[Predictive value of the sFlt1/PlGF ratio for the diagnosis of preeclampsia in high-risk patients]. / Wertigkeit des sFlt1/PlGF-Quotienten als Prädiktionsparameter bei Schwangeren mit erhöhtem Präeklampsierisiko.

BACKGROUND: A dysbalance of proangiogenic [placental growth factor (PlGF)] and antiangiogenic [soluble fms-like tyrosine kinase 1 (sFlt-1)] proteins is known to cause the symptoms of preeclampsia (PE), HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) or intrauterine growth restriction (IUGR). An increased sFlt-1/PlGF ratio ≥85 is considered a reliable diagnostic marker. Altered sFlt1 and PlGF concentrations can be detected several weeks prior to the onset of clinical symptoms. In this study we analysed the role of the sFlt1/PlGF ratio as a predictive marker for preeclampsia in a high-risk patient group. PATIENTS AND MATERIALS: We prospectively included 68 singleton pregnancies with at least one risk factor for PE, HELLP syndrome or IUGR. During the study the patients were divided into one group with symptoms (patient group) and one group without symptoms (control group) for the above-mentioned diseases. The sFlt1/PlGF ratios were measured on admission and during the course of pregnancy. RESULTS: During pregnancy 41% of patients developed PE, HELLP syndrome or IUGR. An increase of the absolute value of the sFlt1/PlGF ratio ≥85 was only observed in the patient group and was found to be a predictive factor for PE, HELLP syndrome or IUGR at 25+0 to 31+0 weeks of gestation (p=0.005) and after 35+0 weeks of gestation (p=0.044). Alterations of the sFlt1/PlGF ratio were observed in all patients but were higher in the patient group from 7-10 weeks prior to delivery and with the highest peak 0-2 weeks prior to delivery. Compared to the control group (mean±SD 66.9±134) absolute values of sFlt1/PlGF ratio were significantly (p=0.021) increased 0-2 weeks prior to delivery in the patient group (mean±SD 393.3±147.4). An increase of the sFlt1/PlGF ratio ≥85 0-2 weeks before delivery has shown to be predictive for one of the mentioned diseases (p=0.025). CONCLUSIONS: In high-risk patients the sFlt1/PlGF ratio can be used for an individual risk assessment with regard to PE, HELLP syndrome or IUGR. Serial measurements permit a risk-adapted prenatal care of these patients.

Leptin is differentially expressed and epigenetically regulated across monochorionic twin placenta with discordant fetal growth.

Severely growth-discordant monochorionic (MC) twins offer a unique opportunity to study fetal and placental growth based on a similar genetic background and maternal host environment where the healthy twin serves as an ideal control. Differences in development of MC twins may therefore be due to differential epigenetic regulation of genes involved in placental development and function. Growth-discordant twins are known for abnormal angio-architecture in the placenta of the smaller twin. Since the reasons for this phenotype are mostly unknown this study was aimed to investigate the expression and regulation of genes known to be involved in angiogenesis. We studied 10 severely growth-discordant MC twin placentas (birthweight difference ≥20%) without twin-twin-transfusion syndrome and 5 growth-concordant MC twin placentas. Growth-discordant twin placentas were phenotyped by histology. Placental mRNA expression of 88 angiogenesis-related genes was measured by PCR array. ELISA assay and immunohistochemistry were used to confirm PCR results. EpiTYPTER for DNA methylation was used to determine if methylation ratios were responsible for differential gene expression. The PCR array analysis showed significant mRNA up-regulation in the placental share of the smaller twin for several genes. These included leptin (24.6-fold, P = 0.017), fms-like tyrosine kinase 1 (Flt1, 2.4-fold, P = 0.016) and Endoglin (Eng, 1.86-fold, P = 0.078). None of the other 84 angiogenesis-related genes showed significant differences. ELISA confirmed significantly increased leptin protein expression (49.22 versus 11.03 pg/ml, P = 0.049) in the smaller twin of the discordant growth cohort. Leptin expression in smaller twins' placentas was associated with elevated DNA methylation of the leptin promotor region suggesting the inhibition of binding of a transcriptional activator/inhibitor in that region. We attempted to overcome the limitation of sample size by careful patient selection. We minimized any bias in placental sampling by random sampling from two different sites and by avoiding sampling from areas with grossly visible abnormalities using a standardized sampling protocol. In conclusion, the smaller twin's placenta is characterized by differentially increased gene expressions for Flt1 and Eng mRNA that may be causally associated with the villous pathology driven by abnormal feto-placental angiogenesis. The substantial up-regulation of leptin mRNA may be epigenetically conferred and relevant to the post-natal risk of metabolic syndrome in intrauterine growth restriction offspring with placental pathology. Growth-discordant MC twins offer unique insights into the epigenetic basis of perinatal programming.

Fetal thoracoamniotic shunting for large macrocystic congenital cystic adenomatoid malformations of the lung.

