Most patients are eligible for an alternative to conventional whole breast irradiation for early‐stage breast cancer: A National Cancer Database Analysis

We evaluated the proportion of patients eligible for alternatives to standard whole breast irradiation (WBI) following breast‐conserving surgery using the National Cancer Database (NCDB). Using the 2016 dataset, Stage I‐III patients were identified. Eligibility for hypofractionated WBI (HFRT), accelerated partial breast irradiation (APBI) and endocrine therapy (ET‐alone) was defined using eligibility from large clinical trials as well as consensus guidelines. For patients with pN0 breast cancer, 20.6% and 37.0% were eligible for ET‐alone based on the CALGB 9343/PRIME‐II trials, respectively. In terms of HFRT, 72.5% and 50.4% were eligible based on IMPORT LOW/ASTRO HFRT guidelines, respectively. Based on IMPORT LOW/GEC‐ESTRO trial/ASTRO guidelines/ABS guidelines/GEC‐ESTRO guidelines, 72.5%, 86.1%, 39.0%, 72.5%, 45.7%, respectively, were eligible for APBI. Of those who qualify for HFRT per ASTRO guidelines, approximately 90% were eligible for APBI and 50% for ET‐alone. This analysis shows that a large proportion of patients with node‐negative breast cancer are eligible for HFRT, APBI and/or ET‐alone after breast‐conserving surgery.     

Generators of the intracranial P50 response in auditory sensory gating

Clarification of the cortical mechanisms underlying auditory sensory gating may advance our understanding of brain dysfunctions associated with schizophrenia. To this end, data from nine epilepsy patients who participated in an auditory paired-click paradigm during pre-surgical evaluation and had grids of electrodes covering temporal and frontal lobe were analyzed. A distributed source localization approach was applied to the intracranial P50 response and the Gating Difference Wave obtained by subtracting the response to the second stimuli from the response to the first stimuli. Source reconstruction of the P50 showed that the main generators of the response were localized in the temporal lobes. The analysis also suggested that the maximum neuronal activity contributing to the amplitude reduction in the P50 time range (phenomenon of auditory sensory gating) is localized at the frontal lobe. Present findings suggest that while the temporal lobe is the main generator of the P50 component, the frontal lobe seems to be a substantial contributor to the process of sensory gating as observed from scalp recordings.     

Targeted gene panel for genetic testing of south Indian children with steroid resistant nephrotic syndrome

Background

Steroid resistant nephrotic syndrome (SRNS) is a genetically heterogeneous disease with significant phenotypic variability. More than 53 podocyte-expressed genes are implicated in SRNS which complicates the routine use of genetic screening in the clinic. Next generation sequencing technology (NGS) allows rapid screening of multiple genes in large number of patients in a cost-effective manner.

Methods

We developed a targeted panel of 17 genes to determine relative frequency of mutations in south Indian ethnicity and feasibility of using the assay in a clinical setting. Twenty-five children with SRNS and 3 healthy individuals were screened.

Results

In this study, novel variants including 1 pathogenic variant (2 patients) and 3 likely pathogenic variants (3 patients) were identified. In addition, 2 novel variants of unknown significance (VUS) in 2 patients (8% of total patients) were also identified.

Conclusions

The results show that genetic screening in SRNS using NGS is feasible in a clinical setting. However the panel needs to be screened in a larger cohort of children with SRNS in order to assess the utility of the customised targeted panel in Indian children with SRNS. Determining the prevalence of variants in Indian population and improvising the bioinformatics-based filtering strategy for a more accurate differentiation of pathogenic variants from those that are benign among the VUS will help in improving medical and genetic counselling in SRNS.

     

Ultrasound of Adnexal Masses

Current advancements in imaging technology, especially three-dimensional/four-dimensional ultrasound and contrast-enhanced imaging, have increased the diagnostic yield of adnexal masses. The benefit of ultrasound is the characterization of an adnexal mass, suggesting the probable etiology of the mass. Masses may be divided as solid, cystic, or complex. It is predominantly the solid and complex masses that need a thorough evaluation. The role of color-flow imaging is now gaining importance and criteria for distinguishing between benign and malignant masses are often possible. Availability of a scoring system enables the differentiation of small adnexal masses. Several benign lesions may present as complex masses but can be distinguished and diagnosed on sonography. The availability of 3D ultrasound has been of great use to understand spatial relations and vascular morphology. Sonography allows a more detailed assessment of morphologic features of an adnexal mass. With a benign-appearing adnexal mass on sonography, the need for any further diagnostic tests is often obviated.     

Cortical inhibition and excitation in abstinent cocaine-dependent patients: a transcranial magnetic stimulation study

Prior transcranial magnetic stimulation studies showed that resting motor threshold is elevated in abstinent cocaine-dependent patients, suggesting a decrease in axonal excitability. In contrast, the increased incidence of seizures and psychosis in this group suggests increased excitability or decreased inhibition. Here, we studied long-interval intracortical facilitation and long-interval intracortical inhibition, paired-pulse transcranial magnetic stimulation measures that are more directly linked to glutamatergic cortical facilitation and GABAergic inhibition, respectively. Ten cocaine-dependent and 10 healthy controls were examined. Resting motor threshold, long-interval intracortical facilitation and long-interval intracortical inhibition were tested from the left motor cortex. The cocaine group showed an elevated resting motor threshold and an increased long-interval intracortical facilitation, whereas long-interval intracortical inhibition was normal. Although the increase in long-interval intracortical facilitation suggests exaggerated cortical glutamatergic excitability, the increase in resting motor threshold may signify a protective mechanism against seizures and psychosis.     

Increased prevalence of antimitochondrial antibodies in first-degree relatives of patients with primary biliary cirrhosis

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disorder that can progress to cirrhosis, shortening life expectancy. PBC patients are often asymptomatic, present with biochemical cholestasis, and test positive (>or=90%) for antimitochondrial antibodies (AMAs) in serum. Although AMA positivity without biochemical cholestasis may indicate increased risk of future PBC development, the contribution of these antibodies to pathogenesis remains enigmatic. Environmental risks and genetic determinants are likely implicated in PBC etiology. Given the familial aggregation of PBC, we hypothesized that AMAs also aggregate among relatives of PBC probands. We investigated the prevalence of AMAs in first-degree relatives (FDRs) of PBC probands to examine whether AMAs aggregate in such pedigrees. Using a PBC family registry, we prospectively screened for AMAs in the serum of 306 FDRs in 145 pedigrees, 350 PBC probands, and 196 controls who were age-matched, sex-matched, race-matched, and residence-matched to probands. The prevalence of AMA in FDRs and controls was 13.1% and 1%, respectively. Greater prevalence of AMA was found in female FDRs of PBC probands [sisters (20.7%), mothers (15.1%), and daughters (9.8%)] than in male FDRs [brothers (7.8%), fathers (3.7%), and sons (0%)]. CONCLUSIONS: AMAs aggregate among FDRs of PBC probands. Our data have clinical implications for FDRs of PBC probands because AMA positivity may suggest susceptibility to PBC. Thus, the identification and follow-up of these relatives may lead to earlier disease diagnosis and treatment. Furthermore, if AMA development is heritable, this trait will provide a basis to dissect the genetic predisposition to PBC.