Diagnosis and management of selective fetal growth restriction in monochorionic twin pregnancies: A cross-sectional international survey.

OBJECTIVE: To identify current practices in the management of selective fetal growth restriction (sFGR) in monochorionic diamniotic (MCDA) twin pregnancies. DESIGN: Cross-sectional survey. SETTING: International. POPULATION: Clinicians involved in the management of MCDA twin pregnancies with sFGR. METHODS: A structured, self-administered survey. MAIN OUTCOME MEASURES: Clinical practices and attitudes to diagnostic criteria and management strategies. RESULTS: Overall, 62.8% (113/180) of clinicians completed the survey; of which, 66.4% (75/113) of the respondents reported that they would use an estimated fetal weight (EFW) of <10th centile for the smaller twin and an inter-twin EFW discordance of >25% for the diagnosis of sFGR. For early-onset type I sFGR, 79.8% (75/94) of respondents expressed that expectant management would be their routine practice. On the other hand, for early-onset type II and type III sFGR, 19.3% (17/88) and 35.7% (30/84) of respondents would manage these pregnancies expectantly, whereas 71.6% (63/88) and 57.1% (48/84) would refer these pregnancies to a fetal intervention centre or would offer fetal intervention for type II and type III cases, respectively. Moreover, 39.0% (16/41) of the respondents would consider fetoscopic laser surgery (FLS) for early-onset type I sFGR, whereas 41.5% (17/41) would offer either FLS or selective feticide, and 12.2% (5/41) would exclusively offer selective feticide. For early-onset type II and type III sFGR cases, 25.9% (21/81) and 31.4% (22/70) would exclusively offer FLS, respectively, whereas 33.3% (27/81) and 32.9% (23/70) would exclusively offer selective feticide. CONCLUSIONS: There is significant variation in clinician practices and attitudes towards the management of early-onset sFGR in MCDA twin pregnancies, especially for type II and type III cases, highlighting the need for high-level evidence to guide management.

Comparison of serial amnioinfusion strategies for isolated early-onset fetal renal anhydramnios.

Introduction The optimal protocol for serial amnioinfusions to maintain amniotic fluid in pregnancies with early onset-fetal renal anhydramnios before 22 weeks is not known. We compared the performance of two different approaches. Methods A secondary analysis was conducted of serial amnioinfusions performed by a single center during the external pilot and feasibility phases of the Renal Agenesis Fetal Therapy (RAFT) trial. During the external pilot, higher amnioinfusion volumes were given less frequently; in the feasibility study, smaller volume amnioinfusions were administered more frequently. Procedural details, complications, and obstetric outcomes were compared between the two groups using Pearson's chi-squared or Fisher's Exact tests for categorical variables and Student's t-tests or Wilcoxon Rank-Sum tests for continuous variables. The adjusted association between procedural details and chorioamniotic separation was obtained through a multivariate repeated measure logistic regression model. Results Eleven participants underwent 159 amnioinfusions (external pilot: three patients, 21 amnioinfusions; feasibility: eight patients, 138 amnioinfusions). External pilot participants had fewer amnioinfusions (7 vs. 19.5 in the feasibility group, p = 0.04), larger amnioinfusion volume (750 vs. 500 mL, p < 0.01), and longer interval between amnioinfusions (6 [4-7] vs. 4 [3-5] days, p < 0.01). In the external pilot, chorioamniotic separation was more common (28.6% vs. 5.8%, p < 0.01), preterm prelabor rupture of membranes (PPROM) occurred sooner after amnioinfusion initiation (28 ± 21.5 vs. 75.6 ± 24.1 days, p = 0.03), and duration of maintained amniotic fluid between first and last amnioinfusion was shorter (38 ± 17.3 vs. 71 ± 19 days, p=0.03), compared to the feasibility group. While delivery gestational age was similar (35.1 ± 1.7 vs. 33.8 ± 1.5 weeks, p=0.21), feasibility participants maintained amniotic fluid longer. Conclusion Small volume serial amnioinfusions performed more frequently maintain normal amniotic fluid volume longer because of delayed occurrence of PPROM.

Sex-specific associations between circadian-related genes and depression in UK Biobank participants highlight links to glucose metabolism, inflammation and neuroplasticity pathways.

Depressive disorders have increased in global prevalence, making improved management of these disorders a public health priority. Prior research has linked circadian clock genes to depression, either through direct interactions with mood-related pathways in the brain or by modulating the phase of circadian rhythms. Using machine learning and statistical techniques, we explored associations between 157,347 SNP variants from 51 circadian-related genes and depression scores from the patient health questionnaire 9 (PHQ-9) in 99,939 UK Biobank participants. Our results highlight multiple pathways linking the circadian system to mood, including metabolic, monoamine, immune, and stress-related pathways. Notably, genes regulating glucose metabolism and inflammation (GSK3B, LEP, RORA, and NOCT) were prominent factors in females, in addition to DELEC1 and USP46, two genes of unknown function. In contrast, FBXL3 and DRD4 emerged as significant risk factors for male depression. We also found epistatic interactions involving RORA, NFIL3, and ZBTB20 as either risk or protective factors for depression, underscoring the importance of transcription factors (ZBTB20, NFIL3) and hormone receptors (RORA) in depression etiology. Understanding the complex, sex-specific links between circadian genes and mood disorders will facilitate the development of therapeutic interventions and enhance the efficacy of multi-target treatments for depression.

