To explore the value of handheld simplified venous excess ultrasound (VExUS) grades in bedside venous congestion assessment in general intensive care unit (ICU) patients and to examine its associations with disease severity scores and fluid overload indicators. This study was a secondary analysis based on data from a single-center prospective observational ICU cohort database. The data were derived from the existing ICU cohort database of the ICU of China-Japan Friendship Hospital. The original study included critically ill patients admitted to the ICU of China-Japan Friendship Hospital from June 14 to August 21 in 2024, all of whom underwent handheld ultrasound and conventional ultrasound VExUS-related examinations. Demographic data, severity of illness scores, laboratory indicators, fluid balance, and supportive treatment information were also collected simultaneously. The main ultrasound variables included the handheld simplified VExUS grading and its key component parameters (inferior vena cava short-to-long axis ratio, hepatic vein S/D ratio, and portal vein pulsatility fraction). Descriptive analysis was used to evaluate the overall distribution of handheld simplified VExUS indicators. Spearman rank correlation analysis was employed to evaluate the relationship between the handheld simplified VExUS grading and its key component parameters with the Acute Physiology And Chronic Health Evaluation II (APACHE II) score, Sequential Organ Failure Assessment (SOFA) score, N-terminal pro-brain natriuretic peptide (NT-proBNP), and fluid balance within 24 hours after ICU admission. The differences in clinical indicators among patients with different handheld simplified VExUS grading were compared, and the primary analysis of continuous ultrasound parameters employed the post-hoc mean values of independent measurements taken by two operators, and sensitivity analysis was conducted separately using the original measurements of the two operators. Multiple comparison correction for the primary correlation analysis was performed using the Benjamini-Hochberg false discovery rate (FDR). The original study included a total of 80 critically ill patients. After excluding 2 minor patients from this study, a total of 78 adult patients were finally included in the overall analysis. The overall disease severity of the 78 adult ICU patients was moderate, with an APACHE II score of 20.0 (15.3, 25.0) and a SOFA score of 7.0 (4.0, 11.0). The handheld simplified VExUS grading was mainly at grades 0 and 1, with 48 cases (62%) at grade 0, 26 cases (33%) at grade 1, and 4 cases (5%) at grade 2. The average values of the inferior vena cava short-to-long axis ratio, hepatic vein S/D ratio, and portal vein pulsatility fraction were 0.763 (0.668, 0.809), 1.358 (1.252, 1.571), and 0.243 (0.180, 0.303), respectively. In the primary correlation analyses, the mean inferior vena cava short-to-long axis ratio was positively correlated with APACHE II score and SOFA score (r values were 0.302 and 0.252, with unadjusted P values of 0.007 and 0.026, respectively), while portal vein pulsatility fraction was positively correlated with 24-hour fluid balance (r=0.290, unadjusted P value was 0.010). However, no significant correlation was observed between the handheld simplified VExUS grading and either the severity of illness scores or the volume overload indices. After Benjamini-Hochberg FDR correction, the correlation between the mean inferior vena cava short-to-long axis ratio and both the APACHE II score and the SOFA score did not reach statistical significance (FDR-corrected P values were 0.080 and 0.139, respectively). Similarly, the correlation between the mean portal vein pulsatility fraction and 24-hour fluid balance also failed to maintain statistical significance (FDR-corrected P value was 0.080). After stratification by the simplified handheld VExUS grading, there were no statistically significant differences in APACHE II score, SOFA score, NT-proBNP level, and 24-hour fluid balance among patients with different grades (all P>0.05). A sensitivity analysis was conducted using the original measurements from two operators on the core pairs with original correlation signals in the main analysis, and the results were largely consistent with the main analysis. However, the previously observed associations did not remain statistically significant after Benjamini-Hochberg FDR correction. In general ICU patients, the handheld simplified VExUS grade showed limited associations with disease severity scores and volume overload indicators. Some key component parameters showed exploratory signals related to disease severity or fluid balance in the original correlation analysis, but did not maintain statistical significance after FDR correction.
