Stress interventions for immigrant parents in the United States: a scoping review protocol.

OBJECTIVE: This review will map stress interventions designed for and implemented among immigrant parents in the United States (US) according to (1) intervention characteristics, (2) participant characteristics, and (3) reported outcomes and measurement tools. INTRODUCTION: In addition to parenting stressors shared with their non-immigrant counterparts, immigrant parents also face immigration stressors. Although stress interventions can effectively manage, reduce, or prevent stress among non-immigrant populations, we know little about stress interventions designed for immigrant parents in the US. This study will be the first to explore stress interventions implemented among immigrant parents in the US. INCLUSION CRITERIA: This scoping review will include published, peer-reviewed quantitative, qualitative, and mixed methods studies that evaluate stress interventions designed specifically for US immigrant parents with at least 1 child under the age of 18 years. Reported interventions must include stress as a primary or secondary outcome or be labeled as a stress intervention. Stress interventions are broadly defined, with no restrictions on the type of stress targeted (eg, job, general, parenting) or the intervention's nature (ie, prevention vs. management/reduction vs. treatment). METHODS: A literature search will be conducted in ProQuest's APA PsycINFO and PsycARTICLES, CINAHL Plus (EBSCOhost), ERIC (ProQuest), Embase, MEDLINE (Ovid), International Bibliography of Social Sciences (ProQuest), and the Cochrane Library. Only English-language publications will be eligible, with no date restrictions. Retrieved titles and abstracts will be screened by at least 2 independent reviewers in duplicate. Data will be extracted using a self-developed data extraction tool. Findings will be presented in tabular or diagrammatic format, accompanied by a narrative summary. DETAILS OF THE REVIEW CAN BE FOUND IN OPEN SCIENCE FRAMEWORK: osf.io/ec39j.

Angiogenic Gene Therapy for Refractory Angina: Results of the EXACT Phase 2 Trial.

BACKGROUND: XC001 is a novel adenoviral-5 vector designed to express multiple isoforms of VEGF (vascular endothelial growth factor) and more safely and potently induce angiogenesis. The EXACT trial (Epicardial Delivery of XC001 Gene Therapy for Refractory Angina Coronary Treatment) assessed the safety and preliminary efficacy of XC001 in patients with no option refractory angina. METHODS: In this single-arm, multicenter, open-label trial, 32 patients with no option refractory angina received a single treatment of XC001 (1×1011 viral particles) via transepicardial delivery. RESULTS: There were no severe adverse events attributed to the study drug. Twenty expected severe adverse events in 13 patients were related to the surgical procedure. Total exercise duration increased from a mean±SD of 359.9±105.55 seconds at baseline to 448.2±168.45 (3 months), 449.2±175.9 (6 months), and 477.6±174.7 (12 months; +88.3 [95% CI, 37.1-139.5], +84.5 [95% CI, 34.1-134.9], and +115.5 [95% CI, 59.1-171.9]). Total myocardial perfusion deficit on positron emission tomography imaging decreased by 10.2% (95% CI, -3.1% to 23.5%), 14.3% (95% CI, 2.8%-25.7%), and 10.2% (95% CI, -0.8% to -21.2%). Angina frequency decreased from a mean±SD 12.2±12.5 episodes to 5.2±7.2 (3 months), 5.1±7.8 (6 months), and 2.7±4.8 (12 months), with an average decrease of 7.7 (95% CI, 4.1-11.3), 6.6 (95% CI, 3.5-9.7), and 8.8 (4.6-13.0) episodes at 3, 6, and 12 months. Angina class improved in 81% of participants at 6 months. CONCLUSIONS: XC001 administered via transepicardial delivery is safe and generally well tolerated. Exploratory improvements in total exercise duration, ischemic burden, and subjective measures support a biologic effect sustained to 12 months, warranting further investigation. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04125732.

Development of Community-Level Capacity of Resilience to Natural Hazards for Environmental- and Social-Justice-Challenged Communities: 1. Approach, Concepts, and Assessment of Existing Information.

