Urogenital cultures and preterm birth in women with cervical cerclage: a single center retrospective cohort study.

BACKGROUND: The leading hypothesis of the pathogenesis of cervical insufficiency suggests a role of cervical inflammation. Urogenital tract infections could play a causative role in this process. To test this hypothesis in women with a cervical cerclage, we aimed to retrospectively examine the relationship between gestational age (GA) at delivery and positive urogenital cultures. METHODS: This single center retrospective study reviewed the records of all women with a singleton pregnancy that underwent cervical cerclage (n = 203) between 2010 and 2020 at the University Hospital of Leuven, Belgium. Transvaginal cerclages were categorized as history indicated (TVC I, n = 94), ultrasound indicated (TVC II, n = 79) and clinically indicated (TVC III, n = 20). Additionally, ten women received transabdominal cerclage (TAC). Urogenital cultures (vaginal and urine) were taken before and after cerclage with 4-week intervals. Urogenital cultures were reported 'positive' if urine and/or vaginal cultures showed significant growth of a microorganism. Treatment decision depended on culture growth and clinical presentation. The primary aim was to evaluate the association between the urogenital culture results and the GA at delivery, for each of the cerclage groups. Secondarily, to investigate the effect of antibiotic treatment of positive cultures on GA at delivery. RESULTS: Positive pre-cerclage urogenital cultures were associated with lower GA at delivery in TVC III (positive culture 26w4d ± 40d vs. negative 29w6d ± 54d, p = 0.036). For TVC I, GA at delivery was longer when pre-cerclage urogenital cultures were positive (positive culture 38w0d ± 26d vs. negative 35w4d ± 42d, p = 0.035). Overall post-cerclage urogenital cultures status was not associated with a different GA at delivery. Treating patients with pre- or post-cerclage positive urogenital cultures did also not change GA at delivery. CONCLUSION: Positive urogenital cultures taken before clinically indicated cerclage intervention may be associated with lower GA at delivery. However, there seems to be no benefit of antibiotic treatment or routine urogenital cultures during follow-up of asymptomatic women after cerclage placement.

Preterm membranes are mechanically more resistant than term membranes.

OBJECTIVE: To compare the biomechanical properties of fetal preterm membranes (20 + 0 weeks to 30 + 0 weeks) to those of the term (37 + 0 to 41 + 0 weeks). METHOD: Amnion and chorion were manually separated and samples were cut to the required geometry. Rectangular samples with (mode 1) and without (uniaxial) a notch, were tested for tearing energy, critical elongation, and tangent stiffness. Suture retention and inter-suture distance testing investigated the effect of suture placement. RESULTS: From the 15 preterm and 10 term placentas studied, no notable differences were observed in uniaxial testing. Mode 1 fracture testing showed a difference in tearing energy between the preterm and term chorion (0.025 ± 0.005 vs. 0.017 ± 0.005 J/m-1 ; p = 0.027) but not in the amnion (0.030 ± 0.017 vs. 0.029 ± 0.009 J/m-1 ; p = 0.895). Both preterm amnion and chorion showed a higher critical elongation compared with term (1.229 ± 0.057 vs. 1.166 ± 0.046; p = 0.019 and 1.307 ± 0.049 vs. 1.218 ± 0.058; p = 0.012). Preterm amnion had a higher suture retention strength than its term counterpart (0.189 ± 0.065 vs. 0.121 ± 0.031 N; p = 0.023). In inter-suture distance tests, no significant interaction was observed beyond 3 mm, but the preterm chorion showed less interaction at 1-2 mm distances. CONCLUSION: Preterm membranes have equivalent or superior tensile properties to term membranes. The chorion appears to contribute to the mechanical integrity of fetal membranes, particularly in preterm stages.

Periarticular infiltration used in total joint replacements: an update and review article.