Management advances for congenital diaphragmatic hernia: integrating prenatal and postnatal perspectives.

In congenital diaphragmatic hernia (CDH), abdominal organs are displaced into the chest, compress the lungs, and cause mediastinal shift. This contributes to development of pulmonary hypoplasia and hypertension, which is the primary determinant of morbidity and mortality for affected newborns. The severity is determined using prenatal imaging as early as the first trimester and is related to the laterality of the defect, extent of lung compression, and degree of liver herniation. Comprehensive evaluation of fetal CDH includes imaging-based severity assessment, severity assessment, and evaluation for structural or genetic abnormalities to differentiate isolated from complex cases. Prenatal management involves multispecialty counseling, consideration for fetal therapy with fetoscopic endoluminal tracheal occlusion (FETO) for severe cases, monitoring and intervention for associated polyhydramnios or signs of preterm labor if indicated, administration of antenatal corticosteroids in the appropriate setting, and planned delivery to optimize the fetal condition at birth. Integrated programs that provide a smooth transition from prenatal to postnatal care produce better outcomes. Neonatal care involves gentle ventilation to avoid hyperinflation and must account for transitional physiology to avoid exacerbating cardiac dysfunction and decompensation. Infants who have undergone and responded to FETO have greater pulmonary capacity than expected, but cardiac dysfunction seems unaffected. In about 25-30% of CDH neonates extracorporeal life support is utilized, and this provides a survival benefit for patients with the highest predicted mortality, including those who underwent FETO. Surgical repair after initial medical management for the first 24-48 hours of life is preferred since later repair is associated with delayed oral feeding, increased need for tube feeds, and increased post-repair ventilation requirement and supplemental oxygen at discharge. With overall survival rates >70%, contemporary care involves management of chronic morbidities in the context of a multidisciplinary clinic setting.

Neurodevelopmental Outcomes in Children After Fetoscopic Endoluminal Tracheal Occlusion for Severe Congenital Diaphragmatic Hernia: Results From a Multidisciplinary Clinic.

BACKGROUND: We compared early neurodevelopmental morbidity in young children with severe CDH who underwent FETO to those without fetal therapy. METHODS: We conducted a prospective study of severe CDH patients undergoing FETO (n = 18) at a single North American center from 2015 to 2021 (NCT02710968). Outpatient survivors (n = 12) were evaluated by a multidisciplinary team and compared to expectantly managed CDH patients. Neurodevelopmental outcomes were assessed using the Capute Scales [Clinical Linguistic and Auditory Milestone Scales (CLAMS) and Cognitive Adaptive Test (CAT)], with a developmental quotient (DQ) < 85 indicative of at-risk for delay. RESULTS: At one year, 58% (n = 7) of FETO patients underwent evaluation, with notable concern for language delay (CLAMS median DQ, 80.1 [interquartile range, 67.6-86.7]). FETO scores improved by 24-months, whereas high severity/non-FETO scores declined [CLAMS median DQ (Difference in DQ), 92.3 (+12.2) vs. 77.1 (-13.4), respectively; p = 0.049]. On the initial CAT, FETO patients had concern for visual motor and problem-solving delays, with a median DQ of 81.3 (62.1-89.4). At 24-months, FETO patients had improving scores [Median CAT DQ, 90.8 (+9.5)], whereas high severity/non-FETO [87.5 (-3.0), p = 0.28] had declining scores. CONCLUSION: These initial data suggest that FETO is associated with favorable neurodevelopmental outcomes at 24-months compared to severe CDH under expectant management. LEVEL OF EVIDENCE: III.

The role of fetal therapy in the management of mirror syndrome: a narrative review.

