Intermittent binocular diplopia is challenging to assess, as symptoms may be absent during examination yet its possible causes range from benign decompensation to serious disease. We outline a practical method to evaluate intermittent diplopia, focusing on four key steps: (1) confirming binocular diplopia, (2) assessing monocular ductions to detect paretic or restrictive deficits, (3) determining comitance (whether the angle of strabismus is equal in all directions of gaze) to distinguish fusional from neurological or orbital causes and (4) evaluating fatigability to identify ocular myasthenia. We emphasise clinical scenarios requiring targeted testing, including giant cell arteritis and malignancy and discuss when orthoptic or ophthalmic referral is more appropriate than extensive neurological investigation. We also describe recognisable neurological entities such as ocular neuromyotonia and superior oblique myokymia. We aim to provide clinicians with an efficient method to assess intermittent diplopia, avoid unnecessary investigations and ensure that important pathology is not missed.
Extracorporeal membrane oxygenation (ECMO) provides lifesaving support for patients with cardiopulmonary failure but poses complex ethical challenges that may generate moral distress for clinicians, patients, and families. We convened a multidisciplinary panel of experts in cardiothoracic surgery, critical care, and palliative medicine to identify recurring ethical issues. The panel includes ECMO specialists working in the US, Canada, and the UK. The panel was nominated by organizers of a national critical care meeting. We analyzed four domains of ethical tension: 1) equitable ECMO candidacy decisions; 2) integration of palliative care and clinical ethics; 3) preservation of patient autonomy when institutional or benchmarking pressures influence care; and 4) responding to requests to continue ECMO when there is no exit strategy. Consensus recommendations emphasize transparent, team-based decisions, early involvement of ethics and palliative care, and consistent processes for ongoing review of candidacy and continuation of ECMO. Programs should recognize and mitigate institutional pressures that may undermine patient-centered care. As ECMO use expands, the development of ethical care frameworks is essential to ensure equity, uphold autonomy, and align treatments with patients' goals and values. This work provides a practical, consensus-based guide for addressing the ethical complexities of ECMO in contemporary critical care.
Pediatric Interventional Radiology (IR) is progressively expanding and gaining popularity as it provides minimally invasive procedures and treatments, with very good outcomes and low adverse event rates. The image-guided body procedures include central venous access, gastrointestinal procedures, such as gastrostomy tubes, biopsies of solid organs and tumors, pleural and abdominal drain placements, endovascular procedures, and embolizations. Pediatric patients who require IR are often medically complex and have significant pathophysiological derangements. Pediatric IR intersects with multiple specialties, including Oncology, Transplant, General Surgery, Genetic Metabolic Diseases, Neurology, and Infectious Diseases. Anesthesiologists play a key role in IR, ensuring safe and effective care, often under complex clinical circumstances. The purpose of this review is to outline key practical considerations in the anesthetic management of pediatric IR, in particular body procedures. We present aspects of the pre-procedure evaluation and preparation and an overview of the IR technique, including considerations about agents commonly used in radiology, and we describe peri-operative considerations, anticipated challenges, and potential complications. Anesthesiologists will learn about image-guided body procedures and peculiarities of the anesthetic management, expanding their familiarity, and gaining confidence with pediatric cases in the IR environment.
The application of chaos theory has positive results in different fields of science. Its nonlinear modeling properties and its vision of dynamic systems have enabled it to capture complex relationships in fields such as physics, financial econometrics, social systems and mathematical demography. This paper reviews the implication of chaos theory in the medical sciences. We carried out a systematic literature review under Cochrane’s international standards. A search strategy was executed with indexed terms (MeSH, DeCS and Emtree) that varied according to each database (Embase, MEDLINE, SciELO, LILACS). The PROSPERO registration number was CRD42023491407. In total, 2598 articles were retrieved, of which 20 were included. Algorithmic applications of chaotic systems were diverse. The medical fields with the largest studies were cardiology, neurology and oncology. The most used software was Matlab, however, in all cases, except one, we did not find open-source codes related to the studies. We found a wide heterogeneity in the studies reviewed, and this was reflected in the scope of research results. While some papers focus on proving the existence of chaotic behavior or understanding the nature of the phenomena being studied, others propose practical implications, such as in prescribing medicines and organizing health units. Not applicable. The online version contains supplementary material available at 10.1186/s42490-026-00111-0.
