IV/IT hUC-MSCs Infusion in RRMS and NMO: A 10-Year Follow-Up Study
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ABSTRACT:
SUBMITTER: Lu Z
PROVIDER: S-EPMC7506071 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
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Project description:Neuromyelitis optica (NMO) is a severe autoimmune inflammatory disease of the central nervous system that affects motor function and causes relapsing disability. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have been used extensively in the treatment of various inflammatory diseases, due to their potent regulatory roles that can mitigate inflammation and repair damaged tissues. However, their use in NMO is currently limited, and the mechanism underlying the beneficial effects of hUC-MSCs on motor function in NMO remains unclear. In this study, we investigate the effects of hUC-MSCs on the recovery of motor function in an NMO systemic model. Our findings demonstrate that milk fat globule epidermal growth 8 (MFGE8), a key functional factor secreted by hUC-MSCs, plays a critical role in ameliorating motor impairments. We also elucidate that the MFGE8/Integrin αvβ3/NF-κB signaling pathway is partially responsible for structural and functional recovery, in addition to motor functional enhancements induced by hUC-MSC exposure. Taken together, these findings strongly support the involvement of MFGE8 in mediating hUC-MSCs-induced improvements in motor functional recovery in an NMO mouse model. In addition, this provides new insight on the therapeutic potential of hUC-MSCs and the mechanisms underlying their beneficial effects in NMO.
| S-EPMC10798960 | biostudies-literature
Project description:A 10-year observational follow-up study to evaluate the changes in sleep architecture during the menopausal transition. Fifty-seven premenopausal women (mean age 46 years, SD 0.9) were studied at baseline and after a 10-year follow-up. At both time points, polysomnography (PSG) was performed, and the serum follicle-stimulating hormone (S-FSH) concentration was measured. Linear regression models were used to study the effects of aging and menopause (assessed as change in S-FSH) on sleep. After controlling for body mass index, vasomotor, and depressive symptoms, higher S-FSH level was associated with longer sleep latency (B 0.45, 95% confidence interval [CI]: 0.07 to 0.83). Aging of 10 years was associated with shorter sleep latency (B -46.8, 95% CI: -77.2 to -16.4), shorter latency to stage 2 sleep (B -50.6, 95% CI: -85.3 to -15.9), decreased stage 2 sleep (B -12.4, 95% CI: -21.4 to -3.4), and increased slow-wave sleep (B 12.8, 95% CI: 2.32 to 23.3) after controlling for confounding factors. This study suggests that PSG measured sleep of middle-aged women does not worsen over a 10-year time span due to the menopausal transition. The observed changes seem to be rather age- than menopause-dependent.
| S-EPMC8193555 | biostudies-literature
Project description:BackgroundFabry disease (FD) is a rare X-linked disorder of sphingolipid metabolism that results in chronic proteinuric nephropathy. Podocytes are one of the most affected renal cells and play an important role in the development and progression of kidney disease. Detached podocytes found in urine (podocyturia) are considered as a non-invasive early marker of kidney injury; however, the dynamics of podocyte loss remains unknown.MethodsIn this 10-year follow-up study, podocyturia and other renal clinical data were evaluated in 39 patients with FD. From 2009 to 2019, podocyturia was assessed in 566 fresh urine samples from 13 male and 26 female FD patients using immunocytochemical detection of podocalyxin.ResultsPodocyturia (number of podocytes per 100 mL of urine) was found in 311/566 (54.9%) of the samples, more frequently (68.9 ± 21.9% versus 50.6 ± 25.9%; P = 0.035) and with higher values (364 ± 286 versus 182 ± 180 number of podocytes per gram of creatinine (Cr) in urine; P = 0.020) in males compared with females. The mean number of assessed samples for each patient was 14.5 (range 3-40) and the frequency of samples with podocyturia ranged from 0% to 100% (median 57%). Podocyturia was already present in 42.9% of patients <20 years of age and in 89.5% of normoalbuminuric patients. Podocyturia correlated with albuminuria (urine albumin:Cr ratio) (r = 0.20, P < 0.001) and a higher incidence and values of podocyturia were observed in patients with lower estimated glomerular filtration rate.ConclusionsOur data demonstrated that podocyturia is an early clinical event in the development of nephropathy. In addition, we found podocyturia to be a discontinuous event with wide variability.
