Prognostic Value of a Laboratory Index of Frailty in Older Patients Hospitalized for COVID-19: The COMEPA Study.

BACKGROUND: Several indexes based on clinical and laboratory tests to identify frailty and to predict mortality have been produced. Only two studies, mixing clinical and laboratory parameters were made about a frailty index made of laboratory tests (FI-Lab) and mortality in older patients hospitalized for COVID-19. The aim of this study was to explore the accuracy and precision of an FI-Lab constructed with some common bio-humoral tests and mortality in a cohort of patients hospitalized for COVID-19. METHODS: The FI-Lab was constructed using 40 different bio-humoral tests during the first four days of hospitalization, with a score from 0 to 1. The association between FI-Lab and mortality was assessed using a multivariate Cox's regression analysis, reported as hazard ratios (HRs) and 95% confidence intervals (CIs). The accuracy of the FI-Lab was reported as area under the curve (AUC) and the precision with the C-Index. RESULTS: 376 patients (mean age: 65 years; 53.7% males) were initially included. During the follow-up period, 41 deceased. After adjusting for five different factors, an FI-Lab value >0.54, the median value of our cohort, was associated with a relative risk about five times greater than lower values. Modeling FI-LAB as a continous variable, each increase in 0.01 points was associated with an increased risk in mortality of 8.4% (HR=1.084; 95%CI: 1.039-2.044). The FI-Lab was highly accurate (AUC=0.91; 95%CI: 0.87-0.95) and precise (C-Index=0.81) in predicting death. CONCLUSIONS: A simple index based on common laboratory tests can be used to predict mortality among older people hospitalized for COVID-19.

Diagnostic accuracy of cell-free DNA in maternal blood in detecting chromosomal anomalies in twin pregnancies: systematic review and meta-analysis.

OBJECTIVES: To report the diagnostic accuracy of cell-free DNA (cfDNA) in maternal blood in detecting chromosomal anomalies in twin pregnancies. METHODS: Medline, Embase and Cochrane databases were searched. The inclusion criteria were twin pregnancies undergoing cfDNA screening for Trisomies 13, 18, 21, monosomy X0 and other sex chromosomal anomalies (SCA). The index test was represented by a positive results of cfDNA test. The reference standard was represented by the karyotype results (obtained either pre or postnatally) or, in case of negative cfDNA result, by a normal neonatal phenotype. The quality of the studies was assessed using the revised tool for the quality assessment of diagnostic accuracy studies (QUADAS-2). Summary estimates of sensitivity, specificity, positive and negative likelihood ratios (LR+ and LR-) and diagnostic odds ratio (DOR), with the corresponding 95% Confidence Intervals (95% CI), were computed using the bivariate random-effects model. RESULTS: Thirty-five studies were included. cfDNA had an overall high accuracy in detecting Trisomy 21 in twin pregnancies with a sensitivity of 98.8% (95% CI 96.5-100), a specificity of 100% (95% CI 99.9-100). Sensitivity and specificity were of 94.9% (95% CI 75.6-99.1) and 100 (95% CI 99.9-100) for Trisomy 18, and 84.6% (95% C% 54.6-98.1) and 100% (95% CI 99.9-100) for Trisomy 13 . We could not compute the diagnostic accuracy of cfDNA in detecting monosomy X0 in twins, while cfDNA had a sensitivity of 100% (95% CI 71.5-100) and a specificity of 99.8% (95% CI 99.7-99.9) in detecting other SCA (11 cases). The accuracy of cfDNA in detecting Trisomy 21, 18 and 13 was similar in dichorionic and monochorionic twin pregnancies. CONCLUSION: cfDNA has a high diagnostic accuracy in detecting Trisomy 18 and 21 in twin pregnancies, irrespective of chorionicity. Accuracy in the detection of Trisomy 13 and SCA was limited by the small number of affected cases and the difficulties in the confirmation of false negative cases in case of SCA and requires confirmation in larger studies. This article is protected by copyright. All rights reserved.

Diagnostic accuracy of prenatal ultrasound in coarctation of aorta: systematic review and individual participant data meta-analysis.

