BACKGROUND: The objective of this study was to determine the prevalence of Chlamydia trachomatis among both men and women seeking help at an infertility clinic, and to prospectively follow the effect ...of previous infection on pregnancy rates and pregnancy outcome after a long follow‐up period (mean 37 months). METHODS: A total of 244 infertile couples was tested for C. trachomatis IgG antibodies, and IgG+ couples were also tested for C. trachomatis DNA by PCR in a first‐void urine sample. Study parameters were serology, PCR results, clinical diagnoses, treatments, pregnancy rates and pregnancy outcome. As controls, age‐matched and spontaneously pregnant women were also tested with serology. RESULTS: The prevalence of IgG antibodies was 24.2, 20.1 and 15.6% among infertile women, infertile men and control women respectively. The prevalence of C. trachomatis DNA was 6.8 and 7.1% among tested women and men respectively. The presence of C. trachomatis IgG antibodies in women was related to tubal factor infertility (TFI) (P = 0.002). Decreased pregnancy rates were seen in couples where the man was IgG+ (P = 0.005) with no relationship to TFI. Among women who achieved pregnancy, there was no difference in pregnancy outcome between IgG+ or negative couples. CONCLUSIONS: C. trachomatis IgG antibodies in the man of the infertile couple was related to decreased pregnancy rates and to the presence of IgG antibodies in the woman. There was a high prevalence of asymptomatic persistent infections among infertile couples.
It has been suggested that the relative importance of oestrogen-metabolising pathways may affect the risk of oestrogen-dependent tumours including endometrial cancer. One hypothesis is that the ...2-hydroxy pathway is protective, whereas the 16α-hydroxy pathway is harmful.
We conducted a case-control study nested within three prospective cohorts to assess whether the circulating 2-hydroxyestrone : 16α-hydroxyestrone (2-OHE1 : 16α-OHE1) ratio is inversely associated with endometrial cancer risk in postmenopausal women. A total of 179 cases and 336 controls, matching cases on cohort, age and date of blood donation, were included. Levels of 2-OHE1 and 16α-OHE1 were measured using a monoclonal antibody-based enzyme assay.
Endometrial cancer risk increased with increasing levels of both metabolites, with odds ratios in the top tertiles of 2.4 (95% CI=1.3, 4.6; P(trend)=0.007) for 2-OHE1 and 1.9 (95% CI=1.1, 3.5; P(trend)=0.03) for 16α-OHE1 in analyses adjusting for endometrial cancer risk factors. These associations were attenuated and no longer statistically significant after further adjustment for oestrone or oestradiol levels. No significant association was observed for the 2-OHE1 : 16α-OHE1 ratio.
Our results do not support the hypothesis that greater metabolism of oestrogen via the 2-OH pathway, relative to the 16α-OH pathway, protects against endometrial cancer.
The Chlamydia IgG antibody test (CAT) shows considerable variations in reported estimates of test accuracy, partly because of the use of different assays and cut-off values. The aim of this study was ...to reassess the accuracy of CAT in diagnosing tubal pathology by individual patient data (IPD) meta-analysis for three different CAT assays.
We approached authors of primary studies that used micro-immunofluorescence tests (MIF), immunofluorescence tests (IF) or enzyme-linked immunosorbent assay tests (ELISA). Using the obtained IPD, we performed pooled receiver operator characteristics analysis and logistic regression analysis with a random effects model to compare the three assays. Tubal pathology was defined as either any tubal obstruction or bilateral tubal obstruction.
We acquired data of 14 primary studies containing data of 6191 women, of which data of 3453 women were available for analysis. The areas under the curve for ELISA, IF and MIF were 0.64, 0.65 and 0.75, respectively (P-value < 0.001) for any tubal pathology and 0.66, 0.66 and 0.77, respectively (P-value = 0.01) for bilateral tubal pathology.
In Chlamydia antibody testing, MIF is superior in the assessment of tubal pathology. In the initial screen for tubal pathology MIF should therefore be the test of first choice.
In recent years, the fallopian tubes have been found to play a critical role in the pathogenesis of ovarian cancer. Therefore, bilateral salpingectomy at the time of hysterectomy has been proposed as ...a preventive procedure, but with scarce scientific evidence to support the efficiency and safety.
Our primary objective was to evaluate the risk of surgical complications and menopausal symptoms when performing bilateral salpingectomy in addition to benign hysterectomy. Furthermore, we sought to compare time in surgery, perioperative blood loss/blood transfusion, duration of hospital stay, days to normal activities of daily living, and days out of work for hysterectomy with bilateral salpingectomy compared with hysterectomy only. A secondary objective was to study the uptake of opportunistic salpingectomy in Sweden.
This was a retrospective observational cohort study based on data from the National Quality Register of Gynecological Surgery in Sweden. Women <55 years of age who had a hysterectomy for benign indications with or without bilateral salpingectomy in 1998 through 2016 were included. Possible confounding was adjusted for in multivariable regression models.
