Cyclic workflow to improve implementation of learning points from morbidity and mortality meetings.

BACKGROUND: Morbidity and mortality meetings (M&MMs) are organized in most hospital departments with an educational purpose to learn from adverse events (AEs) to improve patient care. M&MMs often lack effectiveness due to unsuccessful systematic follow-up of areas of improvement. This can have an effect on improving patient safety and care. Therefore, a new strategy that focuses on implementing areas of improvement into daily practice is necessary. The study aim is to see if we could improve the implementation of meeting outcomes from the M&MM by using a cyclic workflow, and which factors are important to achieve its implementation. METHODS: This prospective study took place at the department of gynecologic oncology of a university hospital. Research was conducted with a participatory action research (PAR) approach using 10 consecutive M&MMs in 2019 and 2020. The cyclical workflow consisted of an action list based on the PDCA-cycle, a check of the implementation of areas for improvement at the next M&MM and regular monitoring of tasks. Each M&MM was observed and each professional with an assigned task was interviewed and gave their informed consent. Thematic content analysis was performed with the program Atlas.ti 8.4.20. RESULTS: Out of the 39 tasks that resulted from 10 M&MMs, 37 (94.8%) followed all the steps in the PDCA-cycle and were implemented. In total, 16 interviews were conducted with consultants, nurses, registrars and residents. Five main factors were important to achieve follow-up of areas for improvement: organizational culture, motivation, commitment, communication to mobilize employees and skills. Repetition of the cyclic workflow at the M&MM and an external person who reminded professionals of their assigned task(s) was important to change habits and motivate professionals. CONCLUSION: Cyclical tools can support the implementation of areas for improvement to optimize the M&MM. A M&MM with an organizational culture where attendees can discuss openly and freely may motivate attendees to take on tasks successfully. A positive stimulant to reach commitment of professionals is team participation. Integrating new habits of reflection may lead to a deeper level of learning from the PDCA-cycle and of the M&MM. Creating a learning environment outside of the M&MM may support professionals to take on actions and engage in improvement practices. Future research may focus on including a comparative analysis to show a success rate of the implementation of learning points from the M&MM more clearly.

Disclosing Adverse Events in Clinical Practice: The Delicate Act of Being Open.

Practicing a "safe" disclosure of adverse events remains challenging for healthcare professionals. In addition, knowledge on how to deliver a disclosure is still limited. This review focuses on how disclosure communication may be practiced based on the perspectives of patients and healthcare professionals. Empirical studies conducted between September 2008 and October 2019 were included from the databases PubMed, Web of Science and Psychinfo. After full text analysis and quality appraisal this scoping review included a total of 23 studies out of 2537 studies. As a first step, the needs of patients and the challenges of healthcare professionals with the practice of providing an effective disclosure were extracted from the empirical literature. Based on these findings, the review demonstrates that specific disclosure communication strategies on the level of interpersonal skills, organization, and supportive factors may facilitate healthcare professionals to provide optimal disclosure of adverse events. These may be relevant to provide patients with a tailored approach that accompanies their preferences for information and recognition. In conclusion, healthcare professionals may need training in interpersonal (verbal and nonverbal) communication skills. Furthermore, it is important to develop an open (organizational) culture that supports the communication of adverse events and disclosure as a standard practice.

Openness to new perspectives created by patient participation at the morbidity and mortality meeting.

OBJECTIVES: Morbidity and mortality meetings (M&MMs) at surgical departments may improve when patients participate, leading to different learning points. A gynecological oncology department invited patients to join their M&MMs. The practical constraints and experiences important from the perspective of patients and their healthcare professionals were evaluated. METHODS: Semi-structured interviews were conducted with patients and professionals who attended M&MMs at a gynecological oncology department between 2016 and 2018. The interviews were transcribed and coded and thematic content analysis was performed. RESULTS: Eight patients and 17 healthcare professionals participated. Eleven themes related to interpersonal dynamics. The five shared themes are: patient-doctor relationship, language, openness of communication, learning and personal impact. All participants suggested maintaining the new practical design of the M&MMs. CONCLUSIONS: Patients and healthcare professionals valued patient participation in the M&MMs. Patient participation is possible when professionals are open to discussing and learning from adverse events (AEs). In this setting, patients feel that they are taken seriously and gain a better understanding of the course of an AE. PRACTICE IMPLICATIONS: Involving patients in M&MMs led to new insights, better understanding, and improved processing of AEs. Collaborating with patients and using their feedback seems to be effective when developing innovations in healthcare.

