Longer time to testosterone recovery impacts favorably on outcomes for prostate cancer following androgen deprivation and radiotherapy.

PURPOSE: To evaluate the impact of sustained hypogonadism after androgen deprivation therapy (ADT) associated with radiotherapy in prostate cancer (PCa) patients with biochemical relapse-free survival (bRFS). METHODS: A retrospective cohort analysis of 213 consecutive PCa patients referred for radiotherapy plus ADT was carried out. Follow-up times including time to testosterone recovery (TTR) and bRFS were calculated from the end of ADT. Univariate and multivariate Cox regression analyses predicting bRFS were used. The optimal cutoffs for TTR and duration of ADT were determined using the maximally selected rank statistics (MSRS). RESULTS: After a median follow-up of 104 months, 18 patients relapsed among those who had recovered testosterone levels and 9 among those who did not. Median ADT duration was 36 months. The optimal cutoff for TTR was determined using MSRS. TTR >48 months was significantly associated with better bRFS (logrank, p < 0.0027). Five-year bRFS was 100% for >48 months vs. 85% for <48 months. TTR was the only significant variable for bRFS in multivariate Cox analysis. CONCLUSION: Our data show an association between longer TTR and bRFS values among PCa patients treated with ADT.

Prenatal Management and Perinatal Outcome in a Large Series of Hydrops Fetalis.

INTRODUCTION: Nonimmune hydrops fetalis (NIHF) is the most frequent etiology of hydrops fetalis (HF), accounting for around 95% of cases. It associates high perinatal mortality and morbidity rates. The aim of the study was, first, to investigate etiology, prenatal management, and perinatal outcome in a large single-center series of HF; second, to identify prenatal prognostic factors with impact on perinatal outcome. MATERIALS AND METHODS: Observational retrospective study of 80 HF diagnosed or referred to a single tertiary center between 2012 and 2021. Clinical characteristics, etiology, prenatal management, and perinatal outcome were recorded. Adverse perinatal outcome was defined as intrauterine fetal death (IUFD), early neonatal death (first 7 days of life) and late neonatal death (between 7 and 28 days). RESULTS: Seventy-six of the 80 cases (95%) were NIHF, main etiology being genetic disorders (28/76; 36.8%). A total of 26 women (32.5%) opted for termination of pregnancy, all of them in the NIHF group. IUFD occurred in 24 of 54 patients (44.4%) who decided to continue the pregnancy. Intrauterine treatment was performed in 29 cases (53.7%). There were 30 newborns (55.6%). Adverse perinatal outcome rate was 53.7% (29/54), significantly higher in those diagnosed <20 weeks of gestation (82.4% < 20 weeks vs. 40.5% ≥ 20 weeks; p = 0.004). Survival rate was higher when fetal therapy was performed compared to the expectantly managed group (58.6% vs. 32%; p = 0.05). Intrauterine blood transfusion and thoraco-amniotic shunt were the procedures that achieved the highest survival rates (88.9% and 100%, respectively, p = 0.003). CONCLUSION: NIHF represented 95% of HF with genetic disorders as the main etiology. Most of them were diagnosed before 20 weeks of gestation, with worse prognosis than cases detected later in gestation. Rates of TOP, IUFD, and early neonatal death were higher in NIHF. Intrauterine therapy, when indicated, improved the perinatal outcome.

LDR brachytherapy offers superior tumor control to single-fraction HDR prostate brachytherapy: A prospective study.

PURPOSE: To compare the clinical outcomes of single-fraction high-dose-rate (HDR) brachytherapy and single-fraction low-dose-rate (LDR) brachytherapy as the sole treatment for primary prostate cancer. MATERIAL AND METHODS: A quasi-randomized study that allocated, from March 2008 to February 2012, 129 low and intermediate risk prostate cancer patients to one single-fraction HDR of 19 Gy (61 patients) or to a 145 Gy 125 I LDR permanent implant (68 patients. Biochemical relapse-free survival (bRFS) and overall survival (OS) were compared using the Kaplan-Meier method and Cox regression analysis. RESULTS: After a median follow-up of 72 months in the HDR group, 26 patients relapsed, and after a median follow-up of 84 months in the LDR group, 7 patients relapsed (p < 0.0001). The 5-year bRFS was significantly better for the LDR group than for the HDR group (93.7% and 61.1%, respectively) (p < 0.0001). The 5-year OS also was significantly better in the LDR group (95.5% vs. 89.9%) (p = 0.0436). CONCLUSIONS: Permanent LDR prostate implant brachytherapy offers better clinical outcomes than single-fraction HDR for prostate cancer.

