Dysregulation of BRD4 Function Underlies the Functional Abnormalities of MeCP2 Mutant Neurons.

Rett syndrome (RTT), mainly caused by mutations in methyl-CpG binding protein 2 (MeCP2), is one of the most prevalent intellectual disorders without effective therapies. Here, we used 2D and 3D human brain cultures to investigate MeCP2 function. We found that MeCP2 mutations cause severe abnormalities in human interneurons (INs). Surprisingly, treatment with a BET inhibitor, JQ1, rescued the molecular and functional phenotypes of MeCP2 mutant INs. We uncovered that abnormal increases in chromatin binding of BRD4 and enhancer-promoter interactions underlie the abnormal transcription in MeCP2 mutant INs, which were recovered to normal levels by JQ1. We revealed cell-type-specific transcriptome impairment in MeCP2 mutant region-specific human brain organoids that were rescued by JQ1. Finally, JQ1 ameliorated RTT-like phenotypes in mice. These data demonstrate that BRD4 dysregulation is a critical driver for RTT etiology and suggest that targeting BRD4 could be a potential therapeutic opportunity for RTT.

Aerosolization of viable Mycobacterium tuberculosis bacilli by tuberculosis clinic attendees independent of sputum-Xpert Ultra status.

Potential Mycobacterium tuberculosis (Mtb) transmission during different pulmonary tuberculosis (TB) disease states is poorly understood. We quantified viable aerosolized Mtb from TB clinic attendees following diagnosis and through six months' follow-up thereafter. Presumptive TB patients (n=102) were classified by laboratory, radiological, and clinical features into Group A: Sputum-Xpert Ultra-positive TB (n=52), Group B: Sputum-Xpert Ultra-negative TB (n=20), or Group C: TB undiagnosed (n=30). All groups were assessed for Mtb bioaerosol release at baseline, and subsequently at 2 wk, 2 mo, and 6 mo. Groups A and B were notified to the national TB program and received standard anti-TB chemotherapy; Mtb was isolated from 92% and 90% at presentation, 87% and 74% at 2 wk, 54% and 44% at 2 mo and 32% and 20% at 6 mo, respectively. Surprisingly, similar numbers were detected in Group C not initiating TB treatment: 93%, 70%, 48% and 22% at the same timepoints. A temporal association was observed between Mtb bioaerosol release and TB symptoms in all three groups. Persistence of Mtb bioaerosol positivity was observed in ~30% of participants irrespective of TB chemotherapy. Captured Mtb bacilli were predominantly acid-fast stain-negative and poorly culturable; however, three bioaerosol samples yielded sufficient biomass following culture for whole-genome sequencing, revealing two different Mtb lineages. Detection of viable aerosolized Mtb in clinic attendees, independent of TB diagnosis, suggests that unidentified Mtb transmitters might contribute a significant attributable proportion of community exposure. Additional longitudinal studies with sputum culture-positive and -negative control participants are required to investigate this possibility.

Consensus statement on the interhospital transfer of patients with acute aortic syndrome: TRAVERSING Delphi study.

BACKGROUND: Standardisation of referral pathways and the transfer of patients with acute aortic syndromes (AAS) to regional centres are recommended by NHS England in the Acute Aortic Dissection Toolkit. The aim of the Transfer of Thoracic Aortic Vascular Emergencies to Regional Specialist INstitutes Group study was to establish an interdisciplinary consensus on the interhospital transfer of patients with AAS to specialist high-volume aortic centres. METHODS: Consensus on the key aspects of interhospital transfer of patients with AAS was established using the Delphi method, in line with Conducting and Reporting of Delphi Studies guidelines. A national patient charity for aortic dissection was involved in the design of the Delphi study. Vascular and cardiothoracic surgeons, emergency physicians, interventional radiologists, cardiologists, intensivists and anaesthetists in the United Kingdom were invited to participate via their respective professional societies. RESULTS: Three consecutive rounds of an electronic Delphi survey were completed by 212, 101 and 58 respondents, respectively. Using predefined consensus criteria, 60 out of 117 (51%) statements from the survey were included in the consensus statement. The study concluded that patients can be taken directly to a specialist aortic centre if they have typical symptoms of AAS on the background of known aortic disease or previous aortic intervention. Accepted patients should be transferred in a category 2 ambulance (response time <18 min), ideally accompanied by transfer-trained personnel or Adult Critical Care Transfer Services. A clear plan should be agreed in case of a cardiac arrest occurring during the transfer. Patients should reach the aortic centre within 4 hours of the initial referral from their local hospital. CONCLUSIONS: This consensus statement is the first set of national interdisciplinary recommendations on the interhospital transfer of patients with AAS. Its implementation is likely to contribute to safer and more standardised emergency referral pathways to regional high-volume specialist aortic units.

