Search Results (93)

Background and Objective: Sex differences in the treatment of people with Parkinson’s disease (PwP) with a device-aided therapy (DAT) have been poorly investigated. Our aim was to analyze sex differences in the management and response to a DAT in PwP in daily clinical practice (DCP). Patients and Methods: Data collected in the DATs-PD GETM Spanish Registry until 30 October 2025 were used. This is a descriptive, observational, prospective, and multicenter clinical registry with progressive inclusion of PwP treated with a DAT in DCP conditions in more than 40 centers from Spain. Sex differences in the DAT received and changes in quality of life (QoL), motor symptoms (MS), non-motor symptoms (NMS), and autonomy for activities of daily living (AADL) after 6 months of treatment were analyzed. Results: A total of 618 PD patients (66.9 ± 9.5 years old; 57.6% men) were treated with a DAT. A significant difference was observed in the DAT type according to sex (p = 0.006), with 73.1% of PwP who were treated with deep brain stimulation being men. At the time of DAT indication, women were older, received a higher levodopa equivalent daily dose, and had a worse health-related QoL and AADL. OFF time decreased, whereas MS and NMS burden and health-related QoL improved at 6 months follow-up in both groups (men and women). AADL improved only in men during the OFF state. Conclusion: Sex differences were detected in the use of DATs in PwP. Improvement in OFF time, MS, NMS, and QoL was detected in both groups. Full article

Background/Objectives: Advanced Parkinson’s disease is characterized by severe motor fluctuations and disabling dyskinesias that often become refractory to conventional oral dopaminergic therapies. Methods: This study aimed to evaluate the clinical efficacy of levodopa–entacapone–carbidopa intestinal gel (LECIG) in 50 patients initiated during a four-year period at a tertiary movement disorders center. Motor outcomes were analyzed using Wilcoxon signed-rank and McNemar’s tests, while multivariable logistic regression was employed to identify predictors of improvement. Results: LECIG initiation significantly reduced mean daily OFF time from 4.63 ± 0.75 to 1.62 ± 1.97 h (p < 0.0001) and total dyskinesia duration by 65% (p < 0.0001). Furthermore, the prevalence of early morning akinesia decreased from 80% to 26%, and delayed ON phenomena were completely eliminated (p < 0.0001). Subgroup analyses indicated that patients with troublesome dyskinesia (≥1 h/day) achieved significantly greater reductions in involuntary movements compared to those with lower baseline dyskinesia levels (p = 0.013). Conclusions: These findings suggest that LECIG provides a meaningful and sustained stabilization of motor complications, highlighting its role as a valuable device-aided therapy in managing advanced Parkinson’s disease. Full article

Parkinson’s disease (PD) is a multifactorial neurodegenerative disorder characterized by progressive motor and non-motor manifestations, including early gastrointestinal dysfunction. Growing evidence implicates the gut microbiota as an active modulator of host immune tone and neurodegenerative vulnerability, extending beyond descriptive taxonomic associations toward functional and metabolic mechanisms. PD-associated dysbiosis is consistently characterized by altered microbial functional capacity, including reduced short-chain fatty acid (SCFA) production, enrichment of pro-inflammatory metabolic traits, and sustained immune stimulation at the intestinal interface. These shifts promote chronic low-grade inflammation and intestinal barrier perturbations, creating conditions that may facilitate abnormal α-synuclein aggregation within the enteric nervous system. Current management predominantly relies on dopaminergic replacement and related symptomatic strategies, such as levodopa combinations, dopamine agonists, monoamine oxidase-B and catechol-O-methyltransferase (COMT) inhibitors, and device-aided therapies, which alleviate symptoms but do not halt underlying neurodegeneration or modify long-term disease course. These therapeutic limitations have intensified interest in upstream mechanisms that might be amenable to disease-modifying interventions, particularly those arising at the level of the gut microbiota and gut–immune–brain axis. This narrative review integrates clinical, metagenomic, metabolomic, and mechanistic evidence to propose a unified model in which microbiota-driven immune and metabolic perturbations may act as upstream drivers converging on α-synuclein pathology, neuroinflammation, and neurovascular dysfunction. Full article