Single fetal demise in monochorionic twins: How to predict cerebral injury in the survivor co-twin?

INTRODUCTION: The aims of the study were to evaluate perinatal outcome in monochorionic (MC) twins complicated with single intrauterine fetal death, spontaneously vs after fetal therapy, and to assess antenatal events that increase the risk of cerebral injury. MATERIAL AND METHODS: Historical cohort study of MC pregnancies with single intrauterine fetal death diagnosed or referred to a tertiary referral hospital (2012-2020). Adverse perinatal outcome included termination of pregnancy, perinatal death, abnormal fetal or neonatal neuroimaging and abnormal neurological development. RESULTS: A total of 68 MC pregnancies with single intrauterine fetal death after 14 weeks of gestation were included. Sixty-five (95.6%) occurred in complicated MC pregnancies (twin to twin transfusion syndrome: 35/68 [51.5%]; discordant malformation: 13/68 [19.1%], selective intrauterine growth restriction: 10/68 [14.7%], twin reversed arterial perfusion sequence: 5/68 [7.3%] and cord entanglement in monoamniotic twins: 2/68 [2.94%]). In 52 cases (76.5%) single intrauterine fetal demise occurred after fetal therapy and in 16 (23.5%) occurred spontaneously. Cerebral damage included 14/68 cases (20.6%): 6/68 cases (8.82%) were prenatal lesions and 8/68 cases (11.8%) were postnatal. Risk of cerebral damage tended to be higher in the spontaneous death group (6/16, 37.5%) compared to the therapy-group (8/52, 15.38%) (p = 0.07). The risk increased with gestational age at intrauterine death (OR 1.21, 95% CI: 1.04-1.41, p = 0.014) and was higher in those surviving co-twins who developed anemia (OR 9.27, 95% CI: 1.50-57.12, p = 0.016). Pregnancies complicated with selective intrauterine growth restriction tended to be at higher risk for neurological damage (OR 2.85, 95% CI: 0.68-11.85, p = 0.15). Preterm birth rate (<37 weeks of pregnancy) was 61.7% (37/60). Seven of eight postnatal cerebral lesions (87.5%) were related to extreme prematurity. Overall perinatal survival rate was 88.3% (57/68) and 7% (4/57) of children had an abnormal neurological outcome. CONCLUSIONS: Risk of cerebral damage in single intrauterine fetal death is especially high when it occurs spontaneously. Gestational age at single intrauterine fetal death, selective intrauterine growth restriction and anemia of the surviving co-twin are the main predictors for prenatal lesions and might be useful in parent counseling. Abnormal postnatal neurological outcome is closely related to extreme prematurity.

Longitudinal changes in fetal head biometry and fetoplacental circulation in fetuses with congenital heart defects.

INTRODUCTION: Objectives were to analyze changes in fetal cephalic biometry and fetoplacental circulation throughout pregnancy in fetuses with congenital heart defects. MATERIAL AND METHODS: Prospective study conducted on three university tertiary referral hospitals. Fetuses with the diagnosis of isolated congenital heart defects attending between 2014 and 2018 were included. Congenital heart defects were divided into two groups according to the oxygen supply to the central nervous system: group I (expected low placental blood content and low oxygen delivery to the brain) and group II (expected intermediate and high placental blood content). Fetal biometry and Doppler parameters were collected between 25-30 weeks of gestation and 34-40 weeks of gestation and transformed into Z scores. The results were compared with healthy controls. Finally, general linear modeling was performed to analyze repeated measurements. RESULTS: In all, 71 fetuses met the inclusion criteria. Fetuses with congenital heart defects had significantly smaller head (biparietal diameter [p < 0.001], head circumference [p = 0.001]) and abdominal circumference (p < 0.001), and lower estimated fetal weight (p < 0.001) than controls. When analyzing according to congenital heart defects type, head size was significantly smaller in group I compared with group II (p = 0.04). Regarding Doppler parameters, fetuses with congenital heart defects showed higher umbilical artery pulsatility index (p < 0.001) and lower cerebroplacental ratio (p = 0.044) than controls. In group I, umbilical artery pulsatility index was above the 95th centile in 15.4% of fetuses compared with 6.7% in group II and 1.9% in controls (p < 0.001); moreover, middle cerebral artery pulsatility index was below the 5th centile in 5.4% of group I fetuses compared with 0% in group II and 1.2% in controls (p = 0.011). General linear model for two measurements showed significant longitudinal changes in biometric parameters. Growth rate of fetal head through pregnancy (head circumference Z score) was lower in fetuses with congenital heart defects compared with controls (p = 0.043). In group I, the head circumference Z score longitudinal decrease was significantly higher than in group II (p < 0.001). CONCLUSIONS: Fetuses with congenital heart defects are at risk of smaller head size and Doppler changes. Growth rate of fetal head throughout pregnancy is also affected. These findings are mainly associated with cardiac defects with expected low oxygen supply to the central nervous system.

