Correlation of aortic valve annular plane assessment by on-table three-dimensional rotational angiography and preprocedural computed tomography.

OBJECTIVES: To assess the correlation between the aortic valve annular plane (AVAP) obtained by preprocedural computed tomography (CT) with on-table three-dimensional rotational angiography (3DRA), in patients undergoing transcatheter aortic valve replacement (TAVR). BACKGROUND: Accurate assessment of the AVAP is critical during TAVR procedures to enable optimal positioning and minimize complications. Most commonly, preprocedural CT has been used to determine the AVAP. However, this can differ from the actual AVAP obtained during the TAVR procedure. METHODS: Consecutive TAVR patients at a single center undergoing both preprocedural CT and 3DRA were included in the study. The AVAP assessment by CT was performed using 3mensio software (Pie Medical Imaging). 3DRA assessment was performed using DynaCT (Siemens). RESULTS: A total of 100 patients were included in the analysis. A difference of ≥5° and ≥10° in both the LAO/RAO and cranial/caudal components of the AVAP projection angle as assessed by CT and 3DRA was recorded in 39% and 10% of patients, respectively. The concordance correlation coefficient for the LAO/RAO and cranial/caudal implantation angles was 0.519 (95% CI: 0.377-0.661) and 0.558 (95% CI: 0.432-0.684), respectively. CONCLUSION: Correlation between preprocedural CT and on-table 3DRA in the prediction of the actual AVAP at the time of TAVR implantation is moderate.

Cell-free DNA screening for trisomies 21, 18, and 13 in pregnancies at low and high risk for aneuploidy with genetic confirmation.

BACKGROUND: Cell-free DNA noninvasive prenatal screening for trisomies 21, 18, and 13 has been rapidly adopted into clinical practice. However, previous studies are limited by a lack of follow-up genetic testing to confirm the outcomes and accurately assess test performance, particularly in women at a low risk for aneuploidy. OBJECTIVE: To measure and compare the performance of cell-free DNA screening for trisomies 21, 18, and 13 between women at a low and high risk for aneuploidy in a large, prospective cohort with genetic confirmation of results STUDY DESIGN: This was a multicenter prospective observational study at 21 centers in 6 countries. Women who had single-nucleotide-polymorphism-based cell-free DNA screening for trisomies 21, 18, and 13 were enrolled. Genetic confirmation was obtained from prenatal or newborn DNA samples. The test performance and test failure (no-call) rates were assessed for the cohort, and women with low and high previous risks for aneuploidy were compared. An updated cell-free DNA algorithm blinded to the pregnancy outcome was also assessed. RESULTS: A total of 20,194 women were enrolled at a median gestational age of 12.6 weeks (interquartile range, 11.6-13.9). The genetic outcomes were confirmed in 17,851 cases (88.4%): 13,043 (73.1%) low-risk and 4808 (26.9%) high-risk cases for aneuploidy. Overall, 133 trisomies were diagnosed (100 trisomy 21; 18 trisomy 18; 15 trisomy 13). The cell-free DNA screen positive rate was lower in the low-risk vs the high-risk group (0.27% vs 2.2%; P<.0001). The sensitivity and specificity were similar between the groups. The positive predictive value for the low- and high-risk groups was 85.7% vs 97.5%; P=.058 for trisomy 21; 50.0% vs 81.3%; P=.283 for trisomy 18; and 62.5% vs 83.3; P=.58 for trisomy 13, respectively. Overall, 602 (3.4%) patients had no-call result after the first draw and 287 (1.61%) after including cases with a second draw. The trisomy rate was higher in the 287 cases with no-call results than patients with a result on a first draw (2.8% vs 0.7%; P=.001). The updated algorithm showed similar sensitivity and specificity to the study algorithm with a lower no-call rate. CONCLUSION: In women at a low risk for aneuploidy, single-nucleotide-polymorphism-based cell-free DNA has high sensitivity and specificity, positive predictive value of 85.7% for trisomy 21 and 74.3% for the 3 common trisomies. Patients who receive a no-call result are at an increased risk of aneuploidy and require additional investigation.

Dramatic cutaneous eruption of nodular purpuric lesions in an otherwise well older man.

We describe a dramatic presentation of a rare condition, presenting as a diffuse ecchymosis-like area. This entity has a predilection to primary cutaneous involvement, placing dermatologists as important primary assessors. Clinical knowledge and a high level of clinical suspicion are essential for timely diagnosis. Click here for the corresponding questions to this CME article.

Euploid First-Trimester Cystic Hygroma: A More Benign Entity than Previously Thought?

