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BackgroundPatients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies.Patients and methodsPatients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients).ResultsA total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality.ConclusionsClinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies.Clinical trial identifierNCT04354701.

BackgroundHeterogenous central nervous system (CNS) neurologic manifestations of polyarteritis nodosa (PAN) are underrecognized. We review three cases of patients with PAN that illustrate a range of nervous system pathology, including the classical mononeuritis multiplex as well as uncommon brain and spinal cord vascular manifestations.Case presentationCase 1 presented with mononeuritis multiplex and characteristic skin findings. Case 2 presented with thunderclap headache and myelopathy due to spinal artery aneurysm rupture. Both patients experienced disease remission upon treatment. Case 3 presented with headache and bulbar symptoms due to partially thrombosed intracranial aneurysms, followed by systemic manifestations related to visceral aneurysms. She demonstrated clinical improvement with treatment, was lost to follow-up, then clinically deteriorated and entered hospice care.ConclusionsAlthough the peripheral manifestations of PAN are well-known, PAN association with CNS neurovascular disease is relatively underappreciated. Clinician awareness of the spectrum of neurologic disease is required to reduce diagnostic delay and promote prompt diagnosis and treatment with immunosuppressants.

PurposeHigh-dimensional image features that underlie COVID-19 pneumonia remain opaque. We aim to compare feature engineering and deep learning methods to gain insights into the image features that drive CT-based for COVID-19 pneumonia prediction, and uncover CT image features significant for COVID-19 pneumonia from deep learning and radiomics framework.MethodsA total of 266 patients with COVID-19 and other viral pneumonia with clinical symptoms and CT signs similar to that of COVID-19 during the outbreak were retrospectively collected from three hospitals in China and the USA. All the pneumonia lesions on CT images were manually delineated by four radiologists. One hundred eighty-four patients (n = 93 COVID-19 positive; n = 91 COVID-19 negative; 24,216 pneumonia lesions from 12,001 CT image slices) from two hospitals from China served as discovery cohort for model development. Thirty-two patients (17 COVID-19 positive, 15 COVID-19 negative; 7883 pneumonia lesions from 3799 CT image slices) from a US hospital served as external validation cohort. A bi-directional adversarial network-based framework and PyRadiomics package were used to extract deep learning and radiomics features, respectively. Linear and Lasso classifiers were used to develop models predictive of COVID-19 versus non-COVID-19 viral pneumonia.Results120-dimensional deep learning image features and 120-dimensional radiomics features were extracted. Linear and Lasso classifiers identified 32 high-dimensional deep learning image features and 4 radiomics features associated with COVID-19 pneumonia diagnosis (P  73% and specificity > 75% on external validation cohort with slight superior performance for radiomics Lasso classifier. Human expert diagnostic performance improved (increase by 16.5% and 11.6% in sensitivity and specificity, respectively) when using a combined deep learning-radiomics model.ConclusionsWe uncover specific deep learning and radiomics features to add insight into interpretability of machine learning algorithms and compare deep learning and radiomics models for COVID-19 pneumonia that might serve to augment human diagnostic performance.

Consumer interest in plant-based milk alternatives is growing, despite extra charges in coffeehouses. While much research exists on non-dairy alternatives, plant-based milks in coffee drinks remain understudied. This study examines consumer preferences and behaviors regarding milk alternatives in coffee, using the Theoretical Domains Framework (TDF) and the Behavior Change Wheel (BCW). A survey of 200 participants from 19 countries explored demographics, coffee habits, attitudes towards non-dairy milk charges, and marketing awareness. Market insights showed taste as the main reason for coffee choice, with a preference for cow’s milk and local cafes for quality. Many opposed the extra charges for non-dairy options, citing lactose intolerance or allergies, especially among Gen Z and Millennials. Regional variations included stronger opposition in the UK and Germany compared to the UAE and USA. The marketing for non-dairy milk was less memorable than general coffee advertisements. Regression analysis confirmed that viewing non-dairy milk as a dietary staple increased consumption, aligning with the TDF’s “Beliefs about Consequences” domain. Finally, within the BCW framework, the intervention strategies centered on training and coercion were discussed. Implementing these approaches could encourage the wider adoption of non-dairy milk options in coffee shops, fostering inclusivity, health awareness, and supporting environmental sustainability efforts.