National action plans for antimicrobial resistance and variations in surveillance data platforms.

Objective: To assess how national antimicrobial susceptibility data used to inform national action plans vary across surveillance platforms. Methods: We identified available open-access, supranational, interactive surveillance platforms and cross-checked their data in accordance with the World Health Organization's (WHO's) Data Quality Assurance: module 1. We compared platform usability and completeness of time-matched data on the antimicrobial susceptibilities of four blood isolate species: Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus and Streptococcus pneumoniae from WHO's Global Antimicrobial Resistance and Use Surveillance System, European Centre for Disease Control's (ECDC's) network and Pfizer's Antimicrobial Testing Leadership and Surveillance database. Using Bland-Altman analysis, paired t-tests, and Wilcoxon signed-rank tests, we assessed susceptibility data and number of isolate concordances between platforms. Findings: Of 71 countries actively submitting data to WHO, 28 also submit to Pfizer's database; 19 to ECDC; and 16 to all three platforms. Limits of agreement between WHO's and Pfizer's platforms for organism-country susceptibility data ranged from -26% to 35%. While mean susceptibilities of WHO's and ECDC's platforms did not differ (bias: 0%, 95% confidence interval: -2 to 2), concordance between organism-country susceptibility was low (limits of agreement -18% to 18%). Significant differences exist in isolate numbers reported between WHO-Pfizer (mean of difference: 674, P-value: < 0.001, and WHO-ECDC (mean of difference: 192, P-value: 0.04) platforms. Conclusion: The considerable heterogeneity of nationally submitted data to commonly used antimicrobial resistance surveillance platforms compromises their validity, thus undermining local and global antimicrobial resistance strategies. Hence, we need to understand and address surveillance platform variability and its underlying mechanisms.

Evaluation of Arterial and Venous Allografts in Subinguinal Bypasses.

BACKGROUND: Autologous saphenous vein is the preferred conduit for below-the-knee bypasses in patients with critical limb-threatening ischemia. Alternative graft must be considered for patients without (autologous saphenous vein). The aim of this article is to evaluate the mid-term performance of arterial allograft (AA) and venous allograft (VA) used as alternative conduits. METHODS: This retrospective study included patients with critical limb-threatening ischemia, with or without a history of homolateral femoropopliteal bypass, and no autologous veins were available who underwent infrainguinal arterial reconstructions using VA or AA from 2008 to 2018. Patients undergoing revision operations for infected bypasses were excluded. Primary patency (PP), primary assisted patency, secondary patency, major amputation, and death from any cause were the endpoints. For each event, a set of analyses were performed. RESULTS: Overall, 111 patients (63 VAs and 48 AAs) were included, with 108 having below-the-knee bypass. The median follow-up time was 27.8 months (15.6-37.4). The difference in PP between the 2 allograft types was significant (P = 0.049), with 65.9% (43.7-81.0), 44.1% (24.2-62.3), and 44.1% (24.2-62.3) in the AA group, respectively, at 6, 12, and 18 months, whereas 55.6% (40.0-68.6), 46.0% (30.6-60.2), and 33.2% (18.2-49.0) in the VA group. The choice of an AA over a VA was an independent factor associated with patency (for PP: hazard ratio [HR] = 0.43 [0.24-0.75], P = 0.003); primary assisted patency: HR = 0.52 (0.30-0.89], P = 0.018; and secondary patency: HR = 0.49 (0.27-0.88), P = 0.016. The allograft type did not affect either the incidence of major amputation or death from any cause (respectively, HR = 1.20 [0.49-2.93], and 0.88 [0.37-2.14]). CONCLUSIONS: The nature of the allograft appears to influence the patency of infrainguinal reconstruction, but not the course of the disease. Performant alternative grafts answering infectious issues are needed.

