Higher body mass index is associated with a lower iloprost infusion rate tolerance and higher iloprost-related adverse events in patients with systemic sclerosis
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ABSTRACT: Background:
Systemic sclerosis (SSc) is an autoimmune disease characterized by vasospasm
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PROVIDER: S-EPMC9685102 | biostudies-literature | 2022 Jan
REPOSITORIES: biostudies-literature
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Project description:Gene expression profiling in circulating endothelial cells before and after Iloprost infusion in patients with progressive Systemic sclerosis.
2010-06-28 | E-MEXP-2769 | biostudies-arrayexpress
Project description: Not available
| S-EPMC10832310 | biostudies-literature
Project description:ObjectiveTo analyze the spectrum and mechanisms of cutaneous adverse events (AEs) in patients with multiple sclerosis treated with daclizumab high-yield process (DAC-HYP).MethodsA total of 31 participants in an institutional review board-approved open-label phase I study of DAC-HYP (NCT01143441) were prospectively evaluated over 42 months for development of cutaneous AEs. Participants provided written informed consent. Fifteen participants were naive to anti-CD25 therapy (cohort B), while 16 had received daclizumab (Zenapax; Hoffmann-La Roche) IV for 4-9 years (mean 5.8 years) prior to enrollment (cohort A). Immunohistochemistry was performed on pretreatment and posttreatment skin biopsies of normal-appearing skin (cohort B only) and on lesional biopsies in participants presenting with rash (both cohorts).ResultsCutaneous AEs occurred in 77% of patients, the majority presenting with patches of eczema requiring no treatment. Moderate to severe rash developed in 6 participants (19%) and required discontinuation of DAC-HYP in 4 (13%). More severe rashes presented psoriasiform phenotype, but lesional biopsies lacked features of either psoriasis or drug hypersensitivity eruptions. Instead, irrespective of clinical severity, lesional biopsies showed nonspecific features of eczematous dermatitis, but with prominent CD56+ lymphocytic infiltrates. Pretreatment and posttreatment biopsies of normal-appearing skin demonstrated no histopathologic changes.ConclusionsObserved cutaneous AEs are likely related to the immunomodulatory effects DAC-HYP exerts on innate lymphoid cells, including natural killer cells. Vigilance and timely management of skin reactions may prevent treatment discontinuation in participants with severe rash.
| S-EPMC4793779 | biostudies-literature
Project description:Background and aimsInflammatory bowel disease may cause long-standing inflammation and fibrosis and may increase the risk of adverse events in colonoscopy. We evaluated whether inflammatory bowel disease and other potential risk factors are associated with bleeding or perforation in a nationwide, population-based, Swedish study.MethodsData from 969 532 colonoscopies, including 164 012 [17%] on inflammatory bowel disease patients, between 2003 and 2019, were retrieved from the National Patient Registers. ICD-10 codes for bleeding [T810] and perforation [T812] within 30 days of the colonoscopy were recorded. Multivariable logistic regression was used to test if inflammatory bowel disease status, inpatient setting, time period, general anaesthesia, age, sex, endoscopic procedures, and antithrombotic treatment were associated with higher odds for bleeding and perforation.ResultsBleeding and perforation were reported in 0.19% and 0.11% of all colonoscopies, respectively. Bleeding [odds ratio 0.66, p <0.001] and perforation [odds ratio 0.79, p <0.033] were less likely in colonoscopies in individuals with inflammatory bowel disease status. Bleeding and perforation were more common in inpatient than in outpatient inflammatory bowel disease colonoscopies. The odds for bleeding but not perforation increased between 2003 to 2019. General anaesthesia was associated with double the odds for perforation.ConclusionsIndividuals with inflammatory bowel disease did not have more adverse events compared with individuals without inflammatory bowel disease status. However, the inpatient setting was associated with more adverse events, particularly in inflammatory bowel disease status. General anaesthesia was associated with a greater risk of perforation.