Parkinson’s disease (PD) is a progressive and heterogeneous neurodegenerative disorder and one of the fastest-growing causes of neurological disability worldwide. Although historically defined by motor manifestations resulting from nigrostriatal dopaminergic degeneration, PD is now recognized as a multisystem disorder. Non-motor features—including autonomic dysfunction, neuropsychiatric symptoms, cognitive impairment, and sleep-related disorders—frequently precede motor onset by years or even decades, delineating a clinically meaningful prodromal phase. The aetiology of PD reflects a complex interplay between genetic susceptibility and environmental exposures. Approximately 20% of cases are linked to identifiable pathogenic variants, most commonly in LRRK2, GBA1, and SNCA, whereas the majority arise from cumulative interactions among environmental factors, lifestyle determinants, and common genetic risk variants rather than from single causal mechanisms. Despite substantial advances in understanding disease biology, current therapies remain fundamentally symptomatic. Dopaminergic pharmacotherapy and device-aided interventions improve motor function and, in selected contexts, functional outcomes, but they do not modify disease progression. Non-motor symptoms remain a dominant driver of disability and reduced quality of life. Recent conceptual frameworks propose redefining PD as a biologically defined α-synucleinopathy. Emerging biomarkers, including α-synuclein seed amplification assays in cerebrospinal fluid and peripheral tissues, offer unprecedented opportunities to define biological disease, enable early detection, and stratify patients. However, biomarker positivity currently informs diagnosis and classification rather than prognostication or therapeutic selection, and validated intermediate endpoints linking biomarker change to sustained functional benefit remain lacking. Consequently, translation into disease-modifying therapies has been constrained by late-stage intervention, reliance on clinically defined populations, limited trial generalizability, and marked global inequities in access to advanced diagnostics and treatments. This narrative review synthesizes current evidence on PD epidemiology, diagnosis, aetiology, progression, and treatment, emphasizing gene–environment interactions, convergence on shared pathogenic pathways, limitations of existing therapeutic paradigms, and the as-yet unrealized potential of biologically informed precision care. Full article

Osteoarthritis (OA) is a progressive musculoskeletal disorder that affects not only older adults but also younger populations, often leading to chronic pain, joint stiffness, functional impairment, and a decline in quality of life. Non-invasive physical rehabilitation plays a critical role in slowing disease progression, alleviating symptoms, and maintaining joint mobility. However, rehabilitation tools such as compression gloves and manual exercise aids are typically passive and provide minimal real-time feedback to patients or clinicians. Others, such as exoskeletons and soft-actuated devices, can be costly or complex to use. This study presents the design and development of an electrically actuated glove integrated with force and flex sensors, intended to assist individuals diagnosed with Stage 2 OA in performing guided finger exercises. The system integrates a digital front-end application that offers real-time feedback and data visualization, enabling more personalized and trackable therapy sessions for both patients and healthcare providers. Preliminary results from an initial human trial with healthy participants demonstrate that the glove enables naturalistic movement without imposing excessive restriction or augmentation of motion. These findings support the glove’s potential in preserving hand coordination and dexterity, key objectives in early-stage OA intervention, and suggest its suitability for integration into home-based or clinical rehabilitation protocols. Full article

Rehabilitation robots are a leading solution towards bridging the gap between the growing number of rehabilitation patients requiring therapy and the limited availability of healthcare professionals. However, existing robotic systems are often bulky and expensive, limiting their ability to provide widespread, repetitive, and intensive exercises. This paper presents the development of an impedance-based control strategy designed to provide safe and compliant upper-body passive and active exercises on the low-cost PlanAID robot, which is built using consumer-grade components. The system’s functionalities are evaluated using a high-precision force sensor. Results show that the PlanAID exhibits performance comparable to seminal devices such as the MIT-Manus, achieving a similar applicable reaction force target of 28 N and reflected inertia of 1.1 kg. Although the overall performance is comparable, the low-cost PlanAID prototype suffers from reduced coupled stability margins, limiting the maximum achievable virtual spring constant to 1100 N/m. Despite this limitation, the stiffness values required in practical applications remain low, suggesting that the PlanAID could potentially be a viable candidate for real-world rehabilitation. Initial user feedback was obtained through a preliminary qualitative trial involving healthy subjects. Full article