The value of surgical staging in patients with apparent early stage epithelial ovarian carcinoma.

OBJECTIVE: The value of surgical staging of apparent early stage epithelial ovarian carcinoma (EOC) is unclear. The aim of this study was to evaluate the importance of surgical staging on the stage of disease and treatment plan. MATERIAL AND METHODS: All patients with apparent stage I EOC undergoing staging from 01/01/2005 to 30/06/2017 in all Danish hospitals and in the Radboud University Hospital Nijmegen, the Netherlands, were evaluated to identify the pathological findings responsible for upstaging and changes in treatment plans. RESULTS: We included 1234 patients with apparent stage I EOC. The staging steps often missed were the biopsy from the right diaphragmatic surface (missed in 96.9% of all patients) and lymph node (LN) sampling or lymphadenectomy (missed in 65.5% of all patients). Upstaging occurred in 393 patients (31.8%) due to microscopic spread to both ovaries (0.8%); ovarian surface (5.8%); positive cytology (10.0%); fallopian tubes (3.1%), ovary (1.5%) and/or uterus serosa (1.2%); pelvic peritoneum (4.3%); LNs (4.7%); omentum (3.7%); abdominal peritoneum (0.6%) and right diaphragmatic surface (2.6%). Of the 393 upstaged patients, 138 (35.1%) had an altered treatment plan due to metastases found by surgical staging. CONCLUSION: Staging was incomplete in most patients, mainly because a biopsy of the diaphragm was omitted. However, surgical staging led to adjuvant treatment in 35.1% of the upstaged patients. Peritoneal biopsies (para-colic gutters and right diaphragm) were of little value, since few patients had an adjustment of treatment plan due to these biopsies. Omitting these biopsies, in the absence of peritoneal abnormalities, is justifiable.

Outcome of surgery in advanced ovarian cancer varies between geographical regions; opportunities for improvement in The Netherlands.

INTRODUCTION: The care for patients with epithelial ovarian cancer(EOC) is organised in eight different geographical regions in the Netherlands. This situation allows us to study differences in practice patterns and outcomes between geographical regions for patients with FIGO stage IIIC and IV. METHODS: We identified all EOC patients who were diagnosed with FIGO stage IIIC or IV between 01.01.2008 and 31.12.2015 from the Netherlands Cancer Registry. Descriptive statistics were used to summarize treatment and treatment sequence(primary cytoreductive surgery(PCS) or neoadjuvant chemotherapy and interval cytoreductive surgery(NACT-ICS)). Moreover, outcome of surgery was compared between geographical regions. Multilevel logistic regression was used to assess whether existing variation is explained by geographical region and case-mix factors. RESULTS: Overall, 6,741 patients were diagnosed with FIGO IIIC or IV disease. There were no differences in the percentage of patients that received any form of treatment between the geographical regions(range 80-86%, P = 0.162). In patients that received cytoreductive surgery and chemotherapy, a significant variation between the geographical regions was observed in the use of PCS and NACT-ICS(PCS: 24-48%, P < 0.001). The percentage of complete cytoreductive surgeries after PCS ranged from 10 to 59%(P < 0.001) and after NACT-ICS from 37 to 70%(P < 0.001). Moreover, geographical region was independently associated with the outcome of surgery, also when adjusted for treatment sequence(P < 0.001). CONCLUSION: We observed a significant variation in treatment approach for advanced EOC between geographical regions in the Netherlands. Furthermore, the probability to achieve no residual disease differed significantly between regions, regardless of treatment sequence. This may suggest that surgical outcomes can be improved across geographical regions.

External validation of three prognostic models for overall survival in patients with advanced-stage epithelial ovarian cancer.