To advance the precise diagnosis and treatment of Parkinson's disease (PD) and related movement disorders, standardize the clinical application of integrated PET/MRI, enhance diagnostic efficacy, and optimize patient management, the Clinical Practice Guideline for Integrated PET/MRI in Parkinson's Disease (2026 Edition) was developed jointly by multiple expert groups. This initiative was led by the Chinese Society of Medical Imaging Technology, the Radiological Society of Chinese Medical Association, the Chinese Society of Nuclear Medicine, the Beijing Society of Nuclear Medicine, and the Beijing Society of Radiology, in collaboration with a multidisciplinary panel of experts from Nuclear Medicine, Radiology, Neurology, and Functional Neurosurgery, following several rounds of consensus meetings. Compared to previous consensus statements or technical specifications, the key updates of this guideline include: in the clinical application pathway, it clarifies the advantages and appropriate scenarios for utilizing integrated PET/MRI over single-modality imaging when the clinical diagnosis of PD is uncertain; it emphasizes the value of simultaneous acquisition and fusion analysis in assessing both the function of the nigrostriatal dopaminergic pathway (e.g., via PET tracers) and structural alterations (e.g., via MRI neuromelanin imaging, diffusion tensor imaging, etc.). With the development and validation of novel tracers, the guideline provides a hierarchical recommendation for the differential diagnosis between PD and atypical parkinsonian syndromes (such as multiple system atrophy, progressive supranuclear palsy, and corticobasal degeneration), based on multimodal imaging biomarkers. Based on the premise of the accessibility of current integrated PET/MRI equipment and tracers in China, and grounded in the latest international and domestic evidence-based research, this guideline is meticulously aligned with the realities of Chinese clinical practice. It systematically delineates the technical specifications, clinical indications, and image interpretation criteria for the use of integrated PET/MRI in the diagnosis, differential diagnosis, disease severity assessment, and therapeutic decision support for PD. The aim is to provide systematic and practical evidence-based guidance for clinicians and imaging specialists involved in the care of patients with Parkinson's disease. 为推进帕金森病及相关运动障碍疾病的精准诊疗，规范一体化PET/MRI在临床中的应用，提升诊断效能并优化患者管理，由中国医学影像技术研究会、中华医学会放射学分会、中华医学会核医学分会、北京医学会核医学分会、北京医学会放射学分会联合组织，集结核医学科、放射科、神经内科、功能神经外科等多学科专家，经多轮共识会议制订了《帕金森病一体化PET/MRI临床应用指南（2026版）》。相较于既往相关共识或技术规范，本指南的主要更新包括：在临床应用路径部分，明确了帕金森病临床诊断不确定时，一体化PET/MRI相较于单一模态影像的优势与适用场景；强调了在评估黑质-纹状体多巴胺能通路功能（如通过PET示踪剂）与结构性改变（如MRI神经黑色素成像、弥散张量成像等）时，同步采集与融合分析的价值。随着新型示踪剂的研发与验证，指南对帕金森病与非典型帕金森综合征（如多系统萎缩、进行性核上性麻痹、皮质基底节变性）的鉴别诊断流程给出了基于多模态影像标志物的分层推荐。本指南以我国现有一体化PET/MRI设备与示踪剂的可及性为前提，以国内外最新循证证据为依据，紧密结合中国临床实践现状，系统阐述了一体化PET/MRI在帕金森病诊断、鉴别诊断、病情评估及治疗决策支持中的技术规范、临床应用指征与影像解读标准，旨在为帕金森病相关临床与影像专业人员提供系统、实用的循证指导。.