Engineering of human brain organoids with a functional vascular-like system.

Human cortical organoids (hCOs), derived from human embryonic stem cells (hESCs), provide a platform to study human brain development and diseases in complex three-dimensional tissue. However, current hCOs lack microvasculature, resulting in limited oxygen and nutrient delivery to the inner-most parts of hCOs. We engineered hESCs to ectopically express human ETS variant 2 (ETV2). ETV2-expressing cells in hCOs contributed to forming a complex vascular-like network in hCOs. Importantly, the presence of vasculature-like structures resulted in enhanced functional maturation of organoids. We found that vascularized hCOs (vhCOs) acquired several blood-brain barrier characteristics, including an increase in the expression of tight junctions, nutrient transporters and trans-endothelial electrical resistance. Finally, ETV2-induced endothelium supported the formation of perfused blood vessels in vivo. These vhCOs form vasculature-like structures that resemble the vasculature in early prenatal brain, and they present a robust model to study brain disease in vitro.

Iliac branch device to treat type Ib endoleak with a brachial access or an "up-and-over" transfemoral technique.

OBJECTIVE: In the present study, we reviewed the results of secondary iliac branch device (IBD) implantation for patients with a type Ib endoleak after prior fenestrated and/or branched (F/B) or infrarenal endovascular aortic aneurysm repair (EVAR) using either brachial access or an "up-and-over" transfemoral technique. METHODS: We performed a retrospective, single-center analysis between January 2016 and October 2021 of consecutive patients who had undergone IBD to correct a type Ib endoleak after prior EVAR or F/B-EVAR. The groups were defined by arterial access, which was either brachial (group 1) or transfemoral (group 2). All implanted IBDs had been manufactured by Cook Medical, Inc (Bloomington, IN). The demographics, anatomic features, technical success, and 30-day major adverse events were recorded in accordance with the current Society for Vascular Surgery standards. The survival curves using the Kaplan-Meier method were calculated. Branch instability was a composite end point of any internal iliac artery (IIA) branch-related complication or reintervention indicated to treat endoleak, kink, disconnection, stenosis, occlusion, or rupture. RESULTS: Overall, 28 patients (93% male; median age, 74 years), who had received 32 IBDs, were included, with 14 patients in each group. The prior endovascular aortic repairs included 23 cases of EVAR and 5 cases of F/B-EVAR, with an interval from the initial repair of 58 months (interquartile range [IQR], 48-70 months). The median pre-IBD maximal aneurysm diameter was 63.5 mm (IQR, 59.0-78.0 mm). The baseline characteristics were similar between the two groups, except for pulmonary status. All procedures were performed in a hybrid operative room. The median total operating time, fluoroscopy time, and dose area product was 120 minutes (IQR, 86-167 minutes), 23 minutes (IQR, 15-32 minutes), and 54 Gyccm2 (IQR, 40-62 Gyccm2), respectively. The total operating time was shorter for group 2 (P = .006). The technical success rate was 100%, and no early deaths occurred. One 30-day major adverse event, medically treated colonic ischemia, had occurred in one patient in group 2. Aortic-related secondary interventions had been required for seven patients (five in group 1 and two in group 2), including three cases of surgical explantation. The median follow-up was 31 months (IQR, 24-42 months) and 6 months (IQR, 3-10 months) for groups 1 and 2, respectively. For group 1, the 2-year freedom from aortic-related secondary intervention and IIA branch instability was 84.6% (IQR, 67.1%-100%) and 92.3% (IQR, 78.9%-100%), respectively. For group 2, the 6-month freedom from aortic-related secondary intervention and IIA branch instability was 87.5% (IQR, 67.3%-100%) and 91.7% (IQR, 77.3%-100%), respectively. CONCLUSIONS: The results from the present study have shown that secondary implantation of an IBD to correct a distal type I endoleak from a previous aortic stent graft is safe with a high technical success rate. The "up-and-over" technique can be considered an alternative to brachial access for patients with suitable anatomy.

Intraoperative cone beam computed tomography to improve outcomes after infrarenal endovascular aortic repair.