BACKGROUND: For various malignancies, prognostic models have shown to be superior to traditional staging systems in predicting overall survival. The purpose of this study was to validate and compare the performance of three prognostic models for overall survival in patients with advanced-stage epithelial ovarian cancer. METHODS: A multi-institutional epithelial ovarian cancer database was used to identify patients and to evaluate the predictive performance of two nomograms, a prognostic index and FIGO (International Federation of Obstetrics and Gynecology) stage. All patients were treated for advanced-stage epithelial ovarian cancer between January 1996 and January 2009 in 11 hospitals in the eastern part of The Netherlands. RESULTS: In total, 542 patients were found to be eligible. Overall performance did not differ between the three prognostic models and FIGO stage. The discriminative performance for Chi's model was moderately good (c indices 0.65 and 0.68) and for the models of Gerestein and Teramukai reasonable (c indices between 0.60 and 0.62). The c indices of FIGO stage ranged between 0.54 and 0.62. After recalibration, the three models showed almost perfect calibration, whereas calibration of FIGO stage was reasonable. CONCLUSION: The three prediction models showed general applicability and a reasonably well-predictive performance, especially in comparison to FIGO stage. To date, there are no studies available that analyse the impact of these prognostic models on decision-making and patient outcome. Therefore, the usefulness of these models in daily clinical practice remains to be investigated.

Robot-assisted versus total laparoscopic radical hysterectomy in early cervical cancer, a review.

OBJECTIVE: The aim of this study was to review current literature on total laparoscopic (TLRH) and robot-assisted radical hysterectomy (RRH) with pelvic lymphadenectomy in the treatment of early stage cervical cancer by analyzing data published in individual case series in order to compare surgical and oncological outcomes. METHODS: Up to January 2010, 27 studies were identified that met the inclusion criteria, together with our own unpublished data of patients, accounted for 342 RRH patients and 914 TLRH patients. RESULTS: There was no statistical difference between the methods in terms of age, BMI or prior abdominal surgery. Estimated mean operative time, blood loss and number of lymph nodes retrieved did not statistically differ between the RRH and TLRH method. Less blood transfusions were needed in patients treated by RRH (5.4%) versus TLRH (9.7%, p<0.05). Both methods were similar in respect to adjuvant chemo- or (chemo)radiation and recurrence rate. When complications were prioritized to severity, major post-operative complications where more frequent in RRH patients (9.6%) than in TLRH patients (5.5%, p<0.05). The length of hospital stay was significantly shorter in RRH compared to TLRH treatment (3.3 versus 6.2days respectively; p:0.04). CONCLUSIONS: Robot-assisted and total laparoscopic radical hysterectomy appears to be equally adequate and feasible. RRH studies had small patient populations and further experience beyond the learning curve phase may improve operative time and complication rate. Both minimal invasive techniques should be investigated in a randomized manner.

Prognostic factors for recurrence in patients with FIGO stage I and II, intermediate or high risk endometrial cancer.

BACKGROUND: The aim of this study was to determine predictors for loco-regional or distant recurrence of disease in a subgroup of intermediate or high risk stage I and II endometrial cancer. METHODS: A retrospective analysis of 295 patients with histopathological stage I and II, intermediate or high risk endometrial cancer is reported. The following factors were studied: stage, grade, age, histologic diagnosis, lymphadenectomy, lymphovascular space invasion, and adjuvant radiotherapy. The Log-Rank test was used for statistical analyses and the Kaplan-Meyer method was used for time-to-event analysis. Multivariate analysis was also performed. RESULTS: Thirty-four (11.5%) patients developed a recurrence; 20 (59%) developed loco-regional recurrence, and 14 (41%) developed distant recurrence. In 20 women (59%), recurrence appeared within 3 years of surgery, and the actuarial survival at 3 years after recurrence was 29%. Multivariate analysis showed that for recurrence, age >60 years was a significant unfavourable prognostic factor (p < 0.05). CONCLUSIONS: We found low rates of recurrence in patients with early stage intermediate or high risk endometrial cancer. Only age was identified as an independent significant predictor for recurrence.

Ethene and other biomarkers of oxidative stress in hypertensive disorders of pregnancy.

