Convalescent Plasma Restores Viral Clearance After Anti-Spike Monoclonal Antibody Failure in Immunocompromised COVID-19 Patients: A Systematic Review and Meta-Analysis of Individual Patient Data

Abstract: Anti-Spike monoclonal antibodies (mAbs) progressively lost efficacy during the COVID-19 pandemic due to the emergence and predominance of resistant SARS-CoV-2 variants. By contrast, high-titre COVID-19 convalescent plasma (CCP) collected from vaccinated donors recently recovered from infection provides a polyclonal source of antibodies that remains effective in clearing SARS-CoV-2 in immunosuppressed patients, unable to mount an adequate immune response against the virus. We conducted a systematic review and individual participant data meta-analysis to examine the effect of CCP in immunocompromised patients persistently positive for SARS-CoV-2 viraemia following mAb therapy, and to evaluate possible biological factors associated with a favourable outcome. Electronic databases were searched for studies published from January 2020 to January 2026. All studies including eligible cases were considered in the systematic review. Unpublished cases were also collected from investigators of the selected studies. The protocol was registered at PROSPERO (CRD420251142891). Forty-seven cases (30 cases from 12 published studies and 17 unpublished cases) were included. In 33 out of 47 patients (70.2%) with a mAb-resistant infection, SARS-CoV-2 clearance occurred following CCP transfusion, with a mean of 2.7 CCP units administered. In logistic regression, total CCP volume transfused was positively associated with SARS-CoV-2 clearance. In conclusion, CCP transfusion was associated with SARS-CoV-2 clearance in persistently positive immunocompromised patients following failure of anti-Spike mAb therapy.

Focosi D
Aiello TF
Casadevall A
Cruciani M
D'Abramo A
De Marco P
Gachoud D
Garcia-Vidal C
Glingani C
Hueso T
Joyner MJ
Lacombe K
Mengoli C
Nicastri E
Richier Q
Rufer N
Senefeld JW
Shoham S
Sullivan DJ
Tomisti L
Weinbergerova B
Zani M
Zaremba S
Franchini M

Humans
Immunocompromised Host
SARS-CoV-2
Antibodies, Monoclonal
COVID-19
Immunization, Passive
COVID-19 Serotherapy
Antibodies, Viral
Spike Glycoprotein, Coronavirus


Cancer Nutrition Education for Black Women: Policy Responsibility in a Systematic Review

Abstract: Introduction/ObjectivesCancer nutrition education supports cancer prevention and survivorship, yet African American/Black (AA/B) women continue to experience nutrition-related inequities across the cancer continuum. This review examined how qualitative studies describe these inequities and assign responsibility within the literature.MethodsPubMed and Scopus were searched in December 2024 and updated in January 2026. Eligible studies involved AA/B women in the United States, addressed cancer-related nutrition experiences, used qualitative methods, and examined nutrition-related inequities across the cancer care continuum. SPIDER-informed criteria guided eligibility, data were synthesized using inductive thematic analysis guided by intersectionality, and study quality was appraised using CASP.ResultsFourteen qualitative studies were included. Responsibility for nutrition-related inequities was located within programmatic, institutional, and structural conditions. Five themes were identified: Universal Nutrition Standards, Feasible Nutrition Guidance, Access and Choices, Concordance and Cultural Relevance, and Community-Driven Co-Design. Participants described adapting nutrition guidance to caregiving demands, cultural food practices, survivorship challenges, and access barriers. Race, gender, caregiving, cultural identity, geography, and socioeconomic conditions were reported across studies.ConclusionsThe literature frames inequities in cancer nutrition education as consequences of programmatic, institutional, and structural conditions. Improving cancer nutrition equity for AA/B women may require culturally relevant, feasible, community-informed approaches and stronger attention to nutrition delivery contexts.

Journal of primary care & community health

Humans
Black or African American
Female
Health Education
Neoplasms
United States


Patient Acceptance and Barriers to IoT Usage in Health Care: Systematic Literature Review

Abstract: The Internet of Things (IoT) represents a transformative paradigm in health care service delivery, offering unprecedented potential to enhance quality of care, operational efficiency, and patient outcomes through interconnected devices and real-time data analytics. Despite rapid adoption, implementation depends on patient acceptance as end users. While literature extensively documents technical and institutional perspectives, a comprehensive understanding of patient acceptance factors remains fragmented, with high technology abandonment rates. Systematic synthesis of patient perspectives is critically needed to inform user-centered design, effective implementation strategies, and supportive policy frameworks. This systematic literature review aims to identify and synthesize factors influencing patient acceptance of IoT technology in health care services, barriers hindering adoption, and effective strategies for enhancing acceptance. Following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 guidelines, we systematically searched eight electronic databases (PubMed/MEDLINE, Scopus, IEEE Xplore, Web of Science, ScienceDirect, ACM Digital Library, ProQuest, and Google Scholar) for empirical studies published between January 2016 and December 2024. Inclusion criteria encompassed peer-reviewed empirical research examining patient perspectives on IoT technology in health care services, published in English or Indonesian. From 2537 initially identified papers, 62 studies met inclusion criteria after systematic screening and full-text evaluation. Quality assessment was conducted using the Mixed Methods Appraisal Tool. The 62 included studies represented diverse geographic contexts (Asia, Europe, North America, and the Middle East) and methodological approaches. Quality assessment revealed 45 (73%) studies of good-to-excellent quality. Perceived usefulness emerged as the strongest acceptance facilitator, identified in 55 of 62 (89%) studies, followed by perceived ease of use in 47 (76%) studies, and trust and security in 42 (68%) studies. Cost-effectiveness was identified in 32 (52%) studies as an important consideration. Primary barriers included data security concerns in 26 (42%) studies, privacy issues in 24 (39%) studies, lack of digital literacy in 22 (36%) studies, and resistance to change in 20 (32%) studies. Interoperability issues and high costs were identified in 19 (31%) studies and 18 (29%) studies, respectively. User-centered design was the most frequently recommended enhancement strategy in 20 (32%) studies, followed by user-friendly interface development in 19 (31%) studies, digital literacy programs in 18 (29%) studies, and health care professional involvement in 15 (24%) studies. Digital literacy functioned as a significant moderator, and trust served as both direct predictor and mediator. Patient acceptance of IoT in health care represents a complex, multidimensional phenomenon requiring holistic approaches that integrate user-centered technology design, comprehensive digital literacy programs, trust-building mechanisms, and supportive policy frameworks. Successful implementation necessitates multilevel strategies addressing individual, organizational, and system factors simultaneously. With evidence-based, patient-centered approaches, IoT technology holds substantial potential to transform health care delivery into more proactive, personalized, and accessible services.

Humans
Internet of Things
Patient Acceptance of Health Care
Digital Health

Journal Article
Systematic Review
Review


Efficacy, safety, and health-related quality of life data of hyaluronic acid for the treatment of interdental papilla deficiency: A systematic review of randomized controlled trials

Abstract: The efficacy of hyaluronic acid (HA) in the treatment of interdental papilla (IDP) deficiency is well documented. This systematic review sought to evaluate clinical studies reporting efficacy, safety, and health-related quality of life (HRQoL) data for HA used in the treatment of IDP deficiency. This review was conducted and reported in accordance with the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. A comprehensive search of electronic databases was conducted for published randomized controlled trials (RCTs) from their inception until March 21, 2024. A total of 9 studies met the inclusion criteria. The sample sizes in the included RCTs ranged from 10 to 31 participants, with the mean patient age between 26.7 and 46.1 years, predominantly females. Of the 9 eligible studies, 6 assessed the use of HA alone, while 3 investigated the effects of HA in combination with other therapies. The most common outcome measures assessed black triangle dimensions (i.e., area, height or width) followed by probing depth (PD). Based on the limited published studies, this review suggests that HA treatment (whether alone or in combination) may offer therapeutic benefits for patients with IDP defects. However, none of the included studies assessed the safety of HA and its effect on HRQoL. There is a need for further research on the long-term efficacy and safety of HA treatment, and its influence on HRQoL.

Hyaluronic Acid
Humans
Quality of Life
Randomized Controlled Trials as Topic
Treatment Outcome
Female


Effect of Combined Aerobic and Resistance Training on Exercise Capacity, Muscle Strength, Quality of Life, and Mortality in Patients with Coronary Heart Disease: A Systematic Review with Meta-analysis

Abstract: CART (combined aerobic and resistance training) has shown important results in exercise-based cardiovascular rehabilitation. However, there are little data concerning the effects of CART on the exercise capacity, muscle strength, health-related quality of life (HRQoL), and mortality of coronary heart disease (CHD) patients. Therefore, the aim of this study was to analyze the published randomized controlled trials (RCTs) that investigated the effects of CART on exercise capacity [peak oxygen consumption (peak VO2) and 6-min walking distance (6MWD)], muscle strength [1-repetition maximum (1-RM), peak torque and handgrip strength], HRQoL, and mortality in patients with CHD. We search for references in MEDLINE/PubMed, Scopus, Cochrane Central Register of Controlled Trials, and EMBASE databases to find RCTs that evaluated the effects of CART for CHD. Mean difference (MD), standardized mean difference (SMD), risk ratio (RR), and 95% confidence intervals (CIs) were calculated. CART improved relative peak VO2 of 2.20 ml/kg/min (P < 0.0001), peak torque of 16.69 N.m (P < 0.0001), handgrip strength of 4.68 kgf (P < 0.0001), and HRQoL of 1.00 (P < 0.00001) and reduced mortality (RR = 0.40; P = 0.002) compared to non-exercising usual care. CART improved (relative and absolute) peak VO2 by 0.28 (P < 0.002), 6MWD by 21.98 m (P = 0.004), 1-RM by 0.61 kg (P < 0.0001), peak torque by 4.03 N.m (P = 0.002), and HRQoL by 0.50 (P < 0.0004) compared to aerobic training. CART improved relative peak VO2 by 1.91 ml/kg/min (P < 0.00001) compared to resistance training. CART was efficient in improving peak VO2, peak torque, handgrip strength, HRQoL, and lower mortality events compared to non-exercising usual care in patients with CHD. CART appears superior to aerobic training in improving peak VO2, 6MWD, 1-RM, peak torque, and HRQoL in patients with CHD. Furthermore, CART was more effective than resistance training for peak VO2 in patients with CHD. CART should be considered as a method in the rehabilitation of patients with CHD.

