Search Results (89)

Objective: To evaluate the real-world efficacy and safety of disitamab vedotin (RC48-ADC) in patients with human epidermal growth factor receptor 2 (HER2) overexpression (immunohistochemistry [IHC] 2+ or 3+), advanced gastric/gastroesophageal junction cancer (GC/GEJC) with metastases who had received at least one line of prior systemic therapy. Patients and methods: Patients with HER2-overexpressing advanced or metastatic GC/GEJC who had previously received the anti-HER2 antibody-drug conjugate disitamab vedotin between December 2022 and April 2024 were enrolled in this study. The patients’ baseline characteristics, treatment procedures, and laboratory or imaging examinations were retrospectively collected and analyzed. The observation items included the objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and treatment-related adverse events (TRAEs). Results: Of the 38 enrolled patients in the study, 27 were found to be HER2-positive. Most patients (29/38) received disitamab vedotin therapy as a third-line or subsequent treatment. A total of 68.4% of patients had previously received anti-HER2 therapy, and 13 patients underwent immunotherapy concurrently. The overall ORR and DCR were 31.6% and 65.8%, respectively. A higher ORR was observed in patients with a single metastatic site compared to those with multiple sites (53.3% vs. 17.4%, p = 0.022). In the general population, the median PFS was 6.5 months (95% confidence interval [CI] 3.3–9.8 months), and OS was 13.5 months (95% CI 9.0–17.9 months). The most common adverse event was anemia (89.5%), and eight patients suffered severe toxicities of grade ≥3. Conclusions: Disitamab vedotin exhibited encouraging anti-tumor effectiveness with a tolerable safety profile for advanced GC/GEJC patients with HER2 overexpression who had failed at least one line of systemic therapy in a real-world setting. Full article

Background: Whilst COVID-19 mainly affects the lungs, multiple other organs were also involved—patients with COVID-19 were reported to be at higher risk of acute coronary syndromes (ACS). Importantly, results show that the risk of ACS may extend well beyond the acute phase of COVID-19 infection. In our study, we sought to investigate optical coherence tomography (OCT)-derived vascular changes, including the prevalence of plaque erosion in patients who had recent COVID-19. Methods: Patients with ACS were divided into two groups: those after COVID-19 infection during the past 12 months (post-COVID group) and those without known prior COVID infection (non-COVID group). We enrolled 35 patients in the post-COVID group and 35 patients in the non-COVID group. Results: The mean time from COVID infection to the imaging in the post-COVID group was 10 ± 1 months. There were no major differences in baseline demographic, clinical, or laboratory characteristics between the two groups. Erosion was the underlying pathology in one-third (34.3%) of the non-COVID group and in one-half (48.6%) of the post-COVID group, although the difference did not reach statistical significance. No calcified nodules were observed. The lipid core tended to be longer in the post-COVID group (9.1 ± 3.6 vs. 12.0 ± 1.9 mm; p = 0.005), and the prevalence of macrophages was higher in patients who had prior COVID-19 infection (48.6 vs. 74.3%; p = 0.027). Conclusions: Our OCT study demonstrated that patients with a prior COVID-19 infection tended to have a higher prevalence of plaque erosion and more vulnerable plaque morphology at the culprit lesion compared to those without a history of prior COVID-19 infection. Full article

We aimed to validate the feasibility of combining ultra-widefield (UWF) fundus photography with targeted swept-source optical coherence tomography (SS-OCT) for clinical decision-making regarding a prophylactic laser therapy. For this purpose we enrolled 119 patients (135 eyes) who, basis on fundus examination, were eligible for prophylactic photocoagulation of degenerative retinal lesions. Eyes were classified into two groups: (1) justified laser, when SS-OCT confirmed vitreoretinal traction and/or subretinal fluid beneath the neurosensory retina; and (2) non-justified laser, when SS-OCT did not confirm these criteria. Using this SS-OCT-guided UWF approach, we found that 25.1% of eyes that initially qualified for laser based on clinical examination did not meet the SS-OCT criteria. Patients in the justified laser group were significantly younger than those in the non-justified group. Horseshoe retinal tears, lattice degeneration and snail-track degenerations, multiple lesions, and lesions located in the far and mid-periphery were significantly more frequent in the justified laser group than in the non-justified group. By contrast, the prevalence of operculated holes, bilateral lesions, and degenerative lesions in patients with a retinal detachment in the fellow eye did not differ between groups. Our findings suggest the SS-OCT-guided UWF imaging may refine patient selection for prophylactic laser therapy. Full article