OBJECTIVES: Mirror syndrome (MS) is a condition characterized by the presence of maternal, fetal, and placental edema and is reversible through delivery or pregnancy termination. As fetal hydrops itself may be amenable to treatment, we sought to determine outcomes for MS primarily managed by fetal therapy through a narrative review of the literature and cases managed at our fetal center. STUDY DESIGN: PubMed, Embase, Web of Science, Scopus, and Google Scholar databases were searched through January 2024 using key words: mirror syndrome, Ballantyne's syndrome, fetal hydrops, maternal hydrops, pseudotoxemia, triple edema, maternal recovery, fetal therapy, and resolution. Manuscripts describing primary management by fetal therapy that included maternal and fetal outcomes were identified. Clinical details of MS patients managed with fetal therapy at our center were also included for descriptive analysis. RESULTS: 16 of 517 manuscripts (3.1%) described fetal therapy as the primary intended treatment in 17 patients. 3 patients managed at our center were included in the analysis. Among 20 patients undergoing primary fetal therapy for management of mirror syndrome, median gestational age of presentation was 24 weeks and 5 days gestation; predominant clinical findings were maternal edema (15/20), proteinuria (10/20), pulmonary edema (8/20), and hypertension (8/20); the primary laboratory abnormalities were anemia (8/20) and elevated creatinine or transaminases (5/20). Condition-specific fetal therapies led to resolution of hydrops in 17 (85%) cases and MS in 19 (95%) cases. The median time to hydrops resolution was 7.5 days and to resolution of mirror syndrome was 10 days. Fetal therapy prolonged pregnancy by a median of 10 weeks with a median gestational age of 35 weeks and 5 days at delivery. All women delivered for indications other than mirror syndrome and 19/20 fetuses survived. CONCLUSION: In appropriately selected cases, MS often resolves after fetal therapy of hydrops allowing for safe pregnancy prolongation with good maternal and infant outcomes.

A Novel Technique for the Management of Persistent Biliary Fistulas Developing After Liver Hydatid Cyst Surgeries: Drain Clamping Technique.

BACKGROUND: External biliary fistula, where the residual cyst is associated with the biliary tree, is one of the most common complications after liver hydatid cyst surgery. Surgical procedures become a consideration for patients in whom the biliary fistula persists despite all endoscopic procedures. However, reoperation for biliary fistula after hydatid cyst surgery leads to additional complications and increases morbidity and mortality. AIM: This study aims to treat persistent biliary fistulas that develop after liver hydatid cyst surgery using a simple noninvasive technique. MATERIALS AND METHODS: External drainage surgery was performed on 295 patients with liver hydatid cysts. Endoscopic treatment methods were used in patients who developed biliary fistula after surgery. Despite all endoscopic treatment methods, 14 patients developed persistent biliary fistulas. These patients were subsequently treated using the drain clamping technique. FINDINGS: All persistent fistulas occluded in 11.86 days (with a range of 8-20 days). No complications were observed in the one-year follow-up visits. CONCLUSION: Drain clamping, a novel approach to the treatment of persistent biliary fistulas developed despite all available endoscopic methods, can be safely used. This technique resulted in a complete recovery in patients without the need for surgical procedures.

Maternal exposure to polyethylene micro- and nanoplastics impairs umbilical blood flow but not fetal growth in pregnant mice.

While microplastics have been recently detected in human blood and the placenta, their impact on human health is not well understood. Using a mouse model of environmental exposure during pregnancy, our group has previously reported that exposure to polystyrene micro- and nanoplastics throughout gestation results in fetal growth restriction. While polystyrene is environmentally relevant, polyethylene is the most widely produced plastic and amongst the most commonly detected microplastic in drinking water and human blood. In this study, we investigated the effect of maternal exposure to polyethylene micro- and nanoplastics on fetal growth and placental function. Healthy, pregnant CD-1 dams were divided into three groups: 106 ng/L of 740-4990 nm polyethylene with surfactant in drinking water (n = 12), surfactant alone in drinking water (n = 12) or regular filtered drinking water (n = 11). At embryonic day 17.5, high-frequency ultrasound was used to investigate the placental and fetal hemodynamic responses following exposure. While maternal exposure to polyethylene did not impact fetal growth, there was a significant effect on placental function with a 43% increase in umbilical artery blood flow in the polyethylene group compared to controls (p < 0.01). These results suggest polyethylene has the potential to cause adverse pregnancy outcomes through abnormal placental function.

Precarious hope: Ethical considerations for offering experimental fetal therapies outside of research after initial studies in humans.

OBJECTIVE: Risks and benefits of experimental fetal therapies can remain uncertain after initial clinical studies, especially long-term effects. Nevertheless, pregnant individuals may request them, hoping to benefit their future child. Guidance about offering experimental fetal therapies outside research (as "innovative therapy") is limited, despite their ethical complexity. We propose points for clinicians and reviewers to consider when deciding whether and how to offer experimental fetal therapies as innovative therapies after initial clinical studies. METHOD: We used conceptual analysis and a current case to develop points for consideration, grounded in broader debates on innovative therapy and the unique challenges associated with experimental fetal therapies. RESULTS: Clinicians should evaluate whether offering experimental fetal therapies as innovative therapy is appropriate for a pregnant individual and their fetus. The anticipated risk-benefit ratio for the fetus should be favorable. For the pregnant individual, risks may outweigh benefits, within reasonable limits. Medical resources should be sufficient to ensure appropriate care. Clinicians should support pregnant individuals in making informed choices. Clinicians offering innovative therapies with more than minimal risk should collect and report data on outcomes. Independent review should take place. CONCLUSION: Considering these points may advance the interests of fetuses, future children, and their families.