Hypertensive kidney disease (HKD) represents a significant contributor to chronic kidney disease and end-stage renal failure, yet its early detection remains challenging due to nonspecific clinical and imaging findings. The lack of a noninvasive diagnostic tool, preventing the use of biopsy and diagnosis by exclusion, suggests the underdiagnosis of patients and overestimation of HKD as the cause of renal replacement therapy. Ultrasonography, including Doppler assessment and renal resistive index measurements, provides a widely accessible, noninvasive approach to evaluate renal structure and hemodynamics, aiding in the identification of early renal impairment or renal artery stenosis. Shear-wave elastography (SWE) has emerged as a promising modality for noninvasive assessment of renal stiffness, potentially detecting structural changes prior to functional deterioration. Current evidence demonstrates SWE’s diagnostic potential in chronic kidney disease and early hypertensive renal disease; however, limitations such as inter-device variability, heterogeneous patient populations, and short follow-up periods constrain its clinical applicability. Neither ultrasonography nor SWE can yet serve as standalone diagnostic tools for HKD, emphasizing the need for standardization, further validation, and longitudinal studies to clarify their role in patient management and prediction. Full article

Total joint arthroplasty is among the most common surgical procedures performed worldwide, with frequency increasing due to demographic changes. Accelerating the diagnostic process using new techniques is crucial for effective therapy. This pilot study aims to test such innovative technology in the context of periprosthetic joint infection (PJI) using Scattered Light Integrating Collector (SLIC) technology. While we wish to evaluate whether SLIC can be used to reliably detect the status of infection within human tissue samples in the future, our current research focused on building its foundation by evaluating steps of sample preparation that allow for heightened growth depiction. It is, to our knowledge, the first study concerning the usage of solid human tissue samples using the SLIC device. Adult patients presenting with native or periprosthetic joint infections were included in this prospective study. Biopsies were obtained using sequential sampling, and bacterial density was optimized through titration series. Cryopreservation and agents influencing coagulation were investigated. Our study demonstrates that simple pretreatment could aid in detecting pathogen growth in infected tissue samples. Findings showed a clear advantage for no addition of agents affecting coagulation. Additionally, our protocols proved reliable after prolonged cryopreservation at −20 °C for up to 8 weeks, showing no significant difference compared to primary testing. AUC comparison showed comparable results for sample storage at −80 °C for up to 8 weeks. Similar outcomes were seen for samples ranging from 25 µL to 300 µL, with biological replicates displaying higher thresholds for larger volumes without significant differences. This study introduces a simple and quick diagnostic tool for detecting bacterial growth using tissue biopsies and develops an SOP for further research with this innovative technique. The suggested SOP enables SLIC to hint at an underlying bacterial infection within 5 h using joint tissue, offering a possible novel approach in diagnosing periprosthetic joint infections and septic arthritis. While not yet designed to compare sensitivity to other culture methods, it provides a solid basis for further clinical research. Full article

Background/Objectives: Hepatocellular carcinoma (HCC), the predominant form of liver cancer, ranks as the third leading cause of cancer-related deaths worldwide. With the shift from viral hepatitis to metabolically dysfunction-associated steatosis liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH) as primary etiologies, we aimed to review ongoing clinical trials in adult HCC patients to highlight emerging treatments, particularly for nonviral HCC cases. Methods: We searched ClinicalTrial.gov (last March 2025) for interventional trials. We included ongoing (recruiting/active/not recruiting), phase I-IV, adults (>18 years old), and HCC-focused only clinical trials. We excluded observational and interventional (biological, genetic, device, or procedure) clinical trials. Results: This review highlights recent advances in HCC treatment, with a focus on the transformative role of immunotherapy. Evidence suggests that nonviral HCC, as well as HCC with MASLD/MASH background livers, may have reduced sensitivity to immunotherapy. Thus, there is a critical need for molecular insights to improve patient stratification. Moreover, we examine how new diagnostic tools, including liquid biopsies, influence treatment decisions and aid in monitoring responses. Limitations limited MASLD/MASH-specific trial data. Conclusions: We review current research and its integration into clinical practice, advancing HCC therapy toward personalized, patient-centered care. Full article

