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Monochorionic twin pregnancies are at increased risk of single intrauterine death (sIUD) and subsequent brain injury in the surviving twin owing to shared placentation. We assessed the association between middle cerebral artery peak systolic velocity (MCA-PSV) and cerebral injury on magnetic resonance imaging (MRI) and examined the association between cerebral findings on diffusion-weighted imaging (DWI) and those on T2-weighted imaging following spontaneous sIUD.This was a retrospective cohort study of monochorionic pregnancies complicated by spontaneous sIUD followed at a tertiary center between January 2008 and January 2020. Pregnancies with sIUD following laser treatment, those with selective feticide, double IUD occurring on the same day or sIUD before 14 weeks' gestation were excluded, as were cases in which MCA-PSV was not measured or DWI-MRI was not performed. The ability of MCA-PSV Doppler to predict subsequent cerebral injury on MRI was assessed, and DWI findings were analyzed and compared with those on susceptibility-weighted imaging (SWI) and T2-weighted MRI to determine its diagnostic accuracy.We assessed 64 monochorionic pregnancies complicated by spontaneous sIUD. Of these, 47 (73.4%) pregnancies underwent fetal brain MRI and met the inclusion criteria. Sixteen (34.0%) of these fetuses demonstrated cerebral injury on MRI. The median interval between the diagnosis of sIUD and MRI examination was 5 days. Fetuses with increased MCA-PSV 1.5 multiples of the median (MoM) following sIUD were significantly more likely to demonstrate cerebral injury on MRI than were those with normal MCA-PSV (68.8% vs 38.7%; P = 0.05). The sensitivity and specificity of MCA-PSV 1.5 MoM for predicting cerebral injury on MRI were 68.8% (95% CI, 41.3-88.9%) and 61.3% (95% CI, 42.2-78.2%), respectively. Patterns of early cerebral injury on T2-weighted and SWI-MRI included acute or subacute tissue swelling (n = 6), parenchymal atrophy (n = 7), loss of cortical ribbon (n = 1) and hemorrhage (n = 8). Early MRI within approximately 2 weeks after the diagnosis of sIUD demonstrated abnormal DWI along with coexisting SWI and T2-weighted sequelae in 56.3% (9/16) of cases. When DWI was normal and a second MRI examination was performed later (n = 7), there were no ischemic changes evident on T2-weighted imaging.Increased MCA-PSV is associated with, but predicts poorly, cerebral injury after sIUD. Early MRI with DWI within approximately 2 weeks after the diagnosis of sIUD is valuable in identifying any cerebral injury. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.

Introduction Although the technology used for extracorporeal life support (ECLS) has improved greatly in recent years, the application of these devices to the patient is quite complex and requires extensive training of team members both individually and together. Human factors is an area that addresses the activities, contexts, environments, and tools which interact with human behavior in determining overall system performance. Hypothesis Analyses of the cognitive behavior of ECLS teams and individual members of these teams with respect to the occurrence of human errors may identify additional opportunities to enhance safety in delivery of ECLS. Results The aim of this article is to support health-care practitioners who perform ECLS, or who are starting an ECLS program, by establishing standards for the safe and efficient use of ECLS with a focus on human factor issues. Other key concepts include the importance of ECLS team leadership and management, as well as controlling the environment and the system to optimize patient care. Conclusion Expertise from other industries is extrapolated to improve patient safety through the application of simulation training to reduce error propagation and improve outcomes.

A growing number of familial Mediterranean fever (FMF) patients in Israel do not have a single country of origin for all four grandparents. We aimed to predict the Mediterranean fever gene (MEFV) variant most likely to be found for an individual FMF patient, by a machine learning approach. This study was conducted at the Sheba Medical Center, a referral center for FMF in Israel. All Jewish referrals included in this study carried an FMF associated variant in MEFV as shown by genetic testing performed between 2001 and 2017. We introduced the term ‘origin score’ to capture the dose and different combinations of the grandparents’ origin. A machine learning approach was used to analyze the data. In a total of 1781 referrals included in this study, the p.Met694Val variant was the most common, and the variants p.Glu148Gln and p.Val726Ala second and third most common, respectively. Of 26 countries of origin analyzed, those that increased the likelihood of a referral to carry specific variants were identified in North Africa for p.Met694Val, Europe for p.Val726Ala, and west Asia for p.Glu148Gln. Fourteen of the studied countries did not show a highly probable variant. Based on our results, it is possible to describe an association between modern day origins of the three most common MEFV variant types and a geographical region. A strong geographic association could arise from positive selection of a specific MEFV variant conferring resistance to endemic infectious agents.

Placental growth factor (PlGF) has shown promise in identification of placental fetal growth restriction (FGR). We aimed to investigate the association between PlGF and sonographic markers of placental dysfunction and assess its ability to diagnose FGR secondary to maternal vascular malperfusion (MVM).A retrospective study of singleton pregnancies with small for gestational age (SGA) fetuses, who had PlGF testing at 16-36 weeks. Fetuses with major chromosomal and/or structural anomalies and pregnancies with missing outcomes were excluded. Sonographic characteristics, perinatal outcomes and placental histopathology were compared between pregnancies with normal and low PlGF (10th percentile for gestational age). The diagnostic accuracy of PlGF for prediction of MVM was calculated.130 fetuses met inclusion criteria. Compared to normal PlGF (n = 65), pregnancies with low PlGF (n = 65) were associated with an estimated fetal weight 5th centile (73.8% (48) vs 53% (35), respectively, p = 0.01), abnormal uterine, umbilical and MCA Dopplers (p = 0.001 for all), fetal demise (18.8% (12) vs 0% respectively, p = 0.01) and preterm delivery (100% (65) vs 39% (59), respectively, p 0.001) . Low PlGF had a 70.1% (58.6-80.0) sensitivity and a 79.6% (64.7-90.2) specificity for identifying MVM, with an AUC of 0.73 (0.63-0.84). Positive and negative predictive values were 85.7% (76.8-91.2) and 60.3% (51.2-68.9), respectively. PlGF outperformed other parameters of placental FGR (uterine, umbilical artery, middle cerebral artery and abdominal circumference 5th centile), in isolation and when combined.PlGF is a useful tool to aid in the diagnosis of placental FGR secondary to MVM.

INTRODUCTION Since 2013, various guidelines for hypertension in pregnancy have been refined, no longer requiring proteinuria as a requisite criterion for preeclampsia. We aimed to evaluate the impact of the new definition on preterm birth (PTB) and adverse pregnancy outcomes. MATERIAL AND METHODS Women delivering in Ontario between April 2012 and November 2016 were included. Delivery

Background and objectiveAlthough total knee arthroplasty (TKA) is an effective treatment for severe knee osteoarthritis (OA), a subset of patients experience significant postoperative pain and dissatisfaction. Several clinical trials support the analgesic benefits of genicular nerve radiofrequency ablation (GN-RFA) for non-operative knee OA, but only one prior trial has examined the effects of this intervention given preoperatively on postoperative outcomes following TKA, showing no analgesic benefit of cooled GN-RFA. The current study evaluated whether conventional thermal GN-RFA performed preoperatively resulted in significant improvements in pain and function following TKA.MethodsThis was a single-center, prospective, randomized, sham-controlled, double-blinded pilot trial in which patients received either conventional GN-RFA (n=30) or sham (n=30) between 2 and 4 weeks prior to their TKA. Baseline measures were obtained preprocedurally on the day of intervention, with follow-up outcomes obtained preoperatively on the day of surgery, and at 2 and 6 weeks postoperatively.ResultsPatients receiving GN-RFA showed no significant improvements relative to sham controls in the primary outcome, pain intensity at rest at 6-week follow-up. Secondary outcomes, including pain with ambulation and physical function, also showed no significant differences between groups at any follow-up assessment.ConclusionsConventional GN-RFA of the superior lateral, superior medial, and inferior medial genicular nerves when performed prior to TKA did not provide clinically significant pain relief or improvement in functional status at 2 or 6 weeks postoperatively.Trial registration numberNCT02947321.