Gois CO
Guimarães ALA
Conceição LSR
Gomes-Neto M
Carvalho VO


Diabetes Mellitus and Long-Distance Running: A Systematic Review

Abstract: Athletes with diabetes increasingly participate in endurance running, benefiting from physiological adaptations and technological advances like continuous glucose monitoring (CGM) for glycemic control. So far, no comprehensive review summarizing the current knowledge has been performed. To identify the prevalence of long-distance runners with diabetes, their performance, methods used for blood glucose monitoring and glycemic control. PubMed, Medline Ovid, Scopus, SPORTDiscus, Cochrane databases, CINAHL, and Web of Science were systematically searched until April 2024 using key terms related to long-distance running and diabetes. An updated search applying the identical strategy was conducted on May 3rd, 2026, to capture subsequently published literature. This study included original research articles, case reports, and case studies published in English or German in peer-reviewed journals, utilizing both quantitative and qualitative methodologies. Eligibility criteria encompassed runners with a confirmed diagnosis of diabetes mellitus, irrespective of type, who participated in endurance events of at least half-marathon distance, including half-marathons, marathons, ultra-marathons, and other ultra-endurance competitions. Patients with prediabetic state, gestational diabetes, or after pancreatic islet-cell transplantation were excluded. For quality assessment, we used the Joanna Briggs Institute of Analytical Cross-Sectional Studies or the Joanna Briggs Institute of Analytical Case Report critical appraisal tool. A total of 656 studies were identified, with 22 meeting the inclusion criteria, comprising 99 runners with diabetes (99.0% Type 1, 1.0% Type 2 diabetes mellitus). Among them, 50.0% used CGM, 27.2% had an insulin pump, 63.6% administered insulin via multiple daily injections, and the method of insulin application was not specified in 7.0% of runners. The weighted mean HbA1c was 7.4% (95% CI 6.9-8.1). Time-in-range varied by race distance: 40-100% for half-marathoners, 51.6% for marathoners, and 47-73% for ultra-marathoners. No cases of symptomatic hypoglycemia were observed during the races. However, asymptomatic late-onset hypoglycemia (occurring 6-15 h post-exercise) was reported in 27 runners. The most common insulin adjustment strategy before competitive races was a 50-80% reduction of basal insulin. Despite limited research, evidence suggests that with proper preparation and multidisciplinary support, athletes with diabetes can safely participate in endurance events, including ultra-marathons, while maintaining stable glycemic control. PROSPERO-CRD42024539281.

Braschler L
Thuany M
Züger T
Nikolaidis PT
Weiss K
Rosemann T
Knechtle B


Successful pre-operative endovascular intraventricular meningioma embolization: a systematic review and pediatric case analysis

Abstract: Intraventricular meningiomas are rare tumors accounting for a small fraction of intracranial meningiomas and are often associated with significant surgical challenges due to their deep location and rich vascular supply. Pre-operative endovascular embolization has been proposed as an adjunct to reduce intraoperative bleeding and facilitate safer resection; however, its role in intraventricular lesions remains poorly defined. We present a case of a 9.5-year-old boy with a highly vascular intraventricular meningioma who underwent pre-operative endovascular embolization followed by surgical resection. Additionally, a systematic review was conducted in accordance with PRISMA guidelines, searching PubMed and Scopus for studies reporting embolization of intraventricular meningiomas. In the presented case, selective embolization of the posterior choroidal artery using a glue-lipiodol mixture was successfully performed without complications, leading to reduced tumor vascularity and enabling gross total resection with minimal blood loss (< 300 mL). The systematic review identified seven cases from six studies. Embolization was successful in six cases, with varying degrees of devascularization. Gross total resection was achieved in all surgically treated patients. Reported intraoperative blood loss ranged from 150 to 1850 mL. Complications occurred in two of seven cases, including postoperative epidural hematoma. Pre-operative endovascular embolization appears to be a technically feasible adjunct in selected cases of intraventricular meningiomas. However, current evidence is limited to case reports and small case series, precluding definitive conclusions regarding its safety or clinical benefit.

Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery

Abdallah AM
Hulliel AF
Saleh D
Mukahal M
Qassim D
Obeidat M

Humans
Meningioma
Male
Embolization, Therapeutic
Meningeal Neoplasms
Child
Cerebral Ventricle Neoplasms
Endovascular Procedures
Preoperative Care

Journal Article
Systematic Review
Case Reports
Review


Efficacy, Effectiveness, and Efficiency of Nurse-Led Interventions: Insights From a Critical Systematic Review

Abstract: Healthcare systems worldwide face mounting pressure to deliver high-quality care while enhancing efficiency and sustainability. Nurse-led interventions have emerged as promising strategies to optimize care delivery, particularly within value-based health systems. However, a comprehensive understanding of their clinical impact and economic value remains limited. This systematic review conducted following PRISMA guidelines, searched nine international databases to identify and synthesize formally evaluated nurse-led interventions, programs, and strategies. Twenty-eight studies were included, encompassing diverse care settings and patient populations. Most studies reported improvements in clinical outcomes, including reduced hospital readmissions, enhanced quality of life, and improved chronic disease management. Several interventions analyzed effectiveness, particularly those involving advanced nursing roles such as nurse practitioners and case managers. Findings suggest that clinical effectiveness does not necessarily translate into increased professional authority: nurse-led interventions consistently generate value across patient, organizational, and systemic dimensions, yet nursing leadership remains structurally subordinate within healthcare governance. A systematic agenda for rigorous economic evaluation embedded in nursing research programs is urgently needed, alongside structural reforms that redistribute authority-not merely develop competencies-within healthcare organizations.

Fontanals-Jimenez A
Trapero-Bertran M
Insa-Calderón E

Systematic Review
Journal Article
Review


A comprehensive systematic review of sarcoptic mange diagnostic methods in wildlife

Abstract: Sarcoptic mange is a parasitic contagious disease that can lead to significant declines in wildlife populations. To identify the most used methods for diagnosing mange in free-ranging wildlife species, a systematic review was conducted across multiple databases: Scopus, PubMed, Web of Science, ProQuest Central and CABI. Citation screening was performed using the web-based platform, Covidence. A customized data extraction form, developed by the authors, was used to collect relevant information. This information was later exported and analyzed using Microsoft Excel. The objectives of this systematic review were to identify the most used detection methods for sarcoptic mange in wildlife globally over the past 30 years, classify them into invasive and non-invasive categories and provide an updated overview of related adjunct techniques and the broader scientific literature on mange detection and documentation in free-ranging animals. A total of 228 studies were analyzed and categorized into two groups-non-invasive and invasive methods. Non-invasive methods (visual observation, camera trapping, spotlighting, detector dogs and infrared thermography) do not require restraining of animals. Invasive methods (skin scraping, molecular diagnosis using mite isolation and polymerase chain reaction (PCR), serological diagnosis using Enzyme Linked ImmunoSorbent Assay (ELISA), histological analysis and immunohistochemistry) typically require taking samples from the animals and clinical or laboratory infrastructure. Across all diagnostic methods, visual observation was the most widely used technique, followed by skin scraping as the second most frequently applied method for confirming sarcoptic mange. Non-invasive approaches like spotlighting and camera traps provided valuable population-level insights without direct animal contact, though laboratory methods such as PCR, ELISA, and histological analysis offered greater accuracy at higher costs. We recommend a combined approach, starting with non-invasive methods to assess overall population health before using invasive techniques on selected animals for definitive diagnosis, with advanced technologies expected to enhance long-range detection capabilities in the future.

Animals
Scabies
Animals, Wild
Sarcoptes scabiei


The prevention of heterotopic ossification around the knee: a scoping review

Abstract: Evidence on prophylactic interventions to prevent heterotopic ossification (HO) around the knee is scarce. We conducted a scoping review to map reported indications, interventions, and outcome reporting. We followed a prospectively developed protocol and searched four major databases (MEDLINE via PubMed, Embase, Cochrane Library, and Web of Science), complemented by searches of trial registries and grey literature using a high-sensitivity strategy. Data extraction was performed in duplicate and summarized descriptively by modality. The search yielded 2,958 records. We included 78 unique publications, comprising 18 expert-opinion sources and 62 clinical publications reporting data on 3,321 patients, of whom 1,579 received the evaluated interventions, with two publications contributing to both syntheses. Modalities comprised continuous passive motion (CPM) in 8, pharmacological prophylaxis in 21, radiotherapy (RT) in 18, surgical techniques in 3, and combination therapy in 14 studies. Most identified studies were case reports or case series. Pharmacological data were largely driven by one large ASA cohort, whereas RT and combination-therapy studies were small and mainly addressed recurrence prophylaxis. One late fatal, potentially RT-induced sarcoma was reported. Because of substantial clinical and methodological heterogeneity, crude reported event proportions should not be compared directly across modalities. Outcome reporting was inconsistent, with limited use of standardized patient-reported outcomes and incomplete adverse-event reporting. Knee HO prophylaxis evidence is dominated by low-level, heterogeneous studies with substantial reporting gaps. Comparative knee-specific studies with standardized outcome definitions, functional outcomes, and systematic safety reporting are needed. This review was prospectively registered on the Open Science Framework (OSF registration ID 5328k).

Römer M
Wurschi G
Mäurer M
Pietschmann K

Humans
Ossification, Heterotopic
Knee Joint
Motion Therapy, Continuous Passive
Combined Modality Therapy
Treatment Outcome

Scoping Review
Journal Article
Systematic Review


End-of-life communication in surgery and neurosurgery: challenges, opportunities, and insights from a systematic review

Abstract: The aim of this systematic review was to synthesize current evidence on end-of-life (EOL) communication in surgical and neurocritical care settings. While effective EOL communication is essential to support patient-centered decision-making and ethical care, its implementation in surgical and neurosurgical contexts remains inconsistent and insufficiently characterized. Using advanced search terms, a systematic review of the literature was conducted, comprising PubMed and Scopus. Studies published from January 2016 to January 2026 were included if they involved adult patients, family members, or clinicians engaged in EOL communication within surgical, neurosurgical, or oncological settings and reported empirical data on communication practices, barriers, ethical issues, family involvement, or training interventions. Observational, interventional, and qualitative studies were eligible. Due to substantial heterogeneity in study design and outcomes, findings were synthesized qualitatively. Twenty-six studies met the inclusion criteria. Across studies, EOL communication was characterized by significant challenges related to time constraints, emotional burden, prognostic uncertainty, and variability in clinician communication skills. Structured training interventions, particularly simulation-based programs, were associated with improved clinician confidence and perceived competence, although their implementation was inconsistent. Neurosurgical and neuro-oncological settings presented distinct challenges, including rapid disease progression, early cognitive impairment, and increased reliance on family members for surrogate decision-making. Ethical dilemmas surrounding medical futility, autonomy, and conflict resolution were recurrent. The available evidence highlights persistent gaps between recommended and actual EOL communication practices in surgical and neurocritical care. Improving outcomes will require earlier and structured communication, formal training embedded in surgical education, and multidisciplinary collaboration. Future research should prioritize prospective designs and standardized outcome measures to strengthen the evidence base and support more informed clinical decision-making for patients, families, and clinicians. Systematic review registration no.: CRD420261320726 (www.crd.york.ac.uk/prospero/).