Microfluidic paper-based analytical devices (µPADs) are ideal for point-of-care diagnostics due to their low cost, compact size, and ease of use. However, current designs have limited multiplexing capabilities, making it difficult to simultaneously detect pathogens and biomarkers in the same sample. In this work, we introduce NanoArrayPAD−X, a novel µPAD design that combines wax-printed microfluidic networks with an array of nanoprobes for the simultaneous detection of multiple targets. This is achieved by distributing the sample through the microfluidic network containing X detection areas. There, targets are captured through physical interactions and recognized by specific antibody-coated nanoprobes released from the nanoprobe array. This generates X dots whose color depends on the concentration of the targets in the sample. A NanoArrayPAD−5 platform capable of detecting five targets was developed to aid in the diagnosis of ventilator-associated pneumonia (VAP). The sensor array could detect Pseudomonas aeruginosa, Klebsiella pneumoniae, Staphylococcus aureus, Escherichia coli, and the inflammatory biomarker myeloperoxidase (MPO) with a total turnaround time of 25 min, which is faster than waiting for an overnight culture and the results of an ELISA. Notably, our prototype successfully detected the targets in 87 bronchial aspirate (BAS) specimens, thus demonstrating the suitability of the platform for analyzing complex samples with sputum-like qualities. These findings establish NanoArrayPAD−X as a promising tool for the rapid, multiplexed screening of respiratory pathogens and biomarkers, with potential for guiding personalized antimicrobial therapy in suspected cases of nosocomial pneumonia. Full article

Hydrogels are hydrophilic, soft polymer networks with high water content and mechanical properties that are tunable; they are also biocompatible. Therefore, as biomaterials, they are of interest to modern medicine. In this review, the main applications of hydrogels in essential clinical applications are discussed. Chemical, physical, or hybrid crosslinking of either synthetic or natural polymers allow for the precise control of hydrogels’ physicochemical properties and their specific characteristics for certain applications, such as stimuli-responsiveness, drug retention and release, and biodegradability. Hydrogels are employed in gynecology to regenerate the endometrium, treat infections, and prevent pregnancy. They show promise in cardiology in myocardial infarction therapy through injectable scaffolds, patches in the heart, and medication delivery. In rheumatoid arthritis, hydrogels act as drug delivery systems, lubricants, scaffolds, and immunomodulators, ensuring effective local treatment. They are being developed, among other applications, as antimicrobial coatings for stents and radiotherapy barriers for urology. Ophthalmology benefits from the use of hydrogels in contact lenses, corneal bandages, and vitreous implants. They are used as materials for chemoembolization, tumor models, and drug delivery devices in cancer therapy, with wafers of Gliadel presently used in clinics. Applications in abdominal surgery include hydrogel-coated meshes for hernia repair or Janus-type hydrogels to prevent adhesions and aid tissue repair. Results from clinical and preclinical studies illustrate hydrogels’ diversity, though problems remain with mechanical stability, long-term safety, and mass production. Hydrogels are, in general, next-generation biomaterials for regenerative medicine, individualized treatment, and new treatment protocols. Full article

Background and Objectives: Automated insulin delivery (AID) systems represent a major advancement in type 1 diabetes (T1D) management, particularly in pediatric populations. However, real-world evidence comparing their effectiveness to conventional multiple daily injection (MDI) therapy in youth remains limited. This study aimed to evaluate the impact of transitioning from MDI therapy to AID systems on glycemic control in children and adolescents with T1D, and to explore potential differences based on baseline HbA1c levels and device type. Materials and Methods: In this single-center, retrospective observational study, 76 children and adolescents with T1D were evaluated before and after switching from MDI to either the Medtronic MiniMed™ 780G or Tandem t:slim X2™ Control-IQ system. Glycemic control was assessed using continuous glucose monitoring (CGM)-derived metrics at three time points: the last 15 days of MDI therapy (T0), 15 days after (T1), and 6 months after (T2) AID initiation. Statistical comparisons were conducted across time points and between subgroups stratified by baseline HbA1c and AID system. Results: Significant improvements in glycemic control were observed as early as 15 days after AID initiation, with sustained benefits at 6 months. Time in range (TIR) increased from 62.0% at baseline to 76.7% at 15 days and 75.8% at 6 months, and time in tight range (TITR) from 39.8% to 53.9% at T1 and 52.1% at T2 (both p < 0.001). Improvements were more pronounced in participants with higher baseline HbA1c (+16.9% for TITR and +22.3% for TIR). No significant differences in glycemic outcomes were observed between device groups, although algorithm-driven differences in insulin delivery patterns were noted. Total daily insulin dose and BMI increased significantly over time (p < 0.001 and p = 0.008, respectively). Conclusions: AID therapy leads to rapid and sustained improvements in glycemic control among youth with T1D, particularly in those with suboptimal baseline control. These benefits highlight the clinical value of AID systems, while also emphasizing the need for monitoring potential metabolic impacts. Full article

