Reply to Rubin, J.M.; Kripfgans, O.D. Comment on "Barbieri et al. Umbilical Vein Blood Flow in Uncomplicated Pregnancies: Systematic Review of Available Reference Charts and Comparison with a New Cohort. J. Clin. Med. 2023, 12, 3132".

We thank the authors for the interest in our paper [...].

The "Preeclampsia and Hypertension Target Treatment" study: a multicenter prospective study to evaluate the effectiveness of the antihypertensive therapy based on maternal hemodynamic findings.

BACKGROUND: Despite major advances in the pharmacologic treatment of hypertension in the nonpregnant population, treatments for hypertension in pregnancy have remained largely unchanged over the years. There is recent evidence that a more adequate control of maternal blood pressure is achieved when the first given antihypertensive drug is able to correct the underlying hemodynamic disorder of the mother besides normalizing the blood pressure values. OBJECTIVE: This study aimed to compare the blood pressure control in women receiving an appropriate or inappropriate antihypertensive therapy following the baseline hemodynamic findings. STUDY DESIGN: This was a prospective multicenter study that included a population of women with de novo diagnosis of hypertensive disorders of pregnancy. A noninvasive assessment of the following maternal parameters was performed on hospital admission via Ultrasound Cardiac Output Monitor before any antihypertensive therapy was given: cardiac output, heart rate, systemic vascular resistance, and stroke volume. The clinician who prescribed the antihypertensive therapy was blinded to the hemodynamic evaluation and used as first-line treatment a vasodilator (nifedipine or alpha methyldopa) or a beta-blocker (labetalol) based on his preferences or on the local protocols. The first-line pharmacologic treatment was retrospectively considered hemodynamically appropriate in either of the following circumstances: (1) women with a hypodynamic profile (defined as low cardiac output [≤5 L/min] and/or high systemic vascular resistance [≥1300 dynes/second/cm2]) who were administered oral nifedipine or alpha methyldopa and (2) women with a hyperdynamic profile (defined as normal or high cardiac output [>5 L/min] and/or low systemic vascular resistances [<1300 dynes/second/cm2]) who were administered oral labetalol. The primary outcome of the study was to compare the occurrence of severe hypertension between women treated with a hemodynamically appropriate therapy and women treated with an inappropriate therapy. RESULTS: A total of 152 women with hypertensive disorders of pregnancy were included in the final analysis. Most women displayed a hypodynamic profile (114 [75.0%]) and received a hemodynamically appropriate treatment (116 [76.3%]). The occurrence of severe hypertension before delivery was significantly lower in the group receiving an appropriate therapy than in the group receiving an inappropriately treated (6.0% vs 19.4%, respectively; P=.02). Moreover, the number of women who achieved target values of blood pressure within 48 to 72 hours from the treatment start was higher in the group who received an appropriate treatment than in the group who received an inappropriate treatment (70.7% vs 50.0%, respectively; P=.02). CONCLUSION: In pregnant individuals with de novo hypertensive disorders of pregnancy, a lower occurrence of severe hypertension was observed when the first-line antihypertensive agent was tailored to the correct maternal hemodynamic profile.

Maternal Hemodynamics from Preconception to Delivery: Research and Potential Diagnostic and Therapeutic Implications: Position Statement by Italian Association of Pre-Eclampsia and Italian Society of Perinatal Medicine.