Periarticular infiltration following total knee and hip arthroplasty has been demonstrated to be equivalent to peripheral nerve blocks for postoperative pain management. The ideal cocktail has not been established yet. We have conducted a literature search on PubMed and Embase. Our search criteria included randomized controlled trials (RCTs) and systematic reviews (SRs). We tried to only include the most recent studies to keep the information current. The included research focused at Dexmedetomidine, Liposomal Bupivacaine, Ropivacaine, Epinephrine, Ketorolac, Morphine, Ketamine and Glucocorticosteroids. Each medication's mode of action, duration, ideal dosage, contraindications, side effects and effectiveness have been summarized in the review article. This article will help the clinician to make an informed evidence-based decision about which medications to include in their ideal cocktail.

Long-term pulmonary and neurodevelopmental impairment in a fetal growth restriction rabbit model.

Fetal growth restriction (FGR) remains one of the main obstetrical problems worldwide, with consequences beyond perinatal life. Animal models with developmental and structural similarities to the human are essential to understand FGR long-term consequences and design novel therapeutic strategies aimed at preventing or ameliorating them. Herein, we described the long-term consequences of FGR in pulmonary function, structure, and gene expression, and characterized neurodevelopmental sequelae up to preadolescence in a rabbit model. FGR was induced at gestational day 25 by surgically reducing placental blood supply in one uterine horn, leaving the contralateral horn as internal control. Neonatal rabbits born near term were assigned to foster care in mixed groups until postnatal day (PND) 21. At that time, one group underwent pulmonary biomechanical testing followed by lung morphometry and gene expression analysis. A second group underwent longitudinal neurobehavioral assessment until PND 60 followed by brain harvesting for multiregional oligodendrocyte and microglia quantification. FGR was associated with impaired pulmonary function and lung development at PND 21. FGR rabbits had higher respiratory resistance and altered parenchymal biomechanical properties in the lungs. FGR lungs presented thicker alveolar septal walls and reduced alveolar space. Furthermore, the airway smooth muscle content was increased, and the tunica media of the intra-acinar pulmonary arteries was thicker. In addition, FGR was associated with anxiety-like behavior, impaired memory and attention, and lower oligodendrocyte proportion in the frontal cortex and white matter. In conclusion, we documented and characterized the detrimental pulmonary function and structural changes after FGR, independent of prematurity, and beyond the neonatal period for the first time in the rabbit model, and describe the oligodendrocyte alteration in pre-adolescent rabbit brains. This characterization will allow researchers to develop and test therapies to treat FGR and prevent its sequelae.

The Effects of Prenatal Pravastatin Treatment in the Rabbit Fetal Growth Restriction Model.

Fetal growth restriction (FGR) remains without an effective prenatal treatment. Evidence from murine FGR models suggests a beneficial effect of prenatal pravastatin. Since the rabbit hemodichorial placenta more closely resembles the human condition, we investigated the effects of prenatal maternal pravastatin administration in the rabbit FGR model. At a gestational age of 25 days (term 31d), pregnant dams underwent partial uteroplacental vessel ligation (UPVL) in one uterine horn to induce FGR, leaving the other horn as a control. Dams were randomized to either receive 5 mg/kg/d pravastatin dissolved in their drinking water or normal drinking water until delivery. At GA 30d, the rabbits were delivered and were divided into four groups: control without pravastatin (C/NoPrav), FGR without pravastatin (FGR/NoPrav), FGR with pravastatin (FGR/Prav), and controls with pravastatin (C/Prav). The newborn rabbits underwent pulmonary functional assessment and neurobehavioral assessment, and they were harvested for alveolar morphometry or neuropathology. The placentas underwent histology examination and RNA expression. Birth weight was lower in the FGR groups (FGR/Prav, FGR/NoPrav), but there was no difference between FGR/Prav and C/NoPrav. No differences were noted in placental zone proportions, but eNOS in FGR/Prav placentas and VEGFR-2 in FGR/Prav and C/Prav were upregulated. There were no differences in pulmonary function assessment and alveolar morphometry. FGR/Prav kittens had increased neurosensory scores, but there were no differences in neuromotor tests, neuron density, apoptosis, and astrogliosis. In conclusion, in the rabbit FGR model, pravastatin upregulated the expression of VEGFR-2 and eNOS in FGR placentas and was associated with higher neurosensory scores, without measurable effects on birthweight, pulmonary function and morphology, and neuron density.

