A prospective, randomized, controlled, interventional clinical trial to evaluate the safety and efficacy of the medical monopoint reperfusion system for aspiration thrombectomy in acute ischemic stroke patients (SUMMIT MAX): Trial rationale and design.

BACKGROUND: Treatment of large vessel occlusion (LVO) using mechanical thrombectomy with or without intravenous thrombolysis has demonstrated better outcomes compared to medical treatment alone. Large-bore aspiration catheters have been recently introduced. Their effectiveness and safety have not been demonstrated in a randomized trial. The SUMMIT MAX study is designed to address this question. METHODS: SUMMIT MAX is a randomized controlled trial where the effectiveness and safety of the large-bore Monopoint Reperfusion system (Route 92 Medical, San Mateo, CA), will be compared to the currently largest available FDA-cleared aspiration thrombectomy device the AXS Vecta Aspiration system (Stryker Neurovascular, Fremont, CA). The study is a multi-center, prospective, randomized, controlled, interventional, open label clinical trial. The hypothesis is that the effectiveness measured by the recanalization rate (modified thrombolysis in cerebrovascular infarction - mTICI) and safety measured by symptomatic intracranial hemorrhage rate (sICH) of the medical monopoint reperfusion system is non-inferior to the AXS Vecta Aspiration system. RESULTS: Up to 250 subjects are enrolled with at least 50% of subjects enrolled by US sites. The primary effectiveness endpoint is successful arterial revascularization defined as an mTICI score ≥ 2b after use of the assigned device adjudicated by an independent core lab. The primary safety endpoint is defined as sICH within 24 h (-8/+24) post-procedure. Secondary endpoints include successful arterial revascularization defined as a mTICI score ≥ 2b after use of the assigned device with or without adjunctive therapy; device-related serious adverse events; all asymptomatic hemorrhages; time from groin puncture to final angiogram; and rate of first pass effect defined as mTICI 2b after first pass with the assigned device stratified by age (≤85, ≥ 86). CONCLUSION: SUMMIT MAX is a randomized controlled trial comparing the effectiveness and safety of a new large bore class of aspiration devices to the currently largest FDA-cleared aspiration device available.

Cranial nerve palsies and intracranial aneurysms: A narrative review of patterns and outcomes.

Background: Cranial nerve palsy (CNP) in patients with intracranial aneurysms (IAs) can impose significant burdens on a patient's quality of life. The literature has a paucity of reviews addressing patterns of overall reported cranial nerve (CN) involvement and outcomes in patients with IA. Methods: The literature systematically reviewed CNP at presentation in the setting of IA using PubMed, Web-of-Science, and Scopus according to the PRISMA guidelines. Results: Fifty-two studies reported a total of 513 patients with IA and 630 CNPs observed at presentation: oculomotor (58.25%), abducent (15.87%), optic (12.06%), trochlear (8.7%), and trigeminal (1.9%). Most common aneurysms are located in a posterior communicating artery (46%) and cavernous internal carotid artery (29.2%). Trends of CNP based on the rupture status of IAs showed that 80% were associated with unruptured IAs and 20% with ruptured IAs. Post-treatment of IA, 55% of patients had complete resolution of CNP, with most (89%; n = 134) resolving within the first 6 months. Stratified by CNP type: Complete resolution rate is 100% in CN VII-IX, 60% in CN VI, 59% in CN IV, 54% in CN III, 45% in CN V, and 43% in CN II. Conclusion: In patients with cranial nerve palsies attributed to IAs, the location and rupture status of the aneurysm could determine the type and severity of the nerve palsy. Most patients experienced favorable outcomes in terms of their resolution and long-term function of the CNP after treatment of the IA.

Re-Envisioning Electronic Health Records to Optimize Patient-Centered Cancer Care, Quality, Surveillance, and Research.

