Search Results (4,897)

Background: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasms of the gastrointestinal tract and are primarily driven by activating mutations in KIT or PDGFRA. Although tyrosine kinase inhibitors (TKIs), particularly imatinib, have substantially improved outcomes, most patients with advanced disease eventually develop resistance, resulting in disease progression. Methods: We performed a narrative review with scoping approach of interventional clinical trials registered on ClinicalTrials.gov between January 2020 and July 2025 to characterize the contemporary investigational therapeutic landscape in GIST. Eligible studies included clinical trials evaluating novel agents, combinations, or alternative strategies beyond current regulatory approvals. Trial characteristics, therapeutic classes, endpoints, enrollment, and funding sources were analyzed. Results: A total of 27 ongoing trials were identified. Most studies were phase I/II and focused on metastatic or unresectable disease, predominantly in the second-line or later settings. TKIs remained the dominant therapeutic class, included in over 70% of trials, either as monotherapy or in combination. Emerging strategies comprised antibody–drug conjugates, immune checkpoint inhibitors, HIF inhibitors, FGFR inhibitors, and epigenetic modulators. Only four phase III trials were identified, reflecting the difficulty of conducting large, randomized studies in GIST. No trial used overall survival or quality of life as a primary endpoint. Conclusions: The current investigational landscape in GIST is largely focused on overcoming TKI resistance in advanced disease. Molecular stratification and personalized approaches dominate ongoing research, but evidence generation remains limited by small sample sizes and slow recruitment. Future trials integrating innovative therapeutic platforms and patient-centered outcomes are essential to improve long-term disease control and quality of life. Full article

Background: The pain experienced by people with fibromyalgia (FM) is thought to be the result of altered nociceptive processing, impaired descending inhibition and reduced tolerance to physical load. However, the relationship between the amount of exercise and pain reduction remains unclear. Methods: This study synthesized randomized controlled trials of exercise interventions for FM to quantify the combined analgesic effects of different types of exercise. A secondary aim was to standardize exposure using metabolic equivalent of task (MET)-based metrics and examine the association between cumulative intervention dose (MET·h) and analgesic response (Hedges’ g) across intervention arms. Following the PRISMA guidelines, a search was conducted in PubMed for randomized controlled trials published up to 31 December 2025. After screening and a full-text assessment, 15 trials were included. The protocols were converted into MET-defined intensity and weekly MET·min exposure, and the cumulative dose was calculated as the total MET·h accrued over the intervention period. Random-effects models were used to estimate the pooled effects within modality subgroups. Results: Across modalities, exercise was associated with reductions in pain, with effects typically falling within the small-to-moderate range. Larger improvements were observed in structured or supervised programs. The dose-response scatter plot showed wide variability across the dose range, with overlapping confidence intervals. An exploratory fourth-degree polynomial fit explained limited variance (R² = 0.1615) and did not indicate a monotonic dose-response pattern. This suggests that cumulative workload alone is a weak proxy for therapeutic response. Conclusions: Based on these findings, a pain-responsive algorithm combining weekly Visual Analogue Scale (VAS), ΔVAS and Talk Test thresholds was implemented as a preliminary online calculator to support the prescription of exercise tailored to symptoms. Full article

Objectives: To map and synthesize the available evidence regarding the use of manual therapy, core stability training, and Pilates Method exercises in the rehabilitation of musculoskeletal conditions in adult dancers. Methods: A scoping review was conducted in accordance with the PRISMA-ScR guidelines. A systematic search across six electronic databases (PubMed, Scopus, Web of Science, SPORTDiscus, CINAHL, and PEDro) was performed. Study eligibility was strictly guided by the Population–Concept–Context (PCC) framework. Two independent reviewers screened the literature and extracted data. Results: A total of 16 studies met the inclusion criteria, encompassing randomized controlled trials, intervention studies, and case-level reports or series. Interventions primarily addressed chronic ankle instability, low back pain, and post-surgical rehabilitation. Results indicate that while individualized manual therapy and Pilates Method protocols are widely utilized in dance medicine, high-level evidence remains limited. Conclusions: Integrated rehabilitation approaches combining manual therapy with motor control exercises (such as the Pilates Method and core training) appear to have potential utility in supporting the safe return of dancers to performance. However, the current literature is heavily reliant on observational and case-driven evidence, highlighting the need for robust clinical trials to establish standardized, dance-specific rehabilitation guidelines. Full article