Utility of Three-Dimensional Ultrasonography to Assess the Position of Essure Tubal Occlusion Device and Its Complications.

BACKGROUND: To determine the utility of three-dimensional (3D) sonography to control the position of hysteroscopic sterilizing device compared to hysterosalpingography (HSG). METHODS: A prospective observational study was carried out on 139 patients who underwent hysteroscopic tubal occlusion method between February 2012 and May 2013. Patients underwent 3D ultrasound scan to control device positioning, and they also underwent HSG as an additional control method. Comparison between both methods was carried out. RESULTS: In all, 17 (12.2%) devices were inserted due to a hydrosalpinx and 122 (87.8%) due to sterilization purposes. In 124 (89.2%) cases, sonography correlated completely to HSG findings. Sonography-positive predictive value was 89.5% to detect correct device positioning. Just 4 (2.8%) patients did not present complete tubal occlusion 3 months after device insertion; one of them presented device expulsion, 2 of them presented previous hydrosalpinx (tubal occlusion was confirmed after 6 months), and the last case rejected to undergo further controls but device seem to be effective. CONCLUSIONS: 3D sonography seems to be effective for the control of sterilization device positioning, but it also detects insertion complications and device migration. Further studies would be required to assess our findings and the role of sonography in case of hydrosalpinx.

[Giant sacrococcygeal teratoma in twin pregnancy]. / Teratoma sacrococcígeo gigante en una gestación gemelar.

UNLABELLED: Sacrococcygeal teratoma tumors are more frequent in infants alive. It is characterized by its benign histology in the majority of the cases diagnosed prenatally; it is necessary to follow narrow to prevent neonatal complications that can lead to urinary tract complications and fecal, high-output heart failure, hydrops and, in extreme cases, the death of the fetus. CASE REPORT: Primigravidae 30 years old, with gestation twins, bicorial, biamniotic in the first trimester of pregnancy to one of the twins is diagnosed sacrococcygeus teratoma giant, with favorable monitoring in the maternal-fetal Medicine Unit of the University Hospital of La Paz in Madrid, and with postnatal resection surgery successful. We review the diagnostic procedures and treatment of this tumor in unique and twin gestations.

Opportunities for nanomaterials in enzyme therapy.

In recent years, enzyme therapy strategies have rapidly evolved to catalyze essential biochemical reactions with therapeutic potential. These approaches hold particular promise in addressing rare genetic disorders, cancer treatment, neurodegenerative conditions, wound healing, inflammation management, and infectious disease control, among others. There are several primary reasons for the utilization of enzymes as therapeutics: their substrate specificity, their biological compatibility, and their ability to generate a high number of product molecules per enzyme unit. These features have encouraged their application in enzyme replacement therapy where the enzyme serves as the therapeutic agent to rectify abnormal metabolic and physiological processes, enzyme prodrug therapy where the enzyme initiates a clinical effect by activating prodrugs, and enzyme dynamic or starving therapy where the enzyme acts upon host substrate molecules. Currently, there are >20 commercialized products based on therapeutic enzymes, but approval rates are considerably lower than other biologicals. This has stimulated nanobiotechnology in the last years to develop nanoparticle-based solutions that integrate therapeutic enzymes. This approach aims to enhance stability, prevent rapid clearance, reduce immunogenicity, and even enable spatio-temporal activation of the therapeutic catalyst. This comprehensive review delves into emerging trends in the application of therapeutic enzymes, with a particular emphasis on the synergistic opportunities presented by incorporating enzymes into nanomaterials. Such integration holds the promise of enhancing existing therapies or even paving the way for innovative nanotherapeutic approaches.