Duration of fetoscopic spina bifida repair does not affect the central nervous system in fetal lambs.

BACKGROUND: Prenatal spina bifida aperta repair improves neurologic outcomes yet comes with a significant risk of prematurity and uterine scar-related complications. To reduce such complications, different fetoscopic techniques, for example, with varying numbers of ports, are being explored. This has an effect on the duration of the procedure, potentially affecting central nervous system development. Both the condition and anesthesia can affect the central nervous system, particularly the hippocampus, a region crucial for prospective and episodic memory. Previous animal studies have shown the potential influence of anesthesia, premature delivery, and maternal surgery during pregnancy on this area. OBJECTIVE: This study aimed to compare the effects of 2- vs 3-port fetoscopic spina bifida aperta repair in the fetal lamb model using neuron count of the hippocampus as the primary outcome. STUDY DESIGN: Based on the hippocampal neuron count from previous lamb experiments, we calculated that we required 5 animals per group to achieve a statistical power of ≥ 80%. A spina bifida aperta defect was developed in fetal lambs at 75 days of gestation (term: 145 days). At 100 days, fetuses underwent either a 2-port or 3-port fetoscopic repair. At 143 days, all surviving fetuses were delivered by cesarean delivery, anesthetized, and transcardially perfused with a mixture of formaldehyde and gadolinium. Next, they underwent neonatal brain and spine magnetic resonance imaging after which these organs were harvested for histology. Hippocampus, frontal cortex, caudate nucleus, and cerebellum samples were immunostained to identify neurons, astrocytes, microglia, and markers associated with cell proliferation, myelination, and synapses. The degree of hindbrain herniation and the ventricular diameter were measured on magnetic resonance images and volumes of relevant brain and medulla areas were segmented. RESULTS: Both treatment groups included 5 fetuses and 9 unoperated littermates served as normal controls. The durations for both skin-to-skin (341±31 vs 287±40 minutes; P=.04) and fetal surgery (183±30 vs 128±22; P=.01) were longer for the 2-port approach than for the 3-port approach. There was no significant difference in neuron density in the hippocampus, frontal cortex, and cerebellum. In the caudate nucleus, the neuron count was higher in the 2-port group (965±156 vs 767±92 neurons/mm2; P=.04). There were neither differences in proliferation, astrogliosis, synaptophysin, or myelin. The tip of the cerebellar vermis was closer to the foramen magnum in animals undergoing the 2-port approach than in animals undergoing the 3-port approach (-0.72±0.67 vs -2.47±0.91 mm; P=.009). There was no significant difference in the ratio of the hippocampus, caudate nucleus, or cerebellar volume to body weight. For the spine, no difference was noted in spine volume-to-body weight ratio for the lower (L1-L2), middle (L3-L4), and higher (L5-L6) levels. Compared with controls, in repaired animals, the cerebellar vermis tip laid closer to the foramen magnum, parietal ventricles were enlarged, and medulla volumes were reduced. CONCLUSION: In the experimental spina bifida fetal lamb model, a 2-port repair took 40% longer than a 3-port repair. However, there was no indication of any relevant morphologic differences in the fetal brain.

Subsequent fertility, pregnancy, and gynaecological and psychological outcomes after maternal-fetal surgery for open spina bifida: A prospective cohort study.

