TCF7L2 Polymorphism rs7903146 (C/T) and Gestational Diabetes Influence on Obstetric Outcome: A Romanian Case-Control Study.

Gestational diabetes mellitus (GDM) is one of the most frequent predictors of obstetric outcome among Romanian pregnant women. Thus, we aimed to investigate the role of rs7903146 (C/T) TCF7L2 gene polymorphism in the presence of GDM and to evaluate the influence on maternal-fetal outcomes in a cohort of pregnant women from Northern Transylvania. Our prospective case-control study was performed in a tertiary maternity center on 61 patients diagnosed with GDM and 55 normal pregnant patients. The patients were genotyped for rs7903146 (C/T) polymorphism of the TCF7L2 gene using the PCR-RFLP method between 24 and 28 weeks of gestation. The minor T allele was associated with a high risk of developing GDM (OR 1.71 [95% CI 0.82-3.59]) if both heterozygote and homozygote types were considered. Also, a higher risk of developing GDM was observed in homozygous carriers (OR 3.26 [95% CI 1.10-9.68]). Women with the TT genotype were more likely to require insulin therapy during pregnancy than other genotypes with a 5.67-fold increased risk ([1.61-19.97], p = 0.015). TT homozygote type was significantly associated with fetal macrosomia for birth weights greater than the 95th percentile (p = 0.034). The homozygous TT genotype is associated with an increased risk of developing GDM. Also, rs7903146 (C/T) TCF7L2 variant is accompanied by a high probability of developing insulin-dependent gestational diabetes mellitus (ID-GDM). The presence of at least one minor T allele was associated with a higher risk of fetal macrosomia.

Spontaneous Fistula and Abdominal Wall Endometriosis Due to Occult Existence of Unicornuate Right Uterus with Rudimentary Non-Communicating Functioning Left Horn.

Accurate diagnosis of Müllerian duct anomalies (MDA) remains a clinical challenge even by direct surgical inspection. Although obstetrical complications are more frequent in women with MDA, some subtypes allow normal reproduction, further delaying the diagnosis. Unicornuate uterus with a rudimentary non-communicating functioning horn is a rare form of MDA, susceptible to many gynecologic and obstetric complications such as miscarriages, premature birth, hematosalpinx, endometriosis, and chronic pelvic pain. We present an entire case pictorial assay including preoperative imaging as well as the surgical correction of the uterine anomaly and the associated complication of an occult unicornuate right uterus with rudimentary non-communicating functioning left horn (Class U4aC0V0/ European Society of Human Reproduction and Embryology/European Society of Gastrointestinal Endoscopy Classification) and its natural evolution following a previous incomplete surgical treatment. The patient had an emergency left adnexectomy for hematosalpinx and ovarian endometrioma at her local county hospital. After five years, the patient presented with severe dysmenorrhea and abdominal endometriosis due to blocked retrograde menstruation from a rudimentary, non-communicating functioning horn. Surgical treatment with the resection of the rudimentary uterine horn, together with the abdominal wall endometriosis lesions, was carried out with good outcomes.

Killer Cell Immunoglobulin-like Receptor Genotypes and Reproductive Outcomes in a Group of Infertile Women: A Romanian Study.

A growing body of evidence suggests that endometrial immune disorders may be responsible for endometrial dysfunctions that can lead to gynecological and obstetrical pathology. The aim of this study was to explore the potential relationship between different killer cell immunoglobulin-like receptor (KIR) genotypes and reproductive outcomes. We conducted a prospective cohort study that included 104 infertile patients undergoing an in vitro fertilization procedure. All participants underwent clinical and ultrasound examination, genetic evaluation (KIR genotyping), endometrial washing fluid sampling for cytokine determination, endometrial tissue sampling for histologic assessment and hysteroscopic evaluation. Our analysis showed statistically significant lower levels of uterine cytokines TNF-α (p = 0.001) and IL-1beta (p = 0.000) in the KIR AA genotype group as compared to KIR AB and BB among study participants with chronic endometritis. The study results suggest that the KIR AA genotype population subgroups may be more susceptible to developing endometrial disorders such as chronic endometritis. The changes in the behavior of NK cells seem to be subtle and expressed as an altered regulatory pattern.