Harnessing the power of thermosensitive liposomes with gold nanoprisms and silica for controlled drug delivery in combined chemotherapy and phototherapy.

In recent years, the scientific community has tried to address the treatment of complex diseases such as cancer in a more appropriate and promising way. Regarding this and benefiting from the unique optical properties of gold nanoprisms (AuNPRs), the physicochemical properties of thermosensitive liposomes (TSLs), and the tunable drug encapsulation and release properties of silica nanoparticles (BioSi@NPs), this study has developed two nanoformulations. These nanoformulations have the potential to integrate chemotherapy and photothermal therapy within a single entity. Once their components were synthesized and characterized separately, two strategies were taken in order to develop these multifunctional nanoformulations: (1) covalent binding of AuNPRs to TSLs and (2) co-encapsulation of both components within BioSi@NPs, without modifying the optical and physicochemical properties of AuNPRs and TSLs. Finally, the suitability of both nanoformulations to carry and release hydrophilic drugs when triggered by a 1064 nm NIR laser has been explored by using the fluorescent probe 5(6)-carboxyfluorescein (CF) as a hydrophilic drug model. Different laser power and time of exposure were also tested evidencing that hydrophilic drugs were only released from TSLs in the presence of AuNPRs and that the drug release profile was dependent on the type of nanoformulation and irradiation conditions used. In conclusion, these multifunctional nanoformulations exhibit promising potential for controlled drug delivery in combined chemotherapy and phototherapy, with the capability to precisely control the release kinetics based on specific therapeutic needs.

The continuing enigma of the fetal echogenic intracardiac focus in prenatal ultrasound.

PURPOSE OF REVIEW: The present article aims to review recent literature about intracardiac echogenic foci (ICEFs), with special emphasis in potential causes, relationships with aneuploidy and cardiac function. RECENT FINDINGS: The presence of an ICEF may be considered as a soft marker that may be of interest only in high-risk populations for chromosomal abnormalities. In cases of isolated ICEF in euploid fetuses there is not evidence of an altered cardiac function and a detailed echocardiogram is not recommended as long as the second trimester scan is normal. Cases of fetal myocardial diffuse or multiple calcifications may be related to inflammatory and hypoxic changes in fetal heart, but the relationships between these conditions and isolated ICEF remain unclear. SUMMARY: The origin of ICEF remains unclear. It is considered a normal developmental variant, but either inflammatory or hypoxic processes could be involved in its appearance. In low-risk populations for aneuploidy, the presence of an ICEF is not an indication for invasive procedures. In high-risk populations this depends on the previous calculated risk. In euploid fetuses, cardiac function is not significantly altered but further studies in specific populations may be justified. Fetuses with diffuse myocardial calcification or multiple foci may need further investigations.

(New) antenatal ultrasound signs of fetal junctional epidermolysis bullosa: A case report and systematic review of literature.

Epidermolysis bullosa is a rare hereditary autosomal disease that is included in the heterogeneous group of genodermatosis. It is characterized by skin and mucous membranes fragility and denudation, and it can be associated with pyloric atresia. Prognosis is often poor, and death can occur in neonatal period due to severe sepsis. We present a case of fetal junctional epidermolysis bullosa in a consanguineous couple, highly suggested by previous obstetric history and several antenatal ultrasound signs, such as polyhydramnios, gastric enlargment, the "snowflake sign", abnormal external ears, signs of skin desquamation, lower limbs anomalies and chorioamniotic membrane separation. We describe a marked perioral hipoecogenicity as a novel sign of skin-mucous denudation, which could be helpful for future diagnosis. A review of literature, focused specifically on the antenatal sonography role, is also reported. Prenatal ultrasound-based diagnosis of epidermolysis bullosa is difficult, especially in apparently low risk contexts, but may be possible.

Remote Activation of Enzyme Nanohybrids for Cancer Prodrug Therapy Controlled by Magnetic Heating.