Aims: To describe lung ultrasound (LUS) features of Mycoplasma pneumoniae pneumonia and their distribution in pediatric age, and to correlate imaging findings with clinical and laboratory data. Methods: This is a multicenter, prospective, pilot study that involved three hospitals. In total, 35 patients aged 1 month to 17 years, admitted with a diagnosis of Mycoplasma pneumoniae infection, were enrolled. History, clinical, microbiological, and ultrasound data were collected. The LUS examination was performed at admission, recording the following features: presence of subpleural consolidation, bronchograms, B lines, or pleural effusion, and their characteristics. The scans were performed using a standardized approach, in which a composite score was obtained by summing the scores of the different parameters. Results: Consolidations were seen in 97% of children (mostly located in basal, posterior, and lateral fields), and 65% of patients had multiple ones. Non-perilesional B lines were found in 43% of cases, principally in the posterior and basal fields. Pleural effusion was found in 37% of children. The univariate logistic regression showed a correlation between the age of the patient and large-sized consolidations. Moreover, increased lymphocyte count was associated with a lower risk of large-sized consolidations. Conclusions: LUS is a low-cost, non-invasive tool that can reveal findings suggestive of Mycoplasma pneumoniae infection and help physicians better manage children with lower respiratory tract infections, supporting a more personalized diagnostic and therapeutic approach, including antibiotic selection. These preliminary findings also indicate that a larger, comparative study involving other bacterial and viral etiologic agents is warranted to confirm whether LUS patterns are pathogen-specific and whether they can predict clinical outcomes. Full article

Background: The aim of this study was to evaluate the significance of serum concentrations of the inflammatory marker osteopontin, the blood–brain barrier damage marker occludin, and the neurodegeneration marker neurofilament light chain (NFL) in patients with relapsing-remitting multiple sclerosis (RRMS) for predicting disease activity and progression. Methods: This prospective cohort study enrolled 150 patients with RRMS. Initial serum levels of NFL, occludin, and osteopontin were compared between patients who met or did not meet the no evidence of disease activity (NEDA) criteria and its components (relapses, magnetic resonance imaging activity, and Expanded Disability Status Scale progression) within 36 months of observation. Independent factors affecting study outcomes at month 36 were identified from baseline data, including age, gender, initial prognostic profile, and serum levels of NFL, occludin, and osteopontin, as well as treatment type. Results: We found lower osteopontin concentrations in patients receiving highly effective treatment compared with those receiving platform therapies (13.64 ± 5.41 ng/mL, CI 11.75–15.53 vs. 17.33 ± 8.00 ng/mL, CI 15.66–18.61; p = 0.03). There was a significant correlation between NFL levels and patient age (Spearman’s rho = 0.3045, p = 0.0002) and between NFL levels and disease duration (Spearman’s rho = 0.1945, p = 0.02). NEDA during the 3-year observation period was achieved by 58 (38.67%) patients. Patients with NEDA showed significantly lower serum concentrations of occludin, NFL, and osteopontin than those without NEDA. Conclusions: Serum levels of NFL, osteopontin, and occludin may serve as biomarkers of disease activity in patients with RRMS. The clinical relevance of these biomarkers should be confirmed through repeated serum marker assessments in MS patients and validation studies involving larger sample sizes. Full article

