Reduced plakoglobin increases the risk of sodium current defects and atrial conduction abnormalities in response to androgenic anabolic steroid abuse.

Androgenic anabolic steroids (AAS) are commonly abused by young men. Male sex and increased AAS levels are associated with earlier and more severe manifestation of common cardiac conditions, such as atrial fibrillation, and rare ones, such as arrhythmogenic right ventricular cardiomyopathy (ARVC). Clinical observations suggest a potential atrial involvement in ARVC. Arrhythmogenic right ventricular cardiomyopathy is caused by desmosomal gene defects, including reduced plakoglobin expression. Here, we analysed clinical records from 146 ARVC patients to identify that ARVC is more common in males than females. Patients with ARVC also had an increased incidence of atrial arrhythmias and P wave changes. To study desmosomal vulnerability and the effects of AAS on the atria, young adult male mice, heterozygously deficient for plakoglobin (Plako+/- ), and wild type (WT) littermates were chronically exposed to 5α-dihydrotestosterone (DHT) or placebo. The DHT increased atrial expression of pro-hypertrophic, fibrotic and inflammatory transcripts. In mice with reduced plakoglobin, DHT exaggerated P wave abnormalities, atrial conduction slowing, sodium current depletion, action potential amplitude reduction and the fall in action potential depolarization rate. Super-resolution microscopy revealed a decrease in NaV 1.5 membrane clustering in Plako+/- atrial cardiomyocytes after DHT exposure. In summary, AAS combined with plakoglobin deficiency cause pathological atrial electrical remodelling in young male hearts. Male sex is likely to increase the risk of atrial arrhythmia, particularly in those with desmosomal gene variants. This risk is likely to be exaggerated further by AAS use. KEY POINTS: Androgenic male sex hormones, such as testosterone, might increase the risk of atrial fibrillation in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC), which is often caused by desmosomal gene defects (e.g. reduced plakoglobin expression). In this study, we observed a significantly higher proportion of males who had ARVC compared with females, and atrial arrhythmias and P wave changes represented a common observation in advanced ARVC stages. In mice with reduced plakoglobin expression, chronic administration of 5α-dihydrotestosterone led to P wave abnormalities, atrial conduction slowing, sodium current depletion and a decrease in membrane-localized NaV 1.5 clusters. 5α-Dihydrotestosterone, therefore, represents a stimulus aggravating the pro-arrhythmic phenotype in carriers of desmosomal mutations and can affect atrial electrical function.

Metal cation crosslinked, partially reduced graphene oxide membranes with enhanced stability for high salinity, produced water treatment by pervaporative separation.

Graphene oxide (GO)-based membranes hold significant promise for applications ranging from energy storage to protective coatings, to saline water and produced water treatment, owing to their chemical stability and unique barrier properties achieving a high selectivity for water permeation. However, unmodified GO membranes are not stable when submerged in liquid water, creating challenges with their commercial utilization in aqueous filtration and pervaporation applications. To mitigate this, we develop an approach to modify GO membranes through a combination of low temperature thermal reduction and metal cation crosslinking. We demonstrate that Zn2+-rGO and Fe3+-rGO membranes had the highest permeation flux of 8.3 ± 1.5 l m-2h-1and 7.0 ± 0.4 l m-2h-1, for saline water separation, respectively, when thermally reduced after metal cross-linking; These membranes maintained a high flux of 7.5 ± 0.7 l m-2h-1, and 5.5 ± 0.3 l m-2h-1for produced water separation, respectively. All the membranes had a salt rejection higher than 99%. Fe3+crosslinked membranes presented the highest organic solute rejections for produced water of 69%. Moreover, long term pervaporation testing was done for the Zn2+-rGO membrane for 12 h, and only a minor drop of 6% in permeation flux was observed, while Zn2+-GO had a drop of 24%. Both modifiers significantly enhanced the stability with Fe3+-rGO membranes displaying the highest mechanical abrasion resistance of 95% compared to non-reduced and non-crosslinked GO. Improved stability for all samples also led to higher selectivity to water over organic contaminants and only slightly reduced water flux across the membrane.

A retrospective multicentre clinical study on management of isolated splenic vein thrombosis: risks and benefits of anticoagulation.

