Objective
To evaluate the efficacy of isosorbide mononitrate (IMN) for stimulating cervical ripening among pregnant women with premature rupture of membranes (PROM) at or post term.
Methods
A ...prospective randomized double‐blind, placebo‐controlled trial at Kasr El‐Ainy Hospital, Cairo, Egypt, from October 2018 to May 2019. Pregnant women at or post term with PROM and unfavorable cervix (Bishop score ≤6) were randomly assigned to receive intra‐vaginal IMN (n = 70) or placebo (n = 70) before admission for induction of labor. The main outcome was induction to the delivery interval. Data were compared between groups by t test.
Results
The mean ± SD duration from the initial dose of IMN/placebo to the beginning of the active phase of labor was significantly shorter in the IMN group than in the control group (9.7 ± 5.6 h vs. 12.9 ± 5.3 h). The IMN group also had a shorter time interval from induction to delivery (P < 0.01). There was no difference in adverse effects between the groups.
Conclusion
Intra‐vaginal IMN for cervical ripening in the induction of labor among pregnant with PROM at or post term was found to be effective and safe with minimal adverse effects, and good neonatal and maternal outcomes.
ClinicalTrials.gov: NCT03665779.
Synopsis
Isosorbide mononitrate was found to be safe and effective for cervical ripening before induction of labor among pregnant women with PROM at or post term.
Aim
As angiogenesis is an essential step for chorionic villi formation. Vascular endothelial growth factor (VEGF) is essential for endothelial cell proliferation. Endothelial nitric oxide synthase ...(eNOS) is a powerful playmaker in hypoxia‐induced angiogenesis. Thrombin‐activatable fibrinolysis inhibitor (TAFI) regulates both fibrinolysis and inflammation. Genetic alterations of these factors may lead to recurrent spontaneous abortion (RSA). We aimed to investigate the combined genetic variants of VEGF G‐1154A and two eNOS genetic variants: T‐786C promoter region and intron 4 variable number of tandom repeats in addition to TAFI C‐1040T among RSA patients.
Methods
The study included 50 patients with RSA and 50 healthy controls. Polymerase chain reaction and restriction fragment length polymorphism were used for genotyping.
Results
Both genetic alterations of eNOS confirmed at least a sixfold increase of RSA risk. Interestingly, they were associated with TAFI C‐1040Tgenetic variant in 21 patients, eight of them had both studied eNOS genetic alterations and TAFI C‐1040Tgenetic variant, while each eNOS genetic variant associated with TAFI C‐1040Tconfirmed an almost one and half fold increase risk of RSA.
Conclusion
These findings highlighted the role of eNOS and nitric oxide metabolism in RSA and opened the gate to investigate the interaction of vasoconstrictive and fibrinolytic inhibitor systems.
The toxicity of cisplatin (CDDP) toward the renal tubules and its severe effects on the proximal tubules limits its further use in cancer therapy. The current study was undertaken to evaluate the ...protective effects of gallic acid-grafted O-carboxymethyl chitosan (GA@CMCS) against nephrotoxicity induced by CDDP in rats. Renal injury was assessed in the GA@CMCS/CDDP-treated rats using kidney injury molecule-1 (KIM-1). Moreover, the levels of reduced glutathione (GSH), malondialdehyde (MDA), and nitric oxide (NO) were measured. The comet assay was performed to measure the DNA damage. The renoprotective activity of GA@CMCS was supported by histo- and immuno-pathological studies of the kidney. GA@CMCS significantly normalized the increases in kidney homogenate of KIM-1, MDA, and NO-induced by CDDP and significantly increased GSH as compared with the CDDP group. GA@CMCS also significantly protects rat kidneys from CDDP-induced histo- and immuno-pathological changes. Both biochemical findings and histo- and immuno-pathological evidence showed the renoprotective potential of GA@CMCS against CDDP-induced oxidative stress, inflammation, and renal dysfunction in rats. In conclusion, GA@CMCS has been shown to mitigate the nephrotoxicity impact of CDDP in cancer therapy.
Abstract Objective To evaluate the efficacy of isosorbide mononitrate (IMN) for stimulating cervical ripening among pregnant women with premature rupture of membranes (PROM) at or post term. Methods ...A prospective randomized double‐blind, placebo‐controlled trial at Kasr El‐Ainy Hospital, Cairo, Egypt, from October 2018 to May 2019. Pregnant women at or post term with PROM and unfavorable cervix (Bishop score ≤6) were randomly assigned to receive intra‐vaginal IMN ( n = 70) or placebo ( n = 70) before admission for induction of labor. The main outcome was induction to the delivery interval. Data were compared between groups by t test. Results The mean ± SD duration from the initial dose of IMN/placebo to the beginning of the active phase of labor was significantly shorter in the IMN group than in the control group (9.7 ± 5.6 h vs. 12.9 ± 5.3 h). The IMN group also had a shorter time interval from induction to delivery ( P < 0.01). There was no difference in adverse effects between the groups. Conclusion Intra‐vaginal IMN for cervical ripening in the induction of labor among pregnant with PROM at or post term was found to be effective and safe with minimal adverse effects, and good neonatal and maternal outcomes. ClinicalTrials.gov : NCT03665779.