OBJECTIVE: We evaluated whether a combination of intraoperative contrast-enhanced cone beam computed tomography (ceCBCT) and postoperative contrast-enhanced ultrasound (CEUS) after infrarenal endovascular abdominal aortic aneurysm repair (EVAR) could reduce late stent graft-related complications and, consequently, reintervention. METHODS: All consecutive patients who had received infrarenal bifurcated stent grafts in our hybrid room (IGS 730; GE Healthcare, Île-de-France, France) during two discrete periods were included in the present study. From November 2012 to September 2013, two-dimensional completion angiography was performed after each EVAR, followed by computed tomography angiography (CTA) before discharge (group 1). From October 2013 to January 2015, intraoperative ceCBCT was performed, followed by CEUS within the first postoperative days (group 2). Comparative analyses of the outcomes were performed. The primary endpoint was late stent graft-related complications, a composite factor incorporating aneurysm-related death, type I or III endoleaks, kink or occlusion of the iliac limb, and aortic sac enlargement after the first 30 postoperative days. The secondary endpoint was all stent graft-related reinterventions. All-cause and aneurysm-related deaths were also recorded. RESULTS: Overall, 100 consecutive patients (50 each in groups 1 and 2) were enrolled, with a median follow-up of 60 months (interquartile range, 41-69 months). At 60 months after the index procedure, the freedom from late stent graft-related complications in each group was 61.6% (95% confidence interval [CI], 47.0%-80.6%) for group 1 and 81.7% (95% CI, 70.1%-95.2%) for group 2 (P = .033). The use of intraoperative ceCBCT was independently associated with a reduced rate of late stent graft-related complications on multivariate analysis (hazard ratio, 0.39; 95% CI, 0.16-0.95; P = .038) but did not appear to significantly protect against stent graft-related reinterventions (hazard ratio, 0.53; 95% CI, 0.20-1.39; P = .198) or all-cause death (P = .47). CONCLUSIONS: To the best of our knowledge, the present study is the first to report the influence of routine ceCBCT on late outcomes after EVAR. The use of ceCBCT shows the potential for reducing late stent graft-related complications associated.

Early Institutional Experience with One-Piece Bifurcated-Fenestrated Stentgraft in the Treatment of Abdominal Aortic Aneurysms.

PURPOSE: To review the early experience of the use of a bifurcated-fenestrated endograft (Bif-FEVAR) to treat abdominal aortic aneurysms (AAA) in a high-volume aortic center. METHODS: A retrospective single-center analysis was conducted between March 2019 and April 2021 including consecutive patients that underwent Bif-FEVAR. Only patients without a proper infrarenal neck and a distance <70 mm between the lowest target artery and the native or prosthetic aortic bifurcation were considered. All Bif-FEVAR custom-made devices were manufactured by Cook Medical (Inc., Bloomington, Indiana). Demographics, anatomical features, technical success, major adverse events, 30-day mortality, and survival according to Kaplan-Meier were analyzed according to Society for Vascular Surgery standards. RESULTS: Overall, 10 patients (100% male with median age 78) were included. The median preoperative maximal aneurysm diameter was 68 mm [51-84]. Eight patients were treated for a proximal type I endoleak after endovascular aneurysm repair. A total of 36 fenestrations were planned. The median operative time was 144 min [127-168], with a median fluoro time of 40.5 min [34-54] and a median dose area product of 73 Gy cm2 [61-89]. Technical success rate was 100%. No patients experienced a major postoperative adverse event. Median follow-up time was 8 months [6-13]. CONCLUSION: Bif-FEVAR is technically feasible when there is a short distance below the lowest target artery and the aortic bifurcation, with favorable short-term results. CLINICAL IMPACT: This study assessed the use of an innovative one-piece bifurcated fenestrated stent-graft as a primary procedure or in the treatment of proximal endoleak after standard infrarenal EVAR. We demonstrated these custom-made devices can be used safely with favorable short-term results. One-piece bifurcated fenestrated stent-grafts extend the indications of FEVAR for patients with an unusually short distance between the lowest renal artery and the aorto-iliac bifurcation or the diverter flow of a preexisting bifurcated infrarenal stent-graft.

Hybrid Room: Does it Offer Better Accuracy in the Proximal Deployment of Infrarenal Aortic Endograft?

