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- A Rare Case of En Bloc Endometrium SheddingPublication . Mamede, R; Costa, C; Djokovic, DThe human endometrium is a unique tissue capable of repeated degradation, loss and self-repair in response to fluctuating levels of sex steroids, in a tightly regulated process. It takes place hundreds of times in a woman’s lifetime, manifesting as vaginal expulsion of blood mixed with cellular debris for a period of several days. The aim of this work is to present a case of en bloc endometrial desquamation in a teenage patient using combined oral contraception. Several mechanisms are proposed, although further studies are needed to better understand this extremely rare phenomenon.
- Review of Piezoelectrical Materials Potentially Useful for Peripheral Nerve RepairPublication . Casal, D; Casimiro, MH; Ferreira, L; Leal, JP; Rodrigues, G; Lopes, R; Lino Moura, D; Gonçalves, L; Lago, J; Pais, D; Santos, PIt has increasingly been recognized that electrical currents play a pivotal role in cell migration and tissue repair, in a process named "galvanotaxis". In this review, we summarize the current evidence supporting the potential benefits of electric stimulation (ES) in the physiology of peripheral nerve repair (PNR). Moreover, we discuss the potential of piezoelectric materials in this context. The use of these materials has deserved great attention, as the movement of the body or of the external environment can be used to power internally the electrical properties of devices used for providing ES or acting as sensory receptors in artificial skin (e-skin). The fact that organic materials sustain spontaneous degradation inside the body means their piezoelectric effect is limited in duration. In the case of PNR, this is not necessarily problematic, as ES is only required during the regeneration period. Arguably, piezoelectric materials have the potential to revolutionize PNR with new biomedical devices that range from scaffolds and nerve-guiding conduits to sensory or efferent components of e-skin. However, much remains to be learned regarding piezoelectric materials, their use in manufacturing of biomedical devices, and their sterilization process, to fine-tune their safe, effective, and predictable in vivo application.
- The sFlt1/PlGF Ratio Predicts Faster Fetal Deterioration in Early Fetal Growth Restriction: a Historical Cohort StudyPublication . Palma dos Reis, C; Brás, S; Meneses, T; Cerdeira, A; Vatish, M; Martins, ATIntroduction: The velocity of fetal deterioration in fetal growth restriction is extremely variable, which makes monitoring and counseling very challenging. The soluble fms-like tyrosine kinase to placental growth factor (sFlt1/PlGF) ratio provides a readout of the vasoactive environment that correlates with preeclampsia and fetal growth restriction and that could be useful to predict fetal deterioration. Previous studies showed a correlation between higher sFlt1/PlGF ratios and lower gestational ages at birth, although it is unclear whether this is due to the increased incidence of preeclampsia. Our goal was to evaluate whether the sFlt1/PlGF ratio predicts faster fetal deterioration in early fetal growth restriction. Material and methods: This was a historical cohort study in a tertiary maternity hospital. Data from singleton pregnancies with early fetal growth restriction (diagnosed before 32 gestational weeks) confirmed after birth monitored between January 2016 and December 2020 were retrieved from clinical files. Cases of chromosomal/fetal abnormalities, infection and medical terminations of pregnancy were excluded. The sFlt1/PlGF ratio was acquired at diagnosis of early fetal growth restriction in our unit. The correlation of log10 sFlt1/PlGF with latency to delivery/fetal demise was assessed with linear, logistic (positive sFlt1/PlGF if >85) and Cox regression excluding deliveries for maternal conditions and controlling for preeclampsia, gestational age at time of ratio test, maternal age and smoking during pregnancy. Receiver-operating characteristic (ROC) analysis tested the performance of sFlt1/PlGF ratio in predicting delivery for fetal reasons in the following week. Results: 125 patients were included. Mean sFlt1/PlGF ratio was 91.2 (SD 148.7) and 28% of patients had a positive ratio. A higher log10 sFlt1/PlGF ratio predicted shorter latency for delivery/fetal demise in linear regression after controlling for confounders, β = -3.001, (-3.713 to -2.288). Logistic regression with ratio positivity confirmed these findings (latency for delivery 5.7 ± 3.32 weeks for ratios ≤85 vs 1.9 ± 1.52 weeks for ratios >85); β = -0.698 (-1.064 to -0.332). Adjusted Cox regression showed that a positive ratio confers a significantly positive hazard ratio (HR) for earlier delivery/fetal demise, HR 9.869 (5.061-19.243). ROC analysis showed an area under the curve of 0.847 (SE ± 0.06). Conclusions: sFlt1/PlGF ratio is correlated with faster fetal deterioration in early fetal growth restriction, independently of preeclampsia.