BackgroundFabry disease (FD) is an X-linked lysosomal disorder leading to multiorgan dysfunction, including renal impairment and the risk of significant accumulation for renally excreted drugs. Migalastat, an approved therapy in FD patients with amenable variants, is primarily eliminated in urine; however, its use had not been studied in patients with end-stage renal disease (ESRD) receiving dialysis therapy. This study investigated the pharmacokinetics (PK), dialyzability, and tolerability of 123 mg migalastat in non-FD subjects with ESRD on stable hemodialysis/hemodiafiltration (EudraCT 2018-003684-57). Results were analyzed by population PK and physiologically based PK (PBPK) modeling and intended to propose dose regimens resulting in negligible migalastat trough levels in plasma and comparable concentrations above the threshold in target tissues in FD patients with ESRD.MethodsSubjects with ESRD received 123 mg migalastat 24 hours before dialysis and, following an 8-day washout, immediately before dialysis. Matched controls with normal renal function (NRF) received migalastat 123 mg. Migalastat concentrations were measured in plasma, urine, and dialysate, and modeled to select regimens providing similar disposition to NRF.ResultsMigalastat was extracted by hemodialysis/hemodiafiltration (74%/72%). PBPK modeling predicted that 123 mg every other week (QOW) with regular dialysis 2-3 times weekly in ESRD subjects produced: a fraction of time above EC50 similar to FD patients with NRF; adequate Cmax for intracellular trafficking of mutant α-galactosidase A to the lysosome; and Ctrough levels near the lower limit of quantification (LLOQ) similar to NRF subjects receiving 123 mg every other day. Migalastat 82 mg weekly produced a greater fraction of time above EC50 and longer duration of concentrations above the LLOQ, potentially resulting in accumulation in tissues.ConclusionMigalastat was well extracted by hemodialysis/hemodiafiltration. Migalastat 123 mg QOW is the proposed dose regimen for further evaluation in FD patients with ESRD, which could inform expansion of treatment options.Trial registrationTrial registration: EU Clinical Trials Register, EudraCT number 2018-003684-57.

Background Dolichoectatic vertebrobasilar aneurysms (DVBAs) carry high morbidity, and treatment options are limited. The tumor necrosis factor α signaling cascade is implicated in DVBA growth and rupture, but the role of anti–tumor necrosis factor α therapy in DVBA has not been studied. Methods A retrospective, case–control study of DVBA at a single institution was performed. Two patients with DVBA were treated with infliximab (tumor necrosis factor α inhibitor) as part of routine therapy for rheumatoid arthritis. Three additional patients diagnosed with DVBA were studied as a control group. Routine brain magnetic resonance imaging/magnetic resonance angiography were measured by 2 blinded neuroradiologists to assess DVBA growth. Baseline comorbidities and clinical outcomes were assessed by chart review. Results The groups were similar with respect to baseline characteristics, and all patients were symptomatic at the time of DVBA diagnosis. One patient who started infliximab during the study period showed a reversal in DVBA growth rate trajectory, with a relative decrease in growth rate by 37% (0.49–0.18 mm2/day). Mean interval DVBA growth rates were lower during infliximab therapy than during noninfliximab observation intervals (0.13 versus 0.50 mm2/day; P = 0.09). Two patients in the control group died during the study period and 1 had a poor outcome (modified Rankin scale = 4). Both patients in the infliximab group had unchanged functional status (modified Rankin scale = 1) and no adverse events related to infliximab. Conclusion This study presents the first investigation of anti–tumor necrosis factor α therapy for DVBA. Infliximab was associated with low and decreasing DVBA growth trajectories with no treatment‐related adverse events. The effect of infliximab on clinical outcomes remains uncertain.

