妊娠中晚期孕妇阴道菌群紊乱的改变对不良妊娠结局的影响

目的探讨妊娠中晚期孕妇阴道菌群紊乱的改变对不良妊娠结局的影响。方法选取产科门诊就诊的妊娠28-34周的患者150例。根据检查结果将其分为菌群正常组48例和菌群失常组102例。观察并对比两组患者的不良妊娠结局。结果 102例菌群失常患者中滴虫6例,假丝酵母菌67例,衣原体17例,淋菌2例,细菌性阴道病10例。假丝酵母菌感染率明显高于其他致病菌(P0.05)。菌群失常组患者早产、胎膜早破、剖宫产、产褥感染发生率分别为15.69%、22.55%、35.29%和18.63%,均明显高于菌群正常组的4.17%、8.33%、18.75%和6.25%(P0.05)。菌群失常组患者新生儿黄疽、新生儿感染和低出生体重儿发生率分别为24.51%、21.57%、16.67%,均明显高于菌群正常组的10.42%、8.33%、4.17%(P0.05),在胎儿窘迫的发生率方面两组比较差异无统计学意义(P0.05)。结论妊娠中晚期阴道菌群紊乱中以假丝酵母菌感染发生率最多,与不良妊娠结局密切相关,增加了早产、胎膜早破、剖宫产、产褥感染、新生儿黄疸、新生儿感染和低出生体重儿等与不良妊娠结局的发生率。     

阴道微生态与围产期不良结局的研究进展

阴道微生态对围产期结局的影响已成为近期医学研究的焦点。阴道内定植有多种微生物,其中优势菌为乳杆菌,维持着阴道内正常pH。当机体免疫防御能力降低或者内分泌系统紊乱时,机会致病菌占据优势,极易诱发阴道炎性病变,严重影响妊娠期女性正常生活,并且对胎儿的发育及健康成长造成威胁,导致早产和胎膜早破等不良妊娠结局的发生。由于阴道菌群毒力强弱具有差异性,感染所致的阴道炎性疾病容易复发且不易根除,因此在治疗方面,临床医师需要根据个体化原则指导用药。本文对近年来阴道微生态与妊娠不良结局的相关性研究进行简要综述。     

肠道菌群与妊娠期甲状腺疾病患者的常见不良妊娠结局

目前, 肠道菌群被认为是影响机体内环境的潜在因素, 一旦失调, 可能导致多系统的疾病。妊娠期妇女由于机体代谢及免疫状态的变化, 是罹患妊娠期甲状腺疾病的高危人群。而妊娠期甲状腺疾病可导致流产、早产和出生体质量过低等常见不良妊娠结局, 对产妇、新生儿及其家庭造成十分恶劣的影响。妊娠期妇女作为特殊群体, 其肠道菌群的研究备受关注, 但目前关于妊娠期甲状腺疾病的肠道菌群研究仍较少。为更好地指导临床以及寻求改善妊娠期甲状腺疾病患者常见不良妊娠结局, 本文对肠道菌群与妊娠期甲状腺疾病患者的常见不良妊娠结局的相关研究进行综述。

     

Maternal exposure to folic acid antagonists and placenta-mediated adverse pregnancy outcomes

Background

In previous studies, maternal exposure to folic acid antagonists was associated with increased risks of neural tube defects, cardiovascular defects, oral clefts and urinary tract defects. The objective of the current study was to assess the possible effects of using folic acid antagonists in pregnancy on placenta-mediated adverse outcomes of pregnancy.

Methods

We used data from an administrative database to retrospectively compare the occurrence of placenta-mediated adverse pregnancy outcomes between pregnant women exposed to folic acid antagonists and women without exposure to these agents.

Results

We included in the analysis a total of 14 982 women who had been exposed to folic acid antagonists and 59 825 women who had not been exposed. Sulfamethoxazole–trimethoprim was the most frequently prescribed dihydrofolate reductase inhibitor (a total of 12 546 exposures during the preconception period and all 3 trimesters), and phenobarbital was the most frequently prescribed among the other folic acid antagonists (a total of 1565 exposures). The risks of preeclampsia (adjusted odds ratio [OR] 1.52, 95% confidence interval [CI] 1.39–1.66), severe preeclampsia (OR 1.77, 95% CI 1.38–2.28), placental abruption (OR 1.32, 95% CI 1.12–1.57), fetal growth restriction defined as less than the 10th percentile (OR 1.07, 95% CI 1.01–1.13), fetal growth restriction defined as less than the 3rd percentile (OR 1.22, 95% CI 1.11–1.34) and fetal death (OR 1.35, 95% CI 1.07–1.70) were greater among mothers with exposure to folic acid antagonists. In general, the risks associated with exposure to other folic acid antagonists were higher than those associated with exposure to dihydrofolate reductase inhibitors. Supplementary analyses involving tight matching with propensity score, restriction of the analysis to women with exposure during the first and second trimesters and restriction of the analysis to specific categories of folic acid antagonists yielded similar results.