INTRODUCTION: Isolated splenic vein thrombosis (iSVT) is a common complication of pancreatic disease. Whilst patients remain asymptomatic, there is a risk of sinistral portal hypertension and subsequent bleeding from gastric varices if recanalisation does not occur. There is wide variation of iSVT treatment, even within single centres. We report outcomes of iSVT from tertiary referral hepatobiliary and pancreatic (HPB) units including the impact of anticoagulation on recanalisation rates and subsequent variceal bleeding risk. METHODS: A retrospective cohort study including all patients diagnosed with iSVT on contrast-enhanced CT scan abdomen and pelvis between 2011 and 2019 from two institutions. Patients with both SVT and portal vein thrombosis at diagnosis and isolated splenic vein thrombosis secondary to malignancy were excluded. The outcomes of anticoagulation, recanalisation rates, risk of bleeding and progression to portal vein thrombosis were examined using CT scan abdomen and pelvis with contrast. RESULTS: Ninety-eight patients with iSVT were included, of which 39 patients received anticoagulation (40%). The most common cause of iSVT was acute pancreatitis n = 88 (90%). The recanalisation rate in the anticoagulation group was 46% vs 15% in patients receiving no anticoagulation (p = 0.0008, OR = 4.7, 95% CI 1.775 to 11.72). Upper abdominal vascular collaterals (demonstrated on CT scan angiography) were significantly less amongst patients who received anticoagulation treatment (p = 0.03, OR = 0.4, 95% CI 0.1736 to 0.9288). The overall rate of upper GI variceal-related bleeding was 3% (n = 3/98) and it was independent of anticoagulation treatment. Two of the patients received therapeutic anticoagulation. CONCLUSION: The current data supports that therapeutic anticoagulation is associated with a statistically significant increase in recanalisation rates of the splenic vein, with a subsequent reduction in radiological left-sided portal hypertension. However, all patients had a very low risk of variceal bleeding regardless of anticoagulation. The findings from this retrospective study should merit further investigation in large-scale randomised clinical trials.

Amniotic fluid gamma-glutamyl transferase for prediction of biliary atresia in cases of non-visualisation of the fetal gallbladder: a retrospective study using a validated analytical platform and local reference range.

INTRODUCTION: The level of amniotic fluid gamma-glutamyl transferase (AFGGT) may help identify biliary atresia (BA) in cases of non-visualisation of the fetal gallbladder (NVFGB). This study aimed to validate a serum/plasma matrix-based gamma-glutamyl transferase (GGT) assay for amniotic fluid (AF) samples, establish a local gestational age-specific AFGGT reference range, and evaluate the efficacy of AFGGT for predicting fetal BA in pregnancies with NVFGB using the constructed reference range. METHODS: The analytical performance of a serum/plasma matrix-based GGT assay on AF samples was evaluated using a Cobas c502 analyser. Amniotic fluid gamma-glutamyl transferase levels in confirmed euploid singleton pregnancies (16+0 to 22+6 weeks of gestation) were determined using the same analyser to establish a local gestational age-specific reference range (the 2.5th to 97.5th percentiles). This local reference range was used to determine the positive predictive value (PPV) and negative predictive value (NPV) of AFGGT level <2.5th percentile for identifying fetal BA in euploid pregnancies with NVFGB. RESULTS: The serum/plasma matrix-based GGT assay was able to reliably and accurately determine GGT levels in AF samples. Using the constructed local gestational age-specific AFGGT reference range, the NPV and PPV of AFGGT level <2.5th percentile for predicting fetal BA in pregnancies with NVFGB were 100% and 25% (95% confidence interval=0, 53), respectively. CONCLUSION: In pregnancies with NVFGB, AFGGT level ≥2.5th percentile likely excludes fetal BA. Although AFGGT level <2.5th percentile is not diagnostic of fetal BA, fetuses with AFGGT below this level should be referred for early postnatal investigation.

Evaluating Antibody Mediated Protection against Alpha, Beta, and Delta SARS-CoV-2 Variants of Concern in K18-hACE2 Transgenic Mice.

SARS-CoV-2 variants of concern (VoC) are impacting responses to the COVID-19 pandemic. Here, we utilized passive immunization using human convalescent plasma (HCP) obtained from a critically ill COVID-19 patient in the early pandemic to study the efficacy of polyclonal antibodies generated to ancestral SARS-CoV-2 against the Alpha, Beta, and Delta VoC in the K18 human angiotensin converting enzyme 2 (hACE2) transgenic mouse model. HCP protected mice from challenge with the original WA-1 SARS-CoV-2 strain; however, only partially protected mice challenged with the Alpha VoC (60% survival) and failed to save Beta challenged mice from succumbing to disease. HCP treatment groups had elevated receptor binding domain (RBD) and nucleocapsid IgG titers in the serum; however, Beta VoC viral RNA burden in the lung and brain was not decreased due to HCP treatment. While mice could be protected from WA-1 or Alpha challenge with a single dose of HCP, six doses of HCP could not decrease mortality of Delta challenged mice. Overall, these data demonstrate that VoC have enhanced immune evasion and this work underscores the need for in vivo models to evaluate future emerging strains. IMPORTANCE Emerging SARS-CoV-2 VoC are posing new problems regarding vaccine and monoclonal antibody efficacy. To better understand immune evasion tactics of the VoC, we utilized passive immunization to study the effect of early-pandemic SARS-CoV-2 HCP against, Alpha, Beta, and Delta VoC. We observed that HCP from a human infected with the original SARS-CoV-2 was unable to control lethality of Alpha, Beta, or Delta VoC in the K18-hACE2 transgenic mouse model of SARS-CoV-2 infection. Our findings demonstrate that passive immunization can be used as a model to evaluate immune evasion of emerging VoC strains.

