scholarly journals A Placebo-Controlled, Double-Blind Randomized (Phase IIB) Trial of Oral Administration with HPV16 E7-Expressing Lactobacillus, GLBL101c, for the Treatment of Cervical Intraepithelial Neoplasia Grade 2 (CIN2)

Vaccines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 329
Author(s):  
Yuji Ikeda ◽  
Katsuyuki Adachi ◽  
Kensuke Tomio ◽  
Satoko Eguchi-Kojima ◽  
Tetsushi Tsuruga ◽  
...  
Keyword(s):  
Cervical Intraepithelial Neoplasia ◽  
Mononuclear Cells ◽  
Intraepithelial Neoplasia ◽  
Complete Regression ◽  
Cervical Intraepithelial Neoplasia Grade ◽  
Double Blind ◽  
Peripheral Blood Mononuclear ◽  
Significant Difference ◽  
Th1 Immune Responses ◽  
To Receive

Cervical intraepithelial neoplasia (CIN), a precursor lesion to cervical cancer, is caused by high-risk human papillomavirus (HPV); high-grade CIN lesions (CIN2-3) are precancerous and require treatment. No globally approved therapy is available for CIN2-3 treatment. This study is a placebo-controlled randomized clinical trial of GLBL101c treatment for CIN2 in 40 patients with HPV16-positive CIN2 who were 1:1 randomized to receive GLBL101c (1 g/daily) or placebo for 5 days at 1, 2, 4, and 8 weeks. No differences were noted between the GLBL101c and placebo groups for patient background and adverse events. Moreover, no statistically significant difference was noted between the two groups at the primary endpoint, pathological regression after 16 weeks of the first oral dose; however, only in the GLBL101c group, two patients had complete regression (CR; regression to normal within 16 weeks). IFNγ production was significantly correlated with the number of spots identified by the interferon gamma enzyme-linked immunospot (IFNγ-ELISPOT) assay using cervical lymphocytes (CxLs) or peripheral blood mononuclear cells. In the two cases of CR, E7-specific Th1 immune responses were observed at week 16. Therefore, we concluded as a novel Lactobacillus-based vaccine with stronger immunogenicity than GLBL101c should be developed.

Long-Term Vitamin D Supplementation and the Effects on Recurrence and Metabolic Status of Cervical Intraepithelial Neoplasia Grade 2 or 3: A Randomized, Double-Blind, Placebo-Controlled Trial

2018 ◽  
Vol 72 (2) ◽  
pp. 151-160 ◽  
Author(s):  
Zahra Vahedpoor ◽  
Samaneh Mahmoodi ◽  
Mansooreh Samimi ◽  
Hamid Reza Gilasi ◽  
Fereshteh Bahmani ◽  
...  
Keyword(s):  
Vitamin D ◽  
Cervical Intraepithelial Neoplasia ◽  
Vitamin D3 ◽  
Controlled Trial ◽  
Intraepithelial Neoplasia ◽  
Vitamin D Supplementation ◽  
Metabolic Status ◽  
Cervical Intraepithelial Neoplasia Grade ◽  
Double Blind ◽  
Double Blind Placebo

Objective: This study was conducted to evaluate the effects of vitamin D supplementation on the recurrence and metabolic status of patients with cervical intraepithelial neoplasia grade 2 or 3 (CIN2/3). Methods: This randomized, double-blind, placebo-controlled trial was carried out among 58 women diagnosed with CIN2/3. Participants were randomly assigned into 2 groups to receive either 50,000 IU vitamin D3 (n = 29) or placebo (n = 29) every 2 weeks for 6 months. Results: The recurrence rate of CIN1/2/3 was 18.5 and 48.1% in the vitamin D and placebo groups respectively (p = 0.02). When we excluded CIN1, the recurrence rate of CIN2/3 became nonsignificant. Vitamin D supplementation significantly decreased fasting plasma glucose (–7.8 ± 9.2 vs. –1.1 ± 8.6 mg/dL, p = 0.006) and insulin levels (–3.2 ± 4.8 vs. –0.9 ± 3.4 µIU/mL, p = 0.03), and significantly increased quantitative insulin sensitivity check index (0.01 ± 0.02 vs. 0.002 ± 0.01, p = 0.02) compared with the placebo. Additionally, there was a significant decrease in high-sensitivity C-reactive protein (–815.3 ± 1,786.2 vs. 717.5 ± 1,827.3 ng/mL, p = 0.002) and a significant increase in total antioxidant capacity (113.4 ± 137.4 vs. –53.7 ± 186.7 mmol/L, p < 0.001) following the supplementation of vitamin D compared with the placebo. Conclusions: Vitamin D3 supplementation for 6 months among women with CIN2/3 had beneficial effects on CIN1/2/3 recurrence and metabolic status; however, it did not affect CIN2/3 recurrence.

