Primary Cardiac Sarcoma: Clinical Characteristics and Prognostic Factors over the Past 2 Decades.

BACKGROUND: Primary cardiac sarcomas (PCS) are extremely rare malignant tumors involving the heart. Only isolated case reports have been described in the literature over different periods of time. This pathology has been associated with a dismal prognosis and given its rarity; treatment options are very limited. Furthermore, there are contrasting data about the effectiveness of current treatment modalities in improving the survival of patients with PCS, including surgical resection which is the mainstay of therapy. There is a paucity of data on the epidemiological characteristics of PCS. This study has the objective of investigating the epidemiologic characteristics, survival outcomes, and independent prognostic factors of PCS. METHODS: A total of 362 patients were ultimately registered in our study from the Surveillance, Epidemiology, and End Results (SEER) database. The study period was from 2000 to 2017. Demographics such as clinical characteristics, overall mortality (OM), and PCS-specific mortality (CSM) were taken into account. A p value of <0.1 in the univariate analysis leads to the incorporation of the variable into multivariate analysis adjusting for covariates. Adverse prognostic factors were represented by a Hazard Ratio (HR) greater than one. The five-year survival analysis was carried out using the Kaplan-Meier method and the log-rank test was used to compare survival curves. RESULTS: Crude analysis revealed a high OM in age 80+ (HR = 5.958, 95% CI 3.357-10.575, p < 0.001), followed by age 60-79 (HR = 1.429, 95% CI 1.028-1.986, p = 0.033); and PCS with distant metastases (HR = 1.888, 95% CI 1.389-2.566, p < 0.001). Patients that underwent surgical resection of the primary tumor and patients with malignant fibrous histiocytomas (HR = 0.657, 95% CI 0.455-0.95, p = 0.025) had a better OM (HR = 0.606, 95% CI 0.465-0.791, p < 0.001). The highest cancer-specific mortality was observed in age 80+ (HR = 5.037, 95% CI 2.606-9.736, p < 0.001) and patients with distant metastases (HR = 1.953, 95% CI 1.396-2.733, p < 0.001). Patients with malignant fibrous histiocytomas (HR = 0.572, 95% CI 0.378-0.865, p = 0.008) and those who underwent surgery (HR = 0.581, 95% CI 0.436-0.774, p < 0.001) had a lower CSM. Patients in the age range 80+ (HR = 13.261, 95% CI 5.839-30.119, p < 0.001) and advanced disease with distant metastases (HR = 2.013, 95% CI 1.355-2.99, p = 0.001) were found to have a higher OM in the multivariate analyses adjusting for covariates). Lower OM was found in patients with rhabdomyosarcoma (HR = 0.364, 95% CI 0.154-0.86, p = 0.021) and widowed patients (HR = 0.506, 95% CI 0.263-0.977, p = 0.042). Multivariate cox proportional hazard regression analyses of CSM also revealed higher mortality of the same groups, and lower mortality in patients with Rhabdomyosarcoma. CONCLUSION: In this United States population-based retrospective cohort study using the SEER database, we found that cardiac rhabdomyosarcoma was associated with the lowest CSM and OM. Furthermore, as expected, age and advanced disease at diagnosis were independent factors predicting poor prognosis. Surgical resection of the primary tumor showed lower CSM and OM in the crude analysis but when adjusted for covariates in the multivariate analysis, it did not significantly impact the overall mortality or the cancer-specific mortality. These findings allow for treating clinicians to recognize patients that should be referred to palliative/hospice care at the time of diagnosis and avoid any surgical interventions as they did not show any differences in mortality. Surgical resection, adjuvant chemotherapy, and/or radiation in patients with poor prognoses should be reserved as palliative measures rather than an attempt to cure the disease.

Intravenous ganaxolone in pediatric super-refractory status epilepticus: A single hospital experience.