OBJECTIVE: The Italian Association of Preeclampsia (AIPE) and the Italian Society of Perinatal Medicine (SIMP) developed clinical questions on maternal hemodynamics state of the art. STUDY DESIGN: AIPE and SIMP experts were divided in small groups and were invited to propose an overview of the existing literature on specific topics related to the clinical questions proposed, developing, wherever possible, clinical and/or research recommendations based on available evidence, expert opinion, and clinical importance. Draft recommendations with a clinical rationale were submitted to 8th AIPE and SIMP Consensus Expert Panel for consideration and approval, with at least 75% agreement required for individual recommendations to be included in the final version. RESULTS: More and more evidence in literature underlines the relationship between maternal and fetal hemodynamics, as well as the relationship between maternal cardiovascular profile and fetal-maternal adverse outcomes such as fetal growth restriction and hypertensive disorders of pregnancy. Experts agreed on proposing a classification of pregnancy hypertension, complications, and cardiovascular states based on three different hemodynamic profiles depending on total peripheral vascular resistance values: hypodynamic (>1,300 dynes·s·cm-5), normo-dynamic, and hyperdynamic (<800 dynes·s·cm-5) circulation. This differentiation implies different therapeutical strategies, based drugs' characteristics, and maternal cardiovascular profile. Finally, the cardiovascular characteristics of the women may be useful for a rational approach to an appropriate follow-up, due to the increased cardiovascular risk later in life. CONCLUSION: Although the evidence might not be conclusive, given the lack of large randomized trials, maternal hemodynamics might have great importance in helping clinicians in understanding the pathophysiology and chose a rational treatment of patients with or at risk for pregnancy complications. KEY POINTS: · Altered maternal hemodynamics is associated to fetal growth restriction.. · Altered maternal hemodynamics is associated to complicated hypertensive disorders of pregnancy.. · Maternal hemodynamics might help choosing a rational treatment during hypertensive disorders..

Preventing HIV mother-to-child transmission in a vertically infected pregnant woman with multiclass drug resistance, role of bis-in-die dolutegravir and neonatal AZT prophylaxis: A case report.

A suppressive antiretroviral therapy (ART) is necessary to prevent mother-to-child transmission (MTCT) of HIV during pregnancy. During this period, it is recommended to continue an ongoing safe and suppressive regimen, but history of multiclass drug-resistance (MDR) might need tailored, uncommon approaches posing tolerability and toxicity issues. This is the case of a 33 years of age, vertically infected woman with MDR HIV infection suppressed on a darunavir/cobicistat + atazanavir regimen switched during pregnancy to lamivudine + darunavir/ritonavir + dolutegravir 50 mg bis-in-die, maintaining complete viral suppression and delivering via caesarian section and without zidovudine (AZT) intrapartum prophylaxis a healthy HIV-negative newborn who received AZT post-exposure prophylaxis and showed regular growth patterns up to 2 years. Our case shows how archived MDR might complicate the preservation of HIV RNA suppression and highlights the importance of a tailored, multidisciplinary approach for pregnant women with MDR HIV and their newborns.

Giant leiomyoma management during elective cesarean section: a case report.

We present the unique case of a 44-year-old gravida 3 para 2 woman with complaints of monolateral perception of fetal movements who underwent elective cesarean section and hysterectomy for the presence of an exceptionally voluminous infralegamentary leiomyoma. Cesarean section required in-depth preoperative planning and was possible only after gravid uterus exteriorization. Myomectomy and hysterectomy were then necessary to reestablish the physio-anatomical pelvic environment. The patient was discharged after regular and uncomplicated postoperative time. In recent years, the paradigma of avoiding cesarean myomectomy due to fear of hemorrhage has been questioned by many authors and in certain cases cesarean myomectomy may even be undeferrable. We describe an innovative surgical technique which could be useful to obstetricians approaching similar uterine masses during cesarean sections.

The Interplay between Maternal Nutrition and Oxidative Stress.

This Special Issue of Nutrients, "The Interplay between Maternal Nutrition and Oxidative Stress", was designed to contribute to our understanding of "oxidative stress" in pregnancy [...].

Different management strategies for cesarean scar pregnancy: Short-term outcomes and reproductive prognosis.