OBJECTIVE: To determine the medium-term maternal impact of open fetal spina bifida repair. DESIGN: Prospective cohort study. SETTING: University Hospitals Leuven, Belgium. POPULATION: Mothers who had open maternal-fetal spina bifida repair between March 2012 and December 2021. METHODS: A patient-reported survey on subsequent fertility, pregnancy, and gynaecological and psychological outcomes. MAIN OUTCOME MEASURES: Complications during subsequent pregnancies, and gynaecological and psychological problems. RESULTS: Seventy-two out of 100 invited women completed the questionnaire (72%). Despite being advised not to, seven of 13 women attempting to conceive became pregnant within 2 years after fetal surgery and one woman delivered vaginally. Two of the 16 subsequent pregnancies were complicated by an open neural tube defect. One pregnancy was complicated by a placenta accreta and one pregnancy was complicated by a uterine rupture, both with good neonatal outcomes. Nearly half of respondents who did not attempt to conceive reported that this was because of their experience of the index pregnancy and caring for the index child. Three out of four respondents reported medium-term psychological problems, mostly anxiety for the health of the index child, fear for recurrence in subsequent pregnancies and feelings of guilt. CONCLUSIONS: Open maternal-fetal surgery for spina bifida did not appear to affect fertility in our cohort. Half of the attempts to conceive took place within 2 years. One uterine rupture and one placenta accreta occurred in 16 subsequent pregnancies. Most respondents reported psychological problems linked to the index pregnancy, which reinforces the need for long-term psychological support.

Low-Cost COTS GNSS Interference Monitoring, Detection, and Classification System.

Interference signals cause position errors and outages to global navigation satellite system (GNSS) receivers. However, to solve these problems, the interference source must be detected, classified, its purpose determined, and localized to eliminate it. Several interference monitoring solutions exist, but these are expensive, resulting in fewer nodes that may miss spatially sparse interference signals. This article introduces a low-cost commercial-off-the-shelf (COTS) GNSS interference monitoring, detection, and classification receiver. It employs machine learning (ML) on tailored signal pre-processing of the raw signal samples and GNSS measurements to facilitate a generalized, high-performance architecture that does not require human-in-the-loop (HIL) calibration. Therefore, the low-cost receivers with high performance can justify significantly more receivers being deployed, resulting in a significantly higher probability of intercept (POI). The architecture of the monitoring system is described in detail in this article, including an analysis of the energy consumption and optimization. Controlled interference scenarios demonstrate detection and classification capabilities exceeding conventional approaches. The ML results show that accurate and reliable detection and classification are possible with COTS hardware.

Evaluation of Low-Complexity Adaptive Full Direct-State Kalman Filter for Robust GNSS Tracking.

This paper evaluates the implementation of a low-complexity adaptive full direct-state Kalman filter (DSKF) for robust tracking of global navigation satellite system (GNSS) signals. The full DSKF includes frequency locked loop (FLL), delay locked loop (DLL), and phase locked loop (PLL) tracking schemes. The DSKF implementation in real-time applications requires a high computational cost. Additionally, the DSKF performance decays in time-varying scenarios where the statistical distribution of the measurements changes due to noise, signal dynamics, multi-path, and non-line-of-sight effects. This study derives the full lookup table (LUT)-DSKF: a simplified full DSKF considering the steady-state convergence of the Kalman gain. Moreover, an extended version of the loop-bandwidth control algorithm (LBCA) is presented to adapt the response time of the full LUT-DSKF. This adaptive tracking technique aims to increase the synchronization robustness in time-varying scenarios. The proposed tracking architecture is implemented in an GNSS hardware receiver with an open software interface. Different configurations of the adaptive full LUT-DSKF are evaluated in simulated scenarios with different dynamics and noise cases for each implementation. The results confirm that the LBCA used in the FLL-assisted-PLL (FAP) is essential to maintain a position, velocity, and time (PVT) fix in high dynamics.

Effects of cumulative duration of repeated anaesthesia exposure on foetal brain development in the ovine model.