Tmax Volumes Predict Final Infarct Size and Functional Outcome in Ischemic Stroke Patients Receiving Endovascular Treatment.

OBJECTIVE: The objective of this paper was to explore the utility of time to maximum concentration (Tmax )-based target mismatch on computed tomography perfusion (CTP) in predicting radiological and clinical outcomes in patients with acute ischemic stroke (AIS) with anterior circulation large vessel occlusion (LVO) selected for endovascular treatment (EVT). METHODS: Patients with AIS underwent CTP within 24 hours from onset followed by EVT. Critically hypoperfused tissue and ischemic core volumes were automatically calculated using Tmax thresholds >9.5 seconds and >16 seconds, respectively. The difference between Tmax > 9.5 seconds and Tmax > 16 seconds volumes and the ratio between Tmax > 9.5 seconds and Tmax > 16 seconds volumes were considered ischemic penumbra and Tmax mismatch ratio, respectively. Final infarct volume (FIV) was measured on follow-up non-contrast computed tomography (CT) at 24 hours. Favorable clinical outcome was defined as 90-day modified Rankin Scale 0 to 2. Predictors of FIV and outcome were assessed with multivariable logistic regression. Optimal Tmax volumes for identification of good outcome was defined using receiver operating curves. RESULTS: A total of 393 patients were included, of whom 298 (75.8%) achieved successful recanalization and 258 (65.5%) achieved good outcome. In multivariable analyses, all Tmax parameters were independent predictors of FIV and outcome. Tmax  > 16 seconds volume had the strongest association with FIV (beta coefficient = 0.596 p <0.001) and good outcome (odds ratio [OR] = 0.96 per 1 ml increase, 95% confidence interval [CI] = 0.95-0.97, p < 0.001). Tmax  > 16 seconds volume had the highest discriminative ability for good outcome (area under the curve [AUC] = 0.88, 95% CI = 0.842-0.909). A Tmax  > 16 seconds volume of ≤67 ml best identified subjects with favorable outcome (sensitivity = 0.91 and specificity = 0.73). INTERPRETATION: Tmax target mismatch predicts radiological and clinical outcomes in patients with AIS with LVO receiving EVT within 24 hours from onset. ANN NEUROL 2022;91:878-888.

Prevalence of depression and anxiety among adults with vitiligo in a Malaysian tertiary hospital.

INTRODUCTION: Vitiligo is a chronic disorder resulting in skin depigmentation with reported global prevalence of 1-2%. This disease is often accompanied by psychosocial distress owing to the cosmetic disfigurement associated with it. The primary objective of this study was to determine the prevalence of depression and anxiety among adults with vitiligo in a local tertiary hospital. In addition, this study also evaluated the association of depression and anxiety with patients' characteristics. MATERIALS AND METHODS: This cross-sectional study was conducted among vitiligo patients aged 18 years and older in Hospital Klang, Selangor between October 2021 and June 2022. Assessment instruments used were Vitiligo Area Scoring Index (VASI) and Hospital Anxiety and Depression Scale (HADS). Demographic data and clinical characteristics of vitiligo patients were recorded. RESULTS: Of the 100 participants, 12 (12%) and 21 (21%) had depression and anxiety, respectively. The mean depression score (HADS-depression component) was 3.4 (SD 3.4) and mean anxiety score (HADS-anxiety component) was 4.7 (SD 3.9). There were significantly higher number of patients with abnormal HADS-D score in the age group of 35-51 years (p=0.029), single status (p=0.001), with employment (p=0.014) and disease duration <2 years (p=0.004). Patients in the divorced/widowed group had a significant association with anxiety (p=0.011). CONCLUSION: The prevalence of depression was 12% while anxiety was 21% in our cohort. Vitiligo has a significant psychosocial impact, thus clinicians should actively evaluate the mental health of these patients with the use of screening tools such as HADS and provide appropriate referrals and management.