Japan has developed one of the world's most established population-based gastric cancer screening systems through more than six decades of continuous refinement in public health policy, technological innovation, and quality assurance. This review summarizes the historical development, technological evolution, quality assurance framework, and future perspectives of gastric cancer screening in Japan, while providing comparisons with major gastric cancer screening programs and prevention initiatives worldwide. Japanese gastric cancer screening can be traced to the postwar adaptation of mass tuberculosis radiographic screening systems, followed by the nationwide implementation of double-contrast upper gastrointestinal radiography. Subsequent advances in gastrointestinal endoscopy, including high-resolution imaging, magnifying endoscopy, and image-enhanced endoscopy, have facilitated the transition toward endoscopic screening and improved early gastric cancer detection. Japan has also established highly standardized quality assurance systems, including structured training, credentialing, standardized examination protocols, defined quality indicators, and continuous program monitoring of screening performance. These efforts have supported the standardization and continuous quality improvement of population-based gastric cancer screening programs. The incidence and risk-factor profile of gastric cancer are changing rapidly because of declining Helicobacter pylori prevalence, population aging, and increasing recognition of Helicobacter pylori-naïve gastric cancer. Consequently, future screening systems will likely require greater incorporation of personalized risk stratification, optimized allocation of endoscopic resources, and emerging technologies such as artificial intelligence-assisted endoscopy and structured digital quality assurance systems. Japan's experience provides a valuable case study illustrating how quality assurance, technological innovation, and public health infrastructure can be integrated to support population-based gastric cancer screening. Gastric cancer remains a major health problem in many parts of the world. Japan has one of the longest-running and most successful national gastric cancer screening programs, developed through more than 60 years of continuous improvement. This review explains how the program has evolved, why it has been successful, and what lessons it may offer to other countries. Japan first introduced gastric cancer screening by adapting X-ray screening programs that had originally been created to detect tuberculosis. As medical technology advanced, screening gradually shifted from X-rays to endoscopy, a procedure in which a small camera is used to examine the inside of the stomach. Improvements in imaging technology have made it easier to find cancer at an earlier and more treatable stage. An important reason for the success of the Japanese program is its strong focus on quality. Healthcare professionals receive standardized training, follow carefully designed examination procedures, and regularly monitor the quality of screening. These measures help ensure that people receive accurate and reliable examinations. The population at risk of gastric cancer is now changing. Fewer people are infected with Helicobacter pylori, a bacterium that has long been the main cause of stomach cancer, while the population is aging and new types of gastric cancer are being recognized. As a result, future screening programs will need to better match screening methods to each person's level of risk, use medical resources more efficiently, and take advantage of new technologies such as artificial intelligence. Japan's experience demonstrates how long-term public health planning, technological advances, and careful quality management can work together to improve cancer screening and may provide useful guidance for countries seeking to strengthen their own screening programs.
To systematically map and synthesize the current evidence on the application of bedside ultrasound in the assessment of gastrointestinal function and the guidance of enteral nutrition in critically ill patients, and to explore its clinical value and future perspectives. PubMed, Web of Science, Embase, Scopus, China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database, Chinese Medical Journals Database, and Chinese Biomedical Literature Database were searched from inception to September 4, 2025 for studies on bedside gastrointestinal ultrasound. After removing duplicate literature using EndNote X9 software and the Rayyan online literature screening platform, the articles were independently screened and cross-checked by two researchers. The following data were independently extracted by two researchers: years, country, study type, study population and sample size, grouping criteria and inter-group comparison factors, assessment protocol, ultrasound scanning protocol and results, and outcome indicators. The Newcastle-Ottawa Scale (NOS) was used to evaluate the methodological quality of included case-control studies and cohort studies, and the Cochrane Risk of Bias tool (RoB 2) was used to evaluate the methodological quality of randomized controlled trials. Through comprehensive analysis of the included literature, the application characteristics and clinical significance of bedside ultrasound in gastrointestinal dysfunction assessment and enteral nutrition implementation in critically ill patients were analyzed. Descriptive grouping and visual methods were used to conduct a variability analysis of the included studies. The studies were categorized according to study design and ultrasound assessment methods. A total of 2 023 records were retrieved, and 36 studies were finally included after deduplication and screening. Included studies were published between 2019 and 2025, and comprised 19 randomized controlled trials, 15 case-control studies, and 2 cohort studies. The quality of case-control studies and cohort studies was evaluated as relatively high overall, while bias risks in randomization process and outcome reporting were found in some randomized controlled trials, with overall moderate quality and generally acceptable risk of bias. The main ultrasound assessment protocols were identified as gastric antral cross-sectional area (CSA), gastric antral motility index (MI), superior mesenteric artery (SMA) blood flow parameters, Acute Gastrointestinal Injury Ultrasound Score (AGIUS), Gastrointestinal and Urinary Tract Sonography (GUTS) score, and combined protocols. By comprehensive analysis of included studies, gastric antral CSA was found to accurately reflect gastric emptying and feeding tolerance, and high feasibility was demonstrated in predicting feeding intolerance and feeding achievement rate; gastric antral motility could be quantified by gastric antral MI, but its clinical application was limited by complex operation and fluid management. Intestinal structure and function could be objectively evaluated by AGIUS and GUTS scores, and high sensitivity and specificity in predicting 28-day mortality were demonstrated by AGIUS score≥2. Gastrointestinal structure, motility, and perfusion status could be comprehensively reflected by the gastric antral CSA combined with intestinal ultrasound protocol, and the diagnostic accuracy of acute gastrointestinal injury (AGI) and the success rate of enteral nutrition were improved. As a noninvasive and repeatable assessment tool, bedside ultrasound provides valuable support for gastrointestinal monitoring and nutritional management in critically ill patients. However, the current body of evidence still has issues such as inconsistency in parameter selection, lack of standardization in measurement methods, and variability in operational procedures. Future multicenter, large-scale studies are warranted to establish unified assessment frameworks and enable precise and dynamic gastrointestinal management.
