Widespread Disruptions of White Matter in Familial Multiple Sclerosis: DTI and NODDI Study

Diffusion tensor imaging (DTI) is a noninvasive, quantitative MRI technique that measures white matter (WM) integrity. Many brain dimensions are heritable, including white matter integrity measured with DTI. Family studies are valuable to provide insights into the interactive effects of non-environmental factors on multiple sclerosis (MS). To examine the contribution of familial factors to the diffusion signals across WM microstructure, we performed DTI and calculated neurite orientation dispersion plus density imaging (NODDI) diffusion parameters in two patient groups comprising familial and sporadic forms of multiple sclerosis and their unaffected relatives. We divided 111 subjects (49 men and 62 women: age range 19–60) into three groups conforming to their MS history. The familial MS group included 30 participants (patients; n = 16, healthy relatives; n = 14). The sporadic group included 41 participants (patients; n = 10, healthy relatives; n = 31). Forty age-matched subjects with no history of MS in their families were defined as the control group. To study white matter integrity, two methods were employed: one for calculating the mean of DTI, FA, and MD parameters on 18 tracts using Tracts Constrained by Underlying Anatomy (TRACULA) and the other for whole brain voxel-based analysis using tract-based spatial statistics (TBSS) on NDI and ODI parameters derived from NODDI and DTI parameters. Voxel-based analysis showed considerable changes in FA, MD, NDI, and ODI in the familial group when compared with the control group, reflecting widespread impairment of white matter in this group. The analysis of 18 tracts with TRACULA revealed increased MD and FA reduction in more tracts (left and right ILF, UNC, and SLFT, forceps major and minor) in familial MS patients vs. the control group. There were no significant differences between the patient groups. We found no consequential changes in healthy relatives of both patient groups in voxel-based and tract analyses. Considering the multifactorial etiology of MS, familial studies are of great importance to clarify the effects of certain predisposing factors on demyelinating brain pathology.

Natural History of Von Hippel-Lindau Disease-associated and Sporadic Clear Cell Renal Cell Carcinoma: a Comparative Study

Purpose: To compare the tumor growth kinetics between sporadic clear cell renal cell carcinoma (ccRCC) and Von Hippel-Lindau disease-associated renal cell carcinoma (VHL-associated RCC). To analyze predictive markers for the growth rate of these two types of RCC.Methods: The clinical data of patients with renal tumors who received active surveillance were collected retrospectively. Immunohistochemical staining was utilized to analyze the expression levels of VHL, PBRM1, H3K36me3, and BAP1 in the postoperative specimens.Results: The age of the VHL group was significantly younger than that of the sporadic group (P<0.0001). The mean linear growth rate (LGR) was significantly faster in the sporadic group (P=0.0004). The tumors of those in the sporadic group tended to have a higher histologic grade (P=0.0011). In the sporadic group, tumor histologic grade was an independent predictor for rapid mean LGR (P=0.0022). In the VHL group, tumor initial MTD was the only independent predictor for rapid mean LGR (P＜0.0001). Tumors with low VHL expression and negative PBRM1 expression showed a faster growth rate in the sporadic group (P=0.001 and P=0.008, respectively). The expression levels of the 4 biomarkers showed no impact on the tumor growth rate in the VHL group.Conclusion: Sporadic ccRCC grew faster than VHL-associated RCC. High histologic grade, low VHL expression and negative PBRM1 expression were predictors of faster growth in sporadic ccRCC. A large initial MTD was a predictor of faster growth for VHL-associated RCC.

On the involution fixity of simple groups

Let $G$ be a finite permutation group of degree $n$ and let ${\rm ifix}(G)$ be the involution fixity of $G$ , which is the maximum number of fixed points of an involution. In this paper, we study the involution fixity of almost simple primitive groups whose socle $T$ is an alternating or sporadic group; our main result classifies the groups of this form with ${\rm ifix}(T) \leqslant n^{4/9}$ . This builds on earlier work of Burness and Thomas, who studied the case where $T$ is an exceptional group of Lie type, and it strengthens the bound ${\rm ifix}(T) > n^{1/6}$ (with prescribed exceptions), which was proved by Liebeck and Shalev in 2015. A similar result for classical groups will be established in a sequel.

