Urinary congophilia in pregnancy: a marker of kidney injury rather than preeclampsia.

BACKGROUND: The differentiation between preeclampsia and similarly presenting kidney disease in pregnancy is a diagnostic challenge. Although some laboratory tests have been utilized, globally validated tools are yet needed, particularly in resource-limited settings. Congophilic proteins are abundantly detected in the urine of pregnant women who develop preeclampsia that is thought to be a marker of disease process. The present study aimed to assess the diagnostic and predictive utility of urinary congophilia in pregnant women with hypertensive disorders of pregnancy as well as kidney diseases. METHODS: This cohort study included 157 pregnant women, classified as healthy controls ( n  = 38), preeclampsia/eclampsia ( n  = 45), gestational hypertension ( n  = 9), chronic hypertension ( n  = 8), chronic kidney disease (CKD) ( n  = 27), and pregnancy-related acute kidney injury (PR-AKI) ( n  = 30). Urinary congophilia was assessed by Congo Red Dot Blot assay. RESULTS: Congo red retention (CRR) values were significantly higher in women with preeclampsia/eclampsia ( P  ≤ 0.001), chronic hypertension ( P  = 0.029), gestational hypertension ( P  = 0.017), CKD ( P  ≤ 0.001), PR-AKI secondary to preeclampsia ( P  ≤ 0.001), and PR-AKI secondary to other causes ( P  = 0.001), compared with healthy controls. Women with preeclampsia, CKD, and PR-AKI (non-preeclampsia related) exhibited the highest levels of CRR. CRR positively correlated to proteinuria ( P  = 0.006) and serum creatinine ( P  = 0.027). CRR did not significantly vary between women who presented antepartum and those presented postpartum after removal of the placenta ( P  = 0.707). CRR at a cut-off point of at least 1.272 had 91% specificity and 61.1% sensitivity in predicting renal recovery in PR-AKI patients. CRR had a poor specificity in discriminating preeclampsia from the other clinical presentations. CONCLUSION: Urinary congophilia could not discriminate preeclampsia from similarly presenting kidney diseases in pregnancy. Further studies are needed to improve differentiation of these conditions.

Angiogenic markers predict kidney injury and obstetric complications in women with preeclampsia and pregnancy-related acute kidney injury.

Pregnancy-related acute kidney injury (PRAKI) particularly on top of preeclampsia (PE) represents a major cause of maternal and fetal morbidity and mortality. Reliable diagnostic tools are needed to further evaluate the diagnosis and prognosis of PRAKI. Our objective was to study the diagnostic and prognostic value of angiogenic markers (e.g., stromal cell-derived factor 1 (SDF-1), vascular endothelial growth factor (VEGF), alarmins as uric acid) in women with PE and PRAKI. This prospective study included three groups; PRAKI, PE patients, and healthy controls that were compared regarding serum levels of the studied markers correlated to renal, maternal, and fetal outcomes. SDF-1, VEGF, and uric acid levels were significantly different between the three included groups and predicted PRAKI diagnosis. Patients with hemolysis, elevated liver enzymes, and low platelet (HELLP) syndrome exhibited the highest titers of SDF-1 and VEGF. A positive correlation was found between SDF-1 and renal recovery. Conclusively, serum assays of SDF-1, VEGF, and uric acid may add a diagnostic value in PRAKI and PE.

Acute kidney injury during pregnancy and puerperium: an Egyptian hospital-based study.

INTRODUCTION: While acute kidney injury (AKI) in pregnancy is currently a rare entity in developed countries, it is still a common occurrence in developing countries, representing a major cause of maternal and fetal morbidity and mortality. Scarce data are published regarding pregnancy-related acute kidney injury (PRAKI) in Middle Eastern and African countries. The aim of this work is to report on the frequency, the underlying causes, and the outcomes of patients with PRAKI in an Egyptian tertiary care hospital. METHODS: This is a prospective observational study that included 40 patients representing all women who presented to the Mansoura Nephrology and Dialysis Unit with PRAKI over two years. All patients were followed up for three months after hospital discharge to assess renal outcome, and till the end of pregnancy to assess the maternal and fetal outcomes. RESULTS: PRAKI was reported  in about 1% of women who presented to the obstetrics service, and accounted for 14% of all AKI patients who presented to the renal service in our hospital. Preeclampsia (PE) and obstetric hemorrhage were the commonest causes of PRAKI. Maternal mortality occurred in 22.5% of PRAKI patients. The majority of survivors (62.5%) fully recovered, while the remaining (37.5%) individuals became dialysis dependent. Unfavorable fetal events occurred in 24 pregnancies (60%). CONCLUSION: In our hospital in Mansoura, Egypt, PRAKI represents a relevant burden with potential ominous outcomes obstetric hemorrhage and preeclampsia were the major causes. Further research is needed to understand the causes and improve the outcomes of pregnancy-related AKI.