Vannuccini S
Della Pepa GM
Marfoli A
Lafuenti L
D'Alessandris QG
Mattogno PP
Doglietto F
Chieffo DPR

Humans
Terminal Care
Communication
Neurosurgery
Neurosurgical Procedures
Decision Making


Endoscopic-Assisted Chronic Subdural Hematoma Evacuation as an Adjunct to Middle Meningeal Artery Embolization: A Case Series and Systematic Review

Abstract: AIM: Chronic subdural hematoma (cSDH) is a common neurosurgical condition in elderly patients, frequently associated with trauma, anticoagulant use, and chronic comorbidities. While surgical evacuation and now middle meningeal artery embolization remain the predominant treatment options, endoscopic-assisted techniques have been increasingly used as a surgical adjunct. We evaluated the safety, clinical outcomes, and recent advancements in endoscopic-assisted evacuation of cSDH through both a retrospective case series and an updated review of the current literature. MATERIAL and METHODS: A retrospective analysis of 39 patients undergoing 44 endoscopic-assisted evacuations of subdural hematomas between October 2021 and May 2025 was performed. Patient demographics, imaging, operative details, complications, and recurrence were analyzed. A systematic review of 15 studies published between 2022 and 2025 was added to a prior review performed by our group to assess outcomes associated with endoscopic approaches to cSDH. RESULTS: Of the 39 patients (67% male, ages 20 to 73), four experienced recurrence, three prior to middle meningeal artery (MMA) embolization and one after. All patients received postoperative subdural drains, and no intraoperative complications related to the endoscope occurred. The literature review included an additional 16 recent studies (n=1060 patients) in addition to 13 studies from a previous systematic review, reporting recurrence rates of 0% to 16.7%. Endoscopic evacuation was associated with reduced recurrence, shorter hospital stays, and improved hematoma clearance compared to traditional techniques. CONCLUSION: Endoscopic-assisted evacuation of cSDH appears to be a safe and effective adjunct to conventional surgical methods through improved visualization, potential coagulation of distal meningeal artery territories, and reduced recurrence. While results are promising, larger prospective studies are needed to confirm long-term benefits and refine patient selection.

Baloi D
Freeman H
Pattillo C
Demir E
Zeinali M
Karsy M

Humans
Hematoma, Subdural, Chronic
Meningeal Arteries
Female
Embolization, Therapeutic
Male
Aged
Middle Aged
Retrospective Studies
Neuroendoscopy
Adult
Treatment Outcome
Young Adult
Recurrence


Comparing the Effectiveness of Different Types of Orthoses in Preventing Diabetic Foot Ulcer Recurrence: A Systematic Review of Randomized Clinical Trials

Abstract: Therapeutic orthoses, such as medical shoes and custom insoles, are used to prevent diabetic foot ulcer (DFU) recurrence. This systematic review with narrative synthesis aimed to evaluate the effectiveness of orthoses in preventing DFU recurrence compared to standard care. We followed PRISMA guidelines for a systematic review. Searches were conducted in PubMed, Cochrane, and Web of Science. RCTs on orthoses for preventing DFU recurrence were included. Risk of bias was assessed using Cochrane tools. Due to heterogeneity, narrative synthesis was used. An initial search of 4166 articles identified ten randomized controlled trials (RCTs) that met the inclusion criteria and were included in this review, focusing on patients living with diabetes at risk of DFU recurrence compared to usual care. Narrative synthesis of the 10 RCTs, involving 1686 participants, showed that custom orthoses reduced recurrence in several studies (e.g., Bus 2013 reported 9.9% recurrence vs. 25% in controls), though the evidence was heterogeneous due to variability in orthosis types and follow-up periods. Orthoses can prevent diabetic foot ulcer recurrence, and we recommend their use where feasible. Further research is needed to optimize their clinical application.

Amini B
Salehi-Pourmehr H
Ghaffarzadehrad S

Humans
Diabetic Foot
Randomized Controlled Trials as Topic
Foot Orthoses
Recurrence
Secondary Prevention
Female
Treatment Outcome
Male
Middle Aged

Journal Article
Systematic Review
Comparative Study


Dietary Intake of Animal and Plant-Based Protein on Adiposity Measurements and Body Composition in Pre- and Postmenopausal Women: A Systematic Review of Randomized Clinical Trials

Abstract: This systematic review investigated the effect of protein intake on anthropometric and body composition markers in pre- to postmenopausal women. Understanding these effects may contribute to the development of nutritional strategies to improve body composition and prevent changes associated with this phase. Searches were conducted in the PubMed, EMBASE, and Cochrane Library databases, following the PRISMA guidelines, and the risk of bias was assessed using the Joanna Briggs Institute (JBI) tool (PROSPERO: CRD420251156313). Fifteen randomized clinical trials, involving 1161 pre- and postmenopausal women, were included. Interventions with animal-based protein (n = 8) showed more consistent effects on weight and body fat reduction, especially when combined with calorie restriction and supervised exercise. Protocols using whey protein, meat, or milk protein demonstrated reductions in body fat over 8-16 weeks, with increases in lean mass in longer interventions. However, these effects are strongly influenced by the use of other strategies, such as energy restriction and physical exercise. Studies with soy protein isolate (n = 7) showed more heterogeneous results, with few changes in short-term interventions and more favorable results when combined with exercise. When analyzed independently of energy restriction and physical exercise, the effects of consuming both proteins on body composition were less consistent, making it impossible to confirm benefits from an isolated increase in protein intake. Animal proteins have more consistent effects on anthropometric markers and body composition in women during the climacteric period, particularly when combined with energy restriction and physical exercise. In contrast, plant-based proteins have more heterogeneous effects, with greater benefits observed when associated with exercise. The findings of this review reinforce the importance of considering protein type, dose, duration of intervention, and other combined strategies when developing nutritional recommendations for changes in body composition.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

Fialho SN
de Souza Ferreira ML
Ribeiro SAV
Kravchychyn ACP
Hermsdorff HHM

Humans
Female
Adiposity
Body Composition
Postmenopause
Randomized Controlled Trials as Topic
Animals
Premenopause
Dietary Proteins
Animal Proteins, Dietary


Beyond Coverage: A Systematic Review and Thematic Analysis of Delivery, Compliance, Equity and Impact in Mass Deworming for Soil-Transmitted Helminths

Abstract: Soil-transmitted helminth (STH) infections affect approximately 1.5 billion people globally. Although the World Health Organization (WHO) aims for 75% mass drug administration (MDA) coverage by 2030, the long-term population benefit remains debated. This review aims to describe the characteristics of recent mass deworming studies, synthesize parasitologic and coverage outcomes, and identify programmatic themes. Search was conducted across Scopus, PubMed, and EBSCO CINAHL, restricted to studies reporting both parasitologic efficacy outcomes and MDA coverage. Following a risk of bias assessment in Review Manager 5.4, qualitative data were processed in Taguette 1.5.1 through a hierarchical thematic analysis to generate basic, organizing, and global themes and supplemented by VOSviewer 1.6.20 overlay visualization. Thirteen eligible studies primarily featured African countries and cross-sectional study designs. While overall risk of bias was low, lack of blinding revealed high performance bias. Thematic analysis, supported by bibliographic visualization, identified four global themes on delivery, compliance, equity and impact. Findings indicate that annual dosing is often insufficient and requires bi-annual schedules and WASH integration. Compliance is hindered by temporal inaccessibility and unreliable decentralized monitoring while equity gaps persist for out-of-school children and pregnant women. Although drug efficacy is confirmed, risks of resistance and diagnostic underreporting via the Kato-Katz method remain critical concerns. This review identifies four interrelated pillars of delivery, compliance, equity, and impact that shape the effectiveness of mass deworming programs and have direct implications for achieving WHO 2030 targets.

Rodriguez HM
Rostata AMB
Salgado JJRCMV
Rivera TLD
Angeles JMM

Helminthiasis
Humans
Soil
Anthelmintics
Mass Drug Administration
Animals
Helminths


A multi-dataset single-cell meta-analysis of human keloid skin across Asian, Black and White populations reveals endothelial and mesenchymal programs linked to ethnic disparities

Abstract: Keloid is a fibroproliferative scar with marked ethnic disparities, disproportionately affecting Asian and Black populations. Single-cell RNA sequencing (scRNA-seq) studies have mapped keloid pathology, but cross-study differences complicate generalization. We performed a meta-analysis to identify composition and transcriptional programs associated with keloid across ethnicities. We aggregated human skin scRNA-seq datasets containing keloid and healthy samples with documented ethnicity (Asian, Black, White). After quality control and batch integration (scVI/scANVI), we annotated cell types and subtypes. Differential abundance was estimated with scCODA, Milo, and propeller. Pseudobulk differential expression was meta-analyzed using random-effects models. Ligand-receptor signaling was inferred with CellChat/NicheNet. The harmonized atlas comprised 112 donors, 147 samples, and 487,293 cells from 8 studies. Keloid demonstrated higher proportions of vascular endothelial cells and fibroblasts across all methods. Ethnicity-stratified analysis revealed endothelial expansion in Asian and Black relative to White populations, while fibroblast expansion was greater in White keloids. Endothelial subtyping showed increased post-capillary venules and arteriolar states. Fibroblast analysis revealed expansion of mesenchymal/ADAM12+ and pro-inflammatory populations. Meta-analysis implicated TGF-β/SMAD, integrin/FAK, and YAP/TAZ mechanotransduction pathways as candidate pathogenic programs warranting functional validation. Cross-study synthesis identifies shared and ethnicity-stratified endothelial and fibroblast programs in keloid. Expansion of post-capillary venules and ADAM12+ fibroblasts provides candidate therapeutic targets pending functional validation and a framework for understanding ethnic disparities in keloid formation.

Alkouz Z
Zhang L
Suwait AA
Alhejairi R
Liu C
Gu X
Yang B


Beyond conventional metrics: a scoping review of cultural food security definitions and indicators for migrant populations

Abstract: The ability to reliably access, afford, or obtain foods that are culturally significant, familiar, and aligned with one's identity, foodways, religious beliefs, and the sociocultural preferences is an important aspect of food and nutrition security in immigrant communities. This is because access to culturally appropriate food is crucial for maintaining perceived healthy dietary and nutritional practices, finding comfort, and growing a sense of place. However, the existing food security measurement scales have been criticized for their limited ability to adequately capture the unique aspects of cultural food security as experienced by newcomer populations. As such, the existing measures under estimate the prevalence and the significant health and wellbeing effects of cultural food security. Furthermore, recent studies have argued for recognition cultural food security as a distinct concept with its own indicators relevant to newcomers, yet limited to no studies exist that have comprehensively reviewed and synthesized the existing conceptualization and definition of cultural food security. We address this knowledge gap by mapping and synthesizing the existing literature on the definition of cultural food security, the adopted indicators, and the associated benefits of cultural food security for immigrants and refugees. The review followed the PRISMA Extension for Scoping Reviews guidelines and synthesized journal articles retrieved from five databases: PubMed, Scopus, Medline, CINAHL Plus, and Academic Search Complete. Flowing Braun and Clarke's Reflexive thematic analysis, we synthesized 18 studies that met the inclusion criteria for this review. We found variability and diversity in the definition of cultural food security. Most of the studies have adopted existing food security scales to estimate cultural food security, yet the scales inadequately capture the food security realities of immigrants, refugees, and ethno-cultural groups in the destination communities. Additionally, cultural food security in migrant communities transcends the conventional food security indicators to embody the unique migration and resettlement experiences. By synthesizing the existing studies that have explored how cultural food security in migrant population has been assessed, this study generates evidence on the relevance of considering the unique indicators of the aspects of food security that appreciates the reciprocal relations with the land, the practice of sharing of food and food cultures, and a collectivist lens to eating of food and to food access, which are relevant to immigrant communities. The evidence is important in creating culturally responsive food security interventions and in ensuring improved sense of place and settlement of newcomers.

