Search Results (546)

Background: Chronic wounds are a growing clinical challenge due to their prolonged healing time and associated healthcare burden. Combined therapeutic approaches, including topical oxygen therapy (TOT) and negative-pressure wound therapy (NPWT), have shown promise in enhancing wound healing. This pilot exploratory study aimed to assess the clinical effectiveness of combined TOT and NPWT in chronic wound treatment and to explore the prognostic value of selected laboratory and thermographic markers. Methods: Eighteen patients with chronic wounds due to type 2 diabetes mellitus or chronic venous insufficiency were treated with either TOT alone (control group) or TOT combined with NPWT (intervention group). Wound characteristics, thermographic data, and laboratory parameters (NLR, MLR, PLR, CRP, and total protein) were collected at baseline and during therapy. The primary endpoints were the total treatment duration and complete wound closure. Statistical analyses were exploratory and used non-parametric tests, correlation analyses, and simple linear regression. Results: Ulcer duration was significantly associated with the wound surface area. Lower serum total protein levels correlated negatively with ulcer duration, wound size, and granulation tissue area. A significant reduction in treatment duration was observed in the intervention group compared to the controls. One strong correlation was found between MLR and peripheral wound temperature on day 7 in the control group. No significant group differences were observed in wound size or thermographic measures after one week of treatment. Conclusions: Combining TOT and NPWT may reduce treatment duration in chronic wound management. Selected laboratory and thermographic markers show promise as prognostic tools. These exploratory findings require confirmation in larger, randomized trials. Full article

Background/Objectives: Cannabidiol (CBD) is a non-intoxicating cannabinoid touted for a variety of medical benefits, including alleviation of anxiety. While legalization of hemp-derived products in the United States (containing ≤0.3% delta-9-tetrahydrocannabinol [d9-THC] by weight) has led to a rapid increase in the commercialization of hemp-derived CBD products, most therapeutic claims have not been substantiated using clinical trials. This trial aimed to assess the impact of 6 weeks of treatment with a proprietary hemp-derived, full-spectrum, high-CBD sublingual solution similar to those available in the marketplace in patients with anxiety. Methods: An open-label pilot clinical trial (NCT04286594) was conducted in 12 patients with at least moderate levels of anxiety. Patients self-administered a hemp-derived, high-CBD sublingual solution twice daily during the 6-week trial (target daily dose: 30 mg/day CBD). Clinical change over time relative to baseline was assessed for anxiety, mood, sleep, and quality of life, as well as changes in cognitive performance on measures of executive function and memory. Safety and tolerability of the study product were also evaluated. Results: Patients reported significant reductions in anxiety symptoms over time. Concurrent improvements in mood, sleep, and relevant quality of life domains were also observed, along with stable or improved performance on all neurocognitive measures. Few side effects were reported, and no serious adverse events occurred. Conclusions: These pilot findings provide initial support for the efficacy and tolerability of the hemp-derived, high-CBD product in patients with moderate-to-severe levels of anxiety. Double-blind, placebo-controlled studies are indicated to obtain robust data regarding efficacy and tolerability of these types of products for anxiety. Full article

Despite growing evidence supporting the efficacy of LSD-assisted psychotherapy in treating major depressive disorder (MDD), identifying reliable psychopharmacological biomarkers remains necessary. Oxytocin, a neuropeptide implicated in social bonding and flexibility, is a promising candidate due to its release following serotonergic psychedelic administration in healthy individuals; however, its dynamics in psychiatric populations are currently unexplored. This observational pilot study aimed to characterize salivary oxytocin dynamics during a single LSD-assisted psychotherapy session in our patients with treatment-resistant MDD. Participants received 100 or 150 µg LSD, and salivary oxytocin was measured at baseline, 60, 90, and 180 min post-LSD. Concurrently, participants rated subjective drug intensity (0–10 scale) at 60, 90, and 180 min. A linear mixed model revealed significant variation of oxytocin levels over time. Perceived psychedelic intensity also significantly varied over time. This supports oxytocin as a potential biomarker. Larger, controlled trials are warranted to replicate these findings and clarify the mechanistic links between oxytocin dynamics and clinical outcomes, including changes in depressive symptoms and mental flexibility. Full article