Background/Objectives: Psoriatic disease is a systemic inflammatory condition associated with increased cardiometabolic risk, but the impact of contemporary systemic therapies and narrowband ultraviolet B (NB-UVB) phototherapy on vascular and systemic inflammatory markers remains incompletely characterized. We aimed to systematically synthesize prospective evidence on treatment-associated changes in vascular inflammation and systemic inflammatory biomarkers in adults with moderate-to-severe psoriatic disease. Specifically, we evaluated changes assessed by 18F-FDG PET/CT imaging and circulating biomarkers following biologic therapies or NB-UVB phototherapy. Methods: We systematically searched MEDLINE, Embase, Web of Science, Scopus, and CENTRAL from inception to 31 January 2026 for prospective interventional and observational studies in adults with psoriasis or psoriatic arthritis treated with biologic agents targeting TNF-α, IL-12/23, IL-17, or IL-23, or with NB-UVB phototherapy. Eligible studies were required to report serial assessments of vascular inflammation by 18F-FDG PET/CT (typically aortic target-to-background ratio) and/or systemic inflammatory markers (high-sensitivity C-reactive protein, interleukin-6, TNF-α, GlycA, or hematologic indices such as the neutrophil-to-lymphocyte ratio) over at least 8 weeks of follow-up. We imposed no language restrictions and included only full-text, peer-reviewed prospective studies. Risk of bias was evaluated using RoB 2 for randomized trials and ROBINS-I for nonrandomized studies. Random-effects meta-analyses were prespecified for outcomes reported by at least two clinically comparable studies; however, because of substantial heterogeneity in reporting and methodology, effect estimates were summarized using a structured narrative synthesis. Results: Thirteen prospective studies (n ≈ 900 adults, published 2015–2025) met inclusion criteria, including four studies with serial 18F-FDG PET/CT imaging and one additional PET/CT study providing baseline observational data on vascular inflammation, as well as eight biomarker-focused prospective cohorts. Across randomized mechanistic trials and observational studies, biologic therapies reduced aortic target-to-background ratio by approximately 6–12% over 12–24 weeks (e.g., mean change from 2.42 to 2.18 with TNF-α inhibition and from 2.51 to 2.20 with IL-17 blockade), and no study reported worsening of PET-derived vascular indices under effective systemic treatment. Biologic and other systemic therapies produced concordant reductions in hs-CRP (typically by 30–50%), IL-6, TNF-α, GlycA, and blood-count-derived indices including neutrophil-to-lymphocyte ratio, with biomarker improvements frequently paralleling reductions in cutaneous disease activity and cardiometabolic risk markers. Two NB-UVB cohorts demonstrated significant hs-CRP reductions of roughly 20–30% and modulation of vitamin D-related inflammatory proteins, suggesting systemic anti-inflammatory effects, although these changes appeared less pronounced than with biologic therapy and were not accompanied by vascular imaging. Conclusions: Contemporary systemic psoriasis therapies, particularly biologic agents targeting the IL-23/Th17 axis and TNF-α, are associated with consistent reductions in aortic vascular inflammation and broad improvements in systemic inflammatory biomarkers, whereas NB-UVB phototherapy confers more modest but measurable systemic anti-inflammatory effects, although the current evidence does not allow differentiation between individual biologic classes in terms of magnitude of effect. Although reductions in vascular and systemic inflammatory markers were observed across therapies targeting TNF-α, IL-12/23, IL-17, and IL-23, the small number of mechanistic imaging studies and absence of head-to-head comparisons do not allow robust differentiation between biologic classes or support a uniform class effect. The convergence of imaging and biomarker data reinforces psoriasis as a clinically relevant model of inflammation-driven atherosclerosis and supports the concept that effective control of psoriatic inflammation may contribute to cardiovascular risk modification, highlighting the need for integrated cardiovascular risk assessment in routine care. However, the imaging evidence base remains limited to four small mechanistic PET/CT studies with relatively short follow-up, which constrains the strength and generalizability of conclusions regarding vascular inflammation. Larger, adequately powered, event-driven prospective trials with standardized imaging and biomarker endpoints are needed to determine whether these vascular and systemic anti-inflammatory effects translate into reduced cardiovascular events in psoriatic disease; because of methodological and reporting heterogeneity across the 13 included studies, these conclusions are based on a structured narrative synthesis rather than a formal quantitative meta-analysis. PROSPERO registration number: CRD420261296646. Full article