RETROSPECTIVE COHORT STUDY: DIFFERENCES AND SIMILARITIES BETWEEN SPORADIC AND FAMILIAL PAPILLARY THYROID CARCINOMA

INTRODUCTION There is a lot of controversy around the study of the familial papillary thyroid carcinoma (CPFT), which has a different behaviour than sporadic. The aim of this investigation is to establish the differences and similarities between sporadic papillary thyroid carcinoma and the familial one in order to determine if the familial type is a more aggressive clinical entity than sporadic. MATERIAL AND METHODS A retrospective cohort study in 231 patients with papillary thyroid carcinoma (CPT) from 2006 to 2018. One group was established according to the presence of two or more relatives as CPFT (n = 46) and the other group were the sporadic cases (n = 185). Throughout this study the clinical-pathological characteristics of both groups were compared based on the analysis of twenty-one variables. RESULTS After having carried out this investigation, statistically significant differences have only been found in the vascular invasion (p &lt; 0.001), presenting 3.8% in the sporadic group compared to the 21.7% found in the CPFT with an Odds Ratio of 7.6. CONCLUSIONS Based on our experience, patients with CPFT present a higher frequency of multifocal neoplasia, capsular invasion, vascular invasion, lymph node invasion and recurrence than sporadic CPT. However, these differences were only significant while analyzing the vascular invasion variable. Although the results of our study have been unable to prove that the CPFT is more aggressive than sporadic CPT, we recommend performing periodic ultrasounds such as the screening of the members of the families with CPFT. Finally, we conclude that more studies are needed.

Gene expression profiles of YAP1, TAZ, CRB3, and VDR in familial and sporadic multiple sclerosis among an Iranian population

Alterations in the regulatory mechanisms that control the process of myelination in the nervous system, may lead to the impaired myelination in the Multiple sclerosis. The Hippo pathway is an important mediator of myelination in the nervous system and might contribute to the pathophysiology of MS. This study examined via qPCR the RNA expression of YAP1, TAZ, and CRB3 as the key effectors of the Hippo pathway and also, VDR in the peripheral blood of 35 sporadic, 37 familial MS patients; and also 34 healthy first-degree relatives of the familial MS patients (HFR) and 40 healthy individuals without a family history of the disease (control). The results showed the increased expression of VDR in the sporadic group, as compared to other groups. There was also an increased expression of TAZ in the familial and HFR groups, as compared to the control group. The familial and sporadic patients displayed a significantly lower level of expression of YAP1 in comparison to the HFR group. The increased expression level in the sporadic patients and control group, as compared to the HFR group, was seen in CRB3. We also assessed different clinical parameters and MRI characteristics of the patients. Overall, these findings suggest that Hippo pathway effectors and also VDR gene may play a potential role in the pathophysiology of the sporadic and familial forms of MS. Confirmation of different gene expression patterns in sporadic and familial MS groups may have obvious implications for the personalization of therapies in the disease.

Expression and clinical significance of IL7R, NFATc2, and RNF213 in familial and sporadic multiple sclerosis

Background Multiple sclerosis (MS) is a chronic inflammatory and autoimmune disorder of the central nervous system characterized by myelin loss and axonal dysfunction. Increased production of inflammatory factors such as cytokines has been implicated in axon destruction in myelin-less areas. In the present study, we compared the expression level of IL7R, NFATc2, and RNF213 genes in the peripheral blood of 72 MS patients (37 familial MS, 35 sporadic MS) and 74 healthy controls (34 individuals with a family history of the disease, 40 healthy controls without a family history) via Real-time PCR. Results Our results showed that the expression level of IL7R was decreased in MS patients versus healthy controls. Also IL7R expression was significantly down-regulated in the sporadic group as compared to other groups. Additionally, there was an increased NFATc2 expression level in MS patients versus healthy controls. Increased expression of NFATc2 in sporadic and familial groups compared to the controls was also seen. Our results represented an increased expression level of RNF213 in the familial patients as compared to the control group. Diagnostic evaluation was performed by ROC curve analysis and area under the curve (AUC) calculation. The correlation of clinical parameters including onset age and EDSS with our gene expression levels were also assessed. Conclusions Overall, decreased expression level of IL7R and increased expression level of NFATc2 may be associated with the pathogenesis of MS disease. The RNF213 should be evaluated further for its potential as a candidate biomarker of inflammatory activity in MS in a larger cohort.