Background/Objectives: Type 2 Diabetes Mellitus (T2DM) represents a significant global health burden, frequently leading to severe complications such as peripheral neuropathy and both micro- and macrovascular dysfunctions. These complications are integral to the pathology of diabetic foot ulcers (DFUs) and are associated with an elevated risk of lower limb amputations. This study investigated lower extremity skeletal muscle perfusion in patients with T2DM and DFUs using [¹⁵O]H₂O PET imaging, in comparison to healthy controls. Methods: A total of 10 healthy controls and 26 patients with T2DM and DFUs were enrolled. Resting skeletal muscle perfusion was quantified using [¹⁵O]H₂O PET. Regional perfusion was assessed in multiple lower leg and foot muscle groups. Distal blood pressure was measured, and foot/leg perfusion ratios were calculated. Results: Patients with T2DM and DFUs exhibited a 58% higher median global foot resting perfusion compared to healthy controls. At the individual muscle level, median perfusion in the flexor hallucis brevis was elevated by up to 210% in the ulcerated foot compared to controls. No significant differences in perfusion were observed in the non-ulcerated foot. The foot/leg perfusion ratio was up to 58% higher in the ulcerated limb of T2DM patients compared to the controls. Conclusions: This study demonstrates localized alterations in skeletal muscle perfusion in patients with T2DM and DFUs, characterized by elevated resting foot perfusion in muscles adjacent to ulcerations. Understanding these perfusion dynamics may contribute to refined DFU management strategies. However, further research is needed to validate the clinical utility of [¹⁵O]H₂O PET imaging in guiding interventions and predicting treatment outcomes for DFUs. Full article

Secure authentication in smart device ecosystems remains a critical challenge, particularly due to the irrevocability of compromised biometric templates in server-based systems. This paper presents a post-quantum secure multi-factor authentication protocol that combines templateless 2D and 3D facial biometrics, liveness detection, and Physical Unclonable Functions (PUFs) to achieve robust identity assurance. The protocol exhibits zero-knowledge properties, preventing adversaries from identifying whether authentication failure is due to the biometric, password, PUF, or liveness factor. The proposed protocol utilizes advanced facial landmark detection via dlib or mediapipe, capturing multi-angle facial data and mapping it. By applying a double-masking technique and measuring distances between randomized points, stabilized facial landmarks are selected through multiple images captured during enrollment to ensure template stability. The protocol creates high-entropy cryptographic keys, securely erasing all raw biometric data and sensitive keys immediately after processing. All key cryptographic operations and challenge-response exchanges employ post-quantum algorithms, providing resistance to both classical and quantum adversaries. To further enhance reliability, advanced error-correction methods mitigate noise in biometric and PUF responses, resulting in minimal FAR and FRR that meets industrial standards and resilience against spoofing. Our experimental results demonstrate this protocol’s suitability for smart devices and IoT deployments requiring high-assurance, scalable, and quantum-resistant authentication. Full article

Objective: Platelet-rich plasma (PRP) therapy has become a popular treatment for knee osteoarthritis. We aimed to determine the outcomes of knee osteoarthritis patients following PRP therapy using magnetic resonance imaging (MRI) findings and patient-reported outcome measures (PROMs). Design: In this retrospective observational cohort study, we enrolled 161 patients (221 knees) with varus knee osteoarthritis who received multiple PRP injections at our hospital from June 2017 to June 2019. Patients underwent whole-body MRI before and 6 months after treatment. Whole-organ MRI score (WORMS) cartilage integrity and synovial fluid volume were assessed for the medial femorotibial (MFTJ), lateral femorotibial (LFTJ), and patellofemoral joints (PFJ). Pain visual analog scale and Knee Injury and Osteoarthritis Outcome scores were used as PROMs. In addition, a historical control group of 30 patients with medial knee osteoarthritis who did not receive intra-articular injections was evaluated by MRI over the same period for comparison. Results: After 6 months of PRP therapy, the mean WORMS cartilage score of the LFTJ and PFJ and the total WORMS cartilage score for all three joints improved significantly, and synovial fluid volume reduced significantly. Moreover, a reduction in synovial fluid volume correlated with improvements in several KOOS subscales but not with VAS, which may explain the lack of association with responder status. These results suggest that synovial fluid reduction reflects functional improvement but is not a direct surrogate for pain relief. In addition, the change score of WORMS PFJ cartilage correlated positively with clinical outcomes in responders. By contrast, in the control group, no compartment demonstrated improvement in WORMS cartilage scores, and several compartments showed a trend toward deterioration. Conclusions: In this retrospective observational study, PRP therapy was associated with improvements in WORMS cartilage integrity scores and reductions in synovial fluid volume, with partial correlations to patient-reported outcomes. The inclusion of a historical control group strengthens the interpretation of these findings, although definitive conclusions cannot be drawn. Further randomized controlled trials are needed to confirm these preliminary observations. Full article