Introduction: University students are vulnerable to psychological distress due to the academic and social demands of this life stage. Mindfulness and self-compassion are effective and adaptable strategies in an academic environment that promote emotional regulation and psychological well-being. This study aims to conduct a systematic review and meta-analysis to evaluate the combined impact of mindfulness- and self-compassion-based interventions (MBSCIs) on psychological distress. It will also analyze their role as predictors of therapeutic change, as well as the moderating influence of sociodemographic and contextual factors. Method: We systematically searched PubMed, Scopus and Web of Science for randomized controlled trials (RCTs) and single-group pre-post trials investigating the effect of MBSCI on anxiety, depression and stress in college students. Studies were combined using the inverse variance method in a random effects model. Additional subgroup and meta-regression analyses were performed, and risk of bias was assessed. The review was pre-registered (PROSPERO registration number: CRD420251003822). Results: Our review included 49 studies with a total of 5043 participants (3721 in the intervention group, and 1322 in the control group). The results provide relevant evidence on the efficacy of MBSCI in the university population, especially in reducing symptoms of stress, anxiety, and depression. The effect sizes observed were moderate-to-large for stress and small-to-moderate for anxiety and depression, supporting their clinical usefulness in university educational settings. However, these findings should be interpreted with caution, as no included study achieved low risk of bias, and heterogeneity was moderate-to-high across most outcomes. Conclusions: The results suggest that MBSCI could alleviate psychological distress in university students. However, these results are limited by some methodological issues (risk of bias, heterogeneity, lack of follow-ups, poor standardization). It would be advisable to integrate these practices into the university curriculum as workshops or complementary activities. Further studies are needed to confirm their effectiveness and explore sustained effects and differences according to individual characteristics. Full article

Background: Corticosteroid injections provide short-term relief for chronic subacromial bursitis but are associated with high recurrence rates. This study investigates the efficacy of a mobile health-supported home-based resistance exercise program compared with exercise education in patients with chronic recurrent subacromial bursitis after ultrasound-guided corticosteroid injections. Methods: Participants with chronic subacromial bursitis were assigned via computer-generated block randomization to either an intervention group receiving ultrasound-guided corticosteroid injections followed by a 12-week home-based exercise program (50 min strengthening and resistance/session, 5 days per week) supported via instant messaging applications, or a control group receiving the same injection followed by printed educational materials covering the same exercise protocol. Shoulder Pain and Disability Index (SPADI) scores, Visual Analog Scale (VAS) pain scores and active pain-free range of motion (ROM) were evaluated by a blinded assessor at weeks 4 and 12. Between-group comparisons were analyzed using two-way ANOVA after confirming normality and homoscedasticity. Results: Fifty-three patients (mean age: 55.6 ± 10.5 years; 47.2% female) were randomized to the intervention (n = 27) or control (n = 26) groups. Significant interaction effects were identified for SPADI (p = 0.040) and ROM (abduction: p = 0.036/ flexion: p = 0.032). Post hoc analysis revealed that the intervention group exhibited a significantly greater reduction in SPADI scores (p = 0.007, d = 0.72) and greater increase in abduction ROM (p = 0.004, d = 0.84) at 12 weeks; both gains surpassed the MCID. Conclusions: A mobile health-supported home-based resistance exercise program can significantly extend the benefits of corticosteroid injections in patients with chronic subacromial bursitis. Trial Registration: NCT06220643, registered 14 December 2023. Full article

