Search Results (442)

Background: Complex regional pain syndrome (CRPS) is a disabling post-traumatic pain condition that may occur after distal radius fracture (DRF), potentially impairing recovery and upper-limb function. Identifying effective preventive strategies after DRF is therefore clinically important. Objective: To synthesize and critically appraise interventions intended to prevent CRPS after DRF, including rehabilitation protocols and clinical prophylaxis strategies. Methods: This systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses PRISMA and was registered in the International Prospective Register of Systematic Reviews PROSPERO (CRD42023408499). Five databases (PubMed, Web of Science, Scopus, ScienceDirect, and B-on) were searched for studies published from January 2013 to 22 September 2023 in English, Portuguese, or Spanish. The primary outcome was CRPS incidence after DRF. Findings were synthesized narratively due to heterogeneity in interventions and diagnostic criteria, and risk of bias was assessed using design-appropriate tools. Results: Nine studies were included (total N = 7075; CRPS cases n = 127). Interventions comprised vitamin C supplementation (2 studies), probiotics, aspirin, polarized/polychromatic light therapy plus conventional treatment, early rehabilitation/home-exercise programs, and general CRPS-prevention protocols after DRF. Probiotics and aspirin did not reduce CRPS incidence. Vitamin C showed mixed findings across the included studies and remains debated in the broader literature. Light therapy was associated with reduced CRPS occurrence in a single study, while early active home-exercise programs appeared promising but were supported by a limited number of studies. Study designs and CRPS diagnostic criteria varied, and risk of bias was moderate-to-serious in several non-randomized studies. Conclusions: Evidence remains insufficient to support a single standardized prevention protocol for CRPS after distal radius fracture. Early active rehabilitation and progressive mobilization appear promising, but the available evidence is still limited and heterogeneous. Adjunctive strategies such as vitamin C and light therapy should be interpreted with caution, as findings for vitamin C remain debated in the literature and the evidence for light therapy is currently based on a single study. Other approaches, including probiotics and aspirin, have shown inconclusive results. Full article

Background/Objectives: Therapeutic drug monitoring (TDM) of immunosuppressants is essential in treating pediatric kidney diseases; however, repeated venipuncture is burdensome in children. We evaluated whether minimally invasive fingerstick capillary sampling combined with liquid chromatography–tandem mass spectrometry (LC-MS/MS) provides results analytically comparable to those of conventional venous sampling. Methods: Capillary whole blood (2.8 µL) was collected via fingersticks from pediatric patients receiving mycophenolate mofetil, with or without tacrolimus (TAC) or cyclosporine A (CsA). Drug concentrations were quantified using a previously validated simultaneous LC-MS/MS method and compared with conventional venous sampling using linear regression and Bland–Altman analyses. Results: Seventy-four paired samples from 21 patients were analyzed. Strong correlations were observed between capillary and venous samples for mycophenolic acid (MPA), TAC, and CsA (R² > 0.90). Hematocrit correction improved agreement for MPA. Bland–Altman analyses demonstrated acceptable bias across analytes. Conclusions: Fingerstick-based microvolume sampling combined with LC-MS/MS provides analytically reliable immunosuppressant quantification in pediatric patients. Although larger clinical validation is required, this minimally invasive approach may reduce procedural burden and may support future outpatient or home-based TDM strategies. Full article