OBJECTIVE: Anaesthesia is required in 0.4-1% of pregnant women, and prolonged and repeated exposures to anaesthesia may be required. It is unknown whether these exposures may result in foetal neurotoxicity in humans. As sheep have a gestation comparable to that of humans, the objective of this study was to analyse the neurodevelopmental outcome of ovine foetuses that had been exposed in utero to repeated and prolonged anaesthesia. DESIGN: Randomized controlled preclinical study. SETTING: Anaesthesia for non-obstetric surgery during pregnancy. ANIMALS: Twenty-four healthy pregnant Swifter ewes. INTERVENTIONS: The ewes were randomized to no anaesthesia exposure (control-group), single exposure (at gestational age 68-70 days), or repeated exposure (at gestational age 68-70 days and 96-98 days) to 2.5 h of sevoflurane anaesthesia and maternal laparotomy. All lambs were delivered at approximately term gestation (gestational age: 140-143 days). MEASUREMENTS: The primary outcome was neuron density in the frontal cortex 24 h after birth for the control-group versus the repeated-exposure-group. Key secondary outcome was the time needed to achieve the milestone of standing. Secondary outcomes included other neurobehavioural assessments (e.g., motoric milestones) and histological parameters quantified in multiple brain regions (neuron density, total cell density, proliferation, inflammation, synaptogenesis, astrocytes and myelination). MAIN RESULTS: Neuron density in the frontal cortex did not differ between groups (mean ±â€¯standard deviation: control-group: 403 ±â€¯39, single-exposure group: 436 ±â€¯23 and repeated-exposure-group: 403 ±â€¯40 neurons/mm2, control-group versus repeated-exposure-group: p = 0.986, control-group versus single-exposure-group: p = 0.097). No significant difference was observed for the time needed to achieve the milestone of standing. Only very limited differences were observed for other histological outcome parameters and neurobehavioural assessments. CONCLUSIONS: There is no evidence for foetal neuronal injury or neurobehavioural impairments after a cumulative duration of 5 h repetitive prenatal anaesthesia in sheep.

Fetal Growth Restriction Impairs Lung Function and Neurodevelopment in an Early Preterm Rabbit Model.

We previously reported the multi-system sequelae of fetal growth restriction, induced by placental underperfusion, in near-term born rabbits, in the immediate neonatal period and up to pre-adolescence. Herein, we describe the pulmonary and neurodevelopmental consequences of FGR in rabbits born preterm. We hypothesize that FGR has an additional detrimental effect on prematurity in both pulmonary function and neurodevelopment. FGR was induced at gestational day (GD) 25 by placental underperfusion, accomplished by partial uteroplacental vessel ligation in one uterine horn. Rabbits were delivered by cesarean section at GD 29, and placentas were harvested for histology. Neonates underwent neurobehavioral or pulmonary functional assessment at postnatal day 1, followed by brain or lung harvesting, respectively. The neurodevelopmental assessment included neurobehavioral testing and multiregional quantification of cell density and apoptosis in the brain. Lung assessment included functional testing, alveolar morphometry, and airway histology. FGR was associated with higher perinatal mortality, lower birth and placental weight, and a similar brain-to-body weight ratio compared to controls. Placental underperfusion decreased labyrinth and junction zone volumes in FGR placentas. FGR impaired pulmonary function, depicted by higher parenchymal resistance, damping, and elastance. Alveolar morphometry and airway smooth muscle content were comparable between groups. Neurobehavioral tests showed motoric and sensorial impairment in FGR rabbits. In FGR brains, cell density was globally reduced, with higher apoptosis in selected areas. In conclusion, in preterm-born rabbits, placental underperfusion leads to higher mortality, FGR, and impaired lung and brain development in early assessment. This study complements previous findings of placental, pulmonary, and neurodevelopmental impairment in near-term born rabbits in this model.

Placental vascular alterations are associated with early neurodevelopmental and pulmonary impairment in the rabbit fetal growth restriction model.