PURPOSE: To investigate the impact on future reproductive potential of systemic methotrexate (MTX) administration, uterine artery embolization (UAE) and expectant management as treatments of caesarean scar pregnancy (CSP) and to assess their efficacy and safety. BASIC PROCEDURES: We retrospectively analysed patients with a diagnosis of CSP treated in a five years' period (2014-2018). Hospitalization, hCG normalization, menstrual cycle recovery, ultrasound restitutio ad integrum times, reproductive desire accomplishment after the resolution of the picture, and outcomes of subsequent pregnancies were considered. Only patients for whom complete diagnosis, treatment and follow-up data were available could be considered for study entry. MAIN FINDINGS: A total of 21 patients were included. Three of them were managed expectantly. In two cases spontaneous abortion occurred and one case underwent caesarean delivery at 35 weeks of gestation for complete placenta previa with hysterectomy for post partum haemorrhage. Seven patients were treated with systemic MTX. Median [IQR] times of hospitalization, hCG normalization, menstrual cycle recovery and ultrasound restitutio ad integrum were 21 days [10-26 days], 52 days [18-64 days], 8 weeks [6-10 weeks] and 8 weeks [6-11 weeks] respectively. At the end of follow up, 80% (95%CI [38-96%]) of patients with reproductive desire achieved at least one live birth. Eleven patients were treated with UAE combined with MTX. Median [IQR] times of hospitalization, hCG normalization, menstrual cycle recovery and ultrasound restitutio ad integrum were 14 days [12-20 days], 43 days [30-52 days], 8 weeks [4-12 weeks] and 8 weeks [8-10 weeks], respectively. Of those who expressed a reproductive desire after treatment, 80% (95%CI [49-94%]) achieved at least one live birth. In all included patients, the menstrual cycle was restored. PRINCIPAL CONCLUSIONS: Reproductive potential of women treated for CSP was preserved after both systemic MTX administration and systemic MTX combined with UAE. Both strategies proved to be safe.

Umbilical Vein Blood Flow in Uncomplicated Pregnancies: Systematic Review of Available Reference Charts and Comparison with a New Cohort.

The objectives of the study were (1) to perform a systematic review of the available umbilical vein blood flow volume (UV-Q) reference ranges in uncomplicated pregnancies; and (2) to compare the findings of the systematic review with UV-Q values obtained from a local cohort. Available literature in the English language on this topic was identified following the PRISMA guidelines. Selected original articles were further grouped based on the UV sampling sites and the formulae used to compute UV-Q. The 50th percentiles, the means, or the best-fitting curves were derived from the formulae or the reported tables presented by authors. A prospective observational study of uncomplicated singleton pregnancies from 20+0 to 40+6 weeks of gestation was conducted to compare UV-Q with the results of this systematic review. Fifteen sets of data (fourteen sets belonging to manuscripts identified by the research strategy and one obtained from our cohort) were compared. Overall, there was a substantial heterogeneity among the reported UV-Q central values, although when using the same sampling methodology and formulae, the values overlap. Our data suggest that when adhering to the same methodology, the UV-Q assessment is accurate and reproducible, thus encouraging further investigation on the possible clinical applications of this measurement in clinical practice.

Human umbilical cord blood cells suffer major modification by fixatives and anticoagulants.

Introduction: Developing techniques for the tagless isolation of homogeneous cell populations in physiological-like conditions is of great interest in medical research. A particular case is Gravitational Field-Flow Fractionation (GrFFF), which can be run avoiding cell fixation, and that was already used to separate viable cells. Cell dimensions have a key role in this process. However, their dimensions under physiological-like conditions are not easily known since the most diffused measurement techniques are performed on fixed cells, and the fixation used to preserve tissues can alter the cell size. This work aims to obtain and compare cell size data under physiological-like conditions and in the presence of a fixative. Methods: We developed a new protocol that allows the analysis of blood cells in different conditions. Then, we applied it to obtain a dataset of human cord blood cell dimensions from 32 subjects, comparing two tubes with anticoagulants (EDTA and Citrate) and two tubes with different preservatives (CellRescue and CellSave). We analyzed a total of 2071 cells by using confocal microscopy via bio-imaging to assess dimensions (cellular and nuclear) and morphology. Results: Cell diameter measured does not differ when using the different anticoagulants, except for the increase reported for monocyte in the presence of citrate. Instead, cell dimensions differ when comparing anticoagulants and cell preservative tubes, with a few exceptions. Cells characterized by high cytoplasm content show a reduction in their size, while morphology appears always preserved. In a subgroup of cells, 3D reconstruction was performed. Cell and nucleus volumes were estimated using different methods (specific 3D tool or reconstruction from 2D projection). Discussion: We found that some cell types benefit from a complete 3D analysis because they contain non-spherical structures (mainly for cells characterized by poly-lobated nucleus). Overall, we showed the effect of the preservatives mixture on cell dimensions. Such an effect must be considered when dealing with problems highly dependent on cell size, such as GrFFF. Additionally, such information is crucial in computational models increasingly being employed to simulate biological events.