OBJECTIVE: To determine the diagnostic accuracy of prenatal ultrasound in detecting coarctation of the aorta (CoA). METHODS: An individual participant data meta-analysis was performed to report on the strength of association and diagnostic accuracy of different ultrasound signs in detecting CoA prenatally. MEDLINE, EMBASE and CINAHL were searched for studies published between January 2000 and November 2021. Inclusion criteria were fetuses with suspected isolated CoA, defined as ventricular and/or great vessel disproportion with right dominance on ultrasound assessment. Individual participant-level data were obtained by two leading teams. PRISMA-IPD and PRISMA-DTA guidelines were used for extracting data, and the QUADAS-2 tool was used for assessing quality and applicability. The reference standard was CoA, defined as narrowing of the aortic arch, diagnosed after birth. The most commonly evaluated parameters on ultrasound, both in B-mode and on Doppler, constituted the index test. Summary estimates of sensitivity, specificity, diagnostic odds ratio (DOR) and likelihood ratios were computed using the hierarchical summary receiver-operating-characteristics model. RESULTS: The initial search yielded 72 studies, of which 25 met the inclusion criteria. Seventeen studies (640 fetuses) were included. On random-effects logistic regression analysis, tricuspid valve/mitral valve diameter ratio > 1.4 and > 1.6, aortic isthmus/arterial duct diameter ratio < 0.7, hypoplastic aortic arch (all P < 0.001), aortic isthmus diameter Z-score of < -2 in the sagittal (P = 0.003) and three-vessel-and-trachea (P < 0.001) views, pulmonary artery/ascending aorta diameter ratio > 1.4 (P = 0.048) and bidirectional flow at the foramen ovale (P = 0.012) were independently associated with CoA. Redundant foramen ovale was inversely associated with CoA (P = 0.037). Regarding diagnostic accuracy, tricuspid valve/mitral valve diameter ratio > 1.4 had a sensitivity of 72.6% (95% CI, 48.2-88.3%), specificity of 65.4% (95% CI, 46.9-80.2%) and DOR of 5.02 (95% CI, 1.82-13.9). The sensitivity and specificity values were, respectively, 75.0% (95% CI, 61.1-86.0%) and 39.7% (95% CI, 27.0-53.4%) for pulmonary artery/ascending aorta diameter ratio > 1.4, 47.8% (95% CI, 14.6-83.0%) and 87.6% (95% CI, 27.3-99.3%) for aortic isthmus diameter Z-score of < -2 in the sagittal view and 74.1% (95% CI, 58.0-85.6%) and 62.0% (95% CI, 41.6-78.9%) for aortic isthmus diameter Z-score of < -2 in the three-vessel-and-trachea view. Hypoplastic aortic arch had a sensitivity of 70.0% (95% CI, 42.0-88.6%), specificity of 91.3% (95% CI, 78.6-96.8%) and DOR of 24.9 (95% CI, 6.18-100). The diagnostic yield of prenatal ultrasound in detecting CoA did not change significantly when considering multiple categorical parameters. Five of the 11 evaluated continuous parameters were independently associated with CoA (all P < 0.001) but all had low-to-moderate diagnostic yield. CONCLUSIONS: Several prenatal ultrasound parameters are associated with an increased risk for postnatal CoA. However, diagnostic accuracy is only moderate, even when combinations of parameters are considered. © 2024 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Midline structures and cortical development in late-onset fetal growth restriction according to Doppler status: prospective study.

OBJECTIVES: Fetuses with late-onset growth restriction (FGR) have a higher risk of suboptimal neurocognitive performance after birth. Previous studies have reported that impaired brain and cortical development can start in utero. The primary aim of this study was to report midline structure growth and cortical development in fetuses with late-onset FGR according to its severity; the secondary aim was to elucidate whether the severity of FGR, as defined by the presence of abnormal Doppler findings, plays a role in affecting brain growth and maturation. METHODS: This was a prospective observational study that included fetuses with late-onset FGR (defined according to the Delphi FGR criteria) undergoing neurosonography between 32 and 34 weeks' gestation. Midline structure (corpus callosum (CC) and cerebellar vermis (CV)) length and cortical development, including the depth of the Sylvian (SF), parieto-occipital (POF) and calcarine (CF) fissures, were compared between late-onset FGR, small-for-gestational-age (SGA) and appropriate-for-gestational-age (AGA) fetuses. Subgroup analysis according to the severity of FGR (normal vs abnormal fetal Doppler) was also performed. Univariate analysis was used to analyze the data. RESULTS: A total of 52 late-onset FGR fetuses with normal Doppler findings, 60 late-onset FGR fetuses with abnormal Doppler findings, 64 SGA fetuses and 100 AGA fetuses were included in the analysis. When comparing AGA controls with SGA fetuses, late-onset FGR fetuses with normal Doppler findings and late-onset FGR fetuses with abnormal Doppler findings, there was a progressive and significant reduction in the absolute values of the following parameters: CC length (median (interquartile range (IQR)), 43.5 (28.9-56.1) mm vs 41.9 (27.8-51.8) mm vs 38.5 (29.1-50.5) mm vs 31.7 (23.8-40.2) mm; K = 26.68; P < 0.0001), SF depth (median (IQR), 14.5 (10.7-16.8) mm vs 12.7 (9.8-15.1) mm vs 11.9 (9.1-13.4) mm vs 8.3 (6.7-10.3) mm; K = 75.82; P < 0.0001), POF depth (median (IQR), 8.6 (6.3-11.1) mm vs 8.1 (5.6-10.4) mm vs 7.8 (6.1-9.3) mm vs 6.6 (4.2-8.0) mm; K = 45.06; P < 0.0001) and CF depth (median (IQR), 9.3 (6.7-11.5) mm vs 8.2 (5.7-10.7) mm vs 7.7 (5.2-9.4) mm vs 6.3 (4.5-7.2) mm; K = 46.14; P < 0.0001). Absolute CV length was significantly higher in AGA fetuses compared with all other groups, although the same progressive pattern was not noted (median (IQR), 24.9 (17.6-29.2) mm vs 21.6 (15.2-26.1) mm vs 19.1 (13.8-25.9) mm vs 21.0 (13.5-25.8) mm; K = 16.72; P = 0.0008). When the neurosonographic variables were corrected for fetal head circumference, a significant difference in the CC length and SF, POF and CF depths, but not CV length, was observed only in late-onset FGR fetuses with abnormal Doppler findings when compared with AGA and SGA fetuses. CONCLUSIONS: Fetuses with late-onset FGR had shorter CC length and delayed cortical development when compared with AGA fetuses. After controlling for fetal head circumference, these differences remained significant only in late-onset FGR fetuses with abnormal Doppler. These findings support the existence of a link between brain development and impaired placental function. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Rehabilitation Modulates High-Order Interactions Among Large-Scale Brain Networks in Subacute Stroke.