Cyclic di-GMP Regulates the Type III Secretion System and Virulence in Bordetella bronchiseptica.

The second messenger cyclic di-GMP (c-di-GMP) is a ubiquitous molecule in bacteria that regulates diverse phenotypes. Among them, motility and biofilm formation are the most studied. Furthermore, c-di-GMP has been suggested to regulate virulence factors, making it important for pathogenesis. Previously, we reported that c-di-GMP regulates biofilm formation and swimming motility in Bordetella bronchiseptica. Here, we present a multi-omics approach for the study of B. bronchiseptica strains expressing different cytoplasmic c-di-GMP levels, including transcriptome sequencing (RNA-seq) and shotgun proteomics with label-free quantification. We detected 64 proteins significantly up- or downregulated in either low or high c-di-GMP levels and 358 genes differentially expressed between strains with high c-di-GMP levels and the wild-type strain. Among them, we found genes for stress-related proteins, genes for nitrogen metabolism enzymes, phage-related genes, and virulence factor genes. Interestingly, we observed that a virulence factor like the type III secretion system (TTSS) was regulated by c-di-GMP. B. bronchiseptica with high c-di-GMP levels showed significantly lower levels of TTSS components like Bsp22, BopN, and Bcr4. These findings were confirmed by independent methods, such as quantitative reverse transcription-PCR (q-RT-PCR) and Western blotting. Higher intracellular levels of c-di-GMP correlated with an impaired capacity to induce cytotoxicity in a eukaryotic cell in vitro and with attenuated virulence in a murine model. This work presents data that support the role that the second messenger c-di-GMP plays in the pathogenesis of Bordetella.

Impact of replacing or adding pregnancy-associated plasma protein-A at 11-13 weeks on screening for preterm pre-eclampsia.

OBJECTIVE: To assess whether pregnancy-associated plasma protein-A (PAPP-A) alters or provides equivalent screening performance as placental growth factor (PlGF) when screening for preterm pre-eclampsia (PE) at 11-13 weeks of gestation. METHODS: This was a secondary analysis of a non-intervention screening study of 6546 singleton pregnancies that were screened prospectively for preterm PE in the first trimester between December 2016 and June 2018. Patient-specific risks for preterm PE were estimated by maternal history, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI), PlGF and PAPP-A. A competing-risks model with biomarkers expressed as multiples of the median was used. All women and clinicians were blinded to the risk for preterm PE. The performance of screening for preterm PE using PlGF vs PAPP-A vs both PAPP-A and PlGF was assessed by comparing areas under the receiver-operating-characteristics (AUC) curves. McNemar's test was used to compare detection rate at a fixed false-positive rate (FPR) of 10%. RESULTS: PlGF and PAPP-A were measured in 6546 women, of whom 37 developed preterm PE. The AUC and detection rate at 10% FPR using PlGF in combination with maternal history, MAP and UtA-PI were 0.854 and 59.46%, respectively. The respective values were 0.813 and 51.35% when replacing PlGF with PAPP-A and 0.855 and 59.46% when using both PAPP-A and PlGF. Statistically non-significant differences were noted in AUC when replacing PlGF with PAPP-A (ΔAUC, 0.04; P = 0.095) and when using both PAPP-A and PlGF (ΔAUC, 0.002; P = 0.423). However, on an individual case basis, screening using PlGF in conjunction with maternal history, MAP and UtA-PI identified three (8.1%) additional pregnancies that developed preterm PE and that were not identified when replacing PlGF with PAPP-A. Screening using PAPP-A in addition to maternal history and other biomarkers did not identify any additional pregnancies. CONCLUSION: On an individual case basis, adoption of a screening strategy that uses PAPP-A instead of PlGF results in reduced detection of preterm PE, consistent with previous literature. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.

Non-visualisation of fetal gallbladder in a Chinese cohort.