Electronic health records (EHRs) are a significant advancement over paper records. However, the full potential of EHRs for improving care quality, patient outcomes, surveillance, and research in cancer care is yet to be realized. The organic evolution of EHRs has resulted in a number of unanticipated consequences including increased time spent by clinicians interfacing with the EHR for daily workflows. Patient access to clinicians and their records has been an important advancement in patient-centered care; however, this has brought to light additional gaps and challenges in EHRs meeting these needs. A significant challenge for EHR design and physician workflows is how best to meet the complex goals and priorities of various stakeholders including providers, researchers, patients, health systems, payors, and regulatory agencies. The National Cancer Policy Forum convened a 2022 workshop, "Innovations in Electronic Health Records for Oncology Care, Research and Surveillance," to address these challenges and to facilitate collaboration across all user groups with the goal of re-envisioning EHRs that will better support shared goals of improving patient outcomes and advancing cancer care and research without overburdening clinicians with administrative tasks. Here, we summarize the current EHR ecosystem as discussed at the workshop and highlight opportunities to improve EHR contributions to oncology evidence and care.

Oxymetazoline as a predictor of turbinate reduction surgery outcomes: Objective support from a prospective, single-blinded, computational fluid dynamics study.

BACKGROUND: A patient's subjective response to topical nasal decongestant is often used to screen for turbinate reduction surgery suitability. However, this anecdotal strategy has not been objectively and quantitatively evaluated. METHODS: Prospective, longitudinal, and single-blinded cohort study employing computational fluid dynamic modeling based on computed tomography scans at baseline, 30 min postoxymetazoline, and 2 months postsurgery on 11 patients with chronic turbinate hypertrophy. RESULTS: Nasal obstruction symptom evaluation (NOSE) and visual analogue scale (VAS) obstruction scores significantly improved from baseline to postoxymetazoline and again to postsurgery (NOSE: 71.82 ± 14.19 to 42.27 ± 25.26 to 22.27 ± 21.04; VAS: 6.09 ± 2.41 to 4.14 ± 2.20 to 2.08 ± 1.56; each interaction p < 0.05), with significant correlation between the latter two states (r∼0.37-0.69, p < 0.05). Oxymetazoline had a broader anatomical impact throughout inferior and middle turbinates than surgery (many p < 0.05); however, the improvement in regional airflow is similar (most p > 0.05) and predominantly surrounding the inferior turbinate. Strong postoxymetazoline to postsurgery correlations were observed in decreased nasal resistance (r = 0.79, p < 0.05), increased regional airflow rates (r = -0.47 to -0.55, p < 0.05) and regional air/mucosa shear force and heat flux (r = 0.43 to 0.58, p < 0.05); however, only increasing peak heat flux significantly correlated to symptom score improvement (NOSE: r = 0.48, p < 0.05). CONCLUSION: We present the first objective evidence that the "topical decongestant test" can help predict turbinate reduction surgery outcomes. The predictive effect is driven by similar improvementin regional airflow that leading to improved air/mucosa stimulations (peak heat flux) rather than through reduced nasal resistance.

The Impact of Social Deprivation on Anterior Urethral Stricture Recurrence After Urethroplasty - A Trauma and Urologic Reconstructive Network of Surgeons (TURNS) Analysis.

INTRODUCTION AND OBJECTIVES: Several factors influence recurrence after urethral stricture repair. The impact of socioeconomic factors on stricture recurrence after urethroplasty is poorly understood. This study aims to assess the impact that social deprivation, an area-level measure of disadvantage, has on urethral stricture recurrence after urethroplasty. METHODS: We performed a retrospective review of patients undergoing urethral reconstruction by surgeons participating in a collaborative research group. Home zip code was used to calculate Social Deprivation Indices (SDI; 0-100), which quantifies the level of disadvantage across several sociodemographic domains collected in the American Community Survey. Patients without zip code data were excluded from the analysis. The Cox Proportional Hazards model was used to study the association between SDI and the hazard of functional recurrence, adjusting for stricture characteristics as well as age and body mass index. RESULTS: Median age was 46.0 years with a median follow up of 367 days for the 1452 men included in the study. Patients in the fourth SDI quartile (worst social deprivation) were more likely to be active smokers with traumatic and infectious strictures compared to the first SDI quartile. Patients in the fourth SDI quartile had 1.64 times the unadjusted hazard of functional stricture recurrence vs patients in the first SDI quartile (95% CI 1.04-2.59). Compared to anastomotic ± excision, substitution only repair had 1.90 times the unadjusted hazard of recurrence. The adjusted hazard of recurrence was 1.08 per 10-point increase in SDI (95% CI 1.01-1.15, P = .027). CONCLUSIONS: Patient social deprivation identifies those at higher risk for functional recurrence after anterior urethral stricture repair, offering an opportunity for preoperative counseling and postoperative surveillance. Addressing these social determinants of health can potentially improve outcomes in reconstructive surgery.

