Preoperative CT-guided ICG injection locating SPNs

Background: Localization of small pulmonary nodules (SPNs) is challenging in minimally invasive pulmonary resection, and it is unknown whether computer tomography (CT) guided by indocyanine green (ICG) can provide accurate localization with minimal complications. Methods: We performed a retrospective study of patients who underwent thoracoscopic resection of pulmonary nodules after CT-guided preoperative localization with ICG from May 2019 to May 2020. Demographics, procedural data, postoperative complications, and pathologic information, were collected, and an analysis of the accuracy and complications after surgery was conducted. Results: In 471 patients, there was a total of 512 peripheral pulmonary nodules that were ≤2 cm in size. The average time for CT-guided percutaneous ICG injection for localization was 18 minutes, and 98.4% (504/512) of the nodules were successfully localized. The average size of the nodules was 9.1 mm, and the average depth from the pleural surface was 8.9 mm. Overall, 5.9% (28/471) of the patients had asymptomatic pneumothorax after localization, but none needed a tube thoracostomy. All the nodules were resected using video-assisted thoracoscopy technique. Conclusions: Preoperative CT-guided transthoracic ICG injection is safe and feasible for localization of small lung nodules for minimally invasive pulmonary resection. This technique should be considered for preoperative CT-guided localization of small lung nodules

Localizing FRBs through VLBI with the Algonquin Radio Observatory 10 m Telescope

The Canadian Hydrogen Intensity Mapping Experiment (CHIME)/FRB experiment has detected thousands of fast radio bursts (FRBs) due to its sensitivity and wide field of view; however, its low angular resolution prevents it from localizing events to their host galaxies. Very long baseline interferometry (VLBI), triggered by FRB detections from CHIME/FRB will solve the challenge of localization for non-repeating events. Using a refurbished 10 m radio dish at the Algonquin Radio Observatory located in Ontario Canada, we developed a testbed for a VLBI experiment with a theoretical λ/D ≲ 30 mas. We provide an overview of the 10 m system and describe its refurbishment, the data acquisition, and a procedure for fringe fitting that simultaneously estimates the geometric delay used for localization and the dispersive delay from the ionosphere. Using single pulses from the Crab pulsar, we validate the system and localization procedure, and analyze the clock stability between sites, which is critical for coherently delay referencing an FRB event. We find a localization of ∼200 mas is possible with the performance of the current system (single-baseline). Furthermore, for sources with insufficient signal or restricted wideband to simultaneously measure both geometric and ionospheric delays, we show that the differential ionospheric contribution between the two sites must be measured to a precision of 1 × 10-8 pc cm-3 to provide a reasonable localization from a detection in the 400-800 MHz band. Finally we show detection of an FRB observed simultaneously in the CHIME and the Algonquin 10 m telescope, the first non-repeating FRB in this long baseline. This project serves as a testbed for the forthcoming CHIME/FRB Outriggers project

Treatment decision for recurrences in non-small cell lung cancer during or after adjuvant osimertinib: an international Delphi consensus report

IntroductionOsimertinib is recommended by major guidelines for use in the adjuvant setting in patients with EGFR mutation-positive NSCLC following the significant improvement in disease-free survival observed in the Phase III ADAURA trials. Due to limited real-world data in the adjuvant setting, little guidance exists on how to approach potential recurrences either during or after the completion of the treatment. This study aimed to reach a broad consensus on key treatment decision criteria in the events of recurrence.MethodsTo reach a broad consensus, a modified Delphi panel study was conducted consisting of two rounds of surveys, followed by two consensus meetings and a final offline review of key statements. An international panel of experts in the field of NSCLC (n=12) was used to provide clinical insights regarding patient management at various stages of NSCLC disease including patient monitoring, diagnostics, and treatment approach for specific recurrence scenarios. This study tested recurrences occurring 1) within or outside the central nervous system (CNS), 2) during or after the adjuvant-osimertinib regimen in NSCLC disease which is 3) amenable or not amenable to local consolidative therapy.ResultsPanellists agreed on various aspects of patient monitoring and diagnostics including the use of standard techniques (e.g., CT, MRI) and tumour biomarker assessment using tissue and liquid biopsies. Consensus was reached on 6 statements describing treatment considerations for the specific NSCLC recurrence scenarios. Panellists agreed on the value of osimertinib as a monotherapy or as part of the overall treatment strategy within the probed recurrence scenarios and acknowledged that more clinical evidence is required before precise recommendations for specific patient populations can be made.DiscussionThis study provides a qualitative expert opinion framework for clinicians to consider within their treatment decision-making when faced with recurrence during or after adjuvant-osimertinib treatment

Titin-truncating variants affect heart function in disease cohorts and the general population

Titin-truncating variants (TTNtv) commonly cause dilated cardiomyopathy (DCM). TTNtv are also encountered in ~1% of the general population, where they may be silent, perhaps reflecting allelic factors. To better understand TTNtv, we integrated TTN allelic series, cardiac imaging and genomic data in humans and studied rat models with disparate TTNtv. In patients with DCM, TTNtv throughout titin were significantly associated with DCM. Ribosomal profiling in rat showed the translational footprint of premature stop codons in Ttn, TTNtv-position-independent nonsense-mediated degradation of the mutant allele and a signature of perturbed cardiac metabolism. Heart physiology in rats with TTNtv was unremarkable at baseline but became impaired during cardiac stress. In healthy humans, machine-learning-based analysis of high-resolution cardiac imaging showed TTNtv to be associated with eccentric cardiac remodeling. These data show that TTNtv have molecular and physiological effects on the heart across species, with a continuum of expressivity in health and disease

Neighborhood socioeconomic status, Medicaid coverage and medical management of myocardial infarction: Atherosclerosis risk in communities (ARIC) community surveillance

<p>Abstract</p> <p>Background</p> <p>Pharmacologic treatments are efficacious in reducing post-myocardial infarction (MI) morbidity and mortality. The potential influence of socioeconomic factors on the receipt of pharmacologic therapy has not been systematically examined, even though healthcare utilization likely influences morbidity and mortality post-MI. This study aims to investigate the association between socioeconomic factors and receipt of evidence-based treatments post-MI in a community surveillance setting.</p> <p>Methods</p> <p>We evaluated the association of census tract-level neighborhood household income (nINC) and Medicaid coverage with pharmacologic treatments (aspirin, beta [β]-blockers and angiotensin converting enzyme [ACE] inhibitors; optimal therapy, defined as receipt of two or more treatments) received during hospitalization or at discharge among 9,608 MI events in the ARIC community surveillance study (1993-2002). Prevalence ratios (PR, 95% CI), adjusted for the clustering of hospitalized MI events within census tracts and within patients, were estimated using Poisson regression.</p> <p>Results</p> <p>Seventy-eight percent of patients received optimal therapy. Low nINC was associated with a lower likelihood of receiving β-blockers (0.93, 0.87-0.98) and a higher likelihood of receiving ACE inhibitors (1.13, 1.04-1.22), compared to high nINC. Patients with Medicaid coverage were less likely to receive aspirin (0.92, 0.87-0.98), compared to patients without Medicaid coverage. These findings were independent of other key covariates.</p> <p>Conclusions</p> <p>nINC and Medicaid coverage may be two of several socioeconomic factors influencing the complexities of medical care practice patterns.</p

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London