Neonatal Hemochromatosis: Systematic Review of Prenatal Ultrasound Findings-Is There a Place for MRI in the Diagnostic Process?

Neonatal hemochromatosis (NH) is an uncommon, severe disorder that results in fetal loss or neonatal death due to liver failure. NH is currently regarded as the phenotypic expression of gestational alloimmune liver disease (GALD). The diagnosis of NH-GALD is rarely prenatally established. In addition to providing a systematic review of the prenatal features that are identifiable using ultrasound (US) and MRI, we suggest a prenatal diagnosis algorithm for use in suspected NH during the first affected pregnancy. From a total of 586 database entries identified in PubMed, Google Scholar, and ResearchGate, we selected 18 studies published from 1993 to 2021 that reported maternal medical and obstetric history, prenatal ultrasound findings, and postpartum outcomes. We investigated the ultrasound and MRI features of these studies, along with the outcome due to this condition. A total of 74 cases were identified. The main reported prenatal US finding was fetal growth restriction (FGR) (33%), followed by oligohydramnios (13%) and hydrops fetalis (13%), with 13% cases described as uneventful. Other rare prenatal findings were fetal anemia, ascites, and abnormal fetal liver and spleen. Most pregnancies ended with fetal/perinatal death or therapeutic interruption of pregnancy. Favorable evolution with treatment (ensanguine transfusion and intravenous immunoglobulin (IVIG)) was reported for only 7% of fetuses. Using T2-weighted MRI, fetal extrahepatic siderosis confirmed prenatally in two cases and postnatally in 11 cases. IVIG treatment throughout subsequent pregnancies was found to significantly improve fetal prognosis. MRI should be indicated in selected cases of oligohydramnios, fetal hydrops, fetal hepatomegaly, ascites, or unexplained FGR or anemia after ruling out all other more frequently encountered conditions. MRI can be used to detect iron overload in the liver and extrahepatic siderosis.

Ultrasound Placental Remodeling Patterns and Pathology Characteristics in Patients with History of Mild SARS-CoV-2 Infection during Pregnancy.

Introduction: This research aims to describe a progressive pattern of ultrasound placental remodeling in patients with a history of SARS-CoV-2 infection during pregnancy. Materials and Methods: This was a longitudinal, cohort study which enrolled 23 pregnant women with a history of former mild SARS-CoV-2 infection during the current pregnancy. Four obstetricians analyzed placental ultrasound images from different gestational ages following COVID infection and identified the presence and degree of remodeling. We assessed the inter-rater agreement and the interclass correlation coefficients. Pathology workup included placental biometry, macroscopic and microscopic examination. Results: Serial ultrasound evaluation of the placental morphology revealed a progressive pattern of placental remodeling starting from 30-32 weeks of gestation towards term, occurring approximately 8-10 weeks after the SARS-CoV-2 infection. Placental changes-the "starry sky" appearance and the "white line" along the basal plate-were identified in all cases. Most placentas presented normal subchorionic perivillous fibrin depositions and focal stem villi perivillous fibrin deposits. Focal calcifications were described in only 13% of the cases. Conclusions: We identified two ultrasound signs of placental remodeling as potential markers of placental viral shedding following mild SARS-CoV-2. The most likely pathology correspondence for the imaging aspect is perivillous and, respectively, massive subchorionic fibrin deposits identified in most cases.

Spectrum of High-Risk Mutations among Breast Cancer Patients Referred for Multigene Panel Testing in a Romanian Population.