Synopsis Isosorbide mononitrate was found to be safe and effective for cervical ripening before induction of labor among pregnant women with PROM at or post term.
Glioblastoma multiforme (GBM) has a poor prognosis-despite aggressive primary treatment composed of surgery, radiotherapy and chemotherapy, median survival is still around 15 months. It starts to ...grow again after a year of treatment and eventually nothing is effective at this stage. Recurrent GBM is one of the most disappointing fields for researchers in which their efforts have gained no benefit for patients. They were directed for a long time towards understanding the molecular basis that leads to the development of GBM. It is now known that GBM is a heterogeneous disease and resistance comes mainly from the regrowth of malignant cells after eradicating specific clones by targeted treatment. Epidermal growth factor receptor, platelet derived growth factor receptor, vascular endothelial growth factor receptor are known to be highly active in primary and recurrent GBM through different underlying pathways, despite this bevacizumab is the only Food and Drug Administration (FDA) approved drug for recurrent GBM. Immunotherapy is another important promising modality of treatment of GBM, after proper understanding of the microenvironment of the tumour and overcoming the reasons that historically stigmatise GBM as an 'immunologically cold tumour'. Radiotherapy can augment the effect of immunotherapy by different mechanisms. Also, dual immunotherapy which targets immune pathways at different stages and through different receptors further enhances immune stimulation against GBM. Delivery of pro-drugs to be activated at the tumour site and suicidal genes by gene therapy using different vectors shows promising results. Despite using neurotropic viral vectors specifically targeting glial cells (which are the cells of origin of GBM), no significant improvement of overall-survival has been seen as yet. Non-viral vectors 'polymeric and non-polymeric' show significant tumour shrinkage in pre-clinical trials and now at early-stage clinical trials. To this end, in this review, we aim to study the possible role of different molecular pathways that are involved in GBM's recurrence, we will also review the most relevant and recent clinical experience with targeted treatments and immunotherapies. We will discuss trials utilised tyrosine receptor kinase inhibitors, immunotherapy and gene therapy in recurrent GBM pointing to the causes of potential disappointing preliminary results of some of them. Additionally, we are suggesting a possible future treatment based on recent successful clinical data that could alter the outcome for GBM patients.
Abstract Objective To investigate the efficacy of intralipid supplementation in women with recurrent spontaneous abortion (RSA) and elevated natural killer cell activity undergoing in vitro ...fertilization/intracytoplasmic sperm injection. Methods Between February 10, 2013, and April 30, 2015, a double-blind randomized controlled study was conducted at a center in Egypt. Women with unexplained secondary infertility, RSA, and elevated levels of natural killer cells (> 12%) were enrolled and randomly assigned to receive intralipid (2 mL diluted at 20% in 250 mL saline) or saline (250 mL) infusion on the day of oocyte retrieval using random numbers and sealed envelopes. Patients and attending physicians were masked to group assignment. The infusions were repeated within 1 week of a positive pregnancy test and then every 2 weeks until the end of the first trimester. The primary outcome was chemical pregnancy 14 days after embryo transfer. Analyses were by intention-to-treat. Results Overall, 296 women were enrolled. Chemical pregnancy was recorded for 84 (58.3%) of 144 women in the intralipid group and 76 (50.0%) of 152 in the control group ( P = 0.129). Conclusion Intralipid supplementation did not increase frequency of chemical pregnancy. However, findings related to ongoing pregnancy and live birth should be investigated further. ClinicalTrials.gov: NCT01788540
To study the effectiveness of clomiphene citrate (CC) in preventing a premature LH surge during controlled ovarian stimulation in women undergoing assisted reproduction.
Prospective, randomized, ...controlled trial.
University hospital.
Two-hundred thirty couples with mild male factor, or unexplained infertility.
Couples were randomized to receive human menopausal gonadotrophins (hMG) followed by CC or hMG alone until the day of hCG.
The primary outcomes were the incidence of a clinical pregnancy and premature LH rise. Secondary outcomes were the E2 levels, number of mature follicles, and endometrial thickness as determined on the day of hCG.
The number of patients who had a premature LH surge was significantly lower in the hMG+CC group (5.45% vs. 15.89%). Additionally, the mean E2 levels (pg/mL) and the number of mature follicles were also significantly higher in the hMG+CC group (360.3±162.9 vs. 280±110.0 and 2.4±0.97 vs. 1.3±1.1, respectively), although there was no significant difference regarding number of canceled cycles, endometrial thickness, or clinical pregnancy rate.