Background: Chronic venous insufficiency (CVI) is characterized by venous dysfunction in the lower extremities, leading to increased venous pressure, edema, and reduced quality of life. Objectives: This study aimed to evaluate the additional effect of a structured home-based calf muscle strengthening exercise program when combined with standard compression therapy, by comparing disease severity, musculoskeletal function, and quality of life over time between patients receiving compression therapy alone and those receiving combined intervention. Methods: A randomized controlled trial was conducted in 50 patients with CVI (CEAP C₃–C₅), who were assigned to an experimental group (n = 25) and a control group (n = 25). Outcomes were assessed at baseline, week 6, and week 12. Disease severity was measured using the Revised Venous Clinical Severity Score (rVCSS), and swelling, muscle, and joint function were assessed using calf muscle strength and ankle range of motion. Quality of life outcomes were assessed using the chronic venous disease quality of life questionnaire (CIVIQ-20). Data were analyzed using two-way repeated measures ANOVA. This trial was registered retrospectively at the Thai Clinical Trials Registry (registration number: TCTR20260307002). Results: Significant group × time interaction effects were observed for disease severity (right leg: F = 81.562, p < 0.001, η²p = 0.630; left leg: F = 73.765, p < 0.001, η²p = 0.606), indicating greater improvement in the experimental group over time. Calf muscle strength significantly increased in the experimental group (right leg: F = 395.246, p < 0.001, η²p = 0.892; left leg: F = 87.278, p < 0.001, η²p = 0.645). Ankle range of motion also improved significantly (p < 0.001). Quality of life showed significant improvement with a group × time interaction effect (F = 66.104, p < 0.001, η²p = 0.579). Conclusions: A structured home-based calf muscle strengthening exercise program combined with compression therapy produced significant improvements in disease severity, musculoskeletal function, and quality of life over time, demonstrating an additive therapeutic effect in patients with CVI. Full article

Telerehabilitation—the remote delivery of rehabilitation services—is undergoing a paradigm shift with the convergence of immersive virtual reality (VR) and wearable biosensor technologies. This perspective article outlines a vision for home-based motor and cognitive rehabilitation that is engaging, personalized, and data-driven. We describe how immersive VR environments (for example, simulations of home settings or supermarkets) coupled with wearable sensors can address current challenges in rehabilitation by increasing patient motivation, enabling real-time biofeedback, and supporting remote clinician supervision. Gamification mechanisms and rich sensory feedback in VR are highlighted as key strategies to enhance user engagement and adherence to therapy. We discuss conceptual innovations such as multi-sensor data integration, dynamic difficulty adaptation, and AI-driven personalization of exercises, derived from recent research and our development experience, and consider their potential benefits for patients with neuro-cognitive-motor impairments (e.g., stroke, Parkinson’s disease, and multiple sclerosis). Implementation scenarios for home-based therapy are presented, emphasizing scalability, standardized digital metrics for monitoring progress, and seamless involvement of clinicians via telehealth platforms. We also critically examine the current limitations of VR and telehealth rehabilitation and how an integrative model could overcome these barriers. More specifically, this perspective defines the engineering requirements of a closed-loop VR-based telerehabilitation framework, including multimodal data synchronization, calibration, signal-quality management, interpretable adaptive control, digital biomarker validation, and practical strategies to improve accessibility, privacy, and scalability in home-based neurological rehabilitation. Full article

Peripheral artery disease (PAD) is a pervasive atherosclerotic condition affecting well over 100 million adults worldwide and associated with major functional limitations, reduced quality of life, and elevated risks of myocardial infarction, stroke, limb events, and mortality. Exercise therapy—preferably supervised or delivered through structured, monitored home-based programs—is a first-line, guideline-endorsed therapy that improves walking performance and patient-reported outcomes and contributes to comprehensive secondary prevention. This review synthesizes mechanistic underpinnings (endothelial, angiogenic, metabolic, and autonomic) and appraises the comparative effectiveness, safety, and implementation models of supervised exercise therapy (SET), structured home-based and hybrid programs, and alternative modalities in PAD. Finally, we summarize policy aspects and persistent gaps to guide clinical practice and future research. Full article