The Ministry of Health Care of the Russian Federation develops on systemic basis the mechanisms designed to increase effectiveness of scientific research in interests of medicine and health care by means of identifying priorities called-for in practical medicine. The list of priorities, formed on the basis of analysis of opinion of experts, is freely available in branch segment of medical science at EGISU RD for use in planning applied scientific studies in interests of medicine and health care. The analysis of showcase of priorities demonstrates that it includes 24 priority areas and 351 priority directions of research and development. The TOP-5 priority areas include cardiology and cardiovascular surgery, neurosurgery, neurology and neuro-rehabilitation, psychiatry, surgery (including maxillofacial and dentistry), traumatology and orthopedics, infectious diseases and oncology. The key types of priorities in research and development in interests of medicine and health care are decreasing of mortality, incapacity and terms of temporary disability, increasing of life quality related to health, orphan diseases, technological trends, import substitution and market superiority (commercial availability). To transform priorities for applied scientific research from the industry segment of EGISU RD into priority topics for fundamental and exploratory research, the Ministry of Health Care of the Russian Federation has developed special classifier adapter. The system of priorities developed by the Ministry of Health Care of the Russian Federation is designed to form thematic directions which results of research and development will be in demand by medicine and health care, ensuring National technological sovereignty and strategic leadership in these industries. Минздравом России на системной основе создаются механизмы, призванные повысить результативность научных исследований в интересах медицины и здравоохранения посредством определения приоритетов, востребованных практической медициной. Перечень приоритетов, сформированный на основании анализа экспертных мнений, размещен в свободном доступе в отраслевом сегменте медицинской науки Единой государственной информационной системы учета результатов научно-исследовательских, опытно-конструкторских и технологических работ (ЕГИСУ НИОКТР) для использования при планировании прикладных научных исследований в интересах медицины и здравоохранения. Анализ Витрины приоритетов показывает, что она включает 24 приоритетные области и 351 приоритетное направление научных исследований и разработок. В топ-5 приоритетных областей входят кардиология и сердечно-сосудистая хирургия, нейрохирургия, неврология и нейрореабилитация, психиатрия, хирургия (в том числе челюстно-лицевая и стоматология), травматология и ортопедия, инфекционные заболевания и онкология. Ключевыми типами приоритетов исследований и разработок в интересах медицины и здравоохранения являются: снижение смертности, инвалидизации, сроков временной нетрудоспособности, повышение качества жизни, связанного с состоянием здоровья, орфанные заболевания, технологические тренды, импортозамещение и рыночное превосходство (коммерческая перспективность). С целью трансформации приоритетов для прикладных научных исследований из отраслевого сегмента ЕГИСУ НИОКТР в приоритетные тематики для фундаментальных и поисковых исследований Минздравом России был разработан специальный классификатор-переходник. Создаваемая Минздравом России система приоритетов предназначена для формирования тематических направлений, результаты исследований и разработок по которым будут востребованы медициной и здравоохранением, обеспечивая технологический суверенитет и стратегическое лидерство нашей страны в этих отраслях.
The distal-to-proximal pressure ratio (dpPR) has emerged as a superior indicator compared to the diameter stenosis rate (DSR) for assessing the functional severity of carotid artery stenosis (CAS). However, unlike DSR, dpPR cannot be directly determined by vascular imaging. In this study, we developed a hemodynamic modeling method to predict dpPR based on medical images available in clinical settings. A multiscale modeling method was employed to integrate a three-dimensional (3D) hemodynamic model of CAS into a lumped-parameter model of systemic hemodynamics, while incorporating patient-specific geometric information of large cerebral arteries derived from computed tomography angiography (CTA) images. The 3D modeling method was validated through in vitro fluid dynamics experiments, while the accuracy of the resulting multiscale model in predicting dpPR was evaluated by comparing model predictions with invasive pressure wire measurements. The model-predicted dpPR values for 27 carotid artery stenoses demonstrated strong agreement with invasive measurements, with a mean relative error of - 0.8% and a standard deviation of 2.5%. dpPR was only moderately correlated with DSR (r = - 0.55, p = 0.003). Further analysis revealed that the anatomical structure of the circle of Willis (CoW) is a major factor influencing the relationship between dpPR and DSR. Constructing a multiscale model based on CTA images provides a practical approach for assessing the hemodynamic impact of CAS. The significant influence of CoW's anatomical structure on the relationship between dpPR and DSR underscores the importance of considering systemic cerebral hemodynamics when evaluating the functional severity of CAS.