Objective: Monochorionic diamniotic twin pregnancies complicated by Type-III selective fetal growth restriction (sFGR) are at high risk of fetal death. The aim of this study was to identify predictors of fetal death in these pregnancies. Methods: This was an international multicenter retrospective cohort study. Type-III sFGR was defined as fetal estimated fetal weight (EFW) of one twin below the 10th percentile and intertwin EFW discordance of ≥ 25% in combination with intermittent absent or reversed end-diastolic flow in the umbilical artery of the smaller fetus. Predictors of fetal death were recorded longitudinally throughout gestation and assessed in univariable and multivariable logistic regression models. The classification and regression trees (CART) method was used to construct a prediction model of fetal death using significant predictors derived from the univariable analysis.Results: A total of 308 twin pregnancies (616 fetuses) were included in the analysis. In 273 (88.6%) pregnancies, both twins were liveborn, whereas 35 pregnancies had single (n = 19 (6.2%)) or double (n = 16 (5.2%)) fetal death. On univariable analysis, earlier gestational age at diagnosis of Type-III sFGR, oligohydramnios in the smaller twin and deterioration in umbilical artery Doppler flow were associated with an increased risk of fetal death, as was larger fetal EFW discordance, particularly between 24 and 32 weeks' gestation. None of the parameters identified on univariable analysis maintained statistical significance on multivariable analysis. The CART model allowed us to identify three risk groups: a low-risk group (6.8% risk of fetal death), in which umbilical artery Doppler did not deteriorate; an intermediate-risk group (16.3% risk of fetal death), in which umbilical artery Doppler deteriorated but the diagnosis of sFGR was made at or after 16 + 5 weeks' gestation; and a high-risk group (58.3% risk of fetal death), in which umbilical artery Doppler deteriorated and gestational age at diagnosis was < 16 + 5 weeks' gestation. Conclusions: Type-III sFGR is associated with a high risk of fetal death. A prediction algorithm can help to identify the highest-risk group, which is characterized by Doppler deterioration and early referral. Further studies should investigate the potential benefit of fetal surveillance and intervention in this cohort.

BackgroundThere is growing evidence of sex differences in placental vascular development. The objective of this study was to investigate the effect of fetal sex on uterine artery pulsatility index (PI) throughout gestation in a cohort of normal and complicated pregnancies.MethodsA prospective longitudinal study was conducted in 240 pregnant women. Pulsed wave Doppler ultrasound of the proximal uterine arteries was performed at a 4-weekly interval between 14 and 40 weeks of gestation. The patients were classified retrospectively as normal or complicated (one or more of maternal preeclampsia, preterm birth, or small for gestational age). To assess if the change in uterine artery PI during gestation differed between normal and complicated pregnancies and between fetal sexes, the uterine artery PI was modeled using a linear function of gestational age and the rate of change was estimated from the slope.ResultsWhile the uterine artery PI did not differ over gestation between females and males for normal pregnancies, the trajectory of this index differed by fetal sex for pregnancies complicated by either preeclampsia, preterm birth, or fetal growth restriction (p< 0.0001). The male fetuses in the complicated pregnancy group had an elevated slope compared to the other groups (p< 0.0001), suggesting a more progressive deterioration in uteroplacental perfusion over gestation.ConclusionsThe uterine artery PI is widely used to assess uteroplacental function in clinical settings. The observation that this metric changes more rapidly in complicated pregnancies where the fetus was male highlights the importance of sex when interpreting hemodynamic markers of placental maturation.

Introduction Although fetal brain injury due to COL4A1 gene mutation is well documented, fetal central nervous system (CNS) and placental histopathology lack description. We report CNS and placental pathology in fetal cases with symptomatic COL4A1 mutation. Methods We retrieved four autopsy cases of COL4A1 related disease, confirmed by genetic sequencing after fetal brain injury was detected. Results One case was a midgestation fetus with residua of ventricular zone hemorrhage and normal placental villi. Three cases were 30-32 week gestation fetuses: two demonstrated CNS small vessel thrombosis, with CNS injury. Both demonstrated high grade placental fetal vascular malperfusion (FVM). One additionally showed villous dysmorphism, the other demonstrated mild villous immaturity. The fetus whose placenta demonstrated high grade FVM was growth restricted. A fourth fetus demonstrated schizencephaly with a CNS arteriopathy with smooth muscle cell degeneration and cerebral infarcts; the placenta demonstrated severe villous dysmorphism and low grade FVM. Discussion These cases confirm that small vessel disease is important in producing intracranial pathology in COL4A1mutation. We report an arteriopathy distinct from microvascular thrombosis and demonstrate that placental pathology is common in fetal COL4A1 related disease. This tentatively suggests that placental pathology may contribute to CNS abnormalities by affecting circulatory sufficiency.

OBJECTIVES: To evaluate the feasibility of using umbilical artery (UA) Doppler waveforms to measure fetal heart rate short term variation (STV) across gestation. METHODS: A prospective longitudinal study was conducted at two study sites in 195 women with pregnancies considered low risk. Pulsed wave Doppler of the UAs was performed at a 4-weekly interval between 14–40 weeks of gestation using a standardized imaging protocol. Up to 12 consecutive UA Doppler waveforms were analyzed using an off-line processing software. Fetal heart rate STV was calculated using average R-to-R intervals extracted from the waveforms and baseline corrected for fetal heart rate. RESULTS: Baseline corrected short term fetal heart rate variation increased significantly with gestational age (conditional R(2) = 0.37, p < 0.0001) and was inversely correlated with fetal heart rate (conditional R(2) = 0.54, p < 0.0001). The short term variation ranged (median (interquartile range)) from 3.5 (2.9–4.1) ms at 14–20 weeks’ gestation to 6.3 (4.8–7.7) ms at 34–40 weeks’ gestation. The change in short term heart rate variation did not differ between study sites, different models of ultrasound machine or individual sonographers. CONCLUSIONS: Umbilical artery Doppler waveforms offer a robust and feasible method to derive short term variation of the fetal heart rate. It needs to be emphasized that the umbilical-Doppler derived short term variation is not interchangeable with measurements derived with computerized cardiotocography. Accordingly, further investigations need to validate associations with outcome to determine the value of concurrent fetal cardiovascular and heart rate evaluation that are possible with the technique described here.

A novel, permanent, bilateral, common carotid artery (CCA) coil filter implant was designed to capture stroke-producing emboli in atrial fibrillation patients. Under ultrasound guidance, it is automatically deployed through a 24-guage needle and is retrievable up to 4 h post-procedure. We assessed the feasibility, safety, and effectiveness of the CCA filter in pre-clinical testing.In a pulsatile flow simulator, the filter's embolic capture efficiency and integrity of simulated (1.2 mm diameter nylon balls) and actual thromboemboli were tested. Implant insertion, retrieval, and chronic safety were tested in sheep by ultrasound and X-ray. At termination, the CCAs were explanted and examined by pathology, histopathology and scanning electron microscopy. The fate of captured emboli was evaluated in sheep 3 weeks after upstream injection of autologous thromboemboli.In the flow simulator, 10 filters captured 29 of 29 (100%) 1.2 mm diameter nylon balls. In the thromboemboli integrity test, all captured thromboemboli (99 of 99) were adherent to the filter, without fragmentation. All sheep (n = 30/60 implants) underwent successful CCA filter implantation. During follow-ups at 4, 12, 13, 23, and 31 weeks (6 sheep/12 implants at each follow-up), there were no (0%) major bleeds, CCA damage/stenosis, implant migration, flow obstruction, or thrombi detected by ultrasound. Two organized microthrombi (100 μm) were observed by histopathology at the puncture site. After 3 weeks, autologous captured thromboemboli (n = 10) either completely regressed (5 of 5) or did not progress (5 of 5).These favorable pre-clinical results prompt clinical testing of the CCA filter in stroke prevention clinical trials.

The dysfunctional chronic pain (Dysfunctional CP) phenotype is an empirically identifiable CP subtype with unclear pathophysiological mechanisms that cuts across specific medical CP diagnoses. This study tested whether the multidimensional pain and psychosocial features that characterize the dysfunctional CP phenotype are associated broadly with elevated oxidative stress (OS). Measures of pain intensity, bodily extent of pain, catastrophizing cognitions, depression, anxiety, sleep disturbance, pain interference, and function were completed by 84 patients with chronic osteoarthritis before undergoing total knee arthroplasty. Blood samples were obtained at the initiation of surgery before incision or tourniquet placement. Plasma levels of F2-isoprostanes and isofurans, the most highly specific measures of in vivo OS, were quantified using gas chromatography/negative ion chemical ionization mass spectrometry. The results indicated that controlling for differences in age, sex, and body mass index, higher overall OS (mean of isoprostanes and isofurans) was associated with significantly (P0.05) greater pain intensity, more widespread pain, greater depressive symptoms and pain catastrophizing, higher pain interference, and lower function. OS measures were not significantly associated with sleep disturbance or anxiety levels (P0.10). The results build on prior case-control findings suggesting that presence of a CP diagnosis is associated with elevated OS, highlighting that it may specifically be individuals displaying characteristics of the dysfunctional CP phenotype who are characterized by elevated OS. Clinical implications of these findings remain to be determined.