Fetal proximal and distal limb anomalies following exposure to mycophenolate mofetil during pregnancy: A case report and review of the literature.

BACKGROUND: Mycophenolate mofetil (MMF) is currently used in a wide spectrum of autoimmune diseases and has been rendered very effective in the management of systemic lupus erythematosus and lupus nephritis. MMF is known to be teratogenic (FDA category D) and therefore, women in childbearing period receiving MMF should be counselled to use effective contraceptive methods to avoid an unplanned pregnancy. CASE: A 22-year-old lady accidentally discovered to be pregnant while using MMF as a treatment of lupus nephritis which was replaced later on by azathioprine. After maternal and fetal evaluation, maternal lupus flare was confirmed and multiple fetal skeletal deformities associated with intrauterine growth restriction (IUGR) were diagnosed by 4-dimensional ultrasound. Termination of pregnancy was decided after shared decision making. CONCLUSION: Women in childbearing period should be advised to postpone pregnancy for at least six weeks after stoppage of MMF therapy because of its potential teratogenic effects during pregnancy.

Intrauterine Bacterial Colonization and Endometrial MicroRNA-17-5p Levels in Association to Endometriosis: A Study in an Egyptian Population.

We aimed to study the relation between both bacterial colonization of the uterine endometrium & endometrial miR-17-5p levels and endometriosis, and then to evaluate endometrial miR-17-5p as a biomarker of endometriosis. A comparative observational study was carried over 51 endometriosis patients and 51 controls admitted into Obstetrics and Gynecology department, Mansoura Faculty of Medicine. Endometrial tissue samples were collected and aimed for bacterial culture and identification of resulting organisms besides estimation of tissue levels of microRNA-17-5p by quantitative real time PCR. G. vaginalis, S. agalactiae, S. aureus, Mobiluncus and E. coli were associated with endometriosis. MicroRNA-17-5p was up-regulated in endometriosis patients (P value was <0.0001*). Its sensitivity and specificity were 90% and 76.5%. MiR-17-5p showed higher results in culture positive than negative cases. On studying the relation between the positivity of endometrial tissue culture and miR-17-5p and so endometriosis, P value was <0.0001*. We concluded that G. vaginalis, S. agalactiae, S. aureus, Mobiluncus and E. coli were associated with development of endometriosis. Endometrial miR-17-5p was elevated in association to positive detection of bacterial species. MiR-17-5p might be a bio- marker of endometriosis. ABBREVIATIONS: CFU/ml: Colony Forming Unit per Milliliter; miR-17-5p: MicroRNA-17-5p; qRT PCR: Quantitative Real Time Polymerase Chain Reaction.

Maternal Serum sEndoglin and Cell-Free Fetal DNA as Probable Markers of Preeclampsia: A Study in Single Center, Egypt.

Background: This study was conducted to compare the levels of maternal serum soluble endoglin (sEng) and cell-free fetal DNA (cffDNA) in pregnant females with PE to normotensive pregnant ones, together with relating these levels to preeclampsia (PE) severity and onset. Method of the study: It was a comparative study in Mansoura University Hospital, Egypt, to detect the levels of serum sEng by ELISA besides the levels of cffDNA by quantitative real-time polymerase chain reaction in 80 pregnant females suffering from PE in addition to 80 normotensive pregnant ones that were included as control. Results: Levels of serum sEng and cffDNA were higher in PE cases than control (p < 0.0001Ù­ both) and were significantly related to the severity of the disease. Levels were also higher in early than late onset PE (p < 0.003Ù­ and <0.002Ù­, respectively). Sensitivities, specificities, positive, and negative predictive values in addition to accuracy of serum sEng and cffDNA were 97.5%, 98.8%, 98.7%, 97.5%, and 98.1% and 97.5%, 93.8%, 94.0%, 97.4%, and 95.6%, respectively. Conclusion: Maternal serum sEng and cffDNA can be good markers for diagnosis of PE in Egyptian patients. They are positively related to the disease severity. Abbreviations: cffDNA; Cell-Free Fetal DNA, sEng; soluble Endoglin, PE; preeclampsia, qRT PCR; Quantitative real-time polymerase chain reaction.