p16INK4a Expression does not predict the outcome of cervical intraepithelial neoplasia grade 2

2007 ◽  
Vol 17 (5) ◽  
pp. 1099-1103 ◽  
Author(s):  
A. C. Guedes ◽  
S. M.F. Brenna ◽  
S. A.S. Coelho ◽  
E. Z. Martinez ◽  
K. J. Syrjänen ◽  
...  
Keyword(s):  
Cervical Intraepithelial Neoplasia ◽  
Spontaneous Regression ◽  
Intraepithelial Neoplasia ◽  
Partial Regression ◽  
Cervical Intraepithelial Neoplasia Grade ◽  
Atypical Squamous Cell ◽  
Papillomavirus Infection ◽  
Significant Difference ◽  
Cox Analysis

Spontaneous regression of cervical intraepithelial neoplasia grade 2 (CIN2) lesions has been recognized since 1955, but predictors of this are poorly understood. Among the predictive markers studied, p16INK4a has been suggested to be of some value in monitoring the diagnosis of CIN2. In this clinical trial, 90 Brazilian women, diagnosed to CIN2 and high-risk human papillomavirus infection, were randomized into two groups of equal size: 45 women whose lesions were excised and 45 women subjected to prospective follow-up at 3-month intervals at least for 1 year (mean 6.8 months). p16INK4a expression was analyzed in paraffin-embedded sections using immunohistochemical staining. Among the 45 women in the follow-up group, 42% experienced spontaneous regression, 11% showed persistence, 22% progressed to CIN3, and 20% had partial regression to CIN1 or ASCUS (atypical squamous cell undetermined signifiance). p16INK4a expression was detected in 68.9% of the patients. In univariate survival (Cox) analysis, no significant difference in regression was obtained between p16INK4a-negative and -positive CIN2 lesions (adjusted HR = 1.1; 95% CI 0.6–2.0). In conclusion, p16INK4a expression could be useful in the diagnosis of CIN2. However, it failed to predict the outcome of CIN2. Because of its high spontaneous regression rate, follow-up could be considered as a management option of CIN2 in young and compliant women.

Solumedrol Treatment for Severe Sepsis in Humans with a Blunted Adrenocorticotropic Hormone-Cortisol Response: A Prospective Randomized Double-Blind Placebo-Controlled Pilot Clinical Trial

2021 ◽  
pp. 088506662110388
Author(s):  
Divya Birudaraju ◽  
Sajad Hamal ◽  
John A. Tayek
Keyword(s):  
Blood Pressure ◽  
Clinical Trial ◽  
Adrenocorticotropic Hormone ◽  
Serum Cortisol ◽  
High Dose ◽  
Cortisol Response ◽  
Acth Stimulation ◽  
Double Blind ◽  
Significant Difference ◽  
To Receive