Onyango E
Owuor P
Otoadese D
Odhiambo S
Ajibade T
Onyango J
Boateng G


Ketamine for substance use disorders: a systematic review and meta-analysis

Abstract: Substance use disorder (SUD) is a major global health issue, contributing significantly to the disease burden. Despite this, effective treatments for SUD remain limited. Ketamine has shown potential as a treatment, yet no meta-analysis has assessed its efficacy for SUD. This study aimed to evaluate the efficacy and safety of ketamine in treating SUD. Multiple databases were systematically searched forrandomized controlled trials (RCTs) on ketamine for SUD treatment. The primary outcome was abstinence rates. Adverse events and dropout rates were also assessed to evaluate safety and acceptability. A random-effects model was used to conduct the meta-analysis. Fifteen RCTs with 798 participants were included; seven RCTs contributed abstinence data to the quantitative synthesis. Ketamine was associated with significantly improved abstinence at <1 month [odds ratio(OR) = 3.27, 95% CI: 1.55-6.92, I2 = 0%, p < 0.01], but not at 1-6 months (OR = 1.74, 95% CI: 0.91-3.30, I2 = 0%, p = 0.09). No significant difference in dropout rates was observed between the ketamine and control groups (OR = 0.74, 95% CI: 0.46-1.21, I2 = 0%, p = 0.23). No significant between group difference was identified in adverse events, although the available evidence was limited and insufficient to establish safety conclusively. Current evidence suggests a short-term efficacy signal for ketamine in SUD, but the evidence remains limited and insufficient to establish its efficacy and safety conclusively. identifier CRD42024607116.

Fang SP
Yang X
Zhao DC
Wen Y
Liu YH
Li Z
Ran MS


Safety and Effectiveness of Indacaterol/Glycopyrronium/Mometasone Dry Powder Inhaler in Asthma: A Prospective Multicenter Phase IV Study

Abstract: Asthma remains a major public health challenge in India, characterized by high disease burden, poor adherence, and suboptimal control despite therapeutic advances. Fixed-dose combination therapy with indacaterol/glycopyrronium/mometasone furoate (IND/GLY/MF; DIFIZMA®), a single-inhaler triple therapy (SITT), offers the potential for improved symptom control and adherence through once-daily dosing. However, real-world and postmarketing surveillance data on the effectiveness and safety of IND/GLY/MF in Indian asthma patients remain limited, underscoring the need for local evidence to guide clinical practice. To evaluate the safety and effectiveness of once-daily IND/GLY/MF dry powder inhaler (DPI) in Indian adults with asthma inadequately controlled on inhaled corticosteroid (ICS)-long-acting β2-agonist (LABA) therapy. This was a prospective, open-label, multicenter, single-arm, phase IV postmarketing study conducted across multiple centers in India. Adults (18-65 years) with persistent asthma symptoms despite ICS ± LABA therapy received IND/GLY/MF DPI (160 µg mometasone furoate, 46 µg glycopyrronium bromide, 114 µg indacaterol acetate) once daily for 24 weeks. The primary endpoint was safety, based on treatment-emergent adverse events (TEAEs), serious TEAEs, and discontinuations. Secondary endpoints included changes from baseline in the asthma control questionnaire (ACQ-7) score, FEV1, FVC, and FEV1/FVC ratio at weeks 4, 12, and 24. A total of 200 patients were enrolled (safety set), of whom 196 were included in the modified intent-to-treat (mITT) analysis and 189 in the per-protocol (PP) population. TEAEs occurred in 9.5% of participants, with 6.5% considered drug-related; all events were mild or moderate in severity. No serious adverse events, severe TEAEs, or deaths were reported. Clinically meaningful and progressive improvements were observed in asthma control and lung function over 24 weeks. The ACQ-7 score decreased from 3.00 ± 0.59 at baseline to 2.36 ± 0.54 at week 4, 1.86 ± 0.54 at week 12, and 1.39 ± 0.61 at week 24, corresponding to mean change of -0.64 ± 0.50, -1.14 ± 0.74, and -1.62 ± 0.89, respectively (all p < 0.0001). Mean FEV1 increased from 1.49 ± 0.51 L at baseline to 1.73 ± 0.60 L at week 4, 1.81 ± 0.53 L at week 12, and 1.95 ± 0.51 L at week 24, with corresponding mean changes of +0.24 L, +0.32 L, and +0.46 L (all p < 0.0001). Mean FVC improved from 2.13 ± 0.63 L at baseline to 2.30 ± 0.70 L, 2.33 ± 0.62 L, and 2.38 ± 0.59 L at weeks 4, 12, and 24, respectively (all p < 0.0001). The FEV1/FVC ratio increased from 71.63 ± 12.76 at baseline to 76.71 ± 11.33, 80.86 ± 12.67, and 84.00 ± 8.93 at weeks 4, 12, and 24, with mean changes of +4.99, +8.91, and +12.10, respectively (all p < 0.0001). No hospitalizations or rescue medication use were reported. Compliance with study medication was 100%, and both patients and physicians reported marked symptom improvement and high treatment satisfaction. Once-daily IND/GLY/MF DPI demonstrated a favorable safety profile and significant, sustained clinical benefits in adults with asthma inadequately controlled on ICS-LABA therapy. The triple combination provided rapid onset and sustained improvement in asthma control and lung function, with excellent adherence and tolerability in real-world Indian clinical practice. These findings support IND/GLY/MF as an effective and practical single-inhaler triple therapy option for optimized asthma management.

The Journal of the Association of Physicians of India

Karmakar S
Bhate AS
Prashanth C
Kadam D
Patel CB
Budhraja A
Nandy U
Lotankar A
Nivangune K
Patel K

Humans
Asthma
Quinolones
Mometasone Furoate
Adult
Female
Glycopyrrolate
Male
Drug Combinations
Dry Powder Inhalers
Prospective Studies
Indans
Middle Aged
Treatment Outcome
India
Administration, Inhalation
Young Adult

Journal Article
Multicenter Study
Clinical Trial, Phase IV


Lactiplantibacillus plantarum Probio87 supplementation improves functional constipation and is associated with peripheral gene-expression responses related to inflammation and the gut-brain axis: a randomized, double-blind, placebo-controlled trial

Abstract: Functional constipation is a common disorder of gut-brain interaction that substantially affects bowel function, psychological well-being, and quality of life. Probiotic supplementation represents a microbiota-targeted nutritional strategy for functional constipation, but associated host-response signals remain incompletely understood. This single-center, randomized, double-blind, placebo-controlled trial enrolled 104 adults who met the Rome IV criteria for functional constipation. Participants received either Lactiplantibacillus plantarum Probio87 or placebo for 8 weeks, followed by a 4-week post-intervention follow-up. The primary endpoint was weekly complete spontaneous bowel movements. Secondary outcomes included Rome IV symptom scores, PAC-QOL, HAMD-24, safety parameters, and exploratory whole-blood gene-expression profiles related to inflammation, immune regulation, neuroendocrine signaling, and gut motility. The trial was registered in the Chinese Clinical Trial Registry (ChiCTR2300075360). Probio87 supplementation significantly increased weekly complete spontaneous bowel movements compared with placebo at Week 8 and Week 12. Improvements were also observed in Rome IV symptom scores, constipation-related quality of life, and HAMD-24 domains related to anxiety, sleep, and retardation. Exploratory whole-blood gene-expression analysis showed differential host-response signals after intervention, characterized by increased BDNF expression and reduced expression of IL-1β, CD117, CXCR5, IDO1, DBH, and MLNR in the probiotic group relative to placebo. No intervention-related adverse events or clinically relevant abnormalities in hematological, hepatic, or renal safety parameters were observed. L. plantarum Probio87 supplementation was associated with sustained improvement in bowel function, constipation-related quality of life, and psychological well-being in adults with functional constipation. Exploratory peripheral gene-expression findings suggest that inflammatory, immune, neuroendocrine, and motility-related host-response pathways may be involved, although causal mechanisms require further validation. https://www.chictr.org.cn/showproj.html?proj=205514, identifier (ChiCTR2300075360).

Zheng F
Yang Y
Zhan Y
Zhang ZW
Lu G
Xie D
Zhang SM
Mageswary U
Lee YY
Liong MT


Effect of a high-dose bioactive components formula on reducing common diseases in term neonates delivered by cesarean section: a randomized, open-label, controlled trial

Abstract: To investigate the effects of a high-dose probiotic-lactoferrin (LF)-milk fat globule membrane (MFGM)-nucleotide combined formula on reducing the incidence risk of common diseases and related symptoms and improving growth and hemoglobin level in neonates born via cesarean section. This trial was a prospective, multicenter, open-label, randomized, controlled 3-month intervention study. A total of 150 eligible neonates were enrolled. All participants completed the full intervention and provided clinical data. All enrolled formula-feeding neonates were randomly assigned to either the intervention group (IG, n = 50) or the control group (CG, n = 50), and 50 exclusively breastfed neonates were assigned to the breastfeeding control group (BCG). The formula used in the IG contained 2 × 109 CFU/100 g probiotics, 200 mg/100 g LF, added MFGM, and 55 mg/100 g nucleotides. In contrast, neonates in the CG were fed a formula containing 45-50 mg/100 g LF and 30-35 mg/100 g nucleotides, without probiotic or MFGM fortification. The primary outcome was the frequency of upper respiratory tract infections (URTIs). Secondary outcomes included the incidence of other respiratory, gastrointestinal, and allergic symptoms and diseases, as well as infant anthropometric indicators (including length, weight and head circumference) and the hemoglobin (Hb) concentration. The incidence of URTIs over the 3-month intervention showed no significant difference among the three groups [the incidences of URTIs in CG, IG, and BCG: 22% (11/50), 18% (9/50), and 14% (7/50), respectively, χ2 = 1.084, p = 0.582] according to both intention-to-treat (TT) and per protocol (PP) analyses [incidence of URTIs in CG, IG, and BCG: 22.9% (11/48), 19.6% (9/46), and 14.9% (7/47), respectively, χ2 = 0.680, p = 0.712]. After the 3-month intervention, compared with infants in the CG, infants in the IG showed a reduced risk ration (RR) for functional dyspepsia [RR = 0.756, 95% confidence interval (95% CI) = 0.587-0.974] and eczema (RR = 0.647, 95% CI = 0.449-0.933). Hb levels in the CG and IG were both significantly higher than those in the BCG (107.35 ± 9.26 vs. 105.99 ± 7.01 vs. 101.42 ± 7.07 g/L for CG, IG, and BCG, respectively; F = 9.629, p < 0.001), with no statistically significant difference between the CG and IG. No significant differences in anthropometric indicators were observed among the three groups (p > 0.05). This study found no adverse effects associated with 3-month supplementation of a high-dose probiotic-LF-MFGM-nucleotide combined formula, supporting its safety for term neonates delivered by cesarean section. The primary outcome, URTI incidence, did not differ significantly among groups. Exploratory analyses suggested lower risks of functional dyspepsia and eczema in the intervention group; however, these findings should be considered preliminary and require confirmation in larger adequately powered studies. The intervention was well tolerated and showed safety comparable to standard feeding practices.

