Search Results (2,529)

Background/Objective: Prehabilitation aims to improve physiological reserve before surgery to enhance postoperative outcomes. Multiple systematic reviews have evaluated preoperative interventions in adult cardiac surgery; however, variability in scope, methodological quality, and overlap of primary trials complicates interpretation. The aim of this study is to synthesise and critically appraise evidence from systematic reviews and meta-analyses evaluating prehabilitation interventions in adults undergoing cardiac surgery. No funding was received for this study. Methods: We conducted an umbrella systematic review following a prospectively registered protocol (PROSPERO: CRD420261292354) and PRISMA 2020 guidance. PubMed, Web of Science, and Scopus were searched from inception to 31 December 2025. Eligible reviews included adults (≥18 years) undergoing cardiac surgery, evaluated and compared preoperative inspiratory muscle training (IMT), respiratory muscle training, and exercise-based, educational, or multimodal prehabilitation with usual care or sham intervention. Reviews focused solely on postoperative interventions or non-cardiac surgery were excluded. Methodological quality was assessed using AMSTAR-2. Certainty of evidence was evaluated using GRADE. Overlap of primary studies was quantified using the Corrected Covered Area (CCA). A structured narrative synthesis with a direction-of-effect framework was applied. Results: Eighteen systematic reviews (published 2012–2025) were included, comprising 46 unique primary studies and more than 6674 participants (exact totals unavailable due to incomplete reporting in at least one review). Overall overlap was high (CCA 12.5%). Respiratory-focused prehabilitation, particularly IMT, demonstrated consistent reductions in postoperative pulmonary complications (PPCs) (risk ratios approximately 0.42–0.53), pneumonia (RR ~0.44–0.45), and atelectasis (RR ~0.49–0.59), favouring prehabilitation over usual care. Hospital length of stay was reduced by approximately 1.5–3 days across multiple reviews. Inspiratory muscle strength improved consistently (mean difference ~+12 to +17 cmH₂O). Effects on ICU length of stay and mechanical ventilation duration were inconsistent or non-significant. Exercise-based programmes improved functional capacity (6 min walk distance increase ~50–75 m) and showed modest reductions in hospital stay, but heterogeneity was substantial. No intervention demonstrated a consistent reduction in postoperative mortality. Evidence was limited by clinical heterogeneity, performance bias in primary trials, inconsistent outcome definitions, and high overlap of key IMT trials across reviews. Mortality outcomes were underpowered. Conclusions: Preoperative IMT provides evidence for reducing pulmonary complications and shortening hospital stays in adult cardiac surgery. Exercise-based prehabilitation improves functional capacity but requires further high-quality, standardised trials. Integration of respiratory prehabilitation into cardiac surgical pathways appears supported by the current evidence. Full article

Background: With the increasing demand for non-surgical facial rejuvenation, injectable collagen biostimulators such as poly-L-lactic acid (PLLA), calcium hydroxyapatite (CaHA), polycaprolactone (PCL), poly-D,L-lactic acid (PDLLA) and powdered polydioxanone (PPDO) have become widely used by facial aesthetic practitioners. These agents stimulate neocollagenesis, providing gradual improvement in skin firmness, elasticity and facial contour with long-lasting results. While manufacturers emphasize the efficacy and favorable safety profile of these products, adverse events such as nodules, edema, inflammatory reactions and, in rare cases, granulomas have been reported. To date, no comprehensive systematic review has evaluated the proportion and nature of adverse effects associated with all major collagen biostimulators in facial aesthetic procedures. This study aims to synthesize current evidence on the proportion of adverse events linked to injectable collagen biostimulators. Methods: The systematic review will include clinical studies involving adults undergoing facial aesthetic procedures with PLLA, PDLLA, CaHA, PCL and PPDO that report adverse events during or after treatment. The search will be conducted in six main databases: CENTRAL, EMBASE, LILACS, PubMed, SCOPUS and Web of Science. No restrictions will be applied regarding language or publication date. The screening process will occur in two phases: first, two independent reviewers will assess titles and abstracts against the eligibility criteria; second, the same reviewers will conduct full-text evaluations. Data will be synthesized narratively, with a meta-analysis of proportions performed if appropriate. Additionally, sample characteristics, treatment protocols, study design and main findings will be reported. The risk of bias will be assessed independently by two reviewers using appropriate tools, based on the study design, with the support of artificial intelligence. PROSPERO registration number: CRD420251062785. Full article