Background: Patients with pancreatic cancer (PC) commonly present with reduced aerobic fitness, sarcopenia, and malnutrition, which may increase perioperative risk and compromise access to chemotherapy treatments. Although exercise-based prehabilitation can improve physical fitness, its implementation is often limited by short diagnostic-to-surgery intervals and treatment-related toxicity. Methods: We conducted a pilot prospective pretest–posttest feasibility study in Torino, Italy. Patients with PC undergoing neoadjuvant chemotherapy prior to surgery were offered a 4-week, partially supervised, home-based bimodal exercise prehabilitation program (single-arm design) combining remotely monitored high-intensity interval training (HIIT) on a cycle ergometer with functional and resistance exercises. The primary outcome was adherence to prescribed exercise frequency, intensity, and duration, objectively assessed via remote monitoring. Secondary outcomes included cardiorespiratory fitness (CPET), muscle function, body composition, fatigue, quality of life, and circulating inflammatory markers. Results: From July 2022 to February 2024, 23 patients were screened; 15 were eligible and 10 enrolled. Four participants discontinued the intervention (two due to asthenia/fatigue, one due to chemotherapy-related adverse events, and one for organizational reasons), leaving six participants who completed the program. Among completers, fatigue and quality of life did not change meaningfully. Aerobic capacity and muscle function outcomes were generally stable, with few pre–post changes exceeding the minimum clinically important difference (MCID) thresholds used. Body composition markers and the assessed circulating cytokines/chemokines remained unchanged except for IL-6 levels, which decreased significantly (p < 0.05). Conclusions: A partially supervised, home-based HIIT-based prehabilitation program is feasible for a subset of PC patients undergoing neoadjuvant therapy, but a substantial attrition rate suggests the need for more flexible symptom-adapted prescriptions and enhanced supportive strategies. Full article

Background/Objectives: The F3 peptide, a tumor-homing peptide known to bind cell-surface nucleolin, is frequently employed as a targeting vector in cancer research. However, the impact of the modification site on its cellular binding properties has not been investigated yet. In this work, we aimed to design an improved F3-based radioconjugate by identifying the optimal conjugation site and establishing a protocol for its biological evaluation in vitro. To achieve this, we compared F3 peptide derivatives modified at their N- or C-termini with DOTA for complexation of indium-111 (¹¹¹In) for SPECT or Auger electron therapy or a fluorophore (FITC) for optical imaging. Methods: N-and C-terminal DOTA-modified F3 peptides were radiolabeled with indium-111 and compared for their in vitro stability in different physiologically relevant media. Suitable nucleolin-positive cell lines for further in vitro studies were identified by confocal microscopy of a FITC-labeled F3 peptide derivative. The radioconjugates were then investigated on MDA-MB-231 (breast cancer) and PC-3 (prostate cancer) cells for nucleolin-specific cell binding and uptake, and several parameters of the in vitro assays were varied to establish a suitable protocol. Results: In general, in vitro assays with F3 peptide conjugates are challenging, as the outcome depends on a number of experimental parameters, leading, in some cases, to varying results. In particular, the presence of Ca²⁺ and Mg²⁺ had a decisive impact on the results, likely because the metal ions compete with the binding of F3 conjugates to nucleolin. The C-terminal modified, ¹¹¹In-labeled F3 radioconjugate performed better than the N-terminal modified analog. While several parameters of the in vitro experiments were optimized, the overall cell uptake in vitro of radioactivity was still low (<2% of applied radioactivity). Conclusions: A standardized in vitro protocol for evaluating F3 peptide conjugates on cancer cells was established, revealing that the C-terminus is the preferred site for modification. Because the cellular uptake of the radiotracer was shown to likely not be sufficient for radiotracer development, further studies on the optimization of the F3 peptide conjugates, including structural modifications, are required. Full article

Background: Joubert syndrome (JS) is a rare ciliopathy characterized by cerebellar and brainstem malformations and the molar tooth sign on magnetic resonance imaging. Motor impairment is primarily driven by axial hypotonia, impaired postural control, and disrupted respiratory-postural integration. Longitudinal reports describing structured neurorehabilitation with standardized functional outcomes remain limited. Case presentation: We report a female child with prenatally suspected vermian hypoplasia and postnatally MRI-confirmed Joubert syndrome. Subsequent molecular testing performed at the age of 3 years and 11 months identified heterozygous variants in the B9D2 gene associated with Joubert syndrome. Early development was marked by axial hypotonia, global motor delay, impaired trunk stabilization, sleep-disordered breathing, and early hip migration. At 2.5 years of age, following motor plateau under conventional therapy, a structured 12-month rehabilitation programme was introduced, combining Vojta-based reflex locomotion, respiratory therapy targeting thoraco-diaphragmatic synchronization, daily home-based practice, and supported standing. Results: After 12 months, gross motor function improved substantially, with GMFM-88 increasing from 12% to 52% (+40 percentage points). PEDI scaled scores improved across all domains, with mobility increasing from 8 to 40, self-care from 15 to 45, and social function from 25 to 50. Ataxia severity decreased from 22 to 15 on the modified Brief Ataxia Rating Scale, consistent with improved trunk stability and coordination. Postural and respiratory organization improved, reflected by a reduction in the subcostal angle from 137° to 90°, an increase in sacral slope from 5° to 10°, and increased expiratory pressure from 10 to 25 mmHg. Caregiver-reported assessment combined with structured clinical observation indicated improved functional visual performance, including enhanced visual attention, visuomotor coordination, and environmental visual interaction. Conclusions: Structured neurorehabilitation was associated with substantial functional improvement across motor, postural, and respiratory domains. These findings support the clinical relevance of mechanism-oriented neurorehabilitation and standardized longitudinal outcome assessment in Joubert syndrome. Full article