BACKGROUND: This work aims to evaluate the impact of hybrid rooms and their advanced tools on the accuracy of proximal deployment of infrarenal bifurcated endograft (EVAR). METHODS: A retrospective single center analysis was conducted between January 2015 and March 2019 including consecutive patients that underwent EVAR. Groups were defined whether the procedure was performed in a hybrid operating room (HOR group) or using a mobile 2D fluoroscopic imaging system (non-HOR group). The accuracy of the proximal deployment was estimated by the distance (mm) between the bottom of the lowest renal artery (LwRA) origin and the endograft radiopaque markers parallax (LwRA/EDG distance) after curvilinear reconstruction. The impact of HOR on the LwRA/EDG distance was investigated using a multiple linear regression model. A composite "proximal neck"-related complications event was studied (Cox models). RESULTS: Overall, 93 patients (87 %male, median age 73 years) were included with 49 in the HOR group and 44 in the non-HOR group. Preoperative CTA analysis of the proximal neck exhibited similar median length, but different median aortic diameter (P = 0.012) and median beta angulation (P = 0.027) between groups. The median LwRA/EDG distance was shorter in the HOR group (multivariate model, P = 0.022). No difference in "proximal neck"-related complications was evidenced between the HOR and non-HOR groups (univariate analysis, P = 0.620). Median follow-up time was respectively 25 [14-28] and 36 months [23-44] in the HOR group and in the non-HOR group (P < 0.001). CONCLUSION: HOR offer more accurate proximal deployment of infrarenal endografts, with however no difference in "proximal neck"-related complications between groups.

Global Epidemiology of Chronic Venous Disease: A Systematic Review With Pooled Prevalence Analysis.

OBJECTIVE: To provide an updated estimate of the global prevalence of CVD and to comprehensively evaluate risk factors associated with this condition. BACKGROUND: CVD is an important cause of morbidity internationally, but the global burden of this condition is poorly characterized. The burden of CVD must be better characterized to optimize service provision and permit workforce planning to care for patients with different stages of CVD. METHODS: A systematic search in Ovid MEDLINE and Embase (1946-2019) identified 1271 articles. Full-text, English language articles reporting on the epidemiology of CVD in a general adult population were included. Data extraction was performed by 2 independent reviewers, in accordance with a preregistered protocol (PROSPERO: CRD42019153656). STATA and Review Manager were used for quantitative analysis. A crude, unadjusted pooled prevalence was calculated for each Clinical (C) stage in the Clinical, Etiologic, Anatomic, Pathophysiologic classification and across different geographical regions. Qualitative analysis was performed to evaluate associated risk factors in CVD. RESULTS: Thirty-two articles across 6 continents were identified. Nineteen studies were included in the overall pooled prevalence for each Clinical (C) stage; pooled estimates were: C0 s: 9%, C1: 26%, C2: 19%, C3: 8%, C4: 4%, C5: 1%, C6: 0.42%. The prevalence of C2 disease was highest in Western Europe and lowest in the Middle East and Africa. Commonly reported risk factors for CVD included: female sex (OR 2.26, 95% confidence intervals 2.16-2.36, P < 0.001), increasing age, obesity, prolonged standing, positive family history, parity, and Caucasian ethnicity. There was significant heterogeneity across the included studies. CONCLUSIONS: CVD affects a significant proportion of the population globally; however, there is significant heterogeneity in existing epidemiological studies.

Outcomes of Preventive Embolization of the Inferior Mesenteric Artery during Endovascular Abdominal Aortic Aneurysm Repair.