Polystyrene micro- and nanoplastics cause placental dysfunction in mice†.

Maternal exposure to microplastics and nanoplastics has been shown to result in fetal growth restriction in mice. In this study, we investigated the placental and fetal hemodynamic responses to plastics exposure in mice using high-frequency ultrasound. Healthy, pregnant CD-1 dams were given either 106 ng/L of 5 µm polystyrene microplastics or 106 ng/L of 50 nm polystyrene nanoplastics in drinking water throughout gestation and were compared with controls. Maternal exposure to both microplastics and nanoplastics resulted in evidence of placental dysfunction that was highly dependent on the particle size. The umbilical artery blood flow increased by 48% in the microplastic-exposed group and decreased by 25% in the nanoplastic-exposed group compared to controls (p < 0.05). The microplastic- and nanoplastic-exposed fetuses showed a significant decrease in the middle cerebral artery pulsatility index of 10% and 13%, respectively, compared to controls (p < 0.05), indicating vasodilation of the cerebral circulation, a fetal adaptation that is part of the brain sparing response to preserve oxygen delivery. Hemodynamic markers of placental dysfunction and fetal hypoxia were more pronounced in the group exposed to polystyrene nanoplastics, suggesting nanoplastic exposure during human pregnancy has the potential to disrupt fetal brain development, which in turn may cause suboptimal neurodevelopmental outcomes.

Cervical pessary to prevent preterm birth and poor neonatal outcome: An integrity meta-analysis of randomized controlled trials focusing on adherence to the European Medical Device Regulation.

BACKGROUND: Findings from randomized trials (RCTs) on cervical pessary treatment to prevent spontaneous preterm birth are inconsistent. OBJECTIVES: Our hypothesis suggests that adhering to the European Medical Device Regulation (MDR) and following the instructions for use are essential prerequisites for successful therapy. Conversely, the non-adherence to these guidelines will probably contribute to its failure. SEARCH STRATEGY AND SELECTION CRITERIA: Based on validated criteria from integrity assessments we performed a systematic review identifying 14 RCTs evaluating the effect of cervical pessaries. DATA COLLECTION AND ANALYSIS: We analyzed the implications of 14 criteria each accounting for 0-2 points of a score reflecting the clinical evaluation plan (CEP) as proposed by the MDR to evaluate the risk-benefit ratio of medical devices. MAIN RESULTS: Seven RCTs in each singleton and twin pregnancies (5193 "cases") were included, detecting a high heterogeneity within control groups (I2 = 85% and 87%, respectively, P < 0.01). The CEP score varied from 11 to 26 points for all studies. The most common reasons for low scores and potential data compromise were poor recruitment rates, no (completed) power analysis, and no pre-registration, but mainly non-adherence to technical, biological, and clinical equivalence to the instructions for use as required by the MDR. All trials with score values greater than 20 had applied audit procedures. Within this group we found significantly reduced rates of spontaneous preterm birth at less than 34 weeks within the pessary group in singleton (odds ratio 0.28; 95% confidence interval 0.12-0.65) and twin pregnancies (odds ratio 0.30; 95% confidence interval 0.13-0.67). Similarly, there was a significant reduction in the composite poor neonatal outcome in singleton (odds ratio 0.25; 95% confidence interval 0.10-0.61) and twin pregnancies (odds ratio 0.54; 95% confidence interval 0.35-0.82) after a pessary as compared with controls. CONCLUSION: Non-audited RCTs and meta-analyses mixing studies of different clinical quality as pre-defined by a CEP and the MDR pose the risk for erroneous conclusions.

Clinical implication of the Naples prognostic score on transcatheter aortic valve replacement in patients with severe aortic stenosis.

BACKGROUND: One of the hallmarks of frailty in patients with severe aortic stenosis (AS) is malnutrition, for which one of the most up-to-date scoring systems is the Naples prognostic score (NPS). This study sought to investigate the predictive role of the NPS in determining mortality in patients undergoing transcatheter aortic valve replacement (TAVR) under long-term follow-up. METHODS: A total of 430 consecutive patients with symptomatic severe AS who underwent TAVR were included retrospectively. The primary endpoint of the study was the long-term all-cause mortality. The study population was divided into two groups according to the NPS value, including Group 1 (NPS 0-2) and Group 2 (NPS 3-4). RESULTS: The all-cause mortality occurred in 250 patients (62.5%) patients during a follow-up time of 40.6 (22.0-69.4) months. During the follow-up period, all-cause mortality was higher in Group 2 compared with Group 1 (87.9% vs. 42.9%, p < 0.001). Older age (p < 0.001), chronic obstructive pulmonary disease (p = 0.015), left ventricular ejection fraction (p = 0.021), and being in Group 2 (high NPS) (hazard ratio: 7.058, 95% confidence interval: 5.174-9.629, p < 0.001) were found to be independent predictors of all-cause mortality at long-term follow-up. CONCLUSION: The NPS as a malnutrition and inflammation marker in patients with severe aortic stenosis who underwent TAVR provides valuable information for all-cause mortality under long-term follow-up.