Herein, we have developed nanohybrids (nHs) to remotely activate a therapeutic enzyme for its use in Directed Enzyme Prodrug Therapy (DEPT). The coencapsulation of magnetic nanoparticles (MNPs) with horseradish peroxidase (HRP) using biomimetic silica as an entrapment matrix was optimized to obtain nanosized hybrids (∼150 nm) for remote activation of the therapeutic enzyme. HRP converts indole-3-acetic acid (3IAA) into peroxylated radicals, whereas MNPs respond to alternating magnetic fields (AMFs) becoming local hotspots. The AMF application triggered an increase in the bioconversion rate of HRP matching the activity displayed at the optimal temperature of the nHs (Topt = 50 °C) without altering the temperature of the reaction media. This showed that enzyme nanoactuation is possible with MNPs even if they are not covalently bound. After an extensive physicochemical/magnetic characterization, the spatial location of each component of the nH was deciphered, and an insulating role of the silica matrix was suggested as critical for introducing remote control over HRP. In vitro assays, using a human pancreatic cancer cell line (MIA PaCa-2), showed that only upon exposure to AMF and in the presence of the prodrug, the enzyme-loaded nHs triggered cell death. Moreover, in vivo experiments showed higher reductions in the tumor volume growth in those animals treated with nHs in the presence of 3IAA when exposed to AMF. Thus, this work demonstrates the feasibility of developing a spatiotemporally controlled DEPT strategy to overcome unwanted off-target effects.

Photonic and magnetic materials for on-demand local drug delivery.

Nanomedicine has been considered a promising tool for biomedical research and clinical practice in the 21st century because of the great impact nanomaterials could have on human health. The generation of new smart nanomaterials, which enable time- and space-controlled drug delivery, improve the limitations of conventional treatments, such as non-specific targeting, poor biodistribution and permeability. These smart nanomaterials can respond to internal biological stimuli (pH, enzyme expression and redox potential) and/or external stimuli (such as temperature, ultrasound, magnetic field and light) to further the precision of therapies. To this end, photonic and magnetic nanoparticles, such as gold, silver and iron oxide, have been used to increase sensitivity and responsiveness to external stimuli. In this review, we aim to report the main and most recent systems that involve photonic or magnetic nanomaterials for external stimulus-responsive drug release. The uniqueness of this review lies in highlighting the versatility of integrating these materials within different carriers. This leads to enhanced performance in terms of in vitro and in vivo efficacy, stability and toxicity. We also point out the current regulatory challenges for the translation of these systems from the bench to the bedside, as well as the yet unresolved matter regarding the standardization of these materials.

Riboflavin-citrate conjugate multicore SPIONs with enhanced magnetic responses and cellular uptake in breast cancer cells.

Breast cancer accounts for up to 10% of the newly diagnosed cancer cases worldwide, making it the most common cancer found in women. The use of superparamagnetic iron oxide nanoparticles (SPIONs) has been beneficial in the advancement of contrast agents and magnetic hyperthermia (MH) for the diagnosis and treatment of cancers. To achieve delivery of SPIONs to cancer cells, surface functionalization with specific ligands are required. Riboflavin carrier protein (RCP) has been identified as an alternative target for breast cancer cells. Here, we report a novel riboflavin (Rf)-based ligand that provides SPIONs with enhanced colloidal stability and high uptake potential in breast cancer cells. This is achieved by synthesizing an Rf-citrate ligand. The ligand was tested in a multicore SPION system, and affinity to RCP was assessed by isothermal titration calorimetry which showed a specific, entropy-driven binding. MRI and MH responses of the coated Rf-SPIONs were tested to evaluate the suitability of this system as a theranostic platform. Finally, interaction of the Rf-SPIONs with breast cancer cells was evaluated by in vitro cellular uptake in MCF-7 breast cancer cells. The overall characterization of the Rf-SPIONs highlighted the excellent performance of this platform for theranostic applications in breast cancer.

Authentication of Atlantic salmon (Salmo salar) using real-time PCR.