OBJECTIVE: To evaluate fetal thoracoamniotic shunting for isolated large macrocystic congenital cystic adenomatoid malformations (CCAM) of the lung. METHODS: This was a retrospective study of 11 fetuses with macrocystic CCAM who underwent thoracoamniotic shunting. This procedure was offered if fetal hydrops or signs of evolving hydrops (such as ascites or polyhydramnios) were present, or when there were very large lesions or lesions rapidly increasing in size. If there were multiple large cysts within the lesion, a single shunt was used, aiming to traverse several cysts. RESULTS: Shunts were inserted at a mean gestational age of 24.6 (range, 17-32) weeks. Marked mediastinal shift was present in all cases. Six fetuses were hydropic and, of the remaining five, one had severe polyhydramnios, three had lesions that were rapidly increasing in size and one had a very large lesion at initial presentation. In total, four cases had polyhydramnios. Shunting one cyst always decompressed the entire lesion and hydrops and/or polyhydramnios resolved in all surviving fetuses. One hydropic fetus that underwent the procedure at 17 weeks died 1 day later. The shunt dislodged in one case and the lesion did not re-expand. No mother went into labor or had ruptured membranes before 35.6 weeks. Mean gestational age at delivery was 38.2 weeks (n = 10). All pregnancies were delivered vaginally, with no maternal complications. All newborns had uneventful lobectomies, and pathology confirmed CCAM in all cases. CONCLUSION: Fetal thoracoamniotic shunting for large macrocystic CCAM is associated with favorable outcome in most cases, and should be considered in severe cases even before hydrops develops.

Serum levels of the adipokine lipocalin-2 are increased in preeclampsia.

BACKGROUND: Preeclampsia (PE) is a serious complication in pregnancy which increases the future risk for vascular and metabolic disease in both mother and newborn. Recently, lipocalin-2 has been introduced as a novel adipokine which contributes to obesity, insulin resistance, and vascular disease. AIM: In the current study, we investigated lipocalin-2 serum levels in PE patients as compared to healthy gestational age-matched controls. SUBJECTS AND METHODS: Lipocalin-2 serum concentrations were quantified by enzyme-linked immunosorbent assay in control (no.=22) and PE (no.=22) patients. Furthermore, lipocalin-2 levels were correlated to clinical and biochemical measures of renal function, glucose, and lipid metabolism, as well as inflammation. RESULTS: Median maternal lipocalin-2 concentrations were significantly increased in PE (121.3 µg/l) as compared to control subjects (99.8 µg/l) (p<0.05). Furthermore, circulating lipocalin 2 correlated positively with diastolic blood pressure, creatinine, and C reactive protein. In multivariate analyses, creatinine and C reactive protein remained independently associated with lipocalin-2 levels. CONCLUSIONS: We demonstrate that maternal lipocalin-2 concentrations are significantly increased in PE. Furthermore, markers of renal function and inflammation independently predict circulating lipocalin-2.

COVID-19associated exfoliative shock syndrome / Síndrome de shock exfoliativo por covid-19

RESUMEN El síndrome de shock exfoliativo(SSE) asociado a COVID- 19 es una enfermedad recientemente descrita con características superpuestas de síndrome de shock tóxico (SST) y síndrome de la piel escaldada estafilocócica (SSSS, por sus siglas en inglés). Clínicamente se presenta con fiebre, hipotensión y erupción cutánea exfoliativa.Se expone un caso en donde las lesiones cutáneas por COVID-19 precedieron a las manifestaciones respiratorias.

ABSTRACT The exfoliative shock syndrome (ESS) associated with COVID-19 is a recently described disease with overlapping features of toxic shock syndrome (TSS) and staphylococcal scalded skin syndrome(SSSS). Clinically it presents with fever, hypotension, and exfoliative skin rash. A case is presented in which the skin lesions by COVID-19 preceded the respiratory manifestations.

Questionnaire study of electronic wear-time tracking as experienced by patients and parents during treatment with removable orthodontic appliances.

OBJECTIVE: To survey how patients and parents rate microelectronic wear-time tracking (TheraMon(®)) during treatment with removable orthodontic appliances. PATIENTS AND METHODS: A total of 125 patients with a mean age of 11.99 years whose treatment involved removable appliances with a built-in microsensor for wear-time documentation were enrolled in a questionnaire study addressing electronic wear-time tracking. Respondents included the patients and their parents. RESULTS: A total of 86% of the patients reported that the orthodontic appliance's comfort was unaffected by the installed sensor. A majority of respondents had a favorable impression of wear-time tracking. Printed wear-time documents from the clinician's computer were considered a "nice certificate of compliance" by 46% of patients, and 38% of them stated that they intended to improve their compliance when faced with a poor record. Indeed, 48% of parents believe that wear-time tracking can improve the therapeutic success, while 32% believe that it can reduce the duration of treatment. Around 10% of respondents felt that the sensors were unnecessary and not recommendable. CONCLUSION: These favorable ratings by patients and their parents may help future patients and users to decide for or against microelectronic wear-time tracking. Randomized studies are needed to demonstrate whether the sheer presence of a wear-time sensor stimulates compliance on its own.

Midterm visual outcome and progression of diabetic retinopathy following cataract surgery. Midterm outcome of cataract surgery in diabetes.

OBJECTIVE: To assess the influence of cataract surgery on progression of diabetic retinopathy and visual acuity. METHODS: 37 patient eyes with mild to moderate diabetic retinopathy at baseline underwent phacoemulsification and intraocular posterior chamber lens implantation. They were examined 3.3 +/- (SD) 0.7 years after surgery. RESULTS: 83.8% of the eyes showed a better final visual acuity, and 67.6% achieved a final visual acuity of 0.5 or better. The retinopathy remained unchanged in 83.8% and progressed in 16.2% of the eyes. No eye progressed to proliferative retinopathy. CONCLUSION: Phacoemulsification and implantation of a posterior chamber intraocular lens is a safe procedure for patients with mild to moderate diabetic retinopathy.