High-risk and low-risk human papilloma virus in association to spontaneous preterm labor: a case-control study in a tertiary center, Egypt.

INTRODUCTION: This study aimed to detect the correlation between human papillomavirus (HPV) and spontaneous preterm labor in Egyptian women and its association to the human papilloma viral load and MPP2 gene expression. MATERIAL AND METHODS: We performed an observational comparative case-control study in Department of Obstetric and Gynecology, Mansoura University Hospitals over women presented with spontaneous preterm labor, besides females admitted for giving birth at full term to detect conserved sequence in HPV-L1 gene (GP5/GP6) followed by genotype detection of high- and low-risk HPVs with quantification of the viral load and the MMP2 gene expression using real-time polymerase chain reaction (PCR). RESULTS: The prevalence of HPV was 18.1% in preterm females, but only 4% in full-term women (p value = 0.019*). Twenty percent were PCR positive for HPV 16 and 40% for HPV 18 whereas none of the control was positive for any of the studied high-risk genotypes. Thirty percent were PCR positive for HPV 6 and 10% were positive for HPV 11. MMP2 gene expression was significantly higher in preterm than full term. Human papilloma viral load was found to be positively correlated to the rate of MMP2 expression and the gestational age was significantly related to the viral load and the rate of expression of MMP2 gene. CONCLUSION: Human pabilloma virus especially high-risk genotypes was correlated to spontaneous preterm labor in Egyptian females through increasing early expression of MMP2 gene. The time of occurrence of preterm labor was affected by the viral load and so the rate of expression of MMP2 gene.

Is early intervention using Mansoura-VV uterine compression sutures an effective procedure in the management of primary atonic postpartum hemorrhage? : a prospective study.

BACKGROUND: Postpartum hemorrhage is the leading cause of maternal death, uterine atony accounts for 75-90% of primary postpartum hemorrhage. The efficacy of the Uterine compression suture in the treatment of atonic postpartum hemorrhage is time-tested and can be said to be almost established.The aim of this study was to assess the role of the Mansoura-VV uterine compression suture as an early intervention in the management of primary atonic postpartum hemorrhage. METHODS: This prospective observational study included 108 women with primary atonic PPH over a period of 44 months. Uterine atony was diagnosed when the uterus was soft and failed to respond to ordinary ecbolics. Early intervention by Mansoura-VV uterine compression sutures was carried out within 15 min of the second dose of ecobolics and before progressing to any further surgical procedure. RESULTS: Following the Mansoura-VV uterine compression sutures, uterine bleeding was controlled in all except one patient (107/108 cases; 99.07%) who required additional bilateral uterine vessels ligation. Another case (0.93%) was subjected to re-laparotomy due to intraperitoneal hemorrhage. Packed RBC transfusion was needed in 10 cases (9.25%). Admission to ICU was needed in 9 cases (8.33%) because of associated medical conditions. One week following the procedure, 1 case (0.93%) was diagnosed with haematometra. CONCLUSION: Early intervention in cases of primary atonic PPH using the Mansoura-VV uterine compression sutures is an easy, rapid and effective method in controlling PPH in low resource settings. TRIAL REGISTRATION: The study was registered at clinicaltrial.gov , Identifiers: NCT03117647 "retrospectively registererd" registered at April 7, 2017.

In vitro activity of nitazoxanide against some metronidazole-resistant and susceptible Trichomonas vaginalis isolates.