Chen K
Zhang X
Chen H
He N
Tang Y
Yang Z
Fang Z
Liu C


Long-term Impact of Intravitreal Injections on the ocular surface; a 2-year follow-up study

Abstract: Intravitreal injection (IVI) therapy is the most frequently performed intraocular procedure worldwide, with topical povidone-iodine (PVP-I) as the standard pre-injection antiseptic. However, PVP-I has been shown to exert cytotoxic effects on the ocular surface. The purpose of this study was to evaluate the impact of two years of serial anti-vascular endothelial growth factor (VEGF) IVI on ocular surface parameters. Patients with neovascular age-related macular degeneration (nAMD) receiving unilateral intravitreal anti-VEGF injections were examined at two time points, separated by a two-year interval. An aseptic protocol with PVP-I was applied prior to each injection. Tear meniscus height (TMH), bulbar redness (BR), and meibomian gland (MG) loss were assessed using the Oculus Keratograph 5M, with the fellow eye serving as control. For statistical analysis, the related-samples Wilcoxon signed-rank test was applied to non-normally distributed data, and the paired-sample Student's t-test to normally distributed data. Sixty patients (mean age, 78.6 ± 8.5 years; range, 55-96) were included. Between examinations, patients received a mean of 15.5 ± 6.5 IVI (range, 5-30). A significant increase in mean BR was observed in untreated fellow eyes compared with baseline measurements (1.68 ± 0.47 vs. 1.41 ± 0.46; p < 0.001). At follow-up, BR was significantly higher in fellow eyes than in treated eyes (p < 0.001), and this difference had increased over the study period. Median TMH increased significantly in untreated eyes (0.42 mm [IQR, 0.28-0.57] vs. 0.31 mm [IQR, 0.23-0.47]; p = 0.003), whereas the increase in treated eyes was not significant (p = 0.74). At follow-up, mean TMH did not differ significantly between treated and fellow eyes (p = 0.15). Both treated and untreated eyes showed significant MG loss after two years of serial IVI; however, no significant differences in mean MG loss were detected between eyes in either the upper or lower eyelid at follow-up. Eyes receiving repeated intravitreal anti-VEGF injections with preoperative PVP-I antisepsis were significantly less hyperemic than fellow untreated eyes, and this difference increased over two years of continued treatment. Potential mechanisms include a beneficial alteration of the ocular surface microbiome by PVP-I or an antiangiogenic effect of anti-VEGF therapy. https://clinicaltrials.gov/study/NCT04458012, identifier NCT04458012.

Malmin A
Olsen MVT
Thomseth VM
Kjellevold Haugen IB
Utheim TP
Forsaa VA


Preliminary safety data from a randomised trial of early versus standard timing of administration of measles-rubella vaccine in Ugandan infants

Abstract: Measles remains a major cause of child morbidity and mortality in low-resource settings. Young infants are particularly at risk of severe disease, with many lacking protective levels of maternal antibodies by six months. Vaccination before nine months in high-burden settings may confer earlier protection; however, concerns exist about its effectiveness at this age. We present early findings on enrolment, safety, and measles infections following the administration of a registered measles-containing vaccine at six months versus nine months (MR1) with a subsequent booster (MR2) at 12 or 18 months of age. We conducted an open-label randomised controlled non-inferiority trial at four health facilities in Kampala, Uganda. Infants aged 24-28 weeks were randomly assigned to receive MR at six and 12 months (group A), nine and 18 months (group B) or six and 18 months (group C). Infants were electronically randomised in a 1:1:1 ratio using block randomisation of varying sizes, stratified by site, maternal HIV status and baseline haemoglobin level. Caretakers recorded solicited reactions on paper diary cards, with safety-related events evaluated. 450 infants received MR1 and were enrolled. No differences in local or systemic post-vaccination events between the six and nine months MR1 groups were observed [Local: 21·2% versus 21·9% (p = 0·959), systemic: 29·2% vs. 27·7% (p = 0·845)]. Most local reactions were mild and within the first four days. The majority (5/6) of hospitalisations followed common childhood illnesses, with one non-vaccine-related death six months post-MR1. Sixteen laboratory-confirmed cases of measles (10) and rubella (6), and three clinical measles cases before MR1 were registered. Most measles cases (70·0%) occurred in group C, with no measles cases registered two weeks post-MR2. We provide further evidence on the safety of administering a measles-containing vaccine at six months of age.Trial registration: The trial was registered on 31st October 2024 with Clinicaltrials.gov with the identifier NCT06667206. The online version contains supplementary material available at 10.1007/s44337-026-00649-x.

Businge G
Marchevsky NG
Mupere E
Kelly S
Kakai I
Kyohere M
Edielu A
Ambangira F
Kakayi B
Tusubira V
Komugisha C
Musoke P
Mujadidi YF
Bijlsma MW
Le Doare K
Voysey M


Homeopathic medication for seasonal allergic rhinitis-a randomised placebo-controlled trial

Abstract: The study aim was to evaluate the efficacy of homeopathic medication in SAR patients. In a double-blind, three-arm randomised trial, patients at eleven outpatient clinics and two medical centres were randomised to receive (1) individualised homeopathic case taking (IHCT) and standardised homeopathic medication with Galphimia Glauca (GG), (2) IHCT and individualised homeopathic treatment (IHG), or (3) IHCT and placebo (PG). Primary outcome was disease-specific quality of life, assessed using the Rhinitis Quality of Life Questionnaire (RQLQ) after three and four weeks. Secondary outcomes included response rate (≥0.5-point change in RQLQ), rescue medication use, and total nasal and non-nasal symptom scores (TNSS, TNNSS). Sixty-two SAR patients (mean age ± SD: 46.9 ± 14.9; 43.5% female) were recruited, approximately 25% of the planned sample size. After weeks three and four, there were no significant differences in RQLQ (p = 0.244) between GG (adjusted mean, 1.2, 95% CI 0.7-1.7), IHG (1.7, 1.2-2.3), and PG (1.4, 0.8-2.0). High response rates were observed (GG: 86.4%, IHG: 66.7%, PG: 81.3%), while RM use was 21.7%, 55.6%, and 29.4%, respectively. There were no relevant differences in RM score, TNSS and TNNSS between the three groups. Eight adverse events but no serious adverse events were reported. Standardised and individualised homeopathic drugs were not superior compared to placebo suggesting that treatment response was not based on study medication. The validity of the study and its conclusions are limited by the fact that the recruitment target was not achieved. This study has been registered in the German Clinical Trial Registry with trial ID DRKS00018081.

Siewert J
Cramer H
Ortiz M
Tissen-Diabaté T
Roll S
Wegscheider K
Linde K
Reinhold T
Willich SN
Teut M
Brinkhaus B


Academic anti CD19 CAR-T cell therapy for relapsed/refractory B-cell lymphomas in real-world clinical practice: a prospective cohort study

Abstract: Chimeric antigen receptor (CAR) T-cell therapy has been the standard of care for relapsed/refractory B-cell lymphomas (r/r BCLs) in recent years. However, high cost of commercial products limits their application in real-world clinical practice. The use of the so-called academic CAR-T cell products can reduce the cost and improve availability and affordability of this therapy option. The aim of the present clinical trial was to assess the efficacy and safety of academic CAR-T cells in r/r BCL patients. From June 2021 to December 2025, this prospective clinical trial enrolled 76 r/r BCL patients treated at the N.N. Alexandrov National Cancer Centre of Belarus (Minsk, Republic of Belarus), ClinicalTrials.gov Identifier: NCT07524816. The patients were 23-68 years of age (median 47 years). The CAR-T cell product was manufactured using lentiviral vector encoding anti-CD19 CAR. The median follow-up was 7.85 months for the entire cohort and 20.12 months for patients without events. Generally, complete response was achieved in 57.5% of patients. The 4-year event-free survival (EFS) rate was 46.2 ± 6.3%, and the 4-year overall survival (OS) rate was 67 ± 5.9%. Among patients with follicular lymphoma (FL), complete response was achieved in 83.3% patients. The 4-year EFS was 81.7 ± 9.6%. The safety profile was acceptable: cytokine release syndrome (CRS) was detected in 43.4% of patients (≥ grade 3 in 2.6%). No cases of grade 4 CRS were reported, and neurotoxicity (ICANS) was identified in 26.3% of patients (≥ grade 3 in 5.3%, grade 4 ICANS occurred in two patients - 2.6%). The anti-CD19 CAR T-cell product demonstrates good efficacy and acceptable toxicity in patients with r/r BCL. The use of such a product is the only available option for patients in countries where commercial products are not accessible. https://clinicaltrials.gov/study/NCT07524816, identifier NCT07524816.

Konoplya NE
Doroshenko TM
Zharkova KY
Savich TV
Seviaryn IM
Bobrova NM
Beleevsky AA
Sarydze EK
Polyakov SL


Safety and feasibility of tumor treating fields initiated before and during radiotherapy for newly diagnosed glioblastoma: results from the Arm A feasibility cohort of a phase I/II trial (PriCoTTF)

Abstract: Tumor Treating Fields improve survival when started after chemoradiotherapy in newly diagnosed glioblastoma, but the safety and feasibility of initiating treatment before and during radiotherapy remain uncertain. PriCoTTF is a prospective, open-label, nonrandomized, multicenter phase I/II trial. Arm A enrolled adults aged 18 to 70 years with newly diagnosed IDH-wildtype glioblastoma or gliosarcoma, Karnofsky Performance Status of at least 60, and planned focal radiotherapy to 60 Gy in 30 fractions. TTFields at 200 kHz were initiated 2 to 4 weeks after surgery and 1 to 2 weeks before radiotherapy. The primary endpoint was protocol-defined treatment-limiting toxicity from TTFields initiation through 4 weeks after radiotherapy. Twenty evaluable patients comprised the Arm A feasibility cohort. No protocol-defined treatment-limiting toxicities occurred (0 of 20 patients; exact 95% CI, 0.0%-16.8%). Grade 3 or higher adverse events occurred in 12 patients (60%), predominantly hematologic toxicity attributable to chemoradiotherapy; lymphopenia occurred in 6 patients (30%). Median usage through visit 4 was 76.5%, and median time to first attainment of at least 75% daily use was 2 days. Median progression-free survival was 6.9 months (95% CI, 2.7-14.0), and median overall survival was 18.0 months (95% CI, 12.1-19.9). Initiation of TTFields before and during radiotherapy was feasible and was not associated with protocol-defined treatment-limiting toxicity in the Arm A cohort. Because the TLT definition was narrow and efficacy analyses were exploratory and exposure-conditioned, these findings should be interpreted as feasibility data rather than evidence of improved tumor control or survival. The results support randomized evaluation of earlier TTFields integration in newly diagnosed glioblastoma. German Clinical Trials Register DRKS00016667, registered 26 February 2019.