Background: Excessive gingival display is frequently associated with upper lip hypermobility and represents a common aesthetic concern. Several therapeutic approaches have been proposed, including botulinum toxin type A injections, lip repositioning surgery (LRS), and combined techniques; however, no clear consensus exists regarding the most effective and stable treatment option. Methods: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA) guidelines. A comprehensive search of multiple electronic databases was performed, leading to the inclusion of 17 human studies that met predefined PICOS criteria. The review protocol was registered in PROSPERO (CRD420261281920). Results: Most included studies reported favorable outcomes in terms of reduction in gingival display, improvement in smile aesthetics, and patient satisfaction. No major adverse effects were reported, suggesting acceptable safety profiles for all therapeutic modalities. Outcomes varied depending on the type of intervention, surgical technique, botulinum toxin dosage and injection protocol, and the initial severity of upper lip hypermobility. Conclusions: Both botulinum toxin injections and LRS demonstrated effectiveness in reducing excessive gingival display. Botulinum toxin provided a rapid but temporary improvement, whereas modified LRS showed greater stability over time. Combined approaches appeared to offer the most consistent long-term results by limiting postoperative relapse. Further standardized protocols and long-term clinical studies are needed to confirm these findings and support evidence-based clinical decision-making. Full article

Background/Objectives: Oral squamous cell carcinoma (OSCC) accounts for over 90% of oral malignancies and remains associated with substantial global morbidity and mortality. Although tobacco and alcohol are established risk factors, they do not fully explain OSCC incidence, highlighting the need to explore additional contributors such as chronic inflammatory conditions. Periodontal disease, characterized by persistent inflammation and microbial dysbiosis, has emerged as a plausible factor in oral carcinogenesis and tumor progression. To systematically evaluate the association between periodontal disease and the risk of developing OSCC, and to assess the prognostic impact of periodontal disease–related factors, particularly intratumoral Porphyromonas gingivalis, on survival outcomes in patients with OSCC. Methods: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines and prospectively registered in PROSPERO (CRD420261296479). Comprehensive searches were performed in PubMed, EMBASE, Web of Science, Scopus, the Cochrane Library, ClinicalTrials.gov, and World Health Organization regional databases. Case–control studies evaluating OSCC risk and cohort studies assessing survival outcomes were included. Random-effects meta-analyses using inverse-variance models were applied. Heterogeneity was assessed using the I² statistic, and robustness was evaluated through Hartung–Knapp adjustment, leave-one-out sensitivity analyses, and Trial Sequential Analysis. Results: Five case–control studies were included in the etiological analysis. Periodontal disease was significantly associated with an increased risk of OSCC (pooled OR = 3.17; 95% CI: 1.94–5.21), with moderate heterogeneity (I² = 58.7%). Two cohort studies were included in the prognostic analysis. High intratumoral expression of P. gingivalis was significantly associated with poorer overall survival (pooled HR = 2.15; 95% CI: 1.33–3.47), with no detected heterogeneity (I² = 0%). Conclusions: Periodontal disease is strongly associated with an increased risk of OSCC, and intratumoral P. gingivalis appears to be an adverse prognostic marker. These findings underscore the relevance of periodontal inflammation and microbial factors across the OSCC continuum, from carcinogenesis to clinical outcomes, and support their consideration as potential targets for risk stratification and prevention strategies. Full article