Clinical Utility of Plasma Microbial Cell-Free DNA Sequencing Among Immunocompromised Patients With Pneumonia.

Background: Plasma microbial cell-free DNA (mcfDNA) sequencing can establish the etiology of multiple infectious syndromes by identifying microbial DNA in plasma. However, data are needed to define the clinical scenarios where this tool offers the highest clinical benefit. Methods: We conducted a prospective multicenter observational study that evaluated the impact of plasma mcfDNA sequencing compared with usual care testing among adults with hematologic malignancies. This is a secondary analysis of an expanded cohort that evaluated the clinical utility of plasma mcfDNA sequencing across prespecified and adjudicated outcomes. We examined the percentage of participants for whom plasma mcfDNA sequencing identified a probable cause of pneumonia or clinically relevant nonpneumonia infection. We then assessed potential changes in antimicrobial therapy based on plasma mcfDNA sequencing results and the potential for early mcfDNA testing to avoid bronchoscopy and its associated adverse events. Results: Of 223 participants, at least 1 microbial detection by plasma mcfDNA sequencing was adjudicated as a probable cause of pneumonia in 57 (25.6%) and a clinically relevant nonpneumonia infection in 88 (39.5%). A probable cause of pneumonia was exclusively identified by plasma mcfDNA sequencing in 23 (10.3%) participants. Antimicrobial therapy would have changed for 41 (18.4%) participants had plasma mcfDNA results been available in real time. Among the 57 participants with a probable cause of pneumonia identified by plasma mcfDNA sequencing, bronchoscopy identified no additional probable cause of pneumonia in 52 (91.2%). Conclusions: Plasma mcfDNA sequencing could improve management of both pneumonia and other concurrent infections in immunocompromised patients with suspected pneumonia.

Middle Meningeal Artery Embolization for "Trial-Ineligible" Chronic Subdural Hematomas.

BACKGROUND AND OBJECTIVES: The benefit of middle meningeal artery embolization (MMAE) in the treatment of chronic subdural hematoma (CSDH) has been recently demonstrated in a series of clinical trials. Whether MMAE benefits "trial-ineligible" patients remains elusive. We thus sought to explore the potential benefit of MMAE in neurologically stable (modified Rankin Scale ≤3) patients with "trial-ineligible" CSDHs because of large size: Thickness >15 mm and/or midline shift ≥5 mm. METHODS: A prospectively maintained database was reviewed to identify trial-ineligible CSDHs undergoing standalone MMAE. Surgical rescue rate, hematoma resolution, and neurological deterioration after hematoma progression were evaluated and compared with trial-eligible counterparts. Effect sizes were adjusted for demographic, clinical, and radiological features using multivariable regression. RESULTS: Of 150 standalone MMAE procedures, 92 (61%) were performed in "trial-ineligible" cases: 41% with CSDH thickness >15 mm, 21% with midline shift ≥5 mm, and 38% with both. The surgical rescue rate was 7.6% in the trial-ineligible cohort. Over a median follow-up of 62.5 days, 88.9% cases achieved satisfactory hematoma resolution (≥50% in thickness); 76% had satisfactory resolution at 90-day follow-up. Antithrombotic resumption was a risk factor for surgical rescue (adjusted odds ratio 9.64 [95% CI, 1.33-69.74]; P = .02). Surgical rescue and hematoma resolution did not significantly differ between trial-ineligible and trial-eligible cohorts (P = .87 for surgical rescue rate and P = .85 for hematoma resolution rate). CONCLUSION: This study emphasizes the considerable prevalence of potentially "trial-ineligible" patients with CSDHs because of large size that may still benefit from standalone MMAE.