OBJECTIVES: Little is known regarding fetal growth patterns in monochorionic twin pregnancy complicated by Type-III selective fetal growth restriction (sFGR). We aimed to assess fetal growth and umbilical artery Doppler pattern in Type-III sFGR across gestation and evaluate the effect of changing Doppler flow pattern on growth and intertwin growth discordance. METHODS: This was a retrospective cohort study of all Type-III sFGR pregnancies managed at nine fetal centers over a 12-year time period. Higher-order multiple pregnancy and cases with major fetal anomaly or other monochorionicity-related complications at presentation were excluded. Estimated fetal weight (EFW) was assessed on ultrasound for each twin pair at five timepoints (16-20, 21-24, 25-28, 29-32 and > 32 weeks' gestation) and compared with singleton and uncomplicated monochorionic twin EFW. EFW and intertwin EFW discordance were compared between pregnancies with normalization of umbilical artery Doppler of the smaller twin later in pregnancy and those with persistently abnormal Doppler. RESULTS: Overall, 328 pregnancies (656 fetuses) met the study criteria. In Type-III sFGR, the smaller twin had a lower EFW than an average singleton fetus (EFW Z-score ranging from -1.52 at 16 weeks to -2.69 at 36 weeks) and an average monochorionic twin in uncomplicated pregnancy (Z-score ranging from -1.73 at 16 weeks to -1.49 at 36 weeks) throughout the entire gestation, while the larger twin had a higher EFW than an average singleton fetus until 22 weeks' gestation and was similar in EFW to an average uncomplicated monochorionic twin throughout gestation. As pregnancy advanced, growth velocity of both twins decreased, with the larger twin remaining appropriately grown and the smaller twin becoming more growth restricted. Intertwin EFW discordance remained stable throughout gestation. On multivariable longitudinal modeling, normalization of fetal umbilical artery Doppler was associated with better growth of the smaller twin (P = 0.002) but not the larger twin (P = 0.1), without affecting the intertwin growth discordance (P = 0.09). CONCLUSIONS: Abnormal fetal growth of the smaller twin in Type-III sFGR was evident early in pregnancy, while EFW of the larger twin remained normal throughout gestation. Normalization of umbilical artery Doppler was associated with improved fetal growth of the smaller twin. © 2021 International Society of Ultrasound in Obstetrics and Gynecology. ispartof: ULTRASOUND IN OBSTETRICS & GYNECOLOGY vol:59 issue:3 pages:371-376 ispartof: location:England status: published

The penetrance of the p.[Met694Val];[Met694Val] genotype of pyrin in adult FMF patients is close to 100%. Disease penetrance of the p.[Met694Val];[Glu148Gln] genotype (M694V/E148Q), and the heterozygous p.[Met694Val];[=] genotype is unknown. A difference in the penetrance of the latter two may indicate functionality for the p.Glu148Gln variant. We performed a penetrance estimation study using controls and patients of North African Jewish (NAJ) decent. FMF in this population is highly prevalent and mutation frequencies are well known. The ratio between the calculated frequencies of the three genotypes obtained from the control cohort and the actual frequency obtained from the patient cohort were used to determine the penetrance of p.[Met694Val];[Glu148Gln] and p.[Met694Val];[=]. We found a penetrance of 0.135 and 0.008 for p.[Met694Val];[Glu148Gln] and.[Met694Val];[=], respectively. Thus the penetrance of p.[Met694Val];[Glu148Gln] is more than 17 times higher than p.[Met694Val];[=], indicating an active role for p.Glu148Gln when combined with p.Met694Val. This article is protected by copyright. All rights reserved.

Objectives Septo‐optic dysplasia (SOD) is a clinical syndrome characterized by varying combinations of optic nerve hypoplasia, pituitary gland hypoplasia and abnormal cavum septi pellucidi. It is suspected on prenatal imaging when there is non‐visualization or hypoplasia of the septal leaflets. Long‐term postnatal outcomes of fetuses with prenatally suspected SOD have been documented poorly. The aims of this study were to describe the natural history of deficient septal leaflets, to quantify the incidence of postnatally confirmed SOD and to document the visual, endocrine and long‐term neurodevelopmental outcomes of these infants. Methods This was an observational retrospective study of all fetuses with prenatal imaging showing isolated septal agenesis, assessed at a single tertiary center over an 11‐year period. Pregnancy, delivery and neonatal outcomes and pre‐ and postnatal imaging findings were reviewed. Neonatal evaluations or fetal autopsy reports were assessed for confirmation of SOD. Ophthalmologic, endocrine, genetic and long‐term developmental evaluations were assessed. Imaging findings and outcome were compared between infants with and those without postnatally confirmed SOD. Results Of 214 fetuses presenting with septal absence on prenatal ultrasound and magnetic resonance imaging (MRI), 18 (8.4%) were classified as having suspected isolated septal agenesis suspicious for SOD. Uniform prenatal MRI findings in cases with suspected SOD included remnants of the leaflets of the cavum septi pellucidi, fused forniceal columns, normal olfactory bulbs and tracts and a normal optic chiasm. Twelve fetuses were liveborn and five (27.8%) had postnatally confirmed SOD. Only two of these five fetuses had additional prenatal imaging features (pituitary cyst, microphthalmia and optic nerve hypoplasia) supporting a diagnosis of SOD. The other three confirmed SOD cases had no predictive prenatal or postnatal imaging findings that reliably differentiated them from cases without confirmed SOD. Visual and endocrine impairments were present in two (40%) and four (80%) cases with confirmed SOD, respectively. In those with visual and/or endocrine impairment, developmental delay (median age at follow‐up, 2.5 (interquartile range, 2.5–7.0) years) was common (80%) and mostly severe. Neonates with isolated septal agenesis and a lack of visual or endocrine abnormalities to confirm SOD had normal development. Conclusions Only a quarter of fetuses with isolated septal agenesis suggestive of SOD will have postnatal confirmation of the diagnosis. Clinical manifestations of SOD are variable, but neurodevelopmental delay may be more prevalent than thought formerly. © 2020 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Background This multi-national study evaluated changes in platelet (PLT) unit distributions at 12 national or regional blood collectors over a 10-year period. Methods Data on the total number of PLT distributions, the collection method, that is apheresis vs whole blood-derived (WBD), the PLT unit characteristics and post-collection modifications were obtained from 12 national or regional blood collectors from 2008 through 2017. Individual WBD PLT units were converted to apheresis equivalent units (i.e. a dose of PLTs) by dividing by 4, the typical pool size; WBD units that were pooled before distribution were counted as a single dose. Results Overall at these 12 blood collectors, the total number of PLTs distributed in 2008 was 1 373 200, which rose by 10·2% to 1 513 803 in 2017. The Japanese Red Cross, which distributes only apheresis PLTs, had a 13·4% increase in the number of distributions between the years 2008 and 2017, while the other 11 blood collectors combined demonstrated a 6·8% increase in distributions between these two years. Between the years 2008 and 2017, the changes in the proportion of apheresis, platelet-rich plasma and buffy coat PLT distributions were -29·9%, -70·7% and 80·0%, respectively. Conclusion The number of PLT distributions increased during the 10-year study period despite prophylactic PLT transfusion thresholds having remained fairly consistent over the last decade. Perhaps this increase is in part driven by increased administration of platelets to patients with massive haemorrhage or an increase in stem cell transplantation. The use of buffy coat PLTs is increasing at these collectors.