Fetoscopic Endoluminal Tracheal Occlusion for Severe, Left-Sided Congenital Diaphragmatic Hernia: The North American Fetal Therapy Network Fetoscopic Endoluminal Tracheal Occlusion Consortium Experience.

OBJECTIVE: To report the outcomes of fetoscopic endoluminal tracheal occlusion in a multicenter North American cohort of patients with isolated, left-sided congenital diaphragmatic hernia (CDH) and to compare neonatal mortality and morbidity in patients with severe left-sided congenital diaphragmatic hernia who underwent fetoscopic endoluminal tracheal occlusion with those expectantly managed. METHODS: We analyzed data from 10 centers in the NAFTNet (North American Fetal Therapy Network) FETO (Fetoscopic Endoluminal Tracheal Occlusion) Consortium registry, collected between November 1, 2008, and December 31, 2020. In addition to reporting procedure-related surgical outcomes of fetoscopic endoluminal tracheal occlusion, we performed a comparative analysis of fetoscopic endoluminal tracheal occlusion compared with contemporaneous expectantly managed patients. RESULTS: Fetoscopic endoluminal tracheal occlusion was successfully performed in 87 of 89 patients (97.8%). Six-month survival in patients with severe left-sided congenital diaphragmatic hernia did not differ significantly between patients who underwent fetoscopic endoluminal tracheal occlusion and those managed expectantly (69.8% vs 58.1%, P =.30). Patients who underwent fetoscopic endoluminal tracheal occlusion had higher rates of preterm prelabor rupture of membranes (54.0% vs 14.3%, P <.001), earlier gestational age at delivery (median 35.0 weeks vs 38.3 weeks, P <.001), and lower birth weights (mean 2,487 g vs 2,857 g, P =.001). On subanalysis, in patients for whom all recorded observed-to-expected lung/head ratio measurements were below 25%, patients with fetoscopic endoluminal tracheal occlusion required fewer days of extracorporeal membrane oxygenation (ECMO) (median 9.0 days vs 17.0 days, P =.014). CONCLUSION: In this cohort, fetoscopic endoluminal tracheal occlusion was successfully implemented across several North American fetal therapy centers. Although survival was similar among patients undergoing fetoscopic endoluminal tracheal occlusion and those expectantly managed, fetoscopic endoluminal tracheal occlusion in North American centers may reduce morbidity, as suggested by fewer days of ECMO in those patients with persistently reduced lung volumes (observed-to-expected lung/head ratio below 25%).

Aspects épidémiologiques, cliniques et évolutifs de la tuberculose multifocale à N'djamena / Epidemiology, Clinical Presentation and Outcome of Multifocal Tuberculosis in N'djamena

Introduction. La tuberculose est dite multifocale (TMF) lorsqu ́il y a l ́atteinte d ́au moins deux sites extra pulmonaires non contigus associée ou non à une atteinte pulmonaire. Cette étude avait pour but d'étudier les aspects épidémiologiques, diagnostics et évolutifs de la TMF au service de pneumo-phtisiologie du CHU-RN de N'Djamena. Matériels et méthode. Il s'agissait d'une étude rétrospective à visée descriptive de 5 ans allant de janvier 2018 à décembre 2022. Les variables étudiées étaient, épidémiologiques, cliniques et évolutives. Résultats. Au total, 185 patients étaient inclus sur 2001 cas de tuberculose, soit une fréquence de 9,24%. L'âge moyen était de 34,1 ans avec des extrêmes de 16 ans et 75 ans. Le sex-ratio était de 1,28. Les patients sans-emploi étaient majoritaire soit 47% des cas. La notion de contage tuberculeux représentait 13,5% des cas, et 66,5% des patients étaient vaccinés au BCG avec une séroprévalence VIH de 54,6%. Tous les signes habituels de la tuberculose étaient présents. La localisation pulmonaire était la plus représentée (66,2%) suivie de la localisation ganglionnaire (48,6%). Dans 80% des cas, la localisationétait bifocale. La mortalité était de 21,6% pour un séjour moyen d'hospitalisation de 20,26 jours. Conclusion. La tuberculose multifocale est une forme rare et grave, qui survient généralement chez les patients infectés par le VIH, mais le sujet immunocompétent peut être aussi touché. Un traitement antituberculeux doit être instauré le plus rapidement possible afind'éviter les complications