Next-generation sequencing has diagnostic utility in challenging small/flat urothelial lesions.

Small/flat urothelial lesions are challenging and currently available ancillary immunohistochemistry testing often cannot reliably distinguish between reactive lesions and urothelial carcinoma (UCa). UCa has a characteristic molecular profile, but small/flat urothelial lesions are typically considered too small to perform next generation sequencing (NGS). Herein, we present our institution's experience with utilizing comprehensive DNA-based NGS to evaluate small/flat urothelial lesions (n = 13 cases). NGS was ordered on 7/13 small/flat urothelial lesions initially diagnosed as urothelial atypia, ordered by the pathologist to aid in further diagnosis; the remaining 6/13 cases were diagnosed as urothelial carcinoma in situ (uCIS), ordered by a treating oncologist. The test was considered as adding value if it yielded pathogenic or likely pathogenic alterations previously associated with urothelial carcinoma in the literature. Macroscopic dissection was determined necessary in all cases and obtained either by scraping (7), punch biopsy (5) or scooping (1) of paraffin tissue blocks. In 4/13 cases, tumor content was considered low (<25%); in 2/13 cases, DNA quantity yield was considered below optimal (<250 ng); all cases met required DNA quantity for testing (>50 ng). Mean target coverage ranged: 498 to 985 (optimal >500 reads). NGS testing identified mutations compatible with urothelial carcinoma in all 7 cases initially diagnosed as atypical; and in one case, the tumor recurred as a lung metastasis. All 6 uCIS had NGS testing results concordant with UCa. In conclusion, despite small sample quantity with low tumor content and DNA concentration yield, NGS testing with appropriate methodology can be considered in the setting of small/flat urothelial lesions to aid in diagnosis or per oncologist request and yield interpretable results.

COVID-19 Pandemic-Related Behavioral and Attitudinal Changes in Caregivers.

Purpose: To identify pandemic-related behavioral and attitudinal changes in caregivers. Methods: A 38-question cross-sectional survey was developed and distributed to English-speaking caregivers accompanying children for dental care in a hospital dental clinic. The questionnaire surveyed caregiver beliefs and behaviors regarding COVID19, whether the pandemic altered their use of medical and dental care or at-home health habits, as well as their attitudes toward medical and dental teams. Results: The 594 respondents varied in age, marital status, education and income level. Trust was high regarding medical and dental teams, government public health management and mask policies for children. However, those respondents who did not think children should be required to wear masks at school if the health department recommended it and respondents who did not think that government agencies would protect them if another pandemic happened were less likely to change perceptions on dental care, preventive dentistry, sugar intake and toothbrushing (P<0.05). No other strong and consistent relationships were found. Conclusions: In a safety-net dental clinic population, over half of caregivers changed dental behaviors and attitudes following the pandemic. Caregivers cynical of mask mandates and governmental pandemic management were not in the group to change their dental attitudes and behaviors. No other consistent pattern of demographic variables offered a clear profile of group beliefs and behaviors, suggesting the necessity of inquiring individuals and families about their oral health perceptions and behaviors.

Improved Outcomes Among Octogenarians with Ruptured Aneurysms: Endovascular Treatment as Right-of-First-Refusal in the Second Post-trial Decade.