Background: Accurate evaluation of the Near Point of Convergence (NPC) is essential for diagnosing and managing convergence insufficiency (CI). Conventional assessment relies on the patient’s verbal feedback and the examiner’s visual observation, making it subjective and examiner-dependent. The AI-based MobileS platform, previously validated for both diagnosis and home-based therapy of CI, enables smartphone-based measurement and visualisation of NPC through eye tracking, without the need for verbal responses or additional equipment. This study, the third stage of our research programme, examined how ophthalmologists interpret NPC data when presented as videos versus AI-derived graphs. Methods: Twenty-two ophthalmologists completed an online questionnaire with 20 NPC test cases from the validated MobileS database, presented as both silent videos and AI-derived graphs. Accuracy was analysed using mixed-effects logistic regression, and continuous error was assessed using clustered bootstrap. Results: Graph-based interpretation showed higher odds of accurate NPC identification than video-based interpretation at the primary ±5 mm threshold (OR = 19.7, 95% CI: 13.50–28.74; p < 0.0001). Absolute error was lower for graphs than videos (Graphs − Videos: −22.73 mm; 95% CI: −26.88 to −18.59; p < 0.0001). “Uncertain” responses occurred in 28.2% of video-based assessments and 0% of graph-based assessments. Off-target errors decreased from 50.2% (videos) to 3.6% (graphs). Conclusions: AI-derived graphs of eye-movement data were associated with improved NPC estimation, suggesting a potential role in supporting clinical and tele-ophthalmology workflows. Full article

Purpose: Castration-resistant prostate cancer (CRPC) responds poorly to conventional chemotherapy. We evaluated a cell-based enzyme–prodrug therapy using adipose-derived stem cells (ADSCs) engineered to express cytosine deaminase (CD) or carboxylesterase 2 (CE2), paired with their respective prodrugs 5-fluorocytosine (5-FC) or irinotecan (CPT-11), to compare their antitumor efficacy. Materials and Methods: Human telomerase reverse transcriptase (hTERT)-immortalized ADSCs were transduced with CD or CE2, and transgene expression and stem cell phenotype were confirmed. CD expression was verified at the transcript level and by functional 5-FC-to-5-fluorouracil (5-FU) conversion, whereas CE2 expression was verified by transcript analysis and immunoblotting. Tumor tropism toward PC3 prostate cancer cells was tested using migration assays and analysis of chemoattractant ligand/receptor expression. Prodrug-induced self-killing and bystander tumor cell killing were assessed through viability assays and co-culture with PC3 cells. For the CE2/CPT-11 system, SN-38 was not directly quantified; functional activity was inferred from prodrug-dependent cytotoxicity and in vivo efficacy. In vivo efficacy was evaluated in nude mice with PC3 tumors treated systemically with engineered ADSCs plus prodrug. Results: CD- and CE2-expressing ADSCs were successfully established and retained mesenchymal stem cell (MSC) characteristics. Both cell types exhibited significant migration toward PC3 cells. The CE2/CPT-11 system produced stronger prodrug-mediated cytotoxicity than CD/5-FC, with CE2-modified ADSCs showing higher sensitivity to CPT-11 and inducing greater apoptosis in co-cultured PC3 cells. In vivo, both treatments suppressed tumor growth, but CE2/CPT-11 achieved greater inhibition (tumor volume ~26% of control vs. ~32% for CD/5-FC at day 14). No overt clinical toxicity was observed based on body weight and daily clinical monitoring; however, hematology/serum chemistry were not assessed. Conclusions: Engineered ADSCs home to CRPC tumors and enable local prodrug activation, producing significant antitumor effects. Within the constraints of our in vitro assays and subcutaneous xenograft model, CE2/CPT-11 demonstrated stronger efficacy outcomes than CD/5-FC. Mechanistic attribution to intratumoral SN-38 exposure should be confirmed by direct metabolite measurements in future studies. Full article