Background: The Middle East and North Africa (MENA) region faces a high cardiovascular disease (CVD) burden alongside endemic serum 25(OH)D (vitamin D) deficiency. This systematic review examines the relationship between vitamin D deficiency and CVD risk factors in MENA populations. Methods: PubMed, Cochrane Library, and Scopus were searched from inception to 18 October 2024, for observational studies in the MENA region examining vitamin D deficiency and cardiovascular risk factors in adults. Independent data extraction was conducted. Study quality was appraised using the Joanna Briggs Institute tool and the Newcastle–Ottawa Scale, with risk of bias visualized using Robvis. Weighted mean differences in cholesterol, body mass index (BMI), and HbA1c between those with and without vitamin D deficiency were computed with random-effects meta-analysis. The protocol was registered in PROSPERO (ID: CRD42025615188) and funded by the Royal College of Surgeons in Ireland—Medical University of Bahrain. Results: Seventeen studies from nine MENA countries were included, predominantly cross-sectional, involving community-based and disease-specific cohorts. Vitamin D deficiency was highly prevalent and consistently associated with higher adiposity and central obesity. Several studies reported significant links between deficiency and poor glycemic control, particularly in obese and prediabetic groups. Meta-analysis demonstrated significantly higher total cholesterol (MD = 0.32; 95% CI = 0.11 to 0.52, p < 0.001), BMI (MD = 1.81; 95% CI = 0.68 to 2.94, p < 0.001), and HbA1c levels (MD = 0.31; 95% CI = 0.06 to 0.57, p = 0.02) in vitamin D deficient individuals, with notable heterogeneity. Conclusions: Vitamin D deficiency is highly prevalent in the MENA region and consistently associated with adiposity-related risk factors. Despite heterogeneity, findings underscore the need for public health strategies and further research to clarify causal pathways and population-specific interventions. Full article

Temporomandibular disorders (TMDs) are the prevalent causes of orofacial pain and dysfunction of the temporomandibular joint (TMJ) and masticatory muscles. Previous studies have revealed that proinflammatory cytokines play a key role in promoting inflammation, pain, and degeneration within the TMJ. In this context, the present systematic review synthesizes current evidence on various cytokines involved in the pathophysiology of TMDs and evaluates their associations with clinical signs and structural TMJ damage. A PRISMA-guided search (PROSPERO: CRD420251163290) was conducted in PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library to identify human-based, in vivo, and in vitro studies (January 2014 to September 2025) that assessed the roles of proinflammatory cytokines in TMDs. The following data were extracted from the identified studies: cytokine profiles, sampling methods, clinical outcomes, and TMJ structural changes. Study quality and risk of bias were systematically evaluated. A total of 15 studies (clinical, animal, and mechanistic) were included in the review. Tumor necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), and interleukin-17 (IL-17) consistently emerged as the major contributors to synovitis, cartilage degradation, nociceptive sensitization, and bone resorption. Human studies showed that high levels of TNF-α, IL-1β, and IL-6 and chemokines such as C-C motif chemokine ligand 2 (CCL2) and regulated on activation, normal T-cell expressed and secreted (RANTES) were associated with TMJ pain, restricted mandibular motion, crepitus, malocclusion, and erosive changes on imaging. An increased ratio of TNF to soluble TNF receptor in synovial fluid correlated with both pain and condylar damage, suggesting that loss of cytokine control contributes to progressive joint destruction. TMDs, particularly inflammatory and degenerative subtypes, are cytokine-driven pathologies rather than purely mechanical disorders. TNF-α, IL-1β, and IL-6 are the promising candidate biomarkers of local inflammation and structural joint pathology. Standardized longitudinal studies are required to validate cytokine-based diagnostics and develop anti-cytokine therapeutics. Full article

Approximately 1–2% of infants have cow’s milk protein allergy (CMPA). From a clinical perspective, diagnosing CMPA using the oral food challenge (OFC) is high risk, necessitating safer alternatives. One possible alternative is component-resolved diagnostics (CRD). This narrative review examines specific IgE (sIgE) thresholds for cow’s milk protein in predicting outcomes of OFCs in European children. Eligible studies focusing on CRD in European pediatric populations were identified through PubMed and Scopus databases. Our findings highlight the crucial role of Bos d 8 (casein) in the diagnostic process. Among the analyzed milk components, Bos d 8 appeared to be a promising marker for predicting positive OFC outcomes in several cohorts. However, due to significant population heterogeneity, conflicting findings exist, with some studies indicating that no single molecular component is consistently superior to whole cow’s milk specific IgE. While other molecules, such as Bos d 6 and lactoferrin, showed limited diagnostic utility, specific IgE to Bos d 8 demonstrated the highest clinical value. Although the double-blind, placebo-controlled food challenge (DBPCFC) remains the gold standard for CMPA diagnosis, the use of Bos d 8 in CRD is a key step toward risk stratification and may help reduce the need for high-risk OFCs in selected patients. Full article