From pandemic to syndemic: microbiota, pregnancy, and environment at a crossroad.

Aim: SARS-CoV2 is the latest pandemic that have plagued the socio-health system as an epiphenomenon resulting from planetary resources abuse, crucial for biodiversity. The Anthropocene best defines the present epoch in which human activity irreversibly manipulates intricate and delicate geological and biological balances established over eons. The devastating ecological and socio-economic implications of COVID-19, underline the importance of updating the present pandemic framework to a syndemic. This paper stems from the need to suggest to scientists, doctors, and patients a mission that integrates responsibility from individual to collective health, from present to trans-generational, from human to the entire biotic network. Today's choices are crucial for the perspective on all levels: political, economic, and health as well as cultural.Methods: Research on PubMed and other specific web-sites journal was performed on the topic "Microbiota", "Covid-19", "Pandemic", "Zoonosis", "SARS-CoV-2", "Environmental Pollutants", "Epigenetics", "Fetal Programming", "Human Extinction". Data collected were analysed for an integrative model of interconnection between environment, pregnancy, SARS-CoV-2 infection, and microbiota. Moreover, systematic literature review allowed to summarise in a table information about the worst pandemics that afflicted the human species recently.Results: This paper offers a broad view of the current pandemic starting with pregnancy, the moment when a new life begins and the health trajectories of the unborn child are defined, which will inevitably have repercussions on his well-being. The fundamental role of the biodiversity-rich microbiota in avoiding the development of severe infectious diseases, is therefore highlighted. It is imperative to adjust the current reductionist paradigm based on mostly immediate symptom management towards a broader understanding of the spatial interconnection of ecological niches with human health and the impacts of today's choices on the future. Health and healthcare are elitist rather than egalitarian, therefore focusing on environmental health forces us to make a concerted and systemic effort that challenges political and economic barriers, which are biologically senseless. A healthy microbiota is essential to well-being, both by preventing chronic degenerative conditions, the infectiousness and pathogenicity of bacterial and viral diseases. SARS-CoV-2 should not be an exception. The human microbiota, forged by the first 1,000 days of life, is fundamental in shaping the health-disease trajectories, and by the everlasting exposome that is dramatically affected by the ecological disaster. Individual health is one world health whereas single and global well-being are interdependent in a space-time perspective.Conclusions: Is it not a convenient reductionism not to consider the COVID-19 emergency as a bio-social epiphenomenon of a far more devastating and multi-faceted crisis whose common denominator is the global biotic network loss of which humans are still part?

Umbilical vein blood flow: State-of-the-art.

Placental blood supply to the fetus can be measured by evaluating the umbilical vein blood flow. Despite its potential application in healthcare, the umbilical vein blood flow volume is still used only in research setting. One of the reasons is a concern regarding its reproducibility, partly due to technology issues. Nowadays, technology improvements make this evaluation accurate and reproducible. The aim of this review is to refresh basic elements of the physiology of umbilical vein blood flow and its analysis. Its evaluation in normal and abnormal fetal growth is also discussed.

Risk of stillbirth in singleton fetuses with advancing gestational age at term: A 10-year experience of late third trimester prenatal screenings of 50,000 deliveries in a referral center in northern Italy.