Purpose To test the benefits of Solumedrol treatment in sepsis patients with a blunted adrenocorticotropic hormone (ACTH)-cortisol response (delta <13 µg/dL) with regard to the number of days on ventilator, days on intravenous blood pressure support, length of time in an intensive care unit (ICU), 14-day mortality, and 28-day mortality. The trial was prospective, randomized, and double-blind. As part of a larger sepsis trial, 54 patients with sepsis had an intravenous ACTH stimulation test using 250 µg of ACTH, and serum cortisol was measured at times 0, 30, and 60 min. Eleven patients failed to increase their cortisol concentration above 19.9 µg/dL and were excluded from the clinical trial as they were considered to have adrenal insufficiency. The remaining 43 patients had a baseline cortisol of 32 ± 1 µg/dL increased to 38 ± 3 µg/dL at 30 min and 40 ± 3 at 60 min. All cortisol responses were <12.9 µg/dL between time 0 and time 60, which is defined as a blunted cortisol response to intravenous ACTH administration. Twenty-one were randomized to receive 20 mg of intravenous Solumedrol and 22 were randomized to receive a matching placebo every 8 h for 7-days. There was no significant difference between the two randomized groups. Data analysis was carried out bya two-tailed test and P < .05 as significant. Results Results: The mean age was 51 ± 2 (mean ± SEM) with 61% female. Groups were well matched with regard to APACHE III score in Solumedrol versus placebo (59 ± 6 vs 59 ± 6), white blood cell count (18.8 ± 2.2 vs 18.6 ± 2.6), and incidence of bacteremia (29 vs 39%). The 28-day mortality rate was reduced in the Solumedrol treated arm (43 ± 11 vs 73 ± 10%; P < .05). There was no change in days in ICU, days on blood pressure agents, or days on ventilator. Seven days of high-dose intravenous Solumedrol treatment (20 mg every 8 h) in patients with a blunted cortisol response to ACTH was associated with an improved 28-day survival. This small study suggests that an inability to increase endogenous cortisol production in patients with sepsis who are then provided steroid treatment could improve survival.

scholarly journals Ten-year follow-up of human papillomavirus vaccine efficacy against the most stringent cervical neoplasia end-point—registry-based follow-up ofthree cohorts from randomized trials

BMJ Open ◽  
2017 ◽  
Vol 7 (8) ◽  
pp. e015867 ◽  
Author(s):  
Matti Lehtinen ◽  
Camilla Lagheden ◽  
Tapio Luostarinen ◽  
Tiina Eriksson ◽  
Dan Apter ◽  
...  
Keyword(s):  
Human Papillomavirus ◽  
Cervical Intraepithelial Neoplasia ◽  
Cancer Registry ◽  
Vaccine Efficacy ◽  
Invasive Cervical Cancer ◽  
Intraepithelial Neoplasia ◽  
Cervical Intraepithelial Neoplasia Grade ◽  
Hpv 16 ◽  
Link Type

ObjectiveDue to long lag time between infection/cancer diagnoses human papillomavirus (HPV) vaccination programs will deliver vaccine efficacy (VE) estimates against cancer end-points late. Cancer registry follow-up of population-based, randomised trial cohorts of vaccinated and unvaccinated women was undertaken for the estimation of VE against cervical intraepithelial neoplasia grade three and invasive cancer (CIN3+).MethodsWe report interim results with 98 561 person years of Finnish Cancer Registry -based follow-up of individually and/or cluster randomised cohorts of HPV-16/18 vaccinated and unvaccinated adolescent women enrolled in June 2003/2005, and between May 2004 and April 2005, respectively. The cohorts comprised 15 627 18- to 19-year-old unvaccinated women (NCT01393470), and 2 401 and 64 16- to 17-year-old HPV-16/18 vaccinated women participating the PATRICIA (NCT00122681) and HPV-012 (NCT00169494) trials, respectively. The age-aligned passive follow-up started 6 months after the clinical trials’ end.ResultsDuring the follow-up of 4.5 to 10 years post enrolment we identified 75 cases of cervical intraepithelial neoplasia grade 3 (CIN3) and 4 cases of invasive cervical cancer (ICC) in the unvaccinated cohort, and 4 CIN3 cases in the HPV-16/18 vaccinated women. Diagnostic blocks were available for HPV typing from 87% of the cases. CIN3+ lesions were detectable in 54 cases. HPV16 was found in 26 of 50 unvaccinated CIN3+ cases, and in 3 CIN3+ cases in the HPV-16/18 vaccinated women. The latter were all baseline positive for cervical HPV16 DNA. Baseline data was not available for the unvaccinated women. Intention-to-treat VE against any CIN3+ was 66% (95% CI 8, 88).ConclusionsTen years post vaccination the AS04-adjuvanted HPV-16/18 vaccine shows continued efficacy against CIN3+ irrespectively of HPV type. Vaccine efficacy was not observed in baseline HPV16 DNA positive subjects.Trial registration numberNCT01393470.