Purpose: We aimed to analyze the effects of age on human tear film (TF) using a novel nanometer resolution TF imaging device (Tear Film Imager, TFI, AdOM, Israel). Methods: 44 healthy adult subjects (≥18 years of age) without ocular or systemic diseases or prior eye treatments with ages spanning seven decades were enrolled in this prospective cross-sectional study. Subjects underwent a comprehensive ophthalmic examination and completed the Ocular Surface Disease Index questionnaire (OSDI). All study participants underwent TF imaging using the TFI, including assessment of muco-aqueous layer thickness (MALT), lipid-layer thickness (LLT), inter-blink interval, and lipid map uniformity. Associations between TFI parameters and age were tested using linear regression (accounting for multiple eyes). Results: A total of 80 eyes (44 subjects) were imaged: 19 eyes from 10 subjects in the 3rd decade of life (aged 20–29); 10 eyes from 5 subjects in the 4th decade of life (aged 30–39); 5 eyes from 3 subjects in the 5th decade of life (40–49); 12 eyes from 7 subjects in the 6th decade of life (50–59), 19 eyes from 11 subjects in the 7th decade of life (60–69); 11 eyes from 6 subjects in the 8th decade of life (70–79); and 4 eyes from 2 subjects in the 9th decade of life (80–89). With increasing age, MALT significantly decreased (p = 0.024), and LLT significantly increased (p = 0.001). No statistically significant linear age effects were found for the other TFI parameters (p > 0.05) or the OSDI scores of study participants of different ages (p = 0.786). Conclusions: Quantitative TF biomarkers varied significantly with advancing age in healthy individuals, highlighting the importance of accounting for age in TF assessments. Full article

Background/Objectives: Parkinson’s disease (PD) and multiple sclerosis (MS) are neurological conditions that result in debilitating non-motor symptoms, such as anxiety and depression, which significantly reduce quality of life and often persist despite pharmacological treatment. As a result, effective alternative treatment strategies are needed. Exercise therapy—particularly aerobic training—has shown promise in alleviating non-motor symptoms, potentially through neuroplastic adaptations. However, traditional aerobic exercise is often time-consuming and monotonous, limiting long-term adherence. High-intensity interval training (HIIT) offers a time-efficient and potentially more engaging alternative, though its effects on non-motor symptoms in PD and MS remain understudied. Methods: This transdiagnostic randomized controlled trial will enroll 48 participants (24 PD, 24 MS) with clinically significant affective symptoms (hospital anxiety and depression scale [HADS] ≥ 8). The participants will be randomly assigned to one of three 8-week interventions: (1) HIIT, 5–6 intervals of 45 s of high-intensity cycling; (2) continuous aerobic training (CAT), 50 min of low-intensity cycling; (3) movement advice (MA), step goals, and physical education. The primary (affective symptoms) and secondary outcomes (cognition, fatigue, sleep, motor function) will be assessed at four time points: 4 and 1 weeks pre intervention, and 1 and 4 weeks post intervention. Weekly blood samples and pre/post brain imaging will be collected to study biofluid and MRI measures for potential neuroplasticity. Linear mixed models will analyze the time and group effects. Discussion: This trial will assess whether HIIT can more effectively improve non-motor and motor symptoms in PD and MS than CAT or MA. A multimodal approach will explore both the clinical outcomes and underlying mechanisms, informing scalable and engaging rehabilitation strategies. Full article

Neonatal calf diarrhea (NCD) remains one of the most prevalent and economically burdensome health challenges in preweaned calves, leading to compromised growth, increased morbidity, and high mortality rates worldwide. While traditional methods such as physical examination and clinical health scoring are widely used, they often require trained personnel, are resource-intensive, and are prone to subjectivity, which limits their scalability in large dairy operations. This observational cohort study investigated the feasibility of using suckle pressure measurement combined with machine learning (ML) techniques for NCD detection. A total of 51 female Holstein calves on a commercial dairy farm were enrolled at birth and health scored daily from 1 to 21 days of age. Suckle pressures were measured at 1, 3, 5, 7, 10, 14, and 21 days, as well as daily following NCD diagnosis until fecal consistency returned to normal. Pressure measurements were captured using impression film-wrapped nipples, producing 349 images, of which 54 were from calves diagnosed with NCD. Image features, including pixel density, color saturation, entropy, and histogram-based features, were extracted for analysis. Multiple ML classifiers—Support Vector Machine, K-Nearest Neighbors, Random Forest, Gradient Boosting, and Easy Ensemble (EE)—were applied to detect NCD status based on image features. The EE classifier achieved the best detection performance, with an accuracy of 0.90, precision of 0.64, and recall of 0.82, effectively handling data imbalance. Notably, the results also demonstrated that NCD onset could be predicted up to one day prior to clinical manifestation by training classifiers on pre-symptomatic suckle pressure data and testing on post-onset data. The EE classifier also outperformed other models in this early prediction window, with an accuracy of 0.74, precision of 0.67, and recall of 0.70. The results of our preliminary study suggest that suckle pressure may offer a novel, non-invasive approach for precision health monitoring in dairy systems, enabling timely intervention to reduce disease severity, improve calf health, and minimize economic losses. Full article

