scholarly journals SUN-607 Iron Parameters in Patients with Partial Lipodystrophy and Impact of Metreleptin Therapy

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Sabine Boutros ◽  
Efe Yagiz Akinci ◽  
Benjamin Ryan ◽  
Pinar Sargin ◽  
Baris Akinci ◽  
...  
Keyword(s):  
Iron Metabolism ◽  
Statistical Significance ◽  
Epidemiological Data ◽  
Serum Samples ◽  
Open Label ◽  
Partial Lipodystrophy ◽  
Iron Stores ◽  
Hepatic Fat ◽  
Iron Parameters ◽  
Hs Crp

Abstract Introduction Intriguing rodent studies and epidemiological data suggest that iron metabolism and adipocytokines crosstalk to regulate glucose metabolism and fuel storage. Iron parameters have not been previously studied in patients with lipodystrophy whereas increased iron stores have been associated with type 2 diabetes. In this study, we sought to investigate the status of iron parameters in patients with partial lipodystrophy (PL) and to interrogate whether the adipocyte hormone leptin can modulate iron metabolism. Methods Serum samples of 19 patients with PL (age: 42, IQR: 34-57, M/F: 3/16) were used from an open-label study previously performed at the University of Michigan evaluating the efficacy of metreleptin in nonalcoholic steatohepatitis (NCT01679197) to measure ferritin, hepcidin, iron, and transferrin soluble receptor levels. High-sensitivity C-reactive protein (hs-CRP) levels were also determined as broader changes in inflammatory pathways may potentially impact circulating ferritin levels. Results were integrated into an existing database of metabolic parameters. Data are presented as median, IQR. Results At baseline, ferritin levels were positively correlated with fasting glucose (r = 0.533; p = 0.023) and HbA1c (r = 0.510; p = 0.031). During the 6 months of therapy period, HbA1c (9.2%, 7.3-10.3 vs. month-3: 8.6%, 7.7-9.6; p = 0.099; and month-6: 8.5%, 6.8-9.5; p = 0.264), triglyceride levels (346 mg/dL, 240-1771 vs. month-3: 346 mg/dl, 237-479; p = 0.047; and month-6: 295 mg/dl, 207-495; p = 0.091), and hepatic fat (12.7%, 9.8-20.6 vs. month-6: 8.9%, 7.0-11.0; p = 0.031)} decreased. Reductions were observed in serum ferritin after metreleptin treatment (83.23 ng/mL, 76.43-178.97 vs. month-3: 73.79 ng/ml, 68.30-78.59; p = 0.007; and month-6: 61.03 ng/mL, 46.45-157.74; p = 0.004). There was a tendency for hepcidin and iron to be decreased, but this did not reach statistical significance. On the other hand, there were notable reductions in hs-CRP levels at 6 months compared to baseline (2.94 mg/L, 1.30-4.80 vs. 1.6 mg/L, 1.00-6.30; p = 0.012). Baseline leptin level was inversely correlated with percent reduction in hs-CRP at month-6 (r = -0.685; p = 0.001). Also, modest correlations were observed between changes in serum iron and triglycerides (r = 0.491, p = 0.033) and hepatic fat (r = 0.412, p = 0.079). Conclusions We observed a significant relationship between ferritin and glucose control in a group of patients with PL. Metreleptin therapy was associated with improvements in triglycerides and hepatic fat and there were also significant decreases in ferritin and hs-CRP levels. These results raise the possibility that metreleptin therapy influences iron metabolism. However, whether the decrease in ferritin indicates a decrease in iron stores or is mediated by an effect on inflammation remains unknown.

scholarly journals Combination of umbilical cord mesenchymal stem cells and standard immunosuppressive regimen for pediatric patients with severe aplastic anemia

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Yang Lan ◽  
Fang Liu ◽  
Lixian Chang ◽  
Lipeng Liu ◽  
Yingchi Zhang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Aplastic Anemia ◽  
Umbilical Cord ◽  
Pediatric Patients ◽  
Statistical Significance ◽  
Severe Aplastic Anemia ◽  
Control Group ◽  
Open Label ◽  
Cell Counts