Several options to treat hospitalized severe COVID-19 patients have been suggested. The study aimed to describe survival in patients treated with convalescent COVID plasma (CCP) and to identify in-hospital mortality predictors. This prospective cohort study examined data from 112 severe COVID-19 patients hospitalized in the Corona Departments in an acute care hospital who received two units of CCP (at least one of them high-titer). Demographic and medical data was retrieved from the patients’ electronic health records (EHR). Possible predictors for in-hospital mortality were analyzed in a univariate analysis and those found to be clinically significant were further analyzed in a multivariable analysis. Median age was 67 years (IQR 55–74) and 66 (58.9%) of them were males. Of them, 20 (17.9%) died in hospital. On multivariable analysis diabetes mellitus (p = 0.004, OR 91.54), mechanical ventilation (p = 0.001, OR 59.07) and lower albumin levels at treatment (p = 0.027, OR 0.74) were significantly associated with increased in-hospital mortality. In our study, in-hospital mortality in patients receiving CCP is similar to that reported for the general population, however certain variables mentioned above were associated with increased in-hospital mortality. In the literature, these variables were also associated with a worse outcome in patients with COVID-19 who did not receive CCP. As evidence points toward a benefit from CCP treatment in immunocompromised patients, we believe the above risk factors can further define COVID-19 patients at increased risk for mortality, enabling the selection of candidates for early treatment in an outpatient setting if possible.

This prospective observational study evaluated preoperative predictors of complex regional pain syndrome (CRPS) outcomes in the 6 months following total knee arthroplasty (TKA). Participants were n = 110 osteoarthritis patients (64.5% female) undergoing unilateral TKA with no prior CRPS history. Domains of negative affect (depression, anxiety, catastrophizing), pain (intensity, widespread pain, temporal summation of pain [TSP]), pain interference, sleep disturbance, and pro-inflammatory status (tumor necrosis factor-alpha [TNF-a]) were assessed preoperatively. CRPS outcomes at 6-week and 6-month follow-up included the continuous CRPS Severity Score (CSS) and dichotomous CRPS diagnoses (2012 IASP criteria). At 6 months, 12.7% of participants met CRPS criteria, exhibiting a "warm CRPS" phenotype. Six-week CSS scores were predicted by greater preoperative depression, anxiety, catastrophizing, TSP, pain intensity, sleep disturbance, and TNF-a (P'slt; .05). Provisional CRPS diagnosis at 6 weeks was predicted by higher preoperative TSP, sleep disturbance, and TNF-a (P'slt; .05). CSS scores at 6 months were predicted by more widespread and intense preoperative pain, and higher preoperative TSP, pain interference, and TNF-a (P'slt; .01). CRPS diagnosis at 6 months was predicted only by more widespread and intense pain preoperatively (P'slt; .05). Risk for CRPS following TKA appears to involve preoperative central sensitization and inflammatory mechanisms. Preoperative negative affect is unlikely to directly influence long-term CRPS risk. PERSPECTIVE: This article identifies preoperative predictors of CRPS features at 6 months following total knee arthroplasty, including more widespread pain and higher pain intensity, temporal summation of pain, pain interference, and tumor necrosis factor-alpha levels. Findings suggest the importance of central sensitization and inflammatory mechanisms in CRPS risk following tissue trauma.

BACKGROUND AND OBJECTIVES: Timely and adequate access to safe blood forms an integral part of universal health coverage, but it may be compromised by natural or man-made disasters. This systematic review provides an overview of the best available scientific evidence on the impact of disasters on blood donation rates and safety outcomes. MATERIALS AND METHODS: Five databases (The Cochrane Library, MEDLINE, Embase, Web of Science and CINAHL) were searched until 27 March 2020 for (un)controlled studies investigating the impact of disasters on blood donation rates and/or safety. Risk of bias and overall certainty of the evidence were assessed using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. RESULTS: Eighteen observational studies were identified, providing very low certainty of evidence (due to high risk of bias, inconsistency and/or imprecision) on the impact of natural (12 studies) and man-made/technological (6 studies) disasters. The available evidence did not enable us to form any generalizable conclusions on the impact on blood donation rates. Meta-analyses could not detect any statistically significant changes in transfusion-transmissible infection (TTI) rates [hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV)-1/2, human T-lymphotropic virus I and II (HTLV-I/II) and syphilis] in donated blood after a disaster, either in first-time or repeat donors, although the evidence is very uncertain. CONCLUSION: The very low certainty of evidence synthetized in this systematic review indicates that it is very uncertain whether there is an association between disaster occurrence and changes in TTI rates in donated blood. The currently available evidence did not allow us to draw generalizable conclusions on the impact of disasters on blood donation rates. ispartof: VOX SANGUINIS vol:117 issue:6 pages:769-779 ispartof: location:England status: published

Currently approved anti-COVID-19 vaccines have been found to be safe and effective and almost 60% of Israeli residents are already vaccinated with BNT162b2 vaccine. This observational study was designed to evaluate the adverse events of vaccine reported by 61 healthcare workers at least 7 days after the 2nd vaccination, and to investigate the correlation of adverse events and anti-SARS-CoV-2 IgG antibody levels. The median participant's age was 51.25 years, 16 men and 45 women; 77% (44% of male and 84.5% of female participants) reported adverse events. Injection site pain, fatigue and fever were the most common symptoms, and significantly higher antibody levels (average 19,387 AU/mL) were found in participants who had fever compared to those who did not experience fever (average antibody levels of 9,977 AU/mL, p 0.001). This finding corresponds to previous observations of higher anti-SARS-CoV-2 IgG antibody levels in COVID-19 patients presented with fever.

Total knee arthroplasty (TKA) is effective for pain reduction in most patients, but 15% or more report unsatisfactory long-term pain outcomes. We tested whether oxidative stress (OS) related to extended tourniquet application during TKA and subsequent ischemic reperfusion (IR) contributed to adverse post-TKA pain outcomes. Blood samples were obtained in 91 patients with osteoarthritis (63% female) undergoing TKA before tourniquet placement (T1), 45 minutes after tourniquet inflation (T2), and 15 minutes after tourniquet removal (T3). Plasma levels of F 2 -isoprostanes and isofurans, the most specific measures of in vivo OS, were quantified. Pain intensity and function were assessed at baseline and again at 6 weeks and 6 months after TKA. Results indicated that higher Combined OS (F 2 -isoprostanes + isofurans/2) at T1 baseline and larger increases in Combined OS from T1 to T2 were associated with higher baseline-corrected past 24-hour worst and average pain intensity (numeric rating scale) and higher past week McGill Pain Questionnaire-2 total scores at 6-month follow-up ( P 's0.05). Increases in Combined OS from T1 to T3, which should most directly capture OS and IR injury related to tourniquet use, were not associated with short-term or long-term post-TKA pain outcomes. Longer ischemia duration was unexpectedly associated with lower baseline-corrected pain intensity at 6-month follow-up. Combined OS was not linked to functional outcomes at either follow-up. Elevated perioperative OS seems to exert small but significant adverse effects on long-term post-TKA pain outcomes, although this OS seems unrelated to IR injury associated with extended tourniquet use.

INTRODUCTION Antiretroviral therapy-naive pregnant women living with HIV are at an increased risk for adverse pregnancy outcomes. It remains controversial whether this risk persists with antiretroviral therapy. We conducted a systematic review and meta-analysis to evaluate whether pregnant women living with HIV and receiving antiretroviral therapy antenatally, are at an increased risk of adverse outcomes compared with HIV-negative controls. MATERIAL AND METHODS We searched MEDLINE, Embase, International Pharmaceutical Abstracts, EBM Reviews, PubMed (non-MEDLINE records), EBSCO CINAHL Complete, Clarivate Web of Science, African Index Medicus, LILACS and Google Scholar for all observational studies comparing pregnant women living with HIV on antiretroviral therapy with HIV-negative controls from 1 January 1994 to 10 August 2021 with no language or geographic restrictions. Perinatal outcomes included preterm birth (PTB), low birthweight, small-for-gestational age and preeclampsia. Using a random-effects model we pooled raw data to generate odds ratio (OR) with 95% confidence intervals (CI) for each outcome. Sub-analyses for high and low resource countries and time of antiretroviral therapy initiation were performed. This systematic review and meta-analysis is registered with PROSPERO, number CRD42020182722. RESULTS Of the 7900 citations identified, 27 were eligible for analysis (12 636 pregnant women living with HIV on antiretroviral therapy and 7 812 115 HIV-negative controls). ORs (95% CI) of PTB (1.88 [1.63-2.17]), small-for-gestational age (1.60 [1.18-2.17]) and low birthweight (2.15 [1.58-2.92]) were significantly higher in pregnant women living with HIV than in HIV-negative women, while the risk of preeclampsia (0.86 [0.57-1.30]) was comparable. The risk of PTB and low birthweight was higher in both high resource and low resource countries, while the risk of small-for-gestational age was higher only in the former. Preconceptional antiretroviral therapy was associated with a higher risk of PTB compared with antenatal initiation. CONCLUSIONS Pregnant women living with HIV on antiretroviral therapy have an increased risk of PTB, low birthweight and small-for-gestational age in high resource countries, as well as PTB and low birthweight in low income countries compared with HIV-negative controls.