PURPOSE: To evaluate the impact of preemptive inferior mesenteric artery (IMA) embolization on outcomes of endovascular abdominal aortic aneurysm (AAA) repair (EVAR). MATERIALS AND METHODS: From January 2015 to July 2017, all patients undergoing elective EVAR or fenestrated EVAR (F-EVAR) for asymptomatic AAA in a single tertiary hospital were retrospectively included. Three groups of patients were defined: patients with a patent IMA who underwent embolization during EVAR/F-EVAR (group 1), those with a patent IMA who did not undergo embolization during EVAR/F-EVAR (group 2), and those with a chronically occluded IMA (group 3). Preoperative aortic morphology, demographics, and procedural details were recorded. Aneurysmal growth (≥5 mm), reintervention, and overall mortality rates were analyzed using multivariate proportional hazard multivariate modeling. Propensity scores were constructed, and inverse probability weighting was applied to a new set of multivariate analyses to perform a sensitivity analysis. RESULTS: A total of 266 patients (male, 95% [n = 249]) with a median age of 70 (65-77) years were included, with F-EVAR procedures comprising 87 (32.7%) of the interventions. There were 52, 142, and 72 patients in groups 1, 2, and 3, respectively. Changes in aneurysmal sac size did not differ between groups, nor did overall survival or reintervention rates at 24 months. IMA embolization was not identified as an independently protective factor for aneurysmal growth during follow-up (relative risk [RR] = 2.82/mm [0.96-8.28], P = .060), whereas accessory renal arteries (RR = 5.07/mm [1.72-14.96], P = .003) and a larger preoperative aneurysmal diameter (RR = 1.09/mm [1.03-1.15], P = .004) were independent risk factors for sac enlargement. CONCLUSIONS: Preventive embolization of the IMA during EVAR or F-EVAR did not promote aneurysmal sac shrinking or decrease the reintervention rate at 2-year follow-up.

Management of Type IA Endoleak After EVAR by Explantation or Custom Made Fenestrated Endovascular Aortic Aneurysm Repair.

OBJECTIVE: Proximal type 1 endoleak after endovascular abdominal aortic aneurysmal repair (EVAR) remains challenging to solve with no existing consensus. This work aims to compare two different surgical strategies to remedy type IA endoleak: endograft explantation (EXP) and aortic reconstruction or relining by custom made fenestrated EVAR (F-EVAR). METHODS: A retrospective single centre analysis between 2009 and 2018 was conducted including patients treated for type IA endoleak after EVAR with either EXP or F-EVAR. The choice of surgical technique was based on morphological factors (F-EVAR eligibility), sac growth rate, emergency presentation and/or patient symptoms. Technical success, morbidity, secondary interventions, 30 day mortality, and long term survival according to Kaplan-Meier were determined for each group and compared. RESULTS: Fifty-nine patients (91% male, mean age 79 years) underwent either EXP (n = 26) or F-EVAR (n = 33) during the study period. The two groups were equivalent in terms of comorbidity and age at the time of procedure. The median time from initial EVAR was 60.4 months (34-85 months), with no difference between groups. The maximum aneurysm diameter was greater in the EXP group compared with the F-EVAR group, 86 mm (65-100) and 70 mm (60-80), respectively (p = .008). Thirty day secondary intervention (EXP: 11.5% vs. F-EVAR: 9.1%) and mortality (EXP: 3.8% vs. F-EVAR: 3.3%) rates did not differ between groups, while major adverse events at 30 days, defined by the current SVS guidelines, were lower in the F-EVAR group (2.4% vs. 13.6%; p = .016). One year survival rates were similar between the groups (EXP: 84.0% vs. F-EVAR: 86.6%). CONCLUSION: Open explantation and endovascular management with a fenestrated device for type IA endoleak after EVAR can be achieved in high volume centres with satisfactory results. F-EVAR is associated with decreased early morbidity. Open explantation is a relevant option because of acceptable outcomes and the limited applicability of F-EVAR.

Bioaerosol sampling of patients with suspected pulmonary tuberculosis: a study protocol.