Studies of biological timekeeping have now matured from investigations of a fascinating and ubiquitous phenomenon into a discipline with practical applications; the excitement surrounding such translation has been overwhelming, perhaps at the expense of eclipsing further pursuit of basic research. Here we advocate that the ultimate success of applying chronobiological principles to address human and environmental needs will depend on the continued support of a robust agenda of fundamental research.
Traumatic foot wounds in patients with diabetes mellitus pose significant reconstructive challenges, especially when tendon exposure limits the feasibility of simple closure techniques and advanced microsurgical options are not available in low-resource settings. Platelet-rich plasma (PRP) is increasingly used as an adjunct to enhance wound bed quality by supporting tissue regeneration and vascularization, potentially improving the success of grafting procedures. We present the case of a 63-year-old man with type 2 diabetes mellitus who sustained a traumatic dorsal foot wound with exposed extensor tendons and was managed with serial wound care and three applications of activated PRP, resulting in progressive granulation tissue formation and improved vascularity. Definitive coverage was achieved using a manually harvested, fenestrated full-thickness skin graft (FTSG) from the medial aspect of the left arm in a resource-limited hospital setting, with primary closure of the donor site. A small central area of partial graft necrosis healed by secondary intention, and complete graft take was ultimately achieved. This case illustrates how PRP-assisted wound bed optimization can facilitate successful FTSG coverage of tendon-exposed traumatic defects in diabetic patients when more complex reconstructive options are unavailable, offering a practical solution in environments with limited resources.
Intravenous thrombolytic therapy significantly improves the prognosis of patients with acute ischemic stroke in a time-dependent manner. This study aims to evaluate the effectiveness of hospital process reengineering in reducing delays to intravenous thrombolysis in patients with acute ischemic stroke. This multicenter, prospective, nonrandomized quasi-experimental (pre-post) study included patients with acute ischemic stroke presenting within 3.5 h of symptom onset. Hospital process reengineering involved key measures such as pre-notification by emergency medical services, simultaneous activation of a multidisciplinary team, standardized communication, and regular feedback to streamline workflows. Data from pre-intervention (July 1-September 30, 2014, Q1) were compared to post-intervention (October 1, 2014-June 30, 2015, Q2-Q4). The primary outcomes included the door-to-needle time and its changes, the proportion of patients receiving intravenous thrombolysis, and the percentage of patients achieving a door-to-needle time <60 min. A total of 2,059 acute ischemic stroke patients were included, with 535 in the pre-intervention period and 1,524 in the post-intervention period. Following the intervention, the median door-to-needle time significantly decreased from 73 to 63 min (p = 0.001); however, the thrombolysis rate remained statistically unchanged, with rates of 63.0% pre-intervention and 63.5% post-intervention (p = 0.849). Moreover, when the post-intervention period was subdivided into three quarters (Q2-Q4), there was a consistent downward trend in the median door-to-needle time (P for trend = 0.001). In addition, the percentage of patients achieving a door-to-needle time of less than 60 min increased from 31.5 to 40.5% (p = 0.003). Hospital process reengineering significantly improved door-to-needle time, highlighting the importance of optimizing workflows in acute stroke care. Although this study was conducted a decade ago, its findings continue to offer valuable insights and practical implications for underdeveloped regions and countries. Clinicaltrials.gov, NCT02631317 (https://clinicaltrials.gov/study/NCT02631317).
