Confocal Microscopy Provides a Rapid Intraoperative Histological Assessment of Brain Neoplasms: Experience with 106 Cases

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.Frozen section histological analysis is the mainstay for intra-procedural tissue diagnosis during resection of intracranial neoplasms and for evaluating tumor margins. However, frozen sections are time-consuming and sometimes inaccurate. This study describes potential advantages of CSM imaging of fresh human brain tumor tissues labeled various fluorophores within the neurosurgical operating room facility.This item is part of the College of Medicine - Phoenix Scholarly Projects 2019 collection. For more information, contact the Phoenix Biomedical Campus Library at [email protected]

Seasonal variation of hip fractures in patients with Benign Paroxysmal Positional Vertigo

Introduction: Seasonal variation of benign paroxysmal positional vertigo (BPPV) presentation has been reported, with higher rates of presentation in months associated with times of lower serum vitamin D levels. The purpose of this study was to examine the association between the timing of hip fracture in patients with BPPV. Methods: A retrospective review (2013 to 2019) of adult patients was performed at a tertiary care academic center to identify patients with hip fracture due to ground level fall (ICD-10 code S72) and a previously established diagnosis of vestibular disorder (ICD-10 codes H81-83, A88.1, and R42). Included patients were matched by age and sex to control for patients who had hip fracture without a vestibular diagnosis. Patient charts were reviewed, and demographic and clinical data were extracted related to hip fracture and prior vestibular diagnosis. Groups were subdivided based on whether patients had a hip fracture from January to June versus July to December. Fisher’s exact test was used to evaluate for a difference in seasonal variation between groups. Results: There were 201 patients with vestibular disorders of whom 27 patients carried the diagnosis of BPPV, with a mean age of 80.4 years. The rates of hip fracture among patients with BPPV was higher in the period extending from January to June (63.0%) versus July to December (37.0%), [odds ratio 1.59, 95% CI 0.66-4.00]. The rate of hip fracture was not significantly different between these time periods for the control group (51.7% versus 48.3%) or the vestibular group (53.2% versus 46.8%). Conclusion: These results offer preliminary evidence that, in addition to an increased presentation for BPPV during months associated with decreased serum vitamin D, injuries due to BPPV may be increased as well. The present study is limited by the statistical power afforded by the small number of patients with BPPV and hip fracture that were identified

DOTA-Derivatives of Octreotide Dicarba-Analogs with High Affinity for Somatostatin sst2,5 Receptors

In vivo somatostatin receptor scintigraphy is a valuable method for the visualization of human endocrine tumors and their metastases. In fact, peptide ligands of somatostatin receptors (sst's) conjugated with chelating agents are in clinical use. We have recently developed octreotide dicarba-analogs, which show interesting binding profiles at sst's. In this context, it was mandatory to explore the possibility that our analogs could maintain their activity also upon conjugation with DOTA. In this paper, we report and discuss the synthesis, binding affinity and conformational preferences of three DOTA-conjugated dicarba-analogs of octreotide. Interestingly, two conjugated analogs exhibited nanomolar affinities on sst(2) and sst(5) somatostatin receptor subtypes

Microvascular Anastomosis Under 3D Exoscope or Endoscope Magnification: A Proof-Of-Concept Study

Background: Extracranial-intracranial bypass is a challenging procedure that requires special microsurgical skills and an operative microscope. The exoscope is a tool for neurosurgical visualization that provides view on a heads-up display similar to an endoscope, but positioned external to the operating field, like a microscope. The authors carried out a proof-of-concept study evaluating the feasibility and effectiveness of performing microvascular bypass using various new exoscopic tools. Methods: We evaluated microsurgical procedures using a three-dimensional (3D) endoscope, hands-free robotic automated positioning two-dimensional (2D) exoscope, and an ocular-free 3D exoscope, including surgical gauze knot tying, surgical glove cutting, placental vessel anastomoses, and rat vessel anastomoses. Image quality, effectiveness, and feasibility of each technique were compared among different visualization tools and to a standard operative microscope. Results: 3D endoscopy produced relatively unsatisfactory resolution imaging. It was shown to be sufficient for knot tying and anastomosis of a placental artery, but was not suitable for anastomosis in rats. The 2D exoscope provided higher resolution imaging, but was not adequate for all maneuvers because of lack of depth perception. The 3D exoscope was shown to be functional to complete all maneuvers because of its depth perception and higher resolution. Conclusion: Depth perception and high resolution at highest magnification are required for microvascular bypass procedures. Execution of standard microanastomosis techniques was unsuccessful using 2D imaging modalities because of depth-perception-related constraints. Microvascular anastomosis is feasible under 3D exoscopic visualization; however, at highest magnification, the depth perception is inferior to that provided by a standard operative microscope, which impedes the procedure

