To assess if miscarriage, whether consecutive or not, is associated with an increased risk of subsequent cardiovascular disease.
A cohort study was performed using women with at least one miscarriage ...or live birth recorded from 1950 to 2010 in the Aberdeen Maternity and Neonatal Databank. The exposed groups consisted of women with non-consecutive, two consecutive or three or more consecutive miscarriages; the unexposed group consisted of all women with at least one live birth and no miscarriages. Women were linked to Scottish Morbidity Records for hospital admissions for cardiovascular conditions, cardiac surgery and death registrations. Main outcome measures were ischaemic heart disease, cerebrovascular disease and a composite outcome of any disease of circulatory system. A sensitivity analysis was performed dividing the women into those who had one, two or three or more miscarriages irrespective of whether these events were consecutive or not.
After excluding women with pre-existing hypertension, type 1 diabetes mellitus, kidney disease and 'disease of circulatory system', 60,105 women were analysed; 9419 with non-consecutive, 940 with two consecutive, 167 with three or more consecutive miscarriages and 49,579 with no miscarriage. In the multivariate analyses, a significant association was found between ischaemic heart disease and women with two (HRs 1.75 (95% CI 1.22 to 2.52)) or three or more (HR 3.18 (95% CI 1.49 to 6.80)) consecutive miscarriages. Similar patterns of risk were observed in the sensitivity analysis.
Women with a history of two or more miscarriages, irrespective of whether consecutive or not, appear to have an increased risk of ischaemic heart disease.
Surgical management of vulvar cancer is associated with high morbidity rates. The main aim of the GROINSS-V studies is reducing treatment-related morbidity by finding safe alternative treatment ...options in early-stage vulvar cancer patients. This article reviews the history, results, and updates of the GROINSS-V studies. The first GROINSS-V study was a multicenter observational study (from 2000 to 2006), which investigated the safety and clinical applicability of the sentinel lymph node procedure in patients with early-stage vulvar cancer. GROINSS-V-I showed that omitting inguinofemoral lymphadenectomy was safe in early-stage vulvar cancer patients with a negative sentinel lymph node, with an impressive reduction in treatment-related morbidity. GROINSS-V-II, a prospective multicenter phase II single-arm treatment trial (from 2005 to 2016) investigated whether radiotherapy could be a safe alternative for inguinofemoral lymphadenectomy in patients with a metastatic sentinel lymph node. This study showed that radiotherapy in patients with sentinel lymph node micrometastases (≤2 mm) was safe in terms of groin recurrence rate and with less treatment-related morbidity. These results, published in August 2021, should be implemented in (inter)national treatment guidelines for vulvar cancer. GROINSS-V-III recently started including patients. This study investigates the effectiveness and safety of chemoradiation in patients with a macrometastasis (>2 mm) in the sentinel lymph node.
To investigate the prevalence of and clinical factors associated with high-grade serous carcinoma (HGSC) at risk-reducing salpingo-oophorectomy (RRSO) in asymptomatic
-pathogenic variant (PV) ...carriers.
We included
-PV carriers who underwent RRSO between 1995 and 2018 from the Hereditary Breast and Ovarian cancer in the Netherlands study. All pathology reports were screened, and histopathology reviews were performed for RRSO specimens with epithelial abnormalities or where HGSC developed after normal RRSO. We then compared clinical characteristics, including parity and oral contraceptive pill (OCP) use, for women with and without HGSC at RRSO.
Of the 2,557 included women, 1,624 had
, 930 had
, and three had both
-PV. The median age at RRSO was 43.0 years (range: 25.3-73.8) for
-PV and 46.8 years (27.6-77.9) for
-PV carriers. Histopathologic review confirmed 28 of 29 HGSCs and two further HGSCs from among 20 apparently normal RRSO specimens. Thus, 24 (1.5%)
-PV and 6 (0.6%)
-PV carriers had HGSC at RRSO, with the fallopian tube identified as the primary site in 73%. The prevalence of HGSC in women who underwent RRSO at the recommended age was 0.4%. Among
PV carriers, older age at RRSO increased the risk of HGSC and long-term OCP use was protective.
We detected HGSC in 1.5% (
-PV) and 0.6% (
-PV) of RRSO specimens from asymptomatic
-PV carriers. Consistent with the fallopian tube hypothesis, we found most lesions in the fallopian tube. Our results highlight the importance of timely RRSO with total removal and assessment of the fallopian tubes and show the protective effects of long-term OCP.
The aim of this study was to describe the long-term outcome of asymptomatic BRCA1/2 germline pathogenic variant (GPV) carriers with high-grade serous carcinoma (HGSC) in their risk-reducing ...salpingo-oophorectomy (RRSO) specimen.