Objective: Seaweed and microalgae provide antioxidants, polyunsaturated fatty acids, and bioactive compounds that may enhance exercise performance and accelerate recovery. However, evidence remains inconsistent. This systematic review and meta-analysis aimed to evaluate the effects of algae-derived supplementation on exercise performance and physiological recovery outcomes in healthy and athletic adults. Methods: This review was registered in PROSPERO (CRD420251166723) and conducted in accordance with PRISMA 2020 guidelines. PubMed, Web of Science, Embase, Cochrane Library, EBSCO, and CNKI were systematically searched for randomized controlled trials (RCTs) evaluating algae supplementation in exercise contexts. Inclusion and exclusion criteria were defined based on the PICOS framework. Primary outcomes included VO₂max, Time to exhaustion (TTE), maximal power output (WRmax), Time-Trial (TT) performance, and creatine kinase (CK). Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model. Subgroup, sensitivity, and publication bias analyses were performed. Results: Twenty-two RCTs (n = 822) investigating Spirulina, Chlorella, brown-algal polysaccharides, or astaxanthin met inclusion criteria. Algae supplementation showed a suggestive improvement in VO₂max (SMD = 0.88, 95%CI: 0.00–1.75) and significantly improved in TTE (SMD = 1.06, 95%CI: 0.16–1.96), with smaller effects on WRmax (SMD = 0.29, 95%CI: 0.03–0.55), and no significant benefit for TT performance (SMD = −0.27, 95%CI: −0.74 to 0.21). Regarding recovery, CK concentrations were significantly reduced (SMD = −0.78, 95%CI: −1.28 to −0.28). Subgroup analysis suggested greater effects for Chlorella supplementation, higher dosages, and aerobic training contexts; reductions in muscle-damage markers were more evident following resistance exercise. Sensitivity analyses supported the robustness of the main findings with minimal evidence of publication bias. Conclusions: Algae-derived supplements—particularly Spirulina and Chlorella—may modestly enhance aerobic exercise performance and attenuate exercise-induced muscle damage under certain conditions. Effects appear to depend on algae species, dosing strategies, intervention duration, and training modality. High-quality, multi-center RCTs incorporating mechanistic endpoints are needed to clarify optimal application and to develop athlete-specific recommendations. Full article

Background: Total hip arthroplasty (THA) for the late sequelae of childhood septic hip arthritis is technically demanding, and infection-related risk remains incompletely defined. This systematic review and meta-analysis address the research question: “In adults undergoing THA after childhood septic arthritis of the hip, what is the incidence of post-THA infection, revision, and mechanical/neurologic complications?” We systematically reviewed and meta-analyzed outcomes after THA in patients with septic hip arthritis diagnosed at ≤18 years. Methods: PubMed, Web of Science, Scopus, and the Cochrane Library were searched from inception to 31 December 2025 (PRISMA). Eligible studies reported THA outcomes after childhood septic arthritis and met a Methodological Index for Non-Randomized Studies (MINORS) threshold (≥9). A random-effects meta-analysis of events per hip was performed. Results: Nine studies were included; eight contributed to the quantitative synthesis (343 hips). The pooled incidence of any post-THA infection was 1.55% (95% CI 0.38–3.48; I² = 23.8%; 5/343); when microbiology was available, no relapse due to the index organism was reported and events were classified as new infections. The pooled incidence of revision for any cause was 4.99% (95% CI 2.27–8.70; I² = 43.4%; 15/334). Non-infectious complications were clinically relevant, including intraoperative fracture (6.95%) and nerve palsy (4.84%). Evidence was limited by retrospective designs and heterogeneous reporting. Conclusions: THA after childhood septic hip arthritis demonstrates a low risk of postoperative infection, with relapse of the original pathogen appearing rare in carefully selected quiescent cases, but a clinically meaningful burden of mechanical and neurologic complications. These findings underscore the importance of careful preoperative assessment, meticulous surgical technique, and highlight the limitations of the current evidence. The protocol was registered in PROSPERO (ID: CRD420261298181). No external funding was received. Full article