| S-EPMC10798860 | biostudies-literature
Project description:ObjectiveResistin is a hormone that has been associated with metabolic syndrome and cardiovascular disease. The role of resistin in patients with peripheral artery disease (PAD) has not been fully explored. This study seeks to understand the relationship between serum resistin, vascular function, and cardiovascular outcomes in patients with PAD.MethodsThere were 106 patients with PAD who were recruited between 2011 and 2016. Patients attended a baseline visit during which a comprehensive vascular physiology assessment including medical and surgical history, radial artery tonometry, and flow mediated-vasodilation (FMD) was completed. A blood sample was drawn, and serum resistin was assayed using enzyme-linked immunosorbent assay kits. Using the time of study enrollment as the time of origin, incident major adverse cardiac events (MACEs) were identified by subsequent chart review and defined as a composite end point of myocardial infarction, coronary revascularization, transient ischemic attack, stroke, or death from a cardiac cause.ResultsPatients had a mean age of 68 ± 8 years, were largely white (75%), and had comorbidities commonly associated with PAD including hypertension (92%), hyperlipidemia (87%), coronary artery disease (37%), and diabetes mellitus (38%). After stratification by resistin quartile, higher resistin quartiles were significantly associated with an older age, a greater number of pack-years smoked, and a lower estimated glomerular filtration rate. Despite similar comorbidities and medication use, endothelial function, as measured by FMD, was significantly lower with increasing resistin quartile (I, 9.1% ± 3.3%; II, 7.1% ± 3.5%; III, 5.8% ± 4.0%; IV, 5.6% ± 3.5%; P = .002). In multivariable linear regression, higher resistin quartiles (III and IV) were associated with lower FMD relative to quartile I after adjusting for several patient characteristics, medications, and comorbidities (III, -2.26 [95% confidence interval (CI), -4.51 to -0.01; P = .05]; IV, -2.53 [95% CI, -4.87 to -0.20; P = .03]). During a median follow-up period of 36 months (interquartile range, 29-45 months), 21 patients experienced the primary end point. In a Cox proportional hazards model adjusted for smoking status, coronary artery disease, and age, each 1 ng/mL increase in resistin was associated with a 10% increased risk of MACEs (hazard ratio, 1.10; 95% CI, 1.00-1.20; P = .04).ConclusionsIn patients with PAD, higher levels of resistin were associated with impaired endothelial function and an increased rate of MACEs. These results suggest that resistin may be a marker or effector of impaired vascular physiology and adverse cardiac outcomes in patients with PAD. Further research is needed to determine the potential mechanisms by which resistin may impair endothelial function and increase MACEs in this population.
| S-EPMC6348018 | biostudies-literature
Project description:INTRODUCTION: Circulating endothelial cells are increased in patients affected by systemic sclerosis (SSc) and their number strongly correlates with vascular damage. The effects of iloprost in systemic sclerosis are only partially known. We aimed at studying the gene expression profile of circulating endothelial cells and the effects of iloprost infusion and gene expression in patients with systemic sclerosis. METHODS: We enrolled 50 patients affected by systemic sclerosis, 37 patients without and 13 patients with digital ulcers. Blood samples were collected from all patients before and 72 hours after either a single day or five days eight hours iloprost infusion. Blood samples were also collected from 50 sex- and age-matched healthy controls. Circulating endothelial cells and endothelial progenitors cells were detected in the peripheral blood of patients with systemic sclerosis by flow cytometry with a four-colour panel of antibodies. Statistical analysis was performed with the SPSS 16 statistical package.Circulating endothelial cells were then isolated from peripheral blood by immunomagnetic CD45 negative selection for the gene array study. RESULTS: The number of both circulating endothelial cells and progenitors was significantly higher in patients affected by systemic sclerosis than in controls and among patients in those with digital ulcers than in patients without them. Circulating endothelial cells and progenitors number increased after iloprost infusion. Gene array analysis of endothelial cells showed a different transcriptional profile in patients compared to controls. Indeed, patients displayed an altered expression of genes involved in the control of apoptosis and angiogenesis. Iloprost infusion had a profound impact on endothelial cells gene expression since the treatment was able to modulate a very high number of transcripts. CONCLUSIONS: We report here that circulating endothelial cells in patients with systemic sclerosis show an altered expression of genes involved in the control of apoptosis and angiogenesis. Moreover we describe that iloprost infusion has a strong effect on endothelial cells and progenitors since it is able to modulate both their number and their gene expression profile.
| S-EPMC2945021 | biostudies-literature
Project description:BackgroundImmune checkpoint inhibition (ICI) represents a novel treatment modality for refractory cancers, and improving prediction of potential responders is critical.MethodWe hypothesized that ICI is a systemic-effecting mechanism. The objective response rate (ORR) for anti-PD-1, anti-PD-L1, anti-CTLA-4, or combination therapy was plotted against the corresponding all-grade and grade 3-4 (G3/4) treatment-related adverse events (TRAEs) across several cancer types using an extensive literature search (MEDLINE and Google Scholar; December 1, 2012-December 30, 2017).ResultsSixty-six eligible studies comprised 76 cohorts and 25 cancer types. A significant correlation was present between all-grade or G3/4 TRAEs and the ORR. The correlation coefficient was 0.5 for all-grade and 0.4 for G3/4 TRAEs, suggesting that >50% of the differences in the ORR across cancer types may be reflected by TRAEs and 40% of ORR differences may be predicted by G3/4 TRAEs. Hodgkin's lymphoma and Merkel cell carcinoma showed a better response, while adrenocortical cancer, breast cancer, and uveal melanoma showed a worse response, compared with that predicted by TRAE.ConclusionThere is a strong relationship between TRAEs and ICI activity across multiple cancers. The toxicity profile compared with the ORR to ICIs should be investigated in phase I trials.