Trichomonas vaginalis cases refractory to metronidazole (MTZ) treatment had been reported. This study aimed to the assessment of in vitro metronidazole resistance among Trichomonas positive cases with treatment failure by determination of metronidazole minimal lethal concentration (MLC), and to the evaluation of the in vitro efficacy of nitazoxanide (NTZ) as compared to metronidazole (MTZ) in both resistant and susceptible isolates. Drug testing was carried out by an aerobic tube assay where suspension of Trichomonas trophozoites was exposed for 24 and 48 h to serial dilution of metronidazole and nitazoxanide. In refractory isolates n = 30, median MLC conc. for MTZ was 100 µg/ml versus 50 µg/ml for NTZ (P < .0001). After 48 h median MLC conc. for MTZ was 25 µg/ml versus 12 µg/ml for NTZ (P < .0001). NTZ against resistant isolates was twice as active as MTZ at 24 h and increased to 2.5 times at 48 h while in susceptible isolates, NTZ was twice as active as MTZ at both 24 h and 48 h. MTZ was about 8 times more active in susceptible than in resistant isolates. So, high doses of metronidazole in resistant cases will likely increase side effects. The study proved the activity of NTZ against trichomoniasis especially in cases with MTZ resistance.

Interleukin-6, intracellular adhesion molecule-1, and glycodelin A levels in serum and peritoneal fluid as biomarkers for endometriosis.

OBJECTIVE: To compare levels of interleukin-6 (IL-6), intracellular adhesion molecule-1 (ICAM-1), and glycodelin A in serum and peritoneal fluid of patients with and without endometriosis, and to correlate levels with disease stage. METHODS: An observational study was undertaken at Mansoura University Hospital, Egypt, between March 2014 and June 2015. Patients aged 21-48 years laparoscopically diagnosed with endometriosis and those without endometriosis who underwent laparoscopy for tubal ligation were included. Levels of IL-6, ICAM-1, and glycodelin A were measured in samples of serum and peritoneal fluid. Receiver operating characteristic curves were used to evaluate diagnostic accuracy. RESULTS: Forty-eight women with endometriosis and 20 without the disorder were included. IL-6 and glycodelin A levels in serum and peritoneal fluid were higher in the endometriosis group than in the control group (P<0.001 for all); ICAM-1 levels did not differ. The sensitivity and specificity values were 93.8% and 80.0% for serum IL-6, 58.3% and 60.0% for serum ICAM-1, and 91.7% and 75.0% for serum glycodelin A. The corresponding values for peritoneal fluid markers were 85.4% and 89.0%, 60.4% and 50.0%, and 89.6% and 90.0%, respectively. IL-6 and glycodelin A levels in serum and peritoneal fluid increased with disease stage (P<0.001 for all). CONCLUSION: IL-6 and glycodelin A, but not ICAM-1, are potential biomarkers for endometriosis and are positively correlated with the disease stage.

Helicobacter pylori, Chlamydiae pneumoniae and trachomatis as probable etiological agents of preeclampsia.

OBJECTIVES: The aim of this study was to evaluate the evidence for Helicobacter pylori, Chlamydiae pneumoniae and trachomatis to act as a probable etiology for preeclampsia (PE), together with estimating the prevalence of such infections in pregnant women with PE. METHODS: We performed a prospective study in Mansoura University Hospitals, Egypt, for detecting H. pylori infection by estimating H. pylori IgG and IgM, in addition to detection of Chlamydiae infections by PCR in 90 pregnant women with PE and 90 normotensive pregnant women of the same age and body mass index who were studied as control. RESULTS: The prevalence of H. pylori infection in preeclamptic pregnant women was 54.4% with a statistically significant association to PE. The prevalence of C. pneumonia was 27.8% whereas that of C. trachomatis was 4.44%. The infected preeclamptic cases showed high levels of leucocytes besides elevated C-reactive protein concentrations. CONCLUSION: Helicobacter pylori was found to act as a cofactor in the development of PE. Occurrence of C. trachomatis was low in pregnant women in our community; however, it showed that it may act as a cofactor in PE, whereas C. pneumoniae was attributed to have no role in PE pathogenesis until supported by further studies.

Aromatase inhibitors or gonadotropin-releasing hormone agonists for the management of uterine adenomyosis: a randomized controlled trial.