| S-EPMC8824799 | biostudies-literature
Project description:BackgroundIn the phase 2 CAMMS223 trial (NCT00050778), alemtuzumab significantly improved clinical and MRI outcomes versus subcutaneous interferon beta-1a over 3 years in treatment-naive patients with relapsing-remitting MS. Here, we assess efficacy and safety of alemtuzumab over 12 years in CAMMS223 patients who enrolled in the CAMMS03409 extension (NCT00930553), with available follow-up through the subsequent TOPAZ extension (NCT02255656).MethodsIn CAMMS223, patients received 2 alemtuzumab courses (12 mg/day; baseline: 5 days; 12 months later: 3 days); 22% received a third course. In the open-label, nonrandomized extensions, patients could receive as-needed additional alemtuzumab or other disease-modifying therapies.ResultsOf 108 alemtuzumab-treated patients in CAMMS223, 60 entered the CAMMS03409 extension; 33% received a total of 2 alemtuzumab courses, and 73% received no more than 3 courses through Year 12. Over 12 years, annualized relapse rate was 0.09, 71% of patients had stable or improved Expanded Disability Status Scale scores, and 69% were free of 6-month confirmed disability worsening. In Year 12, 73% of patients were free of MRI disease activity. Cumulatively throughout the extensions (Years 7-12), 34% of patients had no evidence of disease activity. Adverse event (AE) incidence declined through Year 12. Infusion-associated reactions peaked at first course and declined thereafter. Cumulative thyroid AE incidence was 50%; one immune thrombocytopenia event occurred, and there were no autoimmune nephropathy cases.ConclusionsAlemtuzumab efficacy was maintained over 12 years in CAMMS223 patients, with 73% receiving no more than three courses. The safety profile in this cohort was consistent with other alemtuzumab clinical trials.
| S-EPMC7578137 | biostudies-literature
Project description:Sotos syndrome is caused by a gene deletion with an autosomal dominant pattern of inheritance. Cerebral gigantism, hypotonia and joint hyperextensibility are characteristic features of this syndrome. A percentage of these patients develop progressive scoliosis early in life. In the literature, few studies on the evolution of scoliosis in Sotos syndrome have been published. We retrospectively evaluated eight patients diagnosed with Sotos syndrome and scoliosis treated at the Garrahan Children Hospital between 1988 and March 2009. Clinical charts and imaging studies were assessed. Eight patients (19%) presented with scoliosis and seven of them (87.5%) required surgical treatment. The mean follow-up was 9.5 years (range 3-18). Mean age at first consultation was 5.2 years (range 1.1-11.2). Mean Cobb angle for scoliosis at first consultation was 34.3° (range 20°-42°) and the mean Cobb angle for kyphosis was 45.6° (range 30°-90°). Mean age at surgery was 11.2 years (range 3.7-18.10). The surgical procedures performed were instrumented posterior arthrodesis, alone or combined with anterior arthrodesis, instrumented anterior arthrodesis, while one patient is currently in treatment with growing rods. Preoperative mean Cobb angle for scoliosis was 72.3° (range 54°-130°) and for kyphosis was 59.8° (range 30°-108°); postoperative mean Cobb angle for scoliosis was 45.5° (range 6°-90°) and for kyphosis was 40.2° (range 30°-80°). There were three early complications (pleural effusion in two cases and death due to sepsis in one) and two late complications (kyphosis above the instrumentation area and dislodgement of the proximal hooks). Incidence of scoliosis in Sotos syndrome is high and thus close monitoring of patients with Sotos syndrome during growth is important for early detection of this entity. Joint hyperextensibility and hypotonia that are characteristic of the syndrome should be considered at the moment of surgery to avoid short fusions.
| S-EPMC3111518 | biostudies-literature
Project description:Introduction:The aim of this prospective study was to investigate excessive daytime sleepiness (EDS) over time and in relation to other PD symptoms among people with Parkinson's disease (PD). Methods:Thirty participants younger than 65 years with PD were randomly selected. At inclusion, mean (SD) disease duration was 6.2 (4.8) years and median (min-max) severity of PD was classified as stage II (stages I-III) according to Hoehn and Yahr. Participants were followed annually for 10 years with clinical assessments of their PD status, medications, comorbidities, and a standardized interview about their sleep habits and occurrence of daytime sleepiness. EDS was assessed by the self-reported Epworth Sleepiness Scale (ESS). Seventeen participants completed the 10-year longitudinal follow-up. Results:Fifteen of 30 persons were classified to suffer from EDS (ESS > 10) at baseline. At the group level, EDS remained stable over 10 years and did not deteriorate in parallel with worsening of motor symptoms. Furthermore, EDS was associated with sleep quality, fatigue, anxiety, depression, and axial/postural/gait impairments. Conclusions:EDS did not worsen over 10 years, although other PD aspects did. EDS in PD seems to be a complex nonmotor symptom that is unrelated to deterioration of motor symptoms in PD.