OBJECTIVE: An increase in reactive oxygen species (ROS) and lipid peroxides and a comprised antioxidant status has been implicated in the pathophysiology of severe preeclampsia. This study investigates whether oxidative stress and impaired antioxidant systems also contribute to milder forms of hypertensive disorders in pregnancy. Furthermore, ethene in exhaled air, a noninvasive measure for oxidative stress, was evaluated and compared with two other more established biomarkers. METHODS: Ethene in exhaled air, plasma protein carbonyls, and the ratio of free glutathione/oxidized glutathione (GSHfree/GSHox) as markers for oxidative stress as well as the antioxidants vitamins C and E, uric acid, glutathione, and the oxygen radical absorbance capacity (ORAC) in plasma were measured in 30 healthy nonpregnant, 14 normal pregnant, 9 women with pregnancy-induced hypertension (PIH), and 14 preeclamptic women. Pregnant participants were measured during pregnancy and after delivery. RESULTS: Women suffering from PIH and preeclampsia showed higher levels of the antioxidants vitamin E and uric acid, and lower levels of vitamin C compared with normal pregnant and nonpregnant women. All markers for oxidative stress were comparable between groups. Ethene levels showed a positive correlation with protein carbonyls but no correlation could be demonstrated with the free glutathione/oxidised glutathione ratio. CONCLUSIONS: PIH and preeclampsia are associated with minor alterations in antioxidant levels without signs of oxidative stress. Detection of ethene in exhaled air seems a promising noninvasive method to study lipid peroxidation but further research in more severe preeclampsia is needed.

Gilbert's syndrome is not associated with HELLP syndrome.

The HELLP syndrome has been associated with postpartum unconjugated hyperbilirubinaemia. Several types of disorders cause unconjugated hyperbilirubinaemia, Gilbert's syndrome being the most common. In Caucasians a genetic defect in the TATA box of the promotor region of the gene encoding for bilirubin UDP-glucuronyltransferase is tightly associated with Gilbert's syndrome. This defect was assessed by polymerase chain reaction in 237 women with the HELLP syndrome in their obstetric history and 236 controls. Fifteen percent of the cases and 10% of the controls had a homozygous genetic defect (chi2 = 2.9; P = 0.23). No evidence was found that Gilbert's syndrome is associated with the HELLP syndrome.

A polymorphism in the gene for microsomal epoxide hydrolase is associated with pre-eclampsia.

OBJECTIVE: Microsomal epoxide hydrolase is an important enzyme involved in the metabolism of endogenous and exogenous toxicants. Polymorphic variants of the human epoxide hydrolase gene vary in enzyme activity. We determined whether genetic variability in the gene encoding for microsomal epoxide hydrolase contributes to individual differences in susceptibility to the development of pre-eclampsia with or without the syndrome of Haemolysis, Elevated Liver enzymes, and Low Platelets (HELLP). METHODS: A total of 183 non-pregnant women with a history of pre-eclampsia, 96 of whom had concurrently developed the HELLP syndrome, and 151 healthy female controls were genotyped for the 113Tyr-->His polymorphism in exon 3 and the 139His-->Arg polymorphism in exon 4 of the epoxide hydrolase gene by a polymerase chain reaction-restriction fragment length polymorphism assay. Chi-square analysis was used for statistical evaluation of differences in polymorphic rates. RESULTS: In pre-eclampsia a higher frequency (29%) of the high activity genotype Tyr113 Tyr113 in exon 3 was found as compared to controls (16%, OR 2.0, 95% CI 1.2-3.7). There was no difference between groups for the 139His-->Arg polymorphism. In women with a history of pre-eclampsia, no difference in epoxide hydrolase genotypes was found between women who either did or did not develop the HELLP syndrome. In addition, a significant association was found between predicted EPHX activity and pre-eclampsia. CONCLUSIONS: Women with the high activity genotype in exon 3, which could reflect differences in metabolic activation of endogenous or exogenous toxic compounds, may have enhanced susceptibility to pre-eclampsia. However, polymorphisms in the epoxide hydrolase gene do not seem to influence the risk for concurrent development of the HELLP syndrome.

Hyperhomocysteinaemia: a risk factor for preeclampsia?