This study investigated the feasibility, reliability, and validity of abbreviated versions of four neurocognitive tasks-typically used to assess attention, working memory, and executive functions (i.e., the Oddball, n-Back, Stroop, and Flanker tasks). To reduce the effects of response variability and physiological noise, neurocognitive assessments typically require numerous stimulus trials per task, causing each task to often exceed 20 minutes in duration. Such long durations can contribute to participant fatigue and practical constraints, especially when multiple neurocognitive tasks are administered in a single session to evaluate neurocognitive performance across domains. To address this, we evaluated whether abbreviated versions of the tasks-each limited to a maximum duration of four minutes-could serve as reliable alternatives. A total of 57 healthy young adult participants completed the four aforementioned tasks administered through a custom-built, cross-platform mobile application. Response accuracy and reaction times were then analyzed to assess cognitive performance. Statistical analyses confirmed significant expected effects between different stimuli and experimental conditions within each task. Moreover, high split-half intraclass correlation coefficients (ICCs) indicated excellent internal consistency, demonstrating that the abbreviated versions yielded stable and reproducible results across all tasks. These findings support the use of the presented abbreviated tasks as efficient proxy measures for defined facets of executive functions, offering practical alternatives without compromising data integrity.
Progression Independent of Relapse Activity (PIRA) is a critical measure of disability progression in multiple sclerosis (MS) independent of relapses but lacks a standardized definition. Current reliance on the Expanded Disability Status Scale (EDSS) limits sensitivity to non-motor domains, necessitating a stratified framework to enhance detection and guide management. To develop a novel seven-level stratified PIRA definition and assess its validity, enhanced sensitivity, clinical relevance, and feasibility through expert consensus, and propose a simplified framework based on feedback. A two-stage study: (1) A four-expert panel developed a seven-level PIRA framework (PIRA 1: EDSS-based; PIRA 2: EDSS-plus measures; PIRA 3: stress tests; PIRA 4: patient-reported outcomes [PROs]; PIRA 5: conventional MRI; PIRA 6: advanced MRI; PIRA 7: biomarkers) via literature synthesis. (2) A survey of 90 MS experts (26 responded, 28.9%) from nine countries evaluated each level's validity, sensitivity (vs. EDSS), relevance, and feasibility (1-5 scale), with open-ended comments on barriers and suggestions. High agreement was defined as a score ≥ 4. Qualitative feedback on barriers and improvement suggestions was thematically analyzed. Strong support (24/26; 92.3%) endorsed a stratified PIRA definition. Respondents included primarily clinician-researchers (22/26; 84.6%), with 11/26 (42.3%) reporting more than 20 years of MS experience. High agreement for validity ranged from 15/26 (57.7%) for PIRA 1-23/26 (88.5%) for PIRA 6. Agreement regarding enhanced sensitivity was highest for PIRA 2 (25/26; 96.2%), followed by PIRA 6 (22/26; 84.6%) and PIRA 5 (19/26; 73.1%). Clinical relevance was rated highly for PIRA 1, PIRA 2, and PIRA 6 (each 25/26; 96.2%). Feasibility was highest for PIRA 1 (24/26; 92.3%) and declined for higher levels, particularly PIRA 7. Barriers included inter-rater variability (PIRA 1, 30.8%), subjectivity (PIRA 4, 23.1%), and cost/expertise (PIRA 6-7, 26.9% each). Suggestions included digital tools (PIRA 2-3), AI for MRI (PIRA 5-6), biomarker validation (PIRA 7), and combining PIRA 5-6. PIRA 1-2 were preferred for clinical practice, PIRA 5-7 for research. A three-tier framework was proposed: Probable PIRA (clinical), Definite PIRA (clinical + MRI), and Definite PIRA Plus (clinical + MRI + biomarkers). The proposed seven-level PIRA framework demonstrates strong expert support for its conceptual validity and clinical relevance but highlights feasibility challenges for advanced assessments. A simplified three-tier model may provide a practical structure for standardized evaluation of relapse-independent progression in MS. Further empirical validation in diverse clinical cohorts is required.