Characterisation of the immune-related transcriptome in resected biliary tract cancers

Although biliary tract cancers (BTCs) are known to have an inflammatory component, a detailed characterisation of immune-related transcripts has never been performed. In these studies, nCounter PanCancer Immune Profiling Panel was used to assess the expression of 770 immune-related transcripts in the tumour tissues (TTs) and matched adjacent tissues (ATs) of resected BTCs. Cox regression analysis and Kaplan-Meier methods were used to correlate findings with relapse-free survival (RFS). The first analysis in the TT and AT of an exploratory set (n = 22) showed deregulation of 39 transcripts associated with T-cell activation. Risk of recurrence was associated with a greater number of genes deregulated in AT in comparison to TT. Analysis in the whole set (n = 53) showed a correlation between AT cytotoxic T-lymphocyte antigen-4 (CTLA4) expression and RFS, which maintained statistical significance at multivariate analysis. CTLA4 expression correlated with forkhead box P3 (FOXP3) expression, suggesting enrichment in T regulatory cells. CTLA4 is known to act by binding to the cluster of differentiation 80 (CD80). No association was seen between AT CD80 expression and RFS. However, CD80 expression differentiated prognosis in patients who received adjuvant chemotherapy. We showed that the immunomodulatory transcriptome is deregulated in resected BTCs. Our study includes a small number of patients and does not enable to draw definitive conclusions; however, it provides useful insights into potential transcripts that may deserve further investigation in larger cohorts of patients. TRANSCRIPT PROFILING: Nanostring data have been submitted to GEO repository: GSE90698 and GSE906

Thyroid Cancer and Fibroblasts

Thyroid cancer is the most common type of endocrine cancer, and its prevalence continue to rise. Non-metastatic thyroid cancer patients are successfully treated. However, looking for new therapeutic strategies is of great importance for metastatic thyroid cancers that still lead to death. With respect to this, the tumor microenvironment (TME), which plays a key role in tumor progression, should be considered as a new promising therapeutic target to hamper thyroid cancer progression. Indeed, thyroid tumors consist of cancer cells and a heterogeneous and ever-changing niche, represented by the TME, which contributes to establishing most of the features of cancer cells. The TME consists of extracellular matrix (ECM) molecules, soluble factors, metabolites, blood and lymphatic tumor vessels and several stromal cell types that, by interacting with each other and with tumor cells, affect TME remodeling, cancer growth and progression. Among the thyroid TME components, cancer-associated fibroblasts (CAFs) have gained more attention in the last years. Indeed, recent important evidence showed that thyroid CAFs strongly sustain thyroid cancer growth and progression by producing soluble factors and ECM proteins, which, in turn, deeply affect thyroid cancer cell behavior and aggressiveness. Hence, in this article, we describe the thyroid TME, focusing on the desmoplastic stromal reaction, which is a powerful indicator of thyroid cancer progression and an invasive growth pattern. In addition, we discuss the origins and features of the thyroid CAFs, their influence on thyroid cancer growth and progression, their role in remodeling the ECM and their immune-modulating functions. We finally debate therapeutic perspectives targeting CAFs

Mental Health in Multiple Sclerosis During the COVID-19 Outbreak: A Delicate Balance between Fear of Contagion and Resilience

The current study aimed at exploring the relationship between objective disability, illness perceptions, resilience, fear of COVID-19, and psychological distress (i.e., anxiety, depression, and stress) in people with multiple sclerosis (pwMS) during the second wave of the COVID-19 outbreak. A group of 122 pwMS recruited in an Italian university hospital took part in this cross-sectional monocentric study. Hierarchical multiple linear regression analyses were performed to assess the strength of the hypothesized associations. Results indicated that, differently from cognitive impairment, motor disability was positively associated with anxiety. However, accounting for subjective illness perception, such association was no longer significant. Moreover, accounting for both protective and risk factors in the models, even illness perception was no longer significant, highlighting the central role of resilience and fear of COVID-19 in explaining the negative emotional outcomes. Implications for clinical interventions and psychoeducational trainings are discussed