Anisotropic Bladder Planning Target Volume in Bladder Radiation Therapy

Purpose

This study aimed to investigate 3 planning target volume (PTV) margin expansions and determine the most appropriate volume to be used in bladder preservation therapy when using daily cone beam computed tomography (CBCT). We aimed to establish whether a smaller PTV expansion is feasible without risking geographical miss.

Developing a Brief Neuropsychological Battery for Early Diagnosis of Cognitive Impairment

ObjectivesEarly diagnosis of cognitive impairment is increasingly emphasized in the literature to facilitate timely preventive interventions. Although bedside cognitive tests such as the Montreal Cognitive Assessment (MoCA) are widely used for such early diagnostic purposes, they may not have comparable performance to a full neuropsychological battery (FNB) in diagnosing early cognitive impairment. This study investigated whether a small subset of neuropsychological tests can be added on to MoCA to match its performance to that of the FNB in discriminating mild cognitive impairment and dementia (MCI/dementia) from normal cognition.DesignCross-sectional diagnostic study.SettingAlzheimer's Disease Centers across the United States.ParticipantsOlder participants (≥50 years) who completed MoCA and the FNB (N = 9187).MeasuresThe study sample was split into two: the derivation sample (n = 1837) was used to develop a brief neuropsychological battery that best discriminated MCI/dementia (using the best-subset approach with 10-fold cross-validation); while the validation sample (n = 7350) verified its actual performance in discriminating MCI/dementia.ResultsA 3-item neuropsychological battery was identified, comprising MoCA, Benson Complex Figure Recall, and Craft Story 21 Delayed Recall. It had excellent performance in discriminating MCI/dementia from normal cognition (area under the receiver operating characteristic curve [AUROC] 90.0%, 95% confidence interval [CI] 89.2%-90.7%), which was comparable to that of the FNB (AUROC 88.4%, 95% CI 87.6%-89.2%). By contrast, MoCA alone had significantly worse AUROC (86.9%, 95% CI 86.0%-87.7%) than that of the FNB.Conclusions/ImplicationsUsing rigorous methods, this study developed a brief neuropsychological battery that maintained the brevity of a bedside cognitive test, while rivaling the diagnostic performance of an FNB in early cognitive impairment. This brief battery offers a viable alternative when the FNB is needed but cannot be feasibly administered in nonspecialty clinics. It can have a wider health systems effect of improving patients’ access to accurate diagnosis in early cognitive impairment and facilitating timely interventions to delay the progression of cognitive impairment.     

Increased yield of full GBA sequencing in Ashkenazi Jews with Parkinson's disease

Background

Variants in GBA are the most common genetic risk factor for Parkinson's disease (PD), and are especially prevalent in the Ashkenazi Jewish (AJ) population. However, most studies on GBA in AJ genotype only seven selected Gaucher-associated pathogenic variants rather than sequencing the whole gene, which may leave carriers of PD-associated GBA variants undiscovered.

Circulating immune complexes during immunotherapy.

Chronic immunization may lead to the production of circulating immune complexes (CICs). This study was undertaken to determine the presence of circulating IgG immune complexes in 95 subjects with allergic rhinitis/asthma receiving immunotherapy, 46 individuals with similar diagnosis but not on immunotherapy, and 64 healthy controls. Modified Raji cell and murine leukemia cell (L-1210) assays, selected for a high density of Fc receptors and devoid of Epstein-Barr virus membrane antigen, were used. Other immunological parameters such as immunologlobulins G, A, M, E, and rheumatoid factor activity were also studied. The CIC concentrations in the treated group did not differ significantly from the untreated group, although both groups did have a significantly higher concentration than the healthy controls. The presence of CICs has no relationship with age or sex of patients, dosage of allergen administered, number and nature of allergens received, period between the time of last injection and the blood sampling, and the duration of immunotherapy. Serum IgG, IgA, IgM, and rheumatoid factor activity did not differ between the treated and untreated groups. IgE was significantly higher in the treated group when compared with the untreated, and IgE levels in treated patients with elevated CICs were significantly increased compared with CIC-negative treated patients. These data suggest that CICs are present in serum of atopic diseases such as allergic rhinitis/asthma. Significantly, an association of elevation of CICs with immunotherapy could not be demonstrated.     

Ejaculatory incompetence: a theoretical formulation and case illustration

Three theoretical formulations of ejaculatory incompetence have been proposed in the literature. They include: (1) aversive conditioned inhibition of the ejaculatory reflex, (2) an "autosexual" orientation associated with discrepant levels in the cognitive and physiological dimensions of sexual arousal, and (3) a discriminative learning model. These three models are discussed in relation to their theoretical and therapeutic implications. Clinical data supporting the discriminative view is presented.     

Orbital infarction and melting in a patient with systemic lupus erythematosus

OBJECTIVE: To present a patient with systemic lupus erythematosus who developed infarction and melting of the orbit secondary to her systemic disease. DESIGN: A case report. PARTICIPANT: A 61-year-old white woman with a 5-year history of systemic lupus erythematosus. METHODS: The patient presented with left orbital pain, limitation of extraocular movements, and a fistula from the ethmoid sinus to the upper eyelid. A detailed examination with computerized tomography, ultrasound, and a comprehensive medical evaluation with laboratory testing was performed. Histopathologic analysis with special stains of the orbital tissues was also performed. RESULTS: Histopathologic examination of the biopsy specimens revealed the features of an inflammatory process involving the orbit, similar to a panniculitis. These include a lymphocytic reaction with a predominance of plasma cells, vasculitis with occlusion, and thickening of the vessel walls, necrosis, and hyalinization of fat. CONCLUSION: This is a unique case in which infarction and melting of the entire orbital structures occurred in the presence of systemic lupus erythematosus. The underlying disease process is a lupus-related panniculitis. The authors stress that this is a very rare entity and that other diseases should be ruled out before entertaining this diagnosis.     

Age as a Critical Determinant of Atrial Fibrillation: A Two-sided Relationship

The incidence of atrial fibrillation (AF), the most common sustained arrhythmia and a major public health burden, increases exponentially with age. However, mechanisms underlying this long-recognized association remain incompletely understood. Experimental and human studies have demonstrated the involvement of aging in several arrhythmogenic processes, including atrial electrical and structural remodelling, disturbed calcium homeostasis, and enhanced atrial ectopic activity/increased vulnerability to re-entry induction. Given this wide range of putative mechanisms, the task of delineating the specific effects of aging responsible for AF promotion is not simple, as aging is itself associated with increasing prevalence of a host of AF-predisposing conditions, including heart failure, coronary artery disease, and hypertension. Although we usually think of old age promoting AF, there is also evidence that young age may actually have a protective effect against AF occurrence. For example, the low AF incidence among populations of young patients with significant structural congenital heart disease and substantial atrial enlargement/remodelling suggests that younger age might protect against fibrillation in the diseased atrium; efforts at understating how younger age may prevent AF might be helpful in elucidating missing mechanistic links between AF and age. The goal of this paper is to review the epidemiologic and pathophysiologic evidence regarding mechanisms underlying age-related AF. Although the therapeutic options for AF have recently improved, major gaps still remain and a better understanding of the special relationship between age and AF may be important for the identification of new targets for therapeutic innovation.