Heart failure, a significant global health burden, is divided into heart failure with reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF), characterized by systolic dysfunction and diastolic stiffness, respectively. While HFrEF benefits from pharmacological and device-based therapies, HFpEF lacks effective treatments, with both conditions leading to high rehospitalization rates and reduced quality of life, especially in older adults with comorbidities. This review explores the role of artificial intelligence (AI) in advancing autonomic neuromodulation for heart failure management. AI enhances patient selection, optimizes stimulation strategies, and enables adaptive, closed-loop systems. In HFrEF, vagus nerve stimulation and baroreflex activation therapy improve functional status and biomarkers, while AI-driven models adjust stimulation dynamically based on physiological feedback. In HFpEF, AI aids in deep phenotyping to identify responsive subgroups for neuromodulatory interventions. Clinical tools support remote monitoring, risk assessment, and symptom detection. However, challenges like data integration, ethical oversight, and clinical adoption limit real-world application. Algorithm transparency, bias minimization, and equitable access are critical for success. Interdisciplinary collaboration and ethical innovation are essential to develop personalized, data-driven, patient-centered heart failure treatment strategies through AI-guided neuromodulation. Full article

Background/Objectives: Cochlear implants (CIs) and hearing aids (HAs) have enhanced auditory rehabilitation in elderly individuals, yet limitations in musical perception and psychosocial integration persist. This systematic review aimed to evaluate the effects of music therapy (MT) on the quality of life (QoL), self-esteem, auditory perception, and cognition in older CI and HA users. Methods: A comprehensive search of PubMed was conducted up to March 2022 following PRISMA guidelines. Studies involving participants aged ≥ 60 years with CIs and/or HAs were included. Ten studies (n = 21,632) met eligibility criteria. Data were extracted and assessed using the Newcastle–Ottawa Scale. Results: MT led to improved sound quality, with HISQUI19 scores rising from 60.0 ± 21.8 to 74.2 ± 27.5. Early MT exposure was associated with significantly better MUMU outcomes (p = 0.02). Bilateral CI users showed enhanced stereo detection (52% to 86%), and CI + HA users achieved CNC scores exceeding 95%. Postlingual CI users outperformed prelingual peers in musical discrimination (9.81 vs. 3.48; p < 0.001). Long-term HA use was linked to better a QoL and reduced loneliness. Conclusions: While music therapy appears to support auditory and psychosocial functioning in hearing-impaired older adults, the absence of randomized controlled trials limits causal inference regarding its effects. These results support its integration into hearing rehabilitation strategies for older adults. Full article

Transcatheter aortic valve replacement (TAVR) has become a well-established treatment for severe aortic stenosis across all levels of surgical risk. While transfemoral access remains the default approach, complications arising from vascular access—especially in patients with peripheral artery disease (PAD)—pose significant challenges. Hostile vascular access, characterized by narrow vessel diameters, severe calcification, and tortuosity, complicates the procedure and necessitates alternative strategies. Recent advancements, such as intravascular lithotripsy (IVL), have shown promise in managing severely calcified arteries, improving the feasibility of transfemoral TAVR in patients previously considered ineligible. IVL uses pulsatile sonic waves to fragment arterial calcifications, enhancing vessel compliance and facilitating safe device delivery. Studies have demonstrated that IVL-assisted TAVR improves procedural success and reduces complications in patients with PAD. Additionally, orbital atherectomy, an adjunctive therapy targeting both concentric and eccentric calcifications, may complement the management of complex arterial calcification. The Hostile and passage–puncture scores offer valuable risk stratification tools for predicting vascular complications, aiding in better access site selection. Post-procedural echocardiography, particularly femoral artery sonography, may also play a role in detecting vascular complications early, enabling timely intervention. Finally, alternative access sites are increasingly being explored, with emerging data helping to guide the final access site decision. As TAVR continues to expand into lower risk populations, optimizing vascular access strategies remains essential to improving procedural outcomes. This review highlights the importance of preoperative imaging, endovascular techniques, and post-procedural monitoring in overcoming vascular challenges and ensuring successful TAVR outcomes. Full article