During the study period, 23,369 women had a hysterectomy for benign indications. The frequency of bilateral salpingectomy at the time of hysterectomy increased mainly from 2013, which is why the period 2013 through mid-2016 was selected for further analysis (n = 6892). There was a low frequency of vaginal hysterectomy with bilateral salpingectomy performed in this period, which is why only abdominal and laparoscopic surgeries were selected for comparative analysis (n = 4906). This study indicates an increased risk of menopausal symptoms (adjusted relative risk, 1.33; 95% confidence interval, 1.04–1.69) 1 year after hysterectomy with bilateral salpingectomy compared with hysterectomy only. Hospital stay was 0.1 days longer in women having salpingectomy (P = .01), and bleeding was slightly reduced in the salpingectomy group (–20 mL, P = .04). Other outcome measures were not significantly associated with salpingectomy, albeit a tendency toward higher risk of minor complications was seen (adjusted relative risk, 1.30; 95% confidence interval, 0.93–1.83).
Bilateral salpingectomy at the time of hysterectomy was associated with an increased risk of menopausal symptoms 1 year after surgery. Randomized clinical trials reducing the risk of residual and unmeasured confounding and longer follow-up are needed to correctly inform women on the risks and benefits of opportunistic salpingectomy.
Abstract
Epidemiologic, clinical, molecular and translational research findings support an interrelationship between Chlamydia trachomatis, pelvic inflammatory disease (PID), and epithelial ovarian ...cancer (EOC). Overall, the link between C. trachomatis, PID, and EOC seems to be relatively weak, although nondifferential misclassification bias may have attenuated the results. The predominant tubal origin of EOC and the role of chronic inflammation in tumorigenesis suggest that the association is biologically plausible. Thus, C. trachomatis and PID may represent potential risk factors or risk markers for EOC. However, many steps in this chain of events are still poorly understood and need to be addressed in future studies. Research gaps include time of exposure in relation to the long-term consequences and lag time to EOC. Data of differential risk for EOC between chlamydial and nonchlamydial PID is also needed. Another major research gap has been the absence of high-performance biomarkers for C. trachomatis, PID, and EOC, as well as EOC precursors. Biomarkers for C. trachomatis and PID leading to increased risk of EOC should be developed. If the association is confirmed, C. trachomatis and PID prevention efforts may play a role in reducing the burden of EOC.
Evidence suggests that the hormonal milieu of pregnancy is an important determinant of subsequent cancer and other chronic diseases in both the mother and the offspring. Many of the existing ...maternity and birth cohorts include specimens drawn only once during pregnancy. How well a single blood specimen collected during a pregnancy characterizes exposure to these hormones throughout gestation, and also in subsequent pregnancies, is not well understood.
We used serial serum samples from 71 pregnant women (25 primiparous, 25 multiparous, and 21 with two consecutive pregnancies) with natural, complication-free pregnancies and a healthy offspring at term who participated in a population-based screening trial for congenital infections in Finland between January 1st, 1988 and June 30, 1989 and provided a blood sample in each trimester.
Hormone levels were more strongly correlated between consecutive trimesters of a pregnancy than between the 1st and 3rd trimester (e.g., estradiol, rT1 vs. T2 = 0.51 and rT2 vs. T3 = 0.60, p < 0.01; rT1 vs. T3 = 0.32, p < 0.05). Concentrations of sRANKL remained stable throughout gestation, whereas estradiol, estrone, progesterone, testosterone, prolactin, and osteoprotegerin increased throughout pregnancy. First trimester hormone concentrations explained less of the variation in the third trimester on their own than second trimester hormone levels (e.g. estradiol R(2) T1 = 16 % and R(2) T2 = 42 %). Addition of maternal (e.g., smoking) and/or child characteristics (e.g., sex) improved the accuracy of the 3rd trimester estimates for some of the hormones.
One hormone measurement in early pregnancy, in conjunction with maternal and fetal characteristics, permits estimation of 3rd trimester hormone concentrations. Therefore, single hormone measurements available from maternity cohorts are suitable to quantify hormone exposure during pregnancy. To our knowledge, we provide the first data on correlations between hormone concentrations both across trimesters of a single pregnancy, as well as between two subsequent pregnancies.
Introduction
Complications after gynecological surgery in Sweden are registered in the well‐established Swedish National Quality Register of Gynecological Surgery, GynOp. The aim of this study was to ...analyze interrater reliability in assessing complications according to the methods in GynOp, and to explore physicians' perceptions of registering complications.
Material and methods
A digital survey was sent to gynecologists and residents in gynecology in Sweden. Participating clinics were recruited through the Swedish network for national clinical studies in Obstetrics and Gynecology, SNAKS. Twenty fictional cases, intended to represent normal postoperative course, failure to cure, and varying degrees of complications, were developed by the research group. The clinical scenarios included abdominal and laparoscopic surgery of the uterus and adnexa, vaginal hysterectomies, as well as hysteroscopy. The respondents graded each case on the presence of a complication (yes/no). Type of complication, severity, and what action the complication required according to Clavien‐Dindo was registered if a complication was acknowledged, according to the method in GynOp. Interrater reliability and the opinions of the respondents were presented descriptively. More than 80% of respondents making the same assessment was considered as agreement.