BACKGROUND: Tuberculosis (TB) is transmitted in bioaerosols containing Mycobacterium tuberculosis (Mtb). Despite being central to ongoing TB transmission, no routine diagnostic assay exists to measure Mtb in bioaerosols. Furthermore, published studies of Mtb in bioaerosol samples have been limited to individuals with sputum-positive pulmonary TB. Notably, TB diagnosis is based on clinical symptoms and sputum laboratory findings. This is despite the fact that approximately half of all patients commencing TB treatment are sputum-negative, resulting in a high proportion of presumptive treatments. Here, we propose to use a sensitive air sampling protocol to investigate the prevalence of Mtb-containing bioaerosols in both sputum-positive and sputum-negative TB suspects, at the same time evaluating the potential to identify unrecognized transmitters of TB. METHODS: Our parallel-group design will identify viable Mtb in bioaerosols produced by individuals attending a TB clinic in South Africa. Sampling will be performed on eligible individuals presenting with symptoms indicative of TB and repeated at 14 days if initially positive. Participants will be prospectively classified into three distinct groups based on National TB Control Program (NTBCP) criteria: Group A, TB notification with sputum-based laboratory confirmation; Group B, TB notification with empiric diagnosis; and Group C, individuals not notified. Group C individuals with detectable Mtb bioaerosol will be monitored until resolution of clinical and laboratory status. Collection of bioaerosol specimens will be via two consecutive sampling modalities: (1) direct sampling following a specific respiratory manoeuvre; and (2) indirect sampling during passive respiratory activity. Bioaerosol specimens will be analyzed for viable Mtb using DMN-trehalose staining and live-cell fluorescence microscopy. Mtb genomes and mycobacterial and host lipids will be detected using droplet digital PCR and mass spectrometry analyses, respectively. The primary objective is to determine the prevalence of Mtb bioaerosols in all TB clinic attendees and in each of the groups. Secondary objectives are to investigate differences in prevalence of Mtb bioaerosol by HIV status and current isoniazid preventive therapy (IPT) use; we will also determine the impact of anti-TB chemotherapy on Mtb-containing bioaerosol production. DISCUSSION: Respiratory bioaerosol has a potential role in non-invasive TB diagnosis, infectivity measurement and treatment monitoring. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04241809 . Date of Registration: 27/1/2020.

Correction to: Bioaerosol sampling of patients with suspected pulmonary tuberculosis: a study protocol.

An amendment to this paper has been published and can be accessed via the original article.

Early results of endovascular aneurysm sealing with chimney grafts to treat juxtarenal and suprarenal abdominal aortic aneurysms.

BACKGROUND: The treatment of juxtarenal abdominal aortic aneurysms is challenging. Open surgical repair is not a viable option for many patients. The use of endovascular aneurysm sealing (EVAS) with chimney grafts (Ch-EVAS) has been proposed as an immediately available, off-the-shelf option for individuals with juxtarenal aneurysms who require urgent treatment or are unsuitable for fenestrated or branched devices. This study reports the outcomes from our first patients to undergo this procedure. METHODS: Data were collected prospectively for 62 consecutive patients undergoing Ch-EVAS at our institution. The procedures were undertaken for intact juxtarenal or suprarenal aneurysms in patients who were unfit for open repair or needed urgent treatment or when the aneurysm morphology was unsuitable for treatment with fenestrated or branched endografts. RESULTS: Between July 2013 and June 2016, there were 62 patients who were treated with Ch-EVAS; 77.4% were male, and the mean age was 73.9 years. Median aneurysm diameter was 64.5 mm. Eight suprarenal aneurysms were treated, with three chimney grafts. Of 54 juxtarenal aneurysms treated, 21 cases used two chimney grafts and 33 cases used one chimney graft. Median follow-up was 407 days. Eleven patients underwent reintervention. There were five type IA endoleaks, all successfully treated. One type IB and one type II endoleak occurred, neither requiring treatment. There were four minor strokes. Chimney patency is 97%. CONCLUSIONS: These results in a group of high-risk patients suggest that Ch-EVAS is a viable alternative to custom-made devices in patients who are unfit for open surgery. Longer term follow-up and data from the international registry will determine the widespread applicability and durability of this technique.

Midterm results of endovascular aneurysm sealing to treat abdominal aortic aneurysm.

BACKGROUND: Endovascular aneurysm sealing (EVAS) represents a novel approach to the treatment of abdominal aortic aneurysms. It uses polymer technology to achieve an anatomic seal within the sac of the aneurysm. This cohort study reports the early clinical outcomes, technical refinements, and learning curve during the initial EVAS experience at a single institution. METHODS: Results from 150 consecutive EVAS cases for intact, infrarenal abdominal aortic aneurysms are reported here. These cases were undertaken between March 2013 and July 2015. Preoperative, perioperative, and postoperative data were collected for each patient prospectively. RESULTS: The median age of the cohort was 76.6 years (interquartile range, 70.2-80.9 years), and 87.3% were male. Median aneurysm diameter was 62.0 mm (IQR, 58.0-69.0 mm). Adverse neck morphology was seen in 69 (46.0%) patients, including aneurysm neck length <10 mm (17.3%), neck diameter >32 mm or <18 mm (8.7%), and neck angulation >60 degrees (15.3%). Median follow-up was 687 days (IQR, 463-897 days); 37 patients (24.7%) underwent reintervention. The rates of unresolved endoleak are 1.3% type IA, 0.7% type IB, and 2.7% type I. There were no type III endoleaks. There have been seven secondary ruptures in this cohort; all but one of these patients survived after reintervention. Only one rupture occurred in an aneurysm that had been treated within the manufacturer's instructions for use (IFU). CONCLUSIONS: The rate of unresolved endoleaks is satisfactorily low. The incidence of secondary rupture is of concern; however, when the IFU are adhered to, the rate is very low. The results of this study suggest that working within the IFU yields better clinical results.