INTRODUCTION: Non-visualisation of fetal gallbladder (NVFGB) is associated with chromosomal abnormalities, biliary atresia, cystic fibrosis, and gallbladder agenesis in Caucasian fetuses. We investigated the outcomes of fetuses with NVFGB in a Chinese cohort. METHODS: This retrospective analysis included cases of NVFGB among Chinese pregnant women at five public fetal medicine clinics in Hong Kong from 2012 to 2019. We compared the incidences of subsequent gallbladder visualisation, chromosomal abnormalities, biliary atresia, cystic fibrosis, and gallbladder agenesis between cases of isolated NVFGB and cases of non-isolated NVFGB. RESULTS: Among 19 cases of NVFGB detected at a median gestational age of 21.3 weeks (interquartile range, 20.0-22.3 weeks), 10 (52.6%) were isolated and nine (47.4%) were non-isolated. Eleven (58.0%) cases had transient non-visualisation, four (21.0%) had gallbladder agenesis, three (15.8%) had chromosomal abnormalities (trisomy 18, trisomy 21, and 22q11.2 microduplication), one (5.2%) had biliary atresia, and none had cystic fibrosis. The incidence of serious conditions was significantly higher in the non-isolated group than in the isolated group (44.4% vs 0%; P=0.029); all three cases with chromosomal abnormalities and the only case of biliary atresia were in the non-isolated group, while all four cases with gallbladder agenesis were in the isolated group. The incidences of transient non-visualisation were similar (55.6% vs 60.0%; P=1.000). CONCLUSION: Isolated NVFGB is often transient or related to gallbladder agenesis. While investigations for chromosomal abnormalities and biliary atresia are reasonable in cases of NVFGB, testing for cystic fibrosis may be unnecessary in Chinese fetuses unless the NVFGB is associated with consistent ultrasound features, significant family history, or consanguinity.

Mucosal Immunization with DTaP Confers Protection against Bordetella pertussis Infection and Cough in Sprague-Dawley Rats.

Pertussis is a respiratory disease caused by the Gram-negative pathogen, Bordetella pertussis. The transition from a whole-cell pertussis vaccine (wP and DTP) to an acellular pertussis vaccine (aP, DTaP, and Tdap) correlates with an increase in pertussis cases, despite widespread vaccine implementation and coverage, and it is now appreciated that the protection provided by aP rapidly wanes. To recapitulate the localized immunity observed from natural infection, mucosal vaccination with aP was explored using the coughing rat model of pertussis. Overall, our goal was to evaluate the route of vaccination in the coughing rat model of pertussis. Immunity induced by both oral gavage and intranasal vaccination of aP in B. pertussis challenged rats over a 9-day infection was compared to intramuscular wP (IM-wP)- and IM-aP-immunized rats that were used as positive controls. Our data demonstrate that mucosal immunization of aP resulted in the production of anti-B. pertussis IgG antibody titers similar to IM-wP- and IM-aP-vaccinated controls postchallenge. IN-aP also induced anti-B. pertussis IgA antibodies in the nasal cavity. Immunization with IM-wP, IM-aP, IN-aP, and OG-aP immunization protected against B. pertussis-induced cough, whereas OG-aP immunization did not protect against respiratory distress. Mucosal immunization by both intranasal and oral gavage administration protected against acute inflammation and decreased bacterial burden in the lung compared to mock-vaccinated challenge rats. The data presented in this study suggest that mucosal vaccination with aP can induce a mucosal immune response and provide protection against B. pertussis challenge. This study highlights the potential benefits and uses of the coughing rat model of pertussis; however, further questions regarding waning immunity still require additional investigation.

Reinvestigating the Coughing Rat Model of Pertussis To Understand Bordetella pertussis Pathogenesis.

Bordetella pertussis is a highly contagious bacterium that is the causative agent of whooping cough (pertussis). Currently, acellular pertussis vaccines (aP, DTaP, and Tdap) are used to prevent pertussis disease. However, it is clear that the aP vaccine efficacy quickly wanes, resulting in the reemergence of pertussis. Furthermore, recent work performed by the CDC suggest that current circulating strains are genetically distinct from strains of the past. The emergence of genetically diverging strains, combined with waning aP vaccine efficacy, calls for reevaluation of current animal models of pertussis. In this study, we used the rat model of pertussis to compare two genetically divergent strains Tohama 1 and D420. We intranasally challenged 7-week-old Sprague-Dawley rats with 108 viable Tohama 1 and D420 and measured the hallmark signs/symptoms of B. pertussis infection such as neutrophilia, pulmonary inflammation, and paroxysmal cough using whole-body plethysmography. Onset of cough occurred between 2 and 4 days after B. pertussis challenge, averaging five coughs per 15 min, with peak coughing occurring at day 8 postinfection, averaging upward of 13 coughs per 15 min. However, we observed an increase of coughs in rats infected with clinical isolate D420 through 12 days postchallenge. The rats exhibited increased bronchial restriction following B. pertussis infection. Histology of the lung and flow cytometry confirm both cellular infiltration and pulmonary inflammation. D420 infection induced higher production of anti-B. pertussis IgM antibodies compared to Tohama 1 infection. The coughing rat model provides a way of characterizing disease manifestation differences between B. pertussis strains.