BACKGROUND: Treatment outcomes of octogenarians with aneurysmal subarachnoid hemorrhage (aSAH) are often considered poor. With ongoing advancements and experience in endovascular technology, we sought to evaluate the outcomes of octogenarians treated for aSAH in the second post-International Subarachnoid Aneurysm Trial (ISAT)/Barrow Ruptured Aneurysm Trial (BRAT) decade. METHOD: A single-center database of aSAH was reviewed to identify patients aged 80 years or above undergoing aneurysm treatment. Mortality and favorable neurologic outcome (defined as modified Rankin Scale score <3) were assessed among the series and compared across several subgroups. RESULTS: Octogenarian patients constituted 6% of the aSAH cohort (38 of 619) over the reviewed period. Twenty-one percent were high grade (Hunt-Hess grade 4-5). Endovascular treatment was the first-line modality in 90% of patients. During a median follow-up of 17 months, the overall mortality was 39%. Higher mortality was associated with poor Hunt-Hess grade (100% for grade 5, 47% for III-IV, 13% for 1-2, P = 0.004) and non-independent baseline function status (100% mortality for non-independent vs. 28% for independent group, P = 0.002). At last follow-up, 53% of patients achieved a favorable neurologic outcome. The stratified rate was 80% in Hunt-Hess grade I-II and over 60% in patients with premorbid independent function status or less than 5 frailty components (P ≤ 0.02 vs. poorer counterparts). CONCLUSIONS: Neurologic outcomes of octogenarian patients with aSAH are improving in the second post-trial decade, particularly given the preponderance of endovascular treatment. Baseline functional status and comorbidities of octogenarians should be considered in addition to the Hunt-Hess grade in prognostication.

Pulmonary hypertension associated with left heart disease.

Left heart disease (LHD) is the most common cause of pulmonary hypertension (PH), which may be classified further as isolated post-capillary (ipcPH) or combined post- and pre-capillary PH (cpcPH). The 7th World Symposium on Pulmonary Hypertension PH-LHD task force reviewed newly reported randomised clinical trials and contemplated novel opportunities for improving outcome. Results from major randomised clinical trials reinforced prior recommendations against the use of pulmonary arterial hypertension therapy in PH-LHD outside of clinical trials, and suggested possible harm. Greater focus on phenotyping was viewed as one general strategy by which to ultimately improve clinical outcomes. This is potentially achievable by individualising ipcPH versus cpcPH diagnosis for patients with pulmonary arterial wedge pressure within a diagnostic grey zone (12-18 mmHg), and through a newly developed PH-LHD staging system. In this model, PH accompanies LHD across four stages (A=at risk, B=structural heart disease, C=symptomatic heart disease, D=advanced), with each stage characterised by progression in clinical characteristics, haemodynamics and potential therapeutic strategies. Along these lines, the task force proposed disaggregating PH-LHD to emphasise specific subtypes for which PH prevalence, pathophysiology and treatment are unique. This includes re-interpreting mitral and aortic valve stenosis through a contemporary lens, and focusing on PH within the hypertrophic cardiomyopathy and amyloid cardiomyopathy clinical spectra. Furthermore, appreciating LHD in the profile of PH patients with chronic lung disease and chronic thromboembolic pulmonary disease is essential. However, engaging LHD patients in clinical research more broadly is likely to require novel methodologies such as pragmatic trials and may benefit from next-generation analytics to interpret results.

The Physiological Consequences of and Recovery following the Australian Special Forces Selection Course.

This study aimed to determine the energy requirements, physiological consequences, and recovery rate from the Australian Special Forces Selection Course. Ninety-three male soldiers (mean ± SD, 28.1 ± 3.6 y, 1.81 ± 0.1 m, 85.1 ± 8.1 kg) volunteered for this study. Body composition via dual-energy x-ray absorptiometry, hormones and resting metabolic rate were assessed before, immediately after, and at one, three, five, and eight weeks post-course. Energy expenditure, assessed via doubly-labelled water during the first 10 days of the course significantly exceeded energy intake (expenditure: 7680 ± 1095 kcal.d-1, intake: 3859 ± 704 kcal.d-1). Body mass (△ -6.8 ± 1.9 kg, p<0.01), fat mass (△ -4.2 ± 1.0 kg, p<0.0001) and lean mass (△ -3.0 ± 1.7 kg, p<0.0001) were significantly reduced in response to the course and returned to baseline 1-3 weeks post-course. Total testosterone, free testosterone, free triiodothyronine, free thyroxine and insulin like growth factor-1 significantly (p<0.001) declined following the course, while cortisol and sex hormone binding globulin increased (p<0.001). All hormones, except insulin like growth factor-1, returned to baseline concentrations within 1-3 weeks post-course. Resting metabolic rate decreased (p<0.01) in response to the course, and subsequently rebounded above baseline levels at one week post-course. The Special Forces Selection Course involved high energy output and a substantial caloric deficit, resulting in body mass loss and significant hormonal disruption that took weeks to recover. These results highlight the energy requirements, physiological consequences, and recovery processes from the Australian Special Forces Selection Course.