Protocol-Based Intravenous Fluid Hydration for Newly Created Ileostomies Decreases Readmissions Secondary to Dehydration

Background Newly created ileostomies often result in patient readmission due to dehydration secondary to high ostomy output. Implementation of a mandatory home intravenous hydration protocol can avoid this. We aim to evaluate the impact of mandatory home intravenous hydration for patients with newly created ileostomies. Materials and Methods All patients at a single, tertiary care center who underwent ileostomy creation during a period of sporadic home intravenous hydration (February 2011-December 2013) and mandatory protocol hydration (March 2016-December 2018) were reviewed for incidence of dehydration, readmissions, and emergency department visits. Results 241 patients were evaluated. 119 were in the “sporadic” group and 122 were in the “protocol” group. Operative approach differed among both groups, with hydration protocol patients undergoing 15% less open procedures and 4.9% more hand-assisted laparoscopic procedures ( P = .0017). Prior to protocol implementation, 23.5% of patients were sent home with intravenous hydration. Length of hospital stay after index ileostomy creation was shorter for “protocol” patients by 3.3 days ( P < .0001). 15.1% of “sporadic” patients experienced dehydration as compared to 7.4% of “protocol” patients ( P = .0283). Following protocol implementation, the number of patients readmitted due to dehydration increased from 13 to 14 ( P = .01). Discussion Standardized, mandatory at-home intravenous hydration following ileostomy creation leads to a significant reduction in postoperative incidence of dehydration and dehydration-associated readmissions. This protocol should be followed for all patients with newly created ileostomies, so long as adequate home health nursing support and active surveillance are available.

Stage at Diagnosis and Survival of Colorectal Cancer With or Without Underlying Inflammatory Bowel Disease: A Population-based Study

Background Inflammatory bowel disease [IBD] is a risk factor for colorectal cancer [CRC]. The aim of this study is to determine whether stage at diagnosis and survival differ between sporadic, ulcerative colitis [UC]- and Crohn’s disease [CD]-related CRC. Methods The English National Cancer Registry [NCIN], Hospital Episode Statistics [HES] and Office for National Statistics [ONS] datasets between 2000 and 2010 were linked, providing data on comorbidities, stage and date of death. A logistic regression model determined whether IBD was associated with an early [I/II] or late [III/IV] cancer. Cox regression analysis was used to examine survival differences between sporadic, UC- and CD-related cancers. Results A total of 234 009 patients with CRC were included, of whom 985 [0.4%] and 1922 [0.8%] had CD and UC, respectively. UC, but not CD, was associated with an earlier stage compared with sporadic cancers (odds ratio [OR] 0.88, 95% confidence interval [CI] 0.79 to 0.98, p = 0.02). CD had a significantly worse survival compared with sporadic patients for stage II [HR = 1.71, CI 1.26 to 2.31 p &lt;0.005] and III [1.53, CI 1.20 to 1.96, p &lt;0.005] cancer. UC patients were associated with worse survival compared with the sporadic group for both stage III [1.38, CI 1.17 to 1.63, p &lt;0.0005] and IV [1.13, CI 1.01 to 1.28, p = 0.04] cancer. After excluding sporadic patients, UC was associated with improved survival compared with CD [0.62, CI 0.43 to 0.90, p = 0.01] for stage II cancer. Conclusions Patients with IBD are diagnosed at an earlier stage but tend to have a worse survival compared with sporadic cases of CRC, in particular for nodal disease [stage III].Specifically, patients with CD-related CRC appear to fare worst in terms of survival compared with both the sporadic and UC groups.