With the advent of telecommunication services, dental consultation has advanced from the mere use of telephones to the use of digital imaging and the internet to provide consultation, exchange health information, and maintain electronic health records beyond borders for increased efficiency of dental healthcare delivery to patients. To assess dental professional's perception, attitude, and practice of teledentistry in rural areas of Belagavi district, Karnataka, India. A cross-sectional survey comprising of 450 participants was conducted among dental professionals, which included dental interns, postgraduate students, faculty members of dental colleges, consultants, and private practitioner who works at rural areas of Belagavi district. A 16-item validated questionnaire containing four domains of professional demographic data, perception, attitude, and practices was distributed among the participants. Descriptive analysis was done using IBM SPSS software (Version 20.0, Chicago, Illinois, United States). The level of significance was set at p < 0.05. It was found that 52% of dental professionals had low levels of perception. However, levels of attitude and practice were found to be high. When correlation between perception, attitude, and practice was carried out using Pearson's correlation coefficient, a positive correlation was seen between attitude and practice (p = 0.0001∗). The majority of dental professionals exhibited low perception levels but demonstrated high levels of attitude and practice. The effective implementation of teledentistry could usher in a new era of dental healthcare delivery, improving oral health among rural populations.
Methamphetamine-associated heart failure with reduced ejection fraction is a serious consequence of methamphetamine use often underrecognized in the emergency department (ED). Point-of-care ultrasound (POCUS) offers rapid, non-invasive cardiac screening for high-risk populations. This study evaluated the diagnostic yield of POCUS for detecting methamphetamine-associated heart failure with reduced ejection fraction in ED patients who use methamphetamine. We conducted this prospective cohort study between December 2020-February 2024 at an urban Level I trauma center ED. The primary outcome was diagnostic yield of cardiac POCUS for abnormal left ventricular ejection fraction (LVEF) and abnormal sex-specific left ventricular end-diastolic diameter in patients with methamphetamine use, with secondary analyses assessing associations with use duration and frequency. Diagnostic yield was calculated as the proportion of completed POCUS examinations identifying abnormalities. We used E-point septal separation to calculate LVEF; < 40% was abnormal. Left ventricular end-diastolic diameter abnormality (> 5.8 cm males, > 5.2 cm females) was categorized as mild, moderate, or severe (mild, 5.9-6.3/5.3-5.6; moderate, 6.4-6.8/5.7-6.1; severe, > 6.8/> 6.1 cm males/females). Physician-performed POCUS assessed LVEF and left ventricular end-diastolic diameter in patients with a methamphetamine use history and a comparison group of non-users. Of the 136 enrolled patients, 84 (61.8%) reported methamphetamine use. Among methamphetamine users, diagnostic yield of cardiac POCUS was as follows: reduced LVEF in 22 of 70 with measurable LVEF (31.4% [20.9-43.6%]); any sex-specific left ventricular end-diastolic diameter abnormality in 30 of 84 (35.7% [25.6-46.9%]); and severe sex-specific left ventricular end-diastolic diameter abnormality in 15 of 84 (17.9% [10.4-27.7%]). Corresponding values in non-users were 3 of 52 (5.8% [1.2-16.0%]; P < .001), 10 of 52 (19.2% [9.6-32.5%]; P = .05), and 3 of 52 (5.8% [1.2 - 16.0%]; P = .07), respectively. Longer duration (odds ratio [OR] 6.05, 95% confidence interval [CI] 1.46-25.10) and higher frequency (OR 5.93, 95% CI, 1.52-23.06) of methamphetamine use were associated with reduced LVEF. Cardiac point-of-care ultrasound demonstrated a clinically significant diagnostic yield in detecting methamphetamine-associated heart failure with reduced ejection fraction among methamphetamine users in the ED, suggesting POCUS could aid early detection in this population, potentially streamlining management before disease progression.
To compare motor recovery in children with severe traumatic brain injury (TBI) with findings from functional and imaging diagnostic techniques based on the age-dependent theory of motor development. The study included 43 children (26 boys and 17 girls), aged 5 to 17 years, with severe TBI who underwent rehabilitation at the Department of Rehabilitation of the Research Institute of Emergency Pediatric Surgery and Traumatology (Dr. Roshal Clinic) from 2023 to 2024. The clinical evaluation used the Muscle Strength Scale, the Modified Ashworth Scale, and a classification system for gross motor function. Instrumental assessments of the anatomical and functional state of the corticospinal tract (CST) included diagnostic single-pulse transcranial magnetic stimulation (sTMS) and magnetic resonance (MR) tractography, which analyzed corticomotor neuronal pathways originating from the primary motor cortex (PMC) and supplementary motor area. Improvement in motor deficits during both intermediate and long-term phases post-injury was associated with a reduction in the threshold for motor evoked responses (MER) (AUCs of 0.583 and 0.548, respectively) and an increase in MER amplitude (AUCs of 0.5 and 0.508, respectively). A significant correlation was noted between the deviation of the MER threshold from reference values and the patient's age at the time of injury, with deviations of 9.27% for ages 6-12 years and 26.1% for