Objective: We aimed to quantify multiple sclerosis (MS)-related work productivity and to illustrate the longitudinal trends for relapses, disease progression, and utilization of health care resources in a nationally representative cohort of working North Americans living with MS. Background: The North American Registry for Care and Research in Multiple Sclerosis (NARCRMS) is a multicentered physician-reported registry which prospectively collects clinical information including imaging data over a long period of time from people with MS from sites across the U.S. and Canada. The Health Economics Outcomes Research (HEOR) Advisory Group has also incorporated Health-Related Productivity and Health Resource Utilization questionnaires, which collect information about health care economics of people with MS and its effects on daily life. Design/Methods: This is a prospective observational study utilizing data from NARCRMS. Socio-demographic, clinical, and health economic outcome data were collected through previously validated and structured questionnaires. Logistic regression was used to calculate the relative odds of symptom impact, with a generalized logit link for number of relapses. Cox proportional hazards regression was used to calculate hazard ratios for time to first relapse. Results: Six hundred and eighty-two (682) people with MS were enrolled in NARCRMS and had completed the HEOR questionnaires at the time of the analysis. Among the participants, 61% were employed full-time and 11% were employed part time. Fatigue was the leading symptom reported to impact both work and household chores. Among the employed participants, 13% reported having missed work with a median of 6.8 (IQR: 3.0–9.0) missed hours due to MS symptoms (absenteeism), while 35% reported MS having impacted their work output (presenteeism). The odds of higher disease severity (EDSS 2.0–6.5 vs. 0.0–1.5) were 2.29 (95% CI = 1.08, 4.88; p = 0.011) times higher for participants who identified reduction of work output. Fatigue was the most identified symptom attributed to work output reduction. Among all participants, 33% reported having missed planned household work with a median of 3.0 (IQR: 2.0–5.0) hours. The odds of higher disease severity were 2.49 (95% CI = 1.37, 4.53; p = 0.006) times higher for participants who identified reduction in household work output, and 1.70 (CI = 1.27, 2.49; p = 0.006) times higher for those whose fatigue affected housework output as compared to other symptoms. Conclusions: A preliminary review of the first 682 patients showed that people with MS had reduced work and housework productivity even at an early disease state. Multiple sclerosis (MS) can significantly impair individuals’ ability to function fully at work and at home, with fatigue overwhelmingly identified as the primary contributing factor. The economic value of finding an effective treatment for MS-related fatigue is substantial, underscoring the importance of these findings for policy development, priority setting, and the strategic allocation of healthcare resources for this chronic and disabling condition. Full article

Parvovirus B19 (B19V) re-emerged across Europe in 2024, raising concerns about vertical transmission and neonatal morbidity. We undertook a prospective, single-centre cohort study to characterise the early clinical course of congenitally infected neonates born between April and December 2024. Seventy-one pregnancies with serologically or PCR-confirmed maternal infection were enrolled; seven neonates met laboratory criteria for congenital B19V infection and were followed with serial clinical, biochemical and imaging assessments through the first year of life. Troponin I and CK-MB were measured on days 1, 3, 7 and 15; electrocardiogram (ECG) and echocardiography were repeated in parallel, and cranial ultrasound (US), ophthalmologic and audiologic screening were scheduled prospectively. Mean troponin rose from 50.7 ng L⁻¹ on day 1 to a peak of 120.7 ng L⁻¹ on day 7 (p < 0.01), normalising by one month, while echocardiograms remained structurally normal, and only one transient arrhythmia was recorded. CK-MB exceeded the reference range in 29% of infants but showed no clinical sequelae. Multiple periventricular hyperechogenicities were identified in 8/70 neonates (11%), and moderate anaemia (Hb ≤ 9.8 g/dL) occurred in 2 cases. Serum PCR detected high-level viraemia (>10⁸ genome equivalents mL⁻¹) in 40% of those tested; saliva and urine were consistently negative. No instances of myocarditis or hydrops were observed. Our findings indicate that congenital B19V infection during the current outbreak is marked by transient biochemical myocardial stress and subtle neurosonographic changes rather than overt cardiac disease, supporting an outpatient-focused follow-up strategy incorporating serial biomarkers and targeted neuroimaging. Full article