Abstract Background Defects of bone marrow mesenchymal stem cells (BM-MSCs) in proliferation and differentiation are involved in the pathophysiology of aplastic anemia (AA). Infusion of umbilical cord mesenchymal stem cells (UC-MSCs) may improve the efficacy of immunosuppressive therapy (IST) in childhood severe aplastic anemia (SAA). Methods We conducted an investigator-initiated, open-label, and prospective phase IV trial to evaluate the safety and efficacy of combination of allogenic UC-MSCs and standard IST for pediatric patients with newly diagnosed SAA. In mesenchymal stem cells (MSC) group, UC-MSCs were injected intravenously at a dose of 1 × 106/kg per week starting on the 14th day after administration of rabbit antithymocyte globulin (ATG), for a total of 3 weeks. The clinical outcomes and adverse events of patients with UC-MSCs infusion were assessed when compared with a concurrent control group in which patients received standard IST alone. Results Nine patients with a median age of 4 years were enrolled as the group with MSC, while the data of another 9 childhood SAA were analysed as the controls. Four (44%) patients in MSC group developed anaphylactic reactions which were associated with rabbit ATG. When compared with the controls, neither the improvement of blood cell counts, nor the change of T-lymphocytes after IST reached statistical significance in MSC group (both p > 0.05) and there were one (11%) patient in MSC group and two (22%) patients in the controls achieved partial response (PR) at 90 days after IST. After a median follow-up of 48 months, there was no clone evolution occurring in both groups. The 4-year estimated overall survival (OS) rate in two groups were both 88.9% ± 10.5%, while the 4-year estimated failure-free survival (FFS) rate in MSC group was lower than that in the controls (38.1% ± 17.2% vs. 66.7% ± 15.7%, p = 0.153). Conclusions Concomitant use of IST and UC-MSCs in SAA children is safe but may not necessarily improve the early response rate and long-term outcomes. This clinical trial was registered at ClinicalTrials.gov, identifier: NCT02218437 (registered October 2013).

scholarly journals The Second of Two One-Year, Multicenter, Open-Label, Repeat-Dose, Phase II Safety Studies of PrabotulinumtoxinA for the Treatment of Moderate to Severe Glabellar Lines in Adult Patients

2021 ◽  
Author(s):  
Z Paul Lorenc ◽  
Jeffrey M Adelglass ◽  
Rui L Avelar ◽  
Leslie Baumann ◽  
Kenneth R Beer ◽  
...  
Keyword(s):  
Phase Ii ◽  
Botulinum Toxin Type A ◽  
Study Drug ◽  
Botulinum Toxin Type ◽  
Second Phase ◽  
Repeat Dose ◽  
Serum Samples ◽  
Open Label ◽  
Blurred Vision ◽  
Line Scale

Abstract Background PrabotulinumtoxinA is a 900-kDa botulinum toxin type A produced by Clostridium botulinum. Objectives The authors sought to investigate the safety of prabotulinumtoxinA for treatment of glabellar lines. Methods This was a multicenter, open-label, repeat-dose, 1-year phase II safety study. Adults with moderate to severe glabellar lines at maximum frown, as independently assessed by both investigator and patient on the validated 4-point photonumeric Glabellar Line Scale (0 = no lines, 1 = mild, 2 = moderate, 3 = severe), were enrolled. On day 0, patients received an initial treatment (IT) of 20 U prabotulinumtoxinA (4 U/0.1 mL final vacuum-dried formulation injected into 5 glabellar sites). On and after day 90, patients received a repeat treatment (RT) if their Glabellar Line Scale score was ≥2 at maximum frown by investigator assessment. Safety outcomes were evaluated throughout the study. Results The 570 study patients received a median total dose of 60 U, that is, 3 treatments. Sixty-one patients (10.7%) experienced adverse events (AEs) assessed as possibly study drug related; 6.5% experienced study drug–related AEs after the IT. With each RT, progressively lower percentages of patients experienced study drug–related AEs. Eight patients (1.4%) experienced study drug–related AEs of special interest: 5 experienced eyelid ptosis (0.9%), 3 eyebrow ptosis (0.5%), 1 blepharospasm (0.2%), and 1 blurred vision (0.2%). Seven patients (1.2%) experienced serious AEs, but none were study drug related. A total of 4060 serum samples were tested for antibotulinum toxin antibodies; no seroconversion was observed. Conclusions The safety of RTs of 20 U of prabotulinumtoxinA for moderate to severe glabellar lines was confirmed in this second phase II study based on a broad range of outcomes.