A real-time PCR assay based on LNA TaqMan probe technology was developed for the detection and identification of Atlantic salmon (Salmo salar). Among the advantages it is worth highlighting simplicity, rapidity, highest potential for automation and minor risk of contamination of this technique. The TaqMan real-time PCR is the currently most suitable method for screening, allowing the detection of fraudulent or unintentional mislabelling of this species. The method can be applied to all kind of products, fresh, frozen and processed products, including those undergoing intensive processes of transformation. The developed methodology using specific primers-probe set was validated and further applied to 20 commercial samples labelled as salmon or S. salar in order to determinate if the species used for their manufacturing corresponded to this species. The methodology herein developed is useful to check the fulfilment of labelling regulations for seafood products, verify the correct traceability in commercial trade and for fisheries control.

Severe fetal anemia after umbilical cord occlusion leading to severe neurological injury in monochorionic twins.

We describe two cases of monochorionic twins with severe anemia in the surviving twin after cord occlusion. The first one was a case of discordant malformation (anencephalia) and the second one was a case of early severe selective intrauterine growth restriction type II in a dichorionic triamniotic triplet pregnancy. In both cases, the cord of the occluded fetus had a marginal insertion. Both of them presented hydrops 2 d after the occlusion, having measurements of the peak systolic velocity (PSV) of the middle cerebral artery (MCA) above 1.5 multiples of the median (MoM). In the first one intrauterine transfusion was performed with pretransfusion measurement of fetal hemoglobin of 3.3 g/dL. An extensive area of destruction of brain tissue at the right parietal-temporal-occipital level was diagnosed at 300 weeks. In the second one, expectant management was decided and a grade 3 intraventricular hemorrhage associated with moderate ventriculomegaly was detected at 22 weeks' gestation. We hypothesize that the surviving fetus after the occlusion can become bloodless and hypovolemic when its blood is poured into the placental and umbilical circulation of the occluded twin through the vascular anastomoses between them. It should not be assumed that cord occlusion removes the risk of transfusional brain injury in surviving-cotwins.

Management and perinatal outcome of selective intrauterine growth restriction in monochorionic pregnancies.

INTRODUCTION: Selective intrauterine growth restriction (sIUGR) is a complication observed in about 10-15% of all monochorionic (MC) pregnancies, causing a significant increase in perinatal mortality and morbidity. OBJECTIVE: To evaluate clinical management options and perinatal outcomes of sIUGR in MC pregnancies monitored in a single tertiary center. METHODS: A retrospective study was performed on 55-MC pregnancies with sIUGR between January 2012 and May 2018 at the Fetal Medicine Unit of La Paz Hospital. Cases were classified according to the umbilical artery (UA) Doppler pattern as type I (positive end-diastolic flow; n = 25), type II [persistently absent or reversed end-diastolic flow (AREDF); n = 5] and type III [intermittently absent or reversed end-diastolic flow (iAREDF); n = 25]. Types II and III were then merged together as severe sIUGR cases. Subsequently, two possible approaches were considered: expectant management (EM) with elective preterm delivery in case of fetal deterioration, or in-utero therapy via fetoscopic laser photocoagulation (FLP) of intertwin anastomosis or selective umbilical cord occlusion (CO) of the growth-restricted fetus. RESULTS: Gestational age (GA) at diagnosis was progressively lower with each type. Severe sIUGR cases delivered significantly earlier than type I, showing lower birth weights and higher intertwin biometric discordance. Unintended fetal demise occurred in 14% (6/25) of severe sIUGR pregnancies as opposed to 0% (0/19) in type I, p = .028. A significantly higher proportion of twins was admitted in NICU in severe cases when compared to type I [87% (33/38) versus 47% (18/38), p < .001]. In addition, brain damage at birth was also found to be more prevalent in this group [21% (8/38) versus 11% (4/38), p = .346], especially in the larger twin, when comparing any short-term neurological sequel [30% (7/23) versus 0% (0/19), p = .011] or specifically periventricular leukomalacia [PVL; 22% (5/23) versus 0% (0/19), p = .053]. Although the overall mortality rate was significantly higher in severe sIUGR that underwent CO instead of EM [58% (7/12) versus 11% (4/36), p = .002], NICU admissions were higher in the latter [94% (17/18) versus 40% (2/5), p = .021]. Neurological sequels at birth were similar in both groups [39% (7/18) versus 40% (2/5), p = 1.000], similarly when considering only the larger twin for any brain lesion [28% (5/18) versus 40% (2/5), p = .621] or just PVL [22% (4/18) versus 20% (1/5), p = 1.000]. CONCLUSION: Given the good prognosis of type I sIUGR, expectant management is the first approach to consider. However, due to the poorer clinical evolution of types II and III sIUGR, the decision-making is challenging and needs to be individualized depending on the UA Doppler pattern, GA at diagnosis, severity of growth restriction and biometric discordance, technical issues and parents' preferences.