Impoverished and under-served communities are often exposed to the worst environmental and climate hazards. Identifying these communities and building their resilience capacity to withstand such hazards is a vital justice aspect of environmental management. Building community resilience requires five activities: (1) examination of existing information, (2) community engagement and assessment of local knowledge, (3) development of reasonable strategies to build resilience, (4) implementation and these strategies, and (5) monitoring and transability of the process. This manuscript examines the first component of this process. The attributes of multiple parishes in Louisiana are examined using available data and existing models of human well-being, community resilience, and environmental/climate/socioeconomic justice. These existing models and tools were used to determine parish-level resilience to natural hazards including flooding, hurricanes, and other potential natural climatic hazards in central Louisiana (U.S.). Through consultation with state officials and local community groups, candidate environmental justice (EJ) and social justice (SJ) communities were selected to develop resilience capacity enhancement plans to address potential adverse parish and community outcomes of natural hazard events. Of the available parishes, St. Helena Parish was selected as an entity that would significantly benefit from resilience capacity building. The remaining two activities, community engagement and strategy development, will be examined in sister manuscripts. Continuing studies, to be described elsewhere, will describe community engagement and the determination of strategies, implementation plans, and the monitoring of the success of these strategic implementations.

Quality improvement initiative to increase radial artery usage as a second arterial conduit in coronary artery bypass grafting.

OBJECTIVES: Use of radial artery as a second arterial graft, compared to a saphenous vein, in coronary artery bypass grafting (CABG) can improve late outcomes. However, the radial artery remains underutilized. We initiated a quality improvement (QI) initiative to increase the usage of radial artery grafts. METHODS: During our 4-month lead period, we disseminated evidence for radial artery graft usage to surgeons, developed a radial artery decision-making algorithm and adopted endoscopic harvesting. Our QI initiative was conducted over a 6-month period and included a postoperative survey of decision-making for graft selection and obstacles to radial artery usage. RESULTS: Over the 6-month study period, 247 patients received isolated CABG which included 98 (40%) with radial arteries as a second arterial graft and 144 (58%) with greater saphenous veins. Radial artery usage increased with QI initiative implementation by 67% compared to 6 months prior to the study period (60 radial arteries/252 isolated CABG, 24%) (P = 0.006). The survey response rate was 93% (231/247). Barriers to radial artery graft usage were poor quality target vessel or stenosis <80% (24%), patient age >75 years (20%), ejection fraction ≤35% (8%) and renal insufficiency/dialysis (7%). No patients experienced significant complications from radial artery harvest. CONCLUSIONS: Our institutional QI initiative was successful in (i) increasing the usage of radial artery as a second arterial graft and (ii) understanding barriers to radial artery graft usage. Implementation of a QI program can improve radial artery usage in CABG with low risk of patient morbidity from radial artery harvest.

Surgical recovery from the COVID-19 pandemic in English adult neurosurgical centres.

OBJECTIVES: The COVID-19 pandemic required a change in resource priority from Neurosurgical care in order to treat medically unwell patients suffering from the complications of COVID-19 infections. We demonstrate the impact of COVID-19 on total bed days in 24 Neurosurgical centres in England offering adult Neurosurgery as well as the total spells (single inpatient episodes) for operative Neurosurgical patients between 2020 and 2022 when compared with 2019. METHODS: We used Capse Healthcare Knowledge System software iCompare in order to show the change in total spells for patients undergoing a primary or secondary Neurosurgical procedure as defined using the National Neurosurgical Audit Programme (NNAP) OPCS-4 coding framework between 2019 and 2022. RESULTS: The overall mortality rate of COVID-19 patients was 12.3% and the percentage of total bed days taken up by COVID-19 patients in hospitals at large was on average 7.7%. The total number of spells for all procedures over the 24 centres in 2022 was 39,019 compared with 45,742 in 2019. There was a cumulative deficit of 24,904 spells. The loss of spells was not equally distributed across regions and hospital Trusts. The average number of referral to treatment pathways completed within 18 weeks has declined from 76% to 57% over the study period and the referral to treatment clearance time has risen from 17 to 24 weeks. CONCLUSIONS: The mean elective cranial output in 2022 compared with 2019 is at 88% with spinal output lagging at 69%. If the rate of change year on year were to remain at current levels then we would reach pre-pandemic levels of output by 2026.