In a previously described cohort of asymptomatic BRCA1/2 GPV carriers derived from the Hereditary Breast and Ovarian cancer in the Netherlands (HEBON) study, women with HGSC at RRSO were identified. Main outcome was ten-year disease-free survival (DFS). Secondary outcomes were time to recurrence, ten-year disease-specific survival (DSS), ten-year overall survival (OS). Patient, disease and treatment characteristics associated with recurrence were described.
The 28 included women with HGSC at RRSO were diagnosed at a median age of 55.3 years (range: 33.5–74.3). After staging, eighteen women had (FIGO) stage I, three stage II and five had stage III disease. Two women did not undergo surgical staging and were classified as unknown stage. After a median follow-up of 13.5 years (range: 9.1–24.7), six women with stage I (33%), one woman with stage II (33%), two women with stage III (40%) and none of the women with unknown stage developed a recurrence. Median time to recurrence was 6.9 years (range: 0.8–9.2 years). Ten-year DFS was 68%, ten-year DSS was 88% and ten-year OS was 82%.
Most asymptomatic BRCA1/2 GPV carriers with HGSC at RRSO were diagnosed at an early stage. Nevertheless, after a median follow-up of 13.5 years, nine of the 28 women with HGSC at RRSO developed a recurrence after a median of 6.9 years.
•Three-quarters of the asymptomatic BRCA1/2 GPV carriers with HGSC at RRSO had early stage disease.•The ten-year disease-free survival was 68%, ten-year disease-specific survival was 88% and ten-year overall-survival was 82%.•After a median follow-up of 13.5 years, recurrence rate was 32% with median time to recurrence of 6.9 years (range 0.8–9.2).•Timely RRSO remains the only reliable method of reducing mortality of HGSC in BRCA1/2 GPV carriers.
Objective We sought to compare short- and long-term outcome in Quintero stage 1 twin-to-twin transfusion syndrome (TTTS), managed with laser surgery or conservatively. Study Design We conducted a ...retrospective study of all monochorionic twin pregnancies with stage 1 TTTS referred to our center. Primary outcomes were perinatal survival, neonatal morbidity, and long-term neurodevelopmental outcome. Results Fifty women presented with stage 1 TTTS of which 40% (20/50) was treated with laser and 60% (30/50) was managed conservatively. Perinatal survival of both or at least 1 twin was 65% (13/20) and 85% (17/20) in the laser group, and 77% (23/30) and 97% (29/30) in the conservatively managed group ( P = .52 and P = .29), respectively. Long-term neurodevelopmental impairment of the surviving infants was found in 0% (0/21) vs 23% (7/30), respectively ( P = .03). Conclusion In this retrospective study, long-term outcome in stage 1 TTTS was better after laser surgery than with conservative management, suggesting the need for a randomized controlled trial.
Introduction
Cardiovascular disease is the leading cause of death in women. Observational studies suggest that women with a history of recurrent miscarriage have an increased risk of cardiovascular ...disease.
Material and methods
Women who visited the recurrent miscarriage clinic at Leiden University Medical Center between 2000 and 2010 and who had their third consecutive miscarriage before the age of 31 years, were invited to participate in this follow‐up study (between 2012 and 2014). The reference group consisted of women with at least one uncomplicated pregnancy and no miscarriage, matched by zip code, age, and date of pregnancy. All women were invited for risk factor screening, including physical examination and blood collection. Main outcome measures were the (extrapolated) 10‐ and 30‐year cardiovascular risk scores using the Framingham risk score. A subanalysis was performed for women with idiopathic recurrent miscarriage.
Results
Thirty‐six women were included in both groups. Mean follow up was 7.5 years. Women with recurrent miscarriage had a significantly higher extrapolated 10‐year cardiovascular risk score (mean 6.24%, SD 5.44) compared with women with no miscarriage (mean 3.56%, SD 1.82, P = .007) and a significantly higher 30‐year cardiovascular risk score (mean 9.86%, SD 9.10) compared with women with no miscarriage (mean 6.39%, SD 4.20, P = .04). Similar results were found in women with idiopathic recurrent miscarriage (n = 28).
Conclusions
Women with a history of recurrent miscarriage differ in cardiovascular risk profile at a young age compared with women with no miscarriage. The findings support an opportunity to identify women at risk of cardiovascular disease later in life and a possible moment for intervention.
Introduction
The cause of recurrent pregnancy loss often remains unknown. Possibly, pathophysiological pathways are shared with other pregnancy complications.