Intranasal Immunization with Acellular Pertussis Vaccines Results in Long-Term Immunity to Bordetella pertussis in Mice.

Bordetella pertussis colonizes the respiratory mucosa of humans, inducing an immune response seeded in the respiratory tract. An individual, once convalescent, exhibits long-term immunity to the pathogen. Current acellular pertussis (aP) vaccines do not induce the long-term immune response observed after natural infection in humans. In this study, we evaluated the durability of protection from intranasal (i.n.) pertussis vaccines in mice. Mice that convalesced from B. pertussis infection served as a control group. Mice were immunized with a mock vaccine (phosphate-buffered saline [PBS]), aP only, or an aP base vaccine combined with one of the following adjuvants: alum, curdlan, or purified whole glucan particles (IRI-1501). We utilized two study designs: short term (challenged 35 days after priming vaccination) and long term (challenged 6 months after boost). The short-term study demonstrated that immunization with i.n. vaccine candidates decreased the bacterial burden in the respiratory tract, reduced markers of inflammation, and induced significant serum and lung antibody titers. In the long-term study, protection from bacterial challenge mirrored the results observed in the short-term challenge study. Immunization with pertussis antigens alone was surprisingly protective in both models; however, the alum and IRI-1501 adjuvants induced significant B. pertussis-specific IgG antibodies in both the serum and lung and increased numbers of anti-B. pertussis IgG-secreting plasma cells in the bone marrow. Our data indicate that humoral responses induced by the i.n. vaccines correlated with protection, suggesting that long-term antibody responses can be protective.

Coaching to enhance qualified surgeons' non-technical skills: a systematic review.

INTRODUCTION: The lack of an effective continuing professional development programme for qualified surgeons, specifically one that enhances non-technical skills (NTS), is an issue receiving increased attention. Peer-based coaching, used in multiple professions, is a proposed method to deliver this. The aim of this study was to undertake a systematic review of the literature to summarize the quantity and quality of studies involving surgical coaching of NTS in qualified surgeons. METHODS: A systematic search of the literature was performed through MEDLINE, EMBASE, Cochrane Collaboration and PsychINFO. Studies were selected based on predefined inclusion and exclusion criteria. Data for the included studies was independently extracted by two reviewers and the quality of the studies evaluated using the Medical Education and Research Study Quality Instrument (MERSQI). RESULTS: Some 4319 articles were screened from which 19 met the inclusion criteria. Ten studies involved coaching of individual surgeons and nine looked at group coaching of surgeons as part of a team. Group coaching studies used non-surgeons as coaches, included objective assessment of NTS, and were of a higher quality (average MERSQI 13.58). Individual coaching studies focused on learner perception, used experienced surgeons as coaches and were of a lower quality (average MERSQI 11.58). Individual coaching did not show an objective improvement in NTS for qualified surgeons in any study. CONCLUSION: Surgical coaching of qualified surgeons' NTS in a group setting was found to be effective. Coaching of individual surgeons revealed an overall positive learner perception but did not show an objective improvement in NTS for qualified surgeons.

Outcome of radiofrequency ablation for selective fetal reduction before vs at or after 16 gestational weeks in complicated monochorionic pregnancy.

OBJECTIVE: To investigate whether gestational age at intervention (< or ≥ 16 weeks) and other factors affect the risk of loss of the cotwin after selective fetal reduction using radiofrequency ablation (RFA) in monochorionic (MC) pregnancy. METHODS: This was a single-center retrospective analysis of 63 consecutive RFA procedures performed at our institution from January 2011 to October 2019 for selective fetal reduction in complicated MC pregnancies. Indications for RFA were twin reversed arterial perfusion sequence (13 cases), twin-to-twin transfusion syndrome (12 cases), twin anemia-polycythemia sequence (two cases), selective fetal growth restriction (10 cases), discordant anomalies (17 cases) and multifetal pregnancy reduction in triplets or quadruplets with a MC pair (nine cases). Twenty-six (41.3%) of these procedures were performed before and 37 (58.7%) after 16 weeks. Potential factors that could affect the risk of loss of the cotwin, including gestational age at RFA, order of multiple pregnancy, amnionicity, indication for RFA and number of ablation cycles, were assessed first by univariate analysis and then by multivariate analysis. RESULTS: There were 17 (27.0%) cotwin losses. Ablation cycles numbering four or more was the only factor among those investigated to be associated with loss of the cotwin after RFA (P = 0.035; odds ratio, 5.21), while the indication for RFA, order of multiple pregnancy, amnionicity and gestational age at RFA had no effect. Comparing RFA performed at < 16 vs ≥ 16 weeks, there was no difference in the rate of cotwin loss (23.1% vs 29.7%; P = 0.558) or preterm prelabor rupture of the membranes before 34 weeks (7.7% vs 5.4%; P = 0.853), or in the median gestational age at delivery (36.2 vs 37.3 weeks; P = 0.706). CONCLUSIONS: RFA is a promising tool for early selective fetal reduction in MC pregnancy before 16 weeks. Four or more ablation cycles is a major risk factor for cotwin loss. Careful assessment pre- and post-RFA, together with proficient operative skills to minimize the number of ablation cycles, are the mainstay to ensure that this procedure is effective and safe. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.

