. METHODS: Patients with heart failure admitted to Auckland Hospital were randomised into the management or usual care groups of the Auckland heart failure management study (AHFMS). Patients in the management group were given a heart failure diary for the recording of daily weights, attended a heart failure clinic and were encouraged to attend three education sessions. Patients in the usual care group received routine clinical care, mainly from general practitioners. Patients were followed to 12 months. This study investigated the uptake of self-management by assessing diary use and self-weighing behaviour in the group receiving the heart failure intervention, and compared the level of knowledge of heart failure self-management of the management group to the control group after 12 months. RESULTS: Of the 197 patients in the AHFMS, 100 patients were included in the management group and received a diary and education about heart failure self-management including monitoring weight daily. Of these patients, 76 patients used the diary. These patients were on more medication; were more likely to attend the education sessions, heart failure clinic, and primary care, and had a lower mortality rate over the course of the study. Variables independently associated with use of the diary included less severe symptoms (OR 15, 95% confidence intervals 1.7, 144), frequent attendance at the heart failure clinic (OR 15, 95% CI 3, 78) and attendance at an education session (OR 8, 95% CI 1.5, 42). Of the 76 patients who used the diary, 51 weighed themselves regularly. More of these patients owned scales at home; they were also more likely to attend the education sessions, and experienced fewer hospital admissions than those patients who did not weigh themselves regularly. Variables independently associated with regular self-weighing included the presence of scales at home (OR 6.3, 95% CI 1.7, 14.1), left ventricular ejection fraction >30% (OR 4.3, 95% CI 1.1, 17.5), and attendance at the education session(s) (OR 6.3, 95% CI 1.7, 14.1). Patients in the management group exhibited higher levels of knowledge at 12 months of follow-up and were more likely to monitor their condition using daily weighing, compared to the control group. CONCLUSIONS: At 12 months of follow-up, implementation of self-management strategies including daily weight monitoring and level of education on self-management was significantly higher in the management group than the control group. For the patients in the management group, not using the diary or inability to perform daily weighing were associated with less frequent attendance at the heart failure clinic and education sessions and poorer health outcomes. In this study, attendance at the education sessions was associated with the adoption of self-management, underlining the importance of education in multidisciplinary heart failure programmes. Self-weighing could be increased by provision of scales to all patients. The subset of patients who did not adopt self-management strategies in this study were at high risk of death or readmission.