Renal cell carcinoma: a nomogram for the CT imaging-inclusive prediction of indolent, non-clear cell renal cortical tumours

Aim To develop a nomogram from clinical and computed tomography (CT) data for pre-treatment identification of indolent renal cortical tumours. Patients and methods A total of 1201 consecutive patients underwent dedicated contrast-enhanced CT prior to nephrectomy for a renal cortical tumour between January 2000 and July 2011. Two radiologists evaluated all tumours on CT for size, necrosis, calcification, contour, renal vein invasion, collecting system invasion, contact with renal sinus fat, multicystic tumour architecture, nodular enhancement, and the degree of nephrographic phase enhancement. CT and clinical predictors (gender, body mass index [BMI], age) were incorporated into the nomogram. We employed multivariable logistic regression analysis to predict tumour type and internally validated the final model using the data from reader 1. External validation was performed by using all data from reader 2. We applied Wilcoxon rank sum test and Fisher's exact test to investigate for differences in tumour size, BMI, age, and differences in CT imaging features between patients with aggressive and those with indolent tumours. Results 63.6% (764/1201) of patients had clear-cell or other aggressive non-clear-cell RCC (i.e. papillary RCC type 2, unclassified RCC) and 36.4% (437/1201) had indolent renal cortical tumours (i.e. papillary RCC type 1, chromophobe RCC, angiomyolipoma, or oncocytoma). On CT, indolent tumours were significantly smaller (p < 0.001) than aggressive tumours and significantly associated with well-defined tumour contours (p < 0.001). Aggressive RCC were significantly associated with necrosis, calcification, renal vein invasion, collecting system invasion, contact with renal sinus fat, multicystic tumour architecture, and nodular enhancement (all, p < 0.001). The nomogram's concordance index (C-index) was 0.823 after internal and 0.829 after external validation. Concluding statement We present a nomogram based on 1201 patients combining CT features with clinical data for the prediction of indolent renal cortical tumours. When externally validated, this nomogram resulted in a C-index of 0.829

The Unmet Need for Rapid Epileptic Seizure Termination (REST) Therapy

Approximately 40% of newly diagnosed epilepsy patients will continue to experience resistant breakthrough seizures despite stable antiepileptic drug regimens. Rescue treatments have demonstrated efficacy and safety for select seizure emergencies. There are three regulatory approved and commercially available outpatient, nasally inhaled or rectally administered medications for acute repetitive seizures (ARS), and two injectable benzodiazepine formulations are indicated for parenteral treatment of established status epilepticus. Despite these advances in acute seizure control, no studies have been shown to abort an ongoing seizure following home administration of rescue therapy by the patient or a caregiver at the first clinical sign of seizure onset. Such treatment would require rapid systemic absorption without intravenous access, and clinical trial evidence of seizure cessation within minutes of administration that is superior to placebo (eg, seizure self-regulation). Rapid epileptic seizure termination (REST) therapy may be applicable to multiple types of seizure emergencies beyond ARS. Focal or generalized seizures preceded by an aura, flurries of absence of myoclonic seizures, or prolonged focal and generalized seizures present an increased risk for morbidity and/or progression to status epilepticus and may be responsive to REST therapy. Novel investigational drug-device combination therapies have demonstrated feasibility of intraictal delivery and cessation of epileptiform activity within two minutes. Randomized, placebo-controlled trials of REST treatment for diverse seizure emergencies are ongoing, and if positive, hold the potential to decrease bouts of mental and physical incapacitation in patients with refractory epilepsy

The unmet need for rapid epileptic seizure termination (REST)

•Rapid epileptic seizure termination (REST) treatment aims to abort an ongoing seizure.•Current outpatient rescue medications have not been sufficiently studied as REST treatment.•Successful REST medication requires IV-like pharmacokinetics.•Novel drug delivery systems suitable for REST treatment are in development. Approximately 40% of epilepsy patients will continue to experience breakthrough seizures despite stable antiepileptic drug regimens. Rescue treatments have demonstrated efficacy and safety for select seizure emergencies. Outpatient administered intranasal and rectally delivered medications are regulatory approved for acute repetitive seizures (ARS), and injectable benzodiazepines are indicated for parenteral treatment of established status epilepticus. Despite these advances, no studies have been shown to abort an ongoing seizure following patient or caregiver home administration of therapy at the first clinical sign of seizure onset. Such treatment would require rapid systemic absorption without intravenous access, and evidence of seizure cessation within minutes of administration that is superior to placebo (eg, seizure self-regulation). Rapid epileptic seizure termination (REST) treatment may apply to multiple seizure emergencies beyond ARS, including focal or generalized seizures preceded by an aura, flurries of absence or myoclonic seizures, or prolonged focal and generalized seizures at high risk of progression to status epilepticus. Novel investigational drug delivery systems have demonstrated feasibility of intraictal delivery and seizure cessation by two minutes. Ongoing randomized trials of REST treatment for diverse seizure emergencies hold the potential to decrease bouts of mental and physical incapacitation in patients with drug-resistant epilepsy