BACKGROUND: The risk of intrauterine death (IUD) at term varies from less than one to up to three cases per 1,000 ongoing pregnancies. The cause of death is often largely undefined. Protocols and criteria to prevent and define the rates and causes of stillbirth are the subjects of important scientific and clinical debates. We examined the gestational age and rate of stillbirth at term in a 10-year period at our maternity hub to evaluate the possible favorable impact of a surveillance protocol on maternal and fetal well-being and growth. METHODS AND FINDINGS: Our cohort included all women with singleton pregnancies resulting in early term to late term birth at our maternity hub between 2010 and 2020, with the exclusion of fetal anomalies. As per our protocol for monitoring term pregnancies, all women underwent near term to early term maternal and fetal well-being and growth surveillance. If risk factors were identified, outpatient monitoring was initiated and early- or full-term induction was indicated. Labor was induced at late term (41+0-41+4 weeks of gestation), if it did not occur spontaneously. We retrospectively collected, verified, and analyzed all cases of stillbirth at term. The incidence of stillbirth at each week of gestation, was calculated by dividing the number of stillbirths observed that week by the number of women with ongoing pregnancies in that same week. The overall rate of stillbirth per 1000 was also calculated for the entire cohort. Fetal and maternal variables were analyzed to assess the possible causes of death. RESULTS: A total of 57,561 women were included in our study, of which 28 cases of stillbirth (overall rate, 0.48 per 1000 ongoing pregnancies; 95% CI: 0.30-0.70) were identified. The incidence of stillbirth in the ongoing pregnancies measured at 37, 38, 39, 40, and 41 weeks of gestation was 0.16, 0.30, 0.11, 0.29, and 0.0 per 1000, respectively. Only three cases occurred after 40+0 weeks of gestation. Six patients had an undetected small for gestational age fetus. The identified causes included placental conditions (n = 8), umbilical cord conditions (n = 7), and chorioamnionitis (n = 4). Furthermore, the cases of stillbirth included one undetected fetal abnormality (n = 1). The cause of fetal death remained unknown in eight cases. CONCLUSIONS: In a referral center with an active universal screening protocol for maternal and fetal prenatal surveillance at near and early term, the rate of stillbirth was 0.48 per 1000 in singleton pregnancies at term in a large, unselected population. The highest incidence of stillbirth was observed at 38 weeks of gestation. The vast majority of stillbirth cases occurred before 39 weeks of gestation and 6 of 28 cases were SGA, and the median percentile of the remaining case was the 35th.

Maternal hemodynamic profile during pregnancy and in the post-partum in hypertensive disorders of pregnancy and fetal growth restriction.

BACKGROUND: Maternal cardiovascular changes, occurring since the beginning of pregnancy, are necessary for normal placentation and regular evolution of pregnancy. OBJECTIVE: This study aimed to compare the hemodynamic profiles and cardiac remodeling of women with hypertensive disorders of pregnancy and either appropriate for gestational age fetuses or growth-restricted fetuses, women with normotensive pregnancies complicated by fetal growth restriction, and women with uncomplicated pregnancies, during pregnancy and the postpartum period. STUDY DESIGN: A prospective longitudinal case-control design was used for this study. Over the study period, 220 eligible women with singleton pregnancies were selected for the analysis and divided into 4 groups: (1) hypertensive disorders of pregnancy with appropriate for gestational age fetuses; (2) hypertensive disorders of pregnancy with fetal growth restriction; (3) normotensive fetal growth restriction; and (4) controls. Ultrasound fetal biometry and fetoplacental Doppler velocimetry were performed at recruitment. Maternal hemodynamic assessment using transthoracic echocardiography was performed at the time of recruitment by a dedicated cardiologist blinded to maternal clinical data. The same assessments were performed in 104 patients at 32 weeks (interquartile range, 24-40) after delivery by the same cardiologist. RESULTS: During pregnancy, women in the hypertensive-disorders-of-pregnancy-fetal-growth-restriction group showed significantly lower cardiac output and increased compared with those in the control group. These values were associated with concentric remodeling of the left ventricle owing to relatively increased wall thickness, which was not accompanied by an increase in left ventricular mass. Isolated fetal growth restriction presented similar but less important hemodynamic changes; however, there was no change in relative wall thickness. At postpartum follow-up, the hemodynamic parameters of women in the hypertensive-disorders-of-pregnancy-fetal-growth-restriction and isolated-fetal-growth-restriction groups reverted to values similar to those of the control group. Only 8.3% of women in these groups experienced hypertension even in the postpartum period, and asymptomatic stage-B cardiac failure was observed for 17% at echocardiography. In the group of women with hypertensive disorders of pregnancy and appropriate for gestational age fetuses, cardiac output increased as in normal pregnancies, but total vascular resistance was significantly higher; hypertension then occurred, along with ventricular concentric hypertrophy and diastolic dysfunction. At postpartum follow-up, women in the hypertensive-disorders-of-pregnancy-appropriate-for-gestational-age-fetus group showed significantly higher mean arterial pressure, total vascular resistance, and left ventricular mass compared with those in the control group. Persistent hypertension and asymptomatic stage-B cardiac failure were observed in 39.1% and 13% of women in the former group, respectively. CONCLUSION: Pregnancies with hypertensive disorders of pregnancy and fetal growth restriction and normotensive pregnancies with fetal growth restriction were associated with the hemodynamic profile of lower heart rate and cardiac output, most likely because of abnormal adaptation to pregnancy, as confirmed by abnormal changes from pregnancy to the postpartum period. The heart rates and cardiac output of women in the hypertensive-disorders-of-pregnancy-appropriate-for-gestational-age-fetus group showed changes opposite to those observed in the hypertensive-disorders-of-pregnancy-fetal-growth-restriction and fetal-growth-restriction groups. Obesity and other metabolic risk factors, significantly prevalent in women in the hypertensive-disorders-of-pregnancy-appropriate-for-gestational-age-fetus group, predispose to hypertension and cardiovascular diseases during pregnancy and the postpartum period, potentially offering a window for personalized prevention. Such preventive strategies could differ in women with hypertensive disorders of pregnancy and fetal growth restriction characterized by poor early placental development.