Background Patients treated with percutaneous coronary intervention are often considered to be at a high bleeding risk (HBR). Drug‐eluting stents have been shown to be superior to bare‐metal stents in patients with HBR, even when patients were given abbreviated periods of dual antiplatelet therapy (DAPT). Short DAPT has not been evaluated with the EluNIR ridaforolimus‐eluting stent. The aim of this study was to evaluate the safety and efficacy of a shortened period of DAPT following implantation of the ridaforolimus‐eluting stent in patients with HBR. Methods and Results This was a prospective, multicenter, binational, single‐arm, open‐label trial. Patients were defined as HBR according to the LEADERS‐FREE (Prospective Randomized Comparison of the BioFreedom Biolimus A9 Drug‐Coated Stent versus the Gazelle Bare‐Metal Stent in Patients at High Bleeding Risk) trial criteria. After percutaneous coronary intervention, DAPT was given for 1 month to patients presenting with stable angina. In patients presenting with an acute coronary syndrome, DAPT was given for 1 to 3 months, at the investigator's discretion. The primary end point was a composite of cardiac death, myocardial infarction, or stent thrombosis up to 1 year (Academic Research Consortium definite and probable). Three hundred fifteen patients undergoing percutaneous coronary intervention were enrolled, and 56.4% presented with acute coronary syndrome; 33.7% were receiving oral anticoagulation. At 1 year, the primary end point occurred in 15 patients (4.9%), meeting the prespecified performance goal of 14.1% (P

The World Health Organization (WHO) was born as a normative agency and has looked to global health law to structure collective action to realize global health with justice. Framed by its constitutional authority to act as the directing and coordinating authority on international health, WHO has long been seen as the central actor in the development and implementation of global health law. However, WHO has faced challenges in advancing law to prevent disease and promote health over the past 75 years, with global health law constrained by new health actors, shifting normative frameworks, and soft law diplomacy. These challenges were exacerbated amid the COVID-19 pandemic, as states neglected international legal commitments in national health responses. Yet, global health law reforms are now underway to strengthen WHO governance, signaling a return to lawmaking for global health. Looking back on WHO's 75th anniversary, this article examines the central importance of global health law under WHO governance, reviewing the past successes, missed opportunities, and future hopes for WHO. For WHO to meet its constitutional authority to become the normative agency it was born to be, we offer five proposals to reestablish a WHO fit for purpose: normative instruments, equity and human rights mainstreaming, sustainable financing, One Health, and good governance. Drawing from past struggles, these reforms will require further efforts to revitalize hard law authorities in global health, strengthen WHO leadership across the global governance landscape, uphold equity and rights at the center of global health law, and expand negotiations in global health diplomacy.

Abstract Objective: This study aimed to measure urinary sodium and potassium as a measure of sodium and potassium intake concerning the knowledge, attitude and practice towards sodium intake among a group of healthy residents in the UAE. Design: A cross-sectional study on a sample of healthy adults in the UAE. In addition to the knowledge, attitude and practice questionnaire, sodium and potassium excretions and food records were taken. Setting: The UAE. Participants: A sample of 190 healthy individuals aged between 20 and 60 years. Results: The mean (± s d) age of the sample was 38·6 (± 12·5) years, and 50·5 % were females. The mean urinary sodium and potassium intake were 2816·2 ± 675·7 mg/d and 2533·3 ± 615 mg/d, respectively. The means were significantly different compared with the WHO recommendation of sodium and potassium (P < 0·001). About 65 % of the participants exceeded the WHO recommendations for salt intake, and participants’ knowledge classification for health-related issues was fair, while food-related knowledge was poor (P = 0·001). A two-stage stepwise multiple regression analysis revealed that knowledge, attitude and practice scores were negatively associated with urinary sodium excretion (r = –0·174; P = 0·017) and those older participants and females had lower urinary sodium excretion (P < 0·001). Conclusions: These findings may suggest an increase in the risk of hypertension in the UAE population. Moreover, these findings emphasise the need to establish education and public awareness programmes focusing on identifying the sodium contents of foods and establishing national regulations regarding food reformulation, particularly for staple foods such as bread.

