Fever of unknown origin in pregnancy: A case report.

Systemic lupus erythematosus is an autoimmune disease that primarily affects women of reproductive age. In pregnancy, it can lead to maternal and fetal complications. However, diagnosis in pregnancy is challenging since the disease mimics many features associated with other disorders and some complications related to pregnancy. Here we report a 24-year-old woman at 26 weeks gestation who presented with a fever of unknown origin. She developed tachycardia, nausea, fatigue, rigors, and pancytopenia. Once sepsis and other chronic conditions were ruled out, rheumatology was consulted. Following the diagnosis of systemic lupus erythematosus, a combination of hydroxychloroquine, azathioprine, and corticosteroids was started, and the patient showed rapid improvement. She had an uncomplicated delivery at term. This case report highlights a unique presentation of new-onset systemic lupus erythematous in pregnancy. Delay in diagnosis can lead to maternal and fetal complications; however, prompt diagnosis and treatment can improve symptoms and lead to a favorable pregnancy outcome.

RASopathies are the most common set of monogenic syndromes identified by exome sequencing for nonimmune hydrops fetalis: A systematic review and meta-analysis.

RASopathies are a group of malformation syndromes known to lead to nonimmune hydrops fetalis (NIHF) in severe presentations. Pathogenic variants can be de novo or parentally inherited. Despite being a known frequent presentation, the fraction of monogenic NIHF cases due to RASopathies is limited in the literature. Also, the specific parental contribution of RASopathies to NIHF is not well described. Our objective was to review pooled exome sequencing (ES) diagnostic yield of RASopathies for NIHF and to determine the parental contribution of RASopathy to NIHF. We performed a systematic review of prenatal ES studies from January 1, 2000 to August 1, 2022. Thirty-six studies met inclusion criteria. Cases with RASopathy gene variants were reviewed. NIHF cases were further classified as isolated or non-isolated. Thirty-six ES studies including 46 pregnancies with NIHF and a diagnosed RASopathy were reviewed. Forty-four diagnostic variants and 2 variants of uncertain significance in 12 RASopathy genes were identified. Expanding on what was previously published, a total of 506 NIHF cases were extracted with 191 cases yielding a positive diagnosis by ES. The overall rate of RASopathy diagnosis in clinically diagnosed NIHF cases was 9% (44/506). The rate of RASopathy diagnosis among NIHF cases with positive genetic diagnosis by ES was 23% (44/191). Of the 46 cases identified, 13 (28%) variants were parentally inherited; specifically, 5/13 (38%) maternal, 3/13 (23%) paternal, 2/13 (15%) biparental, and 3/13 (23%) unspecified. Majority of NIHF cases 29/46 (63%) were isolated. Among NIHF cases with positive ES diagnoses, RASopathy diagnostic yield by ES was 23%. NIHF secondary to RASopathies was parentally inherited in 28% of cases. Most cases of NIHF due to RASopathy were isolated, with no prenatal detection of associated anomalies.

Fetal diagnosis of meconium periorchitis: A case report.

Fetal meconium periorchitis (MPO) is rare prenatal diagnosis associated with meconium peritonitis. The prenatal ultrasound finding consists of an enlarged fetal scrotum with echogenic fluid and debris. In this report, we describe a case in which a prenatal diagnosis of MPO was accurately made at 32 weeks of gestation. The neonate delivered without complications, underwent immediate evaluation followed by major surgery, and ultimately had a favorable outcome. An accurate prenatal diagnosis is important to counsel the patient in a multidisciplinary approach. This case highlights the prenatal ultrasound findings as well as the neonatal presentation and the possibility for conservative management by pediatric urology.

The efficiency of ErCr: YSGG laser on the debonding of different thicknesses of ceramic veneers

Aims: To verify the efficacy of Er,Cr:YSGG laser for debonding of lithium disilicate (LD) reinforced glass ceramic veneers of different thicknesses. Methods: Forty bovine teeth were prepared and randomly divided into four groups (n=10/group) according to the ceramic disc thickness: C0.5 (Control group) and L0.5 (Laser irradiated group) in which LD discs had a thickness of 0.5mm and 5mm diameter; C1 and L1 in which LD discs had a thickness of 1mm and 5mm diameter. The lithium disilcate discs (IPS E.max®, shade HTA2) were fabricated following the manufacturer's recommendations and cemented to the prepared tooth surface. The Er,Cr:YSGG laser was applied to the laser groups at 2.5W and 25Hz for 60seconds. Universal testing machine was used to evaluate the shear bond strength for all samples at a cross head speed of 1mm/min in an inciso-gingival direction parallel to the sample surface. After debonding, the samples were examined under stereoscope to evaluate the mode of failure according to the adhesive remnant index (ARI). Results: Laser irradiation significantly diminishes the shear bond strength from 10.868 MPa to 3.778 MPa for C0.5 and L0.5 groups respectively (p=0.00) and from 14.711 MPa to 4.992 MPa for C1 and L1 groups respectively (p=0.00). The shear bond strength required for debonding increased with increasing thickness of discs, but without significant difference (p=0.110). Higher ARI scores were seen in the laser groups (more cement remaining adhered to the tooth) when compared to the control groups. Conclusions: The Er,Cr:YSGG laser could be an effective and useful tool in debonding of lithium disilicate ceramic veneers as it decreases the shear bond strength required for veneer debonding

No association between perinatal mood disorders and hypertensive pregnancies.