Anti-SSA/Ro positivity and congenital heart block: obstetric and foetal outcome in a cohort of anti-SSA/Ro positive pregnant patients with and without autoimmune diseases.

OBJECTIVES: Neonatal lupus (NL) is an acquired disease caused by the transplacental passage of anti-SSA/Ro antibodies. The rate of congenital heart block (CHB), its most serious manifestation, ranges from 1 to 5%. The aim of this study was to retrospectively assess the prevalence of CHB in anti-SSA/Ro positive pregnant women with or without systemic autoimmune diseases from 2010 to 2020. METHODS: Patients underwent monthly visit and a shared follow-up programme of weekly (16th-24th week) foetal heart rate assessment by obstetric ultrasound. RESULTS: 322 pregnancies in 258 anti-SSA/Ro patients were included; 314 were followed from the beginning of pregnancy because of the known presence of anti-SSA/Ro autoantibodies and 1 case of CHB occurred in an anti-SSA/Ro+ asymptomatic subject (0.3%). In the same period, 8 additional patients were referred to our clinics after in utero CHB diagnosis and subsequent discovery of anti-SSA/Ro without a disease diagnosis. Globally, 9 cases of congenital CHB (2.8%) occurred: 7 complete, 1 II-III degree and 1 rst degree CHB. Anti-SSB/La positivity was associated with a higher risk of CHB (7.8% vs. 1.2%; p=0.0071). No differences in maternal or foetal outcomes were found in comparison with a large cohort of unselected pregnancies except for caesarian section. Hydroxychloroquine (HCQ) was used in 58.3% pregnancies, with a different prevalence according with maternal diagnosis. CONCLUSIONS: Our data suggest that anti-SSA/Ro positive patents with a de ned systemic autoimmune disease undergoing a strict follow-up since positive pregnancy test display a low risk of pregnancy complications, including but not limited to NL.

Isolation of single circulating trophoblasts from maternal circulation for noninvasive fetal copy number variant profiling.