Background: Diet quality and food processing patterns are increasingly recognized as important determinants of Crohn’s disease (CD) risk and disease outcomes; however, direct comparisons with healthy populations using integrated nutrient- and processing-based frameworks remain limited. Therefore, we aim to quantify ultra-processed food (UPF) consumption using the NOVA classification, compare UPF intake between CD patients and healthy controls, and assess its association with diet quality indices. Methods: Baseline dietary intake data were analyzed from two randomized controlled trial cohorts: adults with mild to moderately active CD enrolled in the Crohn’s Disease Therapeutic Dietary Intervention (CD-TDI) trial (n = 64; NCT04596566), and healthy adults participating in the MAPMed study (n = 33, NCT06765369). Dietary intake was assessed using two non-consecutive 24 h recalls collected with the Automated Self-Administered 24-Hour Dietary Assessment Tool (ASA24^®). Energy-normalized macronutrient and micronutrient intakes were compared with Dietary Reference Intakes (DRIs). Overall diet quality was evaluated using the Healthy Eating Index-2020 (HEI-2015), Alternate Mediterranean Diet score (aMED), and Dietary Inflammatory Index (DII). Foods were classified according to the NOVA food processing system to estimate total and proportional energy intake from UPFs (NOVA group 4). Results: Both the CD cohort and healthy cohort exhibited suboptimal dietary patterns, with HEI scores indicating a need for improvement, low adherence to the Mediterranean diet (aMED), and neutral-to-pro-inflammatory DII scores, with no significant between-group differences (all p > 0.05). Although total energy intake differed between groups (p = 0.04), the proportion of energy derived from UPFs (NOVA group 4) accounted for half of the total intake in both cohorts (51.3–51.8%; p = 0.55). Higher UPF intake was associated with lower HEI and aMED scores and higher DII scores. Conclusions: In this study, there were no significant differences in the dietary patterns in those with CD compared to healthy controls. The high contribution of UPFs observed in both cohorts underscores widespread suboptimal dietary quality and highlights the utility of NOVA-based food processing measures as complementary to nutrient-based assessments for understanding diet-related inflammatory burden in CD. Full article

Many female athletes experience menstrual cycle issues. We investigated clary sage (Salvia sclarea L.) essential oil inhalation’s effect on dysmenorrhea-related symptoms, antioxidant capacity, and salivary hormone levels in female collegiate athletes. This randomized crossover trial included 20 female collegiate athletes (mean age: 20.2 ± 1.2 years). The participants were randomly assigned to one of two conditions: clary sage essential oil (intervention) or water (control) inhalation. Each condition lasted for one menstrual cycle, with inhalation administered at bedtime for 60 min using a diffuser. Dysmenorrhea-related symptoms and their impact on athletic performance were assessed using a visual analog scale. Biochemical analyses included salivary antioxidant capacity and cortisol, estradiol, and progesterone level measurements. Data from 12 participants who completed the study were analyzed. Compared with water inhalation, clary sage essential oil inhalation significantly reduced menstrual pain, sleep disturbances, irritability, and anxiety (all p < 0.05). The impact of dysmenorrhea-related symptoms on performance and total symptom scores was also significantly lower in the intervention condition than in the control condition (both p < 0.05). Additionally, salivary antioxidant capacity was significantly higher following clary sage essential oil inhalation than after water inhalation (p < 0.05). However, no significant differences were observed in the salivary cortisol, estradiol, or progesterone levels between the intervention and control conditions. Clary sage essential oil inhalation may be an effective nonpharmacological approach for alleviating dysmenorrhea-related symptoms and enhancing antioxidant capacity in female collegiate athletes. The results highlight its potential as a noninvasive and easy-to-use daily method for managing menstrual symptoms. Full article

Microbiome-targeted interventions have shown promise for metabolic health, yet clinical evidence remains inconsistent, particularly across stages of metabolic disease. This study evaluated the metabolic effects, safety, and tolerability of EDC-HHA01, a microbiome-informed, non-pharmacologic intervention, in adults with prediabetes (PD) or Type 2 Diabetes (T2DM). In a randomized, double-blind, placebo-controlled clinical trial, participants received EDC-HHA01 or placebo for six months. The study was adequately powered (≥80%) for the primary endpoint. Outcomes included changes in glycated hemoglobin (HbA1c), indices of insulin resistance, markers of metabolic endotoxemia, safety-related laboratory parameters, and exploratory patient-reported measures. Analyses were stratified by metabolic status and background metformin use. In participants with PD, EDC-HHA01 supplementation was associated with a statistically and clinically meaningful reduction in HbA1c compared with placebo, supported by concordant improvements in fasting insulin, insulin resistance indices, and reductions in endotoxemia markers. In participants with T2DM, changes were directionally similar but attenuated and did not reach statistical significance. The intervention was well tolerated, with no serious adverse events, high adherence, and no clinically relevant adverse changes in renal or lipid parameters. Exploratory patient-reported outcomes indicated favorable acceptability but were not interpreted as efficacy endpoints. EDC-HHA01 was associated with biologically coherent, stage-dependent metabolic effects, most evident in PD. These findings support further investigation of microbiome-informed strategies as metabolic support in early-stage dysregulation. Full article