Kebir S
Oster C
Sharma S
Jekel L
Schmidt T
Grieger J
Cappello G
Kizina K
Lazaridis L
Rauschenbach L
Ahmadipour Y
Dammann P
Junker A
Keyvani K
Feldheim J
Pierscianek D
Scheffler B
Proescholdt M
Hau P
Grosu AL
Krex D
Sure U
Kleinschnitz C
Pöttgen C
Stuschke M
Glas M

Humans
Glioblastoma
Middle Aged
Adult
Female
Aged
Male
Brain Neoplasms
Feasibility Studies
Young Adult
Prospective Studies
Adolescent
Electric Stimulation Therapy
Chemoradiotherapy
Treatment Outcome

Journal Article
Clinical Trial, Phase I
Clinical Trial, Phase II
Multicenter Study


Sex-Related Differences and Predictors of Mortality in Patients Undergoing Major Orthopaedic Surgery: Insights from the ORTHO-START Registry

Abstract: Sex-related differences in outcomes after major orthopaedic surgery remain under-investigated, and the prognostic relevance of a history of venous thromboembolism (VTE) is unclear. The ORTHO-START registry is a prospective, multicenter study including 1,077 consecutive adults undergoing major orthopaedic surgery (elective hip/knee arthroplasty or urgent hip fracture repair) across six Italian centers between July 2018 and March 2022. Baseline characteristics, perioperative complications, and antithrombotic therapy were collected. The primary outcome was all-cause mortality at 24 months; secondary outcomes were thromboembolic and bleeding events. Multivariable logistic regression identified predictors of mortality. Women represented 72.3% (n = 775) of the cohort and were older than men (80.6 ± 10.0 vs. 76.2 ± 13.0 years, p < 0.001). Urgent procedures comprised 65.6% (n = 706) of surgeries, predominantly involving women (n = 542). At 24 months, mortality was higher in men (31 vs. 18%, p = 0.018). Independent predictors of mortality included male sex (odds ratio [OR] = 2.6, 95% confidence interval [CI]: 1.8-4.0), older age, lower body mass index, urgent surgery (OR = 7.2, 95% CI: 4.1-12.4), and prior VTE (OR = 5.7, 95% CI: 1.4-23.9). Causes of death were known for 160/210 (76.2%): neurological complications were most frequent (25%), followed by cardiovascular disease (21.3%) and immobility-related causes (14.4%); pulmonary embolism accounted for 1.3% of deaths. Thrombotic and hemorrhagic events occurred in both sexes without significant differences. Male sex and a history of VTE are independent predictors of long-term mortality following major orthopaedic surgery. Incorporating these factors into preoperative risk assessment may improve management and postoperative outcomes.

Grandone E
Antonucci E
Piazza G
Barcellona D
Rostagno C
Colaizzo D
de Laurenzo A
di Rienzo G
Gorgoglione F
Maccagnano G
Marongiu F
Mastroianno M
Marzolo M
Mirabella L
Moretti B
Moretti AM
Ostuni A
Palareti G
Margaglione M


Lucinactant, a Synthetic Surfactant for the Treatment of Acute Respiratory Distress Syndrome Caused by COVID-19: Phase 1/2A Trial

Abstract: One unique feature of COVID-19-associated acute respiratory distress syndrome (ARDS) is surfactant deficiency because SARS-CoV-2 specifically attacks alveolar type 2 cells. In this study, we evaluated the effects of a synthetic surfactant (lucinactant) therapy in patients with COVID-19-associated ARDS. This open-label multicenter phase 1/2A trial enrolled adult patients with COVID-19-associated ARDS who were within 7 days of mechanical ventilation initiation. Lucinactant (160 mL or approximately 80 mg of total phospholipids per kilogram of lean body weight) was delivered intratracheally. One retreatment was allowed at ≥6-hour intervals. The primary end points were oxygenation index and PO2-to-fraction of inspired oxygen ratio up to day 5 after dosing. Other end points included time to deliver lucinactant and respiratory system compliance (Crs). We monitored peridosing events and adverse events up to 30 days after dosing. A total of 19 treated patients were enrolled (n=14, 73.7% receiving 1 dose; n=5, 26.3% receiving 2 doses). The mean age was 49 (SD 15) years. The mean time to administer lucinactant was 31 minutes. No significant changes were observed in oxygenation index (mean 10.4, SD 5.8 at baseline; 8.6, SD 2.7 at 12 hours; and 5.7, SD 2.4 on day 5; P=.12 via ANOVA) or PO2-to-fraction of inspired oxygen ratio (mean 193, SD 69 at baseline; mean 179, SD 57 at 12 hours; and mean 223, SD 105 on day 5; P=.44 via ANOVA). Crs also did not change significantly (mean 40.7, SD 17.8 mL/H2O at baseline; mean 33.6, SD 8.5 mL/H2O at 12 hours; and mean 55.4, SD 18.5 mL/cmH2O on day 5; P=.12 via ANOVA). A total of 36.8% (n=7) of the participants died (6 from secondary infection and sepsis >13 days after dosing). In total, 15.8% (n=3) of the patients experienced transient peridosing desaturation or surfactant regurgitation. Our study showed that intratracheal instillation of 1 to 2 doses of lucinactant in COVID-19-associated ARDS was generally well tolerated. There were no significant changes in oxygenation parameters or Crs. The data suggest that, when future studies of lucinactant in patients with ARDS with severe surfactant dysfunction are conducted, an earlier and longer treatment protocol using different delivery methods that reach a larger alveolar surface area, such as aerosolization, may be needed to yield any beneficiary effects.

Huang YC
Morris P
Owens R
Guardia C
Keller S
Belloso W
Weinstein L
Simmons P
Simonson S

Humans
Respiratory Distress Syndrome
Male
Female
Middle Aged
COVID-19
COVID-19 Drug Treatment
Aged
Pulmonary Surfactants
Fatty Alcohols
Proteins
Phosphatidylcholines
Glycerides
Treatment Outcome
Drug Combinations
Phosphatidylglycerols

Journal Article
Clinical Trial, Phase II
Multicenter Study
Clinical Trial, Phase I


The analgesic effect of ultrasound-guided fascia hydrorelease around the artery for myofascial neck pain: a prospective single-arm interventional study

Abstract: Myofascial pain syndrome (MPS) is a major cause of chronic neck pain, with tissue ischemia implicated as a contributing factor. This prospective, single-arm interventional study evaluated the analgesic effect of ultrasound-guided fascia hydrorelease (US-FHR) performed around arteries supplying the neck in patients with chronic neck MPS. Thirteen adults (median age 53.0 years; 38.5% female) underwent US-FHR targeting the perivascular fascia of either the transverse cervical or dorsal scapular artery using 2 mL of normal saline. Pain intensity was assessed by visual analog scale (VAS) at rest and during movement; disability by the 5-item Pain Disability Index, Japanese version (PDI-5-J); and arterial blood flow volume before and after the procedure. The primary outcome, pain VAS during movement, decreased from 49.0 mm (interquartile range [IQR], 44.5-64.0) at baseline to 22.0 mm (IQR, 14.5-31.5) at 15 min and 22.0 mm (IQR, 14.0-34.0) at 1 week (Hodges-Lehmann median difference, 30.5 mm [95% CI, 24.5 to 36.5] and 28.5 mm [95% CI, 18.5 to 37.0]; both P < 0.001). Pain VAS at rest improved from 21.0 mm (IQR, 13.0-43.5) to 8.0 mm at 15 min and 1 week (median difference, 14.5 mm [95% CI, 9.0 to 24.0; P = 0.001] and 13.5 mm [95% CI, 6.0 to 21.0; P = 0.007]). PDI-5-J decreased from 17.0 (IQR, 10.5-23.0) to 13.0 (IQR, 4.0-17.5) at 1 week (median difference, 5 [95% CI, 2-8; P = 0.004]). Blood flow volume increased from 11.2 mL/min (IQR, 4.5-14.4) to 17.2 mL/min (IQR, 6.1-23.7) immediately after US-FHR (median difference, + 4.1 mL/min [95% CI, + 2.5 to +8.9; P = 0.001]), although transient. One patient experienced transient bleeding that was promptly controlled. In this single-arm feasibility study, US-FHR around the target artery was simple and safe to perform and was associated with reduced neck pain. Because the study lacked a control group, these preliminary findings should be regarded as hypothesis-generating and require confirmation in controlled trials; they may also inform the future evaluation of MPS in other anatomical regions. Trial registration: UMIN Clinical Trials Registry, UMIN000053612.

Hiroki T
Kimura H
Kobayashi T
Horigome H
Suda M
Fukui S
Suto T
Obata H

Humans
Female
Neck Pain
Middle Aged
Prospective Studies
Male
Pain Measurement
Myofascial Pain Syndromes
Fascia
Adult
Ultrasonography, Interventional
Arteries
Treatment Outcome


Methodologic Standards for Follow-Up Extension in Cardiovascular Trials: A Scientific Statement From the American Heart Association

Abstract: Extension follow-up trials are essential for understanding the long-term safety and efficacy of cardiovascular interventions. Whereas primary randomized trials primarily capture short-term outcomes, extended observation may reveal delayed benefits or harms that are highly relevant to clinical decision-making. However, methodologic standards for extension trials remain poorly defined, leading to inconsistent design, analysis, and reporting. This scientific statement outlines best practices for cardiovascular trial extensions, addressing outcome selection, duration and completeness of follow-up, and analytic strategies suited to evolving treatment effects. Practical considerations, including strategies for participant retention, reconsent, data continuity, and resource allocation, are also discussed.

American Heart Association Leadership Committee of the Council on Clinical Cardiology

Council on Cardiovascular and Stroke Nursing

Council on Lifelong Congenital Heart Disease and Heart Health in the Young


A Multitask Deep Learning Model for Pediatric Echocardiography Analysis

Abstract: Congenital heart defects afflict ≈1% of all births worldwide. Although deep learning has shown significant promise in automating and improving adult echocardiography analysis, existing pediatric-based models are often limited to single tasks and specific echocardiographic views. To address this, we introduce EchoAI-Peds, a multitask deep learning model for pediatric echocardiography. Our model was developed using the most comprehensive set of pediatric labels to date and is designed to integrate information from multiple views simultaneously. We trained a video-based vision transformer to simultaneously detect 28 congenital heart defects, structural and functional abnormalities, repairs, and interventions directly from complete pediatric echocardiography studies with multiple videos. Our model was developed using >700 000 videos derived from >12 000 studies performed at Stanford Medicine between 2014 and 2021. Specifically, our model was trained on 10 815 studies (median age, 8 [IQR 2-14] years; 45% girls) and validated on 1294 studies (median age, 9 [IQR 2-15] years; 46% girls). Model efficacy was tested on an internal held-out data set of 1336 studies from that same period. In addition, model generalizability was tested on a spatially and temporally distinct patient cohort at the Children's Hospital of Philadelphia using 2121 studies performed between 2024 and 2025. Our model achieved macroaveraged (area under the receiver operating characteristic curve (AUROC) values of 0.91 (95% CI, 0.90-0.92) on the internal test set (median age, 8 [IQR 2-14] years; 47% girls) and AUROC values of 0.89 (95% CI, 0.88-0.90) on the external test set (median age 6 [IQR 0.92-13] years; 44.4% girls). Moreover, EchoAI-Peds significantly outperformed adult-based echocardiography foundation models trained on substantially larger data sets, including EchoCLIP (internal AUROC=0.58, 95% CI, 0.56-0.60; external AUROC=0.61, 95% CI, 0.59-0.62) and EchoPrime (internal AUROC=0.58, 95% CI, 0.57-0.61; external AUROC=0.60, 95% CI, 0.59-0.62). Finally, our model demonstrated robust performance across patient age, patient sex, and studies with varying number of videos. Our findings demonstrate the remarkable potential for multitask deep learning models to aid the interpretation of pediatric echocardiograms. In addition, our results underscore the need for models that are specifically tailored to pediatric populations.