(1) Background: Multigene panel testing for Hereditary Breast and Ovarian Cancer (HBOC) using next generation sequencing (NGS) is becoming a standard in medical care. There are insufficient genetic studies reported on breast cancer (BC) patients from Romania and most of them are focused only on BRCA 1/2 genes (Breast cancer 1/2). (2) Methods: NGS was performed in 255 consecutive cases of BC referred for management in our clinic between 2015-2019. (3) Results: From the 171 mutations identified, 85 were in the high-penetrance BC susceptibility genes category, 72 were pathogenic genes, and 13 genes were in the (variants of uncertain significance) VUS genes category. Almost half of the mutations were in the BRCA 1 gene. The most frequent BRCA1 variant was c.3607C>T (14 cases), followed by c.5266dupC (11 cases). Regarding BRCA-2 mutations we identified c.9371A>T (nine cases), followed by c.8755-1G>A in three cases, and we diagnosed VUS mutations in three cases. We also identified six pathogenic variants in the PALB2 gene and two pathogenic variants in (tumor protein P 53) TP53. (4) Conclusions: The majority of pathogenic mutations in the Romanian population with BC were in the BRCA 1/ 2 genes, followed by PALB2 (partner and localizer of BRCA2) and TP53, while in the CDH1 (cadherin 1) and STK11 (Serine/Threonine-Protein Kinase) genes we only identified VUS mutations.

Echogenic Content in the Fetal Gallbladder: Systematic Review of Ultrasound Features and Clinical Outcome.

It is rare to detect echogenic content in the fetal gallbladder. The etiology, natural course, and prognosis of this condition remain unclear. In addition to providing a systematic review of this topic, we suggest a plan for patient follow-up. From a total of 100 database entries identified in PubMed, EMBASE, and ICTRP reviews, we selected 34 studies in which we investigated the ultrasound features and outcome of this condition. There were 226 fetuses with gallbladder echogenic content identified. Seventy-two fetuses were found to have biliary sludge; thirty cases had a single hyperechogenic focus, and one hundred fetuses had multiple foci in the gallbladder. There were 16 cases of distal shadowing, 37 fetuses with comet tail and twinkling, and 26 cases with no acoustic artifacts. Nine cases of spontaneous resolution before birth have been documented; nine fetuses exhibited no echogenic content at birth, and 138 cases of resolution of echogenic content within the first year of life have been described. Typically, the condition resolves spontaneously during the postnatal period. After adequately reassuring the parents, the patients should be monitored for spontaneous resolution; medical or surgical intervention is not indicated. Asymptomatic patients can be managed with a wait-and-see strategy.

Impact of Follicle Stimulating Hormone Receptor (FSHR) Polymorphism on the Efficiency of Co-Treatment with Growth Hormone in a Group of Infertile Women from Romania.

"Poor responders" (PR) are an important category of infertile women who experience a modest response to controlled ovarian stimulation. In this study, we evaluated response to growth hormone (GH) administration among PR patient subtypes stratified by follicle stimulation hormone receptor (FSHR) polymorphism (c.2039A > G p.Asn680Ser). We conducted a cohort study of 125 women with poor ovarian response, 58 of whom received GH in addition to the standard treatment, and 67 of whom received the standard treatment only. The Ala307Thr polymorphism genotypes were analyzed using a polymerase chain reaction-restriction fragment length polymorphism method, and the FSHR gene polymorphism was analyzed using a predesigned TaqMan SNP Genotyping Assay (rs6166). A comparative analysis detected statistically significant differences in mean mature follicles (p = 0.0002), metaphase-II oocytes (p = 0.0005), progesterone levels (p = 0.0036), and IGF levels (follicle IGF1, p = 0.0004) between GH-treated and non-GH-treated participants with the FSHR (Ser/Ser) polymorphism. However, the differences were modest among participants with the other two FSHR polymorphisms (Ser/Asn and Asn/Asn). The subcategory of patients with the FSHR Asn680Ser (Ser/Ser) polymorphism showed a stronger response when GH was added to the IVF protocol.

Umbilical Cord Biometry and Fetal Abdominal Skinfold Assessment as Potential Biomarkers for Fetal Macrosomia in a Gestational Diabetes Romanian Cohort.