OBJECTIVES—: To determine the relationship between blood flow in the fetal descending aorta and discordant umbilical arteries (UAs). METHODS—: Pulsed wave Doppler of both UAs and the descending aorta was performed at 4-weekly intervals between 14 and 40 weeks of gestation in 209 pregnant women. In datasets with discordant UAs, a linear mixed effects model was used to determine the categorical relationship between the UA pulsatility index (PI) (high, low and average) and the descending aorta PI. RESULTS—: Of the 209 cases, 81 had a discordance of greater than 25% in UA PI during one of their visits. There were no differences in birth outcomes between the groups with concordant and discordant UA PIs. In the cases with discordant UA PIs, the descending aorta PI was most strongly associated with both the average UA PI (P = .008), and with the UA with the lower PI (P = .008). CONCLUSIONS—: The relationship between blood flow in the descending aorta and UAs is consistent with the law for combining resistances in parallel. Measurements of the descending aorta PI, particularly in a scenario with discordant UAs, may inform the stability of the feto-placental circulation where discordant UA PIs are found.

Background: The current global pandemic has created unprecedented challenges in the blood supply network. Given the recent shortages, there must be a civilian plan for massively bleeding patients when there are no blood products on the shelf. Recognizing that the time to death in bleeding patients is less than 2 h, timely resupply from unaffected locations is not possible. One solution is to transfuse emergency untested whole blood (EUWB), similar to the extensive military experience fine-tuned over the last 19 years. While this concept is anathema in current civilian transfusion practice, it seems prudent to have a vetted plan in place. Methods and Materials: During the early stages of the 2020 global pandemic, a multidisciplinary and international group of clinicians with broad experience in transfusion medicine communicated routinely. The result is a planning document that provides both background information and a high-level guide on how to emergently deliver EUWB for patients who would otherwise die of hemorrhage. Results and Conclusions: Similar plans have been utilized in remote locations, both on the battlefield and in civilian practice. The proposed recommendations are designed to provide high-level guidance for experienced blood bankers, transfusion experts, clinicians, and health authorities. Like with all emergency preparedness, it is always better to have a well-thought-out and trained plan in place, rather than trying to develop a hasty plan in the midst of a disaster. We need to prevent the potential for empty shelves and bleeding patients dying for lack of blood.

Objective This study was aimed to assess the utility of diagnostic tests of maternal and fetal infection in the evaluation of stillbirth. Study Design A single-center retrospective study from January 2011 to December 2016 of all women presenting to the hospital with intrauterine fetal death at or after 20 weeks of gestation. Standard evaluation included review of medical records, clinical and laboratory inflammatory workup, maternal serologies, fetal autopsy, placental pathology, and fetal and placental cultures. A suspected infectious etiology was defined as meeting at least two diagnostic criteria, and only after exclusion of any other identifiable stillbirth cause. Results During the 7-year study period, 228 cases of stillbirth were diagnosed at our center. An infectious etiology was the suspected cause of stillbirth in 35 cases (15.3%). The mean gestational age of infection-related stillbirth was 28 1/7 (range: 22–37) weeks, while for a noninfectious etiology, it was 34 0/7 (range: 25–38) weeks (p = 0.005). Placental histological findings diagnostic of overt chorioamnionitis and funisitis were observed in 31 (88.5%) cases. In 16 (45.7%) cases the placental and fetal cultures were positive for the same pathogen. Serology of acute infection was positive in three (8.5%) of the cases. Conclusion Maternal and fetal infectious workup is valuable in the investigation of stillbirth, particularly before 30 weeks of gestation and should be considered a part of standard evaluation.

Traffic sign comprehension is significantly affected by their compliance with ergonomics design principles. Despite the UN Convention, designs vary among countries. The goal of this study was to establish theoretical and methodological bases for evaluating the design of conventional and alternative signs. Thirty-one conventional signs and 1–3 alternatives for each conventional sign were evaluated for their compliance with three ergonomics guidelines for sign design: physical and conceptual compatibility, familiarity and standardisation. Twenty-seven human factors and ergonomics experts from 10 countries evaluated the signs relative to their compliance with the guidelines. Analysis of variance across alternatives revealed that for 19 of the 31 signs, an alternative design received a significantly higher rating in its ergonomics design than the conventional sign with the same meaning. We also found a very high correlation between the experts’ ratings and comprehension from previous studies. In conclusion, many countries use signs for which better alternative designs exist, and therefore UN Convention signs should be re-examined, and ergonomics experts evaluation can serve as a good surrogate for road users’ comprehension surveys. Practitioner summary: This study presents theoretical and methodological bases for evaluating the design of UN Conventional and alternative traffic signs. Human factors and ergonomics experts evaluated 31 conventional and 68 alternative road signs, based on ergonomics principles for sign design. Results indicated the need to re-examine poorly designed UN Convention signs.

BACKGROUND: Recent studies suggest that the prevalence of celiac disease is rising. We previously established the prevalence of celiac disease in healthy blood donors in 2002. OBJECTIVE: The purpose of this study was to examine whether the prevalence of celiac disease and celiac disease autoimmunity has changed over time by performing a similar prospective study. METHODS: Healthy blood donors (n = 1908) were tested for tissue transglutaminase antibodies and for anti-endomysial antibodies when positive. Further evaluation followed accepted criteria for diagnosis. RESULTS: Overall, 32 donors had abnormal tissue transglutaminase antibodies (1.68%). Eight donors had tissue transglutaminase antibodies >3 × upper limit of normal (0.42%), two of them with tissue transglutaminase antibodies >10 × upper limit of normal, while 24 donors had tissue transglutaminase antibodies

Objective This study aimed to identify the frequency of potentially preventable causes of stillbirth in a large heterogeneous population. Study Design This is a retrospective study of all stillbirth cases between January 2011 and December 2016 at a single tertiary medical center. Deliveries resulting from a nonviable fetus prior to 24 weeks of gestation, intrapartum fetal death, and incomplete stillbirth workup were excluded. Potentially preventable stillbirth was defined as that of a nonanomalous fetus that most likely resulted from one or more of the following: (1) placental-mediated complications, (2) postterm pregnancy, (3) monochorionicity-associated complications, (4) cholestasis of pregnancy, (5) preventable or treatable infections, and (6) isoimmunization. Results During the study period, 312 stillbirths were identified, 228 of which met the inclusion criteria. Of the 110 cases with a recognized cause, 47 (20.6%) were potentially preventable. The most common causes were placental-mediated complications and preventable or treatable infections, accounting for 75 and 9% of all potentially preventable causes, respectively. There were no recognizable maternal risk factors for potentially preventable stillbirth. Conclusion One-fifth of all causes of stillbirth are potentially preventable. Due to the significant contribution of placental-mediated complications to preventable stillbirth, close sonographic surveillance and timely delivery may decrease risk substantially.

Background Extracorporeal life support (ECLS) describes the use of blood perfusion devices to provide advanced cardiac or respiratory support. Advances in percutaneous vascular cannula insertion, centrifugal pump technologies, and the miniaturization of extracorporeal devices have simplified ECLS. The intention of this discussion is to review the role of ECLS as a potential rescue method for emergency department (ED) clinicians in critical clinical scenarios and to focus on the prerequisites for managing an ECLS program in an ED setting. Discussion Possible indications for ECLS cannulation in the ED include ongoing circulatory arrest, shock or refractory hypoxemia and pulmonary embolism with refractory shock. Severe trauma, foreign body obstruction, hypothermia and near drowning are situations in which patients may potentially benefit from ECLS. Early stabilization in the ED can provide a time window for a diagnostic workup and/or urgent procedures, including percutaneous coronary intervention, rewarming or damage control surgery in trauma. The use of ECLS is resource intensive and can be associated with a high risk of complications, especially when performed without previous training. Therefore, ECLS should only be used when the underlying problem is potentially reversible, and the resources are available to address the etiology of organ dysfunction. Conclusion Emergent ECLS has a role in the ED for selected indications in the face of life-threatening conditions. ECLS provides a bridge to recovery, definitive therapy, intervention or surgery. ECLS program requires an appropriately trained staff (physicians, nurses and ECLS specialists), equipment resources and logistical planning.