Interpretation

Maternal exposure to folic acid antagonists appears to increase the risk of placenta-mediated adverse outcomes of pregnancy.     

Clinical characteristics and outcomes of immune checkpoint inhibitor-induced diabetes mellitus

ObjectiveTo better understand immune checkpoint inhibitor (ICI)-induced diabetes mellitus (DM) in cancer patients.Design and methodWe present a case of ICI-induced diabetic ketoacidosis (DKA) and conduct a systematic review of the PubMed and Web of Science databases up to September 2021 to identify all published cases of ICI-induced diabetes.ResultsIn addition to our case, a total of 171 published cases were identified during the literature search. Summary and statistical analyzes were conducted for all 172 cases. The median onset time from ICI initiation to DM diagnosis was 12 weeks (range: 0–122). DKA was present in 67.4% (116/172) of the cases, and low C-peptide levels were detected in 91.8% (123/134), indicating an acute onset of diabetes. Patients with positive glutamic acid decarboxylase antibodies (GADA) had an earlier onset of ICI-induced diabetes (median time 7 weeks vs. 16 weeks for GADA-negative patients, p < 0.001) and a higher frequency of DKA development (82.8 vs. 62.1%, p = 0.006). All but two patients developed insulin-dependent diabetes permanently. Immunotherapy rechallenge was reported in 53 cases after glycemia was well controlled.ConclusionICI-induced DM is a serious adverse event that often presents with life-threatening ketoacidosis. GADA positivity is related to an earlier onset of ICI-induced diabetes and a higher frequency of DKA development. Close monitoring of glucose levels is needed in patients receiving ICI treatment. ICI-induced DM is usually insulin-dependent since damage to β cells is irreversible. On the premise of well-controlled glycemia, immunotherapy rechallenge is feasible.     

妊娠中晚期阴道微生态失调及乳酸菌胶囊干预对不良妊娠结局的作用

目的 观察妊娠中晚期妇女阴道微生态状况,探讨应用乳杆菌活菌胶囊纠正阴道微生态失调对不良妊娠结局的预防价值。方法 选择孕13~36周单胎妊娠期妇女560例,取其阴道分泌物,经革兰染色后油镜下观察,进行阴道微生态（阴道菌群的密集度、多样性、优势菌、炎症反应等）状况评价,检测阴道分泌物成分、阴道病原菌类型。对阴道微生态失调孕妇,根据是否接受乳杆菌活菌胶囊治疗分为治疗组和对照组,治疗组给予乳杆菌活菌胶囊,对照组不采用药物干预。追踪随访所有孕妇的妊娠情况,比较阴道微生态正常组、微生态失调治疗组及微生态失调对照组的不良妊娠结局。结果 560例研究对象中,阴道微生态正常 335 例（59.82%）,微生态失调225例（40.18%）。225例微生态失调孕妇中,细菌性阴道病（bacterial vaginosis,BV）32例（14.22%）,阴道假丝酵母菌病（vulvovaginal candidiasis,VVC）56例（24.89%）,滴虫性阴道炎（triehomonal vaginitis,TV）11例（4.89%）,BV和VVC混合感染4例（1.78%）,BV和TV混合感染3例（1.33%）,菌群增殖过度75例（33.33%）,菌群抑制44例（19.56%）。微生态失调组pH值>4.5、过氧化氢、白细胞酯酶、唾液酸苷酶、脯氨酸氨基肽酶、乙酰氨基葡萄糖苷酶阳性比例均明显高于微生态正常组（χ2=55.59~340.06,Ps0.05）。结论 妊娠中晚期容易导致阴道微生态失调,造成不良妊娠结局,乳杆菌活菌胶囊纠正阴道微生态失调对于改善不良妊娠结局有较好的预防作用。     

Proteomic signature of periodontal disease in pregnancy: Predictive validity for adverse outcomes