Backgroundand Objectives: Gestational diabetes mellitus (GDM) is a pregnancy-associated pathology commonly resulting in macrosomic fetuses, a known culprit of obstetric complications. We aimed to evaluate the potential of umbilical cord biometry and fetal abdominal skinfold assessment as screening tools for fetal macrosomia in gestational diabetes mellitus pregnant women. Materials and methods: This was a prospective case−control study conducted on pregnant patients presenting at 24−28 weeks of gestation in a tertiary-level maternity hospital in Northern Romania. Fetal biometry, fetal weight estimation, umbilical cord area and circumference, areas of the umbilical vein and arteries, Wharton jelly (WJ) area and abdominal fold thickness measurements were performed. Results: A total of 51 patients were enrolled in the study, 26 patients in the GDM group and 25 patients in the non-GDM group. There was no evidence in favor of umbilical cord area and WJ amount assessments as predictors of fetal macrosomia (p > 0.05). However, there was a statistically significant difference in the abdominal skinfold measurement during the second trimester between macrosomic and normal-weight newborns in the GDM patient group (p = 0.016). The second-trimester abdominal circumference was statistically significantly correlated with fetal macrosomia at term in the GDM patient group with a p value of 0.003, as well as when considering the global prevalence of macrosomia in the studied populations, 0.001, when considering both populations. Conclusions: The measurements of cord and WJ could not be established as predictors of fetal macrosomia in our study populations, nor differentiate between pregnancies with and without GDM. Abdominal skinfold measurement and abdominal circumference measured during the second trimester may be important markers of fetal metabolic status in pregnancies complicated by GDM.

SERS liquid biopsy in breast cancer. What can we learn from SERS on serum and urine?

SERS analysis of biofluids, coupled with classification algorithms, has recently emerged as a candidate for point-of-care medical diagnosis. Nonetheless, despite the impressive results reported in the literature, there are still gaps in our knowledge of the biochemical information provided by the SERS analysis of biofluids. Therefore, by a critical assignment of the SERS bands, our work aims to provide a systematic analysis of the molecular information that can be achieved from the SERS analysis of serum and urine obtained from breast cancer patients and controls. Further, we compared the relative performance of five different machine learning algorithms for breast cancer and control samples classification based on the serum and urine SERS datasets, and found comparable classification accuracies in the range of 61-89%. This result is not surprising since both biofluids show striking similarities in their SERS spectra providing similar metabolic information, related to purine metabolites. Lastly, by carefully comparing the two datasets (i.e., serum and urine) we show that it is possible to link the misclassified samples to specific metabolic imbalances, such as carotenoid levels, or variations in the creatinine concentration.

The Evaluation of the Four-Chamber Cardiac Dissection Method of the Fetal Heart as an Alternative to Conventional Inflow-Outflow Dissection in Small Gestational-Age Fetuses.

The examination of very small fetal hearts requires special equipment and a specialist that are not available in many general pathology laboratories. Compared to conventional examination, the four-chamber cardiac dissection (4CCD) method can be performed by any pathologist using instruments generally available in pathology services. The aim of this study is to evaluate the efficiency of the 4CCD method in the examination of small fetal hearts using post-mortem magnetic resonance imaging (pm-MRI) at 7T as the standard. Twelve fetuses with gestational ages between 13 and 19 weeks have been included in this study. All fetuses underwent pm-MRI examination prior to pathologic examination. The 4CCD method was used for the cardiac examination in all cases following the same guidelines for cardiac sectioning. The 4CCD was able to identify all cardiac anatomic structures as compared to pm-MRI at 7T, demonstrating a sensibility of 95.8% (95% CI, 94.5-95.8) and specificity of 100% (95% CI, 32.3-100). The overall accuracy in identifying cardiac anatomic structures was 95.8% (95% CI, 93.4-95.8). Additionally, the 4CCD method was able to detect cardiac anomalies with an overall diagnostic accuracy of 91% (95% CI, 85.8-94.2), sensibility of 67.6% (95% CI, 54.5-75.3), and specificity of 97% (95% CI, 93.7-99) as compared to pm-MRI at 7T. The four-chamber view dissection method can be considered as an alternative to the conventional inflow-outflow dissection method in selected cases.

First trimester sonographic diagnosis of limb-body wall defect associating both cephalic and thoraco-abdominal defects - a case report and literature update.