Conventional drug delivery systems often suffer from problems such as limited targeting specificity, short half-lives, poor biocompatibility, and systemic toxicity, which significantly limit their therapeutic efficacy against major diseases like cancer. Blood cells, as native components of the human circulatory system, offer distinct advantages including low immunogenicity, long circulation times, remarkable mechanical flexibility, and innate ability to home to disease sites. These attributes make blood cells a promising platform for next-generation targeted drug carriers. In this review, we examine the biological and mechanical properties of red blood cells, white blood cells, platelets, and cell-derived membrane vesicles. We highlight recent advances in how these cells are engineered and loaded with drugs, and their application in tumor-targeted therapy, while also considering their potential in other diseases. We also discuss current technical challenges and outline future directions for clinical translation, offering a practical perspective on advancing blood cell-based delivery technologies. Full article

Objectives: Persistent amblyopia often shows limited response to occlusion therapy once visual acuity improvement plateaus. This study evaluated the efficacy of a two-phase protocol combining occlusion therapy and home-based perceptual learning (PL) in children with persistent amblyopia, including those with congenital pathology. Methods: This longitudinal case series included 40 patients (mean age 9.4 ± 3.4 years). Phase I consisted of occlusion therapy until best-corrected visual acuity (BCVA) plateaued. Phase II combined continued occlusion with home-based PL training until BCVA in amblyopic eye reached 0.00 logMAR or treatment was discontinued. BCVA and stereoacuity (TNO test) were assessed at baseline, after Phase I, after Phase II when applicable, and at a prospective evaluation visit. Treatment success was defined as a gain of ≥2 logMAR lines or a final BCVA ≤0.10 logMAR. Patients were stratified according to cumulative training exposure (<10 h vs. ≥10 h). Results: After Phase I, mean BCVA improved from 0.45 ± 0.23 to 0.26 ± 0.19 logMAR (p < 0.01). After Phase II, BCVA further improved to 0.13 ± 0.16 logMAR (p < 0.01). Stereoacuity showed a modest but significant improvement, from 928 ± 505 to 748 ± 558 arcsec (p = 0.01). Treatment success was achieved in 72% of patients completing ≥10 h of perceptual learning compared with 40% in those completing <10 h (RR = 1.94, 95% CI 1.01–3.73). Patients with non-pathological amblyopia achieved greater final BCVA than those with congenital pathology. Conclusions: The combination of occlusion therapy and home-based PL was associated with further improvement in visual acuity and modest gains in stereoacuity in children with persistent amblyopia. Greater cumulative training exposure was associated with higher treatment success, supporting PL as a clinically valuable adjunct to standard amblyopia management. Full article

Background: Functional Electrical Stimulation (FES) for post-stroke drop foot is commonly applied in acute and subacute stroke rehabilitation or as part of long-term home-based programs in chronic patients. Evidence supporting short facility-based rehabilitation programs incorporating FES in chronic populations remains limited. The aim of this study was to explore functional outcomes associated with such a program in a chronic population. Materials and methods: A 10-day facility-based rehabilitation program incorporating FES therapy followed by 3-month follow-up was delivered to 14 chronic post-stroke patients with foot drop (8 women; aged 62.6 ± 12.2 years). FES was applied during walking with stimulation synchronized to the swing phase of gait (35 Hz, 300 μs, 15 min per session). Activities of daily living and mobility were assessed using clinical outcome measures. Statistical significance (p < 0.05), effect sizes, and minimal clinically important difference (MCID) responder rates were evaluated. Results: Statistically significant improvements were observed across all outcome measures post-treatment and at follow-up, with MCID responder rates exceeding 50%. Conclusions: A short facility-based multimodal rehabilitation program incorporating FES was associated with functional improvements in chronic post-stroke patients. Given the multimodal design, these findings cannot be attributed to FES alone and should be interpreted as exploratory. Full article