Preeclampsia represents one of the most frequent complications of pregnancy, however, little is known about its aetiology. Damage of the endothelial layer lining the blood vessel wall is thought to play an important role in the pathophysiology of preeclampsia, accordingly, mild hyperhomocysteinaemia has been reported to be more prevalent among preeclamptic women. Therefore, we investigated the role of hyperhomocysteinaemia in preeclampsia by measuring plasma levels of homocysteine and studying the prevalence of the 677(C-->T) polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, which may lead to reduced MTHFR enzyme activity and subsequently to higher plasma homocysteine levels. Plasma samples of 10 healthy non-pregnant women, 10 normotensive pregnant women, and 20 women with preeclampsia were analysed for total homocysteine levels by high performance liquid chromatography. Furthermore, 167 Dutch non-pregnant women previously hospitalised for preeclampsia and 403 population-based controls were analysed for the 677(C-->T) polymorphism by polymerase chain reaction followed by restriction fragment length polymorphism analysis (PCR/RFLP). In normotensive pregnancy homocysteine levels were lower compared with levels in healthy non-pregnant controls (8.4 versus 13.7micromol/l, P<0.001). Women with preeclampsia showed higher concentrations than women during normotensive pregnancy (13.3 versus 8.4micromol/l, P<0.02). However, levels of homocysteine in preeclampsia were comparable to those found in healthy non-pregnant women. PCR/RFLP showed no significant difference in the incidence of the 677(C-->T) polymorphism in the MTHFR gene between preeclamptic women with or without HELLP syndrome and controls (13 and 9% homozygous for the less common T-allele, respectively; OR 1.5, 95% CI 0.8-2.6, P=0.17). In contrast with previous reports, we cannot confirm that mild hyperhomocysteinaemia is a risk factor for preeclampsia. Pregnancy induced hyperhomocysteinaemia found in preeclampsia might better be explained by fluctuations in plasma volume than by the presence of the 677(C-->T) polymorphism in the MTHFR gene.

Protein carbonyls in decidua and placenta of pre-eclamptic women as markers for oxidative stress.

Enhanced levels of reactive oxygen species (ROS) and decreased levels of antioxidants may contribute to the development of pre-eclampsia. Protein carbonyls may be sensitive biomarkers for ROS-mediated protein damage, whereas the ferric reducing ability of plasma (FRAP) value may serve as marker for antioxidant capacity.Twenty-two healthy pregnant women and 50 patients with severe pre-eclampsia, 25 of whom with concurrent (haemolysis, elevated liver enzymes, low platelets) HELLP syndrome were investigated prospectively with respect to placental and decidual levels of protein carbonyls and FRAP antioxidant capacity. Measurements were evaluated using the Kruskal-Wallis or Mann-Whitney U -tests for comparison between groups, and the Wilcoxon signed-rank test for comparison within groups. Spearman's correlation tests were used for correlation analyses. Placental and decidual protein carbonyl levels were higher in pre-eclampsia with HELLP than in healthy pregnancy, whereas FRAP levels were lower. Differences between pre-eclampsia and healthy pregnancy showed the same trend, but did not reach statistical significance. In pre-eclampsia with HELLP syndrome carbonyl levels as well as FRAP levels were significantly higher in placenta as compared with decidua.Higher levels of protein carbonyls and lower antioxidant capacity in both placenta and decidua in pre-eclampsia with concurrent HELLP syndrome as compared to healthy pregnancy may indicate that considerable ROS-mediated damage occurs in this disorder.

Oxidized and free whole blood thiols in preeclampsia.

OBJECTIVE: To measure levels of oxidized and free thiols in whole blood of normotensive pregnant and preeclamptic women and evaluate the role of oxidative stress. METHODS: We measured whole blood oxidized and free levels of cysteine, homocysteine, cysteinylglycine, and glutathione by high performance liquid chromatography in women with normotensive pregnancies (n = 50), preeclampsia (n = 29), and preeclampsia complicated by the hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome (n = 16). RESULTS: Oxidized and free levels (median [range], micromol/L) of cysteine and homocysteine were higher in women with preeclampsia than normotensive pregnancies (45 [27-81] versus 29 [9-91], P <.001, and 98 [57-193] versus 69 [33-215], P <.001; 0.8 [0.2-4.4] versus 0.4 [0.01-1.6], P <.001, and 2.1 [0.7-9.4] versus 1.2 [0.2-21.2], P <.01; respectively). The ratios of free to oxidized cysteine, homocysteine, and cysteinylglycine were lower in preeclampsia than normotensive pregnancy (2.2 [1.3-3.0] versus 2.4 [1.7-4.3], P <.001; 2.3 [0.5-5.4] versus 2.9 [1.1-24], P <.001; 4.1 [2.3-11.6] versus 5.4 [2.6-24.3], P <.02, respectively), indicating a shift in favor of the oxidized form of those thiols. In HELLP syndrome, levels of oxidized and free cysteine and levels of oxidized homocysteine were higher than normal (44 [33-63] versus 29 [9-91], P <.001, and 102 [82-133] versus 69 [33-215], P <.001; 1.0 [0.3-2.9] versus 0.4 [0.01-1.6], P <.001, respectively). No significant differences were found in oxidized glutathione levels in women with preeclampsia (22 [5-49] versus 17 [2- 60], P =.06) or free levels in preeclamptic women with HELLP syndrome (757 [624-993] versus 842 [539-1516], P =.09) as compared with normotensive pregnant women. The ratios of free to oxidized cysteinylglycine and glutathione were higher in women with HELLP syndrome than in those with preeclampsia (5.4 [3.3-12.7] versus 4.1 [2.3-11.6], P =.02, and 56 [28-124] versus 45 [16-166], P =.02, respectively). CONCLUSION: Significantly lower ratios of free to oxidized cysteine, homocysteine, and cysteinylglycine in preeclampsia might indicate oxidative stress.