Usability of an Automated System for Real-Time Monitoring of Shared Decision-Making for Surgery: Mixed Methods Evaluation.

BACKGROUND: Improving shared decision-making (SDM) for patients has become a health policy priority in many countries. Achieving high-quality SDM is particularly important for approximately 313 million surgical treatment decisions patients make globally every year. Large-scale monitoring of surgical patients' experience of SDM in real time is needed to identify the failings of SDM before surgery is performed. We developed a novel approach to automating real-time data collection using an electronic measurement system to address this. Examining usability will facilitate its optimization and wider implementation to inform interventions aimed at improving SDM. OBJECTIVE: This study examined the usability of an electronic real-time measurement system to monitor surgical patients' experience of SDM. We aimed to evaluate the metrics and indicators relevant to system effectiveness, system efficiency, and user satisfaction. METHODS: We performed a mixed methods usability evaluation using multiple participant cohorts. The measurement system was implemented in a large UK hospital to measure patients' experience of SDM electronically before surgery using 2 validated measures (CollaboRATE and SDM-Q-9). Quantitative data (collected between April 1 and December 31, 2021) provided measurement system metrics to assess system effectiveness and efficiency. We included adult patients booked for urgent and elective surgery across 7 specialties and excluded patients without the capacity to consent for medical procedures, those without access to an internet-enabled device, and those undergoing emergency or endoscopic procedures. Additional groups of service users (group 1: public members who had not engaged with the system; group 2: a subset of patients who completed the measurement system) completed user-testing sessions and semistructured interviews to assess system effectiveness and user satisfaction. We conducted quantitative data analysis using descriptive statistics and calculated the task completion rate and survey response rate (system effectiveness) as well as the task completion time, task efficiency, and relative efficiency (system efficiency). Qualitative thematic analysis identified indicators of and barriers to good usability (user satisfaction). RESULTS: A total of 2254 completed surveys were returned to the measurement system. A total of 25 service users (group 1: n=9; group 2: n=16) participated in user-testing sessions and interviews. The task completion rate was high (169/171, 98.8%) and the survey response rate was good (2254/5794, 38.9%). The median task completion time was 3 (IQR 2-13) minutes, suggesting good system efficiency and effectiveness. The qualitative findings emphasized good user satisfaction. The identified themes suggested that the measurement system is acceptable, easy to use, and easy to access. Service users identified potential barriers and solutions to acceptability and ease of access. CONCLUSIONS: A mixed methods evaluation of an electronic measurement system for automated, real-time monitoring of patients' experience of SDM showed that usability among patients was high. Future pilot work will optimize the system for wider implementation to ultimately inform intervention development to improve SDM. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.1136/bmjopen-2023-079155.

18F-FDG PET/CT and radiolabeled leukocyte SPECT/CT imaging for the evaluation of cardiovascular infection in the multimodality context: ASNC Imaging Indications (ASNC I2) Series Expert Consensus Recommendations from ASNC, AATS, ACC, AHA, ASE, EANM, HRS, IDSA, SCCT, SNMMI, and STS.

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I2) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multi-societal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multi-focal or diffuse heterogenous intense 18F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more.

18F-FDG PET/CT and radiolabeled leukocyte SPECT/CT imaging for the evaluation of cardiovascular infection in the multimodality context: ASNC Imaging Indications (ASNC I2) Series Expert Consensus Recommendations from ASNC, AATS, ACC, AHA, ASE, EANM, HRS, IDSA, SCCT, SNMMI, and STS.

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I2) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multi-societal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multi-focal or diffuse heterogenous intense 18F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more.