OBJECTIVE: Studies summarizing the outcome of first-trimester septated cystic hygroma are generally based on small studies or from multiple centers with limited ascertainment. We reviewed the natural history of a large cohort of such cases from a single tertiary referral center, with the aim being to establish contemporary outcome data, particularly in the setting of normal karyotype. METHODS: A retrospective cohort study from 2007 to 2017 was conducted at a single tertiary referral prenatal diagnosis center. Data were analyzed from a prospectively collated fetal anomaly database. Search terms were "increased nuchal translucency (NT)," "cystic hygroma," and "septated cystic hygroma." All cases were confirmed to have NT >3 mm with septations. Cases of simple increased NT without septations were excluded. RESULTS: During the study period, over 110,000 pregnancies were delivered at our center, resulting in 410 cases of septated cystic hygroma diagnosed prior to 14 weeks' gestation. Pregnancy outcome was obtained in 99% (405/410) of cases, with detailed pathology outcome available in 92% (378/410). A total of 87% (351/405) underwent invasive prenatal testing, and postnatal chromosome status was established in further 27 cases. A total of 61% (230/378) had abnormal chromosomal status. Of the 39% (148/378) with normal chromosomal status, only 13% (19/148) had a significant structural fetal abnormality, which included 7 cardiac and 12 noncardiac abnormalities. Overall, the perinatal loss was 62% (253/405). The total survival rate in the setting of euploid cystic hygroma without structural abnormality was 84% (108/129). CONCLUSIONS: Counseling regarding outcomes in the setting of first-trimester septated cystic hygroma initially focuses on the strong likelihood of an abnormal karyotype, which occurs in 61% of cases. However, once fetal chromosomal abnormality is excluded, our results demonstrate only a 13% incidence of major structural fetal abnormality, which appears significantly less than previously reported. Normal fetuses have a 77% survival rate. These data represent the largest single-center study of first-trimester cystic hygroma with complete outcome data and therefore will be useful for contemporary patient counseling. Such counseling can be more positive than previously expected, once chromosomal abnormality is first excluded.

Ipilimumab plus nivolumab in patients with symptomatic melanoma brain metastasis requiring corticosteroids.

STUDY AIM: To investigate the efficacy of PD-1-directed antibody-based therapy in patients with symptomatic melanoma brain metastases (MBM) and concurrent treatment with corticosteroids. METHODS: This retrospective cohort study included patients with cutaneous melanoma with symptomatic MBM and concurrent treatment with corticosteroids who received PD-1-directed antibody-based treatment at the Royal Marsden Hospital London between 2016 and 2021. The primary outcome was overall survival (OS), secondary outcomes were intracranial response rate (ORR) and duration of response (DOR). We used the Kaplan-Meier method to describe survival. RESULTS: Between 2016 and 2021, 256 patients presented with metastatic melanoma, of whom 29 were eligible with symptomatic MBM requiring corticosteroids and receiving ipilimumab plus nivolumab. Median age was 54 (interquartile range 44, 66). Median OS was 5.45months (95% confidence interval (CI) 2.89, 29.40), with 21% of patients (95% CI 9%, 47%) alive after 3years. ORR was 28% (8/29) and DOR was 7.85months (95% CI 7.85, not estimably [NE]). Responding patients had a median OS of 56.4months (95% CI 46.03, NE). Elevated lactate dehydrogenase and Eastern Cooperative Oncology Group PS> 2 were associated with poorer outcomes (median OS 29.4 versus 3.12months and 6.44 versus 5.13months), no such association was observed for corticosteroid dose, number of lesions, or line of treatment. CONCLUSION: Patients with symptomatic MBM derive only modest benefit from combination immunotherapy treatment. Nevertheless, those with disease response have the potential to derive long-term benefit, justifying ipilimumab plus nivolumab in this group in the absence of other more effective treatment options.

Immunological assessment of SARS-CoV-2 infection in pregnancy from diagnosis to delivery: A multicentre prospective study.

BACKGROUND: Background Population-based data on SARS-CoV-2 infection in pregnancy and assessment of passive immunity to the neonate, is lacking. We profiled the maternal and fetal response using a combination of viral RNA from naso-pharyngeal swabs and serological assessment of antibodies against SARS-CoV-2. METHODS: This multicentre prospective observational study was conducted between March 24th and August 31st 2020. Two independent cohorts were established, a symptomatic SARS-CoV-2 cohort and a cohort of asymptomatic pregnant women attending two of the largest maternity hospitals in Europe. Symptomatic women were invited to provide a serum sample to assess antibody responses. Asymptomatic pregnant women provided a nasopharyngeal swab and serum sample. RT-PCR for viral RNA was performed using the Cobas SARS-CoV-2 6800 platform (Roche). Umbilical cord bloods were obtained at delivery. Maternal and fetal serological response was measured using both the Elecsys® Anti-SARS-CoV-2 immunoassay (Roche), Abbott SARS-CoV-2 IgG Assay and the IgM Architect assay. Informed written consent was obtained from all participants. RESULTS: Ten of twenty three symptomatic women had SARS-CoV-2 RNA detected on nasopharyngeal swabs. Five (5/23, 21.7%) demonstrated serological evidence of anti-SARS-CoV-2 IgG antibodies and seven (30.4%, 7/23) were positive for IgM antibodies. In the asymptomatic cohort, the prevalence of SARS-CoV-2 infection in RNA was 0.16% (1/608). IgG SARS-CoV-2 antibodies were detected in 1·67% (10/598, 95% CI 0·8%-3·1%) and IgM in 3·51% (21/598, 95% CI 2·3-5·5%). Nine women had repeat testing post the baseline test. Four (4/9, 44%) remained IgM positive and one remained IgG positive. 3 IgG anti-SARS-CoV-2 antibodies were detectable in cord bloods from babies born to five seropositive women who delivered during the study. The mean gestation at serological test was 34 weeks. The mean time between maternal serologic positivity and detection in umbilical cord samples was 28 days. CONCLUSION: Using two independent serological assays, we present a comprehensive illustration of the antibody response to SARS-CoV-2 in pregnancy, and show a low prevalence of asymptomatic SARS-CoV2. Transplacental migration of anti-SARS-CoV-2 antibodies was identified in cord blood of women who demonstrated antenatal anti-SARS-CoV-2 antibodies, raising the possibility of passive immunity.