Sustained efficacy of angioplasty for cerebral vasospasm after aneurysmal subarachnoid hemorrhage: Risk features and device comparison.

BACKGROUND: Cerebral vasospasm is a leading source of delayed morbidity and mortality after aneurysmal subarachnoid hemorrhage (aSAH). Angioplasty may improve vasospasm, while optimal target and device selection remains controversial. This study aimed to identify features and devices associated with sustained efficacy. METHODS: We identified consecutive patients who underwent angioplasty for aSAH vasospasm. The primary outcome was a composite of adequate angioplasty (residual narrowing < 50 %) without complications. Secondary outcomes included rates of refractory/recurrent vasospasm and sustained improvement at follow-up. Associated features were identified through multivariable analysis. Outcomes were compared between balloon and Comaneci/stentriever in a propensity-score-matched cohort. RESULTS: A total of 149 vasospastic segments underwent angioplasty: 61.7 % in the proximal anterior circulation (ICA, M1, A1), 20.1 % in distal segments (A2 and M2) and 18.1 % in the posterior circulation. Adequate angioplasty was achieved without complication in 83.2 % of vessels, with a sustainable effect in 84.3 % at follow-up. Refractory/recurrent vasospasm was observed in 17.4 %, yielding a 10.1 % retreatment rate. Notably, only 35.3 % of vessels undergoing inadequate angioplasty demonstrated improvement at follow-up. Angioplasty targeting distal MCA (adjusted OR, 0.10) or BA-V4 (aOR, 0.10), and inadequate angioplasty (aOR, 0.03) were unfavorable predictors for sustained improvement. Efficacy outcomes were similar between balloon and Comaneci/stentriever in a matched subgroup analysis. CONCLUSION: Angioplasty, when achieving residual narrowing < 50 %, demonstrated sustained improvement for vasospasm. Novel devices may exhibit comparable efficacy to balloon angioplasty for selected segments.

Safety and efficacy of same-day discharge for premature ventricular complex ablations.

AIMS: Patients undergoing catheter ablation (CA) of ventricular arrhythmias (VAs) are generally observed overnight in the hospital given the concern for complications. To evaluate the efficacy and safety of same-day discharge (SDD) of patients undergoing elective CA of premature ventricular complexes (PVCs). METHODS AND RESULTS: A retrospective evaluation of all patients undergoing elective VA ablation at Ascension St Vincent Hospital from 1 January 2018 to 31 December 2019 was undertaken. Of those, the patients undergoing PVC ablation were divided into SDD and non-SDD. Patients underwent SDD at the discretion of the operator. The primary safety outcome was the 30-day incidence of complications and death. The primary efficacy outcome was procedural success. Among 188 patients who underwent VA ablation, 98 (52.1%) were PVC ablations, and of those, 55 (56.1%) were SDD. There was no difference in age, gender, comorbidities, or ejection fraction between the two groups. Patients that were non-SDD were more likely to be on chronic anticoagulation (P = 0.03), have ablation in the LV (P = 0.04), have retrograde access (P = 0.03), and receive heparin during the procedure (P = 0.01). There were no complications in the SDD group compared with one (2.3%) in the non-SDD group. There was no difference in primary efficacy between the two groups with a 90.9% acute success in the SDD and 88.4% in the non-SDD (P = 0.68). CONCLUSION: Same-day discharge for CA of PVCs is feasible and could lower healthcare resource utilization without compromising outcomes in this unique population.

Structural basis for allosteric regulation of human phosphofructokinase-1.

