Dokumentation

Zusammenfassung  Alle Maßnahmen zur Behandlung von Patienten sind zu dokumentieren. Einerseits handelt es sich dabei um vorwiegend organisatorische Maßnahmen, für die der Krankenhausträger und der von ihm beauftragte Chefarzt oder Belegarzt verantwortlich sind und andererseits um die ärztlichen Maßnahmen am Patienten selbst. Zu dokumentieren ist daher die Erfüllung

Adiponectin,Leptin and Ghrelin Levels in Obese Adolescent Girls with Polycystic Ovary Syndrome

Study ObjectiveTo evaluate the differences in adipokines, namely adiponectin, leptin, and ghrelin, in obese adolescent girls with or without polycystic ovary syndrome (PCOS).DesignCase-control study.SettingUniversity hospital.Participants38 adolescent girls (age 15-20 years). Group I: 17 Obese adolescent girls with PCOS (BMI ≥ 30 kg/m²); Group II: Control group of 21 obese adolescent girls (BMI ≥ 30 kg/m²).Main Outcome MeasuresAdiponectin, leptin, and ghrelin measurements.ResultsLH, LH/FSH, and cortisol levels were significantly higher in the obese PCOS girls compared to the obese controls (6.94 ± 3.28 vs 4.44 ± 1.79; 1.50 ± 0.72 vs 0.90 ± 0.36; 16.02 ± 4.28 vs 12.46 ± 5.29; P < .05, respectively). Adiponectin, leptin, and ghrelin levels were similar between the obese PCOS girls and the obese controls (11.13 ± 6.00 vs 15.26 ± 12.66; 23.66 ± 11.54 vs 23.11 ± 11.17; 665.69 ± 402.12 vs 650.22 ± 467.73, respectively). Adiponectin negatively correlated with BMI (r = ?0.32; P = .04) and positively correlated with fasting glucose (r = 0.40; P = .01). Leptin positively correlated with BMI (r = 0.534; P = .001), estradiol (r = 0.354; P = .02), and TSH (r = 0.374; P = .02). No significant correlation was found between ghrelin and the test parameters.ConclusionAmong obese adolescents with PCOS, adiponectin, and leptin levels do not seem to be determined by the existence of PCOS, while ghrelin presents no significant correlation.     

In-vivo stretch of term human fetal membranes

IntroductionFetal membranes (FM) usually fail prior to delivery during term labor, but occasionally fail at preterm gestation, precipitating preterm birth. To understand the FM biomechanical properties underlying these events, study of the baseline in-vivo stretch experienced by the FM is required. This study's objective was to utilize high resolution MRI imaging to determine in-vivo FM stretch.MethodsEight pregnant women (38.4 ± 0.4wks) underwent abdominal-pelvic MRI prior to (2.88 ± 0.83d) caesarean delivery. Software was utilized to determine the total FM in-vivo surface area (SA) and that of its components: placental disc and reflected FM. At delivery, the SA of the disc and FM in the relaxed state were measured. In-vivo (stretched) to delivered SA ratios were calculated. FM fragments were then biaxially stretched to determine the force required to re-stretch the FM back to in-vivo SA.ResultsTotal FM SA, in-vivo vs delivered, was 2135.51 ± 108.47 cm² vs 842.59 ± 35.86 cm²; reflected FM was 1778.42 ± 107.39 cm² vs 545.41 ± 22.90 cm², and disc was 357.10 ± 28.08 cm² vs 297.18 ± 22.14 cm². The ratio (in-vivo to in-vitro SA) of reflected FM was 3.26 ± 0.11 and disc was 1.22 ± 0.10. Reflected FM re-stretched to in-vivo SA generated a tension of 72.26 N/m, corresponding to approximate pressure of 15.4 mmHg. FM rupture occurred at 295.08 ± 31.73 N/m corresponding to approximate pressure of 34 mmHg. Physiological SA was 70% of that at rupture.DiscussionFM are significantly distended in-vivo. FM collagen fibers were rapidly recruited once loaded and functioned near the failure state during in-vitro testing, suggesting that, in-vivo, minimal additional (beyond physiological) stretch may facilitate rapid, catastrophic failure.     