| S-EPMC7783260 | biostudies-literature
Project description:IntroductionAnti-disialoganglioside 2 (anti-GD2) monoclonal antibodies (mAbs) are associated with Grade ≥3 (≥G3) adverse events (AEs) such as severe pain, hypotension, and bronchospasm. We developed a novel method of administering the GD2-binding mAb naxitamab, termed "Step-Up" infusion (STU), to reduce the risk of AEs of severe pain, hypotension, and bronchospasm.MethodsForty-two patients with GD2-positive tumors received naxitamab under "compassionate use" protocols and administered via either the standard infusion regimen (SIR) or the STU regimen. The SIR comprises a 60-min infusion of 3 mg/kg/day on Day 1 of cycle 1 and a 30- to 60-min infusion on Day 3 and Day 5, as tolerated. The STU regimen uses a 2-h infusion on Day 1, initiated at a rate of 0.06 mg/kg/h during 15 min (0.015 mg/kg) and which increases gradually to a cumulative dose of 3 mg/kg; on Days 3 and 5, the 3-mg/kg dose is initiated at 0.24 mg/kg/h (0.06 mg/kg) and delivered in 90 min according to the same gradual-increase strategy. AEs were graded according to Common Terminology Criteria for Adverse Events version 4.0.ResultsThe frequency of infusions with an associated G3 AE was reduced from 8.1% (23/284 infusions) with SIR to 2.5% (5/202 infusions) with STU. The odds of an infusion being associated with a G3 AE reduced by 70.3% with STU vs. SIR (odds ratio: 0.297; p = 0.037). Mean serum naxitamab levels pre- and post-STU (11.46 µg/ml pre-infusion; 100.95 µg/ml post-infusion) were within the range reported for SIR.DiscussionThe comparable pharmacokinetics of naxitamab during SIR and STU may indicate that switching to STU reduces G3 AEs without impact on efficacy.
| S-EPMC10196122 | biostudies-literature
Project description:ObjectiveTo evaluate the association between physical activity (PA) and multiple sclerosis (MS) disease activity, depression, and fatigue in a cohort of children with MS and monophasic acquired demyelinating syndrome (mono-ADS).MethodsIn this cross-sectional study of consecutive patients attending a specialized pediatric MS clinic, we administered the PedsQL Multidimensional Fatigue Scale, Center for Epidemiological Studies Depression Scale, and Godin Leisure-Time Exercise Questionnaire. Quantitative MRI analysis was performed to obtain whole brain and T2 lesion volume in a subset of participants (n = 60).ResultsA total of 110 patients (79 mono-ADS; 31 MS; 5-18 years; M:F 1:1.2) were included. Patients with MS reported less strenuous (33.21 ± 31.88 metabolic equivalents [METs] vs 15.97 ± 22.73 METs, p = 0.002) and total (44.48 ± 39.35 METs vs 67.28 ± 59.65 METs; p = 0.0291) PA than those with mono-ADS. Patients with MS who reported greater amounts of moderate PA METs had fewer sleep/rest fatigue symptoms (r = -0.4). Participation in strenuous PA was associated with smaller T2 lesion volumes (r = -0.66) and lower annualized relapse rate (r = -0.66). No associations were found between total brain volume and participation in PA.ConclusionsChildren with MS are less physically active than children with mono-ADS. Reasons for this are unclear, but may be related to ongoing disease activity, perceived limitations, or symptoms such as depression or fatigue. Children with MS reporting higher levels of strenuous PA had lower T2 lesion volumes and lower relapse rates, suggesting a potential protective effect of strenuous PA in this population. Further longitudinal studies are needed to establish the relationship of PA to MS symptoms and disease activity in this population.
| S-EPMC4653106 | biostudies-literature
Project description:Frontotemporal lobar degeneration, the neuropathological substrate of frontotemporal dementia (FTD), is characterized by the deposition of protein aggregates, including tau. Evidence has shown concomitant amyloid pathology in some of these patients, which seems to contribute to a more aggressive disease. Our aim was to evaluate cerebrospinal fluid (CSF) amyloid-beta as a predictor of the mortality of FTD patients. We included 99 patients diagnosed with FTD-both behavioral and language variants-with no associated motor neuron disease, from whom a CSF sample was collected. These patients were followed prospectively in our center, and demographic and clinical data were obtained. The survival analysis was carried through a Cox regression model. Patients who died during follow up had a significantly lower CSF amyloid-beta1-42 than those who did not. The survival analysis demonstrated that an increased death rate was associated with a lower CSF amyloid-beta1-42 (HR = 0.999, 95% CI = [0.997, 1.000], p = 0.049). Neither demographic nor clinical variables, nor CSF total tau or p-tau were significantly associated with this endpoint. These results suggest that amyloid deposition in FTD patients may be associated with a higher mortality.
| S-EPMC6963225 | biostudies-literature