ages 12-18 years (p<0.05). Additionally, an increase in the fractional anisotropy coefficient of CST was observed in children with various degrees of motor impairment following severe TBI within the first-year post-trauma. The findings suggest that instrumental diagnostic methods can effectively assess the severity of motor deficits in children with severe TBI and diminished consciousness. The interpretation of these results should incorporate the age-dependent theory of locomotor behavior development. Сопоставить клиническое восстановление моторной функции у детей с черепно-мозговой травмой (ЧМТ) тяжелой степени с результатами функциональных и лучевых методов исследования с учетом возрастзависимой теории формирования двигательного поведения. В исследование включены 43 ребенка (26 мальчиков и 17 девочек) в возрасте от 5 до 17 лет с ЧМТ тяжелой степени, проходивших реабилитацию на базе отделения восстановительного лечения НИИ «НДХиТ — Клиника доктора Рошаля» в период 2023—2024 гг. Оценка клинического статуса проводилась с использованием шкалы оценки мышечной силы, модифицированной шкалы оценки спастичности Эшворта и системы классификации больших моторных функций. Инструментальные методы оценки анатомо-функционального состояния кортикоспинального тракта (КСТ) включали диагностическую одностимульную транскраниальную магнитную стимуляцию (ос ТМС) и магнитно-резонансную (МР) трактографию кортико-мотонейрональных проекций от первичной моторной коры (ПМК) и дополнительной моторной зоны. Регрессу моторного дефицита в промежуточном и отдаленном периодах болезни сопутствовали снижение порога вызванного моторного ответа (ВМО) (AUC 0,583 и 0,548) и увеличение его амплитуды (AUC 0,5 и 0,508). Установлена взаимосвязь между отклонением порога ВМО от нормативных значений и возрастом ребенка на момент повреждающего события (9,27% в возрасте 6—12 лет и 26,1% в возрасте 12—18 лет, (p<0,05)). Выявлено повышение коэффициента фракционной анизотропии КСТ у детей с разной степенью выраженности моторного дефицита после ЧМТ тяжелой степени в течение 1-го года болезни. Полученные данные указывают на возможность объективизации степени выраженности моторного дефицита у детей с ЧМТ тяжелой степени и сниженным уровнем сознания инструментальными методами диагностики. Интерпретацию результатов исследования необходимо проводить с учетом возрастзависимой теории формирования локомоторного акта.
Semantic fluency is commonly assessed in the diagnostic work-up of individuals with suspected cognitive impairment due to neurodegenerative disease. Semantic fluency has a predictive value for survival in clinical AD and in healthy elderly individuals, but it is unknown if this also applies to biomarker-confirmed AD and non-AD memory clinic patients. Potential associations with and added value of imaging biomarkers of amyloid pathology and neurodegeneration have yet to be explored. From our clinical registry, we included patients who were assessed at a memory clinic with the neuropsychological assessment battery of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-NAB) and whose vital status could be retrieved in 07/2024. We tested the association of semantic fluency performance at first assessment and over time (and, for comparison, further CERAD-NAB subtest scores) with mortality risk using age-adjusted single-predictor Cox proportional hazard models. Amyloid status (positive vs negative on clinical PET reads) and global cognitive impairment (MMSE) were included as covariates. In addition, we explored associations between semantic fluency performance and both regional cortical glucose metabolism (FDG PET) and global amyloid load (centiloids; PiB PET). Finally, the predictive value of global amyloid load and glucose metabolism in comparison to and in combination with semantic fluency performance was assessed. 583 patients were included (age 68.9 ± 8.7, 45% female). 280 patients (48%) had died and 303 (52%) were alive after a median of 8.0 years [95% C.I. 7.7-8.4]. Better semantic fluency (age-, sex- and education adjusted Z score, based on normative data) was significantly associated with lower mortality risk (HR = 0.71 [0.63 - 0.80], Bonferroni-corrected p < 0.001). Its predictive value was higher than that of all other CERAD-NAB subscores (e.g., memory, visuospatial abilities). Semantic fluency remained a significant predictor when amyloid status and global cognitive impairment were accounted for (HR = 0.75 [0.61 - 0.91], p = 0.0035). In patients with more than one assessment (N = 163), longitudinal change of semantic fluency (derived from a linear mixed effects model) was also a significant predictor (HR = 0.66 [0.53-0.83], p < 0.001). In 218/583 patients who had received amyloid and FDG PET, worse semantic fluency was associated with decreased FDG uptake of left inferior and middle temporal, dorsolateral frontal, and posterior parietal cortical regions (Bonferroni-corrected p < 0.05), but not with amyloid load. FDG uptake of the left IFG (pars opercularis) was itself a predictor of survival (HR = 0.68 [0.55 - 0.84], Bonferroni-corrected p < 0.05), but to a lesser degree than semantic fluency (and MMSE, naming and figure drawing). Predictive accuracy of semantic fluency was further improved by including FDG uptake of the right anterior cingulate (Bonferroni-corrected p = 0.078). Global amyloid load was not associated with survival. Survival of memory clinic patients can be predicted by semantic fluency, independently from amyloid status and global cognitive impairment. Anterior cortical glucose metabolism is itself a significant predictor of survival and slightly improves prediction by semantic fluency.