A comparative study between the effect of 17-β estradiol and antioxidants combination on some menopausal changes in oophorectomised rats

BackgroundAs oxidative stress is proposed to be responsible for many of the menopause associated disorders, antioxidants may play an important role in this situation. The aim of this work was to compare between the effects of oestrogen replacement therapy and antioxidant supplements of vitamin C and low dose of vitamin A on some menopause associated changes in oophorectomised rats.Materials and methodsForty albino female rats were divided into 4 groups: normal control group, oophorectomised group, oophorectomised group treated with 17-β estradiol (oophorectomised + E₂) and oophorectomised group treated with vitamins (oophorectomised + vit).The following were measured: total antioxidant (TAO) and malondialdehyde (MDA), lipid profile, serum insulin, glucose and homeostasis model assessment-insulin resistance (HOMA-IR), bone specific alkaline phosphatase (BALP), urinary hydroxyproline, weight gain and visceral fat.ResultsA positive correlation was found between MDA and low density lipoprotein-cholesterol (LDL) (r = 0.694 and P = 0.000), HOMA-IR (r = 0.691 and P = 0.000.) and BALP (r = 0.563 and P = 0.000) and urinary hydroxyproline level (r = 0.761 and P = 0.000). Those results denoted that OS might be a cause of dyslipidemia, insulin resistance and osteoporosis associated with menopause.Both E₂ and vitamins in oophorectomised rats led to a significant decrease in MDA (F = 33.402, P = 0.000), weight gain, visceral fat (F = 7.589, p = 0.000 and F = 3.748, P = .019, respectively), cholesterol (F = 40.748, P = 0.0001), LDL cholesterol (F = 55.168, P = 0.0001), and significant increase in HDL (F = 18.393, P = 0.0001) and TAO levels (F = 14.781, P = 0.000) compared to oophorectomised rats. Also, both treatments led to a significant decrease of HOMA-IR (F = 18.933, P = 0.000, respectively), BALP (F = 13.202, P = 0.000) and urinary hydroxylproline (F = 220.012, P = 0.000). An interesting finding was detected where oophorectomised rats showed a decrease in triglyceride level which was significantly increased by E₂ administration whereas antioxidant administration produced no change (F = 34.267, P = 0.0001).ConclusionOur results denote similar effects of both E₂ and antioxidant’ supplements (vitamin C and low dose vitamin A) administration in surgically induced menopause in rats regarding oxidative stress, weight gain, atherogenic lipid profile changes, insulin sensitivity and bone turnover. However differences between preclinical and clinical studies must be taken into consideration especially when moving from animal studies to clinical trials.     

Effect of delayed umbilical cord clamping on blood gas analysis

Objective

To ascertain if there are differences in umbilical cord blood gas analysis between immediate and delayed cord clamping.

Study design

In a prospective observational study on 60 vaginally delivered healthy term newborns, we sampled umbilical cord blood immediately after delivery and at the time umbilical cord pulsation spontaneously ceased.

Results

There were significant decreases in pH, oxygen saturation (sO₂), glycemia, oxygen content (ctO₂), bicarbonate (HCO₃⁻) and base excess (BE). Lactate and PCO₂$P_{{\text{CO}}_2}$ increased. Delayed cord clamping pH correlated with immediate cord clamping pH, PO₂$P_{{\text{O}}_2}$, ctHb, sO₂ and time (r² = 0.77, p < 0.000). Delayed cord clamping lactate was associated with immediate cord clamping lactate and time (r² = 0.83, p < 0.000). Delayed BE was associated with previous pH, lactate, glycemia, ctHb and time (r² = 0.83, p < 0.000).

Conclusions

Delayed cord clamping alters acid–base parameters and lactate values compared to immediate cord clamping. Those variations depend mainly on time, prior pH and lactate.     