Early identification of neurodegenerative disorders in older adults remains a major challenge in geriatric clinical practice. Olfactory dysfunction is a common feature of several neurodegenerative disorders, particularly synucleinopathies, where it often precedes motor and cognitive symptoms, whereas in primary tauopathies olfactory function is usually preserved or only mildly impaired. This study aimed to evaluate the diagnostic utility of the 12-item Sniffin' Sticks Test (SST-12) for identifying neurodegenerative disease in older adults. A total of 120 individuals were included: 72 with synucleinopathies, 23 with tauopathies, and 25 healthy controls. Olfactory function was assessed using the SST-12. Group differences were analyzed using ANOVA, Fisher's exact test, and post hoc procedures. Diagnostic accuracy was evaluated by ROC analysis. Anosmia occurred in 58.3% of synucleinopathy patients and 65.2% of tauopathy patients but was absent in controls (p < 0.0001). Women performed better on several items, while an age effect was observed only for odor T5 (banana) (p = 0.011). Subjective olfactory complaints had limited diagnostic value. The full SST-12 showed good accuracy in distinguishing patients from controls (AUC = 0.818; 95% CI 0.744-0.891). A shortened nine-odor version achieved slightly higher accuracy (AUC = 0.844; 95% CI 0.777-0.912). No significant difference was observed between synucleinopathies and tauopathies, including after adjustment for age and sex. These findings support the clinical usefulness of brief olfactory testing in older adults and highlight the potential of selected odor subsets to improve screening efficiency. The SST-12 is a sensitive and practical tool for detecting olfactory dysfunction in neurodegenerative disorders. Brief olfactory screening may represent a useful addition to routine geriatric assessment.
To integrate current evidence and expert consensus on safe, effective exercise prescription in Duchenne and Becker muscular dystrophy (DMD/BMD), translating key pathophysiological principles into practical clinical guidance. Proceedings from the June 2025 Parent Project Muscular Dystrophy meeting, Translating Exercise Research in Dystrophinopathy to the Clinic, were synthesized. Faculty reviewed dystrophinopathy pathology and exercise physiology, analyzed data from clinical trials and pilot studies, summarized outcome-measure selection, and discussed pragmatic solutions to overcome barriers. Through interactive discussion, expert opinion on clinical management was aligned with exercise prescription frameworks (FITT) and clinic resources. Exercise modality and dosing are understudied in dystrophinopathies yet represent critical factors for safe and effective interventions. In DMD, assisted low-intensity cycling can stabilize function and moderate isometric protocols can increase strength without evidence of injury. In BMD, aerobic training and supervised low-intensity resistance generally improve fitness/strength, whereas high-intensity loads may pose risks. Pragmatic assessments support monitoring and anticipatory care. Individualized prescriptions, supervised onboarding, and social engagement may mitigate dosing uncertainty, equipment access, and adherence barriers. The clinical framework should emphasize movement observation, postural strategies, oculomotor and cognitive-motor screening, and documentation for insurance coverage. Safety guidance emphasizes physician clearance, submaximal dosing, fatigue management, and clear "red flag" escalation pathways. Contemporary data and expert consensus support integrating conservative, systematically monitored exercise as an essential adjunct to DMD/BMD care. Available evidence indicates low-to-moderate aerobic activity and moderate-intensity isometric exercise appear feasible and safe when individualized and supervised. Further controlled studies should refine dosing and strengthen disease-stage-specific guidance.
Developmental and epileptic encephalopathies (DEEs) are a group of pediatric seizure syndromes, accompanied by developmental delay or regression and cognitive, psychiatric, and/or behavioral impairment. Seizures can be frequent and are typically refractory to treatment with antiseizure medications. In addition to the high burden of disease endured by patients, DEEs are also associated with negative psychosocial impacts and reduced quality of life for parents and caregivers. Stiripentol is an antiseizure medication approved for the treatment of seizures associated with Dravet syndrome in children 6 months of age and older currently taking clobazam. Early studies in children with drug-resistant seizures provided preliminary evidence of the efficacy and safety of adjunctive stiripentol in seizure syndromes other than Dravet syndrome. These studies have since been followed by additional studies in cohorts of children with different DEEs, as well as studies in children with a specific non-Dravet DEE diagnosis, which have demonstrated association of add-on stiripentol treatment with improvements in seizure control, increased rates of seizure freedom, reductions in rates of status epilepticus, and, in a few studies, improvements in cognitive outcomes. Given stiripentol's favorable safety and tolerability profile, these results suggest a potential role of stiripentol in the treatment of refractory patients with DEE. The purpose of this paper is to review the available evidence of the efficacy and safety of stiripentol in children with non-Dravet DEEs. Practical considerations regarding the use of stiripentol in clinical practice to treat pediatric patients with DEE will also be discussed.