The rate of preterm birth is a public health concern worldwide because it is increasing and efforts to prevent it have failed. We report a Clinically Relevant Complex Systematic Review (CSCSR) designed to identify and evaluate the best available evidence in support of the association between periodontal status in women and pregnancy outcome of preterm low birth weight. We hypothesize that the traditional limits of research synthesis must be expanded to incorporate a translational component. As a proof-of-concept model, we propose that this CSCSR can yield greater validity of efficacy and effectiveness through supplementing its recommendations with data of the proteomic signature of periodontal disease in pregnancy, which can contribute to addressing specifically the predictive validity for adverse outcomes. For this CRCSR, systematic reviews were identified through The National Library of MedicinePubmed, The Cochrane library, CINAHL, Google Scholar, Web of Science, and the American Dental Association web library. Independent reviewers quantified the relevance and quality of this literature with R-AMSTAR. Homogeneity and inter-rater reliability testing were supplemented with acceptable sampling analysis. Research synthesis outcomes were analyzed qualitatively toward a Bayesian inference, and converge to demonstrate a definite association between maternal periodontal disease and pregnancy outcome. This CRCSR limits heterogeneity in terms of periodontal disease, outcome measure, selection bias, uncontrolled confounders and effect modifiers. Taken together, the translational CRCSR model we propose suggests that further research is advocated to explore the fundamental mechanisms underlying this association, from a molecular and proteomic perspective.     

A proposed model of the treatment of diabetes mellitus in pregnancy

A model of management of pregnant diabetic patients is proposed. Such a model has been implemented at the Voivodeship Out-patient Clinic for Diabetics. Proposed model includes recent data on diabetes mellitus complications and the effect of coexisting diseases on the mother and fetus health. Management was adapted to the real and potential possibilities of health service in Poland. A decrease in the rate of mortality of fetuses under 7% was achieved. It is worth emphasizing despite higher value than those reported in the literature.     

Proteomic signature of periodontal disease in pregnancy: Predictive validity for adverse outcomes

The rate of preterm birth is a public health concern worldwide because it is increasing and efforts to prevent it have failed. We report a Clinically Relevant Complex Systematic Review (CSCSR) designed to identify and evaluate the best available evidence in support of the association between periodontal status in women and pregnancy outcome of preterm low birth weight. We hypothesize that the traditional limits of research synthesis must be expanded to incorporate a translational component. As a proof-of-concept model, we propose that this CSCSR can yield greater validity of efficacy and effectiveness through supplementing its recommendations with data of the proteomic signature of periodontal disease in pregnancy, which can contribute to addressing specifically the predictive validity for adverse outcomes. For this CRCSR, systematic reviews were identified through The National Library of MedicinePubmed, The Cochrane library, CINAHL, Google Scholar, Web of Science, and the American Dental Association web library. Independent reviewers quantified the relevance and quality of this literature with R-AMSTAR. Homogeneity and inter-rater reliability testing were supplemented with acceptable sampling analysis. Research synthesis outcomes were analyzed qualitatively toward a Bayesian inference, and converge to demonstrate a definite association between maternal periodontal disease and pregnancy outcome. This CRCSR limits heterogeneity in terms of periodontal disease, outcome measure, selection bias, uncontrolled confounders and effect modifiers. Taken together, the translational CRCSR model we propose suggests that further research is advocated to explore the fundamental mechanisms underlying this association, from a molecular and proteomic perspective.     

Serum levels of irisin in gestational diabetes mellitus during pregnancy and after delivery

ObjectiveIrisin has recently been introduced as a novel an exercise-inducible myokine which improves glucose metabolism in mice. However, regulation of circulating irisin in gestational diabetes mellitus (GDM) and in the peripartal period has not been assessed so far.MethodsCirculating irisin was quantified in 74 GDM patients and in 74 healthy, pregnant, gestational age-matched controls. In a subset of these patients (44 GDM, 41 controls), postpartum follow-up data were also available. In a second study population of 40 healthy women with singleton pregnancies undergoing elective Cesarean section, irisin was assessed in maternal serum before and within 24 h after delivery, as well as in umbilical cord blood and in placental tissue.ResultsIn the first study population, median [interquartile range] irisin levels were significantly higher in GDM patients as compared to controls after delivery (previous GDM: 446.3 [146.9] μg/l; controls: 378.0 [111.4] μg/l) but not during pregnancy (GDM: 482.1 [132.1] μg/l; controls: 466.6 [178.0] μg/l). Interestingly, fasting insulin (FI) was independently and positively associated with serum irisin in multivariate analysis during pregnancy. In agreement with these findings, relative changes (ratio) of FI independently and positively predicted relative changes of irisin (ratio) in the second study population.ConclusionsThe myokine irisin is independently associated with FI in pregnancy. The physiological significance of these findings needs to be assessed in future experiments.     