The effect of metformin treatment on ovarian stromal blood flow in women with polycystic ovary syndrome

Objective  To evaluate the effects of metformin on the ovarian stromal blood perfusion in the patients with polycystic ovary syndrome (PCOS). Methods  Twenty-five women with PCOS who underwent a Doppler examination of the ovarian stroma was evaluated; hormonal, anthropometric, and biochemical parameters of patients were determined. After the patients were treated with 850 mg metformin twice a day for 6 months, the same parameters were evaluated in the same patients. Results  After metformin treatment, although pulsatility index (PI) was increased from 1.80 ± 1.23, 1.84 ± 1.28 to 2.20 ± 1.10, 2.19 ± 0.83 in the right and left ovary, respectively, and resistance index was increased from 0.84 ± 0.25, 0.83 ± 0.23 to 1.16 ± 0.37, 1.10 ± 0.26 in the right and left ovary respectively (P < 0.05), peak systolic velocity (PSV) was decreased from 12.30 ± 1.72, 12.34 ± 1.55 to 10.25 ± 0.97, 10.53 ± 1.33 in the right and left ovary respectively (P < 0.05). PI and RI did not show any difference between the homeostatic model assessment insulin resistance index (HOMA-IR) ≥ 2.38 and HOMA-IR < 2.38 groups before and after metformin treatment (P > 0.05). However, PSV was decreased significantly from 13.05 ± 1.35, 12.82 ± 2.02 to 11.03 ± 0.71, 10.25 ± 0.42 in HOMA-IR ≥ 2.38 group in the right and left ovary, respectively, and PSV was decreased from 11.50 ± 2.67, 11.28 ± 0.26 to 9.10 ± 0.58, 9.28 ± 0.25 in HOMA-IR < 2.38 group in the right and left ovary, respectively, before and after metformin treatment (P < 0.05). PSV for both ovaries were positively correlated with HOMA scores before and after metformin treatment [(r = 0.713, P = 0.000; r = 0.617, P = 0.04 and r = 0.635, P= 0.03; r = 0.483, P = 0.031 respectively]. Conclusion  Metformin treatment affected ovarian stromal blood flow in PCOS patients.     

Uterine artery embolization followed by dilation and curettage within 24 hours compared with systemic methotrexate for cesarean scar pregnancy

Objective

To assess the efficacy of uterine artery embolization (UAE) combined with dilation and curettage (D&C) within 24 hours for the treatment of a cesarean scar pregnancy (CSP), compared with methotrexate and D&C.

Methods

A retrospective cohort study of 119 women with CSP was conducted at two tertiary hospitals in Guangzhou and Shenzhen, China, during 2009–2012. Twenty-six women received systemic methotrexate followed by D&C, and 93 women were treated with UAE followed by D&C within 24 hours.

Results

Mean blood loss was 261.0 ± 357.4 mL in the methotrexate group versus 14.1 ± 40.6 mL in the UAE group (P < 0.001). The time to resolution of the level of β-human chorionic gonadotropin was 40.5 ± 17.2 days versus 15.4 ± 7.7 days (P < 0.001), respectively. The duration of hospitalization was 14.6 ± 9.2 days versus 6.2 ± 3.7 days (P < 0.001), respectively. An additional intervention was needed in 9 (35%) women in the methotrexate group and in 5 (5%) in the UAE group (P < 0.001).

Conclusion

UAE combined with D&C within 24 hours was an effective uterine preservation treatment for CSP, and was associated with less blood loss and a shorter hospital stay than administration of methotrexate followed by D&C.     

Neonatal outcome in preterm deliveries between 23 and 27 weeks’ gestation with and without preterm premature rupture of membranes