Buparlisib in Kombination mit Tamoxifen: Rationale für zielgerichtete Therapie bei PIK3CA-mutiertem metastasierten Mammakarzinom bestätigt

2021 ◽  
pp. 1-3
Author(s):  
Carlota Claussen ◽  
Maggie Banys-Paluchowski
Keyword(s):  
Breast Cancer ◽  
Endocrine Therapy ◽  
Pik3ca Mutation ◽  
Progression Free Survival ◽  
Breast Cancer Patients ◽  
Serum Samples ◽  
Open Label ◽  
Pik3ca Mutations ◽  
Hormone Receptor Positive ◽  
Pi3k Inhibition

The PIKTAM study evaluated the efficacy and safety of the PI3K inhibitor buparlisib in combination with tamoxifen in hormone receptor-positive (HR+), HER2-negative advanced breast cancer patients after failure of prior endocrine therapy. In this open-label, single-arm phase II trial, 25 patients were enrolled in 11 sites in Germany. Patients were stratified according to PIK3CA mutation status (tissue and cfDNA from serum samples) and/or loss of PTEN expression. Patients received buparlisib (100mg) and tamoxifen (20mg) once daily on a continuous schedule (28-day cycle) until progression or unacceptable toxicity. Primary endpoint was overall 6-month progression-free survival (PFS) rate. Key secondary endpoints included the 6-month PFS rate in subpopulations, PFS, overall survival, overall response rate (ORR), disease control rate (DCR), and safety. Overall, the 6-month PFS rate was 33.3% (n/N = 7/21, one-sided 95% CI 16.8–100) and median PFS was 6.1 (CI 2.6–10.6) months. The ORR and DCR were 12.5% and 44%. The PIK3CA-mutated subgroup consistently showed the highest 6-month PFS rate (62.5%, n/N = 5/8), median PFS (8.7 months), ORR (40%), and DCR (80%). No new safety signals emerged. Most common adverse events were gastrointestinal disorders (56%), psychiatric/mood disorders (48%), skin rash/hypersensitivity (44%), cardiovascular (40%), and hepatic (32%) events. The trial was prematurely terminated due to the substantially altered risk – benefit profile of buparlisib. Nevertheless, PIK3CA mutations emerged as a clinically feasible and useful biomarker for combined PI3K inhibition and endocrine therapy in patients with HR+ breast cancer. Further biomarker – stratified studies with isoform – specific PI3K inhibitors are warranted. EudraCT No: 2014–000599–24.

Basal high-sensitivity-C-reactive protein levels in patients with spontaneous venous thromboembolism

2005 ◽  
Vol 93 (03) ◽  
pp. 488-493 ◽  
Author(s):  
Rainer Vormittag ◽  
Thomas Vukovich ◽  
Verena Schönauer ◽  
Stephan Lehr ◽  
Erich Minar ◽  
...  
Keyword(s):  
Risk Factor ◽  
Venous Thromboembolism ◽  
Statistical Significance ◽  
Factor V Leiden ◽  
High Sensitivity ◽  
Prothrombin G20210a ◽  
Factor V ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Hs Crp

