Prenatal diagnosis of a novel pathogenic variation in the ACAN gene presenting with isolated shortening of fetal long bones in the second trimester of gestation: a case report.

BACKGROUND: Heterozygous mutations of the ACAN gene are a major cause of different evolutive growth defects in the pediatric population, but were never described as a cause of fetal skeletal dysplasia. CASE PRESENTATION: A G1 at 21w + 3d came to our institution for the second-trimester ultrasound and a skeletal dysplasia with prevalent involvement of limb's rhizomelic tracts was suspected. Amniocentesis followed by CGH-array was performed, with normal results. An examination by NGS of some genes associated with skeletal dysplasias showed a novel pathogenic variant of the ACAN gene: c.2677delG. CONCLUSION: Sequence variations of ACAN were never described as a possible cause of fetal skeletal anomalies to date. In this case report, we describe the first prenatal diagnosis of skeletal dysplasia associated with a pathogenic variant of ACAN.

Effect of music on labor and delivery in nulliparous singleton pregnancies: a randomized clinical trial.

BACKGROUND: Women's experience of pain during labor varies greatly, and pain control is a major concern for obstetricians. Several methods have been studied for pain management for women in labor, including drug and non-drug interventions. OBJECTIVE: To test the hypothesis that in nulliparous women with singleton pregnancies at term, listening to music would reduce the pain level during labor. METHODS: Parallel group non-blinded randomized clinical trial conducted at a single center in Italy. Nulliparous women in spontaneous labor with singleton pregnancies and vertex presentation admitted in labor and delivery room between 37 0/7 and 42 0/7 weeks of gestation for active phase of labor were eligible, and were randomized in a 1:1 ratio to receive music during labor or no music during labor. Music in labor was defined listening to music from the randomization until the delivery of the baby. The primary endpoint was the pain level during the active phase of labor, recorded using the visual analogue scale (VAS) for pain, ranging from 0 (no pain) to 10 (unbearable pain). The effect of music use during labor on each outcome was quantified as the mean difference (MD) with 95% confidence interval (CI). RESULTS: During the study period, 30 women agree to take part in the study, underwent randomization, and were enrolled and followed up. 15 women were randomized in the music group, and 15 in the control group. No patients were lost to follow up for the primary outcome. Pain level during the active phase of labor was scored 8.8 ± 0.9 in the music group, and 9.8 ± 0.3 in the control group (MD - 1.00 point, 95% CI - 1.48 to - 0.52; P < 0.01). Music during labor and delivery was also associated with a decreased pain at 1 h postpartum (MD - 2.40 points, 95% CI - 4.30 to - 0.50), and decreased anxiety level during active phase of labor (MD - 19.90 points, 95% CI - 38.72 to - 1.08), second stage of labor (MD - 49.40 points, 95% CI - 69.44 to - 29.36), and at 1 h postpartum (MD - 27.00 points, 95% CI - 47.37 to - 6.63). CONCLUSION: In nulliparous women with singleton pregnancies at term, listening to music reduces the pain level, and the anxiety level during labor. TRIAL REGISTRATION: Clinicaltrials.gov NCT03779386.

Prenatal ultrasound diagnosis of duplication gallbladder: a multicenter study.

BACKGROUND: Gallbladder duplication is a rare anatomic anomaly characterized by the presence of an accessory gallbladder. OBJECTIVE: To appraise the prevalence and significance of prenatal diagnosis of duplication of gallbladder in a multicenter study. METHODS: This was a multicenter case series with literature review. Clinical records of all consecutive pregnant women with a prenatal diagnosis of duplication of gallbladder, who were referred to our Centers were included in this study. The diagnosis of duplication of gallbladder was based on the evidence of double gallbladder in the standard abdominal circumference plane using grey scale. Postnatal magnetic resonance cholangiopancreatography (MRCP) 3D and postnatal neonatal abdominal ultrasound scan were offered soon after birth to confirm the diagnosis of double gallbladder. The systematic review was conducted using electronic databases from inception of each database through December 2019. RESULTS: Five studies, including a total of seven cases, were identified as relevant and included in the systematic review. Gestational age at diagnosis ranged from 20 to 32 weeks of gestation. Associated findings were reported in only one case, where the fetus presented with a left-sided gallbladder, and bilateral renal agenesis with Potter sequence. None of the included cases reported abnormal karyotype. Our cases series included nine cases (0.03%) of double gallbladder with postnatal confirmation, with an overall incidence of this anomaly of 0.03%.Associated findings were reported in only two cases, one with IUGR and omphalocele, that opted for I-TOP, and one with single umbilical artery. Except for the I-TOP, neonatal outcome was favorable in all cases. CONCLUSIONS: Duplication of the gallbladder is a very rare malformation with only seven cases reported in the literature diagnosed prenatally. This anomaly is not associated with abnormal karyotype, and the neonatal outcome is favorable if there are no other associated abnormalities.