Cho J
Mathur M
Kaur D
Duda M
Dahlan A
Krishnan A
Leipzig M
Shad R
Gonzalez AK
Logan J
Seidman C
Fong R
Kumar A
Zakka C
Carter E
Padiyath A
Jones A
Quartermain MD
Langlotz CP
Jolley MA
Hiesinger W


Risk-Guided Screening for Atrial Fibrillation Using Electronic Health Records

Abstract: Screening for atrial fibrillation (AF) on the basis of AF risk may be more effective. We aimed to develop, externally validate, and prospectively test a machine learning prediction model using electronic health records (EHRs) to guide AF screening. We developed and validated a random forest prediction model for new AF within 6 months, using age, sex, and 10 comorbidities (Future Innovations in Novel Detection of Atrial Fibrillation [FIND-AF] 2.0) in EHRs in the United Kingdom (n=2 081 139), Japan (n=7 795 244), Israel (n=2 166 795), Canada (n=627 919), and China (n=149 145). We conducted a prospective study where participants ≥30 years old without AF and with a CHA2DS2-VASc score ≥2 in men and ≥3 in women, stratified by FIND-AF 2.0 into high and low risk, undertook 4 ECG recordings per day for 3 weeks using a handheld ECG recorder, with a primary outcome of newly diagnosed AF. We estimated stroke risk associated with nonanticoagulated AF in patients with high FIND-AF 2.0 risk in the FinACAF (Finnish Anticoagulation in Atrial Fibrillation) registry of patients with AF (n=229 565). FIND-AF 2.0 was applicable to all EHRs and showed good to excellent prediction performance (United Kingdom: area under the receiver operating characteristic curve [AUROC], 0.819 [95% CI, 0.809-0.829]; Israel: AUROC, 0.835 [95% CI, 0.828-0.842]; Japan: AUROC, 0.751 [95% CI, 0.745-0.757]; Canada: AUROC, 0.747 [95% CI, 0.741-0.753]; China: AUROC, 0.753 [95% CI, 0.725-0.771]), with AUROC>0.7 in men and women in all cohorts, and improved performance compared with CHA2DS2-VASc and C2HEST. Of 1923 participants from 15 sites in the prospective study (mean age, 70.2 [SD 9.4] years), with a mean of 74.8 (SD, 19.4) ECG recordings, AF was diagnosed in 5 of 902 (0.6%) with low FIND-AF 2.0 risk and 46 of 1021 (4.5%) with high FIND-AF 2.0 risk (odds ratio, 8.46 [95% CI, 3.35-21.40], P<0.001). Median AF burden among high FIND-AF 2.0 risk-detected cases was 33.4% (interquartile range, 5.1%-91.6%), and 96.1% initiated oral anticoagulants. In the FinACAF registry, the rate of ischemic stroke for patients with high FIND-AF 2.0 risk, AF, and no anticoagulants was 6.0 events per 100 patient-years. The EHR-based machine learning model, FIND-AF 2.0, identifies a high-risk subpopulation for AF diagnosis among patients at elevated risk of stroke and could enable scalable, EHR-driven, risk-guided AF screening.

Nadarajah R
Wu J
Wahab A
Reynolds C
Haris M
Joseph T
Raveendra K
Hurdus B
Kazi K
Bennett S
Hayward C
Mercer B
Kang J
Gao C
Nakao YM
Kawakami K
Chang C
Wai A
Zhou J
Tse G
Benita TR
Rokach L
Arbel R
Haim M
Zahger D
Labib D
Flewitt J
White JA
Teppo K
Lehto M
Langén V
Winstén AK
Airaksinen KEJ
Haukka J
Halminen O
Putaala J
Hartikainen J
Linna M
Freedman B
Svennberg E
Camm AJ
Lip GYH
Gale CP


Cardiovascular-Kidney-Metabolic Syndrome: A User's Guide to the Guidelines


Telehealth for Community-Engaged Cardiovascular Care in Rural Populations


Letter by Zhang and Zhang Regarding Article, "Short-Term Anticoagulation Versus Dual Antiplatelet Therapy for Preventing Device Thrombosis Following Left Atrial Appendage Closure: The ANDES Randomized Clinical Trial"


2026 Cardiovascular-Kidney-Metabolic Guidelines: Practical Implementation Strategies


Cardiovascular-Kidney-Metabolic Syndrome: A Historic Perspective


Major Adverse Cognitive Events (MACE-Cog): A New "MACE" Framework for Cognitive Outcomes in Cardiovascular Diseases and Stroke

Abstract: Cardiovascular diseases, particularly stroke, are leading causes of dementia. Several common cardiac interventions such as coronary artery bypass grafting and transcatheter aortic valve implantation are also associated with cognitive decline. However, cognitive outcomes continue to be poorly collected in clinical trials of cardiovascular diseases. In this article, we review the limitations of current approaches to cognitive assessment in cardiovascular disease studies. When assessed, there is wide variation in cognitive tasks used, and tasks have limited population-specific validation, are subject to floor and ceiling effects, and may suffer from sociocultural and linguistic biases. Many tasks are not available in multilingual formats and often rely on face-to-face testing with trained coordinators. All conventional cognitive outcomes in cardiovascular trials are associated with substantial incompletion, especially among older and more impaired individuals, the very people most important to capture. This nonrandom missingness generates survivor and attrition biases, an unacceptable situation for any trial outcome. Last, the meaning of measured cognitive outcomes is often unclear for patients, caregivers, clinicians, and regulators. To help address these limitations, we propose a new framework, major adverse cognitive events (MACE-Cog), to better capture cognitive outcomes in stroke and other cardiovascular populations. As an inclusive construct reflecting the multidimensional nature of cognitive decline, major adverse cognitive events do not rely solely on performance on cognitive testing but also consider inability to complete cognitive testing due to cognitive-behavioral factors, reported symptoms of cognitive decline, impairment in activities of daily living as a result of cognitive impairment, new clinical diagnoses of dementia, and care home admission. We hope that the proposed composite outcome and multiple use cases presented spark progress in cardiovascular research toward more inclusive approaches to the study of cognitive outcomes that move beyond the confines of cognitive tests alone.

Ganesh A
Sujanthan S
Muir RT
Joundi RA
Hill MD
Quinn TJ
Menon B
Sajobi T
Rabin JS
Dainty KN
Barense MD
Lanctôt KL
Kennedy J
Kharbanda RK
Lee DS
Gaudio MFL
Fremes S
Masterson Creber RM
Smith EE
Swartz RH

Humans
Stroke
Cardiovascular Diseases
Cognition
Cognition Disorders
Cognitive Dysfunction


Response by Xu et al to Letter Regarding Article, "Geometric Features of Ventricular Tachycardia Corridors in Patients with Ischemic Cardiomyopathy"

Xu L
Hrybouski S
Ernie Liao TW
Dong J
Khoshknab M
Callans D
Marchlinski FE
Witschey WR
Desjardins B
Nazarian S


Agentic and Generative AI for Drug Discovery


Medial Arterial Calcification in a 4500-Year-Old Egyptian King: A Deep-Time View of a Vascular Calcification Continuum

Eppenberger P
Van Schaik KD
Hajdas I
Ibrahim M
Wood AE
Rühli F
Othman MM


Letter by Nayyar Regarding Article, "Geometric Features of Ventricular Tachycardia Corridors in Patients With Ischemic Cardiomyopathy"


Response by Rodés-Cabau et al to Letter Regarding Article, "Short-Term Anticoagulation Versus Dual Antiplatelet Therapy for Preventing Device Thrombosis Following Left Atrial Appendage Closure: The ANDES Randomized Clinical Trial"

Rodés-Cabau J
Nombela-Franco L
Pavesi M
Côté M
Salaun E


Letter by Li and Xiong Regarding Article, "Short-Term Anticoagulation Versus Dual Antiplatelet Therapy for Preventing Device Thrombosis Following Left Atrial Appendage Closure: The ANDES Randomized Clinical Trial"


Predictive Value of Coronary Artery Calcium Score From Nongated Chest CT Scans Compared With Gated Scans and Incidence of Cardiovascular Events

Abstract: Data on the prognostic value of incidental coronary artery calcium (CAC) from nongated chest computed tomography scans are limited. Using paired computed tomography scans from the MESA (Multi-Ethnic Study of Atherosclerosis) exam 5, we evaluated the relationship between nongated CAC, gated CAC, and future cardiovascular events. Between April 2010 and December 2011, a total of 2601 participants underwent same-day gated and nongated chest computed tomography scans. After excluding 106 with previous coronary heart disease or cardiovascular disease and 23 for missing covariates, 2472 participants formed the study population. Gated and nongated scans were interpreted at a core laboratory, blinded to acquisition methodology. Cox regression examined associations between CAC (gated and nongated) and incident coronary heart disease/cardiovascular disease events. Correlation was assessed with Pearson coefficients, model performance with receiver operating characteristic curves and C-statistic, and overall accuracy with Brier scores. Among the 2472 participants, 53% were female, 38% white, 13% Chinese, 26% Black, and 23% Hispanic/Latino. Compared with participants with zero CAC, those with moderate (101-299) and severe (≥300) nongated CAC had higher coronary heart disease risk (hazard ratio, 2.67 [95% CI, 1.14-6.27]; hazard ratio, 5.22 [95% CI, 2.37-11.5]) and cardiovascular disease risk (hazard ratio, 1.32 [95% CI, 1.32-4.04]; hazard ratio, 2.89 [95% CI, 1.68-4.96]). Gated and nongated log-standardized CAC highly correlated (r=0.961; P<0.001). The area under the receiver operating characteristic curves, C-statistic, and Brier scores were statistically similar for gated and nongated CAC. Nongated CAC predicts cardiovascular events with performance comparable to gated CAC. Given the large number of nongated scans performed annually, incorporating their quantification into clinical practice offers a scalable approach to personalized preventive care. Our findings are particularly relevant in light of the recent 2026 American College of Cardiology/American Heart Association dyslipidemia guidelines, which endorse the use of incidental CAC from nongated computed tomography scans for atherosclerotic cardiovascular disease risk stratification and guiding lipid-lowering therapy.