18F-FDG PET/CT and Radiolabeled Leukocyte SPECT/CT Imaging for the Evaluation of Cardiovascular Infection in the Multimodality Context: ASNC Imaging Indications (ASNC I2) Series Expert Consensus Recommendations From ASNC, AATS, ACC, AHA, ASE, EANM, HRS, IDSA, SCCT, SNMMI, and STS.

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I2) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multi-societal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multi-focal or diffuse heterogenous intense 18F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more.

18F-FDG PET/CT and radiolabeled leukocyte SPECT/CT imaging for the evaluation of cardiovascular infection in the multimodality context: ASNC Imaging Indications (ASNC I2) Series Expert Consensus Recommendations from ASNC, AATS, ACC, AHA, ASE, EANM, HRS, IDSA, SCCT, SNMMI, and STS.

This document on cardiovascular infection, including infective endocarditis, is the first in the American Society of Nuclear Cardiology Imaging Indications (ASNC I2) series to assess the role of radionuclide imaging in the multimodality context for the evaluation of complex systemic diseases with multi-societal involvement including pertinent disciplines. A rigorous modified Delphi approach was used to determine consensus clinical indications, diagnostic criteria, and an algorithmic approach to diagnosis of cardiovascular infection including infective endocarditis. Cardiovascular infection incidence is increasing and is associated with high morbidity and mortality. Current strategies based on clinical criteria and an initial echocardiographic imaging approach are effective but often insufficient in complicated cardiovascular infection. Radionuclide imaging with 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and single photon emission computed tomography/CT leukocyte scintigraphy can enhance the evaluation of suspected cardiovascular infection by increasing diagnostic accuracy, identifying extracardiac involvement, and assessing cardiac implanted device pockets, leads, and all portions of ventricular assist devices. This advanced imaging can aid in key medical and surgical considerations. Consensus diagnostic features include focal/multi-focal or diffuse heterogenous intense 18F-FDG uptake on valvular and prosthetic material, perivalvular areas, device pockets and leads, and ventricular assist device hardware persisting on non-attenuation corrected images. There are numerous clinical indications with a larger role in prosthetic valves, and cardiac devices particularly with possible infective endocarditis or in the setting of prior equivocal or non-diagnostic imaging. Illustrative cases incorporating these consensus recommendations provide additional clarification. Future research is necessary to refine application of these advanced imaging tools for surgical planning, to identify treatment response, and more.

Real-time monitoring and feedback to improve shared decision-making for surgery (the ALPACA Study): protocol for a mixed-methods study to inform co-development of an inclusive intervention.

INTRODUCTION: High-quality shared decision-making (SDM) is a priority of health services, but only achieved in a minority of surgical consultations. Improving SDM for surgical patients may lead to more effective care and moderate the impact of treatment consequences. There is a need to establish effective ways to achieve sustained and large-scale improvements in SDM for all patients whatever their background. The ALPACA Study aims to develop, pilot and evaluate a decision support intervention that uses real-time feedback of patients' experience of SDM to change patients' and healthcare professionals' decision-making processes before adult elective surgery and to improve patient and health service outcomes. METHODS AND ANALYSIS: This protocol outlines a mixed-methods study, involving diverse stakeholders (adult patients, healthcare professionals, members of the community) and three National Health Service (NHS) trusts in England. Detailed methods for the assessment of the feasibility, usability and stakeholder views of implementing a novel system to monitor the SDM process for surgery automatically and in real time are described. The study will measure the SDM process using validated instruments (CollaboRATE, SDM-Q-9, SHARED-Q10) and will conduct semi-structured interviews and focus groups to examine (1) the feasibility of automated data collection, (2) the usability of the novel system and (3) the views of diverse stakeholders to inform the use of the system to improve SDM. Future phases of this work will complete the development and evaluation of the intervention. ETHICS AND DISSEMINATION: Ethical approval was granted by the NHS Health Research Authority North West-Liverpool Central Research Ethics Committee (reference: 21/PR/0345). Approval was also granted by North Bristol NHS Trust to undertake quality improvement work (reference: Q80008) overseen by the Consent and SDM Programme Board and reporting to an Executive Assurance Committee. TRIAL REGISTRATION NUMBER: ISRCTN17951423; Pre-results.