Material and methods
All women with ...secondary recurrent pregnancy loss (SRPL) visiting Leiden University Medical Center (January 2000–2015) were included in this retrospective cohort to assess whether women with SRPL have a more complicated first pregnancy compared with control women. SRPL was defined as three or more consecutive pregnancy losses before 22 weeks of gestation, with a previous birth. The control group consisted of all Dutch nullipara delivering a singleton (January 2000–2015). Information was obtained from the Dutch Perinatal Registry. Outcomes were preeclampsia, preterm birth, post‐term birth, intrauterine growth restriction, breach position, induction of labor, cesarean section, congenital abnormalities, perinatal death and severe hemorrhage in the first ongoing pregnancy. Subgroup analyses were performed for women with idiopathic SRPL and for women ≤35 years.
Results
In all, 172 women with SRPL and 1 196 178 control women were included. Women with SRPL were older and had a higher body mass index; 29.7 years vs. 28.8 years and 25.1 kg/m2 vs. 24.1 kg/m2, respectively. Women with SRPL more often had a post‐term birth (OR 1.86, 95% CI 1.10–3.17) and more perinatal deaths occurred in women with SRPL compared with the control group (OR 5.03, 95% CI 2.48–10.2). Similar results were found in both subgroup analyses.
Conclusions
The first ongoing pregnancy of women with (idiopathic) SRPL is more often complicated by post‐term birth and perinatal death. Revealing possible links between SRPL and these pregnancy complications might lead to a better understanding of underlying pathophysiology.
Yersinia pestis was introduced to Brazil during the third plague pandemic and currently exists in several recognized foci. There is currently limited available phylogeographic data regarding Y. ...pestis in Brazil. We generated whole genome sequences for 411 Y. pestis strains from six Brazilian foci to investigate the phylogeography of Y. pestis in Brazil; these strains were isolated from 1966 to 1997. All 411 strains were assigned to a single monophyletic clade within the 1.ORI population, indicating a single Y. pestis introduction was responsible for the successful establishment of endemic foci in Brazil. There was a moderate level of genomic diversity but little population structure among the 411 Brazilian Y. pestis strains, consistent with a radial expansion wherein Y. pestis spread rapidly from the coast to the interior of Brazil and became ecologically established. Overall, there were no strong spatial or temporal patterns among the Brazilian strains. However, strains from the same focus tended to be more closely related and strains isolated from foci closer to the coast tended to fall in more basal positions in the whole genome phylogeny than strains from more interior foci. Overall, the patterns observed in Brazil are similar to other locations affected during the 3rd plague pandemic such as in North America and Madagascar.
•KCl and CaCl2 did not cause changes in the myofibrillar proteins.•CaCl2 decreased the degradation of sarcoplasmic proteins.•KCl decreased the sample firmness.•CaCl2 increased the hardness of the ...samples.•CaCl2 decreased the firmness of the samples over storage time.
The effect of a 50% reduction of NaCl and its replacement by KCl, CaCl2, and a blend of KCl and CaCl2 (1:1) on the proteolysis and rheological properties of dry fermented sausages was investigated. The reduction or replacement of NaCl by KCl did not cause changes in the electrophoretic profile and the addition of CaCl2 decreased the degradation of sarcoplasmic proteins during the manufacturing process. Samples with a 50% reduction of NaCl showed a higher content of the amino acids Arg, Glu, His, Val, Cys, Lys, and Trp, whereas the samples containing CaCl2 had a higher content of the amino acids Asp, Thr, Ala, Met, Leu, Ile, and Phe. The reduction or replacement of NaCl by KCl decreased sample firmness, whereas the addition of CaCl2 increased the hardness of the samples.
Yersinia pestis was introduced to Brazil during the third plague pandemic and currently exists in several recognized foci. There is currently limited available phylogeographic data regarding Y. ...pestis in Brazil. We generated whole genome sequences for 411 Y. pestis strains from six Brazilian foci to investigate the phylogeography of Y. pestis in Brazil; these strains were isolated from 1966 to 1997. All 411 strains were assigned to a single monophyletic clade within the 1.ORI population, indicating a single Y. pestis introduction was responsible for the successful establishment of endemic foci in Brazil. There was a moderate level of genomic diversity but little population structure among the 411 Brazilian Y. pestis strains, consistent with a radial expansion wherein Y. pestis spread rapidly from the coast to the interior of Brazil and became ecologically established. Overall, there were no strong spatial or temporal patterns among the Brazilian strains. However, strains from the same focus tended to be more closely related and strains isolated from foci closer to the coast tended to fall in more basal positions in the whole genome phylogeny than strains from more interior foci. Overall, the patterns observed in Brazil are similar to other locations affected during the 3rd plague pandemic such as in North America and Madagascar.
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