Amorphous calcium phosphate (ACP) is a well-established bioceramic material known to promote the remineralization of dental hard tissues. White spot lesions (WSLs) represent the initial stage of enamel demineralization and are frequently observed in patients with fixed orthodontic appliances or inadequate oral hygiene. Although recommendations for remineralizing agents include both the prevention of lesion progression and the stimulation of tissue remineralization, the clinical efficacy of ACP-based materials remains under debate. This systematic review, registered in the PROSPERO database (CRD42024540595), aims to evaluate the clinical efficacy of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP)-based products in the remineralization of WSLs and to compare these outcomes with those achieved using non-bioceramic approaches. Inclusion criteria comprised randomized clinical trials, prospective cohort studies, and pilot studies conducted on human subjects with WSLs affecting permanent teeth. Studies involving artificial WSLs or non-cariogenic enamel lesions were excluded. The quality of the included studies was assessed using the Cochrane Risk of Bias 2 (RoB 2) tool. Fourteen articles met the inclusion criteria and were analyzed. The main findings indicate that CPP-ACP is clinically effective in promoting the remineralization of WSLs, although the results were inconsistent across studies. Comparisons with placebo and resin infiltration treatments revealed greater efficacy for CPP-ACP. The combination of CPP-ACP with fluoride appeared to further enhance the remineralizing effect on WSLs. Additional standardized clinical studies with longer follow-up periods are warranted to confirm these outcomes. Full article

Background: Sodium–glucose cotransporter 2 (SGLT2) inhibitors have transformed type 2 diabetes mellitus (T2DM) management by promoting glucosuria, lowering glycated hemoglobin (HbA1c), blood pressure, and weight; however, their use is limited by genitourinary infections and ketoacidosis. Phytocannabinoids—bioactive compounds from Cannabis sativa—exhibit multi-target pharmacology, including interactions with cannabinoid receptors, Peroxisome Proliferator-Activated Receptors (PPARs), Transient Receptor Potential (TRP) channels, and potentially SGLT2. Objective: To evaluate the potential of phytocannabinoids as novel modulators of renal glucose reabsorption via SGLT2 and to compare their efficacy, safety, and pharmacological profiles with synthetic SGLT2 inhibitors. Methods: We performed a narrative review encompassing the following: (1) the molecular and physiological roles of SGLT2; (2) chemical classification, natural sources, and pharmacokinetics/pharmacodynamics of major phytocannabinoids (Δ⁹-Tetrahydrocannabinol or Δ⁹-THC, Cannabidiol or CBD, Cannabigerol or CBG, Cannabichromene or CBC, Tetrahydrocannabivarin or THCV, and β-caryophyllene); (3) in silico docking and drug-likeness assessments; (4) in vitro assays of receptor binding, TRP channel modulation, and glucose transport; (5) in vivo rodent models evaluating glycemic control, weight change, and organ protection; (6) pilot clinical studies of THCV and case reports of CBD/BCP; (7) comparative analysis with established synthetic inhibitors. Results: In silico studies identify high-affinity binding of several phytocannabinoids within the SGLT2 substrate pocket. In vitro, CBG and THCV modulate SGLT2-related pathways indirectly via TRP channels and CB receptors; direct IC₅₀ values for SGLT2 remain to be determined. In vivo, THCV and CBD demonstrate glucose-lowering, insulin-sensitizing, weight-reducing, anti-inflammatory, and organ-protective effects. Pilot clinical data (n = 62) show that THCV decreases fasting glucose, enhances β-cell function, and lacks psychoactive side effects. Compared to synthetic inhibitors, phytocannabinoids offer pleiotropic benefits but face challenges of low oral bioavailability, polypharmacology, inter-individual variability, and limited large-scale trials. Discussion: While preclinical and early clinical data highlight phytocannabinoids’ potential in SGLT2 modulation and broader metabolic improvement, their translation is impeded by significant challenges. These include low oral bioavailability, inconsistent pharmacokinetic profiles, and the absence of standardized formulations, necessitating advanced delivery system development. Furthermore, the inherent polypharmacology of these compounds, while beneficial, demands comprehensive safety assessments for potential off-target effects and drug interactions. The scarcity of large-scale, well-controlled clinical trials and the need for clear regulatory frameworks remain critical hurdles. Addressing these aspects is paramount to fully realize the therapeutic utility of phytocannabinoids as a comprehensive approach to T2DM management. Conclusion: Phytocannabinoids represent promising multi-target agents for T2DM through potential SGLT2 modulation and complementary metabolic effects. Future work should focus on pharmacokinetic optimization, precise quantification of SGLT2 inhibition, and robust clinical trials to establish efficacy and safety profiles relative to synthetic inhibitors. Full article