Fetal growth restriction is one of the leading causes of perinatal mortality and morbidity and has consequences that extend well beyond the neonatal period. Current management relies on timely delivery rather than improving placental function. Several prenatal strategies have failed to show benefit in clinical trials after promising results in animal models. Most of these animal models have important developmental and structural differences compared to the human and/or are insufficiently characterized. We aimed to describe placental function and structure in an FGR rabbit model, and to characterize the early brain and lung developmental morbidity using a multimodal approach. FGR was induced in time-mated rabbits at gestational day 25 by partial uteroplacental vessel ligation in one horn. Umbilical artery Doppler was measured before caesarean delivery at gestational day 30, and placentas were harvested for computed microtomography and histology. Neonates underwent neurobehavioral or pulmonary functional assessment the day after delivery, followed by brain or lung harvesting, respectively. Neuropathological assessment included multiregional quantification of neuron density, apoptosis, astrogliosis, cellular proliferation, and oligodendrocyte progenitors. Brain region volumes and diffusion metrics were obtained from ex-vivo brain magnetic resonance imaging. Lung assessment included biomechanical tests and pulmonary histology. Fetal growth restriction was associated with labyrinth alterations in the placenta, driven by fetal capillary reduction, and overall reduced vessels volume. FGR caused altered neurobehavior paralleled by regional neuropathological deficits and reduced fractional anisotropy in the cortex, white matter, and hippocampus. In addition, FGR kittens presented functional alterations in the peripheral lung and structurally underdeveloped alveoli. In conclusion, in a uteroplacental insufficiency FGR rabbit model, placental vascular alterations coincide with neurodevelopmental and pulmonary disruption.

Prenatal interventions for fetal growth restriction in animal models: A systematic review.

Fetal growth restriction (FGR) in human pregnancy is associated with perinatal mortality, short- and long-term morbidities. No prenatal therapy is currently established despite decades of research. We aimed to review interventions in animal models for prenatal FGR treatment, and to seek the next steps for an effective clinical therapy. We registered our protocol and searched MEDLINE, Embase, and The Cochrane Library with no language restrictions, in accordance with the PRISMA guideline. We included all studies that reported the effects of any prenatal intervention in animal models of induced FGR. From 3257 screened studies, 202 describing 237 interventions were included for the final synthesis. Mice and rats were the most used animals (79%) followed by sheep (16%). Antioxidants (23%), followed by vasodilators (18%), nutrients (14%), and immunomodulators (12%) were the most tested therapy. Two-thirds of studies only reported delivery or immediate neonatal outcomes. Adverse effects were rarely reported (11%). Most studies (73%), independent of the intervention, showed a benefit in fetal survival or birthweight. The risk of bias was high, mostly due to the lack of randomization, allocation concealment, and blinding. Future research should aim to describe both short- and long-term outcomes across various organ systems in well-characterized models. Further efforts must be made to reduce selection, performance, and detection bias.

Are there differences between monochorionic twin placentas after spontaneous and assisted conception?

INTRODUCTION: No data are available on the placental characteristics of monochorionic twin pregnancies conceived by in vitro fertilization (IVF). This study investigates the differences between placentas from monochorionic diamniotic (MCDA) twin pregnancies conceived spontaneously and those conceived after IVF. METHODS: This is a retrospective analysis of placental data from a consecutive series of MCDA twin pregnancies followed from the first trimester. The following placental characteristics were compared between IVF versus spontaneous MCDA pregnancies: placental sharing and birth weight discordance relative to placental sharing, the placental angioarchitecture (number, type, and size of anastomoses), and the umbilical cord insertion types. RESULTS: Of the 256 MCDA placentas included in this analysis, 32 (12%) were conceived through IVF and 224 (88%) spontaneously. MCDA twin placentas after IVF did not differ significantly from MCDA twin placentas after spontaneous conception regarding placental sharing, birthweight discordance relative to sharing discordance, and angioarchitecture. There was a trend toward more discordant cord insertions (combination eccentric and velamentous) in IVF (25%) than in spontaneously conceived placentas (12%) (P = 0.05). DISCUSSION: No differences could be demonstrated between MCDA placentation after spontaneous conception and IVF. Any differences in pregnancy outcome between spontaneous and IVF conceived MCDA twins may not be related to differences in placental sharing, angioarchitecture and cord insertion type.

