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The c.2299delG mutation is prevalent and accounts for 24.5% USH2A pathogenic variants, with promising prospects for customized gene therapy. We compared the ocular and auditory phenotypes in a retrospective cohort of 169 Usher type 2 patients, with and without the c.2299delG allele, including visual acuity, slit-lamp examination, optical coherence tomography, kinetic perimetry, and audiometric assessment to define the hearing disability. Statistical methods used were covariate balancing propensity score and adjusted survival curves log-rank test for the analysis of visual acuity. We compare 54 Usher patients (31%) carrying at least one c.2299delG allele to 109 patients without this variant. The mean ages at onset of night blindness (14 years) and onset of peripheral vision deficiency (24 years) were similar in both groups, as was the severity of hearing loss (p = 0.731), even in homozygotes (p = 0.136). Based on the covariate balancing propensity score, the c.2299delG carrier patients developed cataract and reached a BCVA of 20/63 earlier than patients without this mutation (mean age 36 versus 42 y.o.; and 52.2 versus 55.1 y.o., respectively). Using adjusted survival curves and a log-rank test based on inverse probability weighting, patients with the c.2299delG variant reach blindness (BCVA <20/400) at 42.3 years old instead of 79.8 years for other USH2A pathogenic variants. We conclude that c.2299delG is associated with a more severe phenotype of the Usher type 2, in homozygotes and in compound heterozygotes. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the failure rate and performance of cell-free DNA (cfDNA) testing as a first-line screening method for major trisomies, performed by two laboratories using different analytical methods: a targeted chromosome-selective method (Harmony® prenatal Test) versus a home-brew genome-wide (GW) massively parallel sequencing method (HB-cfDNA test), and to evaluate the clinical value of incidental findings for the latter method.Methods: CfDNA testing was performed in 3137 pregnancies with the Harmony® prenatal Test and in 3373 pregnancies with the HB-cfDNA test. Propensity score analysis was used to match women between both groups for maternal age, weight, gestational age at testing, in vitro fertilization, rate of twin pregnancies and that of aneuploidies. Detection rates for trisomy 21 were compared between the 2 laboratories. For the HB-cfDNA test, cases with rare incidental findings were reported, including their clinical follow-up.Results: The Harmony® prenatal Test failed at the first attempt in 90 (2.9%) of 3114 women and the HB-cfDNA test in 413 (12.2%) of 3373 women. Postmatched comparisons of the women's characteristics indicate a significantly lower failure rate in the Harmony® group (2.8%) than in the HB cfDNA group (12.4%; p < .001). Of the 90 women in whom the Harmony® prenatal Test failed, 61 had a repeat test, which still failed in 10, and of the 413 women in whom the HB-cfDNA test failed, 379 had a repeat test, which still failed in 110. The total failure rate after one or two attempts was therefore 1.3% (39/3114) for Harmony® and 4.3% (144/3373) for the HB cfDNA test. After the first or second Harmony® prenatal Test, a high-risk result was noted in 17 of the 17 cases with trisomy 21, in 5 of the seven cases with trisomy 18, and a no-call in two cases, and in the one case with trisomy 13. The respective numbers for the HB-cfDNA test are 17 of the 18 cases with trisomy 21, and a no-call in one case, 2 of the two cases with trisomy 18, and in 2 of the three cases with trisomy 13, and a no-call in one. Of the 3373 women with the HB-cfDNA test, a rare incidental finding was noted in 28 (0.8%) of the cases, of which only 2 were confirmed on amniocytes (one with microduplication 1q21.1q21.2 and one with a deletion Xp21.1), and in another case a deletion rather than a duplication of the long arm of chromosome 8 was found. In all 28 cases, there was normal clinical follow-up.Conclusions: Comparison of cfDNA testing between these two laboratories showed a four-fold lower failure rate with the Harmony® prenatal Test, with a similar detection rate for trisomy 21. We showed no clinical relevance of disclosing additional findings beyond common trisomies with the GW HB-cfDNA test. [ABSTRACT FROM AUTHOR]