Safety of gadoterate meglumine in children younger than 2 years of age.

BACKGROUND: Few studies on the safety of gadolinium-based contrast agents have been performed in children with even fewer focusing on children younger than 2 years of age. OBJECTIVE: To assess the safety of gadoterate meglumine (Dotarem) in patients younger than 2 years of age by evaluating adverse events following contrast administration. MATERIALS AND METHODS: Pediatric patients younger than 2 years of age undergoing magnetic resonance imaging (MRI) with and without contrast were prospectively enrolled and received a weight-based intravenous dose of gadoterate meglumine (0.1 mmol/kg). The occurrence of adverse events was assessed at the time of injection, 2 h after MRI, and by phone contact using a standard questionnaire 24 h after MRI. Adverse events were documented including the time of onset, duration of symptoms, intensity, causality and subsequent outcome. Descriptive statistics were used to characterize patient information. RESULTS: One hundred fifty exams were completed in 150 patients (median age: 12.1 months, age range: 0.25-23 months; males: 56%). Almost all patients (97.3%) received sedation/anesthesia before and during MRI. Thirty-four adverse events were reported in 23 patients overall (15.3%; male: 73.9%; median age: 11 months, age range: 3-23 months). Within the initial 2 h after the injection, there was one report of transient flushing/warmth and one report of vomiting, the latter of which was related to drinking formula too soon after anesthesia. Twenty-two patients (14.7%), who had all received sedation/anesthesia, experienced minor adverse events within 24 h, most physiological. Fourteen patients (9.3%) reported emesis, eight (5.3%) reported transient flushing/warmth, seven (4.7%) reported nausea, one (0.7%) reported altered taste and one (0.7%) reported dizziness. No patient experienced anaphylaxis. Two patients (1.3%) reported allergic-like reactions, which consisted of wheezing or sneezing. CONCLUSION: No patient experienced adverse events directly related to gadoterate meglumine. Only two adverse events were reported to have occurred in the initial 2 h after the exam, while the rest were reported on the 24-h follow-up call. The higher reported rate of adverse events in this study may be related to concomitant sedation/anesthesia as well as to overreporting from parents on the 24-h follow-up questionnaire. The study confirms a good safety profile for gadoterate meglumine in this very sensitive population.

Confirmatory Study of Time-Dependent Computed Tomographic Perfusion Thresholds for Use in Acute Ischemic Stroke.

Background and Purpose- Computed tomographic perfusion (CTP) thresholds associated with follow-up brain infarction may differ by time from symptom onset to imaging and reperfusion. We confirm CTP thresholds over time to imaging and reperfusion in patients with acute ischemic stroke from the HERMES collaboration (Highly Effective Reperfusion Evaluated in Multiple Endovascular Stroke Trials) data. Methods- Patients with occlusion on CT angiography were acutely imaged with CTP. Noncontrast CT and magnetic resonance-diffusion weighted imaging at 24 to 48 hours defined follow-up infarction. Reperfusion was assessed on conventional angiogram. Tmax, cerebral blood flow (CBF), and cerebral blood volume maps were derived from delay-insensitive CTP postprocessing. These parameters were analyzed using receiver operator characteristics to derive optimal thresholds based on time from stroke onset-to-CTP or to reperfusion. ANOVA and linear regression were used to test whether the derived CTP thresholds were different by time. Results- One hundred thirty-seven patients were included. Tmax thresholds of >15.7 s and >15.8 s and absolute CBF thresholds of <8.9 and <7.5 mL·min-1·100 g-1 for gray matter and white matter respectively were associated with infarct if reperfusion was achieved <90 minutes from CTP with stroke onset-to-CTP <180 minutes. The discriminative ability of cerebral blood volume was modest. There were no statistically significant relationships between stroke onset-to-CTP time and Tmax, CBF, and cerebral blood volume thresholds (all P>0.05). A statistically significant relationship was observed between CTP-to-reperfusion time and the optimal thresholds for Tmax (P<0.001) and CBF (P<0.001). Similar but more modest relationship was noted for onset-to-reperfusion time and optimal thresholds for CBF (P≤0.01). Conclusions- CTP thresholds based on stroke onset and imaging time and taking into account time needed for reperfusion may improve infarct prediction in patients with acute ischemic stroke.