We present the first trimester prenatal ultrasonography and pathological assessment of a case diagnosed with limb-body wall complex (LBWC) presenting both exenchephaly and a complex thoraco-abdominal wall defect. Ectopia cordis is demonstrated with a movie showing the heart beating outside the body of the fetus after its expulsion. Also, we discuss the pathogenesis and possible etiology of LBWC and associated malformations and we provide an update of the literature of this very rare anomaly.

Diagnostic value of virtual autopsy using pm-MRI at 3T on malformed second trimester fetuses vs classic autopsy.

OBJECTIVE: To determine the diagnostic value of virtual autopsy using post mortem-MRI (pm-MRI) at 3Tesla (T) compared to classic autopsy for the confirmation of fetal structural anomalies and secondly to establish which cases of termination of pregnancy would benefit mostly from a virtual autopsy. METHODS: In each of 32 fetuses included in the study, 32 anatomical structures were assessed, after termination of pregnancy in the second trimester. All cases were evaluated by prenatal ultrasonography, virtual autopsy and classic autopsy, and then divided into four groups: Cerebral Group, Cardiac Group, Renal Group and Other Group (miscellaneous group). The concordance of virtual autopsy with classic autopsy was calculated overall and for each group and each structural item. Also, the concordance between the two methods was assessed using a diagnostic error score (DgE_score), calculated as the absolute value of the difference between the number of malformations detected by classic autopsy per case (CA score) and the number of malformations detected at virtual autopsy per case (VA score). RESULTS: Overall virtual autopsy demonstrated a diagnostic sensitivity (Se) compared to classic autopsy of 67.33% [95% CI 57.28-76.33], with a specificity (Sp) of 98.37% [95% CI 97.33-99.09], a positive predictive value (PPV) of 81.93% [95% CI 71.95-89.52], a negative predictive value (NPV) of 96.49% [95% CI 95.11-97.57] achieving a diagnostic accuracy of 95.31% [95% CI 93.83-96.52]. Overall, no statistic significant correlation was demonstrated between DgE_score and the gestational age of the fetuses or between DgE_score and the weight of the fetuses, but a significant correlation was revealed between the virtual autopsy and classic autopsy score. The diagnostic utility of virtual autopsy using pm-MRI at 3 T as compared to classic autopsy for each category of termination of pregnancy revealed in the Cerebral Group a Se of 80.00% [95% CI 28.36-99.49], with a 96.30% [95% CI 81.03-99.91], a PPV of 80.00% [95% CI 35.75-96.64] a NPV of 96.30% [95% CI 81.81-99.34], with a diagnostic accuracy of 93.75% [95% CI 79.19% to 99.23] and a Cohen's Kappa coefficient of 0.76 [95% CI 0.4494-1.0765]; in the Renal Group a Se and Sp of 100%, but in the Cardiac Group the Se was only 60.00% [95% CI 26.24-87.84], Sp 75% [95% CI 34.91-96.81], the PPV 75.00% [95% CI 44.92-91.69], NPV 60% [95% CI 38.87-77.96], with a diagnostic accuracy of 66.67% [95% CI 40.99-86.66] and a Cohen's Kappa coefficient of 0.32 [95% CI -0.07-0.76]. CONCLUSIONS: The results support virtual autopsy using pm-MRI at 3T as a reliable alternative to classic autopsy for the non-forensic analysis of second trimester fetuses. Analyzing the diagnostic utility of virtual autopsy using pm-MRI at 3 T for the confirmation of prenatal ultrasound findings in second trimester fetuses as compared to classic autopsy, the best results were obtained in the Cerebral and Renal Group. Reserved results were found in the Cardiac Group. Therefore, for the pregnancies with termination of pregnancy for cerebral or renal abnormalities, virtual autopsy by pm-MRI at 3T can be taken into consideration as a first-line investigation to confirm the prenatal findings.