Background/Objectives: Embryo selection in IVF is traditionally based on morphology, yet many high-quality embryos fail to implant. Preimplantation genetic testing for aneuploidy (PGT-A) using next-generation sequencing (NGS) has been proposed to improve selection by identifying euploid embryos. However, its effectiveness in women of advanced maternal age remains unclear due to limited randomized data. This pilot trial assessed the feasibility of a full-scale RCT comparing PGT-A to morphology-based selection in women aged 35–42. Methods: This single-centre, two-arm parallel RCT (NCT05009745) enrolled women aged 35–42 undergoing IVF/ICSI with ≥3 good-quality day-3 embryos. Participants were randomized (1:1) to either embryo selection by morphology with fresh transfer or PGT-A with frozen transfer of a single euploid embryo. Allocation concealment was achieved via a secure web-based randomization platform; patients and clinicians were unblinded, but the biostatistician remained blinded. The primary outcome was feasibility of recruitment, randomization, and adherence. Results: Between June 2021 and January 2023, 138 women consented (recruitment rate: 55.8%, 95% CI: 49.7–62.0%) and 100 were randomized. Protocol adherence was 94%. Barriers to recruitment included preference for private PGT-A (19%) or fresh transfer (6%). Among biopsied embryos, 51.4% were euploid and 6.6% low-level mosaic. Intention-to-treat analysis showed no significant differences between PGT-A and control groups in clinical pregnancy rate (50% vs. 40%), live birth rate (50% vs. 38%), or miscarriage rate (12% vs. 8%). Cumulative live birth rate after up to three SETs was 72% vs. 52%, respectively (p > 0.05). No multiple pregnancies occurred. Conclusions: RCTs of PGT-A in older women are feasible. A multicentre design with broader inclusion criteria could improve recruitment and allow better assessment of clinical benefit. Full article

Background: Peritoneal stretching from CO₂ insufflation is a primary mechanism of pain associated with laparoscopy. Cyclooxygenase-2 inhibitors are promising anti-inflammatory and analgesic agents. This study aimed to evaluate the effect of celecoxib on postoperative pain reduction and associated changes in peritoneal gene expression after laparoendoscopic single-site (LESS) surgery for benign gynecologic disease. Methods: In this randomized, double-blind, placebo-controlled pilot study, 70 patients were randomly assigned to receive either celecoxib or placebo (400 mg) 40 min before surgery. Peritoneal tissues were collected before and after CO₂ insufflation. We analyzed changes in expressions of prostaglandin I₂ synthase, prostaglandin E synthase (PTGES), PTGES3, aldo-keto reductase family 1 member C1, and 15-hydroxyprostaglandin dehydrogenase (HPGD). Numeric Rating Scale (NRS) pain scores were also compared between groups. Results: A total of 62 patients completed the study: 30 in the celecoxib group and 32 in the placebo group. The mean CO₂ exposure time was 60.4 min. In a quantitative real-time polymerase chain reaction analysis, HPGD mRNA expression significantly increased after surgery in patients exposed to CO₂ for more than 60 min. Patients treated with celecoxib showed a significantly higher rate of grade 3 expression (83.3% vs. 37.5%; p = 0.01) and a level 2 increase in HPGD expression on in situ hybridization (58.3% vs. 12.5%; p = 0.01), despite no significant difference on immunohistochemistry. Moreover, celecoxib effectively reduced NRS pain scores compared to placebo. Conclusions: In this pilot study, celecoxib appeared to reduce postoperative pain and was associated with increased HPGD mRNA expression in the peritoneal tissue of patients with prolonged CO₂ exposure during LESS surgery. These exploratory findings warrant confirmation in larger trials with functional validation of HPGD expression (ClinicalTrials.gov, NCT03391570). Full article