Objectives  To characterize neonatal morbidity and mortality rates in extreme preterm deliveries (between 23 and 27 weeks’ gestation) with and without PPROM, and to evaluate the association between PPROM and chorioamnionitis. Methods  A retrospective population-based study was conducted on preterm singleton pregnancies delivered between 23 and 27 weeks’ gestation from 1988 to 2007. Immediate neonatal morbidity and mortality rates in pregnancies complicated by PPROM were compared to pregnancies with intact membranes. A multivariate analysis was conducted in order to determine the independent association between PPROM and chorioamnionitis. Results  Out of 1,437 preterm deliveries, 236 (16.4%) were complicated with PPROM. There were more neonates with low 1 min (61.0 vs. 42.5%; P = 0.001) and low 5 min (30.1 vs. 23.8%; P = 0.042) Apgar scores (of less than 7) in pregnancies complicated by PPROM than in the comparison group. There were more cases of chorioamnionitis in the PPROM group born at 23–24 weeks’ gestation (33.8 vs. 17.0%; P < 0.001), and in the PPROM group born at 25–27 weeks (42.0 vs. 15.5%; P < 0.001). In the group born at 23–24 weeks’ gestation, there were more postpartum deaths (PPD) in the PPROM group (70.0 vs. 54.8%; P = 0.013); however, there was no significant difference in PPD in the groups born at 25–27 weeks. In the group born at 23–24 weeks, as well as at 25–27 weeks, there were fewer antepartum deaths (APD) in the PPROM group as compared to the control group (16.3 vs. 32.6%; P = 0.002, and 5.3 vs. 36.3%; P < 0.001; respectively). After adjusting for gestational age and gender, using a multivariate analysis, the association between PPROM and chorioamnionitis remained significant (OR = 3.32; 95% CI 2.43–4.51, P < 0.001). Conclusions  PPROM is associated with adverse perinatal outcome in deliveries between 23 and 27 weeks’ gestation. Moreover, PPROM is an independent risk factor for chorioamnionitis.     

Plasma and placental nitric oxide levels in women with and without pre-eclampsia living at different altitudes

Objective

To investigate the nitric oxide (NO) levels in the plasma and the placentas of pregnant women with pre-eclampsia and women without pre-eclampsia, and to determine the effect of high or low altitude of residence.

Methods

NO was determined by chemoluminescence and group comparisons were performed.

Results

Women with pre-eclampsia (n = 63) had higher plasma NO levels (38.6 ± 17.44 vs 30.6 ± 12.44 µmol/L, P = 0.004) and higher placental NO levels (38.5 ± 17.0 vs 24.3 ± 7.16 ng/mg protein, P < 0.05) compared with women without pre-eclampsia. A similar trend was found when comparisons were made according to altitude of residence. NO levels were significantly higher in the plasma of pre-eclamptic women living at sea level (41.11 ±18.78 vs 28.96 ± 9.57 µmol/L, P = 0.003), and in the placentas of women living at high altitude (39.51 ± 16.98 vs 21.91 ± 6.64 ng/mg protein, P < 0.0001).

Conclusion

Women with pre-eclampsia had higher plasma and placental NO levels and the differences were associated with altitude of residence.     

Dynamic thiol/disulphide homeostasis and ischemic modified albumin levels in isolated oligohydramnios

ObjectiveOligohydramnios is defined as amniotic fluid index in ultrasonographic measurement is less than 5 percentile according to gestational age, the amniotic fluid volume is ≤ 5 cm, or if the single deepest dial is < 2 cm. The condition of oligohydramnios that not with fetal structural/chromosomal abnormalities, intrauterine growth retardation, intrauterine infection and maternal disease is described as isolated oligohydramnios (IO). The aim of this study is to examine whether oxidative stress and reactive oxygen species (ROS) have a place in the pathophysiology of IO.Materials and methodsIn this prospective case–control study, a total of 126 participants were included. The patient group consisted of 65 patients who were diagnosed IO, and the control group consisted of 61 healthy normal pregnants. Native thiol (-SH), total thiol (-SH + -SS), dynamic disulfide (-SS), IMA values from maternal serum were measured and compared between groups.ResultsMaternal serum -SH and -SH + -SS values were significantly lower in the IO group than in the control group (409.47 ± 55.36 μmol/L vs. 437.40 ± 48.68 μmol/L, p = 0.03 and 457.40 ± 63.01 μmol/L vs. 484.59 ± 52.75 μmol/L, p = 0.01). In the IO group when -SS/-SH and -SS/-SH + -SS ratio was found to be statistically significantly higher than control group (5.84 ± 1.1 vs 5.41 ± 0.71, p = 0.01 and 5.2 ± 0.88 vs 4.8 ± 0.58, p = 0.01), -SH/-SH + -SS ratio was significantly lower (89.56 ± 1.7 vs 90.24 ± 1.16, p = 0.01). There was no significant difference in terms of -SS value (p = 0.66). IMA value was significantly higher in the IO group than control group (0.76 ± 0.10 ABSU vs 0.68 ± 0.06, p < 0.01). It is seen as a result of ROC analysis that -SH, -SH + -SS, -SS/-SH, -SS/-SH + -SS, -SH/-SH + -SS and IMA values have a diagnostic value for IO (p < 0.05).ConclusionThe thiol/disulfide balance shifted towards oxidative stress in IO compared to control group. So oxidative stress and ROS have a place in the pathophysiology of IO.     