- Congenital Malformations of the Female Genital Tract: a Review of Available Classification SystemsPublication . Pereira Amaral, P; Ambrósio, P; Coelho, A; Condeço, R; Bello, A; Djokovic, DCongenital malformations of the female genital tract are being diagnosed more frequently due to advances in imaging techniques. A broad international consensus on their classification is still lacking. This paper aimed to comparatively summarize the most frequently and widely used, as well as the most recently developed classification systems of congenital female genital malformations. A non-systematic review was done through a search on major databases with the medical subject heading (MeSH) term ‘‘congenital abnormalities” in combination with ‘‘classification” and ‘‘female genitalia”. All available systems, including, among others, the American Fertility Society Classification (1988), the Acien and Acien classification (1992, 2004), the VCUAM system (2005), the European Society for Human Reproduction and Embryology - European Society for Gynecological Endoscopy classification (2013), the Congenital Uterine Malformation Experts (CUME) group recommendations, and the American Society for Reproductive Medicine Classification (2021) possess the advantages and disadvantages listed in this article. Regarding the most common situations, the criteria for differentiating physiologic arcuate and discrete partial septate uteri vary widely between classifications, while difficulties also persist with the rarer complex abnormalities that cannot be easily classified, contributing to a gap in clinical and research protocols. The main factor compromising any attempt to reach an ideal classification system is the lack of evidence-based data, justifying the need for comparative multicenter international randomized control trials in this field. Pending new research data and a broad international consensus, it seems essential for adequate patient orientation to describe each detected malformation in detail and to correlate it with the clinical presentation, regardless the type of classification used.
- Prevenção do Tromboembolismo Venoso na Gravidez, Parto e Pós-Parto: Norma de Orientação ClínicaPublication . Lima, J; Domingues, AP; Amaral, AC; Borges, A; Nogueira-Silva, C; Serrano, F; Marques, I; Pinto, L; Guimarães, M
- Fístula Vesicovaginal Associada a Ruptura UterinaPublication . Reis Correia, A; Ferreira, C; Bernardo, MJVesicovaginal fistula (VVF) is an obstetric complication rarely reported in developed countries. The occurrence of uterine rupture is a potentially catastrophic event, and its incidence is estimated in 1/1146 (0.07%) pregnancies.The main risk factorsfor its occurrence are: congenital uterine changes, multiparity, history of previous cesarean or myomectomy,fetal macrosomia and induced labor. Association between uterine rupture and bladder lesions has been rarely reported. The authors describe a case of a VVF associated with uterine rupture
- Repercussions of the COVID-19 Pandemic in the Emergency Department of Gynecology and Obstetrics at a Referral Hospital in PortugalPublication . Jovina Domingues, S; Ormonde, M; Miguel, A; Martins, A; Saavedra, I; Silva, MCObjective. COVID-19 has spread worldwide and Portugal decreed the State of Emergency on March 18th, 2020. During this period, the population was encouraged to stay at home. Still, there were no restrictions on access to health care. Therefore, we aimed to compare the major causes for attending the Obstetrics and Gynaecology Emergency Department (ED) from a referral centre (Maternidade Dr. Alfredo da Costa, in Lisbon). Materials and Methods. Several variables were collected and compared between two periods of time: from 19th March to 2nd April 2020 and the same period of 2019. Results. During the COVID-19 pandemic period, 49.4% fewer patients visited the ED. We observed a higher number of urgent patients and hospitalization rate than previous year. Conclusions. We experienced a reduction number of admissions to the Obstetrics and Gynaecology ED, but apparently the severity of cases that visited the ED increased.
- Risk of Complications in Patients with Conservatively Managed Ovarian Tumours (IOTA5): a 2-Year Interim Analysis of a Multicentre, Prospective, Cohort StudyPublication . Froyman, W; Landolfo, C; Cock, B; Wynants, L; Sladkevicius, P; Testa, A; Van Holsbeke, C; Domali, E; Fruscio, R; Epstein, E; Santos Bernardo, MJ; Franchi, D; Kudla, M; Chiappa, V; Alcazar, JL; Leone, F; Buonomo, F; Hochberg, L; Coccia, ME; Guerriero, S; Deo, N; Jokubkiene, L; Kaijser, J; Coosemans, A; Vergote, I; Verbakel, J; Bourne, T; Van Calster, B; Valentin, L; Timmerman, DBackground: Ovarian tumours are usually surgically removed because of the presumed risk of complications. Few large prospective studies on long-term follow-up of adnexal masses exist. We aimed to estimate the cumulative incidence of cyst complications and malignancy during the first 2 years of follow-up after adnexal masses have been classified as benign by use of ultrasonography. Methods: In the international, prospective, cohort International Ovarian Tumor Analysis Phase 5 (IOTA5) study, patients aged 18 years or older with at least one adnexal mass who had been selected for surgery or conservative management after ultrasound assessment were recruited consecutively from 36 cancer and non-cancer centres in 14 countries. Follow-up