Objective: This umbrella review synthesizes and critically appraises the evidence on the efficacy and safety of tegoprazan-based versus proton pump inhibitor (PPI)-based regimens for Helicobacter pylori (H. pylori) eradication. Methods: This umbrella review was pre-registered in PROSPERO (CRD420251271120). Systematic reviews and meta-analyses published between 1 January 2018 and 10 December 2025 were identified through MEDLINE/PubMed, EMBASE, and the Cochrane Library. Reviews comparing tegoprazan-based and PPI-based eradication regimens in adult patients were included. Methodological quality was assessed using AMSTAR-2, risk of bias with ROBIS, and certainty of evidence with GRADE. Pooled relative risks (RRs) were calculated, with subgroup analyses by study design, treatment duration, and therapeutic regimen. Results: Eight systematic reviews and meta-analyses encompassing 17 primary studies and 12,714 participants were included. Tegoprazan-based regimens were associated with a statistically significant improvement in eradication efficacy compared with PPI-based therapies (RR = 1.019; 95% CI: 1.003–1.035; p = 0.021). In randomized controlled trials, the benefit was more pronounced (RR = 1.037; 95% CI: 1.015–1.061; p = 0.001), whereas no statistically significant benefit was observed in non-randomized studies (RR = 1.014; 95% CI: 0.991–1.037; p = 0.235). The efficacy advantage was mainly confined to quadruple therapy regimens (RR = 1.044; 95% CI: 1.002–1.088; p = 0.038). Tegoprazan-based regimens were associated with a lower incidence of overall adverse events compared with the PPI group (RR = 0.930; 95% CI: 0.885–0.976; p = 0.003). Conclusions: Tegoprazan-containing regimens were associated with a modest but statistically significant improvement in H. pylori eradication compared with PPI-containing regimens, particularly in randomized controlled trials and quadruple therapy regimens. Full article

Introduction: Major Depressive Disorder (MDD) has been increasingly associated with inflammatory dysregulation, particularly involving tumor necrosis factor-alpha (TNF-α). Genetic polymorphisms within the TNFA promoter region have been investigated as potential modulators of depressive susceptibility, symptom expression, treatment response, and inflammatory comorbidity. However, findings remain inconsistent across populations and clinical contexts. Methods: This systematic review adhered to PRISMA 2020 guidelines and was registered in PROSPERO (CRD420251242724). Observational and interventional studies evaluating associations between TNFA polymorphisms—specifically rs1800629 (−308 G/A), rs1799724 (−857 C/T), and rs1799964 (−1031 T/C)—and MDD-related outcomes in adults were included. Data extraction and methodological quality assessment were performed independently using an adapted GRIPS framework. Results: Eleven studies met the inclusion criteria, with eight investigating MDD without cardiovascular comorbidity and three assessing cardiovascular populations. Across diverse cohorts, rs1800629 and rs1799724 did not demonstrate consistent associations with MDD susceptibility. Although isolated population-specific findings were reported, genotype and allele distributions were generally comparable between cases and controls. Rs1799724 was associated with symptom dimensions and altered TNF-α expression in two cohorts. Rs1799964 was not linked to disease occurrence but showed potential association with antidepressant response and adverse cardiovascular outcomes in patients with chronic heart failure and comorbid depression. Overall, findings were heterogeneous and influenced by population characteristics, sample size, and clinical context. Conclusions: Current evidence does not support a robust etiological role for TNFA promoter polymorphisms in major depressive disorder. These variants may exert context-dependent modulatory effects on symptom expression, treatment response, or inflammatory-cardiovascular interactions rather than serving as primary susceptibility determinants. Larger, ethnically diverse studies integrating genetic, inflammatory, and clinical data are required to clarify the contribution of inflammatory genetic variability in depressive disorders. Full article

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: Magnetic resonance imaging (MRI) is the reference standard for evaluating temporomandibular joint (TMJ) disorders, particularly for assessing disc position, joint effusion, and degenerative changes. With increasing imaging demands and advances in deep learning, artificial intelligence (AI) has emerged as a potential adjunct to expert interpretation. This systematic review aimed to compare the diagnostic performance of AI-based models with that of human experts in TMJ MRI analysis. Methods: This review was conducted in accordance with the PRISMA 2020 guidelines and prospectively registered in PROSPERO (CRD420251174127). A systematic search of PubMed/MEDLINE, ScienceDirect, Wiley Online Library, and Springer Nature Link was performed for studies published between 2020 and 2026. Eligible studies included human participants undergoing TMJ MRI and evaluated AI, machine learning, or deep learning models against human expert interpretation. Extracted outcomes included sensitivity, specificity, accuracy, area under the receiver operating characteristic curve (AUC), and agreement metrics. Risk of bias was assessed using QUADAS-2. Due to substantial heterogeneity, a narrative synthesis was conducted. Results: Five retrospective diagnostic accuracy studies were included, comprising sample sizes ranging from 118 to 1474 patients. Target conditions included anterior disc displacement, joint effusion, osteoarthritis, and disc perforation. AI models demonstrated strong discriminative performance, with reported AUC values ranging from 0.79 to 0.98. In direct comparisons, AI achieved diagnostic accuracy comparable to experienced radiologists. AI systems frequently demonstrated higher specificity and similar overall accuracy, whereas human experts often showed higher sensitivity. In osteoarthritis assessment, AI performance approached expert level and exceeded that of less experienced readers. All studies were retrospective and predominantly single-center, with heterogeneous reference standards and limited external validation. Conclusions: AI achieves diagnostic performance comparable to experienced clinicians in TMJ MRI interpretation and shows promise as a decision-support tool. Nevertheless, it should be regarded as complementary to, rather than a replacement for, expert radiological assessment pending further rigorous validation. Full article