Placental oxidative DNA damage and its repair in preeclamptic women with fetal growth restriction

Preeclampsia is frequently accompanied by fetal growth restriction (FGR). Preeclampsia increases oxygen free radical production, and the resulting oxidative stress impairs placental blood flow. To determine whether placental oxidative stress is associated with FGR in preeclamptic women, we evaluated placental oxidative DNA damage and its repair in 13 preeclamptic women with FGR, 10 preeclamptic women without FGR, and 11 healthy pregnant women without complications. We measured maternal and umbilical serum derivatives of reactive oxygen metabolites (d-ROMs), as a marker of oxygen free radicals, and pulsatility index (PI) of uterine and umbilical arteries, and performed an immunohistochemical analysis to measure the proportion of nuclei in the placental trophoblast that stained positive for 8-hydroxy-2′-deoxyguanosin (8-OHdG), an indicator of oxidative DNA damage, and redox factor-1 (ref-1), indicative of the repair function towards oxidative DNA damage. D-ROMs were increased in the maternal blood of both preeclamptic groups (with FGR, 687.3 ± 50.4 CARR U, p < 0.01; without FGR, 750.4 ± 87.2 CARR U, p < 0.001) compared with controls (504.7 ± 25.0 CARR U). In contrast, d-ROM levels in the umbilical artery were elevated in preeclamptic women with FGR (134.9 ± 13.3 CARR U, p < 0.01), but not in preeclamptic women without FGR (44.0 ± 7.3 CARR U) compared with controls (38.2 ± 5.0 CARR U). Mean PI for uterine arteries was significantly increased in both preeclamptic groups, and the PI in preeclamptic women with FGR was significantly greater than that in women without FGR (0.94 ± 0.07 vs. 1.31 ± 0.07, p < 0.001). The PI for umbilical arteries was significantly increased in preeclamptic women with FGR (0.90 ± 0.05vs. 1.19 ± 0.07, p < 0.001), but not in preeclamptic women without FGR. The proportion of nuclei positive for 8-OHdG was higher in both groups of preeclamptic women than in the control group, but was higher in preeclamptic women with FGR (0.21 ± 0.05 vs. 0.87 ± 0.01, p < 0.001). The proportion of nuclei positive for ref-1 was higher in preeclamptic women without FGR (0.54 ± 0.06, p < 0.001) than in the control group, whereas the proportion did not differ significantly between normal and preeclamptic women with FGR. Our findings indicate that increased oxidative stress and disrupted compensatory reaction against placental oxidative DNA damage may be associated with FGR in preeclamptic women.     

Predictors of severe and febrile neutropenia during primary chemotherapy for ovarian cancer

Objective

To identify factors that increase the risk of neutropenic events in women with advanced ovarian carcinoma receiving initial chemotherapy.

Methods

Multi-center retrospective study of women with FIGO stage III-IV epithelial ovarian cancer treated postoperatively with multi-agent intravenous chemotherapy from 1995 to 2008. Outcomes were severe (SN; absolute neutrophil count [ANC] < 500/mm³) and febrile neutropenia (FN; ANC < 1000/mm³ and temperature > 38.1 °C). Cumulative risk of neutropenic events was estimated by Kaplan Meier method. Multivariate analysis was by Cox proportional hazard regression.

Results

Three hundred twenty-six patients met inclusion criteria. There were 251 SN events among 140 (43%) patients and 24 FN events among 22 (7%) patients. Univariate predictors of SN were body surface area < 2.0 m² (p = 0.03), body mass index (BMI) < 30 kg/m² (p < 0.01), Caucasian race (p < 0.01), treatment on research protocols (p < 0.01), non-carboplatin-containing regimens (p < 0.01), and planned relative dose intensity (RDI) > 85% of standard (p = 0.02). Women over age 60 were more likely to develop FN (p = 0.05). Multivariate predictors of SN were treatment on research protocols (hazard ratio [HR] 1.93; p < 0.01), Caucasian race (HR 2.13; p = 0.01), and planned RDI > 85% (HR 1.69; p = 0.05); predictors of FN were age > 60 (HR 2.84; p = 0.05) and non-carboplatin containing regimens (HR 4.06; p < 0.01).