Background: Propofol sedation has become increasingly popular for colonoscopy. Different modes of propofol administration have been described, but their influence on psychomotor recovery time remains largely unknown. This prospective randomized assessor-blinded study tested the hypothesis that target-controlled infusion system (TCI) combined with sedation depth monitoring should be associated with a more stable sedation than intermittent bolus application with clinical monitoring of sedation depth, resulting in a faster psychomotor skills recovery. Methods: One hundred sixty-four patients undergoing colonoscopy were randomized to receive propofol with the former (TCI group) or the latter (bolus group) mode of administration. Psychomotor skill recovery was assessed using the Choice Reaction Time (CRT) performed before and every ten minutes after waking up from propofol sedation. Clinical recovery was also assessed using the modified Post-anesthetic Discharge Scoring System (PADS). Results: Induction and wake up times were longer in the TCI group, where patients received more propofol than those in the bolus group. Evolution of CRT was similar in both groups. Twenty minutes after arrival in the post-anesthesia care unit, 35 (49%) of patients in the TCI group and 43 (54%) in the bolus group achieved CRT values equal or shorter than their baseline values. Interestingly, according to the PADS score, most of the patients were considered fit for discharge at that moment. Incidence of adverse event was not different between groups. Conclusion: In the conditions of our study characterized by short procedure duration, target-controlled infusion of propofol does not offer any benefit in terms of psychomotor skills recovery over intermittent bolus application. [ABSTRACT FROM AUTHOR]

We conducted an international multicenter retrospective cohort study, PregOuTCOV, to examine the effect of gestational age at time of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on obstetric and neonatal outcomes. We included all singleton pregnancies with a live fetus at 10 weeks' gestation in which pregnancy outcomes were known. The exposed group consisted of patients infected with SARS-CoV-2, whereas the unexposed group consisted of all remaining patients during the same period. Primary outcomes were defined as composite adverse obstetric outcomes and composite adverse neonatal outcomes. Of 10,925 pregnant women, 393 (3.60%) were infected with SARS-CoV-2 (exposed group). After matching for possible confounders, we identified statistically significant increases in the exposed group of composite adverse obstetric outcomes at >20 weeks' gestation and of composite adverse neonatal outcomes at >26 weeks' gestation (p<0.001). Vaccination programs should target women early in pregnancy or before conception, if possible. [ABSTRACT FROM AUTHOR]

Background and Aims: Pulse pressure variation (ΔPP) is considered as one of the best predictors of fluid responsiveness in patients under mechanical ventilation. Pleth Variability Index (PVI) has been proposed as a noninvasive alternative. However, pneumoperitoneum has been recently suggested as a limitation to their interpretation. The aim of this study was to compare changes in ΔPP and PVI related to autotransfusion associated with a Trendelenburg maneuver before and during pneumoperitoneum. Methods: 50 patients undergoing elective abdominal laparoscopic surgery were enrolled in this prospective observational study. All patients were equipped with an invasive radial artery catheter and a PVI probe. After obtaining a stable signal with both ΔPP and PVI, baseline values were recorded, before and after head‑down tilts of 10°, with or without abdominal insufflation (10‑12 mmHg). All measurements were made before any fluid challenge under standardized anaesthesia, while patients were paralyzed and mechanically ventilated with 8 mL/kg tidal volume. Results: Changes in ΔPP and PVI associated with the Trendelenburg maneuver before and after insufflation of the pneumoperitoneum were significantly different (P < 0.001). In baseline conditions, the Trendelenburg maneuver was associated with a significant decrease in heart rate while mean arterial pressure remained unchanged. Both ΔPP and PVI decreased. After insufflation of the pneumoperitoneum, the Trendelenburg maneuver was associated with a significant decrease in heart rate and ΔPP and an increase in mean arterial pressure while PVI remained unchanged. Conclusion: Pneumoperitoneum did not alter the response of ΔPP to autotransfusion associated with the Trendelenburg maneuver, which was not the case for the PVI. This latter decreased during Trendelenburg maneuver performed alone and remained unchanged during Trendelenburg maneuver performed after insufflation of the pneumoperitoneum. [ABSTRACT FROM AUTHOR]