Outcomes of Monoamniotic Twin Pregnancies from the First Trimester Onward.

INTRODUCTION: Monochorionic monoamniotic (MCMA) twins are rare, and information is lacking on pregnancy outcomes from the first trimester onward. This study compares the pregnancy and neonatal outcomes between MCMA and monochorionic diamniotic (MCDA) twin pregnancies from the first trimester onward. We also report on the outcomes of MCMA twin pregnancies continuing after 28 weeks and on the neurodevelopmental outcomes of MCMA twins. METHODS: A retrospective single-center cohort study of MCMA and MCDA twin pregnancies followed from the first trimester with a fortnightly ultrasound scan. We excluded pregnancies with a major anomaly diagnosed on the first-trimester ultrasound scan. MCMA twin pregnancies were offered inpatient monitoring from 28 weeks onward, and an elective cesarean section was advised between 32 and 33 weeks. MCDA pregnancies were managed as inpatients only if medically indicated, and an elective birth between 36 and 37 weeks was recommended. RESULTS: We analyzed the outcomes of 52 MCMA and 671 MCDA twin pregnancies. In MCMA twins, the fetal and neonatal survival rate was 81/104 (78%) versus 1,192/1,342 (89%) in MCDA twins (p = 0.016). Double intrauterine demise (IUD) was more common in MA than in DA pairs (13% vs. 3%) (p = 0.002). No IUD occurred in the 40 MCMA pregnancies that continued after 28 weeks, but five women (13%) required an urgent cesarean section for fetal distress. Thirty-eight of 52 eligible infants (73%) underwent a neurodevelopmental assessment. Thirty-three (87%) had cognitive and motor development scores within normal limits. Four infants had mild cognitive or motor impairment, and one infant was diagnosed with spastic diplegia. CONCLUSION: MCMA twins are associated with decreased survival rates compared to MCDA due to increased rates of double IUD. After 28 weeks, about one in eight women required an urgent delivery for fetal distress. Most infants had normal neurodevelopmental outcomes.

Uterine hemangioma in pregnancy: A case report and review of the literature.

INTRODUCTION: Uterine hemangioma is a rare benign vascular tumor which can cause bleeding problems in various age groups. Current knowledge on this rare condition in pregnancy is limited. We report on a recent case of uterine hemangioma in a pregnancy that was already diagnosed during her first trimester. We also provide a literature review to summarize the characteristics and outcomes of uterine hemangioma cases in pregnant women. MATERIAL AND METHODS: A systematic search was done of all published literature up to February 2021 using PubMed and Scopus databases. The selection process was registered using the online tool Rayyan QCRI. All data was described in a narrative format. The protocol was prospectively registered on PROSPERO (CRD42021237519). RESULTS: Fifteen case reports were included. In most cases, the diagnosis was established by antenatal ultrasound. More than half of the women developed a postpartum hemorrhage, necessitating a hysterectomy for bleeding control in half of the cases, although the risk for both seemed lower in those women in whom the hemangioma was diagnosed before delivery. One case of maternal mortality and two cases of fetal death were reported. There was one case of neonatal respiratory morbidity, although the neonatal data were not routinely reported upon. CONCLUSION: Current knowledge on uterine hemangioma in pregnancy is limited, but it seems to hold substantial risks for both pregnant women and their unborn child. We recommend routine screening for this condition at the standard mid-trimester anomaly scan. Pregnant women with uterine hemangioma should ideally be cared for in centers of expertise. An international registry will help to build a better understanding of this rare pathology.

Drug concentration at the site of disease in children with pulmonary tuberculosis.