COASY-related disorders (CRDs) are a spectrum of autosomal recessive conditions caused by the dysfunction of CoA synthase, an enzyme responsible for the final steps of CoA synthesis. Clinical manifestations of CRDs are highly variable, ranging from perinatal lethal pontocerebellar hypoplasia to childhood-onset neurodegenerative brain iron accumulation, which is often recognized after clinical regression. Recent reports have described a few individuals with CRD who screened positive for carnitine palmitoyltransferase-I deficiency by newborn screening (NBS). However, heterogeneous clinical presentations, conflicting biochemical/molecular sequencing of CPT1A, and a lack of metabolic characterization have led to lengthy, costly diagnostic journeys. To address some of these aspects, this investigation retrospectively evaluated NBS acylcarnitine patterns in five CRD cases using Collaborative Laboratory Integrated Reports (CLIR). A total of 25 metabolites/ratios were identified to deviate significantly from reference ranges and were primarily composed of elevated free carnitine and reduced long-chain acylcarnitine levels. While low acylcarnitine concentrations are often not reported due to a lack of lower reference cutoffs, ratios involving these metabolites relative to short-chain acylcarnitines could aid in identifying CRD cases via NBS. When comparing this pattern to CPT-Ia cases, we confirmed a nearly identical acylcarnitine pattern between these, and thus support the need to consider CRD in cases with NBS results suggestive of CPT-Ia. This study is the first case series to characterize NBS patterns in patients with CRD and highlights the unique opportunity for early detection, particularly in cases that are neonatally asymptomatic and have unremarkable confirmatory biochemical results. Full article

Background: Oral biofilms are a major etiological factor in dental caries, periodontal disease, peri-implantitis, and endodontic infections. Increasing antimicrobial resistance and the limitations of conventional therapies have intensified interest in antimicrobial photodynamic therapy (aPDT). Hypericin, a natural photosensitizer derived from Hypericum perforatum, demonstrates potent reactive oxygen species generation and broad antimicrobial activity; however, its dental applications remain insufficiently synthesized. Objective: To systematically evaluate the antimicrobial efficacy, treatment parameters, safety, and clinical potential of hypericin-mediated aPDT against oral biofilms and infections in dentistry. Methods: This systematic review was conducted according to PRISMA 2020 and registered in PROSPERO CRD42024617727. Electronic searches of PubMed/MEDLINE, Embase, Scopus, and the Cochrane Library (January 2010 to December 2025) were performed. Studies assessing hypericin-mediated aPDT in oral or dental contexts were included. Methodological quality was evaluated using a predefined nine-domain risk-of-bias tool. Results: Eleven studies met the inclusion criteria. Hypericin-mediated aPDT demonstrated strong antimicrobial effects, achieving up to 99% planktonic inactivation and significant biofilm reduction across bacterial and fungal species. Activity was particularly pronounced against Gram-positive organisms, including Staphylococcus aureus and Enterococcus faecalis. However, efficacy against mature biofilms was variable and often dependent on formulation and irradiation parameters. Most studies showed moderate methodological quality, with frequent deficiencies in reporting light calibration and dosimetry. Advanced delivery systems, including liposomal and nanoparticle formulations, improved photodynamic performance. Conclusions: Hypericin-mediated aPDT shows promising antimicrobial activity against oral pathogens and biofilms, with favorable selectivity and safety profiles. Nevertheless, the evidence remains predominantly preclinical and heterogeneous. Standardized protocols and well-designed clinical trials are required before routine dental implementation can be recommended. Full article