Background: This paper presents a systematic review and meta-analysis to identify the effects of Rhythmic Auditory Stimulation (RAS) delivered via wearable devices on the gait and balance in patients with Parkinson’s disease. Method: The PICO criteria were established according to the PRISMA 2020 guidelines, and literature searches were performed across five databases covering studies published between 2015 and 2025: PubMed, Embase, Cochrane, Scopus, and Web of Science. After applying the inclusion criteria, eleven randomized controlled trials (RCTs) were selected. The quality of the studies was evaluated using the PEDro Scale and ROB-2. Statistical analyses were performed using Review Manager 5.4 based on the number of samples, means, and standard deviations to calculate the effect sizes. Result: The analysis results showed that wearable RAS significantly improved the gait speed (SMD = 0.49, p < 0.05) and balance ability (SMD = 0.40, p < 0.05), while no significant differences in the gait pattern, FOG-Q, or UPDRS-III were observed. The heterogeneity among studies was low, and the funnel plots were distributed symmetrically, indicating minimal publication bias. The average PEDro score was 7.33, suggesting moderate-to-high methodological quality. Conclusion: wearable RAS was identified as an evidence-based intervention effective in improving the gait speed and balance in patients with Parkinson’s disease. Full article

Background/Objectives: Psilocybin has re-emerged as a promising intervention for neuropsychiatric disorders including major depressive disorder, treatment-resistant depression, anxiety associated with life-threatening illness, obsessive compulsive disorder, and substance use disorders. However, conventional randomized controlled trials (RCTs)—the current gold standard in evidence-based medicine—may not adequately capture the therapeutic complexity of psilocybin, which depends not only on pharmacological action but also on contextual, psychological, and interpersonal factors. This critical narrative review aimed to evaluate the adequacy of existing clinical research frameworks for assessing psilocybin’s therapeutic potential and to explore alternative methodologies that may better reflect real-world clinical conditions. Methods: Using the Web of Science Core Collection database, we identified and analysed the ten most cited clinical studies on psilocybin published between 2015 and 2025 inclusive. Additional literature was included through reference cross-checking, systematic reviews, meta-analyses, and interdisciplinary sources covering neurobiology, history, and real-world evidence (RWE). The review synthesizes clinical outcomes, methodological constraints, and epistemic considerations relevant to psychedelic-assisted therapy. Results: Evidence from highly cited trials demonstrates rapid and sustained antidepressant and anxiolytic effects of psilocybin, with notable benefits also observed in addiction treatment. However, significant methodological limitations were identified, including selection bias, challenges in placebo design and blinding, small sample sizes, and the underrepresentation of diverse populations. Psilocybin outcomes were strongly influenced by subjective experience and contextual factors such as set and setting. Emerging RWE studies revealed heterogeneous patterns of response and provided insights unattainable through RCTs alone. Conclusions: Psilocybin shows considerable therapeutic promise, but current RCT methodologies capture only part of its clinical effects. Comprehensive evaluation will require larger and more diverse clinical trials, long-term follow-up, standardized psychotherapeutic protocols, and the integration of RWE to reflect real-world practice. Psychedelic-assisted therapy should be conceptualized as a complex intervention that combines pharmacological and psychotherapeutic components. Full article

Background: Ataxic symptoms are characterized by causing motor, balance and coordination disorders. Virtual reality-based interventions (VRBIs) including video games and exergames can improve ataxic symptoms. The aim of this systematic review with meta-analysis was to assess the effectiveness of VRBI on severity of ataxia, postural balance, mobility and manual dexterity in patients with ataxia. Methods: According to the PRISMA guidelines, we searched PubMed Medline, SCOPUS, WOS, CINAHL, PEDro and other sources for randomized controlled trials (RCTs) that assessed the effectiveness of VRBI, compared to others, on the severity of ataxia, balance, mobility and manual dexterity in patients with ataxia. The pooled effect was calculated using Cohen’s standardized mean difference (SMD) and a 95% confidence interval (95% CI). Results: With data from seven RCTs, providing data from 171 patients with ataxia, our meta-analysis elucidated that VRBI is effective in reducing the severity of ataxia (SMD = −0.43; 95% CI −0.84 to −0.03; p = 0.04) and increasing functional balance (SMD = 0.97; 95% CI 0.16 to 1.78; p = 0.02) and manual dexterity (SMD = −0.63; 95% CI −1.16 to −0.11; p = 0.018). Conclusions: Our findings suggest that VRBI could be a promising and effective therapeutic approach in reducing ataxia disability and increasing balance and manual dexterity in ataxic patients. Full article