Adrenal Mass Biopsy in Patients Without Extraadrenal Primary Malignancy: A Multicenter Study.

BACKGROUND. Adrenal washout CT is not useful for evaluating incidental adrenal masses in patients without known or suspected primary extraadrenal malignancy. OBJECTIVE. The purpose of our study was to evaluate the diagnostic utility of adrenal mass biopsy in patients without known or suspected extraadrenal primary malignancy. METHODS. This retrospective six-center study included 69 patients (mean age, 56 years; 32 men, 37 women) without known or suspected extraadrenal primary malignancy who underwent image-guided core needle biopsy between January 2004 and June 2021 of a mass suspected to be arising from the adrenal gland. Biopsy results were classified as diagnostic or nondiagnostic. For masses resected after biopsy, histopathologic concordance was assessed between diagnoses from biopsy and resection. Masses were classified as benign or malignant by resection or imaging follow-up, and all nondi-agnostic biopsies were classified as false results. RESULTS. The median mass size was 7.4 cm (range, 1.9-19.2 cm). Adrenal mass biopsy had a diagnostic yield of 64% (44/69; 95% CI, 51-75%). After biopsy, 25 masses were resected, and 44 had imaging follow-up. Of the masses that were resected after diagnostic biopsy, diagnosis was concordant between biopsy and resection in 100% (12/12). Of the 13 masses that were resected after nondiagnostic biopsy, the diagnosis from re-section was benign in eight masses and malignant in five masses. The 44 masses with imaging follow-up included one mass with diagnostic biopsy yielding benign adenoma and two masses with nondiagnostic biopsy results that were classified as malignant by imaging follow-up. Biopsy had overall sensitivity and specificity for malignancy of 73% (22/30) and 54% (21/39), respectively; diagnostic biopsies had sensitivity and specificity for malignancy of 96% (22/23) and 100% (21/21), respectively. Among nine nondi-agnostic biopsies reported as adrenocortical neoplasm, six were classified as malignant by the reference standard (resection showing adrenocortical carcinoma in four, resection showing adrenocortical neoplasm of uncertain malignant potential in one, imaging follow-up consistent with malignancy in one). CONCLUSION. Adrenal mass biopsy had low diagnostic yield, with low sensitivity and low specificity for malignancy. A biopsy result of adrenocortical neoplasm did not reliably differentiate benign and malignant adrenal masses. CLINICAL IMPACT. Biopsy appears to have limited utility for the evaluation of incidental adrenal masses in patients without primary extraadrenal malignancy.

A Randomized Phase I Study of the Anti-Interleukin-33 Antibody Tozorakimab in Healthy Adults and Patients With Chronic Obstructive Pulmonary Disease.

Tozorakimab is a human monoclonal antibody that neutralizes interleukin (IL)-33. IL-33 is a broad-acting epithelial "alarmin" cytokine upregulated in lung tissue of patients with chronic obstructive pulmonary disease (COPD). This first-in-human, phase I, randomized, double-blind, placebo-controlled study (NCT03096795) evaluated the safety, tolerability, pharmacokinetics (PKs), immunogenicity, target engagement, and pharmacodynamics (PDs) of tozorakimab. This was a 3-part study. In part 1, 56 healthy participants with a history of mild atopy received single escalating doses of either intravenous or subcutaneous tozorakimab or placebo. In part 2, 24 patients with mild COPD received multiple ascending doses of subcutaneous tozorakimab or placebo. In part 3, 8 healthy Japanese participants received a single intravenous dose of tozorakimab or placebo. The safety data collected included treatment-emergent adverse events (TEAEs), vital signs, and clinical laboratory parameters. Biological samples for PKs, immunogenicity, target engagement, and PD biomarker analyses were collected. No meaningful differences in the frequencies of TEAEs were observed between the tozorakimab and placebo arms. Three tozorakimab-treated participants with COPD experienced treatment-emergent serious adverse events. Subcutaneous or intravenous tozorakimab demonstrated linear, time-independent PKs with a mean half-life of 11.7-17.3 days. Treatment-emergent anti-drug antibody frequency was low. Engagement of tozorakimab with endogenous IL-33 in serum and nasal airways was demonstrated. Tozorakimab significantly reduced serum IL-5 and IL-13 levels in patients with COPD compared with placebo. Overall, tozorakimab was well tolerated, with a linear, time-independent serum PK profile. Additionally, biomarker studies demonstrated proof of mechanism. Overall, these data support the further clinical development of tozorakimab in COPD and other inflammatory diseases.