Female Representation and Implicit Gender Bias at the 2017 American Society of Colon and Rectal Surgeons' Annual Scientific and Tripartite Meeting.

BACKGROUND: Women surgeons are underrepresented in academic surgery and may be subject to implicit gender bias. In colorectal surgery, women comprise 42% of new graduates, but only 19% of Diplomates in the United States. OBJECTIVE: We evaluated the representation of women at the 2017 American Society of Colon and Rectal Surgeons Scientific and Tripartite Meeting and assessed for implicit gender bias. DESIGN: This was a prospective observational study. SETTING: The study occurred at the 2017 Tripartite Meeting. MAIN OUTCOME MEASURES: The primary outcome measured was the percentage of women in the formal program relative to conference attendees and forms of address. METHODS: Female program representation was quantified by role (moderator or speaker), session type, and topic. Introductions of speakers by moderators were classified as formal (using a professional title) or informal (using name only), and further stratified by gender. RESULTS: Overall, 31% of meeting attendees who are ASCRS members were women, with higher percentages of women as Candidates (44%) and Members (35%) compared with Fellows (24%). Women comprised 28% of moderators (n = 26) and 28% of speakers (n = 80). The highest percentage of women moderators and speakers was in education (48%) and the lowest was in techniques and technology (17%). In the 41 of 47 sessions evaluated, female moderators were more likely than male moderators to use formal introductions (68.7% vs 54.0%, p = 0.02). There was no difference when female moderators formally introduced female versus male speakers (73.9% vs 66.7%, p = 0.52); however, male moderators were significantly less likely to formally introduce a female versus male speaker (36.4% vs 59.2%, p = 0.003). LIMITATIONS: Yearly program gender composition may fluctuate. Low numbers in certain areas limit interpretability. Other factors potentially influenced speaker introductions. CONCLUSIONS: Overall, program representation of women was similar to meeting demographics, although with low numbers in some topics. An imbalance in the formality of speaker introductions between genders was observed. Awareness of implicit gender bias may improve gender equity and inclusiveness in our specialty. See Video Abstract at http://links.lww.com/DCR/A802.

Diagnostic accuracy of non-contrast magnetic resonance enterography in detecting active bowel inflammation in pediatric patients with diagnosed or suspected inflammatory bowel disease to determine necessity of gadolinium-based contrast agents.

BACKGROUND: Pediatric patients with inflammatory bowel disease (IBD) are at increased risk of gadolinium deposition given the potential need for multiple contrast-enhanced magnetic resonance enterography (MRE) exams over their lifetime. OBJECTIVE: To determine whether gadolinium-based contrast agents are necessary in assessing active bowel inflammation on MRE in pediatric patients with known or suspected IBD. MATERIALS AND METHODS: We conducted a retrospective study of 77 patients (7-18 years; 68.8% male) with known (n=58) or suspected (n=19) IBD and endoscopy with biopsy performed within 30 days of MRE without and with contrast evaluated bowel and non-bowel findings. During three visual analysis sessions, two radiologists reviewed pre-, post-, and pre-/post-contrast MRE images. A third radiologist independently reviewed 27 studies to assess inter-reader reliability. We used Cohen kappa (κ), Fleiss kappa, (κF), McNemar test, and sensitivity and specificity to compare MRE readings to combined endoscopic/histopathological findings (the reference standard). RESULTS: The pre- and pre-/post-contrast-enhanced MRE vs. combined endoscopic/histopathological results had moderate agreement (85.7%; κ 0.713, P<0.001; P-value 0.549). Compared to combined endoscopy/histopathology, pre- vs. pre-/post-contrast sensitivity (67%, confidence interval [CI] 0.53-0.79 vs. 67%, CI 0.53-0.79) and specificity (80%, CI 0.59-0.92 vs. 68%, CI 0.46-0.84) varied little (κ 0.42, P<0.001 and κ 0.32, P=0.003, respectively). The three readers had moderate agreement (85.2%; κ 0.695, P=0.001; P-value 0.625). More penetrating complications were identified following contrast administration (P-value 0.04). CONCLUSION: Use of a contrast agent does not improve the detection of active inflammation in the terminal ileum and colon compared to non-contrast MRE, although use of a contrast agent does aid in the detection of penetrating disease.