Chronic autoimmune thyroiditis (CAT), a common autoimmune thyroid disorder, is the leading cause of hypothyroidism in iodine-sufficient regions and is characterized by thyroid autoimmunity, chronic inflammation, and progressive structural thyroid changes. Although levothyroxine (LT4) restores biochemical euthyroidism, it does not directly address the underlying autoimmune process, highlighting the need for adjunctive therapeutic strategies. Photobiomodulation (PBM), also known as low-level laser therapy (LLLT), has been proposed as a non-invasive intervention with potential immunomodulatory and tissue-level effects. A systematic narrative review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting principles. PubMed/MEDLINE, Google Scholar, and additional databases were searched for original human clinical studies evaluating PBM/LLLT in CAT, including studies using the term Hashimoto’s thyroiditis (HT), and reporting thyroid-related outcomes. Due to heterogeneity in study designs and PBM protocols, findings were synthesized narratively. Six eligible clinical studies published between 2010 and 2025 were identified. Across studies, PBM was associated with reductions in thyroid autoantibodies, improvements in thyroid hormone indices, and decreases in LT4 dose requirements. Longer follow-up studies reported ultrasonographic changes, while one sham-controlled trial demonstrated improvements in oxidative stress markers and quality of life (QoL) without short-term endocrine changes. However, current evidence is limited by the small number of human studies, heterogeneous PBM protocols, and the frequent use of concomitant interventions such as selenium or vitamin D. Overall, PBM may represent a promising adjunctive approach in CAT, although randomized sham-controlled trials are required before clinical implementation. Full article

Background: Intrinsic foot muscle strengthening and orthotic devices such as toe spacers are commonly used to improve foot alignment and function. However, evidence regarding the combined effects of strengthening exercises and interdigital spacers remains limited. Objective: To examine whether adding a silicone toe spacer to a foot strengthening exercise program provides additional benefits compared with exercise alone. Design: Randomized controlled trial. Setting: University biomechanics laboratory. Participants: Twenty-five healthy adults (mean age 23.8 ± 1.3 years) without lower limb injury or neurological disorders were randomly allocated to one of two intervention groups. Interventions: Participants performed a six-week foot strengthening program (22 sessions). One group performed exercises alone, while the second group performed the same exercises while wearing a silicone interdigital toe spacer. Main outcome measures: The primary outcome was hallux valgus angle. Secondary outcomes included active and passive hallux range of motion (ROM), ankle dorsiflexion ROM (weight-bearing lunge test), navicular drop, and postural stability during single-leg stance assessed using center-of-pressure (CoP) measures. Results: Both groups demonstrated improvements over time in hallux valgus angle (p = 0.001, η² = 0.361), active hallux range of motion (p < 0.001, η² = 0.545), and ankle dorsiflexion (p < 0.001). However, no significant between-group differences were observed for the primary outcome or most secondary outcomes. A significant time × group interaction was observed only for passive hallux range of motion (p = 0.040, η² = 0.170), indicating greater improvement in the exercise-only group. Navicular drop and postural stability variables did not change significantly. Conclusions: A six-week foot strengthening program improved hallux alignment, hallux mobility, and ankle dorsiflexion in healthy adults. The addition of a silicone toe spacer did not provide additional short-term benefits compared with exercise alone. Full article

The 2025–2030 Dietary Guidelines introduce an important shift in public health nutrition, emphasizing minimally processed foods, higher protein intake, greater inclusion of full-fat dairy, and a food-based advice centered on “real food” consumption. While several of these recommendations align with accumulating evidence, particularly the discouragement of ultra-processed foods and added sugars, substantial concerns remain regarding their internal coherence, population-level applicability, risk of misinterpretation, as well as environmental footprint. This critical narrative review evaluates whether the scope, emphasis, and framing of the new guideline components are proportionate to the strength, consistency, and context of the underlying evidence. Using a novel framework that distinguishes between nutritional adequacy, optimization, and therapeutic application, we assess the scientific coherence of key recommendations. A structured literature search was conducted in PubMed, Scopus, and Web of Science focusing on systematic reviews and meta-analyses of randomized controlled trials and large prospective cohort studies relevant to the updated guidelines. Particular attention is given to protein and saturated fat intakes, carbohydrate restriction in chronic disease, and the balance between simplification and scientific precision. Overall, the new guidelines represent a positive shift toward food-based recommendations; however, clearer differentiation between population-level guidance and context-specific interventions is required to preserve scientific rigor, reduce misinterpretation, and enhance public health relevance. Full article