Background: The identification of women at risk for preterm birth should allow interventions which could improve neonatal outcome. Fetal fibronectin, a glycoprotein which acts normally as glue between decidua and amniotic membranes could be a good marker of impending labour when its concentration in cervicovaginal secretions between 22 and 36 weeks of gestation is ≥50 ng/mL. Many authors worldwide have tested this marker with many different methodologies and clinical settings, but conclusions about its clinical use are mixed. It is time for a comprehensive update through a systematic review and meta-analysis.Methods: We searched PubMed, Cochrane Library, and Embase, supplemented by manual search of bibliographies of known primary and review articles, international conference papers, and contact with experts from 1-1990 to 2-2018. We have selected all type of studies involving fetal fibronectin test accuracy for preterm delivery. Two authors independently extracted data about study characteristics and quality from identified publications. Contingency tables were constructed. Reference standards were preterm delivery before 37, 36, 35, 34, and 32 weeks, within 28, 21, 14, or 7 d and within 48 h. Data were pooled to produce summary likelihood ratios for positive and negative tests results.Results: One hundred and ninety-three primary studies were identified allowing analysis of 53 subgroups. In all settings, none of the summary likelihood ratios were >10 or <0.1, thus indicating moderate prediction, particularly in asymptomatic women and in multiple gestations.Conclusions: The fetal fibronectin test should not be used as a screening test for asymptomatic women. For high-risk asymptomatic women, and especially for women with multiple pregnancies, the performance of the fetal fibronectin test was also too low to be clinically relevant. Consensual use as a diagnostic tool for women with suspected preterm labor, the best use policy probably still depends on local contingencies, future cost-effectiveness analysis, and comparison with other more recent available biochemical markers. [ABSTRACT FROM AUTHOR]

Open in new tab Download slide Open in new tab Download slide OBJECTIVES: The upcoming release of aprotinin in paediatric cardiac surgery prompted a re-evaluation of its use in comparison to tranexamic acid (TXA) focusing on their effect on exposure to blood transfusions as well as severe postoperative morbidity or mortality. METHODS: This retrospective study was conducted in a tertiary children hospital from 2002 to 2015. Patients receiving aprotinin (Aprotinin group: 2002–2007) were compared with those receiving TXA group (2008–2015) using propensity score analysis. Primary outcome measures were 'exposure to blood products' and 'severe postoperative morbidity or mortality'. High-risk subgroups that included neonates, complex (Risk Adjusted Classification for Congenital Heart Surgery-1 ≥ 3) and redo surgery were also analysed. RESULTS: The study included 2157 patients, 1136 in the Aprotinin group and 1021 in the TXA group. Exposure to blood products was significantly higher in the Aprotinin group (78% vs 60%; P  < 0.001) as well as in the complex and redo surgery subgroups. Incidence of mortality and/or severe morbidity was higher in the Aprotinin group (33% vs 28%; P  = 0.007), as well as in the neonate group. However, cardiopulmonary bypass priming volume and intraoperative fluid balance were significantly decreased, and the use of modified ultrafiltration significantly increased in the TXA group. CONCLUSIONS: In our population, children receiving aprotinin were more frequently transfused and were at a higher risk of developing severe postoperative morbidity or mortality than those receiving TXA. Subgroups at high risk of bleeding or inflammation did not seem to benefit from aprotinin. These differences might be explained by a safer profile of TXA, but also attributed to major changes in our patient blood management strategies over years. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the clinical usefulness and reproducibility of (semi‐)automated kinetic perimetry of the Octopus 900 and Humphrey field analyzer 3 (HFA3) compared to Goldmann perimetry as reference technique. Methods: A prospective interventional study of two study groups, divided into three subgroups. The first study group consisted of 28 patients, performing one visual field examination on each of the three devices. A second group of 30 patients performed four examinations, one on Goldmann and three on Octopus 900 with the following testing strategies: (1) with reaction time (RT) vector, no headphone; (2) without RT vector, no headphone; and (3) without RT vector, with headphone. Comparisons for V4e