The addition of CC to hMG has been proven to be effective in reducing premature LH surges without compromising the pregnancy rate.
To study the significance of progesterone/estradiol (P/E2) ratio on the outcome of ICSI cycles and if this relation would differ in obese vs. non-obese patients.
Retrospective analysis of the results ...of 143 patients undergoing their first ICSI cycles at kaser-elaini ART unit. All the included patients had long protocol for ovarian stimulation. P/E2 ratio was correlated to the pregnancy rate in all the included patients then they were classified into two groups according to their BMI into two groups. Group 1: with BMI>30 and group 2: with BMI<30. Different outcome parameters were compared between the two groups including peak estradiol and progesterone levels on day of HCG, P/E2 ratio in addition to the number of retrieved oocytes, their maturity, fertilization rate and the pregnancy rate.
Although elevated levels of peak estradiol in non-obese patients 4.43±5.02 compared to obese patients 3.27±2.24 and the difference is statistically significant (p value=0.017) in addition to significant difference in levels of peak progesterone which is elevated in non-obese patients 1.64±1.38 compared to obese patients 1.41±1.1 (p value=0.038). However, no significant difference was detected between the two groups regarding the progesterone/estradiol ratio (p value=0.989), also no statistical difference was found regarding the number of retrieved oocytes, number of mature oocytes and the rate of fertilization in each group. The pregnancy rate showed near values in each group 36.9% in non-obese patients’ vs. 29.4% in obese patients which was not found to be statistically significant between the two groups.
P/E2 ratio cannot be used as a reliable predictor for pregnancy rate, and this is not different between obese and non-obese patients. No significant difference was found between obese and non-obese patients regarding peak progesterone, estradiol level on day of neither HCG nor other ICSI outcomes including number of retrieved oocytes, fertilization rate or the pregnancy rate.
Preterm labor (PTL) can lead to preterm birth, which can cause neonatal mortality and morbidity. Preterm premature rupture of membranes (PPROM) and severe PTL (SPTL) are serious PTL subtypes. Hereby, ...we aimed to investigate risk factors associated with PPROM and SPTL, among Egyptian women.
In this case-control study, 117 women were enrolled without any known medical risk for PTL. The control group (n = 45) had term labor (≥37 gestational weeks), while the case group (n = 72) had PTL (<37 gestational weeks). The PTL group was subdivided into those with PPROM (n = 18) and those with intact membranes (n = 54). Fifty-two PTL women, with accurate gestational age, were subdivided into SPTL (n = 31, ≤34 gestational weeks) and mild preterm labor (MPTL; n = 21, 35-36 gestational weeks). All groups were examined for different demographic characteristics, obstetrical history, clinical signs, and vaginal and urinary tract infections. Nominal logistic regression was applied to investigate significant variables associated with PPROM and intact membranes PTL, while ordinal logistic regression was used to estimate significant variables associated with SPTL and MPTL.
The final multivariate nominal model identified abortion history, heavy vaginal bleeding history, and elevated vaginal pH as significant predictors of PPROM. The same model identified age <20 years old, abortion history, heavy growth of vaginal organisms, and any growth of Gram-negative bacilli as the significant predictors of intact membranes PTL. The final multivariate ordinal model identified age <20 years old, abortion history, vaginal pH, and heavy growth of vaginal organisms as the significant predictors of SPTL and MPTL.
Age <20 years old, abortion history, heavy vaginal bleeding, vaginal pH, and heavy growth of vaginal organisms were reported as risk factors for PPROM and SPTL. Most of these factors are related to infection; therefore, proper infection control is recommended during prenatal and antenatal care.
Recurrent spontaneous abortion (RSA) is defined as 3 or more consecutive pregnancy failures. Thrombin-activatable fibrinolysis inhibitor (TAFI) is a plasma zymogen that regulates both fibrinolysis ...and inflammation. The TAFI 1040C/T polymorphism could alter the circulating levels of TAFI with a reduced capacity to remove the fibrin clots from the circulation; therefore, it could be considered a molecular risk factor for RSA. The TAFI 1040C/T polymorphism was studied in 50 patients with RSA by polymerase chain reaction–restriction fragment length polymorphism technique and compared to 50 age- and gender-matched healthy volunteers as a control group to verify its possible association with RSA. In case group, the wild genotype (C/C) and heterozygous genotype (C/T) did not reduce the risk of RSA (odds ratio: 0.368 and 0.767, respectively), even when compared to the number of RSA (P = .71). A higher frequency of C allele in the control group and a higher frequency of T allele in the case group were observed but with no statistical significance. In conclusion, our study revealed that TAFI 1040C/T could not be considered a molecular predictive factor for RSA in Egyptians.
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