Prenatal diagnosis of fetal skeletal dysplasias in a tertiary Hospital in Spain.

OBJECTIVE: To assess the diagnostic accuracy of prenatal ultrasound for detecting fetal skeletal dysplasias and to describe its role in orienting genetic studies. STUDY DESIGN: Observational study of pregnant women surveyed in our hospital, between 2011 and 2018, with fetal long bones below the 3rd centile (shortened long bones), either as an isolated finding or associated to other skeletal anomalies. We used a systematic protocol for the ultrasound evaluation and selection of those fetuses suspected of having a skeletal dysplasia. We report the demographics of these patients along with the sonographic follow-up of their fetuses, the genetic results and the outcome of the pregnancies and the newborn in the entire group and also compare data between the two sub-groups (isolated shortened long bones vs shortened long bones associated to other anomalies). RESULTS: A total of 81 pregnancies with a suspected fetal skeletal dysplasia were included, with a complete follow-up available in 75 cases, 22 with isolated shortened long bones and 53 cases that presented shortened long bones with other skeletal anomalies. In the shortened long bones sub-group, a total of five (23 %) were born healthy neonates, 10 (45 %) were small for gestational age or intrauterine growth restricted (one of them of genetic origin) and seven (32 %) had a skeletal dysplasia (6 of them with genetic diagnosis). Whilst among the 53 cases that presented with shortened long bones + other skeletal anomalies, three (6%) were healthy neonates, five (9%) were small for gestational age/intrauterine growth restricted (two of genetic origin) and 45 (85 %) had a skeletal dysplasia (19 genetically confirmed and 26 with a clinical diagnosis). These differences in frequencies between the two sub-groups were determined to be statistically significant (χ2: p = 0.02). CONCLUSION: Around one third of fetuses with isolated shortened long bones will have a skeletal dysplasia. If abnormal skeletal ultrasound findings are associated with shortened long bones, the risk for skeletal dysplasia is significantly increased (85 %). Prenatal systematic approach in a multidisciplinary unit is useful in the orientation of genetic studies.

[Sudden-onset bilateral hearing loss: case report]. / Sordera brusca bilateral: a propósito de un caso.

An ischaemic infarction of the anterior inferior cerebellar artery (AICA) is usually associated with vertigo, hearing loss, facial palsy, nystagmus, or truncal ataxia; it is often accompanied by other brainstem or cerebellar signs. Sudden- onset bilateral hearing loss without associated neurological symptoms is infrequent in the literature. We report a case of sudden bilateral hearing loss, later diagnosed as AICA infarction without other symptoms.

Patterns of fetal lung growth in fetuses with isolated left-sided congenital diaphragmatic hernia.

OBJECTIVE: To evaluate right lung growth pattern in fetuses with isolated left-sided congenital diaphragmatic hernia (iL-CDH) and to analyze the pattern according to postnatal outcome. METHODS: Lung-to-head ratio (LHR) and observed-to-expected LHR (O/E LHR) were obtained in 58 cases. Correlation and regression analysis for the total number of measurements, general linear models for those cases with a least three serial measurements and linear mixed effect models were used to analyze the influence of gestational age on the right lung size. Cases expectantly managed and those with fetal endoscopic tracheal occlusion were analyzed separately. RESULTS: LHR, but not O/E LHR, increased significantly with gestational age (GA) (r = 0.43, p = 0.003 and r = -0.13, p = 0.30, respectively). According to neonatal mortality, in those fetuses that died, LHR remained unchanged and O/E LHR decreased significantly with GA (r = 0.07, p = 0.65 and r = -0.37, p = 0.02, respectively). In those cases with at least three serial measurements, the same two patterns were found. Similarly, in cases with expectant management, surviving fetuses showed a significantly higher weekly increase in LHR (p = 0.01) and a trend to a lower weekly decrease in O/E LHR (p = 0.17) than in those that died. CONCLUSIONS: Patterns of right lung growth in iL-CDH differ according to postnatal survival. Serial measurements, but not a single one, might increase the prediction of neonatal death.