SummaryThe role of C-reactive protein (CRP) in venous thromboembolism (VTE) is still under discussion because of controversial results in the literature. Conflicting data may have partly been due to bias by exogenous factors altering CRP levels. We investigated CRP concentrations in patients with spontaneous VTE applying a study design that allowed the measurement of basal high sensitivity (hs)-CRP levels. Patients with a history of deep vein thrombosis (DVT, n=117) and pulmonary embolism (PE, n=97) were compared to healthy individuals (n=104). Hs-CRP levels (mg/dl) were significantly higher in patients (n=214, median/interquartile range: 0.171/0.082–0.366) than in controls (0.099/0.053–0.245, p=0.001). The unadjusted odds ratio (OR) for VTE per 1 mg/dl increase of CRP was 2.8 [95% confidence interval (CI): 1.1–6.8, p=0.03]. This association remained significant after adjustment for factor V Leiden, prothrombin G20210A and factor VIII activity above 230% (OR = 2.9, 95% CI [1.1–7.5]), but became remarkably attenuated and lost its statistical significance after adjustment for BMI alone (OR = 1.7 [0.7–4.0]). CRP was also not independently associated with VTE in subgroups of patients (those with DVT without symptomatic PE, those with PE and patients without established risk factor) in multiple regression analysis. In summary, we observed significantly higher basal hs-CRP levels in patients with spontaneous VTE compared to healthy controls. This association was independent of hereditary and laboratory risk factors for VTE, but lost its significance after adjustment for BMI. Increased basal CRP levels do not appear to represent an independent risk factor for VTE.

scholarly journals PREVALENCE OF PARACOCCIDIOIDOMYCOSIS INFECTION BY INTRADERMAL REACTION IN RURAL AREAS IN ALFENAS, MINAS GERAIS, BRAZIL

2014 ◽  
Vol 56 (4) ◽  
pp. 281-285 ◽  
Author(s):  
Evandro Monteiro de Sá Magalhães ◽  
Carla de Fátima Ribeiro ◽  
Carla Silva Dâmaso ◽  
Luiz Felipe Leomil Coelho ◽  
Roberta Ribeiro Silva ◽  
...  
Keyword(s):  
Rural Areas ◽  
Alcohol Intake ◽  
Paracoccidioides Brasiliensis ◽  
Statistical Significance ◽  
Epidemiological Data ◽  
Population Based ◽  
Minas Gerais ◽  
Delayed Type Hypersensitivity ◽  
Local Health ◽  
Cross Sectional

This study aimed to estimate the prevalence of paracoccidioidal infection by intradermal reaction (Delayed-Type Hypersensitivity, DTH) to Paracoccidioides brasiliensis in rural areas in Alfenas, Southern Minas Gerais (MG) State, Brazil, and to assess risk factors (gender, occupation, age, alcohol intake and smoking) associated with infection. We conducted a population-based cross-sectional study using intradermal tests with gp 43 paracoccidioidin in 542 participants, who were previously contacted by local health agents and so spontaneously attended the test. Participants underwent an interview by filling out a registration form with epidemiological data and were tested with an intradermal administration of 0.1 mL of paracoccidioidin in the left forearm. The test was read 48 hours after injection and was considered positive if induration was greater than or equal to 5 mm. Out of 542 participants, 46.67% were positive to the skin test. Prevalence increased in accordance with an increase of age. There was statistical significance only for males. Occupation, alcohol intake and smoking habits were not significantly associated with the risk of paracoccidioidomycosis infection. There is relevance of paracoccidioidomycosis infection in such rural areas, which suggests that further epidemiological and clinical studies on this mycosis should be done in the southern part of Minas Gerais State.

scholarly journals Circulating Levels of Free 25(OH)D Increase at the Onset of Rheumatoid Arthritis

2019 ◽  
Author(s):  
Vidyanand Anaparti ◽  
Xiaobo Meng ◽  
Hemsekhar Mahadevappa ◽  
Irene Smolik ◽  
Neeloffer Mookherjee ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Vitamin D ◽  
Linear Regression Analysis ◽  
Autoimmune Disorder ◽  
Joint Inflammation ◽  
Epidemiological Studies ◽  
Vitamin D Metabolites ◽  
Serum Samples ◽  
Hs Crp ◽  
Circulating Levels