This study assessed the efficacy and safety of fluoroscopy-guided intraligamentous steroid injections in managing mucoid degeneration of the anterior cruciate ligament (MDACL) in patients resistant to oral medication and intra-articular steroid injections. A retrospective review of 294 knees diagnosed with MDACL via magnetic resonance imaging between October 2014 and June 2023 was conducted. After applying exclusion criteria and excluding patients who were asymptomatic or showed improvement with conservative treatment, 82 knees were included in the final analysis. Intraligamentous steroid injections were performed under C-arm fluoroscopy by a single orthopedic surgeon. Clinical data collected included the duration of the pain-free period, patient-reported outcome measures (PROMs; pain numeric rating scale, the International Knee Documentation Committee subjective score, Lysholm score, and Knee Injury and Osteoarthritis Outcome Score), range of motion, and other radiological measures. Symptom recurrence rates were determined using the Kaplan-Meier survival analysis. The average age at the time of injection was 64.0 years (range, 39-83 years), and the mean follow-up period was 19.5 months (range, 12-90 months). Pain improvement was noted in 78 of 82 knees (95.1%), with an average effect duration of 7.8 months (standard deviation, 9.1). Improvement of limitation of knee motion was observed in 49 of 50 cases (98.0%). Kaplan-Meier analysis indicated symptom recurrence rates of 19.5% at 3 months, 39.0% at 6 months, and 48.8% at 1 year. All PROMs significantly improved after injection for 6 months (p < 0.01) and then slightly declined. No patients reported post-procedure instability. Fluoroscopy-guided intraligamentous steroid injection demonstrated short-term efficacy in relieving pain and improving knee motion in MDACL patients resistant to conventional treatments, although further studies are warranted to confirm these findings.
Incorporation of fluorine into pharmaceuticals, agrochemicals, and molecular-imaging agents is of growing importance. Multiple synthetic fluorination methods have recently emerged, and metalloenzymes that are potentially capable of C(sp3)-H fluorination have been reported. Nevertheless, direct, regioselective fluorination of aliphatic carbon centers remains an unsolved problem. Here, we show for the iron(II) and 2-oxoglutarate-dependent (Fe/2OG) l-lysine 4-chlorinase, BesD, which might be envisaged to support C(sp3)-H fluorination by the direct cognate of its native chlorination mechanism, that the enzyme can (1) coordinate F- at its Fe(II) cofactor, (2) activate O2 to form a cis-FeIV(O)(F) (fluoroferryl) intermediate, and (3) use the intermediate to abstract hydrogen from its substrate. In what would be the key final step, fluorine (F•) coupling to the substrate radical is unable to compete with the hydroxyl-radical (HO•) "rebound" step characteristic of related hydroxylases. Electron paramagnetic resonance (EPR) and X-ray absorption spectroscopic (XAS) data establish that fluorine remains bonded to the iron cofactor through steps 1-3 and therefore available for transfer to the substrate radical. QM/MM calculations suggest that the F•-coupling step is associated with an activation barrier considerably higher than that of HO• rebound, consistent with the observed outcome. The findings experimentally verify prior proposals that the impediment to C(sp3)-H fluorination by the canonical mechanism of an Fe/2OG halogenase lies solely in the final radical-coupling step and set the stage for exploration of whether a potentially surmountable geometric barrier or an insurmountable electronic one is primarily responsible.
Lung cancer associated with cystic airspaces (LCCA) is a rare and distinct subtype of lung cancer. Patients are often without specific clinical symptoms in the early stage, and the radiological features can be easily confused with pulmonary bullae, benign pulmonary cysts, and other cystic lung lesions, resulting in a high rate of missed diagnosis and misdiagnosis. We report the case of a middle-aged woman with LCCA pathologically confirmed following surgical resection. A chest computed tomography (CT) scan performed during a routine health examination initially revealed an air-containing lesion adjacent to the oblique fissure in the right lower lobe, measuring approximately 1.1 cm×0.8 cm. Serial CT examinations over a 12-year period demonstrated gradual evolution of the lesion, with the development of a lobulated contour, interlobar pleural indentation, and vascular convergence, raising suspicion for malignancy. The patient subsequently underwent surgical resection. Based on histopathological and immunohistochemical findings, the lesion was finally diagnosed as invasive lung adenocarcinoma (lepidic predominant, 60%; acinar, 30%; papillary, 10%). No evidence of tumor recurrence or metastasis was observed during postoperative outpatient follow-up. 囊腔型肺癌（LCCA）是一种罕见的特殊类型肺癌。患者早期多无特异性临床症状，影像学表现易与肺大泡、良性肺囊肿等病变相混淆，临床漏诊及误诊率较高。本文报道1例经外科手术切除后病理确诊为囊腔型肺癌的中年女性患者，因体检行胸部CT检查发现右肺下叶斜裂旁气腔影，大小约1.1 cm×0.8 cm。此后12年连续胸部CT随访，病灶逐步出现分叶征、叶间胸膜凹陷征、血管穿行征等恶性征象。予外科手术治疗后，根据组织病理学和免疫组化检查结果最终诊断为浸润性肺腺癌（贴壁型60%+腺泡型30%+乳头型10%），术后门诊随访无肿瘤复发及转移征象。.