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Background and Objectives Passive immunization using investigational COVID‐19 convalescent plasma (CCP) is a promising therapeutic strategy and could improve outcome if transfused early and contain high levels of anti‐SARS‐CoV‐2 antibodies. We report the management of a national CCP collection and distribution program in Israel. Materials and Methods From 1 April 2020 to 15 January 2021, 4020 volunteer donors donated 5221 CCP units and 837 (20.8%) donors donated more than once. Anti‐nucleocapsid IgG antibodies were determined using chemiluminescent immunoassay method (Abbott). A statistical model based on repeated IgG tests in sequential donations was created to predict the time of antibody decline below sample/cut‐off (S/CO) level of 4.0. Results Ninety‐six percent of CCP donors suffered a mild disease or were asymptomatic. Older donors had higher antibody levels. Higher antibody levels (S/CO ≥4) were detected in 35.2% of the donors. Low positive (S/CO ≥1.4–3.99) were found in 37%, and 27.8% had undetectable antibodies (S/CO ≤1.4). The model predicted decrease antibody thresholds of 0.55%/day since the first CCP donation, providing guidance for the effective timing of future collections from donors with high antibody levels. Conclusions An efficient CCP collection and distribution program was achieved, based on performing initial and repeated plasma collections, preferably from donors with higher antibody levels, and only antibody‐rich units were supplied for therapeutic use. The inventory met the quantity and quality standards of the authorities, enabled to respond to the growing demand of the medical system and provide a product that may contribute to improve prognosis in patients with COVID‐19.

Israel is currently struggling with the Coronavirus Disease (COVID-19) caused by SARS CoV-2. Transmission is increasing, with higher morbidity and mortality among populations at risk. Over-representation of blood type A was reported in COVID-19 patients with increased respiratory failure, while blood type O seems to have a protective effect. This may be caused by interference of anti-A antibodies in viral binding to the ACE receptor, different neutralization antibodies potency or variations in the stability of von Willebrand factor (VWF) multimers in different blood types. Since transfusion of convalescent COVID19 Plasma (CCP) is an accepted therapeutic modality, the Ministry of Health initiated a national project whereby CCP is collected by Magen David Adom (MDA) Blood Services using apheresis procedures and transfusions are approved by an experts committee, as part of the clinical trial or as compassionate treatment. Preliminary analysis of 49/170 patients treated so far shows improvement in 49%, with important relations with the anti-SARS-CoV-2 IgG antibodies level in the transfused plasma. Anti-SARS-CoV-2 antibodies were found in 83% of 1100 CCP donors, but a 13% decrease in antibodies level was detected in repeat donations. Blood type A was more predominant among CCP donors, when compared to MDA blood donors' data. A transfusion of CCP is a feasible and relatively safe therapeutic modality, mainly for patients with moderate COVID 19. CCP also serves as a source for the production of hyperimmune globulin for the treatment of COVID 19 and for passive immunization for populations at risk.

Background Several tools have been proven to predict the need for massive transfusion in trauma casualties, yet tools that are easily applicable in the prehospital setting for predicting the need for any blood product transfusion in the emergency department (ED) are lacking. Methods A retrospective analysis of the cross-referenced Israeli Defense Forces Trauma Registry and the Israeli National Trauma Registry databases was performed to identify predictors for any blood product transfusion in the ED. A scoring system was developed after internally validating the prediction model. Division to risk groups was performed. Results Seven variables (systolic blood pressure, heart rate, arterial oxygen saturation, trunk involvement, mechanism of injury, chest decompression, and tourniquet application) were included in the scoring system, ranging from 0 to 11.5. Risk groups for ED transfusion included very low (0.8%), low (3.2%), intermediate (8.5%), and high (31.2%) risk. Conclusion A scoring system for predicting the need for any blood product transfusion in the ED was developed, based on information readily available in the early stages of prehospital resuscitation, allowing the receiving medical facility to prepare for that need.

Background Fetal sex is known to affect pregnancy outcomes. In current clinical practice, monitoring of fetal well-being is based on Doppler ultrasound measurements of major placental and fetal vessels. The objective of this study was to investigate the effect of fetal sex on Doppler parameters throughout gestation in healthy pregnancy. Methods A prospective study was conducted in 240 pregnant women with ultrasound examinations at a 4-weekly interval between 12 and 38 weeks of gestation. Pulsed Doppler spectra were collected for the umbilical arteries (UAs), middle cerebral artery (MCA), descending abdominal aorta (DAo), and ductus venosus (DV). Linear mixed effects models were used to determine if the pulsatility indices (PIs) of these vessels depended on gestational age and fetal sex. Results While there were no differences in the MCA PI and DV PIV over gestation between female and male fetuses, the trajectory of the UA and DAo PIs differed by fetal sex (p = 0.02 and p = 0.01, respectively). Conclusions Doppler ultrasound parameters were found to be dependent on fetal sex for some vessels and not for others in healthy pregnancies. Further investigations are needed to understand the physiological mechanisms for these sex differences and the relevance for disease processes in pregnancy.

Disclaimer: Veno-arterial extracorporeal membrane oxygenation (ECMO) is increasingly being deployed for selected patients in cardiac arrest who do not attain a native circulation with conventional CPR (ECPR). This ELSO guideline is intended to be a practical guide to implementing ECPR and the early management following establishment of ECMO support. Where a paucity of high-quality evidence exists, a consensus has been reached amongst the authors to provide guidance to the clinician. This guideline will be updated as further evidence in this field becomes available.

Objective Type-III selective intrauterine growth restriction (sIUGR) is associated with a high and unpredictable risk of fetal death and fetal brain injury. The objective of this study was to describe the prospective risk of fetal death and the risk of adverse neonatal outcome in a cohort of twin pregnancies complicated by Type-III sIUGR and treated according to up-to-date guidelines. Methods We reviewed retrospectively all monochorionic diamniotic twin pregnancies complicated by Type-III sIUGR managed at nine fetal centers over a 12-year period. Higher-order multiple gestations and pregnancies with major fetal anomalies or other monochorionicity-related complications at initial presentation were excluded. Data on fetal and neonatal outcomes were collected and management strategies reviewed. Composite adverse neonatal outcome was defined as neonatal death, invasive ventilation beyond the resuscitation period, culture-proven sepsis, necrotizing enterocolitis requiring treatment, intraventricular hemorrhage Grade > I, retinopathy of prematurity Stage > II or cystic periventricular leukomalacia. The prospective risk of intrauterine death (IUD) and the risk of neonatal complications according to gestational age were evaluated. Results We collected data on 328 pregnancies (656 fetuses). After exclusion of pregnancies that underwent selective reduction (n = 18 (5.5%)), there were 51/620 (8.2%) non-iatrogenic IUDs in 35/310 (11.3%) pregnancies. Single IUD occurred in 19/328 (5.8%) pregnancies and double IUD in 16/328 (4.9%). The prospective risk of non-iatrogenic IUD per fetus declined from 8.1% (95% CI, 5.95-10.26%) at 16 weeks, to less than 2% (95% CI, 0.59-2.79%) after 28.4 weeks and to less than 1% (95% CI, -0.30 to 1.89%) beyond 32.6 weeks. In otherwise uncomplicated pregnancies with Type-III sIUGR, delivery was generally planned at 32 weeks, at which time the risk of composite adverse neonatal outcome was 29.0% (31/107 neonates). In twin pregnancies that continued to 34 weeks, there was a very low risk of IUD (0.7%) and a low risk of composite adverse neonatal outcome (11%). Conclusions In this cohort of twin pregnancies complicated by Type-III sIUGR and treated at several tertiary fetal centers, the risk of fetal death was lower than that reported previously. Further efforts should be directed at identifying predictors of fetal death and optimal antenatal surveillance strategies to select a cohort of pregnancies that can continue safely beyond 33 weeks' gestation. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

The spillover of animal coronaviruses (aCoVs) to humans has caused SARS, MERS, and COVID-19. While antibody responses displaying cross-reactivity between SARS-CoV-2 and seasonal/common cold human coronaviruses (hCoVs) have been reported, potential cross-reactivity with aCoVs and the diagnostic implications are incompletely understood. Here, we probed for antibody binding against all seven hCoVs and 49 aCoVs represented as 12,924 peptides within a phage-displayed antigen library. Antibody repertoires of 269 recovered COVID-19 patients showed distinct changes compared to 260 unexposed pre-pandemic controls, not limited to binding of SARS-CoV-2 antigens but including binding to antigens from hCoVs and aCoVs with shared motifs to SARS-CoV-2. We isolated broadly reactive monoclonal antibodies from recovered COVID-19 patients that bind a shared motif of SARS-CoV-2, hCoV-OC43, hCoV-HKU1, and several aCoVs, demonstrating that interspecies cross-reactivity can be mediated by a single immunoglobulin. Employing antibody binding data against the entire CoV antigen library allowed accurate discrimination of recovered COVID-19 patients from unexposed individuals by machine learning. Leaving out SARS-CoV-2 antigens and relying solely on antibody binding to other hCoVs and aCoVs achieved equally accurate detection of SARS-CoV-2 infection. The ability to detect SARS-CoV-2 infection without knowledge of its unique antigens solely from cross-reactive antibody responses against other hCoVs and aCoVs suggests a potential diagnostic strategy for the early stage of future pandemics. Creating regularly updated antigen libraries representing the animal coronavirome can provide the basis for a serological assay already poised to identify infected individuals following a future zoonotic transmission event.