Mental health disorders such as anxiety and/or depression are the most common mental health disorders seen among reproductive aged women and can increase during pregnancy. Many sociodemographic risk factors have been associated with anxiety and/or depression in pregnancy, which can lead to adverse maternal and infant outcomes including the risk of a hypertensive pregnancy. The current study prospectively examined self-reported anxiety, depression and stress in pregnant women without a history of fetal loss or mood disorders beginning at 20-26 weeks. At each study visit, circulating immune factors associated with perinatal mood disorders were measured in blood samples that were collected. A total of 65 women were eligible for data analysis, 26 of which had hypertensive pregnancies. There was not a significant difference in self-reported depression, anxiety or stress between hypertensive disorders of pregnancy and normotensive women. Black women were more likely to have a hypertensive pregnancy and develop a perinatal mood disorder compared to non-black women. Both the inflammatory cytokines interleukin-17 and tumor necrosis factor-alpha were increased in patients with perinatal mood disorders. However, additional research is needed in a larger sample to truly understand the relationship between these factors along with the underlying etiologies and the associated outcomes.

Evidence of Anxiety, Depression and Learning Impairments following Prenatal Hypertension.

BACKGROUND: Hypertensive disorders of pregnancy, such as Preeclampsia (PreE) and HELLP (hemolysis, elevated liver enzyme, low platelet) syndrome, affects approximately 5-10% of pregnancies and increases the risk of women developing disorders, such as anxiety or depression, in the postpartum period. Using preclinical rodent models, we set out to determine whether rats with a history of PreE or HELLP had evidence of anxiety, depression or cognitive impairment and whether immune suppression during pregnancy prevented these changes in mood and/or cognition. METHODS: Timed-pregnant rats were infused with sFlt-1 and/or sEng to induce PreE or HELLP beginning on gestational day 12. After delivery, a battery of validated behavioral assays was used to assess post-partum depression, anxiety and learning. RESULTS: There was no negative effect on maternal pup interaction due to PreE or HELLP; however, hypertensive dams spent more time immobile in the forced swim test (p < 0.0001). Hypertensive dams also spent less time in the open area of the open field (p = 0.001). There were no significant changes in recognition memory (p = 0.08); however, spatial learning was impaired in hypertensive dams (p = 0.003). Immobility time in the forced swim test was positively correlated with increased circulating S100B (p = 0.04), while increased time spent in the outer zones of the open field was negatively correlated with BDNF levels (p < 0.0001). CONCLUSION: The results from this study suggest that hypertensive pregnancy disorders are associated with depression, anxiety and learning impairments in the post-partum period.

Acute kidney injury during pregnancy leads to increased sFlt-1 and sEng and decreased renal T regulatory cells in pregnant rats with HELLP syndrome.

BACKGROUND: The incidence of acute kidney injury (AKI) during pregnancy precedes a high maternal mortality rate of 20-40%. AKI during pregnancy has multiple etiologies; however, the more common are maternal hypertensive disorders, which include preeclampsia and HELLP (hemolysis, elevated liver enzyme, low platelet) syndrome. Therefore, we sought to assess the impact of AKI on blood pressure, kidney injury, and anti-angiogenic factors during pregnancies with and without HELLP syndrome. METHODS: On gestational day (GD) 12, mini-osmotic pumps were inserted into a subset of normal pregnant (NP) rats infusing 4.7 µg/kg soluble fms-like tyrosine kinase-1 (sFlt-1) and 7 µg/kg soluble endoglin (sEng) to induce HELLP syndrome. On GD18, the renal pedicles were occluded for 45 min to induce AKI via bilateral ischemia reperfusion in a subset of NP (n = 18) or HELLP (n = 20) rats. Control NP (n = 20) and HELLP (n = 20) rats underwent a SHAM surgery on GD18. Plasma, urine, and maternal organs were saved for further analysis. Renal injury was assessed via renal histopathology, glomerular filtration rate (GFR), T cell infiltration, and assessment of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Data was measured via two-way analysis of variance with Tukey's test for post hoc analysis. RESULTS: Blood pressures were increased in HELLP+AKI rats (p = 0.0001); both NP+AKI and HELLP+AKI rats had increased lactate dehydrogenase (p < 0.0001) and aspartate aminotransferase levels (p < 0.0001), and decreased platelet levels (p < 0.001) vs. NP rats. HELLP+AKI (p = 0.002) and HELLP rats (p = 0.0002) had evidence of renal fibrosis vs. NP rats. GFR was decreased in HELLP+AKI (p = 0.01) rats vs. NP rats. Urinary KIM-1 was increased in NP+AKI rats vs. NP (p = 0.003) and HELLP rats (p = 0.01). HELLP+AKI rats had increased urinary KIM-1 vs. NP (p = 0.0008) and HELLP rats (p = 0.004) and increased NGAL vs. HELLP rats (p = 0.002). HELLP+AKI rats had increased sFlt-1 (p = 0.009) vs. NP rats. NP+AKI (p = 0.02) and HELLP+AKI (p = 0.007) rats had increased sEng vs. NP rats. CD3+CD4+ T cells were significantly increased in HELLP+AKI rats vs. NP (p = 0.0002) and NP+AKI (p = 0.05) rats. T regulatory cells were significantly decreased in HELLP+AKI (p = 0.03) and NP+AKI (p = 0.02) rats vs. NP rats; there were no changes between groups in T helper 17 cells (p = 0.34). CONCLUSION: The findings in this study suggest that AKI during pregnancy contributes to increased blood pressure and biochemical markers for HELLP syndrome, creates an anti-angiogenic imbalance, and exacerbates kidney injury as shown on histopathology, GFR, and kidney injury markers.