Changes to the relative abundance of amyloid-beta (Aβ) peptides are hallmarks of Alzheimer's disease. Induced pluripotent stem cell (iPSC)-derived neurons offer a physiological model of Aβ production. We employed unbiased, data-driven analyses to investigate combinations of Aβ peptides as Alzheimer's disease biomarkers and the relative contribution of peptides to Alzheimer's disease pathogenesis. We measured Aβ37, Aβ38, Aβ40, Aβ42 and Aβ43 in 10 iPSC-neuronal cultures from PSEN1 mutation carriers. We combined these data with published cell model data and used linear weighted combinations to (i) distinguish Alzheimer's disease from controls, and (ii) predict age-at-onset for PSEN1 mutations. Data-driven approaches distinguished Aβ42 and Aβ43 from shorter peptides, providing unbiased evidence for a greater association of Aβ42 and Aβ43 to disease pathogenesis, compared with shorter peptides (Aβ37, Aβ38 and Aβ40). Weighted linear combinations of Aβ peptides outperform Aβ42/40 and provide insights into relative peptide contribution as biomarkers. A representative weighted composite value ratio (wCVR) derived from all data, balancing both disease classification and age-at-onset prediction, was ( 21 ⋅ A β 37 + 10 ⋅ A β 38 + 69 ⋅ A β 40 ) /   ( 94 ⋅ A β 42 + 6 ⋅ A β 43 ) . This work suggests a practical non-parametric harmonization approach to employing Aβ ratios as biomarkers for Alzheimer's disease, from multiple sites and assays. Building on this foundation, we applied a new model using weighted composite value ratios, which outperform existing biomarkers across all tasks. This underscores the value of integrating multiple peptides and assigning optimized weightings. The study confirms the association of Aβ42 and Aβ43 with Alzheimer's disease pathogenesis in a data-driven manner. Peptide weights further provide mechanistic insights into the relative contribution of each peptide to disease, such as a greater contribution of Aβ37 compared to Aβ38. The algorithm used herein can be further refined to improve biomarkers for Alzheimer's disease.
Disseminated histoplasmosis remains a major cause of morbidity and mortality among people living with advanced HIV disease (AHD), particularly in Latin America, where delayed diagnosis and limited access to optimal antifungal therapy persist. Accurate tools to assess disease severity and predict mortality are essential to guide clinical decision-making, including hospitalization, intensive care unit admission, and treatment strategies. We conducted a retrospective observational cohort study of hospitalized adults with AHD (CD4 ≤ 200 cells/mm³) and a first episode of probable or proven disseminated histoplasmosis at a tertiary referral center in São Paulo, Brazil, between 2013 and 2023. Disease severity at admission was assessed using four tools: the World Health Organization (WHO) severity classification, the Histoplasmosis Fatality Score (HFS), the Sequential Organ Failure Assessment (SOFA), and the quick SOFA (qSOFA). The primary outcome was in-hospital mortality. Eighty-nine individuals were included; most were male (77.5%), with a median age of 39 years and profound immunosuppression (median CD4 count 24 cells/mm³). In-hospital mortality was 34.8%. Individuals who died had significantly higher HFS and SOFA scores. In multivariable analysis, HFS, SOFA score, and serum creatinine were independently associated with in-hospital mortality, whereas qSOFA was not. HFS showed the best discriminatory performance (AUC 0.798; 95% CI 0.707-0.889). The combination of HFS and elevated creatinine further improved discrimination, outperforming the WHO classification, SOFA, and qSOFA in predicting in-hospital mortality. These findings support the use of HFS as a practical and reliable tool for stratifying disease severity, optimizing resource allocation, and guiding clinical decision-making in high-burden settings. In-hospital mortality due to disseminated histoplasmosis in HIV individuals reached 34.8% in our cohort. The Histoplasmosis Fatality Score, combined with creatinine level, had the best discriminatory performance to predict mortality, then it can be applied to guide severity stratification and clinical decisions.