and I4e stimuli were made of the mean isopter radius (MIR) and of the distances of the isopter to the central visual axis in four directions. Statistical analysis was made with the R software version 3.2.2. Results: For V4e stimuli, the mean isopter radius showed no statistic significant difference comparing Goldmann to HFA3 [p‐value = 0.144; confidence interval (CI) −0.152 to 0.019] and comparing Goldmann to Octopus 900 without RT vector, either with (p‐value = 0.347; CI −0.023 to 0.081) or without headphone (p‐value = 0.130; CI −0.011 to 0.095). Octopus 900 with RT vector produced a significantly larger MIR for V4e stimuli in comparison to Goldmann (p‐value < 0.001). I4e stimuli produced statistically significantly larger visual field areas when comparing HFA3 and Octopus 900 to Goldmann perimetry. Conclusion: Humphrey field analyzer 3 and Octopus 900 without RT vector are promising successors of Goldmann perimetry. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the failure rate and performance of cell-free DNA (cfDNA) testing, mainly in terms of detection rates for trisomy 21, performed by 2 laboratories using different analytical methods.Methods: cfDNA testing was performed on 2,870 pregnancies with the HarmonyTM Prenatal Test using the targeted digital analysis of selected regions (DANSR) method, and on 2,635 pregnancies with the "Cerba test" using the genome-wide massively parallel sequencing (GW-MPS) method, with available outcomes. Propensity score analysis was used to match patients between the 2 groups. A comparison of the detection rates for trisomy 21 between the 2 laboratories was made.Results: In all, 2,811 patients in the Harmony group and 2,530 patients in the Cerba group had no trisomy 21, 18, or 13. Postmatched comparisons of the patient characteristics indicated a higher no-result rate in the Harmony group (1.30%) than in the Cerba group (0.75%; p = 0.039). All 41 cases of trisomy 21 in the Harmony group and 93 cases in the Cerba group were detected.Conclusions: Both methods of cfDNA testing showed low no-result rates and a comparable performance in detecting trisomy 21; yet GW-MPS had a slightly lower no-result rate than the DANSR method. [ABSTRACT FROM AUTHOR]

This prospective study investigates long-term functional outcome after total trapeziometacarpal joint replacement with the Ivory arthroplasty for trapeziometacarpal joint osteoarthritis. Clinical outcome, overall function, pain, and radiologic outcome after a minimum of 10 years were evaluated for 26 Ivory arthroplasty in 24 patients. Two patients had bilateral arthroplasties. The female to male ratio was 22:2, and the mean age was 71 years (range 57–83). The mean follow-up period was 130 months (range 120–142). Overall functioning as defined by the QuickDASH score and visual analogue pain score improved by 50% and 81%, respectively, when compared with the preoperative status. However, these outcomes deteriorated beyond 5 years after surgery. Long-term results suggest the Ivory arthroplasty to be a reliable treatment for trapeziometacarpal osteoarthritis since it improves overall function and reduces pain up to 10 years postoperatively. However, revision within 10 years after surgery was needed in four of 26 cases.Level of evidence: II [ABSTRACT FROM AUTHOR]

Objectives To compare the outcomes of sickle cell disease patients diagnosed through neonatal screening with those who were not. Methods In an observational multicenter study in Belgium, 167 screened and 93 unscreened sickle cell disease patients were analyzed for a total of 1116 and 958 patient-years of follow-up, respectively. Both groups were compared with propensity score analysis, with patients matched on three covariates (gender, genotype, and central Africa origin). Bonferroni correction was applied for all comparisons. Results Kaplan–Meier estimates of survival without bacteremia were significantly higher in the screened group than the unscreened group (94.47%; [95% CI, 88.64–97.36%] versus 83.78% [95% CI, 72.27–90.42%]), p = 0.032. Non-significant differences between both groups were reported for survival without acute chest syndrome, acute anemia, cerebral complication, severe infection, and vaso-occlusive crisis. Significantly lower hospitalization rate and days per 100 patient-years were observed in the screened compared with the unscreened group (0.27 vs. 0.63 and 1.25 vs. 2.82, p = 0.0006 and <0.0001). Conclusion These data confirm the benefit of a neonatal screening programme in reducing bacteremia and hospitalization. [ABSTRACT FROM AUTHOR]