Synaptic GABAA receptor (GABAAR) internalization contributes to the drug resistant nature of super-refractory status epilepticus (SRSE). Ganaxolone is a 3ß-methylated synthetic analog of the endogenous neuroactive steroid, allopregnanolone, that has positive allosteric modulatory activity on synaptic and extrasynaptic GABAA receptors. Ganaxolone is currently in clinical trials to treat rare pediatric seizure disorders and established and refractory SE. Two pediatric patients with SRSE (age 17 and age 7) were treated under emergency investigational new drug (E-IND) applications with intravenous (IV) ganaxolone administered as an initial bolus and a maintenance infusion for up to 4.5 days with intermittent IV boluses as-needed followed by taper on day 5 and transitioned to chronic treatment using ganaxolone suspension. Adjunctive ganaxolone was effective in terminating SRSE in both patients, safely permitting IV anesthetics to be weaned. Seizure control has been maintained after transitioning to enteric ganaxolone. Further investigation of ganaxolone as a safe and effective treatment for SRSE is warranted.

Mirtazapine for sleep disturbances in Angelman syndrome: a retrospective chart review of 8 pediatric cases.

STUDY OBJECTIVES: Angelman syndrome (AS) is a rare neurodevelopmental disorder that is characterized by developmental delay, intellectual disability, seizures, a characteristic happy personality, gait ataxia, tremulousness of the limbs, microcephaly, and anxiety. Severe sleep disturbances with the diminished need for sleep and abnormal sleep-wake cycles are seen in up to 90% of patients with AS. AS is caused by absent maternal expression of the gene UBE3A located in the 15q11.2-q13 locus. We hypothesized that selective antagonism of 5-HT2 and 5-HT3 serotonin receptors with mirtazapine would benefit sleep disturbances in patients with AS. METHODS: Institutional Review Board approval was obtained at Vanderbilt University Medical Center. Medical records of individuals seen in the Comprehensive Angelman Syndrome clinic were retrospectively reviewed to determine the use of mirtazapine for disordered sleep. Parents were asked to respond to a survey to assess the phenotypic features of sleep and behavioral disturbances in AS. They were asked about the use of medications for sleep, focusing on the benefits and risks of mirtazapine. RESULTS: A cohort of 8 individuals with AS, ranging in age from 3 to 16 years old with histories of sleep challenges, were treated with 3.75 to 30 mg of mirtazapine at bedtime for 0 to 36 weeks. Nocturnal awakenings were the most common sleep challenge reported. Seven of eight patients reported benefits from mirtazapine, including increased total sleep time, decreased nocturnal awakenings, and decreased time to fall asleep. The most significant side effects of mirtazapine were hyperphagia and weight gain. CONCLUSIONS: Individuals with AS have abnormal sleep-wake cycles and a high unmet medical need. Mirtazapine helped with sleep onset and nighttime awakenings in 7 of 8 patients, with 2 patients reporting a positive benefit with respect to behavior. These data suggest that mirtazapine may be considered for the treatment of sleep difficulties in patients with AS who remain refractory to more conventional therapies. Weight gain was a common side-effect and led to discontinuation of treatment in 1 patient.

Predicting palliative care needs and mortality in end stage renal disease: use of an at-risk register.

INTRODUCTION: The Gold Standard Frameworks (GSF) Committee devised Prognostic Indicator Guidance in November 2007 to 'aid identification of adult patients with advanced disease, in the last months or year of life, who are in need of supportive or palliative care'. METHODS: This research used the GSF `surprise question' to formulate a list of patients predicted to die within 1 year with end stage renal failure and to establish the specificity and sensitivity of this register. RESULTS: 58 patients were added to the list during the follow-up period of which 28 (48.3%) died during the same period giving an annual mortality of 32.2%. In comparison with the patients who died during the follow-up period but were not added to the at-risk register, those on the register had a much higher mortality rate (32.2% vs 7.8%). Identification of patients with chronic kidney disease and reduced life expectancy by this method appears to have a high sensitivity (66.7%) and specificity (77.9%). In particular, the negative predictive value for mortality for those on the at-risk register appears to be very high (88.3%), indicating the very low mortality among those not on the register. CONCLUSIONS: Patients with chronic kidney disease and a reduced life expectancy can be accurately identified by a multi-disciplinary team using the surprise trigger question with a relatively high sensitivity and specificity. The accurate identification of patients with reduced life expectancy allows appropriate end of life care planning to begin in keeping with patients' wishes and within published guidelines.