Introduction. Tuberculosisis called multifocal (TMF) when there is involvement of at least two non-contiguous extrapulmonary sites, whether or notassociated with pulmonary involvement. This study aimed to study the epidemiological, diagnostic and evolutionary aspects of FMT in the pneumo-phthisiology department of the CHU-RN of N'Djamena. Materials and method. This was a 5-year retrospective study with a descriptive aim from January 2018 to December 2022. The variables studied were epidemiological, clinical and progressive. Results. In total, 185 patients were included out of 2001 cases of tuberculosis, i.e. a frequency of 9.24%. The average age was 34.1 years with extremes of 16 and 75 years. The sex ratio was 1.28. Unemployed patients were the majority, i.e. 47% of cases. The notion of tuberculosis contagion represented 13.5% of cases, and 66.5% of patients were vaccinated with BCG with an HIV seroprevalence of 54.6%. All the usual signs of tuberculosis were present. The pulmonary location was the most represented (66.2%) followed by the lymph node location (48.6%). In 80% of cases, bifocal localization. Mortality was 21.6% for an average hospital stay of 20.26 days. Conclusion.Multifocal tuberculosis is a rare and serious form, which generally occurs in patients infected with HIV, but immunocompetent subjects can also be affected. Anti-tuberculosis treatment must be started as quickly as possible to avoid complications.

Neonatal Survival After Serial Amnioinfusions for Bilateral Renal Agenesis: The Renal Anhydramnios Fetal Therapy Trial.

Importance: Early anhydramnios during pregnancy, resulting from fetal bilateral renal agenesis, causes lethal pulmonary hypoplasia in neonates. Restoring amniotic fluid via serial amnioinfusions may promote lung development, enabling survival. Objective: To assess neonatal outcomes of serial amnioinfusions initiated before 26 weeks' gestation to mitigate lethal pulmonary hypoplasia. Design, Setting, and Participants: Prospective, nonrandomized clinical trial conducted at 9 US fetal therapy centers between December 2018 and July 2022. Outcomes are reported for 21 maternal-fetal pairs with confirmed anhydramnios due to isolated fetal bilateral renal agenesis without other identified congenital anomalies. Exposure: Enrolled participants initiated ultrasound-guided percutaneous amnioinfusions of isotonic fluid before 26 weeks' gestation, with frequency of infusions individualized to maintain normal amniotic fluid levels for gestational age. Main Outcomes and Measures: The primary end point was postnatal infant survival to 14 days of life or longer with dialysis access placement. Results: The trial was stopped early based on an interim analysis of 18 maternal-fetal pairs given concern about neonatal morbidity and mortality beyond the primary end point despite demonstration of the efficacy of the intervention. There were 17 live births (94%), with a median gestational age at delivery of 32 weeks, 4 days (IQR, 32-34 weeks). All participants delivered prior to 37 weeks' gestation. The primary outcome was achieved in 14 (82%) of 17 live-born infants (95% CI, 44%-99%). Factors associated with survival to the primary outcome included a higher number of amnioinfusions (P = .01), gestational age greater than 32 weeks (P = .005), and higher birth weight (P = .03). Only 6 (35%) of the 17 neonates born alive survived to hospital discharge while receiving peritoneal dialysis at a median age of 24 weeks of life (range, 12-32 weeks). Conclusions and Relevance: Serial amnioinfusions mitigated lethal pulmonary hypoplasia but were associated with preterm delivery. The lower rate of survival to discharge highlights the additional mortality burden independent of lung function. Additional long-term data are needed to fully characterize the outcomes in surviving neonates and assess the morbidity and mortality burden. Trial Registration: ClinicalTrials.gov Identifier: NCT03101891.

Maternal exposure to polystyrene nanoplastics alters fetal brain metabolism in mice.

INTRODUCTION: Plastics used in everyday materials accumulate as waste in the environment and degrade over time. The impacts of the resulting particulate micro- and nanoplastics on human health remain largely unknown. In pregnant mice, we recently demonstrated that exposure to nanoplastics throughout gestation and during lactation resulted in changes in brain structure detected on MRI. One possible explanation for this abnormal postnatal brain development is altered fetal brain metabolism. OBJECTIVES: To determine the effect of maternal exposure to nanoplastics on fetal brain metabolism. METHODS: Healthy pregnant CD-1 mice were exposed to 50 nm polystyrene nanoplastics at a concentration of 106 ng/L through drinking water during gestation. Fetal brain samples were collected at embryonic day 17.5 (n = 18-21 per group per sex) and snap-frozen in liquid nitrogen. Magic angle spinning nuclear magnetic resonance was used to determine metabolite profiles and their relative concentrations in the fetal brain. RESULTS: The relative concentrations of gamma-aminobutyric acid (GABA), creatine and glucose were found to decrease by 40%, 21% and 30% respectively following maternal nanoplastic exposure when compared to the controls (p < 0.05). The change in relative concentration of asparagine with nanoplastic exposure was dependent on fetal sex (p < 0.005). CONCLUSION: Maternal exposure to polystyrene nanoplastics caused abnormal fetal brain metabolism in mice. The present study demonstrates the potential impacts of nanoplastic exposure during fetal development and motivates further studies to evaluate the risk to human pregnancies.