Poor differentiation and microvascular invasion (MVI) are crucial prognostic indicators for hepatocellular carcinoma (HCC), but evaluating them before surgery is still difficult. Our goal was to develop a reproducible framework for ultrasound localization microscopy (ULM) using a clinical ultrasound system and assess its effectiveness in predicting tumor differentiation and MVI. Participants were prospectively enrolled and underwent contrast-enhanced ultrasound and ULM imaging. We first compared frame selection strategies by calculating coefficients of variation (COVs) of ULM parameters derived from motion-variance curve (MVC) alone versus MVC combined with time-intensity curve (TIC). ULM resolution and parameter stability were then assessed across low (0-399), medium (400-699), and high (700-1000) frame counts. Regions of interest (ROIs) were manually drawn on grayscale ultrasound and mapped to ULM images. Inter-operator agreement was evaluated using intraclass correlation coefficients (ICCs). Participants were grouped by pathological differentiation and MVI status. The predictive performance of ULM parameters was assessed with multivariable logistic regression. Sixty-one HCC participants were enrolled (11 poorly differentiated, 50 well differentiated; 30 MVI-positive, 31 MVI-negative). The MVC+TIC strategy yielded significantly lower COVs, indicating higher repeatability of ULM parameters. Medium frame counts (400-699) provided high resolution (minimum vessel diameter 91.3 ± 22.7 μm) and stable parameters (COV < 20%), and were therefore selected for ULM reconstruction. All ULM parameters showed high inter-operator agreement (ICC 0.876-0.988). Based on the established ULM framework, higher intratumoral mean curvature was independently associated with poor differentiation [area under the curve (AUC) 0.91], and higher peritumoral mean curvature independently predicted MVI status (AUC 0.78). The reproducible ULM framework enables stable, high-resolution microvascular imaging of HCC. ULM-derived parameters hold potential as novel biomarkers for predicting differentiation grade and MVI status of HCC.
The first therapeutic assessment of locally advanced (LA) head and neck squamous cell carcinomas (HNSCCs) is often performed 10-12 weeks after the end of chemoradiotherapy as a result of the delayed action of radiotherapy. Diagnostic uncertainty between persistent disease and treatment-related changes (oedema, necrosis) can delay confirmation of residual cancer. According to data in the literature, a correlation exists between the detection of circulating tumour DNA (ctDNA) at the end of chemoradiotherapy treatment and residual disease. However, additional data are required before this molecular tool can be used in routine clinical practice. The aim of this clinical trial (NeckTAR-IN) is to assess the usefulness of ctDNA to detect residual disease 3 months after the end of chemoradiotherapy among patients with LA HNSCC. At M3, objective response (clinical and radiological) will be set against the detection or not of ctDNA in the blood. This is an interventional, multicentre, prospective trial, ancillary to the NeckTAR study. All the patients included in the NeckTAR study are eligible for the NeckTAR-IN study. We expect to enrol 59 patients in this ancillary trial. A blood sample will be taken 1 month and 3 months after the end of chemoradiotherapy. Approval from the ethics committee was granted on 29 August 2025. The study protocol obtained approval from the French Ethics Committee (N°25.02461.000435). The results will be published in scientific journals and presented at conferences. NCT07178847.
To compare the reliability of four commonly used structured tools for risk-of-bias assessment in prognostic cohort studies and evaluate their agreement with expert appraisal. Methodological comparison study. Secondary analysis of published prognostic cohort studies in patients with acute pulmonary embolism from a previously conducted systematic review. Sixty-three cohort studies assessing the prognostic role of echocardiography in patients with acute pulmonary embolism. Four independent reviewers assessed study quality/risk of bias using the Newcastle-Ottawa Scale (NOS), Risk Of Bias in Non-Randomised Studies of Interventions (ROBINS-I), Quality In Prognostic Studies (QUIPS) and Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). Concomitantly and independently, expert reviewers' implicit global judgements were used as an external comparator. Inter-rater reliability, agreement with expert appraisal, internal consistency and floor/ceiling effects were assessed. Inter-rater agreement was fair for NOS (Gwet's agreement coefficient 1, 0.25, 95% CI 0.15 to 0.34), ROBINS-I (0.38, 95% CI 0.28 to 0.47) and QUADAS-2 (0.35, 95% CI 0.27 to 0.43) and almost perfect for QUIPS (0.85, 95% CI 0.73 to 0.93). Agreement with expert appraisal was limited for all tools except ROBINS-I, which showed fair concordance. QUIPS frequently classified studies as low risk of bias, suggesting potential overestimation of study quality. Internal consistency was generally low across tools, while ceiling effects were observed for NOS and QUIPS. ROBINS-I showed the most balanced distribution of ratings. Structured tools for risk-of-bias assessment in prognostic cohort studies have variable reliability and limited agreement with expert appraisal. ROBINS-I showed the strongest concordance with expert judgement, whereas QUIPS may provide optimistic ratings. These findings support further refinement and standardisation of risk-of-bias assessment methods for observational prognostic research.
BACKGROUND An anomalous origin of a coronary artery from the opposite sinus of Valsalva (ACAOS) is a rare congenital coronary abnormality that is usually asymptomatic throughout life. However, an anomalous coronary artery arising from an atypical aortic location can lead to myocardial ischemia, exertional symptoms, or even sudden cardiac death. Therefore, early recognition and risk stratification are essential. Clinical management of ACAOS should be highly individualized and guided by detailed anatomical features, clinical symptoms, and evidence of ischemia. This report describes an older woman who presented with new-onset chest pain as the first clinical manifestation of previously undiagnosed ACAOS. CASE REPORT A 70-year-old woman presented with 5 days of progressive chest tightness and 20 days of recurrent dizziness associated with poorly controlled hypertension. Initial conventional medical therapy provided inadequate symptom relief. Subsequent coronary angiography revealed an anomalous left circumflex artery originating independently from the right sinus of Valsalva, with 3 separate coronary ostia and concurrent clinically significant atherosclerotic stenosis. She underwent uncomplicated percutaneous coronary intervention of the right coronary artery, achieving successful revascularization and complete resolution of her presenting symptoms. CONCLUSIONS This report describes a rare case of ACAOS presenting with de novo chest pain in an older woman, highlighting the critical importance of accurate anatomical characterization and tailored, individualized management for optimal clinical outcomes.