The recovery of motor functions after stroke is fostered by the functional integration of large-scale brain networks, including the motor network (MN) and high-order cognitive controls networks, such as the default mode (DMN) and executive control (ECN) networks. In this paper, electroencephalography signals are used to investigate interactions among these three resting state networks (RSNs) in subacute stroke patients after motor rehabilitation. A novel metric, the O-information rate (OIR), is used to quantify the balance between redundancy and synergy in the complex high-order interactions among RSNs, as well as its causal decomposition to identify the direction of information flow. The paper also employs conditional spectral Granger causality to assess pairwise directed functional connectivity between RSNs. After rehabilitation, a synergy increase among these RSNs is found, especially driven by MN. From the pairwise description, a reduced directed functional connectivity towards MN is enhanced after treatment. Besides, inter-network connectivity changes are associated with motor recovery, for which the mediation role of ECN seems to play a relevant role, both from pairwise and high-order interactions perspective.

Uterine artery Doppler in early labor and perinatal outcome in low-risk term pregnancy: prospective multicenter study.

OBJECTIVE: The prediction of adverse perinatal outcomes in low-risk pregnancies is poor, mainly owing to the lack of reliable biomarkers. Uterine artery (UtA) Doppler is closely associated with placental function and may facilitate the peripartum detection of subclinical placental insufficiency. The objective of this study was to evaluate the association of mean UtA pulsatility index (PI) measured in early labor with obstetric intervention for suspected intrapartum fetal compromise and adverse perinatal outcome in uncomplicated singleton term pregnancies. METHODS: This was a prospective multicenter observational study conducted across four tertiary maternity units. Low-risk term pregnancies with spontaneous onset of labor were included. The mean UtA-PI was recorded between uterine contractions in women admitted for early labor and converted into multiples of the median (MoM). The primary outcome of the study was the occurrence of obstetric intervention, i.e. Cesarean section or instrumental delivery, for suspected intrapartum fetal compromise. Secondary outcomes were the occurrence of adverse perinatal outcomes, including 5-min Apgar score < 7, low cord arterial pH, raised cord arterial base excess, admission to the neonatal intensive care unit (NICU) and postnatal diagnosis of small-for-gestational-age fetus. Composite adverse perinatal outcome was defined as the occurrence of at least one of the following: acidemia in the umbilical artery, defined as pH < 7.10 and/or base excess > 12 mmol/L, 5-min Apgar score < 7 or admission to the NICU. RESULTS: Overall, 804 women were included, of whom 40 (5.0%) had abnormal mean UtA-PI MoM. Women who had an obstetric intervention for suspected intrapartum fetal compromise were more frequently nulliparous (72.2% vs 53.6%; P = 0.008), had a higher frequency of increased mean UtA-PI MoM (13.0% vs 4.4%; P = 0.005) and had a longer duration of labor (456 ± 221 vs 371 ± 192 min; P = 0.01). On logistic regression analysis, only increased mean UtA-PI MoM (adjusted odds ratio (aOR), 3.48 (95% CI, 1.43-8.47); P = 0.006) and parity (aOR, 0.45 (95% CI, 0.24-0.86); P = 0.015) were independently associated with obstetric intervention for suspected intrapartum fetal compromise. Increased mean UtA-PI MoM was associated with a sensitivity of 0.13 (95% CI, 0.05-0.25), specificity of 0.96 (95% CI, 0.94-0.97), positive predictive value of 0.18 (95% CI, 0.07-0.33), negative predictive value of 0.94 (95% CI, 0.92-0.95), positive likelihood ratio of 2.95 (95% CI, 1.37-6.35) and negative likelihood ratio of 0.91 (95% CI, 0.82-1.01) for obstetric intervention for suspected intrapartum fetal compromise. Pregnancies with increased mean UtA-PI MoM also showed a higher incidence of birth weight < 10th percentile (20.0% vs 6.7%; P = 0.002), NICU admission (7.5% vs 1.2%; P = 0.001) and composite adverse perinatal outcome (15.0% vs 5.1%; P = 0.008). CONCLUSION: Our study, conducted in a cohort of low-risk term pregnancies enrolled in early spontaneous labor, showed an independent association between increased mean UtA-PI and obstetric intervention for suspected intrapartum fetal compromise, albeit with moderate capacity to rule in, and poor capacity to rule out, this condition. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.