Risk Factors for Neonatal/Maternal Morbidity and Mortality in African American Women with Placental Abruption.

Background and Objectives: Risk factors for neonatal/maternal morbidity and mortality in placental abruption have been incompletely studied in the current literature. Most of the research overlooked the African American population as mostly Caucasian populations are selected. We aimed to find which risk factor influence the neonatal and maternal outcome in cases of placental abruption occurring in African American pregnant women in an inner-city urban setting. Materials and Methods: We performed a retrospective cohort study at St. Joseph's Regional Medical Center, NJ United States of America (USA), between 1986 and 1996. Inclusion criteria were African American race, singleton pregnancy with gestational age over 20 weeks and placental abruption. Maternal age, gravidity, parity, gestational age at delivery/occurrence of placental abruption and mode of delivery were collected. Risk factors for placental abruption such as placenta previa, hypertensive disorders of pregnancy, cigarette smoking, crack/cocaine and alcohol use, mechanical trauma, preterm premature rupture of membranes (PPROM), and premature rupture of membranes (PROM) were recorded. Poor neonatal outcome was considered when anyone of the following occurred: 1st and 5th minute Apgar score lower than 7, intrauterine fetal demise (IUFD), perinatal death, and neonatal arterial umbilical cord pH less than 7.15. Poor maternal outcome was considered if any of the following presented at delivery: hemorrhagic shock, disseminated intravascular coagulation (DIC), hysterectomy, postpartum hemorrhage (PPH), maternal intensive care unit (ICU) admission, and maternal death. Results: A population of 271 singleton African American pregnant women was included in the study. Lower gestational age at delivery and cesarean section were statistically significantly correlated with poor neonatal outcomes (p = 0.018; p < 0.001; p = 0.015) in the univariate analysis; only lower gestational age at delivery remained significant in the multivariate analysis (p = < 0.001). Crack/cocaine use was statistically significantly associated with poor maternal outcome (p = 0.033) in the univariate analysis, while in the multivariate analysis, hemolysis, elevated enzymes, low platelet (HELLP) syndrome, crack/cocaine use and previous cesarean section resulted significantly associated with poor maternal outcome (p = 0.029, p = 0.017, p = 0.015, p = 0.047). PROM was associated with better neonatal outcome in the univariate analysis, and preeclampsia was associated with a better maternal outcome in the multivariate analysis. Conclusions: Lower gestational age at delivery is the most important risk factor for poor neonatal outcome in African American women with placental abruption. Poor maternal outcome correlated with HELLP syndrome, crack/cocaine use and previous cesarean section. More research in this understudied population is needed to establish reliable risk factors and coordinate preventive interventions.

Peripheral Anti-Angiogenic Imbalance during Pregnancy Impairs Myogenic Tone and Increases Cerebral Edema in a Rodent Model of HELLP Syndrome.

Using an animal model of hemolysis elevated liver enzymes low platelets (HELLP) that has systemic inflammation and neuroinflammation we wanted to determine if blood brain barrier (BBB) permeability, cerebral edema, vascular tone, and occludin expression were altered in pregnant rats. Anti-angiogenic proteins sFlt-1 and sEng (4.7 and 7 µg/kg/day, respectively) were chronically infused into normal pregnant (NP) rats beginning on gestational day 12 via a mini-osmotic pump. On gestational day 19, blood pressure was measured via a carotid catheter and brains were collected. BBB permeability was assessed in select brain regions from rats infused with 0.5 mg/mL Texas Red Dextran and phenylephrine. Occludin, sFlt-1, and sEng were analyzed via western blot or ELISA. Infusion of sFlt-1 and sEng into NP rats increased hemolysis and liver enzymes, and decreased platelets and led to hypertension. HELLP rats had significant impairment in the myogenic response and increased BBB permeability in the posterior cortex and brainstem. Brain water content in the posterior cortex was increased and sEng protein expression in the brainstem was significantly increased in HELLP rats. The results from this study suggest that a peripheral anti-angiogenic imbalance during pregnancy is associated with decreased myogenic tone, vasogenic edema, and an increase in BBB permeability, but not anti-angiogenic imbalance in the brain.