Metabolic fitness of IgA+ plasma cells in the gut requires DOCK8.

Dedicator of cytokinesis 8 (DOCK8) mutations lead to a primary immunodeficiency associated with recurrent gastrointestinal infections and poor antibody responses but, paradoxically, heightened IgE to food antigens, suggesting that DOCK8 is central to immune homeostasis in the gut. Using Dock8-deficient mice, we found that DOCK8 was necessary for mucosal IgA production to multiple T cell-dependent antigens, including peanut and cholera toxin. Yet DOCK8 was not necessary in T cells for this phenotype. Instead, B cell-intrinsic DOCK8 was required for maintenance of antigen-specific IgA-secreting plasma cells (PCs) in the gut lamina propria. Unexpectedly, DOCK8 was not required for early B cell activation, migration, or IgA class switching. An unbiased interactome screen revealed novel protein partners involved in metabolism and apoptosis. Dock8-deficient IgA+ B cells had impaired cellular respiration and failed to engage glycolysis appropriately. These results demonstrate that maintenance of the IgA+ PC compartment requires DOCK8 and suggest that gut IgA+ PCs have unique metabolic requirements for long-term survival in the lamina propria.

Restorative neurostimulation for chronic mechanical low back pain - Three year results from the United Kingdom post market clinical follow-up registry.

Introduction: Mechanical chronic low back pain is often associated with impaired neuromuscular control of the lumbar multifidus muscles, the most important stabilizers of the lumbar spine. Restorative neurostimulation is a modality for the treatment for this specific subset of patients aimed to facilitate restoration of neuromuscular control by bilateral stimulation of the L2 medial branches. Evidence from both prospective and randomised clinical trials to date has demonstrated substantial improvements in clinical outcomes such as pain, disability and health-related quality of life. Methods: This study is an open label prospective follow-up for the treatment of chronic mechanical low back pain of nociceptive origin with restorative neurostimulation. Patients completed assessments for pain, disability and health-related quality of life. Outcomes were collected at 45, 90 and 180 days, and 1, 2 and 3 years after the activation visit. Results: Forty-two patients were implanted with the device and 33 (79%) were available at the 3-year appointment. Patients in this cohort presented with severe chronic low back pain (NRS = 7.0 ± 0.2) and severe disability (ODI 46.6 ± 12.0). The health-related quality of life was also severely impacted at baseline (EQ-5D 0.426 ± 0.061). Changes in pain, disability and quality of life at three-year follow-up demonstrated a statistically significant improvement between baseline and 1, 2 and 3 years. After 3 years of therapy, average NRS scores had reduced to 2.7± 0.3 and mean ODI score to 26.0 ± 3.1 while EQ-5D-5L index improved to 0.707 ± 0.036. Conclusions: The ongoing follow-up of this post market cohort continues to demonstrate that restorative neurostimulation provides a statistically significant, clinically meaningful and durable response across pain, disability and quality-of life scores for patients suffering chronic mechanical low back pain that has been refractory to conventional management. Trial Registration: ClinicalTrials.gov Identifier: NCT01985230.

Infarct exclusion repair of postmyocardial infarction ventricular septal rupture with a hybrid patch and septal occluder device compared with patch only.