Background: Heart failure (HF) is frequently associated with skeletal muscle wasting, reduced functional capacity, and malnutrition. High-protein diets offer a promising nutritional intervention to improve these outcomes in individuals with HF. Objective: This systematic review evaluated randomized controlled trials of high-protein dietary interventions in HF populations, with emphasis on intervention characteristics, quantitative benefits, and risk of bias. Methods: We conducted a comprehensive search in PubMed, MEDLINE, Embase, and Cochrane CENTRAL from inception to June 2025. Eligible studies enrolled adults (≥18 years) with HF, implemented high-protein regimens (≥1.1 g/kg/day or ~25–30% of energy), and reported on functional capacity, body composition, muscle strength, clinical outcomes, or biochemical markers. Two reviewers independently screened, extracted data, and assessed bias (Cochrane RoB 2). Heterogeneity in dosing, duration, and outcomes precluded meta-analysis; we therefore provide a narrative synthesis. Results: Ten trials (nine randomized controlled trials, one pilot) involving 1080 patients (median n = 38; range 21–652) were included. High-protein interventions yielded mean improvements in six-minute walk distance of +32 ± 14 m, lean body mass gain of +1.6 ± 0.9 kg, and 9 ± 4% enhancement in quality-of-life scores; muscle strength effects varied from −2% to +11%. Two studies reported an 18% reduction in HF readmissions (p < 0.05). The risk-of-bias assessment identified two low-risk, three moderate-risk, and one high-risk study. Key limitations include small sample sizes, varied protein dosing (1.1–1.5 g/kg/day), short follow-up (2–6 months), and outcome heterogeneity. Conclusions: High-protein dietary strategies appear to confer modest, clinically relevant gains in functional capacity, nutritional status, and HF readmission risk. Larger, well-powered trials with standardized dosing and longer follow-up are necessary to establish optimal protein targets, long-term efficacy, and safety. Full article

Cardiovascular disease (CVD), particularly atherosclerotic cardiovascular disease (ASCVD), is the leading cause of death worldwide, driven by factors like oxidative stress, inflammation, and lipid metabolism disorders. Although phenolic compounds such as Tyrosol (Tyr) and Hydroxytyrosol (HTyr) found in extra virgin olive oil (EVOO) have shown promising antioxidant and anti-inflammatory effects, their specific roles in modulating oxidative stress biomarkers and high-density lipoprotein (HDL) functionality in elderly populations, especially in those with prior myocardial infarction, are not fully understood. This study aimed to investigate the effects of EVOO phenolic compounds on oxidative stress biomarkers and HDL functionality, and related metabolic outcomes in both healthy and post-myocardial infarction (post-MI) elderly individuals. This pilot randomized clinical trial study included healthy and post-MI participants aged 65–85 years. Participants in each group were randomly assigned to consume 25 mL per day of one of three types of olive oils: high phenolic (HTyr/Tyr) extra virgin olive oil (HP-EVOO), extra virgin olive oil (EVOO), or refined olive oil (ROO) for a period of 26 weeks. Blood samples were collected at baseline and post-intervention to assess key biomarkers. Plasma levels of (poly)phenols, malondialdehyde (MDA), total antioxidant capacity (FRAP), lecithin-cholesterol acyltransferase activity (LCAT), and serum paraoxonase-1 (PON-1) activity were measured. A total of 34 individuals completed the study (mean age: 74 years). Baseline characteristics, including sex, age, body mass index (BMI), weight, blood pressure, and inflammatory markers like C-reactive protein (CRP) levels, did not differ significantly between the two groups. A significant increase in both FRAP levels and PON-1 activity was observed in post-MI participants following HP-EVOO consumption compared to baseline (p = 0.014). No significant changes were observed in MDA levels, LCAT activity, or plasma (poly)phenols. These results indicate that HP-EVOO may enhance antioxidant capacity, particularly FRAP and PON-1 activity, in elderly post-MI individuals. The observed differences between groups suggest that underlying cardiometabolic status may influence the response to olive oil phenolic compounds. Further studies are needed to explore the long-term cardiovascular effects. Full article

Background/Objectives: Childhood cancer, although relatively rare, has a profound impact on the quality of life of affected children and their families. Technological advances have facilitated the development of mobile applications (apps) aimed at enhancing symptom monitoring and improving communication with healthcare teams. This systematic review aimed to analyse the effect of mobile applications on the health of children with cancer, with a specific focus on health-related quality of life (HRQoL). Methods: A systematic review was conducted in accordance with PRISMA 2020 guidelines. Searches were performed in PubMed (Medline), CINAHL, Cochrane and Scopus databases using MeSH terms such as Smartphone, Mobile Applications, Child Health, Neoplasms, and Digital Health, with no date restrictions, and including studies published in English, Spanish or Portuguese. We included original research studies that examined the use of mobile apps in paediatric oncology patients. The search was completed in January 2025. Results: Of the 324 records initially identified, 14 studies (mainly pilot studies, early-phase clinical trials, and observational designs) met the inclusion criteria. Interventions commonly focused on symptom tracking (pain, nausea, fatigue), promoting treatment adherence, and delivering educational content. Several studies reported high user acceptance and a potential positive impact on HRQoL, particularly when gamification strategies were incorporated to sustain children’s engagement. Conclusions: Despite the preliminary nature and small sample sizes of most studies, mobile applications appear to be effective in supporting symptom management, communication, and health education in paediatric oncology. Their use may contribute to improvements in HRQoL. Further high-quality research involving younger children and diverse socio-cultural contexts is required to confirm their effectiveness. Full article