Prenatal Diagnosis of an Intrathoracic Left Kidney Associated with Congenital Diaphragmatic Hernia: Case Report and Systematic Review.

INTRODUCTION: A congenital intrathoracic kidney (ITK) is a rare anomaly that is recognized to have four causes: renal ectopia with an intact diaphragm, diaphragmatic eventration, diaphragmatic hernia, and traumatic diaphragmatic rupture. We report a case of a prenatal-diagnosed ITK related to a congenital diaphragmatic hernia (CDH) and conducted a systematic review of all cases of the prenatal diagnosis of this association. CASE PRESENTATION: A fetal ultrasound scan at 22 gestational weeks showed left CDH and ITK, hyperechoic left lung parenchyma, and mediastinal shift. The fetal echocardiography and karyotype were normal. Magnetic resonance imaging at 30 gestational weeks confirmed the ultrasound suspicion of left CDH in association with bowel and left kidney herniation. The fetal growth, amniotic fluid, and Doppler indices remained within the normal range over time. The woman delivered the newborn via an at-term spontaneous vaginal delivery. The newborn was stabilized and underwent non-urgent surgical correction; the postoperative course was uneventful. CONCLUSIONS: CDH is the rarest cause of ITK; we found only eleven cases describing this association. The mean gestational age at diagnosis was 29 ± 4 weeks and 4 days. There were seven cases of right and four cases of left CDH. There were associated anomalies in only three fetuses. All women delivered live babies, the herniated kidneys showed no functional damage after their surgical correction, and the prognosis was favorable after surgical repair. The prenatal diagnosis and counseling of this condition are important in planning adequate prenatal and postnatal management in order to improve neonatal outcomes.

Fetal Cerebellar Area: Ultrasound Reference Ranges at 13-39 Weeks of Gestation.

BACKGROUND AND OBJECTIVES: The present study aims to provide prenatal 2-dimensional ultrasonographic (2D-US) nomograms of the normal cerebellar area. MATERIALS AND METHODS: This is a prospective cross-sectional analysis of 252 normal singleton pregnancies, ranging from 13 to 39 weeks of gestation. The operator performed measurements of the fetal cerebellar area in the transverse plane using 2D-US. The relationship between cerebellar area and gestational age (GA) was determined through regression equations. RESULTS: A significant, strong positive correlation was investigated between the cerebellar area with GA (r-value = 0.89), and a positive correlation indicates that with increasing GA, the cerebellar area increased in all the participants of the study. Several 2D-US nomograms of the normal cerebellar area were provided, and an increase of 0.4% in the cerebellar area each week of GA was reported. CONCLUSIONS: We presented information on the typical dimensions of the fetal cerebellar area throughout gestation. In future studies, it could be evaluated how the cerebellar area changes with cerebellar abnormalities. It should be established if calculating the cerebellar area in addition to the routine transverse cerebellar diameter may help in discriminating posterior fossa anomalies or even help to identify anomalies that would otherwise remain undetected.

The unpredictable clinical course of an abdominal cyst diagnosed in the prenatal period: A case report.

Enteric duplication cysts are rare congenital malformations of the gastrointestinal tract. Prenatal diagnosis can be achieved through ultrasound, which may reveal a cystic mass, though the differential diagnosis is broad. We report a case in which the prenatal ultrasound detection of an abdominal cystic mass prompted postnatal magnetic resonance imaging, leading to the diagnosis of an enteric duplication cyst. At 6 weeks of age, the infant developed an obstruction of the small bowel, requiring urgent surgical intervention. This case underscores the difficulties in differentiating abdominal cysts prenatally. Thorough prenatal and neonatal follow-up is crucial, and postnatal magnetic resonance imaging is sometimes essential for accurate diagnosis. The clinical course can be unpredictable, and complications that may arise could necessitate urgent surgical treatment.