Chronic atrophic gastritis and intestinal metaplasia (IM) are gastric precancerous conditions (GPCs) associated with an increased risk of gastric cancer. Early detection and accurate characterization of GPC are therefore crucial for risk stratification and the implementation of preventive strategies. In the absence of clear mucosal changes observed through white-light imaging (WLI) or virtual chromoendoscopy, endocytoscopy can help unveil the presence of GPC by enabling in vivo assessment of nuclear and cellular structures at ultra-high magnification. Endocytoscopy is typically performed using WLI following dye-based staining of the mucosa. In this case, we demonstrate that combining endocytoscopy with the texture and color enhancement imaging (TXI) mode substantially improves the assessment of the gastric mucosa. In a 61-year-old man undergoing esophagogastroduodenoscopy, WLI showed multifocal erythema in the stomach, without clearly visible lesions on either WLI or narrow-band imaging. Conventional endocytoscopy revealed multiple small spots of IM with characteristic changes in glandular structures, which were even more evident when using the TXI mode. Histological analysis of targeted biopsies confirmed small foci of IM in both the antrum and corpus. The patient was enrolled in a surveillance program because of his clinical background. The combination of endocytoscopy with the TXI mode significantly enhances the delineation of mucosal and cellular architecture, supporting a more accurate optical diagnosis. Full article

Pelvic organ prolapse (POP) is a common pelvic floor disorder with substantial impact on women’s quality of life, necessitating accurate and reproducible diagnostic methods. This study investigates the use of three-dimensional (3D) transperineal ultrasound, integrated with artificial intelligence (AI), to evaluate pelvic floor biomechanics and identify correlations between biometric parameters and prolapse severity. Thirty-seven female patients diagnosed with genital prolapse (mean age: 65.3 ± 10.6 years; mean BMI: 29.5 ± 3.8) were enrolled. All participants underwent standardized 3D transperineal ultrasound using the Mindray Smart Pelvic system, an AI-assisted imaging platform. Key biometric parameters—anteroposterior diameter, laterolateral diameter, and genital hiatus area—were measured under three functional states: rest, maximal Valsalva maneuver, and voluntary pelvic floor contraction. Additionally, two functional indices were derived: the distensibility index (ratio of Valsalva to rest) and the contractility index (ratio of contraction to rest), reflecting pelvic floor elasticity and muscular function, respectively. Statistical analysis included descriptive statistics and univariate correlation analysis using Pelvic Organ Prolapse Quantification (POP-Q) system scores. Results revealed a significant correlation between laterolateral diameter and prolapse severity across multiple compartments and functional states. In apical prolapse, the laterolateral diameter measured at rest and during both Valsalva and contraction showed positive correlations with POP-Q point C, indicating increasing transverse pelvic dimensions with more advanced prolapse (e.g., r = 0.42 to 0.58; p < 0.05). In anterior compartment prolapse, the same parameter measured during Valsalva and contraction correlated significantly with POP-Q point AA (e.g., r = 0.45 to 0.61; p < 0.05). Anteroposterior diameters and genital hiatus area were also analyzed but showed weaker or inconsistent correlations. AI integration facilitated real-time image segmentation and automated measurement, reducing operator dependency and increasing reproducibility. These findings highlight the laterolateral diameter as a strong, reproducible anatomical marker for POP severity, particularly when assessed dynamically. The combined use of AI-enhanced imaging and functional indices provides a novel, standardized, and objective approach for assessing pelvic floor dysfunction. This methodology supports more accurate diagnosis, individualized management planning, and long-term monitoring of pelvic floor disorders. Full article