OBJECTIVE: To compare the efficacy of aromatase inhibitor vs. gonadotrophin-releasing hormone agonists in treating premenopausal women with uterine adenomyosis. DESIGN: A prospective randomized controlled study. SETTING: A university hospital and a private practice setting. POPULATION: Thirty-two patients with uterine adenomyosis. METHODS: Patients were randomly allocated to receive oral letrozole (2.5 mg/day) or a subcutaneous gonadotropin-releasing hormone agonist (goserelin, 3.6 mg) for 12 weeks. Uterine and adenomyoma volumes were determined at baseline and during treatment at four, eight and 12 weeks. OUTCOME MEASURES: Measurements were performed at baseline and during treatment at four, eight 8 and 12 weeks, and mean values were calculated. Symptoms at the start and after 12 weeks were evaluated. RESULTS: No significant differences in the total uterine size between the post treatment uterine volumes in the two groups (20.1, 15.4 and 13.0 cm(3) vs. 21.7, 15.1 and 11.7 cm(3) , at four, eight and 12 weeks, respectively). Total adenomyoma volume decreased by 8.6, 29.7 and 40.9% vs. 5.7, 34.6 and 49.1% after four, eight and 12 weeks of treatment, in group A and B, respectively. Two patients became pregnant in group A during treatment. CONCLUSIONS: Aromatase inhibitors are as effective as gonadotropin-releasing hormone agonists in reducing adenomyoma volume and improving symptoms.

Extended letrozole therapy for ovulation induction in clomiphene-resistant women with polycystic ovary syndrome: a novel protocol.

OBJECTIVE: To evaluate the outcome of long letrozole therapy for induction of ovulation in patients with clomiphene-resistant polycystic ovary syndrome (PCOS). DESIGN: Prospective randomized controlled study. SETTING: University teaching hospital and a private practice. PATIENT(S): The study comprised 218 patients with clomiphene-resistant PCOS. INTERVENTION(S): Patients were randomly allocated to treatment with either long letrozole therapy (n = 108; 219 cycles) or short letrozole therapy (n = 110; 225 cycles). MAIN OUTCOME MEASURE(S): Number of growing and mature follicles, serum E(2) (pg/mL), serum P (ng/mL), endometrial thickness, occurrence of pregnancy and miscarriage. RESULT(S): The number of ovulating patients was greater in the long letrozole group (65.7% vs. 61.8%), but without statistical differences. The total numbers of follicles during stimulation was significantly greater in the long letrozole group (6.7 +/- 0.3 vs. 3.9 +/- 0.4). The numbers of follicles > or =14 mm and > or =18 mm were significantly greater in the long letrozole group. There was no significant difference in the pretreatment endometrial thickness or endometrial thickness at the time of hCG administration between the two groups. Pregnancy occurred in 28 of 225 cycles in the short group (12.4%) and 38 of 219 cycles (17.4%) in the long letrozole group, and the difference was statistically significant. CONCLUSION(S): The long letrozole protocol (10 days) can produce more mature follicles and subsequently more pregnancies than the short letrozole therapy (5 days).

Treatment options and pregnancy outcome in women with idiopathic recurrent miscarriage: a randomized placebo-controlled study.

OBJECTIVE: To compare the use of enoxaparin alone with combination therapy of prednisone, aspirin and progesterone in the treatment of women with idiopathic recurrent miscarriage (IRM) in terms of live births and pregnancy outcome. METHODS: A prospective, randomized, single-blinded, placebo-controlled trial was conducted at a tertiary referral obstetric hospital. The participants were 170 women with a diagnosis of IRM. Women were recruited after full investigative screening. Women with > or =3 fetal losses and after exclusion of all known causes of recurrent miscarriage were randomly allocated to receive either enoxaparin alone, combination treatment consisting of prednisone, aspirin, and progesterone or placebo. Rates of live births, antenatal complications, delivery and neonatal outcomes were recorded prospectively. Data were statistically analyzed as appropriate. RESULTS: Ten patients were dropped out after random assignment. Eighty-one percent of the enoxaparin (46/57) group and 85% of the combination-treated group (45/53) were delivered of live infants compared to 48% (24/50) of the placebo (P < 0.05). Women who were treated with combination therapy had a 4.2% higher live birth rate than enoxaparin group. This difference was not significant. Miscarriage rates were significantly lower in the treated groups compared with placebo (P < 0.05). There were no significant differences in late obstetric complications or neonatal mortality between groups. CONCLUSIONS: A combination treatment consisting of high-dose, low-duration prednisone, progesterone and aspirin might be an effective treatment as enoxaparin alone. Both regimens were associated with a good pregnancy outcome.