| S-EPMC6748198 | biostudies-other
Project description:ObjectiveTo define the long-term outcome of delayed orthostatic hypotension (OH).HypothesisDelayed OH is an early and milder form of OH that progresses over time.MethodsWe reviewed the medical records of 230 previously reported patients who completed autonomic testing at our center from January 1, 2002, through December 31, 2003. All available information on clinical diagnosis, mortality, medication use, and autonomic testing were extracted and included in the reported outcomes. Standard criteria were used to define OH and delayed OH.ResultsForty-eight individuals with delayed OH, 42 individuals with OH, and 75 controls had complete follow-up data. Fifty-four percent of individuals with delayed OH progressed to OH. Thirty-one percent of individuals with delayed OH developed an α-synucleinopathy. The 10-year mortality rate in individuals with delayed OH was 29%, in individuals with baseline OH was 64%, and in controls was 9%. The 10-year mortality of individuals who progressed to OH was 50%. Progression to OH was associated with developing an α-synucleinopathy, baseline diabetes, and abnormal baseline autonomic test results.ConclusionDelayed OH frequently progresses to OH with a high associated mortality.
| S-EPMC4626242 | biostudies-literature
Project description:Continuous intraperitoneal insulin infusion (CIPII) with an implantable pump is a treatment option for patients with type 1 diabetes mellitus (T1DM). Aim of the present study was to describe the long-term course of glycaemic control, complications, health related quality of life (HRQOL) and treatment satisfaction among T1DM patients treated with CIPII.Nineteen patients that participated in a randomized cross-over trial comparing CIPII and subcutaneous (SC) therapy in 2006 were followed until 2012. Laboratory, continuous glucose monitoring, HRQOL and treatment satisfaction measurements were performed at the start of the study, the end of the SC-, the end of the CIPII treatment phase in 2006 and during CIPII therapy in 2012. Linear mixed models were used to calculate estimated values and to test differences between the moments in time.In 2012, more time was spent in hyperglycaemia than after the CIPII treatment phase in 2006: 37% (95% CI 29, 44) vs. 55% (95% CI 48, 63), mean difference 19.8% (95% CI 3.0, 36.6). HbA1c was 65 mmol/mol (95% CI 60, 71) at the end of the SC treatment phase in 2006, 58 mmol/mol (95% CI 53, 64) at the end of the CIPII treatment phase and 65 mmol/mol (95% CI 60, 71) in 2012, respectively (p?>?0.05). In 2012, the median number of grade 2 hypoglycaemic events per week (1 (95% CI 0, 2)) was still significantly lower than during prior SC therapy (3 (95% CI 2, 4)): mean change -1.8 (95% CI -3.4, -0.4). Treatment satisfaction with CIPII was better than with SC insulin therapy and HRQOL remained stable. Pump or catheter dysfunction of the necessitated re-operation in 7 patients. No mortality was reported.After 6 years of CIPII treatment, glycaemic regulation is stable and the number of hypoglycaemic events decreased compared to SC insulin therapy. Treatment satisfaction with CIPII is superior to SC insulin therapy, HRQOL is stable and complications are scarce. CIPII is a safe and effective treatment option for selected patients with T1DM, also on longer term.
| S-EPMC4029992 | biostudies-literature
Project description:In 2016, to address the historical overrepresentation of male subjects in biomedical research, the US National Institutes of Health implemented a policy requiring investigators to consider sex as a biological variable. In order to assess the impact of this policy, we conducted a bibliometric analysis across nine biological disciplines for papers published in 34 journals in 2019, and compared our results with those of a similar study carried out by Beery and Zucker in 2009. There was a significant increase in the proportion of studies that included both sexes across all nine disciplines, but in eight of the disciplines there was no change in the proportion studies that included data analyzed by sex. The majority of studies failed to provide rationale for single-sex studies or the lack of sex-based analyses, and those that did relied on misconceptions surrounding the hormonal variability of females. Together, these data demonstrate that while sex-inclusive research practices are more commonplace, there are still gaps in analyses and reporting of data by sex in many biological disciplines.
| S-EPMC7282816 | biostudies-literature
Project description:Background: Marfan syndrome, a rare hereditary connective tissue disorder caused by mutations in fibrillin-1, can affect many organ systems, especially the cardiovascular system. Previous research has paid less attention to health-related quality of life and prospective studies on this topic are needed. The aim of this study was to assess changes in health-related quality of life after 10 years in a Norwegian Marfan syndrome cohort.Methods: Forty-seven Marfan syndrome patients ??18 years were investigated for all organ manifestations in the 1996 Ghent nosology and completed the self-reported questionnaire, Short-Form-36 Health Survey, at baseline in 2003-2004 and at follow-up in 2014-2015. Paired sample t tests were performed to compare means and multiple regression analyses were performed with age, sex, new cardiovascular and new non-cardiovascular pathology as predictors.Results: At 10-year follow-up: a significant decline was found in the physical domain. The mental domain was unchanged. Older age predicted a larger decline in physical health-related quality of life. None of the chosen Marfan-related variables predicted changes in any of the subscales of the Short-Form 36 Health Survey or in the physical or the mental domain.Conclusion: Knowledge of decline in the physical domain, not related to organ affections, may be important in the follow-up of Marfan syndrome patients.
| S-EPMC7706277 | biostudies-literature