Objective: We developed a hybrid technique for repairing post-myocardial infarction (MI) ventricular septal defect (VSD) that combines infarct exclusion with patch and a nitinol-mesh septal occluder device (SOD) to provide a scaffold to support the damaged septal wall. Here, we compare outcomes of patients with post-MI VSD repaired using patch only or hybrid patch/SOD. Methods: Patients undergoing post-MI VSD repair at our institution from 2013 to 2022 who received patch alone or patch/SOD repair were analyzed. Primary outcome was survival to hospital discharge. Clinical outcomes and echocardiograms were also analyzed. Results: Over a 9-year period, 24 patients had post-MI VSD repair at our institution with either hybrid patch/SOD (n = 10) or patch only repair (n = 14). VSD size was 18 ± 5.8 mm for patch/SOD and 17 ± 4.6 mm for patch only. In the patch/SOD repair cohort, average size of SOD implant was 23.6 ± 5.6 mm. Mild left ventricular dysfunction was present prerepair and was unchanged postrepair in both groups; however, moderate-to-severe right ventricular (RV) dysfunction was common in both groups before repair. RV function worsened or persisted as severe in 10% of hybrid versus 54% of patch-only patients postrepair. Tricuspid annular systolic excursion and RV:left ventricle diameter ratio, quantitative metrics of RV function, improved after patch/SOD repair. No intraoperative mortality occurred in either group. Postoperative renal, hepatic, and respiratory failure requiring tracheostomy was common in both groups. Survival to hospital discharge in both cohorts was 70%. Conclusions: Post-MI VSD repair with patch/SOD has comparable short-term outcomes with patch alone. Addition of a SOD to patch repair provides a scaffold that may enhance the repair of post-MI VSD with patch exclusion.

Protocol for establishing primary human lung organoid-derived air-liquid interface cultures from cryopreserved human lung tissue.

Primary human lung organoid-derived air-liquid interface (ALI) cultures serve as a physiologically relevant model to study human airway epithelium in vitro. Here, we present a protocol for establishing these cultures from cryopreserved human lung tissue. We describe steps for lung tissue cryostorage, tissue dissociation, lung epithelial organoid generation, and ALI culture differentiation. We also include quality control steps and technical readouts for monitoring virus response. This protocol demonstrates severe acute respiratory syndrome coronavirus 2 infection in these cultures as an example of their utility. For complete details on the use and execution of this protocol, please refer to Diana Cadena Castaneda et al. (2023).1.

Scoping review of percutaneous mechanical aspiration for valvular and cardiac implantable electronic device infective endocarditis.

BACKGROUND: Percutaneous mechanical aspiration (PMA) of intravascular vegetations is a novel strategy for management of patients with infective endocarditis (IE) who are at high risk of poor outcomes with conventional cardiac surgery. However, clear indications for its use as well as patient outcomes are largely unknown. OBJECTIVES: To conduct a scoping review of the literature to summarize patient characteristics and outcomes of those undergoing PMA for management of IE. METHODS: Two independent reviewers screened abstracts and full text for inclusion and independently extracted data. DATA SOURCES: MEDLINE, Embase, and Web of Science. STUDY ELIGIBILITY CRITERIA: Studies published until February 21, 2023, describing the use of PMA for management of patients with cardiac implantable electronic device (CIED) or valvular IE were included. ASSESSMENT OF RISK OF BIAS: As this was a scoping review, risk of bias assessment was not performed. METHODS OF DATA SYNTHESIS: Descriptive data was reported. RESULTS: We identified 2252 titles, of which 1442 abstracts were screened, and 125 full text articles were reviewed for inclusion. Fifty-one studies, describing a total of 294 patients who underwent PMA for IE were included in our review. Over 50% (152/294) of patients underwent PMA to debulk cardiac implantable electronic device lead vegetations prior to extraction (152/294), and 38.8% (114/294) of patients had a history of drug use. Patient outcomes were inconsistently reported, but few had procedural complications, and all-cause in-hospital mortality was 6.5% (19/294). CONCLUSIONS: While PMA is a promising advance in the care of patients with IE, higher quality data regarding patient outcomes are needed to better inform the use of this procedure.