Background/Objectives: The effects of combining chemotherapy with hormonal therapy based on hormone receptor (HR) expression in epithelial ovarian, fallopian tube, or primary peritoneal (EOC) remain unclear. This study evaluated the efficacy and safety of physician-chosen chemotherapy combined with hormonal therapy in patients with heavily pretreated advanced EOC, stratified by HR expression. Methods: This phase II, multicenter, pilot study included patients with heavily pretreated advanced EOC, allocated to estrogen receptor (ER)-dominant or progesterone receptor (PR)-dominant arms. Patients in the ER-dominant arm received tamoxifen plus physician-selected chemotherapy, while those in the PR-dominant arm received megestrol acetate (MA) plus chemotherapy. The primary outcome was the best objective response rate (ORR) for six months, assessed using an optimal two-stage Simon design. Results: Among 33 ER-dominant patients with high-grade serous carcinoma (HGSC), the six-month best ORR was 27.3% (3% complete response, 24.2% partial response). The six-month ORR and clinical benefit rate (CBR) were 18.8% and 37.5%, respectively, with 62.5% experiencing progressive disease (PD). Among three PR-dominant patients (two clear cell carcinoma and one HGSC), the six-month best ORR was 0%. The six-month ORR and CBR were also 0%, and all experienced PD within six months. No unacceptable toxicity related to tamoxifen or MA was encountered. Conclusions: In heavily pretreated advanced HGSC patients with ER-dominant expression, chemotherapy combined with tamoxifen showed encouraging clinical activity with favorable safety. While limited by the study design, these findings suggest a potential role for tailored hormonal therapy combined with chemotherapy based on HR expression in heavily pretreated advanced EOC. Clinical Trial Registration: KCT0004571 Full article

Background: Parkinson’s disease (PD) presents a significant challenge due to its wide range of motor, non-motor, and treatment-related symptoms. Non-invasive interventions like transcranial magnetic stimulation (TMS) are being explored for potential therapeutic benefits. This study aimed to assess if a high-frequency repetitive TMS protocol (HF-rTMS) consisting of 10 trains of 100 pulses of rTMS at 25 Hz over the motor cortex (M1) at 80% of the resting motor threshold could be effective in treating motor or non-motor symptoms in patients with PD with levodopa-induced dyskinesias. Methods: A randomized, single-blinded, placebo-controlled pilot trial was conducted with eleven PD patients. Nine patients received HF-rTMS, while two received sham stimulation. Patients were exhaustively evaluated using validated clinical scales to assess motor and non-motor symptoms. The study followed a rigorous protocol to avoid bias, with assessments conducted by a neurologist specialized in single-blinded movement disorder. Results: The HF-rTMS group experienced a statistically significant slight worsening in both motor and non-motor symptoms, particularly in the mood/cognition and gastrointestinal domains. However, positive effects were observed in some non-motor symptoms, specifically reduced excessive sweating and weight. No adverse effects were reported. Conclusions: Although HF-rTMS did not produce significant motor improvements, its potential benefit on specific non-motor symptoms, such as autonomic regulation, warrants further investigation. Full article

Topical percutaneous drug delivery has recently emerged as a novel strategy for the treatment of allergic diseases, offering targeted drug delivery to mucosal tissues adjacent to the skin. Unlike conventional topical approaches that act on the skin surface or mucosal membranes, topical percutaneous drug delivery enables non-invasive pharmacologic modulation of deeper structures such as the conjunctiva, nasal mucosa, and trachea. This review explores the rationale, pharmacokinetic foundation, clinical data, and future prospects of transdermal therapy in allergic conjunctivitis, allergic rhinitis, and asthma-related cough. In allergic conjunctivitis, eyelid-based transdermal delivery of antihistamines such as diphenhydramine and epinastine has shown rapid and long-lasting symptom relief, with epinastine cream recently approved in Japan following a randomized controlled trial (RCT) demonstrating its efficacy. Preclinical and clinical pharmacokinetic studies support the eyelid’s unique permeability and sustained drug release profile, reinforcing its utility as a delivery site for ocular therapies. In allergic rhinitis, diphenhydramine application to the nasal ala demonstrated symptomatic improvement in patients intolerant to intranasal therapies, though anatomical separation from the inflamed turbinates may limit consistent efficacy. Similarly, cervical tracheal application of steroids and antihistamines has shown potential benefit in asthma-related cough, especially for patients refractory to inhaled treatments, despite anatomical and depth-related limitations. Overall, site-specific anatomy, skin permeability, and disease localization are critical factors in determining therapeutic outcomes. While trans-eyelid therapy is supported by robust data, studies on the nasal ala and trachea remain limited to small-scale pilot trials. No major adverse events have been reported with nasal or tracheal application, but eyelid sensitivity requires formulation caution. To validate this promising modality, further RCTs, pharmacokinetic analyses, and formulation optimization are warranted. Topical percutaneous drug delivery holds potential as a non-invasive, site-directed alternative for managing allergic diseases beyond dermatologic indications. Full article