Background/Objectives: Therapeutic drug monitoring (TDM) is essential for optimizing immunosuppressive therapy in solid-organ transplant recipients by maintaining efficacy, while minimizing adverse effects. However, conventional TDM relies on venous sampling and separate assays for tacrolimus (TAC) in whole blood and mycophenolic acid (MPA) in plasma, thereby increasing patient burden and procedural complexity. To address these limitations, we investigated the clinical utility of a microvolume, liquid-phase microsampling device (MSW2™) in combination with liquid chromatography–tandem mass spectrometry (LC-MS/MS). Methods: We established and applied an LC-MS/MS method for simultaneous quantification of TAC, MPA, and mycophenolic acid β-D-glucuronide (MPAG) using only 2.8 µL of whole blood collected with MSW2™, which eliminates drying or extraction steps. Hematocrit-based correction was applied to estimate plasma MPA concentrations from whole-blood measurements. The method was evaluated in 60 renal transplant recipients with paired venous samples for comparison. Analytical performance was assessed using regression, Bland–Altman analyses, predictive metrics, and stability testing under different storage conditions. Results: Microsampled and venous concentrations were strongly correlated (R² > 0.95). Estimated plasma MPA concentrations derived from whole blood closely approximated plasma concentrations (bias < 5%). Reducing the sample volume from 5.6 µL to 2.8 µL improved precision and increased the success rate of blood collection from 72.9% to 94.0%. All analytes remained stable for up to 72 h at ≤25 °C. Conclusions: This approach enables accurate, simultaneous quantification of multiple immunosuppressants from trace blood volumes. By reducing sampling burden and simplifying logistics, it provides a clinically feasible and patient-centered strategy for precision TDM, supporting broader implementation of limited sampling strategies and expanding applicability to pediatric, home-based, and telemedicine settings. Full article

Background/Objectives: Disruptive behavior problems are common in early childhood, yet access to evidence-based parent training remains limited in many communities due to workforce shortages and service delivery barriers. Behavioral Skills Training for Families (BSF) is a Parent–Child Interaction Therapy (PCIT)-informed, home-based behavioral skills practice model designed to be delivered by bachelor’s-level paraprofessionals under close supervision. This pilot study evaluated the feasibility and preliminary caregiver and child outcomes associated with the Child-Directed Interaction (CDI) module of BSF to inform refinement of training and implementation protocols and guide future evaluation. Methods: Using a non-randomized pre–post design embedded within routine services, caregiver–child dyads (children ages 2–10 years) receiving BSF CDI across community-based agencies in Minnesota were included. Outcomes were assessed using observational coding of caregiver skills (Dyadic Parent–Child Interaction Coding System; DPICS) and caregiver-reported child behavior measures (Eyberg Child Behavior Inventory [ECBI]; Weekly Assessment of Child Behavior–Positive [WACB-P]). Paired-sample t-tests with intent-to-treat analyses examined changes from the baseline to the last attended CDI session. Results: Caregivers demonstrated statistically significant and large increases in observed positive parenting skills and reductions in negative verbalizations during child-led play. Children showed significant reductions in disruptive behavior intensity and problem scores on the ECBI, reflecting movement toward clinically meaningful improvement. No significant change was observed in caregiver-reported positive child behaviors on the WACB-P. Post hoc analyses were conducted to further explore these differences and found consistent changes in the ECBI for cases, regardless of no reported changes in positive child behaviors on the WACB. Conclusions: The results provide preliminary evidence that a structured, PCIT-informed CDI skills practice model can be feasibly implemented by paraprofessionals and is associated with meaningful improvements in caregiver behavior and child behavior outcomes in the first 2–3 months following service initiation. The findings support BSF as a promising workforce-embedded approach and inform future controlled studies examining effectiveness, sustainability, and broader implementation outcomes. Full article