Perinatal mortality and adverse pregnancy outcomes in a low-income rural population of women who smoke

We describe adverse pregnancy outcomes, including congenital anomalies, fetal, neonatal, and infant mortality among a Missouri population of low-income, rural mothers who participated in two randomized smoking cessation trials. In the Baby BEEP (BB) trial, 695 rural women were recruited from 21 WIC clinics with 650 women's pregnancy outcomes known (93.5% retention rate). Following the BB trial, 298 women who had a live infant after November 2004 were recruited again into and completed the Baby Beep for Kids (BBK) trial. Simple statistics describing the population and perinatal and postneonatal mortality rates were calculated. Of the adverse pregnancy outcomes (n = 79), 29% were spontaneous abortions of less than 20 weeks' gestation, 23% were premature births, and 49% were identified birth defects. The perinatal mortality rate was 15.9 per 1000 births (BB study) compared with 8.6 per 1000 births (state of Missouri) and 8.5 per 1000 births (United States). The postneonatal infant mortality rate was 13.4 per 1000 live births (BBK) compared with 2.1 per 1000 live births (United States). The health disparity in this population of impoverished, rural, pregnant women who smoke, particularly in regard to perinatal and infant deaths, warrants attention.     

乳酸菌阴道胶囊对妊娠中晚期外阴阴道假丝酵母菌病患者不良妊娠结局的预防作用

目的探讨乳酸菌阴道胶囊对妊娠中晚期外阴阴道假丝酵母菌病(VVC)患者不良妊娠结局的预防作用。方法将136例妊娠中晚期VVC患者随机分为联合组和对照组各68例。联合组患者予以乳酸菌阴道胶囊(0.25g/晚)及制霉菌素(50万IU/晚)联合阴道上药治疗(两药使用间隔4~6h);对照组患者予以单纯的制霉菌素阴道上药治疗,剂量及用法同联合组,两组均连用10d。观察并记录两组治疗后的临床效果,并比较两组不良妊娠结局。结果治疗结束后1个月,在临床总有效率方面联合组患者明显优于对照组(92.65%vs 80.88%)(χ2=4.10,P0.05);联合组患者在早产、胎膜早破和产褥病等不良妊娠结局发生率明显低于对照组(2.94%、4.41%、7.35%vs 11.76%、14.71%、19.12%)(χ2=3.89、4.17、4.10,P0.05),两组新生儿黄疸和低体重儿等不良妊娠结局发生率方面比较差异无统计学意义(P0.05)。结论乳酸菌阴道胶囊辅助治疗妊娠中晚期VVC的疗效较确切,能明显改善其临床症状及特征,对早产、胎膜早破和产褥病等不良妊娠结局具有良好的预防作用。     

The effect of diabetes mellitus on pharmacokinetics,pharmacodynamics and adverse drug reactions of anticancer drugs

Diabetes mellitus (DM) and cancer are global problems carrying huge human, social, and economic impact. Type 2 diabetes (T2DM) is associated with an increased risk for a number of cancers, including breast, pancreatic, and liver cancer. Moreover, adverse drug reactions are higher in paitents with cancer with T2DM compared to cancer patients without T2DM. Cellular mechanisms of hyperglycemia and chemotherapy efficacy may be different depending upon the particular cancer type and the condition of the patient. This review evaluates the effect of DM on the pharmacokinetic, pharmacodynamic, and adverse drug reactions of commonly used anticancer drugs such as cisplatin, methotrexate, paclitaxel, doxorubicin, and adriamycin in both clinical and animal models. A literature search was conducted in scientific databases including Web of Science, PubMed, Scopus, and Google Scholar including the relevant keywords. The results of the effectiveness of anticancer therapies in patients with DM are, however, inconsistent because DM can negatively impact multiple diverse entities including nerves and vascular structures, insulin-like growth factor 1, the function of the innate immune system, drug pharmacokinetics, the expression levels of hepatic CYP₄₅₀, Mdr _1b and enzymes that then lead to drug toxicity. However, in a few circumstances, DM led to attenuation of the toxicity of anticancer drugs secondary to attenuation of the energy-dependent renal uptake process. Overall, the impact of DM on patients with cancer is variable because of the diverse types of cancers and the spectrum of anticancer drugs. With respect to the evidence for cancer involvement in DM pathophysiology and the response to anticancer treatment in patients with DM, many questions still remain and further clinical trials are needed.