Serial lung mass volume ratios as prognostic indicators of neonatal respiratory morbidity in fetal pulmonary malformations.

BACKGROUND: Several studies have shown that the congenital pulmonary airway malformation volume ratio is a useful prognosticator of neonatal outcome in prenatally diagnosed lung lesions. However, there remains a lack of consensus on which congenital pulmonary airway malformation volume ratio values have the best predictive value because of operator dependence, inherent changes in lung lesion size throughout gestation, and the widespread use of maternal steroids. OBJECTIVE: This study sought to determine the association between serial congenital pulmonary airway malformation volume ratio measurements and neonatal outcomes among fetuses with lung malformations. STUDY DESIGN: This was a retrospective cohort study of fetuses with a prenatally diagnosed lung malformation managed at 2 major fetal centers from January 2010 to December 2021. Prenatal variables, including prospectively measured congenital pulmonary airway malformation volume ratio measurements (initial, maximum, and final), were analyzed. The results were correlated with 3 outcome measures, namely surgical resection before 30 days of life, a need for supplemental O2 at birth, and endotracheal intubation at birth. Statistical analyses were performed using receiver operating characteristic curve analyses, Welch 2 sample t tests, and multivariable logistic regressions (P<.05). RESULTS: There were 123 fetuses with isolated lung lesions identified. Eight (6.5%) had hydrops. The mean initial congenital pulmonary airway malformation volume ratio was 0.67±0.61 cm2 at 22.9±3.9 weeks' gestation. The mean maximum congenital pulmonary airway malformation volume ratio was 1.08 ± 0.94 cm2 at 27.0 ± 4.0 weeks' gestation. The mean final congenital pulmonary airway malformation volume ratio was 0.58±0.60 cm2 at 33.2±4.1 weeks' gestation. At a mean gestational age at delivery of 38.3±2.6 weeks, 15 (12.2%) underwent neonatal lung resection for symptomatic disease. In a multivariable regression, all 3 congenital pulmonary airway malformation volume ratio measurements showed a significant correlation with neonatal lung resection (P<.001). Optimal congenital pulmonary airway malformation volume ratio cutoffs were established based on an initial congenital pulmonary airway malformation volume ratio of ≥0.8 cm2, maximum congenital pulmonary airway malformation volume ratio of ≥1.5 cm2, and a final congenital pulmonary airway malformation volume ratio of ≥1.3 cm2 with associated areas under the curve of 0.89, 0.97, and 0.93, respectively. The final congenital pulmonary airway malformation volume ratio had the highest specificity for predicting surgical lung resection in the early postnatal period. CONCLUSION: Measuring congenital pulmonary airway malformation volume ratios throughout pregnancy in fetuses with pulmonary malformations has clinical value for prenatal counseling and planning care transition after delivery. Fetuses with a final congenital pulmonary airway malformation volume ratio of more than 1.3 cm2 are likely to require neonatal surgery and therefore should be delivered at tertiary care centers with a neonatal intensive care unit and pediatric surgical expertise.

Relationship between systemic immune-inflammation index and no-reflow in percutaneous coronary intervention for saphenous grafts.

Objective: In this study, we investigated the occurrence of no-reflow (NR) in percutaneous coronary intervention (PCI) for saphenous vein grafts (SVGs) and its relationship with a new systemic immune-inflammation index (SII) that determines inflammation. Methods: We studied 303 patients with acute coronary syndrome without ST elevation who underwent PCI for SVG disease. Results: NR formation during SVG PCI was significantly higher in patients with high SII (p < 0.001). NR occurrence was 12.8% when SII was ≤548 and 41.9% when SII was >548. Conclusion: Our study is the first to investigate SII as the state of inflammation and its effect on the SVG PCI. Patients with higher SII have a higher risk of NR during an SVG for PCI.

This study is about a type of surgery called bypass surgery, which is done to help when the heart is not working properly. During this surgery, doctors sometimes use veins in the leg to create new pathways for blood to flow around the heart. However, after a while these vessels can narrow or become blocked, so another procedure, stenting, is done to open them. Even after the stent is placed, the blood flow through the vein is sometimes not as good as it should be. This is called 'no reflow'. We wanted to investigate how often this problem occurs and whether it is related to a marker called the systemic immune-inflammation index (SII), which is a measure of inflammation in the body. We analyzed 303 patients who underwent stenting after a heart attack. We divided them into two groups according to their SII scores and investigated whether there was a difference in no-reflow occurrence between the two groups. We found that patients with a higher SII score were more likely to have no reflow during the stenting procedure, and an increased risk of no reflow if the SII score was above 548. This study was the first to look at SII and how it affects the stenting procedure for vessels used in bypass surgery.