Monoamniotic twin pregnancies are rare, but early diagnosis of such pregnancies is critical, as the incidence of complications in these pregnancies is much higher than in diamniotic or dichorionic twin pregnancies. Overall, only 70% of all monoamniotic twins will survive. Furthermore, approximately half of fetal deaths in these pregnancies are because of the high incidence of fetal anomalies (15%-25%), such as twin reversed arterial perfusion sequence and conjoined twinning. Therefore, early anatomy screening in the first trimester of pregnancy is recommended. Other causes of fetal death in these pregnancies include twin-twin transfusion syndrome, tight cord entanglement, or acute hemodynamic imbalances through the large placental vascular anastomoses. After viability, fetal surveillance can be intensified, as this decreases the risk of in utero death. Both inpatient and outpatient surveillance are reasonable. If otherwise uncomplicated, monoamniotic twins should be delivered at 33 to 34 weeks' gestation. Most centers will deliver by cesarean delivery, but some continue to advocate for vaginal delivery. Lastly, neonatal morbidity is high in monoamniotic twin pregnancies and is mainly related to prematurity.

Extracorporeal membrane oxygenation (ECMO) is a mechanical way to provide oxygenation, ventilation, and perfusion to patients with severe cardiopulmonary failure. Extracorporeal cardiopulmonary resuscitation (ECPR) describes the use of ECMO during cardiac arrest. ECPR requires an organized approach to resuscitation, cannula insertion, and pump initiation. Selecting the right patients for ECPR is an important aspect of successful programs. A solid understanding of the components of the ECMO circuit is critical to troubleshooting problems. Current evidence suggests a substantial benefit of ECPR compared with traditional CPR for refractory cardiac arrest but is limited by lack of randomized trials to date.

Background Maternally administered corticosteroids are routinely used to accelerate fetal lung maturation in pregnancies at risk of early preterm delivery. Although, among the subgroup with growth restriction, a majority show a temporary improvement in umbilical artery Doppler waveforms that may be sustained up to 7 days, a minority will acutely decompensate in response to corticosteroids in association with deteriorating umbilical and fetal Doppler waveforms. The basis for such acute Doppler changes is presently unknown. Our group has developed a noninvasive ultrasound methodology to measure wave reflections in the umbilical artery and have established that wave reflection metrics are sensitive to structural changes in the placental vasculature and to acute changes in vascular tone. Using this approach, we demonstrated in healthy pregnant mice that fetoplacental vascular resistance decreased in betamethasone-treated mice compared with saline-treated controls. Objective This study aimed to investigate the effects of betamethasone administration on the wave reflection metrics in a mouse model of fetal growth restriction and to compare these findings with equivalent measurements in human fetuses. Study Design Pregnant CD-1 mice were housed from embryonic day 14.5 to embryonic day 17.5 in either a normoxic (21% O2, n=24) or hypoxic environment (11% O2, n=22), the latter being an established mouse model of fetal growth restriction. To investigate the effect of maternally administered betamethasone on the fetoplacental vasculature, ultrasound imaging was performed at baseline and 4 hours after treatment (either betamethasone or sterile saline). Umbilical artery wave reflection metrics were compared between the groups and for the effect of fetal sex. In addition, a cohort of 10 pregnant women with elevated umbilical artery pulsatility index and evidence of fetal growth restriction and 6 controls were imaged before and after corticosteroid administration. Results In the mouse model, after betamethasone administration, the female fetuses from the hypoxia group showed a 15% increase in umbilical artery diameter, a 98% increase in umbilical artery blood flow, and a 27% decrease in umbilical artery reflection coefficient, whereas the males from the hypoxia group showed no substantial changes. In agreement with our mouse findings, umbilical artery reflections were found to be larger in human growth-restricted fetuses than controls in women at risk of preterm birth. Conclusion Our studies provide insight into the mechanism whereby the human growth-restricted fetus may exhibit a temporary favorable fetoplacental vascular response to maternally administered corticosteroids. Further investigations are needed to understand why the male growth-restricted fetus seems unable to mount this favorable vascular response.

Purpose of Review A novel permanent carotid filter device for percutaneous implantation was developed for the purpose of stroke prevention. In this review, we cover rationale, existing preclinical and clinical data, and potential future directions for research using such a device. Recent Findings The Vine™ filter was assessed for safety in sheep and in 2 observational human studies, the completed CAPTURE 1 (n = 25) and the ongoing CAPTURE 2 (planned n = 100). CAPTURE 1 has shown high procedural and long-term implant safety. A control group was not available for comparison. Summary A mechanical filter for permanent stroke prevention can be implanted bilaterally in the common carotid artery safely and efficiently. A randomized trial is planned for 2021 (n = 3500, INTERCEPT) to demonstrate superiority of a filter + anticoagulation strategy over anticoagulation alone in patients at high risk for ischemic stroke.

Objectives FMF results from mutations in the Mediterranean fever (MEFV) gene. The p. E148Q protein alternation is one of the most frequent in the MEFV gene, yet the exact E148Q genotype–phenotype correlation remains unclear. The aim of this study was to examine clinical significance of heterozygous E148Q variant in a paediatric FMF cohort. Methods We compared the clinical manifestations and disease severity score of four genetic subgroups: (group 1) patients harbouring a single heterozygous p. E148Q variant (n = 6); (group 2) patients harbouring a single p. M694V heterozygous variant (n = 88); (group 3) patients harbouring compound heterozygous p. M694V and p. E148Q variants (n = 36); and (group 4) homozygotes for p. M694V variant (n = 160). Results Of 646 FMF children from our centre, only 1% (six patients) of our genetically characterized FMF cohort had a single E148Q variant, most presenting with recurrent fevers and abdominal pain. None of the participants was found to harbour homozygous E148Q. Overall, M694V/E148Q compound heterozygosity did not exhibit a more severe phenotype compared with patients with a single M694V variant. The former group were less likely to have abdominal pain and exertional leg pain (P Conclusion Our findings demonstrate that a single heterozygous E148Q variant is unlikely to cause FMF in children and that E148Q/M694V is clinically indistinguishable from a single M694V variant. Thus, E148Q heterozygosity does not result in clinically meaningful phenotype in children.