Predictive role of altered leptin, adiponectin and 3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid secretion in gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy, leading to considerable maternal and fetal risks. The main aim of this study was to determine the predictive value of the levels of adiponectin (AN), leptin (L) and CMPF (3-carboxy-4-methyl-5-propyl-2-furanpropanoic acid) in the development of GDM. We conducted a prospective longitudinal study on 68 pregnant women that were not at risk of developing GDM, in whom we determined AN, L, CMPF levels at 11-13 weeks +6 days of pregnancy during the first trimester screening. Twenty-one of all the patients included in the study developed GDM during pregnancy. Oral glucose tolerance test (OGTT)/75 g was performed at 24-28 weeks of gestation. L levels were significantly higher in patients who developed GDM than in those who did not develop diabetes (P<0.001). The AN/L ratio was significantly lower in patients with GDM (P=0.03). AN and CMPF levels were not associated with GDM. The probability of developing gestational diabetes was higher in patients with L levels above the L cut-off value of 16 ng/ml [area under the curve (AUC), 0.775; 95% confidence interval (CI) 0.658-0.867], sensitivity 100% (95% CI 83.9-100), specificity 48.9% (95% CI 34.1-63.9) (P<0.001). Advanced maternal age and higher L levels were found to be predictive factors [odds ratio (OR)=1.16 and OR=1.06, respectively] independently associated with gestational diabetes. In as far as general factors are concerned, the patient BMI (body mass index) at the beginning of the pregnancy and smoking were found to be the main risk factors for the onset of GDM. This study showed that elevated L levels are a strong predictor of GDM, while AN and CMPF levels are not, as they failed to show a significant association.

Fetal Ovarian Cysts: Prenatal Diagnosis Using Ultrasound and MRI, Management and Postnatal Outcome-Our Centers Experience.

The present study provides our clinical experience regarding the imaging diagnosis, management and postnatal outcome of neonates prenatally suspected of having developed ovarian cysts. This multicenter observational study included patients diagnosed prenatally with fetal ovarian cysts and follow-up in the postnatal period. Descriptive statistics were used to render the information regarding the prenatal imaging aspect of the fetal pelvic masses using ultrasound and/or MRI, prenatal surveillance and postnatal neonate's immediate outcome, indications leading to surgery and pathologic aspect. The inclusion criteria were fulfilled by 21 patients. The mean gestational age at the time of initial diagnosis was 31.28 weeks of gestation (WG). Only five out of 21 cysts regressed completely during pregnancy without postnatal complications. In addition, 11 out of 21 infant's required surgical treatment in the first two weeks after birth, mainly for ovarian torsion. Five out of 21 neonates were referred to postnatal follow-up clinically and by ultrasound, but three out of five cases required emergency surgical treatment for acute complications. Ultrasound plays a major role in the diagnostic of fetal ovarian cyst. From our experience, MRI does not bring supplementary data or change the management. Spontaneous resolution of fetal ovarian cysts is to be expected but the ovarian mass could lead to serious complications, if resolution does not occur in due time.

Fetal cardiovascular alterations in twin-to-twin transfusion syndrome.

Twin-to-twin transfusion syndrome (TTTS) is the consequence of vascular anastomoses of the shared placenta of monochorionic twin pregnancies. Both circulating inter-twin blood flow and vasoactive mediators imbalance cause hypovolemia in the donor and hypervolemia in the recipient fetus. If left untreated, TTTS has a high perinatal mortality rate and adverse long-term outcomes mainly cardiovascular and neurological. The recipient has cardiovascular changes including atrioventricular valve regurgitation, diastolic dysfunction and pulmonary stenosis/atresia. The maladaptive response to vascular changes determines a constant decreased blood flow in the donor that permanently modifies the arterial structure leading to postnatal alterations in the vascular system. Fetoscopic LASER surgery of placental vascular anastomoses may disrupt the underlying pathophysiology and improves cardiovascular function with normalization of systolic and diastolic function within weeks after treatment. The impact of cardiovascular changes is relevant for the safety of the management of a TTTS case. The improvement of the perinatal survival after intrauterine surgery leads to viable infants with the longer-term sequelae. Therefore accurate quantification of cardiovascular involvement is essential for clinicians for pregnancy management but also for patient counseling about the potential treatment options the outcome.

Potential clinical benefits and limitations of fetal virtopsy using high-field MRI at 7 Tesla versus stereomicroscopic autopsy to assess first trimester fetuses.