OBJECTIVE: To develop a multi-step workflow for the isolation of circulating extravillous trophoblasts (cEVTs) by describing the key steps enabling a semi-automated process, including a proprietary algorithm for fetal cell origin genetic confirmation and copy number variant (CNV) detection. METHODS: Determination of the limit of detection (LoD) for submicroscopic CNV was performed by serial experiments with genomic DNA and single cells from Coriell cell line biobank with known imbalances of different sizes. A pregnancy population of 372 women was prospectively enrolled and blindly analyzed to evaluate the current workflow. RESULTS: An LoD of 800 Kb was demonstrated with Coriell cell lines. This level of resolution was confirmed in the clinical cohort with the identification of a pathogenic CNV of 800 Kb, also detected by chromosomal microarray. The mean number of recovered cEVTs was 3.5 cells per sample with a significant reverse linear trend between gestational age and cEVT recovery rate and number of recovered cEVTs. In twin pregnanices, evaluation of zygosity, fetal sex and copy number profiling was performed in each individual cell. CONCLUSION: Our semi-automated methodology for the isolation and single-cell analysis of cEVTS supports the feasibility of a cell-based noninvasive prenatal test for fetal genomic profiling.

Three-Dimensional Transperineal Ultrasound Guiding Early Secondary Repair of Obstetric Anal Sphincter Injury in an Incontinent Patient without Suture Dehiscence.

We present the case of a 36-year-old primigravida who gave birth to a 3200 g baby by vacuum-assisted (Kiwi OmniCup™) operative vaginal delivery with mediolateral episiotomy. A "y"-shaped perineal tear with a grade IIIC obstetric anal sphincter injury (OASI) was diagnosed and repaired. Two days after delivery, in the absence of suture dehiscence, she started experiencing complete anal incontinence. A decision was made in association with a proctologic surgeon for an early secondary repair. Before surgery, a Three-dimensional transperineal ultrasound (TPUS) was performed. The exam revealed a major defect of the external anal sphincter at the 11 o'clock position. This allowed for the reopening of only a circumscribed area of the perineal suture and repair of the sphincters using the end-to-end technique. The symptoms regressed completely, and follow-up TPUS demonstrated the gradual wound healing process. Anal incontinence, secondary to obstetric anal sphincter injury (OASI), has a severe negative impact on women's quality of life. TPUS is an effective method to detect sphincter defects and monitor the healing process. This report investigates the feasibility of identifying the sphincter tear in an incontinent puerperal patient without suture dehiscence in order to target early secondary repair while minimizing its extent. TPUS has proven a safe and effective tool to guide early secondary repair of symptomatic OASI complications while minimizing the invasiveness of the procedure. Multidisciplinary management is crucial to ensure the adequate standard of care.

Glycation-Driven Inflammation: COVID-19 Severity in Pregnant Women and Perinatal Outcomes.

The link between being pregnant and overweight or obese and the infectivity and virulence of the SARS CoV-2 virus is likely to be caused by SARS-CoV-2 spike protein glycosylation, which may work as a glycan shield. Methylglyoxal (MGO), an important advanced glycation end-product (AGE), and glycated albumin (GA) are the results of poor subclinical glucose metabolism and are indices of oxidative stress. Forty-one consecutive cases of SARS-CoV-2-positive pregnant patients comprising 25% pre-pregnancy overweight women and 25% obese women were recruited. The aim of our study was to compare the blood levels of MGO and GA in pregnant women with asymptomatic and symptomatic SARS-CoV-2 infection with pregnant women without SARS-CoV-2 infection with low risk and uneventful pregnancies and to evaluate the relative perinatal outcomes. The MGO and GA values of the SARS-CoV-2 cases were statistically significantly higher than those of the negative control subjects. In addition, the SARS-CoV-2-positive pregnant patients who suffered of moderate to severe COVID-19 syndrome had higher values of GA than those infected and presenting with mild symptoms or those with asymptomatic infection. Premature delivery and infants of a small size for their gestational age were overrepresented in this cohort, even in mild-asymptomatic patients for whom delivery was not indicated by the COVID-19 syndrome. Moreover, ethnic minorities were overrepresented among the severe cases. The AGE-RAGE oxidative stress axis on the placenta and multiple organs caused by MGO and GA levels, associated with the biological mechanisms of the glycation of the SARS-CoV-2 spike protein, could help to explain the infectivity and virulence of this virus in pregnant patients affected by being overweight or obese or having gestational diabetes, and the increased risk of premature delivery and/or low newborn weight.