Background: Elective caesarean section is performed mainly under spinal anaesthesia using hyperbaric bupivacaine combined with opioids. Despite rapid onset, good quality anaesthesia, bupivacaine provides a long duration of motor block and is related to maternal hypotension. Current policies appeal for implementation of enhanced recovery procedures after caesarean section. Hyperbaric prilocaine is an intermediate-acting local anaesthetic known for its efficacy in ambulatory surgery. Evidence on the clinical relevance of intrathecal prilocaine use for caesarean section is currently lacking., Objectives: We aimed to investigate whether hyperbaric prilocaine would offer a shorter motor block and recovery than bupivacaine, when comparing equipotent doses. We also assessed the characteristics of sensory block, maternal haemodynamics and side effects for both mother and newborn., Design: Prospective, randomised, double-blind, controlled, two-centre, clinical trial., Setting: One university teaching hospital and one general teaching hospital in Brussels, Belgium., Patients: American Society of Anesthesiologists' physical status 2 parturients (n = 40) undergoing caesarean section under spinal anaesthesia., Interventions: Patients were randomly assigned to receive spinal anaesthesia using hyperbaric prilocaine 50 mg or hyperbaric bupivacaine 10 mg, both given with sufentanil 2.5 μg and morphine 100 μg. An epidural catheter was introduced as a backup in case of failure., Main Outcomes: The primary outcome was the motor block regression (modified Bromage scale 1 to 6). Secondary outcomes included sensory block characteristics, first unassisted ambulation, maternal side effects, newborns' parameters and overall satisfaction., Results: Median [IQR] motor block was significantly shorter in the hyperbaric prilocaine group (110 [104 to 150] min versus 175 [135 to 189] min, P = 0.001). First unassisted ambulation was achieved earlier after prilocaine (204.5 [177 to 246.5] min versus 314 [209.25 to 400] min, P = 0.007), and the incidence of maternal hypotension was significantly higher with bupivacaine (P = 0.033). No supplementary epidural analgesia was needed., Conclusion: Prilocaine provides shorter motor block, faster recovery and better haemodynamic stability than bupivacaine while offering equivalent surgical anaesthesia., Trial Registration: Clinicaltrials.gov: NCT02973048, EudraCT: 2016-003010-26., (Copyright © 2021 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Background: Unbalanced fluid solutions cause metabolic acidosis and could be associated with impaired coagulation and increased blood loss., Objective: To investigate whether the use of a balanced colloid compared with a saline colloid for peri-operative fluid therapy in children undergoing cardiac surgery is associated with decreased blood loss and exposure to blood products., Design: Double-blinded randomised controlled trial., Setting: Tertiary children's hospital from 2013 to 2016., Patients: Children older than 29 days and younger than 3 years admitted for cardiac surgery with cardiopulmonary bypass (CPB). Exclusion criteria were emergency cardiac surgery, moribund (American Society of Anesthesiologists 5), Jehovah's witnesses, coagulopathy, renal failure, liver injury, intracranial haemorrhage and electrolyte disturbances. From the 128 patients eligible, 88 were included in the study., Intervention: Random assignment of patients to either a saline colloid (6% hydroxyethyl starch 130/0.4 in 0.9% NaCl) or a balanced-electrolyte colloid (6% hydroxyethyl starch 130/0.4 in an isotonic solution) for CPB priming and intra- and postoperative fluid therapy during the first postoperative 48 h., Main Outcome Measure: The primary outcome measure was calculated blood loss until the third postoperative day (POD3)., Results: A total of 44 patients were included in each study arm. Calculated blood loss at POD3 was not significantly different between the groups (saline colloid 19.9 [IQR 13.8 to 26.1] ml kg-1 versus balanced colloid 15.9 [IQR 9.0 to 25.3 ml kg-1], P = 0.409). Secondary outcomes related to bleeding, exposure to blood products and coagulation were not different between groups. There was also no difference in length of mechanical ventilation, intensive care and hospital length of stay between groups., Conclusion: The use of a balanced colloid for peri-operative fluid therapy compared with a saline one is not associated with decreased blood loss or exposure to blood products., Trial Registration: EudraCT identifier: 2012-006034-17 and ClinicalTrial.gov identifier: NCT02584868., (Copyright © 2021 European Society of Anaesthesiology and Intensive Care. Unauthorized reproduction of this article is prohibited.)