scholarly journals Cholesterol Transporters ABCA1 and ABCG1 Gene Expression in Peripheral Blood Mononuclear Cells in Patients with Metabolic Syndrome

Cholesterol ◽  
2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Zahra Tavoosi ◽  
Hemen Moradi-Sardareh ◽  
Massoud Saidijam ◽  
Reza Yadegarazari ◽  
Shiva Borzuei ◽  
...  
Keyword(s):  
Gene Expression ◽  
Metabolic Syndrome ◽  
Mononuclear Cells ◽  
Fasting Blood Glucose ◽  
Control Group ◽  
Regulation Mechanism ◽  
Healthy Individuals ◽  
Peripheral Blood Mononuclear ◽  
Significant Difference ◽  
Abca1 Expression

ABCA1 and ABCG1 genes encode the cholesterol transporter proteins that play a key role in cholesterol and phospholipids homeostasis. This study was aimed at evaluating and comparing ABCA1 and ABCG1 genes expression in metabolic syndrome patients and healthy individuals. This case-control study was performed on 36 patients with metabolic syndrome and the same number of healthy individuals in Hamadan (west of Iran) during 2013-2014. Total RNA was extracted from mononuclear cells and purified using RNeasy Mini Kit column. The expression of ABCA1 and ABCG1 genes was performed by qRT-PCR. Lipid profile and fasting blood glucose were measured using colorimetric procedures. ABCG1 expression in metabolic syndrome patients was significantly lower (about 75%) compared to that of control group, while for ABCA1 expression, there was no significant difference between the two studied groups. Comparison of other parameters such as HDL-C, FBS, BMI, waist circumference, and systolic and diastolic blood pressure between metabolic syndrome patients and healthy individuals showed significant differences (P<0.05). Decrease in ABCG1 expression in metabolic syndrome patients compared to healthy individuals suggests that hyperglycemia, related metabolites, and hyperlipidemia over the transporter capacity resulted in decreased expression of ABCG1. Absence of a significant change in ABCA1 gene expression between two groups can indicate a different regulation mechanism for ABCA1 expression.

Duloxetine augmentation in resistant obsessive compulsive disorder: Surveying a new medication for challenges in treatment of OCD

2017 ◽  
Vol 41 (S1) ◽  
pp. S415-S415
Author(s):  
A. Mowla
Keyword(s):  
Obsessive Compulsive Disorder ◽  
Primary Outcome Measure ◽  
Controlled Clinical Trial ◽  
Double Blind Study ◽  
Obsessive Compulsive ◽  
Double Blind ◽  
Compulsive Disorder ◽  
Significant Difference ◽  
Competing Interest ◽  
To Receive

IntroductionUp to 50% of patients with OCD have failed to respond in SSRI trials, so looking for pharmacological alternatives in treatment of obsessive compulsive disorder (OCD) seems necessary.ObjectivesSurveying duloxetine augmentation in treatment of resistant OCD.AimsStudy the effects of serotonin-norepinephrine enhancers for treatment of OCD.MethodsThis augmentation trial was designed as an 8-week randomized controlled, double blind study. Forty-six patients suffering from OCD who had failed to respond to at least 12 weeks of treatment with a selective serotonin reuptake inhibitor (fluoxetine, citalopram or fluvoxamine) were randomly allocated to receive duloxetine or sertraline plus their current anti OCD treatment. Yale-Brown Obsessive Compulsive Scale (Y-BOCS) was the primary outcome measure.ResultsForty-six patients (24 of 30 in duloxetine group and 22 of 27 in sertraline group) completed the trial. Both groups showed improvement over the 8-week study period (mean Y-BOCS total score at week 8 as compared with baseline: P < 0.001 and P < 0.001) without significant difference (P = 0.861). Those receiving duloxetine plus their initial medications experienced a mean decrease of 33.0% in Y-BOCS score and the patients with sertraline added to their initial medication experienced a mean decrease of 34.5% in Y-BOCS.ConclusionsOur double blind controlled clinical trial showed duloxetine to be as effective as sertraline in reducing obsessive and compulsive symptoms in resistant OCD patients. However, it needs to be noted that our study is preliminary and larger double blind placebo controlled studies are necessary to confirm the results.Disclosure of interestThe authors have not supplied their declaration of competing interest.

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