Neutrophil oxygen radical production in pre-eclampsia with HELLP syndrome.

OBJECTIVE: To determine whether severe pre-eclampsia complicated by hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome alters neutrophil oxygen radical production. MATERIALS AND METHODS: Neutrophils were obtained from 10 healthy non-pregnant, 9 normal pregnant and 9 women with severe pre-eclampsia with concurrently HELLP syndrome. Oxygen radical production was evaluated using luminol-enhanced chemiluminescence and measured by cytochrome C reduction. Furthermore we incubated sera from cases and controls with isolated healthy neutrophils and measured their capacity to generate oxygen radicals. RESULTS: Unstimulated neutrophil oxygen radical production was significantly lower in severe pre-eclamptics compared with healthy non-pregnant and pregnant subjects, whereas phorbol ester-induced oxygen radical production did not differ among categories. Cytochrome C reduction of unstimulated neutrophils showed similar results. Healthy neutrophils incubated with sera from pre-eclamptics enhanced the oxygen radical production significantly more than neutrophils incubated with sera from the healthy subjects. CONCLUSIONS: Severe pre-eclampsia is characterised by decreased unstimulated neutrophil oxygen radical production. This may be the result of an exhausted cellular response due to stimulation by a factor present in the serum of these patients.

Methylenetetrahydrofolate reductase polymorphisms in preeclampsia and the HELLP syndrome.

OBJECTIVE: To investigate the prevalence of the 677 (C --> T) and 1298 (A --> C) polymorphisms in the methylenetetrahydrofolate reductase (MTHFR) gene in our preeclamptic population. For a summary estimation of the risk of the 677 (C --> T) polymorphism for preeclampsia, we also performed a meta-analysis on four previously published case-control studies to which our results were added. METHODS: Genotypes were analyzed by polymerase chain reaction followed by restriction enzyme analysis. The results of 176 nonpregnant women, previously hospitalized for preeclampsia in a tertiary care center, were compared with 403 Dutch population-based controls. Results were statistically analyzed with a chi-square test. MEAN OUTCOME MEASURES: The incidence of the 677 (C --> T) and 1298 (A --> C) polymorphisms in the MTHFR gene. RESULTS: The incidence of both MTHFR missense polymorphisms was not significantly different between cases and controls. We found an odds ratio (OR) of 1.5 [95% confidence interval (CI) 0.8-2.6, p = 0.17] and an OR of 1.0 (95% CI 0.6-1.9, p = 0.23) for the 677 (C --> T) and the 1298 (A --> C) polymorphism, respectively, in cases comparing the prevalence of the homozygous genotype versus the other two genotypes. The meta-analysis resulted in a significant OR of 2.0 (95% CI 1.4-2.9). CONCLUSIONS: In contrast to four previous studies, we were neither able to confirm an increased risk for preeclampsia to the 677 (C --> T) polymorphism nor did we find an increased risk for preeclampsia to the 1298 (A --> C) polymorphism. From the meta-analysis, however, we conclude that it cannot be ruled out that the homozygous 677TT genotype is a modest but significant risk factor for preeclampsia.

Deficient detoxifying capacity in the pathophysiology of preeclampsia.

An imbalance between oxidative stress and maternal detoxification or antioxidant capacity may explain the symptoms of preeclampsia and the haemolysis-elevated liver enzymes-low platelets (HELLP) syndrome. Oxidative stress is known to induce damage of the endothelium, which is one of the pathophysiological features of preeclampsia and the HELLP syndrome. Administration of N-acetylcysteine, an antioxidant itself and a precursor of the endogenous antioxidant glutathione, might stabilize or even partly recover the process of endothelial damage and may lead to prolongation of pregnancy.