Lumbar puncture (LP) is an essential tool in everyday clinical neuropsychiatric practice. It has been demonstrated that, among junior doctors, the procedure is associated with elevated levels of stress and anxiety, which can ultimately result in patient suffering. Notwithstanding the evident challenges, innovative teaching methodologies have not yet become a standard in daily clinical practice, despite the existence of different LP simulators. The prospective case-control study comprised 20 undergraduate medical students who participated in a tutorial that encompassed both theoretical knowledge and practical training regarding LP, utilizing a simulation model ("tutorial group"). Twenty-one students who were instructed in LP technique according to teaching methods from everyday clinical practice were used as controls ("control group"). A questionnaire was administered to all students, enquiring about confidence levels, theoretical knowledge, and their proficiency when handling the puncture needles. Moreover, the success rate in performing their initial 4 LPs was measured. The students in the tutorial group demonstrated significantly higher success rates in performing their first 4 LPs (median 3 vs. 1, p < 0.001). Furthermore, confidence levels and safety when handling the puncture needles were significantly higher in the tutorial group, as well as knowledge regarding theoretical backgrounds. Higher confidence and safety in needle handling were strongly associated with a higher success rate. Short simulator-based tutorials have been shown to be an effective method of increasing the skills of young physicians and students in LP, and thus enhancing patient safety. Analogous approaches should be implemented on a large scale in medical education.
This review offers information and practical guidance for professionals who care for patients with disorders of gut-brain interaction (DGBI). It summarizes evidence-based psychosocial approaches for adult and pediatric populations, organized into 4 sections: background, assessment, management, and training. The review begins by establishing a biopsychosocial framework, highlighting the bidirectional influences of biological and psychosocial factors on gut physiology and brain mechanisms. It then outlines key assessment strategies, including targeted patient interview questions and guidance on interpreting responses followed by empirically supported psychosocial treatments suitable for integrated and standalone care settings. The final section presents curriculum recommendations for providers in DGBI-specific psychosocial care. Emphasizing the brain-gut axis and the importance of the patient-provider relationship, this review underscores the need for accurate psychosocial assessment and contextually informed intervention. It concludes with future directions for training and research to enhance clinical outcomes in this complex and multifaceted domain.
Chronic migraine is a debilitating disorder characterized by central sensitization and impaired habituation. Although OnabotulinumtoxinA (OnabotA) is an established preventive treatment, its precise mechanism of action and predictors of therapeutic response remain elusive. In this prospective cohort study, we integrated clinical parameters with algometric assessments, a recognized tool for evaluating peripheral sensitization, to develop machine learning-based predictive models to forecast migraine treatment response and effectiveness. Seventy-six patients underwent comprehensive clinical evaluations and pressure pain threshold measurements. Key clinical and algometric variables were identified using a feature selection algorithm and incorporated into linear regression models for continuous outcomes (reductions in migraine days, headache days, symptomatic medication use, and triptan use) and an ordinal logistic regression model for categorical treatment response considering percentage of decrease in headache days (three classes: Low (<50%), moderate (50-75%), and high (>75%) responders). The linear regression models yielded significant correlations, exemplified by a reduction in migraine days (ρ = 0.762, RMSE = 5.70) and symptomatic medication days (ρ = 0.503, RMSE = 7.84). Similarly, the ordinal logistic regression model achieved an overall accuracy of 56.6% to predict treatment effectiveness (κ = 0.334 for three classes), as well as 71.1%, 64.5%, and 77.6% accuracies to predict high, moderate, and low OnabotA response. Notably, incorporating algometric data significantly enhanced predictive performance compared to models based solely on clinical variables. These findings support the potential of combined clinical and algometric evaluation as a practical biomarker for optimizing OnabotA therapy in chronic migraine, warranting further validation in larger, multicenter studies.