OBJECTIVE: The aim of this study was to establish the diagnostic accuracy of high-field magnetic resonance imaging (MRI) at 7 Tesla (T) compared with that of stereomicroscopic autopsy for assessing first trimester fetuses. METHODS: Nine consecutive cases of first trimester fetuses resulting from spontaneous and therapeutic pregnancy termination were considered. The cases were divided into two groups according to gestational age: the Embryo Group with cases of nine to 10 gestational weeks (GWs) and the Fetus Group with cases of 13 GWs. The first group was scanned using three-dimensional fast imaging with steady state precession (3D FISP), and the second group was scanned using a two-dimensional (2D) turbo spin-echo high-resolution T2-weighted imaging (T2 WI) protocol. A radiologist and two embryologists interpreted the images. All cases were evaluated by invasive autopsy, with pathologist blinded to the imaging results. In total, the database included 270 items for evaluation (9 cases × 30 structures/case). RESULTS: The global agreement between fetal high-field virtopsy and microscopic or stereomicroscopic autopsy was evaluated using 225 evaluation items visible by both methods. Overall, using microscopic examination and stereomicroscopic autopsy as the gold standard, fetal high-field virtopsy had a sensitivity of 94.6% [95% CI, 87.2-98.3] and a specificity of 97.6% [95% CI, 95-98.8]. The positive predictive value (PPV) was 93% [95% CI, 85.7-96.6], and the negative predictive value (NPV) was 98.2% [95% CI, 95.7-99.4]. Cohen kappa coefficient of agreement was k = 0.92 [95% CI, 0.82-0.97], and the McNemar test showed p = 1.00. CONCLUSIONS: Virtual autopsy using high-field MRI at 7 T can be considered a safe alternative approach to stereomicroscopic autopsy for the assessment of fetal structural anomalies at the end of the first trimester of pregnancy.

The decrease of some serum free amino acids can predict breast cancer diagnosis and progression.

This study was targeted on a metabolomic approach to compare the blood serum free amino acid profiles and concentration of confirmed breast cancer (stages I-III) patients to healthy controls in order to establish reliable biomarkers of early detection and prediction of breast cancer. The ultra-high-performance liquid chromatography coupled with mass spectrometry using positive ionization electrospray was applied for the picoline-derivatized serum free amino acids using the EZ:faastTM kit. Multivariate statistical analysis principal component analysis, partial least squares discrimination analysis and univariate analysis were applied in order to discriminate between patient groups and putative amino acid biomarkers for breast cancer. A significant decrease of amino acid concentrations between the breast cancer group and the control group was positively correlated with breast cancer progression. Arginine, Alanine, Isoleucine, Tyrosine and Tryptophan were identified as being good potential discriminants (AUROC ≥0.85) and suitable candidates to diagnose and predict the breast cancer progression.

Blue nevus-like melanoma of the uterine cervix. Case report and review of the literature.

We present the clinical and pathological aspects of a patient diagnosed with a very rare tumor, a blue nevus-like melanoma of the uterine cervix. The patient turned to our Service for a second opinion regarding a cervical polyp causing vaginal bleeding, polyp which has been excised in another Hospital and interpreted initially as a pleomorphic sarcoma. In the presentation, we emphasize upon the stages of solving a difficult diagnosis, pathological description and treatment of these rare, aggressive tumors with poor prognosis, which represent the fundamental precondition in order to formulate the best therapeutic strategy.

Multidisciplinary approach of assessing malformed fetuses exemplified in a rare case of pentalogy of Cantrell associated with craniorachischisis, pulmonary extrophy and right-sided aortic arch with aberrant brachiocephalic artery.

We present the imagistic and pathological assessment of a unique case of complete pentalogy of Cantrell associated with craniorachischisis, pulmonary extrophy and right-sided aortic arch with aberrant brachiocephalic artery. For this particular case, the complete and correct diagnosis required a post-mortem imagistic high-resolution magnetic resonance imaging (MRI) at 7 T and detailed stereomicroscopic autopsy. Also, we discussed the pathogenesis and possible etiology of pentalogy of Cantrell and the associated malformations of the case presented.