Initial Management Strategy and Long-Term Outcomes in 186 Cases of Spontaneous Coronary Artery Dissection.

Spontaneous coronary artery dissection (SCAD) is a rare but important nonatherosclerotic cause of acute coronary syndrome. Indications for revascularization and long-term outcomes of SCAD remain areas of active investigation. We report our experience with initial management strategy and long-term outcomes in SCAD. We reviewed all patients treated at our institution from 1996-2021 with a SCAD diagnosis. Demographics, comorbidities, clinical presentations, angiography findings, and management strategies were obtained by chart review. The primary outcome was a composite of cardiac death, recurrent/progressive SCAD, subsequent diagnosis of congestive heart failure, or subsequent/repeat revascularization after the initial management. Unadjusted Kaplan-Meier survival analysis was performed. Of 186 patients with a SCAD diagnosis treated at our institution, 149 (80%) were female. Medical management was the initial treatment in 134 (72.0%) patients, percutaneous coronary intervention (PCI) in 43 (23.1%), and coronary artery bypass grafting in 9 (4.8%). Surgery/PCI intervention was associated with younger age (38.8 vs 47.7 years, P = 0.01), ST elevation myocardial infarction on presentation (67.0% vs 34.0%, P < 0.001), lower ejection fraction (45.0% vs 55.0%, P = 0.002), and left anterior descending coronary artery dissection (75.0% vs 51.0%, P = 0.006). Ten-year freedom from our composite outcome was similar between revascularized patients and those managed with medical therapy (P = 0.36). Median follow-up time was 4.5 years. SCAD in the setting of ST elevation myocardial infarction, left anterior descending coronary artery involvement, or decreased cardiac function suggests greater ischemic insult and was associated with initial percutaneous or surgical revascularization. Despite worse disease on initial presentation, long-term outcomes of patients undergoing revascularization are similar to medically managed patients with SCAD.

EXACT Trial: Results of the Phase 1 Dose-Escalation Study.

BACKGROUND: New therapies are needed for patients with refractory angina. Encoberminogene rezmadenovec (XC001), a novel adenoviral-5 vector coding for all 3 major isoforms of VEGF (vascular endothelial growth factor), demonstrated enhanced local angiogenesis in preclinical models; however, the maximal tolerated dose and safety of direct epicardial administration remain unknown. METHODS: In the phase 1 portion of this multicenter, open-label, single-arm, dose-escalation study, patients with refractory angina received increasing doses of encoberminogene rezmadenovec (1×109, 1×1010, 4×1010, and 1×1011 viral particles) to evaluate its safety, tolerability, and preliminary efficacy. Patients had class II to IV angina on maximally tolerated medical therapy, demonstrable ischemia on stress testing, and were angina-limited on exercise treadmill testing. Patients underwent minithoracotomy with epicardial delivery of 15 0.1-mL injections of encoberminogene rezmadenovec. The primary outcome was safety via adverse event monitoring over 6 months. Efficacy assessments included difference from baseline to months 3, 6 (primary), and 12 in total exercise duration, myocardial perfusion deficit using positron emission tomography, angina class, angina frequency, and quality of life. RESULTS: From June 2, 2020 to June 25, 2021, 12 patients were enrolled into 4 dosing cohorts with 1×1011 viral particle as the highest planned dose. Seventeen serious adverse events were reported in 7 patients; none were related to study drug. Six serious adverse events in 4 patients were related to the thoracotomy, 3 non-serious adverse events were possibly related to study drug. The 2 lowest doses did not demonstrate improvements in total exercise duration, myocardial perfusion deficit, or angina frequency; however, there appeared to be improvements in all parameters with the 2 higher doses. CONCLUSIONS: Epicardial delivery of encoberminogene rezmadenovec via minithoracotomy is feasible, and up to 1×1011 viral particle appears well tolerated. A dose response was observed across 4 dosing cohorts in total exercise duration, myocardial perfusion deficit, and angina class. The highest dose (1×1011 viral particle) was carried forward into phase 2. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT04125732.