Probabilistic models including clinical risk factors with or without bone mineral density (BMD) have been developed to estimate the 5- or 10-year absolute fracture risk. We investigated the performance of the FRAX and Garvan tools in a well-characterized population-based cohort of 3560 postmenopausal, volunteer women, aged 60 to 85 years at baseline, included in the Fracture Risk Brussels Epidemiological Enquiry (FRISBEE) cohort, during 5 years of follow-up. Baseline data were used to calculate the estimated 10-year risk of hip and major osteoporotic fractures (MOFs) for each participant using FRAX (Belgium). We computed the 5-year risk according to the Garvan model with BMD. For calibration, the predicted risk of fracture was compared with fracture incidence across a large range of estimated fracture risks. The accuracy of the calculators to predict fractures was assessed using the area under the receiver operating characteristic curves (AUC). The FRAX tool was well calibrated for hip fractures (slope 1.09, p  < 0.001; intercept -0.001, p  = 0.46), but it consistently underestimated the incidence of major osteoporotic fractures (MOFs) (slope 2.12, p  < 0.001; intercept -0.02, p  = 0.06). The Garvan tool was well calibrated for "any Garvan" fractures (slope 1.05, p  < 0.001; intercept 0.01, p  = 0.37) but largely overestimated the observed hip fracture rate (slope 0.32, p  < 0.001; intercept 0.006, p  = 0.05). The predictive value for hip fractures was better for FRAX (AUC: 0.841, 95% confidence interval [CI] 0.795-0.887) than for Garvan (AUC: 0.769, 95% CI 0.702-0.836, p  = 0.01). The Garvan AUC for "any Garvan" fractures was 0.721 (95% CI 0.693-0.749) and FRAX AUC for MOFs was 0.708 (95% CI 0.675-0.741). In conclusion, in our Belgian cohort, FRAX estimated quite well hip fractures but underestimated MOFs, while Garvan overestimated hip fracture risk but showed a good estimation of "any Garvan" fractures. Both models had a good discriminatory value for hip fractures but only a moderate discriminatory ability for MOFs or "any Garvan" fractures. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., (© 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

This prospective study investigates long-term functional outcome after total trapeziometacarpal joint replacement with the Ivory arthroplasty for trapeziometacarpal joint osteoarthritis. Clinical outcome, overall function, pain, and radiologic outcome after a minimum of 10 years were evaluated for 26 Ivory arthroplasty in 24 patients. Two patients had bilateral arthroplasties. The female to male ratio was 22:2, and the mean age was 71 years (range 57-83). The mean follow-up period was 130 months (range 120-142). Overall functioning as defined by the QuickDASH score and visual analogue pain score improved by 50% and 81%, respectively, when compared with the preoperative status. However, these outcomes deteriorated beyond 5 years after surgery. Long-term results suggest the Ivory arthroplasty to be a reliable treatment for trapeziometacarpal osteoarthritis since it improves overall function and reduces pain up to 10 years postoperatively. However, revision within 10 years after surgery was needed in four of 26 cases. Level of evidence: II.