Conclusion

While SN is fairly common, FN occurs infrequently in women with EOC undergoing taxane and platin-based chemotherapy and primary prophylactic growth factor support is not indicated. However, women older than 60 years of age receiving non-carboplatin containing regimens are at higher risk for FN and warrant closer surveillance.     

High-throughput interrogation of PIK3CA,PTEN, KRAS,FBXW7 and TP53 mutations in primary endometrial carcinoma

ObjectiveEndometrial cancer patients may benefit from systemic adjuvant chemotherapy, alone or in combination with targeted therapies. Prognostic and predictive markers are needed, however, to identify patients amenable for these therapies.MethodsPrimary endometrial tumors were genotyped for > 100 hot spot mutations in genes potentially acting as prognostic or predictive markers. Mutations were correlated with tumor characteristics in a discovery cohort, replicated in independent cohorts and finally, confirmed in the overall population (n = 1063).ResultsPIK3CA, PTEN and KRAS mutations were most frequently detected, respectively in 172 (16.2%), 164 (15.4%) and 161 (15.1%) tumors. Binary logistic regression revealed that PIK3CA mutations were more common in high-grade tumors (OR = 2.03; P = 0.001 for grade 2 and OR = 1.89; P = 0.012 for grade 3 compared to grade 1), whereas a positive TP53 status correlated with type II tumors (OR = 11.92; P < 0.001) and PTEN mutations with type I tumors (OR = 19.58; P = 0.003). Conversely, FBXW7 mutations correlated with positive lymph nodes (OR = 3.38; P = 0.045). When assessing the effects of individual hot spot mutations, the H1047R mutation in PIK3CA correlated with high tumor grade and reduced relapse-free survival (HR = 2.18; P = 0.028).ConclusionsMutations in PIK3CA, TP53, PTEN and FBXW7 correlate with high tumor grade, endometrial cancer type and lymph node status, whereas PIK3CA H1047R mutations serve as prognostic markers for relapse-free survival in endometrial cancer patients.     

Cupping therapy for treating knee osteoarthritis: The evidence from systematic review and meta-analysis

ObjectiveCupping therapy is widely used in East Asia, the Middle East, or Central and North Europe to manage the symptom of knee osteoarthritis (KOA). The purpose of this systematic review was to evaluate the available evidence from randomized controlled trials (RCTs) of cupping therapy for treating patients with KOA.MethodsThe following databases were searched from their inception until January 2017: PubMed, Embase, the Cochrane Central Register of Controlled Trials and four Chinese databases [WanFang Med Database, Chinese BioMedical Database, Chinese WeiPu Database, and China National Knowledge Infrastructure (CNKI)]. Only the RCTs related to the effects of cupping therapy on KOA were included in this systematic review. A quantitative synthesis of RCTs will be conducted using RevMan 5.3 software. Study selection, data extraction, and validation was performed independently by two reviewers. Cochrane criteria for risk-of-bias were used to assess the methodological quality of the trials.ResultsSeven RCTs met the inclusion criteria, and most were of low methodological quality. Study participants in the dry cupping therapy plus the Western medicine therapy group showed significantly greater improvements in the pain [MD = −1.01, 95%CI (−1.61, −0.41), p < 0.01], stiffness [MD = −0.81, 95%CI (−1.14, −0.48), p < 0.01] and physical function [MD = −5.53, 95%CI (−8.58, −2.47), p < 0.01] domains of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) compared to participants in the Western medicine therapy group, with low heterogeneity (Chi² = 0.00 p = 1.00, I² = 0% in pain; Chi² = 0.45 p = 0.50, I² = 0% in stiffness; Chi² = 1.09 p = 0.30, I² = 9% in physical function). However, it failed to do so on a Visual Analog Scale (VAS) [MD = −0.32, 95%CI (−0.70, 0.05), p = 0.09]. In addition, when compared with Western medicine therapy alone, meta-analysis of four RCTs suggested favorable statistically significant effects of wet cupping therapy plus western medicine on response rate [MD = 1.06, 95%CI (1.01, 1.12), p = 0.03; heterogeneity: Chi² = 1.13, p = 0.77, I² = 0%] and Lequesne Algofunctional Index (LAI) [MD = −2.74, 95%CI (−3.41, −2.07), p < 0.01; heterogeneity: Chi² = 2.03, p = 0.57, I² = 0% ].ConclusionOnly weak evidence can support the hypothesis that cupping therapy can effectively improve the treatment efficacy and physical function in patients with KOA.     