BACKGROUND: Current TB treatment for children is not optimized to provide adequate drug levels in TB lesions. Dose optimization of first-line antituberculosis drugs to increase exposure at the site of disease could facilitate more optimal treatment and future treatment-shortening strategies across the disease spectrum in children with pulmonary TB. OBJECTIVES: To determine the concentrations of first-line antituberculosis drugs at the site of disease in children with intrathoracic TB. METHODS: We quantified drug concentrations in tissue samples from 13 children, median age 8.6 months, with complicated forms of pulmonary TB requiring bronchoscopy or transthoracic surgical lymph node decompression in a tertiary hospital in Cape Town, South Africa. Pharmacokinetic models were used to describe drug penetration characteristics and to simulate concentration profiles for bronchoalveolar lavage, homogenized lymph nodes, and cellular and necrotic lymph node lesions. RESULTS: Isoniazid, rifampicin and pyrazinamide showed lower penetration in most lymph node areas compared with plasma, while ethambutol accumulated in tissue. None of the drugs studied was able to reach target concentration in necrotic lesions. CONCLUSIONS: Despite similar penetration characteristics compared with adults, low plasma exposures in children led to low site of disease exposures for all drugs except for isoniazid.

Performance Evaluation of Adaptive Tracking Techniques with Direct-State Kalman Filter.

This paper evaluates the performance of robust adaptive tracking techniques with the direct-state Kalman filter (DSKF) used in modern digital global navigation satellite system (GNSS) receivers. Under the assumption of a well-known Gaussian distributed model of the states and the measurements, the DSKF adapts its coefficients optimally to achieve the minimum mean square error (MMSE). In time-varying scenarios, the measurements' distribution changes over time due to noise, signal dynamics, multipath, and non-line-of-sight effects. These kinds of scenarios make difficult the search for a suitable measurement and process noise model, leading to a sub-optimal solution of the DSKF. The loop-bandwidth control algorithm (LBCA) can adapt the DSKF according to the time-varying scenario and improve its performance significantly. This study introduces two methods to adapt the DSKF using the LBCA: The LBCA-based DSKF and the LBCA-based lookup table (LUT)-DSKF. The former method adapts the steady-state process noise variance based on the LBCA's loop bandwidth update. In contrast, the latter directly relates the loop bandwidth with the steady-state Kalman gains. The presented techniques are compared with the well-known state-of-the-art carrier-to-noise density ratio (C/N0)-based DSKF. These adaptive tracking techniques are implemented in an open software interface GNSS hardware receiver. For each implementation, the receiver's tracking performance and the system performance are evaluated in simulated scenarios with different dynamics and noise cases. Results confirm that the LBCA can be successfully applied to adapt the DSKF. The LBCA-based LUT-DSKF exhibits superior static and dynamic system performance compared to other adaptive tracking techniques using the DSKF while achieving the lowest complexity.

Wide-Band Interference Mitigation in GNSS Receivers Using Sub-Band Automatic Gain Control.

The performance of global navigation satellite system (GNSS) receivers is significantly affected by interference signals. For this reason, several research groups have proposed methods to mitigate the effect of different kinds of jammers. One effective method for wide-band interference mitigation (IM) is the high-rate DFT-based data manipulator (HDDM) pulse blanker (PB). It provides good performance to pulsed and frequency sparse interference. However, it and many other methods have poor performance against wide-band noise signals, which are not frequency-sparse. This article proposes to include automatic gain control (AGC) in the HDDM structure to attenuate the signal instead of removing it: the HDDM-AGC. It overcomes the wide-band noise limitation for IM at the cost of limiting mitigation capability to other signals. Previous studies with this approach were limited to only measuring the carrier-to-noise density ratio (C/N0) performance of tracking, but this article extends the analysis to include the impact of the HDDM-AGC algorithm on the position, velocity, and time (PVT) solution. It allows an end-to-end evaluation and impact assessment of mitigation to a GNSS receiver. This study compares two commercial receivers: one high-end and one low-cost, with and without HDDM IM against laboratory-generated interference signals. The results show that the HDDM-AGC provides a PVT availability and precision comparable to high-end commercial receivers with integrated mitigation for most interference types. For pulse interferences, its performance is superior. Further, it is shown that degradation is minimized against wide-band noise interferences. Regarding low-cost receivers, the PVT availability can be increased up to 40% by applying an external HDDM-AGC.