Background/Objectives: Chronic illness after COVID-19 vaccination (longvax) lacks a therapeutic protocol anchored in pathophysiology. Persistent vaccine derived spike protein appears to trigger microvascular fibrin amyloid microclots, immune dysfunction, pathogen reactivation and multisystem injury. This article proposes an integrative approach, Vaxtherapy, to tackle these mechanisms. Methods: A narrative synthesis of peer reviewed literature from 2021 to 2025 on spike related injury and vaccine adverse events was conducted, supplemented by clinical case series and mechanistic observations from long COVID. The findings were arranged into a four stage therapeutic sequence ordered by pathophysiological precedence. Results: Stage one aims to reopen hypoperfused tissue through oral fibrinolytics that degrade fibrin amyloid resistant microclots; stage two intends to neutralise circulating or tissue bound spike via a receptor binding domain monoclonal antibody cocktail; stage three seeks to eliminate reactivated viral or microbial reservoirs with targeted antivirals or antimicrobials once perfusion is improved; and stage four aspires to support tissue repair with mitochondrial supplements and, when indicated, cell based therapies. Omitting or reordering stages may reduce efficacy or foster resistance. Conclusions: This hypothesis driven framework outlines a biologically plausible roadmap for longvax research. By matching interventions to specific mechanisms (fibrinolysis, spike neutralisation, pathogen clearance and regeneration), it aims to guide controlled trials and compassionate pilot programs directed at durable recovery rather than chronic symptom management. Full article

Background: Patient satisfaction is a critical outcome in the rehabilitation of edentulous patients. While conventional fabrication methods are widely used, digital workflows are emerging as viable alternatives. However, direct comparative evidence from the patient’s perspective remains limited. Objective: To compare patient satisfaction between conventional complete dentures (C-CD) and digital complete dentures (D-CD) in maxillary edentulous patients, including changes in perceptions over time and final prosthesis preference. Methods: A prospective, randomized crossover clinical trial was conducted in 2023–2024 involving 40 completely maxillary edentulous patients meeting specific inclusion criteria. Participants were randomly allocated into two sequence groups: Group 1 (n = 20) received C-CD first, and Group 2 (n = 20) received D-CD first, each for 6 months (T1), followed by crossover to the alternate denture for another 6 months (T2). Patient satisfaction was measured using a 10-item questionnaire at 6 and 12 months. Statistical analysis: Wilcoxon signed-rank tests were used for within-subject comparisons of denture types, and Mann–Whitney U tests for between-group comparisons, with significance set at p ≤ 0.05. Results: Using the paired crossover analysis, D-CD showed significantly better comfort than C-CD (p < 0.05). D-CD scored significantly higher than C-CD in most satisfaction domains, including comfort, retention, speech, esthetics, and need for adjustments (p ≤ 0.05). Median scores for retention, speech, esthetics, and other domains were slightly higher with D-CD but did not reach statistical significance (p > 0.05). Additionally, the D-CD required fewer post-insertion adjustment visits than the C-CD (p < 0.05). By the end of the trial, 28 patients (70%) preferred the digital denture as their final prosthesis, whereas 12 patients (30%) preferred the conventional denture. Conclusions: Incorporating digital technology in the fabrication of complete dentures significantly enhances patient satisfaction compared to conventional methods. This study highlights the clinical relevance of modern dental prosthesis technology and supports the wider integration of digital workflows. Within the limitations of this pilot study, digitally fabricated complete dentures provided overall patient satisfaction comparable to conventional dentures, with the D-CD offering a notable improvement in comfort. The majority of patients ultimately favored the digital denture, supporting the clinical viability of CAD/CAM workflows. Full article