Association between maternal haemoglobin at 27–29 weeks gestation and intrauterine growth restriction

ObjectiveTo examine the relationship between maternal haemoglobin concentration (Hb) at 27–29 weeks’ gestation and fetal growth restriction (FGR).DesignThis was a retrospective, case control study.SettingA University hospital in London, UK.PopulationPregnant women attending for routine antenatal care at 27–29 weeks of pregnancy.MethodsMaternal Hb, measured routinely at 27–29 weeks in pregnancies complicated by FGR (n = 491) was compared to normal controls (n = 491). Multiple regression analysis was used to examine the association between Hb and maternal characteristics.Main outcome measuresBirthweight z-score, admission to the Neonatal Unit (NNU) and adverse perinatal outcome.ResultsIncreased Hb at 27–29 weeks gestation is associated with reduced birthweight, with an inverse relationship between maternal Hb and fetal birthweight z-score (R² = 0.10, p < 0.0001). In addition, for the prediction of admission to the NNU (R² = 0.24, p < 0.0001) and serious adverse neonatal outcome (R² = 0.10, p < 0.0001), maternal Hb is an independent predictor with a linear and quadratic relationship, respectively. Therefore, both increased and decreased maternal Hb levels increase the risk of serious neonatal complications.ConclusionsRaised Hb at 27–29 weeks gestation is associated with FGR and with an increased risk of admission to the NNU and adverse fetal outcome.     

Somatic copy number alterations predict response to platinum therapy in epithelial ovarian cancer

ObjectivePlatinum resistance remains an obstacle in the treatment of epithelial ovarian cancer (EOC). The goal of this study was to profile EOCs for somatic copy number alterations (SCNAs) as predictive markers of platinum response.MethodsSCNAs were assessed in a discovery (n = 86) and validation cohort (n = 115) of high risk stage I or stage II-IV EOCs using high-resolution SNP arrays. ASCAT and GISTIC identified all significantly overrepresented amplified or deleted chromosomal regions. Cox regression and univariate analysis assessed which SCNAs correlated with overall survival (OS), progression-free survival (PFS), platinum-free interval (PFI) and platinum response. Relevant SCNAs were also assessed in a pooled analysis involving both cohorts and published SCNA data from The Cancer Genome Atlas (TCGA; n = 227).ResultsWe identified 53 regions to be significantly overrepresented in EOC. Of these, 6 were associated with OS, PFS or PFI in the discovery cohort at P < 0.05. In the validation cohort, amplifications of chromosomal region 14q32.33, which contains AKT1 as a potential driver gene, also correlated with OS (OR = 1.670; P = 0.018). In a pooled analysis of 428 tumors, involving the discovery, validation and TCGA cohorts, 14q32.33 amplifications significantly reduced OS, PFS and PFI (HR = 2.69, P = 1.7 × 10^− 4; HR = 1.82, P = 1.9 × 10^− 2 and HR = 1.80, P = 2.2 × 10^− 2 respectively). Moreover, AKT1 mRNA expression correlated with the number of chromosomal copies of the 14q32.33 region (P = 2.8 × 10^− 11;R² = 0.26).ConclusionsWe established that amplifications in 14q32.33 were associated with reduced OS, PFS, PFI and platinum resistance in three independent cohorts, suggesting that AKT1 amplifications act as a potentially predictive marker for EOC treated with platinum-based chemotherapy.