Results
The response rate was 41%, with 104 responding physicians from 16 gynecological clinics. Type and severity of complication was considered relevant to register by 88% and 89% of respondents, respectively. Agreement on whether the case described a complication was >80% in 85% (17/20) of cases and agreement using the Clavien‐Dindo classification was >90% in 80% (16/20) of cases. There was high agreement in assessments of classically severe complications, such as pulmonary embolism and ureteral damage, in both presence of complication and severity, as well as Clavien‐Dindo (>90% for all methods). Cases with agreement <80% on whether the case described a complication were bordering between normal postoperative course and minor complication.
Conclusions
This study provides validation for the methods used to register complications after gynecological surgery according to the GynOp register, including the use of Clavien‐Dindo in gynecology. However, the results indicate a need to define what should be considered symptoms inherent to each type of surgery.
The methods used to register complications in The Swedish National Quality Register of Gynecological Surgery has high interrater reliability. However, a definition of what should be considered symptoms inherent to type of surgery is needed.
The HOPPSA trial is a multi-center national registry-based randomized controlled trial to test the safety and effectiveness of performing opportunistic salpingectomy at hysterectomy to reduce the ...risk of epithelial ovarian cancer (EOC). The study protocol was first published in January 2019 and is available at https://trialsjournal.biomedcentral.com/articles/10.1186/s13063-018-3083-8 . Here, we report amendments made to the study protocol since commencement of the trial.
The primary outcomes analyses have been changed. (1) Complications will be analyzed using binomial generalized estimating equation (GEE) with log link function, while the unadjusted analyses according to Miettinen and Nurminen will be performed as a sensitivity analysis. (2) Absolute change in Menopause Rating Scale (MRS) will primarily be analyzed using a mixed effects model, adjusted for baseline MRS and center as a random effect. (3) Time to EOC will be analyzed using the mixed effects Cox regression model with center as random effect, while the unadjusted log-rank test will be performed as a sensitivity analysis. The primary outcome Complications will be based solely on the specific assessment in the GynOp quality registry. The Clavien-Dindo classification will be evaluated as a secondary outcome. Furthermore, MRS is also measured three years postoperatively to better pinpoint the onset of menopausal symptoms.
The changes to the protocol mainly concern the analyses of data. No changes to recruitment, randomization, intervention, or follow-up of primary outcomes have been made. An interim analysis during 2021 concluded that the study should continue until the target sample size is reached.
ClinicalTrials.gov, NCT03045965 . Registered 8 February 2017.
Treatment of patients after organ transplantation with the immunosuppressive drug cyclosporin A (CsA) is often accompanied
by impaired glucose tolerance, thus promoting the development of diabetes ...mellitus. In the present article we show that 2
to 5 μM CsA diminishes glucose-induced insulin secretion of isolated mouse pancreatic islets in vitro by inhibiting glucose-stimulated
oscillations of the cytoplasmic free-Ca 2+ concentration Ca 2+ c . This effect is not due to an inhibition of calcineurin, which mediates the immunosuppressive effect of CsA, because other
calcineurin inhibitors, deltamethrin and tacrolimus, did not affect the oscillations in Ca 2+ c of the B-cells. The CsA-induced decrease in Ca 2+ c to basal values was not caused by a direct inhibition of L-type Ca 2+ channels. CsA is known to be a potent inhibitor of the mitochondrial permeability transition pore (PTP), which we recently
suggested to be involved in the regulation of oscillations. Consequently, CsA also inhibited the oscillations of the cell
membrane potential, and it is shown that these effects could not be ascribed to cellular ATP depletion. However, the mitochondrial
membrane potential ÎΨ was affected by CsA by inhibiting the oscillations in ÎΨ. Interestingly, the observed reduction in Ca 2+ c could be counteracted by the K + ATP channel blocker tolbutamide, indicating that the stimulus-secretion coupling was interrupted before the closure of K + ATP channels. It is concluded that CsA alters B-cell function by inhibiting the mitochondrial PTP. This terminates the oscillatory
activity that is indispensable for adequate insulin secretion. Thus, CsA acts on different targets to induce the immunosuppressive
and the diabetogenic effect.
ATP and luciferin are not only substrates of firefly luciferase, but can, in addition, modulate its activity. High concentrations of luciferin induce a conformational change of the enzyme that ...temporarily reduces the catalytic rate. Re-activation takes approx. 20 min and is independent of variation in the concentration of enzyme or ATP, but lengthens with increasing luciferin concentration. High concentrations of albumin reduce this luciferin effect. The kinetic properties of firefly luciferase determined from initial rates and at steady state after 1 min of catalysis have been analysed according to Michaelis-Menten kinetics. There is only one active site for each of the substrates. At steady state the Km and Vmax values for both substrates are reduced in an uncompetitive manner. Hyperbolic Lineweaver-Burk plots indicate an activation by ATP probably by binding to an allosteric site. A model is presented which incorporates luciferin induced de- and re-activation effects. Experimental conditions to avoid the regulatory effects of substrates during ATP monitoring are proposed.
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