Phosphofructokinase-1 (PFK1) catalyzes the rate-limiting step of glycolysis, committing glucose to conversion into cellular energy. PFK1 is highly regulated to respond to the changing energy needs of the cell. In bacteria, the structural basis of PFK1 regulation is a textbook example of allostery; molecular signals of low and high cellular energy promote transition between an active R-state and inactive T-state conformation, respectively. Little is known, however, about the structural basis for regulation of eukaryotic PFK1. Here, we determine structures of the human liver isoform of PFK1 (PFKL) in the R- and T-state by cryoEM, providing insight into eukaryotic PFK1 allosteric regulatory mechanisms. The T-state structure reveals conformational differences between the bacterial and eukaryotic enzyme, the mechanisms of allosteric inhibition by ATP binding at multiple sites, and an autoinhibitory role of the C-terminus in stabilizing the T-state. We also determine structures of PFKL filaments that define the mechanism of higher-order assembly and demonstrate that these structures are necessary for higher-order assembly of PFKL in cells.

Epidemiology of Travel-Associated Dengue from 2007 to 2022: A GeoSentinel Analysis.

BACKGROUND: Dengue is a leading cause of febrile illness among international travellers. We aimed to describe the epidemiology and clinical characteristics of imported dengue in returning travellers evaluated at GeoSentinel sites from 2007-2022. METHODS: We retrieved GeoSentinel records of dengue among travellers residing in non-endemic countries. We considered dengue confirmed when diagnosed by a positive DENV-specific RT-PCR, positive NS-1 antigen, and/or anti-DENV IgG seroconversion, and probable when diagnosed by single anti-DENV IgM or high titre anti-DENV IgG detection. Severe dengue was defined as evidence of clinically significant plasma leakage or bleeding, organ failure, or shock, according to the 2009 WHO guidance. Complicated dengue was defined as either severe dengue or dengue with presence of any warning sign. Analyses were descriptive. RESULTS: This analysis included 5958 travellers with confirmed (n = 4859; 81.6%) or probable (n = 1099; 18.4%) dengue. The median age was 33 years (range: < 1-91); 3007 (50.5%) travellers were female. The median travel duration was 21 days (interquartile range [IQR]: 15-32). The median time between illness onset and GeoSentinel site visit was 7 days (IQR: 4-15). The most frequent reasons for travel were tourism (67.3%), visiting friends or relatives (12.2%), and business (11.0%). The most frequent regions of acquisition were Southeast Asia (50.4%), South-Central Asia (14.9%), the Caribbean (10.9%), and South America (9.2%). Ninety-five (1.6%) travellers had complicated dengue, of whom 27 (0.5%) had severe dengue, and one died. Of 2710 travellers with data available, 724 (26.7%) were hospitalized. The largest number of cases (n = 835) was reported in 2019. CONCLUSIONS: A broad range of international travellers should be aware of the risk of acquiring dengue and receive appropriate pretravel counselling regarding preventive measures. Prospective cohort studies are needed to further elucidate dengue risk by destination and over time, as well as severe outcomes and prolonged morbidity (long-dengue) due to travel-related dengue.

Femoral versus radial access for middle meningeal artery embolization for chronic subdural hematomas: multicenter propensity score matched study.

BACKGROUND: With transradial access (TRA) being more progressively used in neuroendovascular procedures, we compared TRA with transfemoral access (TFA) in middle meningeal artery embolization (MMAE) for chronic subdural hematoma (cSDH). METHODS: Consecutive patients undergoing MMAE for cSDH at 14 North American centers (2018-23) were included. TRA and TFA groups were compared using propensity score matching (PSM) controlling for: age, sex, concurrent surgery, previous surgery, hematoma thickness and side, midline shift, and pretreatment antithrombotics. The primary outcome was access site and overall complications, and procedure duration; secondary endpoints were surgical rescue, radiographic improvement, and technical success and length of stay. RESULTS: 872 patients (median age 73 years, 72.9% men) underwent 1070 MMAE procedures (54% TFA vs 46% TRA). Access site hematoma occurred in three TFA cases (0.5%; none required operative intervention) versus 0% in TRA (P=0.23), and radial-to-femoral conversion occurred in 1% of TRA cases. TRA was more used in right sided cSDH (58.4% vs 44.8%; P<0.001). Particle embolics were significantly higher in TFA while Onyx was higher in TRA (P<0.001). Following PSM, 150 matched pairs were generated. Particles were more utilized in the TFA group (53% vs 29.7%) and Onyx was more utilized in the TRA group (56.1% vs 31.5%) (P=0.001). Procedural duration was longer in the TRA group (median 68.5 min (IQR 43.1-95) vs 59 (42-84); P=0.038), and radiographic success was higher in the TFA group (87.3% vs 77.4%; P=0.036). No differences were noted in surgical rescue (8.4% vs 10.1%, P=0.35) or technical failures (2.4% vs 2%; P=0.67) between TFA and TRA. Sensitivity analysis in the standalone MMAE retained all associations but differences in procedural duration. CONCLUSIONS: In this study, TRA offered comparable outcomes to TFA in MMAE for cSDH in terms of access related and overall complications, technical feasibility, and functional outcomes. Procedural duration was slightly longer in the TRA group, and radiographic success was higher in the TFA group, with no differences in surgical rescue rates.

