The effect of bone marrow-derived mesenchymal stem cell co-transplantation with hematopoietic stem cells on liver fibrosis alleviation and survival in patients with class III ß-thalassemia major.

BACKGROUND: Hepatic fibrosis is a common complication in transfusion-dependent thalassemia patients. Data on the co-transplantation of mesenchymal stem cells (MSCs) with hematopoietic stem cells (HSCs) in beta-thalassemia major patients are scarce. Therefore, we aimed to evaluate the effect of co-transplantation of bone marrow-derived MSC with HSCs on the liver fibrosis alleviation and transplant outcomes in class III beta-thalassemia major. METHODS: Between April 1998 and January 2017, a total of 224 consecutive patients with class III beta-thalassemia major underwent allogeneic HSCT in the Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran. To assess liver fibrotic changes after transplantation, 47 patients participated in the MSC plus HSC group and 30 patients in the HSC only group at the end of the follow-up period. All patients underwent laboratory tests, especially serum ferritin and liver function testing, hepatic T2* MRI, liver biopsy, and FibroScan before and 2 years after transplantation. Kaplan-Meier curves were derived to determine survival and were compared using the log-rank test. Repeated-measure, mixed-effect linear regression models were used to examine the changes in liver fibrosis over time. RESULTS: The 10-year OS rate was 71.84% in the mesenchymal group and 61.89% in the non-mesenchymal group (P value = 0.294), while the 10-year TFS rate was 63.64% in the mesenchymal group and 52.78% in the non-mesenchymal group (P value = 0.285). No significant difference was observed in the 10-year NRM, rejection rate, ANC engraftment, platelet engraftment, acute GvHD, and chronic GvHD between the two groups. In addition, the results of repeated-measure, mixed-effect linear regression models showed that none of the variables determining hepatic fibrosis had a significant difference between patients receiving MSCs and patients who did not receive MSCs. CONCLUSIONS: Based on the results of this study, a single infusion of MSCs at the time of HSCT to patients with class III beta-thalassemia major could not significantly improve the liver fibrosis alleviation and transplantation outcomes, including OS, TFS, TRM, rejection rate, ANC engraftment, platelet engraftment, acute GvHD, and chronic GvHD.

Channelopathy-related SCN10A gene variants predict cerebellar dysfunction in multiple sclerosis.

OBJECTIVE: To determine the motor-behavioral and neural correlates of putative functional common variants in the sodium-channel NaV1.8 encoding gene (SCN10A) in vivo in patients with multiple sclerosis (MS). METHODS: We recruited 161 patients with relapsing-onset MS and 94 demographically comparable healthy participants. All patients with MS underwent structural MRI and clinical examinations (Expanded Disability Status Scale [EDSS] and Multiple Sclerosis Functional Composite [MSFC]). Whole-brain voxel-wise and cerebellar volumetry were performed to assess differences in regional brain volumes between genotype groups. Resting-state fMRI was acquired from 62 patients with MS to evaluate differences in cerebellar functional connectivity. All participants were genotyped for 4 potentially functional SCN10A polymorphisms. RESULTS: Two SCN10A polymorphisms in high linkage disequilibrium (r(2) = 0.95) showed significant association with MSFC performance in patients with MS (rs6795970: p = 6.2 × 10(-4); rs6801957: p = 0.0025). Patients with MS with rs6795970(AA) genotype performed significantly worse than rs6795970(G) carriers in MSFC (p = 1.8 × 10(-4)) and all of its subscores. This association was independent of EDSS and cerebellar atrophy. Although the genotype groups showed no difference in regional brain volumes, rs6795970(AA) carriers demonstrated significantly diminished cerebellar functional connectivity with the thalami and midbrain. No significant SCN10A-genotype effect was observed on MSFC performance in healthy participants. CONCLUSIONS: Our data suggest that SCN10A variation substantially influences functional status, including prominent effects on motor coordination in patients with MS. These findings were supported by the effects of this variant on a neural system important for motor coordination, namely cerebello-thalamic circuitry. Overall, our findings add to the emerging evidence that suggests that sodium channel NaV1.8 could serve as a target for future drug-based interventions to treat cerebellar dysfunction in MS.

Relationship between CT volumetric measurements and Doppler perfusion indices in gastrointestinal liver metastasis.

PURPOSE: This study investigated how the volume of hepatic metastatic lesions can affect liver haemodynamics and whether these perfusion parameters may help to differentiate benign and malignant liver lesions. MATERIALS AND METHODS: The Doppler perfusion index (DPI the ratio of arterial to total liver blood flow) was measured in 46 patients aged 29-83 years, exhibiting up to four focal hyperechoic liver lesions at ultrasound examination. They comprised histopathologically proven liver metastasis of colorectal (19 cases) and gastric (10 cases) adenocarcinoma without local recurrence at the site of the previously resected primary tumour, along with 17 subjects with haemangioma. All patients underwent volumetric assessment using multislice computed tomography to calculate total volume of hepatic lesions. RESULTS: The mean DPI of patients with colorectal (36 ± 2 %) and gastric (39 ± 6 %) metastasis was significantly higher than those with haemangioma (14 ± 2 %) (both p < 0.001), whereas metastatic groups did not exhibit any difference in terms of mean DPI. Statistically significant correlations were found between DPI values and calculated total volume of lesions in patients with colorectal and gastric metastasis (r = 0.55, p = 0.01 and r = 0.85, p = 0.002, respectively) while this correlation was not demonstrated in the haemangioma group. Simple linear regression analysis revealed that every 1 cm(3) increment in total volume of metastatic lesions increased DPI by 0.2 % [95 % confidence interval (CI) 0.1-0.3, p = 0.001]. CONCLUSION: Doppler perfusion index alterations are directly correlated with total volume of metastatic deposits, and DPI measurement can be a valuable method to distinguish haemangioma from hyperechoic colorectal and gastric metastatic lesions.

Breast arterial calcification and risk of carotid atherosclerosis: focusing on the preferentially affected layer of the vessel wall.

OBJECTIVE: To assess the relationship between breast arterial calcification (BAC) detected on screening mammography and atherosclerosis of carotid arteries considering the most likely involved layer of the arterial wall. MATERIALS AND METHODS: A total of 537 consecutive women who underwent screening mammography were enrolled in this study. Seventy-nine subjects having BAC, aged 46-75 years, and 125 age-matched controls from those without BAC were selected for ultrasound examination of carotid arteries assessing intima-media thickness (IMT) and plaque presence. Participants were divided into three groups of risk including, low-risk: IMT<0.6mm without plaque, medium-risk: 0.6mm≤IMT≤0.8mm without plaque and high-risk: IMT>0.8mm and/or plaque. Risk factors for atherosclerosis were obtained from medical records for independent effects. RESULTS: BAC was present in 14.7% of mammograms. According to multivariable logistic regression analyses, significant association was identified between the carotid atherosclerosis risk and presence of BAC. Compared to women with IMT<0.6mm, those with 0.6mm≤IMT≤0.8mm and IMT>0.8mm had OR (95% CI) of 4.88 (1.47-16.16) and 23.36 (4.54-120.14), respectively. The OR (95% CI) for carotid plaque was 3.13 (1.3-7.57). There was no interaction between IMT category and plaque. Significant associations were also detected with postmenopausal duration (P=0.02) and hypertension (P=0.004). CONCLUSION: The risk of carotid atherosclerosis increases with the presence of BAC. Women with BAC are more likely to have thicker IMT than plaque, which could be attributed to the preferentially similar affected layer of media causing thick IMT rather than plaque.