Omphalocele Secondary to Spontaneous Rupture of Allantoic Cyst in the Third Trimester of Pregnancy.

OBJECTIVE: We report the first case in which the onset of omphalocele was after the spontaneous rupture of an allantoic cyst. We hypothesize a causal link between the spontaneous rupture of the cyst and the herniation of the viscera. Case Presentation. A 36-year-old woman was diagnosed with an allantoic cyst during the first trimester. The allantoic cyst underwent spontaneous rupture during the 32nd week of gestation, and an omphalocele developed secondary to the cyst's rupture. Two days after birth, the peritoneum covering intestinal loops broke spontaneously and the newborn underwent successful urgent surgery. CONCLUSIONS: This case may suggest that the relative benignity of the allantoid cysts may recommend a close ultrasound follow-up in order to identify the onset of any complications, as a late third trimester onset of omphalocele. Prenatal diagnosis of such complications may allow multidisciplinary management of the pregnancy with planned cesarean section, prenatal pediatric surgery consultation, and neonatal surgery.

Gardnerella vaginalis and Trichomonas vaginalis infections as risk factors for persistence and progression of low-grade precancerous cervical lesions in HIV-1 positive women.

Gardnerella vaginalis (GV) and Trichomonas vaginalis (TV) infections have been proposed as risk factors for persistence and/or progression of low-grade cervical precancerous lesions (CIN1/L-SIL). In patients with Human Immunodeficiency Virus (HIV), who have an increased baseline risk of CIN1/L-SIL progression, the role of GV and TV is undefined. We aimed to investigate the prognostic impact of GV and TV infections on CIN1/L-SIL in HIV-positive women. HIV-1-positive women with L-SIL were retrospectively included. The risk of persistence or progression in the case of any infection (primary outcome), only GV (GV+), only TV (TV+), or GV and TV coinfection (secondary outcomes) was calculated compared to women with no GV or TV infections (NI), by using relative risk (RR) and multivariate logistic regression, with a significant p-value>0.05;. One hundred and ninety-two patients were included (18.2 %GV+, 15.6 %TV+, 5.2 % coinfection, 60.9 %NI); 58 CIN1/L-SIL showed persistence and 46 progression. RR for persistence/progression of CIN1/L-SIL in the case of any infection was 1.56 (1.21-2.01; p = 0.0006) compared to NI. RR for persistence alone was 1.91 (1.25-2.09; p = 0.0026) in GV+, 1.2 (0.63-2.3; p = 0.5736) in TV+, and 2.06 (1.09-3.9; p = 0.0254) in coinfection. RR for progression alone was 1.94 (1.06-3.4; p = 0.0311) in GV+, 2.14 (1.25-3.67; p = 0.0058) in TV+, and 2.73 (1.39-5.37; p = 0.0036) in coinfection. On multivariate analysis, the presence of any infection was significantly associated with persistence/progression (p = 0.002), GV + with persistence (p = 0.019) and TV + with progression (p = 0.016). In conclusion, GV infection is a risk factor for persistence of CIN1/L-SIL in HIV-positive women, while TV infection is a risk factor for progression. Women with these infections may require a closer and more careful follow-up of CIN1/L-SIL.

Intrahepatic persistent fetal right umbilical vein: a retrospective study.

INTRODUCTION: To appraise the incidence and value of intrahepatic persistent right umbilical vein (PRUV). METHODS: This was a single-center study. Records of all women with a prenatal diagnosis of intrahepatic PRUV were reviewed. The inclusion criteria were women with gestational age greater than 13 weeks of gestation. Exclusion criteria were fetuses with situs abnormalities, due to the hepatic venous ambiguity, and extrahepatic PRUV. The primary outcome was the incidence of intrahepatic PRUV in our cohort. The secondary outcomes were associated malformations. RESULTS: 219/57,079 cases (0.38%) of intrahepatic PRUV were recorded. The mean gestational age at diagnosis was 21.8 ± 2.9 weeks of gestations. PRUV was isolated in the 76.7%, while in 23.3% was associated with other major or minor abnormalities. The most common associated abnormalities were cardiovascular abnormalities (8.7%), followed by genitourinary abnormalities (6.4%), skeletal abnormalities (4.6%), and central nervous system abnormalities (4.1%). Within the cardiovascular abnormalities, the most common one was ventricular septal defect (six cases). CONCLUSION: In most cases PRUV is an isolated finding. Associated minor or major malformations are presented in the 23.3% of the cases, so this finding should prompt detailed prenatal assessment of the fetus, with particular regard to cardiovascular system.

