ABSTRACT
Background: Vestibular loss and dysfunction has been associated with cognitive deficits, decreased spatial navigation, spatial memory, visuospatial ability, attention, executive function, and processing speed among others. Superior semicircular canal dehiscence (SSCD) is a vestibular-cochlear disorder in humans in which a pathological third mobile window of the otic capsule creates changes to the flow of sound pressure energy through the perilymph/endolymph. The primary symptoms include sound-induced dizziness/vertigo, inner ear conductive hearing loss, autophony, headaches, and visual problems; however, individuals also experience measurable deficits in basic decision-making, short-term memory, concentration, spatial cognition, and depression. These suggest central mechanisms of impairment are associated with vestibular disorders; therefore, we directly tested this hypothesis using both an auditory and visual decision-making task of varying difficulty levels in our model of SSCD. Methods: Adult Mongolian gerbils (n = 33) were trained on one of four versions of a Go-NoGo stimulus presentation rate discrimination task that included standard ("easy") or more difficult ("hard") auditory and visual stimuli. After 10 days of training, preoperative ABR and c+VEMP testing was followed by a surgical fenestration of the left superior semicircular canal. Animals with persistent circling or head tilt were excluded to minimize effects from acute vestibular injury. Testing recommenced at postoperative day 5 and continued through postoperative day 15 at which point final ABR and c+VEMP testing was carried out. Results: Behavioral data (d-primes) were compared between preoperative performance (training day 8-10) and postoperative days 6-8 and 13-15. Behavioral performance was measured during the peak of SSCD induced ABR and c + VEMP impairment and the return towards baseline as the dehiscence began to resurface by osteoneogenesis. There were significant differences in behavioral performance (d-prime) and its behavioral components (Hits, Misses, False Alarms, and Correct Rejections). These changes were highly correlated with persistent deficits in c + VEMPs at the end of training (postoperative day 15). The controls demonstrated additional learning post procedure that was absent in the SSCD group. Conclusion: These results suggest that aberrant asymmetric vestibular output results in decision-making impairments in these discrimination tasks and could be associated with the other cognitive impairments resulting from vestibular dysfunction.
ABSTRACT
Background: Inflammatory bowel disease (IBD), subdivided into Crohn's disease (CD) and ulcerative colitis (UC), is an auto-inflammatory gastrointestinal condition with an established increased risk of certain malignancies. Compared to sporadic cancers in the general population, IBD-associated malignancies present unique challenges to providing quality care. Radiation therapy (RT) targeting IBD-associated malignancies may directly impact inflamed bowel, with special considerations for the risk of toxicities. Historically, patients with IBD have been less likely to receive radiotherapy in proximity to bowel due to a poor understanding of the potential for acute and chronic toxicities and unclear treatment outcomes. We present a scoping review, to more fully assess IBD-associated malignancies and their treatment. As opposed to a systematic review, this approach allows us to analyze the broadest range of literature, including experimental and non-experimental research, and reflect on current guidelines and practices. Methods: Literature search: a systematic, scoping search of published literature was conducted using applicable PRISMA scoping review (ScR) guidelines. The literature search was conducted on PubMed and was searched systematically by screening all publications from January 1990 to June 2021. Citations from the included articles were also manually searched. Relevant National Comprehensive Cancer Network guidelines were reviewed. Final query was December 2021 in editing. Articles were selected for full text reading if the abstract reported on malignancy in IBD or bowel toxicities. Results: The pelvic malignancies found in the IBD patient population, including colorectal carcinoma, anal carcinoma, lymphoma, small bowel adenocarcinoma (SBA), and prostate cancer (PCa) are outlined in this scoping review. Additional cancers that have a contested relationship with IBD, including cervical, bladder, and upper GI cancers, are also explored. This review provides literature guided recommendations on the eligibility of patients with IBD to receive RT, management of IBD during and after treatment, and counseling for radiation-induced toxicities. Conclusions: After review of the literature, IBD should not be considered an absolute contraindication to radiation therapy, given the lack of evidence for increased toxicities, and the evolution of RT techniques which limit radiation dose to the bowel.