ABSTRACTObjectiveEpidemiological studies suggest vitamin D deficiency as a potential risk factor for rheumatoid arthritis (RA) development, a chronic autoimmune disorder highly prevalent in indigenous North American (INA) population. We therefore profiled the circulating levels of 25-hydroxyvitaminD [25(OH)D], an active metabolite of vitamin D, in a cohort of at-risk first-degree relatives (FDR) of INA RA patients, a subset of whom subsequently developed RA (progressors).Methods2007 onward, serum samples from INA RA patients and FDR were collected at the time of a structured baseline visit and stored at −20°C. Anti-citrullinated protein antibodies (ACPA), 25(OH)D, hs-CRP, vitamin-D binding protein (VDBP) levels were determined using ELISA and rheumatoid factor (RF) seropositivity was determined by nephelometry.ResultsWe demonstrate that 25 (OH) D concentrations were lower in winter than summer (P=0.0538), and that serum 25(OH)D levels were higher in samples collected and stored after 2013 (P<0.0001). Analysis of samples obtained after 2013 demonstrated that 37.6% of study participants were 25(OH)D insufficient (<75nmol/L). Also, seropositive RA patients and FDR had lower 25(OH)D levels compared to ACPA-/FDR (P<0.05, P<0.01 respectively). Linear regression analysis showed 25(OH)D insufficiency was inversely associated with presence of RA autoantibodies. Longitudinal samples from 14 progressors demonstrated a consistent increase in 25(OH)D levels at the time they exhibited clinically detectable joint inflammation, without any significant change in VDBP levels.ConclusionWe demonstrate that 25(OH)D levels in serum increased at RA onset in progressors. The potential role that vitamin D metabolites and their downstream effects play in RA transition requires further investigation.

scholarly journals Examining Metabolic Profiles in Opioid-‎Dependent Patients ‎

2020 ◽  
Vol 10 (3) ◽  
pp. 28681
Author(s):  
Nader Molavi ◽  
Amir Ghaderi ◽  
Hamid Reza Banafshe
Keyword(s):  
Control Group ◽  
Study Group ◽  
Metabolic Profiles ◽  
Opioid Use ◽  
Serum Samples ◽  
Social Burden ◽  
Study Results ◽  
Significant Difference ◽  
Hs Crp ◽  
Opioid Users

Background: Drug abuse is a social burden and a public health disorder. Previous evidence suggested numerous illicit substances (e.g., opioids, amphetamines, cocaine, & cannabis) affect immune system functions, oxidative stress mechanisms, inflammatory cytokines, and reactive oxygen species production. This study aimed to determine the extent of these metabolic parameters in opioid-dependent patients. We also compared these patients with a healthy control group. Methods: This study was conducted in Amirie Clinic, Kashan, Iran. Plasma and serum samples from 50 illicit opioid users (study group) and 50 non-opioid users (control group) were studied. Metabolic levels for MDA, NO, TAC, GSH, Insulin, HOMA-IR, and hs-CRP were assessed in both research groups (N=100). Results: There was a significant difference in the status of MDA (P=0.003), NO (P=0.01), TAC (P=0.003), GSH (P=0.001), insulin (P=0.04), HOMA-IR (P=0.02), and hs-CRP (P=0.001) between the study and control groups. Furthermore, there was a significant correlation among the duration of illicit opioid use and MDA concentrations (r=-0.424, P=0.002), as well as TAC levels (r=0.314, P=0.02). Conclusion: The study results suggested metabolic profiles were impaired in the study group, compared to the controls.  

scholarly journals Prevalence and Associated Factors of Hypertension Among Adults living in the City of Bandundu, Republic Democratic Republic of the Congo. A Population-Based Cross-Sectional Study.