Isolated bone marrow involvement in sarcoidosis is a rare condition, mostly manifested by cytopenia, hypercalcemia and/or hypercalciuria. We present the case of a 48-year-old man with a prolonged fever meeting the criteria for fever of unknown origin, in whom a suspicion of sarcoidosis only emerged after non-necrotizing granulomas were identified in the bone marrow, one year after the onset of the disease. The patient exhibited only mild anemia, moderate leukocytosis, thrombocytosis, and increased erythrocyte sedimentation rate, C-reactive protein levels. Other potential causes of fever of unknown origin and bone marrow non-necrotizing granulomas were ruled out. Although serum angiotensin-converting enzyme levels were elevated, they did not reach diagnostic thresholds. The diagnosis of sarcoidosis was confirmed by newly detected intra-abdominal lymphadenopathy on computed tomography and whole-body 18F-fluorodeoxyglucose positron emission tomography with computed tomography, along with the presence of multiple sarcoid-type non-necrotizing granulomas in the intra-abdominal lymph nodes. Treatment with prednisolone normalized the patient's body temperature, improved laboratory-inflammatory profile, and enhanced the patient's quality of life. In cases where fever of unknown origin is present and sarcoidosis is suspected, a bone marrow biopsy may be considered, even in the absence of cytopenia, hypercalcemia, or hypercalciuria.
Late-onset unexplained epilepsy (LOUE) represents a substantial proportion of epilepsies with onset after 50 years and often manifests as temporal lobe epilepsy (LO-TLE). Although a link with Alzheimer disease (AD) has been suggested, only a subset of LO-TLE shows AD-related biomarkers, indicating biological heterogeneity. This study aims to characterize the cognitive and CSF phenotype of LO-TLE and compare it with healthy controls (HCs) and patients with mild cognitive impairment due to AD (MCI-AD). This Italian cross-sectional cohort study included LO-TLE patients with normal CSF β-amyloid (Aβ) biomarkers, MCI-AD, and age-matched and sex-matched HC. Participants underwent structural MRI, neuropsychological assessment, and CSF biomarkers assay, including neurofilament light chain (NfL) and the phosphorylated-to-total tau ratio (p/t-tau). Cortical thickness and subcortical volumes were quantified from structural MRI. Cognitive performance was summarized using principal component analyses. Group differences in imaging, cognition, and CSF biomarkers were assessed, and associations between CSF markers and cognition were examined within groups. The study included 18 LO-TLE, 24 MCI-AD, and 17 HC. LO-TLE showed preserved cortical thickness and subcortical volumes comparable with HC, whereas MCI-AD exhibited widespread cortical thinning and medial temporal atrophy. Despite normal imaging, LO-TLE showed lower performance compared with HC in episodic memory (t(53) = -7.79, pFDR < 0.001), short-term memory (t(53) = -2.94, pFDR = 0.007), language (t(53) = 4.12, pFDR < 0.001), and executive functions (t(53) = -3.76, pFDR < 0.001), while attention was preserved. Global cognitive performance further distinguished LO-TLE from MCI-AD, with the former group performing better (t(53) = 4.21, pFDR < 0.001). LO-TLE CSF profiles were characterized by low NfL levels and a p/t-tau ratio below the proposed cutoff of 0.17, whereas MCI-AD showed pathologic Aβ and tau alterations, elevated NfL, and p/t-tau ratio above 0.17. In LO-TLE, a higher p/t-tau ratio was associated with better performance on global cognition (rs = 0.585, pFDR = 0.032) and short-term memory (rs = 0.588, pFDR = 0.032), whereas no associations emerged in MCI-AD. LO-TLE with normal CSF AD biomarkers is characterized by distinct cognitive and biological features compared with MCI-AD, suggesting a disease process independent of AD. The low p/t-tau ratio may reflect alternative pathophysiologic mechanisms and warrants further investigation in larger longitudinal studies to clarify the underlying pathology and clinical trajectories.
Rapid detection of pyrethroid pesticide residues in food is critical to ensure human health. In this work, based on rationally-designed Eu-doped MOFs with dual functions of effective adsorption and fluorescent sensing to pyrethroid pesticides metabolite 3-phenoxybenzaldehyde, we designed a portable glass vials (GV) platform which can achieve simple separation and rapid determination of pyrethroid pesticides residues in food. Specifically, PCN-777 was in-situ grown on the inner surface of GV through rational ligand selection, followed by Eu3+ incorporation to construct a novel fluorescent composite (Eu-PCN-777@GV). The organic ligand of PCN-777 not only provides strong host-guest interactions with targets, but also efficiently sensitizes Eu3+ through "antenna effect", giving rise to intense red fluorescence emission. The hydrolysis product of pyrethroids 3-phenoxybenzaldehyde, significantly quenched the red fluorescence of Eu-PCN-777@GV through "inner filter effect". Combined with smartphone imaging, a portable fluorescent sensing platform was constructed, with detection limits 7.06 mg kg-1, 6.52 mg kg-1, and 8.04 mg kg-1 for lambda-cyhalothrin, permethrin and cypermethrin, respectively, and linear ranges of 10-200 mg kg-1. This method has been successfully applied to the extraction and detection of pyrethroid pesticides residues in tea. Spiked recoveries in samples ranged from 95.60% to 105.60%, showing high agreement with HPLC measurements. This work provides an integrated adsorption-detection platform for on-site pesticides analysis, featuring efficient analyte enrichment, rapid response, and good reusability. More importantly, it offers a design strategy to construct integrated adsorption-detection materials for broader application scenarios.