How much is the long-term quality of life impaired in cholecystectomy-related biliary tract injury?

Objectives: Iatrogenic bile duct injury (IBDI) is a serious complication of cholecystectomy that may crucially affect long-term quality of life and have major morbidities. Furthermore, even after reconstructive surgical treatment, such injuries still reduce the long-term quality of life. Therefore, there remains a need to investigate long-term quality of life of the patients since it is considered that there is a long-term decrease in both physical and mental quality of life. Accordingly, this study aimed to investigate the clinical evaluations and long-term quality of life of the patients who had undergone reconstructive surgery for iatrogenic bile duct injury. Material and Methods: This clinical study included 49 patients (38 females/11 males) with cholecystectomy-associated bile duct injury and who underwent reconstruction surgery. Several parameters, including the type of bile duct injury, reconstructive surgical procedures, length of hospital stay, and complications were evaluated. Moreover, the effects of reconstructive surgical timing (perioperative, early postoperative, late postoperative) on quality of life were assessed. Long term quality of life (LTQL) levels were evaluated using the SF-36 questionnaire in patients whose follow-ups ranged from two to nine years. The SF-36 questionnaire scores were compared to the average SF-36 norm values of the healthy Turkish population. Results: Our results showed that 73.5% of biliary tract injuries occurred after a laparoscopic surgery while 26.5% after open cholecystectomy. Of the injuries, 32.7% developed in patients with acute cholecystitis. Thirty of the patients were treated with hepaticojejunostomy. When SF-36 questionnaire scores of the study were compared to those of the healthy Turkish population, energy-vitality was found to be lower significantly in male patients (p= 0.041). However, there was no significant deterioration in female patients. Although general health perception was better in hepaticojejunostomy according to the type of reconstructive surgery performed, no significant difference was observed in the quality of life. Mental health, energy-vitality (p= 0.019), and general health perception (p= 0.026) were found to be lower in women who had E1 -E2 injuries. Only seven of the injuries were detected perioperatively. Physical function (p= 0.033) and general health perception (p= 0.035) were found to be lower in the early postoperative treatment group in male patients in terms of the time of reconstructive surgery. Conclusion: IBDIs cause serious morbidity. Furthermore, even after reconstructive surgical treatment, such injuries still reduce LTQL. Our results suggest that LTQL is lower, especially in male patients undergoing postoperative early biliary repair for Strasberg E3 -E4 type injuries.

Potential higher risk of tethered spinal cord in children after prenatal surgery for myelomeningocele: A systematic review and meta-analysis.

INTRODUCTION: We performed a systematic review and meta-analysis on the incidence of secondary tethered spinal cord (TSC) between prenatal and postnatal closure in patients with MMC. The objectives was to understand the incidence of secondary TSC after prenatal surgery for MMC compared to postnatal surgery for MMC. MATERIAL AND METHODS: On May 4, 2023, a systematic search was conducted in Medline, Embase, and the Cochrane Library to gather relevant data. Primary studies focusing on repair type, lesion level, and TSC were included, while non-English or non-Dutch reports, case reports, conference abstracts, editorials, letters, comments, and animal studies were excluded. Two reviewers assessed the included studies for bias risk, following PRISMA guidelines. TSC frequency in MMC closure types was determined, and the relationship between TSC occurrence and closure technique was analyzed using relative risk and Fisher's exact test. Subgroup analysis revealed relative risk differences based on study designs and follow-up periods. A total of ten studies, involving 2,724 patients, were assessed. Among them, 2,293 patients underwent postnatal closure, while 431 received prenatal closure for the MMC defect. In the prenatal closure group, TSC occurred in 21.6% (n = 93), compared to 18.8% (n = 432) in the postnatal closure group. The relative risk (RR) of TSC in patients with prenatal MMC closure versus postnatal MMC closure was 1.145 (95%CI 0.939 to 1.398). Fisher's exact test indicated a statistically non-significant association (p = 0.106) between TSC and closure technique. When considering only RCT and controlled cohort studies, the overall RR for TSC was 1.308 (95%CI 1.007 to 1.698) with a non-significant association (p = .053). For studies focusing on children up until early puberty (maximum 12 years follow-up), the RR for tethering was 1.104 (95%CI 0.876 to 1.391), with a non-significant association (p = 0.409). CONCLUSION AND DISCUSSION: This review found no significant increase in relative risk of TSC between prenatal and postnatal closure in MMC patients, but a trend of increased TSC in the prenatal group. More long-term data on TSC after fetal closure is needed for better counseling and outcomes in MMC.