2021 ◽  
Author(s):  
Ferdinand Mukoso ◽  
Aliocha Nkodila ◽  
François Lepira ◽  
Pascal Bayauli ◽  
Yves Lubenga ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Sleep Duration ◽  
Subclinical Atherosclerosis ◽  
Statistical Significance ◽  
Epidemiological Data ◽  
Cluster Sampling ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Factors Associated

Abstract Background and aim: In limited resource settings, reliable epidemiological data generated from hypertension high risk geographical areas or people is a prerequisite for the planning of proven and effective interventions. The aim of the present survey was to assess the prevalence, awareness, control and factors associated with hypertension in adults living in the port City of Bandundu, located in the southwestern part of DRC.Methods: a cross-sectional survey using a modified WHO STEPwise questionnaire for data collection during face-to face interviews was conducted from 1st May to 30th October 2018. A multistage cluster sampling method was used and inclusion criteria were age ≥18 years and informed consent. Information on demographic parameters, behavioral lifestyles, anthropometric and blood pressure (BP) measurements was obtained. Hypertension was defined as an average of two BP ≥ 140/90 mmHg or self-reported history of antihypertensive medication use. Independent factors associated with hypertension were identified using logistic regression analysis. P<0.05 defined the level of statistical significance. Results: The prevalence of hypertension was 34,5% (Women 36,6 %). Older age (p<0.001), subclinical atherosclerosis (p= 0.021), sleep duration <8 hours (p<0.002), diabetes mellitus (p<0.001), and obesity (p= 0.009) emerged as main cardiovascular risk factors associated with hypertension.Conclusion: Hypertension was characterized by a high prevalence, low rate of awareness and suboptimal BP control, high cardiovascular risk and associated sleep duration and obesity as modifiable risk factors.

Evaluation of Serum Biomarkers Associated with Radiographic Progression in Methotrexate-naive Rheumatoid Arthritis Patients Treated with Methotrexate or Golimumab

2013 ◽  
Vol 40 (5) ◽  
pp. 590-598 ◽  
Author(s):  
Carrie Wagner ◽  
Dion Chen ◽  
Hongtao Fan ◽  
Elizabeth C. Hsia ◽  
Michael Mack ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Radiographic Progression ◽  
Statistical Significance ◽  
Tumor Necrosis Factor Inhibitor ◽  
Cd40 Ligand ◽  
Joint Space ◽  
Protein Profiling ◽  
Serum Samples ◽  
Markers Of Inflammation ◽  
Factor Inhibitor

Objective.To evaluate associations between biomarkers and radiographic progression in methotrexate (MTX)-naive patients with rheumatoid arthritis (RA) treated with MTX or golimumab, a tumor necrosis factor inhibitor (with or without MTX).Methods.Serum samples from 152 MTX-naive adults with active RA who received placebo + MTX (n = 37) or golimumab (combined 50 mg + MTX or 100 mg ± MTX; n = 115) were analyzed for selected markers of inflammation and bone/cartilage turnover. One hundred patients were randomly selected for additional protein profiling using multianalyte profiles (HumanMap v1.6, Rules Based Medicine). Radiographs at baseline, Week 28, and Week 52 were scored using van der Heijde-Sharp (vdH-S) methodology. Correlations were assessed between biomarker levels (baseline and change at Week 4) and joint space narrowing, erosion, and total vdH-S scores (changes at Weeks 28 and 52). Statistical significance was defined as a correlation coefficient with an absolute value ≥ 0.3 and p < 0.05.Results.Biomarker correlations with changes in vdH-S scores at Week 28 and/or 52 were observed predominantly in the placebo + MTX group and rarely in the combined golimumab treatment group. Changes in epidermal growth factor (EGF) and CD40 ligand (CD40L) at Week 4 were positively correlated with changes in total vdH-S scores at Weeks 28 and 52 in the placebo + MTX group.Conclusion.These preliminary findings indicate that EGF and CD40L may have utility in monitoring MTX-treated patients with RA who are more likely to have radiographic progression as measured by increases in vdH-S scores.

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