Verghese D
Trujillo R
Abraham D
McClelland RL
Kinninger A
Manubolu S
Aldana J
Cubeddu RJ
Drachman D
Inglessis-Azuaje I
Wang DD
Fahed A
Brumback L
Blaha MJ
Allison M
Budoff MJ

Humans
Female
Male
Aged
Predictive Value of Tests
Incidence
Tomography, X-Ray Computed
Coronary Artery Disease
Vascular Calcification
Aged, 80 and over
Middle Aged
Coronary Vessels
Risk Factors


Opportunistic Coronary Artery Calcium Screening: Time for Clinical Implementation


Contextualizing Results and Recommendations


Cardiovascular-Kidney-Metabolic Syndrome: Population and Policy Implications: 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome


Translational Cardiovascular Science for the Circulation Community


Association of Pulmonary Vascular Remodeling With Cardiac Structure and Function, Pulmonary Pressure, and Heart Failure in Late Life: The Atherosclerosis Risk in Communities (ARIC) Study

Abstract: Aging is associated with increases in pulmonary pressure related to concomitant age-associated left ventricular remodeling, diastolic dysfunction, and declines in pulmonary function. Little is known regarding morphological changes in the pulmonary arterial vasculature underlying these associations. Our aim was to determine the associations between pulmonary vascular arterial remodeling, reflected in distal pruning and proximal dilation, and cardiac structure and function, pulmonary pressure, and functional outcomes. Among 2275 participants in the community-based Atherosclerosis Risk in Communities study (ARIC) who underwent echocardiography and noncontrast cardiac computed tomography at study visit 7 (2018-2019), we quantified the fraction of total pulmonary vascular area comprised of arterial vessels with cross-sectional area <5 mm2 (aBV5/aTBV) and arterial vessels with cross-sectional area >10 mm2 (aBVg10/aTBV) using a validated image processing approach. We assessed the associations of aBV5/aTBV and aBVg10/aTBV with echocardiographic measures of cardiac structure and function and pulmonary artery systolic pressure using multivariable linear regression models adjusted for demographics and cardiovascular risk factors. We also evaluated associations of pulmonary vascular arterial remodeling metrics with circulating NT-proBNP (N-terminal pro-B-type natriuretic peptide), self-reported dyspnea, and incident heart failure. Mean age was 80±4 years, 61% were women, 22% reported Black race, and mean left ventricular ejection fraction was 64±7%. Mean aBV5/aTBV was 0.30±0.08, and aBVg10/aTBV was 0.45±0.09. Lower aBV5/aTBV, reflecting greater distal pruning, and higher aBVg10/aTBV, reflecting greater proximal dilation, were both associated with greater left ventricular remodeling, worse diastolic function, and worse systolic function. Lower aBV5/aTBV and higher aBVg10/aTBV demonstrated nonlinear associations with greater pulmonary artery systolic pressure. Both lower aBV5/aTBV and higher aBVg10/aTBV were associated with higher circulating NT-proBNP and greater odds of moderate to severe dyspnea. Higher aBVg10/aTBV, in particular, was associated with greater risk of incident heart failure over a 4-year follow-up with a hazard ratio of 1.25 (95% CI, 1.03-1.51) per one SD in aBVg10/TBV. Among older adults, pulmonary vascular arterial remodeling is associated with greater left ventricular remodeling, worse diastolic and systolic dysfunction, greater pulmonary artery systolic pressure, greater odds of significant dyspnea, and greater risk of heart failure development. Our findings clarify the morphologic changes in the pulmonary vasculature that link cardiac dysfunction to higher pulmonary pressure in late life and may appear before symptomatology.

Dewanjee A
Lamberson V
Yang Y
Giugni FR
Claggett BL
Matsushita K
Blaha MJ
Washko G
San José Estépar R
Nardelli P
San José Estépar R
Shah AM


Effects of a "Food Is Medicine" Intervention on Glucose Control Among Medicaid-Insured Patients With Type 2 Diabetes: A Randomized Controlled Trial

Abstract: Although medically tailored groceries (MTG) hold promise to improve food and nutrition security and health among patients with diet-related illnesses and social needs, few randomized trials have been performed. We enrolled 460 Medicaid-insured adults with type 2 diabetes and elevated hemoglobin A1c (HbA1c) between November 2021 and July 2022 in a randomized controlled trial of MTG in southern California. Eligibility was based on at least 2 HbA1c measurements ≥7.5% in the past year. Participants were randomized 1:1:1 to usual-care (N=153), lower-dose MTG (N=153), or higher-dose MTG (N=154) for 6 months, with the prespecified primary assessment comparing the combined MTG groups with control. MTG was provided as weekly home deliveries of healthy produce, scaled to household size ($100 to $170 per month for the lower dose and $135 to $210 per month for the higher dose), along with matched recipes and telenutrition counseling. The primary outcome was a change in HbA1c at 6 months. Secondary outcomes included changes in food security and nutrition security, measured by surveys, and hypertension and body mass index, measured during clinical care encounters; evaluation of dose-response comparing the lower-dose and higher-dose arms; and effects in key population subgroups. At baseline, mean (SD) age was 59.2 (13.2) years, 284 (64.8%) were women, 373 (85.2%) reported Hispanic ethnicity, 254 (58%) reported food insecurity, and mean (SD) HbA1c was 9.40 (1.53). Among intervention participants, 244 (83.3%) reported eating most or all food provided, and 63 (21.5%) engaged in telenutrition counseling. Compared with baseline, HbA1c declined by 0.66 points in the intervention and 0.25 points in the control group, a treatment difference of -0.40 points (95% CI, -0.73, -0.08; P=0.016). Higher-dose and lower-dose MTG produced similar reductions. Odds of food security and nutrition security increased by 2.12 (95% CI, 1.13, 3.99; P=0.020) and 3.65 (95% CI, 1.84, 7.25; P<0.001), respectively. Hypertension and body mass index did not significantly change. Results were consistent in prespecified subgroup analyses by sex, education, baseline food security, baseline nutrition security, and baseline HbA1c level. Findings were similar in analyses adjusting for baseline demographics, food insecurity, nutrition insecurity, self-reported health, comorbidities, and medication changes. In this randomized trial among Medicaid-insured, racially/ethnically diverse patients with type 2 diabetes, MTG lowered HbA1c and improved food and nutrition security. URL: https://clinicaltrials.gov; Unique identifier: NCT05407376.

Nau C
Wu JHY
Han B
Habib M
Li X
Padilla A
Nelson C
Chao C
Schwartz P
Mozaffarian D


Ethics of Navigating Organ Scarcity in Heart Transplantation


Diagnostic Approach to Cardiac Sarcoidosis

Abstract: Cardiac sarcoidosis is a granulomatous myocarditis, classified by some authorities as an infiltrative cardiomyopathy and by others as an inflammatory cardiomyopathy, that carries an elevated risk of life-threatening arrhythmias, heart failure, and sudden cardiac death. Despite its clinical importance, diagnosis remains challenging. No single modality achieves both high sensitivity and specificity, and the 4 major consensus documents-comprising expert consensus statements, clinical practice guidelines, and a scientific statement-differ in diagnostic thresholds and can yield discordant diagnoses when applied to the same patient. Genetic cardiomyopathies account for a meaningful fraction of patients diagnosed with presumed isolated cardiac sarcoidosis. This primer organizes the diagnostic approach around 2 clinical contexts: de novo cardiac presentation with unexplained atrioventricular block, ventricular arrhythmia, or heart failure without previous sarcoidosis; and cardiac screening in patients with established extracardiac sarcoidosis. In nonurgent presentations, concordant cardiac magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography abnormalities are accepted as sufficient for diagnosis; endomyocardial biopsy is indicated when imaging is inconclusive or giant cell myocarditis must be excluded. Advanced imaging should precede permanent device implantation in all de novo presentations. Isolated cardiac sarcoidosis represents the most diagnostically challenging phenotype. A 5-step pathway is presented that integrates advanced imaging, tissue acquisition when it would change management, and genetic evaluation. Expert opinion on histologic confirmation in nonurgent presentations is divided, and no diagnostic approach has been prospectively validated.

Humans
Sarcoidosis
Cardiomyopathies
Positron-Emission Tomography


Rapid Ultraoxygenated Recovery Without Preimplant Reanimation Using Older Donation After Circulatory Death Heart Donors

Williams AM
Wang CC
McGann KC
Trahanas J
Lima B
Ahmad A
Petrovic M
Absi T
Quintana E
England B
Schlendorf K
Bacchetta M
Shah AS
Bommareddi S


Cracking the Code of Cardiac ATP-Dependent Citrate Lyase With Wet and Dry Tools


Cold Oxygenated Rapid Recovery in Heart Donation After Circulatory Death

Bashian EJ
O'Shea TF
Campbell DN
Justison GA
Zhan J
Ambardekar AV
Kopecky BJ
Rove JY
Aftab M
Reece TB
Cleveland JC
Teman NR
Cain MT
Hoffman JRH


From Discovery to Impact in the Circulation Life Cycle


Stent-Free PCI: Have We Found the SELUTION?


Does Characterization of Phenotypic Heterogeneity Provide Mechanistic Insights or Influence the Response to Treatment? Experience in Positive and Neutral Trials in Patients With Heart Failure and a Preserved Ejection Fraction

Abstract: At a time when there was no unifying hypothesis and no broadly effective treatments for heart failure with a preserved ejection fraction (HFpEF), it was proposed that HFpEF represented a multitude of different disorders. Accordingly, characterization of phenotypic heterogeneity was envisioned as a means of identifying novel causal pathways that could lead to new treatments while simultaneously discerning patients who would selectively benefit from a specific therapy. However, efforts over the past decade to characterize phenotypic diversity in diverse and complex ways have not achieved these goals. Subgroup analyses of neutral HFpEF trials have failed to reliably identify responders to treatments. Neither proteomics nor unsupervised cluster analysis across multiple phenotypic domains has yielded reproducible results (even in the same dataset), elucidated novel mechanistic pathways for new drug development, or identified patients most likely to benefit from treatment. In marked contrast to these efforts to characterize phenotypic heterogeneity, large-scale trials in HFpEF enrolled patients using broad eligibility criteria, and they established the benefits of sodium-glucose cotransporter 2 inhibitors and mineralocorticoid receptor antagonists without evidence for subgroup effects. However, it is noteworthy that patients enrolled in recent large-scale HFpEF trials were characterized by general uniformity with respect to the presence of excess adiposity, with central obesity being a feature of the vast majority of enrolled participants. Of note, patients with obesity showed particularly large benefits when treated with effective drugs for HFpEF. These observations raise the possibility that, if these trials had permitted the participation of patients with class III obesity or with lower natriuretic peptide levels, the magnitude of the observed treatment effects might have been greater than originally reported. These findings are consistent with a central role for visceral adiposity (and the secretion of an altered suite of adipokines) in the pathogenesis of HFpEF. Therefore, because the field of HFpEF has a unifying hypothesis (applicable to the large majority of patients), enrolled a broad population of patients in large-scale trials without subgroup interactions, and has several broadly applicable effective treatments (as is true for heart failure with a reduced ejection fraction), the motivation to characterize phenotypic heterogeneity in HFpEF in complex ways may no longer be supported or needed.

Packer M
Schiattarella GG
Petrie MC
Burkhoff D
Butler J
Lam CSP
Zannad F
Vaduganathan M
Borlaug BA

Humans
Heart Failure
Stroke Volume
Phenotype
Treatment Effect Heterogeneity
Treatment Outcome
Clinical Trials as Topic