Ki67 as a prognostic marker in uterine leiomyosarcoma: A quantitative systematic review.

Ki67 labeling index (LI) has been proposed as a prognostic factor in uterine leiomyosarcoma (uLMS), although the evidence in this field is still unclear. We aimed to assess the prognostic value of ki67 LI in uLMS. A systematic review was performed by searching electronic databases from their inception to August 2020 for all studies assessing the prognostic value of ki67 LI in uLMS. Ki67 LI was assessed to the nearest 10% to define the most prognostically accurate threshold. Cox regression survival analysis with calculation of hazard ratio (HR) of death was performed; a p-value < 0.05 was considered significant. Ten studies were included in the qualitative review, out of which 6 were suitable for quantitative review. The absolute risk of death was 0.29 for a ki67 LI < 10%, remained stable at 0.49 in the 10%-39% LI range and increased to 0.65 for a LI ≥ 40%. On univariate analysis, both 10% and 40% thresholds were significantly associated with the hazard of death, with HRs of 3.349 (p = 0.007) and 3.172 (p = 0.001), respectively. On multivariate analysis, only the 10% threshold was significantly associated with the hazard of death (HR = 2.712; p = 0.028). In conclusion, a Ki67 LI ≥ 10% is a significant prognostic factor in uLMS.

Proliferative vasculopathy and hydranencephaly-hydrocephaly syndrome or Fowler syndrome: Report of a family and insight into the disease's mechanism.

BACKGROUND: Fowler syndrome is a rare autosomal recessive disorder characterized by hydranencephaly-hydrocephaly and multiple pterygium due to fetal akinesia. To date, around 45 cases from 27 families have been reported, and the pathogenic bi-allelic mutations in FLVCR2 gene described in 15 families. The pathogenesis of this condition has not been fully elucidated so far. METHODS: We report on an additional family with two affected fetuses carrying a novel homozygous mutation in FLVCR2 gene, and describe the impact of known mutants on the protein structural and functional impairment. RESULTS: The present report confirms the genetic homogeneity of Fowler syndrome and describes a new FLVCR2 mutation affecting the protein function. The structural analysis of the present and previously published FLVCR2 mutations supports the hypothesis of a reduced heme import as the underlying disease's mechanism due to the stabilization of the occluded conformation or a protein misfolding. CONCLUSION: Our data suggest the hypothesis of heme deficiency as the major pathogenic mechanism of Fowler syndrome.

Mini-invasive Implant Placement in Combination with Maxillary Sinus Membrane Perforation During Transcrestal Sinus Floor Elevation: A Retrospective Study.

The aim of this retrospective study was to report preliminary outcomes of a modified technique for transcrestal sinus floor elevation with simultaneous implant placement. A total of 165 implants were placed in 110 patients using a modified Summers technique. During implant site preparation, after fracturing the sinus floor, a small perforation of the membrane was made using the first osteotome. After grafting with anorganic bovine bone mixed with venous blood, standard-length implants were inserted. The prosthetic phase occurred after 4 to 5 months. Patients were followed for at least 2 years after loading. During the follow-up, sinus condition was assessed by cone beam computed tomography. Periapical radiographs were taken to assess graft height and peri-implant bone levels. Three implants failed within 2 months of placement, yielding an overall implant survival of 98.2%. The mean follow-up was 38.3 months (range: 28 to 60 months) from placement. All other implants were stable and peri-implant soft tissues were healthy throughout the observation period. Peri-implant bone loss averaged 0.62 ± 0.26 mm after 1 year of function. No biologic or biomechanical complications occurred. No evidence of graft material dispersion into the sinus space was detected, except for two cases that resolved spontaneously. After 1 year of loading the graft height averaged 4.8 ± 1.3 mm above the sinus floor level. In the presence of sinus membrane perforation, the proposed modified osteotome technique may allow a predictable rehabilitation of the atrophic posterior maxilla by means of standard length implants without the occurrence of adverse events.