To describe the postnatal outcome of fetal meconium peritonitis and identify prenatal predictors of neonatal surgery. We retrospectively reviewed all fetuses with ultrasound findings suspicious for meconium peritonitis at a single center over a 10-year period. A systematic review and meta-analysis were then performed pooling our results with previous studies assessing prenatally diagnosed meconium peritonitis and postnatal outcome. Prenatal sonographic findings were analyzed to identify predictors for postnatal surgery. 34 cases suggestive of meconium peritonitis were diagnosed at our center. These were pooled with cases from 14 other studies yielding a total of 244 cases. Postnatal abdominal surgery was required in two thirds of case (66.5 %). The strongest predictor of neonatal surgery was meconium pseudocyst (OR [95 % CI] 6.75 [2.53-18.01]), followed by bowel dilation (OR [95 % CI] 4.17 [1.93-9.05]) and ascites (OR [95 % CI] 2.57 [1.07-5.24]). The most common cause of intestinal perforation and meconium peritonitis, found in 52.2 % of the cases, was small bowel atresia. Cystic fibrosis was diagnosed in 9.8 % of cases. Short-term neonatal outcomes were favorable, with a post-operative mortality rate of 8.1 % and a survival rate of 100 % in neonates not requiring surgery. Meconium pseudocysts, bowel dilation, and ascites are prenatal predictors of neonatal surgery in cases of meconium peritonitis. Fetuses with these findings should be delivered in centers with pediatric surgery services. Though the prognosis is favorable, cystic fibrosis complicates postnatal outcomes.ZIEL: Beschreibung des postnatalen Outcomes der fetalen Mekoniumperitonitis und Identifizierung pränataler Prädiktoren für die neonatale Chirurgie. Wir untersuchten an einem einzigen Zentrum über 10 Jahre hinweg retrospektiv alle Föten mit Ultraschallbefunden, bei denen der Verdacht einer Mekoniumperitonitis bestand. Eine systematische Übersicht und eine Metaanalyse wurden daraufhin durchgeführt, um unsere Ergebnisse mit früheren Studien zur Beurteilung der pränatalen Mekoniumperitonitis und des postnatalen Outcomes zusammenzufassen. Die pränatalen sonografischen Befunde wurden analysiert, um Prädiktoren für die postnatale Chirurgie zu identifizieren. In unserem Zentrum gab es 34 Fälle mit Verdachtsdiagnose Mekoniumperitonitis. Diese wurden mit Fällen aus 14 anderen Studien zusammengefasst, sodass sich insgesamt 244 Fälle ergaben. In 2 Drittel der Fälle (66,5 %) war eine postnatale abdominale Operation erforderlich. Der stärkste Prädiktor für die neonatale Chirurgie war eine Mekonium-Pseudozyste (OR 6,75; 95 %-KI 2,53–18,01), gefolgt von Darmdilatation (OR 4,17; 95 %-KI 1,93–9,05) und Aszites (OR 2,57; 95 %-KI 1,07–5,24). Die häufigste Ursache für Darmperforation und Mekoniumperitonitis, die in 52,2 % der Fälle gefunden wurde, war die Dünndarmatresie. Mukoviszidose wurde in 9,8 % der Fälle diagnostiziert. Das Kurzzeit-Outcome bei Neugeborenen war günstig, mit einer postoperativen Mortalitätsrate von 8,1 % und einer Überlebensrate von 100 % bei Neugeborenen, die nicht operiert werden mussten. Mekonium-Pseudozysten, Darmdilatation und Aszites sind pränatale Prädiktoren für eine neonatale Chirurgie bei Mekoniumperitonitis. Bei Föten mit diesen Befunden sollte die Entbindung in Zentren mit dem Schwerpunkt Neugeborenenchirurgie erfolgen. Obwohl die Prognose günstig ist, erschwert Mukoviszidose das postnatale Outcome.

Background The Israeli Defense Force Medical Corps (IDF-MC) recently implemented the use of low titer group O whole blood (LTOWB) in the airborne combat search and rescue unit (CSAR) for both military and civilian patients during transport to definitive care. LTOWB is preferentially used by the CSAR instead of red blood cell units and freeze-dried plasma (FDP) for patients with signs of hemorrhagic shock. Ten percent of group O donors were eligible to donate LTOWB as they had anti-A and -B IgM titers of Methods All patients treated by CSAR providers with LTOWB between July 2018 and June 2019 were included. Results Between July 2018 and June 2019, eight patients have received 10 units of LTOWB. All patients suffered blunt injuries, 6 out of 8 (75%) of whom were due to motor vehicle accidents. Four patients (4 out of 8, 50%) received a single LTOWB unit, two patients (2 out of 8, 25%) received two units. Two pediatric patients received fewer than one unit of LTOWB. Median (range) heart rate was 130 (30-150) bpm, median systolic blood pressure was 107 (80-124) mmHg, and median Glasgow coma scale was 8 (on a scale of 3-15). For four (4 out of 8, 50%) patients, LTOWB was the only blood product used for volume resuscitation. All six adult patients were treated with 1 g of tranexamic acid at the point of injury. Conclusions The CSAR has successfully implemented a LTOWB program for the pre-hospital treatment of bleeding patients, and as its experience grows this product will be made available to other units and in civilian hospitals.

Background A walking blood bank (WBB) refers to the use of fellow combatants for battlefield blood donation. This requires pretesting combatants for infectious diseases and blood type. A fundamental prerequisite for this technique is that the donating soldier will suffer minimal physiological and mental impact. The purpose of the current study is to assess the effect of blood shedding on battlefield performance. Methods This is a double-blind randomized control trial. Forty Israel Defense Forces combatants volunteered for the study. Participants underwent baseline evaluation, including repeated measurement of vital signs, cognitive evaluation, physical evaluation, and a strenuous shooting test. Three weeks after the baseline evaluation, subjects were randomized to either blood donation or the control group. For blinding purposes, all subjects underwent venous catheterization for the duration of a blood donation. Repeated vital signs and function evaluation were then performed. Results Thirty-six patients were available for randomization. Baseline measurements were similar for both groups. Mean strenuous shooting score was 80.5 ± 9.5 for the control group and 82 ± 6.6 for the test group (p = 0.58). No clinically or statistically significant differences were found in tests designed to evaluate cognitive performance or physical functions. Vital signs taken multiple times were also similar between the test and control groups. Conclusions Executive, cognitive, and physical functions were well preserved after blood donation. This study supports the hypothesis that a WBB does not decrease donor combat performance. The categorical prohibition of physical exercise following blood donation might need to be reconsidered in both military and civilian populations.

Background The ambient exposure does not always reflect the internal levels of pollution absorbed in the body. While human biomonitoring (HBM) could provide a valid estimate of exposure extent, it is usually an expensive and a heavily manpowered enterprise. Using samples collected during blood donations for HMB may provide a more efficient platform for a routine biomonitoring. Methods The current study is aimed to explore the feasibility of using the national blood banking system for the purposes of HBM, to compare between residents of a suspected polluted area in northern Israel (Haifa Bay) to the rest of the country. Specifically, we will assemble a geographically representative sample of blood donors residing in the study area and of the general population, to test for four industry and traffic-related metals: lead (Pb), cadmium (Cd), arsenic (As) and chromium (Cr). Samples of whole blood from donors will be tested in the Laboratory of Public Health Services managed by the Ministry of Health. The information on donors’ biomarkers levels will be further linked with the air pollution and meteorological data assessed at the location of the blood collection sites (short-term exposure) and donors’ permanent address (long-term exposure), as recorded by the monitoring stations spread throughout Israel and the satellite-based exposure models. The association between biomarkers and ambient environmental exposures will be assessed. The samples’ collection is planned for 2 years of 2020–2021. Discussion The information collected in this study could lead to environmental regulations within Haifa Bay area aimed to prevent exposure to high levels of hazardous chemicals.

Background Monogenic autoinflammatory diseases are caused by pathogenic variants in genes that regulate innate immune responses, and are characterized by sterile systemic inflammatory episodes. Since symptoms can overlap within this rapidly expanding disease category, accurate genetic diagnosis is of the utmost importance to initiate early inflammation-targeted treatment and prevent clinically significant or life-threatening complications. Initial recommendations for the genetic diagnosis of autoinflammatory diseases were limited to a gene-by-gene diagnosis strategy based on the Sanger method, and restricted to the 4 prototypic recurrent fevers (MEFV, MVK, TNFRSF1A, and NLRP3 genes). The development of best practices guidelines integrating critical recent discoveries has become essential. Methods The preparatory steps included 2 online surveys and pathogenicity annotation of newly recommended genes. The current guidelines were drafted by European Molecular Genetics Quality Network members, then discussed by a panel of experts of the International Society for Systemic Autoinflammatory Diseases during a consensus meeting. Results In these guidelines, we combine the diagnostic strength of next-generation sequencing and recommendations to 4 more recently identified genes (ADA2, NOD2, PSTPIP1, and TNFAIP3), nonclassical pathogenic genetic alterations, and atypical phenotypes. We present a referral-based decision tree for test scope and method (Sanger versus next-generation sequencing) and recommend on complementary explorations for mosaicism, copy-number variants, and gene dose. A genotype table based on the 5-category variant pathogenicity classification provides the clinical significance of prototypic genotypes per gene and disease. Conclusions These guidelines will orient and assist geneticists and health practitioners in providing up-to-date and appropriate diagnosis to their patients.