of patients managed conservatively is ongoing at present. In this 2-year interim analysis, we analysed patients who were selected for conservative management of an adnexal mass judged to be benign on ultrasound on the basis of subjective assessment of ultrasound images. Conservative management included ultrasound and clinical follow-up at intervals of 3 months and 6 months, and then every 12 months thereafter. The main outcomes of this 2-year interim analysis were cumulative incidence of spontaneous resolution of the mass, torsion or cyst rupture, or borderline or invasive malignancy confirmed surgically in patients with a newly diagnosed adnexal mass. IOTA5 is registered with ClinicalTrials.gov, number NCT01698632, and the central Ethics Committee and the Belgian Federal Agency for Medicines and Health Products, number S51375/B32220095331, and is ongoing. Findings: Between Jan 1, 2012, and March 1, 2015, 8519 patients were recruited to IOTA5. 3144 (37%) patients selected for conservative management were eligible for inclusion in our analysis, of whom 221 (7%) had no follow-up data and 336 (11%) were operated on before a planned follow-up scan was done. Of 2587 (82%) patients with follow-up data, 668 (26%) had a mass that was already in follow-up at recruitment, and 1919 (74%) presented with a new mass at recruitment (ie, not already in follow-up in the centre before recruitment). Median follow-up of patients with new masses was 27 months (IQR 14-38). The cumulative incidence of spontaneous resolution within 2 years of follow-up among those with a new mass at recruitment (n=1919) was 20·2% (95% CI 18·4-22·1), and of finding invasive malignancy at surgery was 0·4% (95% CI 0·1-0·6), 0·3% (<0·1-0·5) for a borderline tumour, 0·4% (0·1-0·7) for torsion, and 0·2% (<0·1-0·4) for cyst rupture. Interpretation: Our results suggest that the risk of malignancy and acute complications is low if adnexal masses with benign ultrasound morphology are managed conservatively, which could be of value when counselling patients, and supports conservative management of adnexal masses classified as benign by use of ultrasound.
- Alvarez Waves in Pregnancy: a Comprehensive ReviewPublication . Russo, S; Batista, A; Esgalhado, F; Palma dos Reis, C; Serrano, F; Vassilenko, V; Ortigueira, MAlvarez waves are local rhythmic contractions of the myometrium with high frequency and low intensity. They can be detected using internal or external tocography and electrohysterography. Some researchers correlate these small contractions with the initiation of labor, since they have been described as a pattern representing the uterine response to prostaglandin production. Other authors either do not validate a causality relation between Alvarez waves and labor or suggest that they have low predictive value for preterm labor. Alvarez waves' research has become a multidisciplinary subject with inputs ranging from medical science, biomedical engineering, and related areas. A comprehensive review is herein conducted to summarize the state of the art regarding Alvarez waves and their role in the initiation of labor, namely in preterm birth. The results show that a large number of studies have analyzed and characterized Alvarez waves without necessarily digging into their relationship with labor. Publications were categorized in three groups: (A) reports about morphology and characterization of Alvarez waves; (B) publications reporting a positive causality relation between Alvarez waves and labor; and (C) publications reporting an absence of causality regarding the previous hypothesis. Studies in group B outnumbered those in group C. A critical analysis is presented.
- Immune and Spermatogenesis-Related Loci are Involved in the Development of Extreme Patterns of Male InfertilityPublication . Cerván-Martín, M; Tüttelmann, F; Lopes, AM; Bossini-Castillo, L; Rivera-Egea, R; Garrido, N; Lujan, S; Romeu, G; Santos-Ribeiro, S; Castilla, JA; Carmen Gonzalvo, M; Clavero, A; Maldonado, V; Vicente, FJ; González-Muñoz, S; Guzmán-Jiménez, A; Burgos, M; Jiménez, R; Pacheco, A; González, C; Gómez, S; Amorós, D; Aguilar, J; Quintana, F; Calhaz-Jorge, C; Aguiar, A; Nunes, J; Sousa, S; Pereira, I; Pinto, MG; Correia, S; Sánchez-Curbelo, J; López-Rodrigo, O; Martín, J; Pereira-Caetano, I; Marques, PI; Carvalho, F; Barros, A; Gromoll, J; Bassas, L; Seixas, S; Gonçalves, J; Larriba, S; Kliesch, S; Palomino-Morales, RJ; Carmona, FDWe conducted a genome-wide association study in a large population of infertile men due to unexplained spermatogenic failure (SPGF). More than seven million genetic variants were analysed in 1,274 SPGF cases and 1,951 unaffected controls from two independent European cohorts. Two genomic regions were associated with the most severe histological pattern of SPGF, defined by Sertoli cell-only (SCO) phenotype, namely the MHC class II gene HLA-DRB1 (rs1136759, P = 1.32E-08, OR = 1.80) and an upstream locus of VRK1 (rs115054029, P = 4.24E-08, OR = 3.14), which encodes a protein kinase involved in the regulation of spermatogenesis. The SCO-associated rs1136759 allele (G) determines a serine in the position 13 of the HLA-DRβ1 molecule located in the antigen-binding pocket. Overall, our data support the notion of unexplained SPGF as a complex trait influenced by common variation in the genome, with the SCO phenotype likely representing an immune-mediated condition.