Circulating Biomarkers of Endothelial Dysfunction Associated With Ventilatory Ratio and Mortality in ARDS Resulting From SARS-CoV-2 Infection Treated With Antiinflammatory Therapies.

BACKGROUND: The association of plasma biomarkers and clinical outcomes in ARDS resulting from SARS-CoV-2 infection predate the evidence-based use of immunomodulators. RESEARCH QUESTION: Which plasma biomarkers are associated with clinical outcomes in patients with ARDS resulting from SARS-CoV-2 infection treated routinely with immunomodulators? STUDY DESIGN AND METHODS: We collected plasma from patients with ARDS resulting from SARS-CoV-2 infection within 24 h of admission to the ICU between December 2020 and March 2021 (N = 69). We associated 16 total biomarkers of inflammation (eg, IL-6), coagulation (eg, D-dimer), epithelial injury (eg, surfactant protein D), and endothelial injury (eg, angiopoietin-2) with the primary outcome of in-hospital mortality and secondary outcome of ventilatory ratio (at baseline and day 3). RESULTS: Thirty patients (43.5%) died within 60 days. All patients received corticosteroids and 6% also received tocilizumab. Compared with survivors, nonsurvivors demonstrated a higher baseline modified Sequential Organ Failure Assessment score (median, 8.5 [interquartile range (IQR), 7-9] vs 7 [IQR, 5-8]); P = .004), lower Pao2 to Fio2 ratio (median, 153 [IQR, 118-182] vs 184 [IQR, 142-247]; P = .04), and higher ventilatory ratio (median, 2.0 [IQR, 1.9-2.3] vs 1.5 [IQR, 1.4-1.9]; P < .001). No difference was found in inflammatory, coagulation, or epithelial biomarkers between groups. Nonsurvivors showed higher median neural precursor cell expressed, developmentally down-regulated 9 (NEDD9) levels (median, 8.4 ng/mL [IQR, 7.0-11.2 ng/mL] vs 6.9 ng/mL [IQR, 5.5-8.0 ng/mL]; P = .0025), von Willebrand factor domain A2 levels (8.7 ng/mL [IQR, 7.9-9.7 ng/mL] vs 6.5 ng/mL [IQR, 5.7-8.7 ng/mL]; P = .007), angiopoietin-2 levels (9.0 ng/mL [IQR, 7.9-14.1 ng/mL] vs 7.0 ng/mL [IQR, 5.6-10.6 ng/mL]; P = .01), and syndecan-1 levels (15.9 ng/mL [IQR, 14.5-17.5 ng/mL] vs 12.6 ng/mL [IQR, 10.5-16.1 ng/mL]; P = .01). Only NEDD9 level met the adjusted threshold for significance (P < .003). Plasma NEDD9 level was associated with 60-day mortality (adjusted OR, 9.7; 95% CI, 1.6-60.4; P = .015). Syndecan-1 level correlated with both baseline (ρ = 0.4; P = .001) and day 3 ventilatory ratio (ρ = 0.5; P < .001). INTERPRETATION: Biomarkers of inflammation, coagulation, and epithelial injury were not associated with clinical outcomes in a small cohort of patients with ARDS uniformly treated with immunomodulators. However, endothelial biomarkers, including plasma NEDD9, were associated with 60-day mortality.