Short Stay EVAR is Safe and Cost Effective.

OBJECTIVE: Reducing length of stay (LOS) following surgery offers the potential to improve resource utilisation. Endovascular aneurysm repair (EVAR) is now delivered with a low level of morbidity and as such may be deliverable as a "23 hour stay" intervention. This systematic review aims to assess safety, feasibility and cost effectiveness of a short stay EVAR pathway. METHODS: A database search of Ovid MEDLINE (1996 - April 2018) and Embase (1974 - April 2018) was completed. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were used. A Newcastle-Ottawa Scale was applied to assess study bias. RESULTS: In total, 570 papers were identified through the literature search, of which 32 abstracts were screened. This led to nine papers being assessed for eligibility. From five suitable studies, 450 (75%) patients were successfully discharged the same or next day after EVAR. Complications most often occurred within 3 hours of surgery, and major complications requiring intensive treatment unit admission occurred within 6 hours. Readmission rates were 0-5% for those discharged early, with no difference in 30 day readmission. Early discharge led to a statistically significant cost saving of £13,360 (LOS four days) to £9844 (LOS one day). CONCLUSION: Selected patients can safely undergo EVAR using a short stay pathway. A period of monitoring 6 h post-operatively for low risk patients would be sufficient. Reducing length of stay after EVAR in the UK from the current median of three days to 1.5 days would free 4361 bed days and lead to a saving of approximately £1,800,000 annually.

Protocol Adaptation of Optical Coherence Tomography in Lower Limb Arteries Revascularization.

In lower limb arteries, assessment of stent apposition and/or the single opening of the diseased artery remains poor since this relies on 2-dimensional angiogram. Extrapolating experience gained with coronary arteries, optical coherence tomography (OCT) could provide 3-dimensional reconstructions of the arterial wall and the stent implanted. A modified protocol of OCT acquisition, which usually includes large amount of iodine contrast flush, is presented here in 3 patients with long and complex occlusion of the superficial femoral artery. Its potential benefits and wider application to improve patient outcomes are discussed.

Transthoracic Ultrasound Evaluation of Arch and Descending Thoracic Aortic Pathology.

BACKGROUND: Duplex ultrasonography (DUS) currently has limited applicability in the diagnosis and surveillance of thoracic aortic pathologies because of associated limitations. This study investigates the feasibility of using an optimised DUS protocol to detect descending thoracic aortic pathology. METHODS: This was a prospective, case control cohort study. Patients with computed tomography (CT) confirmed thoracic aortic pathology underwent DUS of the thoracic aorta. A control group known to have no thoracic pathology also underwent DUS. The sonographer performing DUS was blinded to the CT findings, and recorded the presence of pathology or any dilated aortic segment where visualised. Diameter cutoff points of 35 mm and 40 mm were compared. RESULTS: Forty patients were scanned (20 cases and 20 controls). All patients but one had a technically adequate assessment of the thoracic aorta (at least one view of the descending thoracic aorta). Using a size threshold of 40 mm, 16 out of 19 cases and two out of 20 control patients would have been recommended for definitive imaging. Using a cutoff of 35 mm, this became 18 out of 19 cases and six of 20 controls. Sensitivity and specificity were 100% and 70% for a threshold of 35 mm, and 84% and 90% for a threshold of 40 mm. CONCLUSIONS: DUS has the potential to be used as a diagnostic modality for thoracic aortic pathology, and may have a role in surveillance for some patients for whom CT scanning is contraindicated. Further validation and refinements to this technique are required. However, this study provides proof of concept.