Abstract Intravital microscopy (IVM) allows spatial and temporal imaging of different cell types in intact live tissue microenvironments. IVM has played a critical role in understanding cancer biology, invasion, metastases, and drug development. One considerable impediment to the field is the inability to interrogate the tumor microenvironment and its communication cascades during disease progression and therapeutic interventions. Here, a new implantable perfusion window chamber (PWC) is described that allows high‐fidelity in vivo microscopy, local administration of stains and drugs, and longitudinal sampling of tumor interstitial fluid. This study shows that the new PWC design allows cyclic multiplexed imaging in vivo, imaging of drug action, and sampling of tumor‐shed materials. The PWC will be broadly useful as a novel perturbable in vivo system for deciphering biology in complex microenvironments.

The project ‘Quality Decision-making by women and providers’ (QUALI-DEC) combines four non-clinical interventions to promote informed decision-making surrounding mode of birth, improve women’s birth experiences, and reduce caesarean sections among low-risk women. QUALI-DEC is currently being implemented in 32 healthcare facilities across Argentina, Burkina Faso, Thailand, and Viet Nam. In this paper, we detail implementation processes and the planned process evaluation, which aims to assess how and for whom QUALI-DEC worked, the mechanisms of change and their interactions with context and setting; adaptations to intervention and implementation strategies, feasibility of scaling-up, and cost-effectiveness of the intervention. We developed a project theory of change illustrating how QUALI-DEC might lead to impact. The theory of change, together with on the ground observations of implementation processes, guided the process evaluation strategy including what research questions and perspectives to prioritise. Main data sources will include: 1) regular monitoring visits in healthcare facilities, 2) quantitative process and output indicators, 3) a before and after cross-sectional survey among post-partum women, 4) qualitative interviews with all opinion leaders, and 5) qualitative interviews with postpartum women and health workers in two healthcare facilities per country, as part of a case study approach. We foresee that the QUALI-DEC process evaluation will generate valuable information that will improve interpretation of the effectiveness evaluation. At the policy level, we anticipate that important lessons and methodological insights will be drawn, with application to other settings and stakeholders looking to implement complex interventions aiming to improve maternal and newborn health and wellbeing. Trial registration: ISRCTN67214403.

Background and Purpose: The management of unruptured intracranial aneurysms remains controversial. The decisions to treat are heavily informed by estimated risk of bleeding. However, these estimates are imprecise, and better methods for stratifying the risk or tailoring treatment strategy are badly needed. Here, we demonstrate an initial proof-of-principle concept for endovascular biopsy to identify the key molecular pathways and gene expression changes associated with aneurysm formation. We couple this technique with single cell RNA sequencing (scRNAseq) to develop a roadmap of the pathogenic changes of a dolichoectatic vertebrobasilar aneurysm in a patient with polyarteritis nodosa. Methods: Endovascular biopsy and fluorescence activated cell sorting was used to isolate the viable endothelial cells (ECs) using the established techniques. A single cell RNA sequencing (scRNAseq) was then performed on 24 aneurysmal ECs and 23 patient-matched non-aneurysmal ECs. An integrated panel of bioinformatic tools was applied to determine the differential gene expression, enriched signaling pathways, and cell subpopulations hypothesized to drive disease pathogenesis. Results: We identify a subset of 7 (29%) aneurysm-specific ECs with a distinct gene expression signature not found in the patient-matched control ECs. A gene set enrichment analysis identified these ECs to have increased the expression of genes regulating the leukocyte-endothelial cell adhesion, major histocompatibility complex (MHC) class I, T cell receptor recycling, tumor necrosis factor alpha (TNFα) response, and interferon gamma signaling. A histopathologic analysis of a different intracranial aneurysm that was later resected yielded a diagnosis of polyarteritis nodosa and positive staining for TNFα. Conclusions: We demonstrate feasibility of applying scRNAseq to the endovascular biopsy samples and identify a subpopulation of ECs associated with cerebral aneurysm in polyarteritis nodosa. Endovascular biopsy may be a safe method for deriving insight into the disease pathogenesis and tailoring the personalized treatment approaches to intracranial aneurysms.