Serous endometrial intraepithelial carcinoma (SEIC) is a rare, non-invasive lesion of the endometrial epithelium, typically characterised by p53 abnormalities. Although regarded as a precursor lesion, recent classification systems increasingly position SEIC within the broader spectrum of serous carcinomas and current guidelines place non-invasive p53-abnormal serous lesions in an uncertain risk category due to limited outcome data. As a result, SEIC is not consistently addressed as a distinct diagnosis, contributing to variation in clinical management. Complete surgical staging, including pelvic and para-aortic lymph node assessment, is frequently performed, yet supporting evidence remains scarce. This study aims to collect longitudinal data to evaluate surgical management strategies in relation to clinical outcomes, survival and quality of life. This multicentre prospective observational cohort will enrol patients diagnosed with SEIC or equivalent non-invasive serous lesions who provide informed consent. Data will be collected using electronic case report forms (Castor Electronic Data Capture). Baseline clinical, pathological, molecular and treatment data will be collected, including imaging, histopathology, immunohistochemistry and molecular classification when available. Patient-reported outcomes will be assessed using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30), European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Endometrial Cancer Module (EORTC QLQ-EN24) and EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L) questionnaires at baseline, 6 months, 2 years and 5 years after diagnosis. The primary outcome is progression-free survival, secondary outcomes include overall survival, health-related quality of life and adverse events. Analyses will be primarily descriptive. Survival outcomes will be estimated using Kaplan-Meier methods, with Cox proportional hazards modelling used to explore predictors of outcome where feasible. The study will be conducted in accordance with the Declaration of Helsinki and applicable regulations. Ethical approval was obtained at the Erasmus MC (MEC-2025-0368). Results will be disseminated through peer-reviewed publications and scientific meetings. NCT06677242.
Sarcomatoid carcinoma of the pancreas (SCP) is an exceptionally rare variant of pancreatic ductal adenocarcinoma. A detailed evaluation of its clinical manifestations, laboratory findings, and imaging characteristics may contribute to earlier detection and intervention, thereby improving survival outcomes and quality of life. We retrospectively reviewed the clinical presentation, laboratory investigations, and imaging findings of a patient with pathologically confirmed SCP. In addition, relevant literature was analyzed to summarize strategies for early screening and diagnosis. A 78-year-old female presented with persistent dull epigastric pain accompanied by nausea and vomiting. Laboratory evaluation revealed elevated CA19-9 levels. Imaging demonstrated a mass in the pancreatic body and tail. Dynamic contrast-enhanced CT showed moderate heterogeneous enhancement in the arterial phase with progressive enhancement during the portal venous phase. Dynamic contrast-enhanced MRI revealed rim enhancement. The integration of serum CA19-9 measurement with characteristic imaging features may facilitate the early identification of SCP.
Societal guidance recommends sequential noninvasive testing for metabolic dysfunction-associated steatotic liver disease (MASLD), using Fibrosis-4 (FIB-4) ≥1.3 as a gatekeeper before second-line assessment with the Enhanced Liver Fibrosis (ELF) score (<7.7 as a rule-out). The impact of this pathway design on the detection of fibrotic MASH remains uncertain. We aimed to evaluate the performance of guideline-endorsed sequential testing and to determine optimized ELF thresholds within alternative strategies. In this prospective study, patients with or at risk for MASLD underwent FIB-4, ELF testing, magnetic resonance elastography (MRE), and liver biopsy within 1 month. Fibrotic MASLD was defined as fibrosis stage ≥2 on histology or liver stiffness ≥3.1 kPa on MRE. Diagnostic performance of ELF was assessed, and sequential (ELF applied after FIB-4 ≥1.3) and concurrent (either test positive) testing strategies were compared.Results:Among 186 participants (median age 51 years; 69% women), fibrotic MASLD was present in 71 (38%). ELF demonstrated AUROC 0.77 (95% CI 0.70-0.84); the cohort-derived cutoff was 9.4 (80% sensitivity, 65% specificity). Lower cutoffs (8.7 and 7.7) increased sensitivity (≥90% and 100%) but low specificity (34% and 4%). FIB-4 ≥1.3 showed limited sensitivity (57%), resulting in 43% of fibrotic MASH cases being excluded from second-line testing. Sequential application of ELF, therefore, failed to overcome this sensitivity ceiling. A concurrent strategy using FIB-4 ≥1.3 or ELF ≥9.4 improved sensitivity to 87% with 64% specificity. Sequential FIB-4-based testing substantially limits the detection of fibrotic MASLD due to gatekeeping sensitivity constraints. Concurrent first-line testing with FIB-4 and ELF improves case identification, underscoring the importance of pathway design in optimizing noninvasive fibrosis assessment.