Methodological Heterogeneity Research Articles

Development of a Core Outcome Set for Endodontics (COS-ENDO). Part 4: COS-ENDO for Studies of Vital Pulp Therapy in Permanent Teeth.

Methodological heterogeneity and reporting bias complicate interpreting endodontic outcomes. Supported by the American Association of Endodontists (AAE) and its Foundation, this study developed the Core Outcome Set for Endodontics (COS-ENDO) to standardize reporting for studies of Nonsurgical Root Canal Treatment/Retreatment, Surgical Endodontics, Vital Pulp Therapy, Apexification, and Regenerative Endodontics. This manuscript, Part 4 of a 5-part series, focuses on COS-ENDO for Vital Pulp Therapy, while other parts address the remaining treatments. Outcomes were identified through a scoping review and a web-based survey of AAE practicing members. In a two-round Delphi survey, clinicians, patients, and researchers rated outcomes on a 9-point scale. Ratings were assessed against consensus criteria, and a virtual meeting finalized COS-ENDO. Of the 97 invited participants to Round 1, 77 registered, and 73 (24 Academicians/Researchers, 26 Clinicians, and 23 Patients or their parents/caregivers) assessed 46 outcomes, with 17 excluded. The remaining outcomes-4 achieving consensus for inclusion and 25 lacking consensus-advanced to Round 2 for re-rating by 70 participants. This resulted in 10 outcomes achieving consensus for inclusion, and 19 lacking consensus. In the final meeting, 16 participants finalized the COS-ENDO for Vital Pulp Therapy studies, including Tooth survival, Pain, Signs of infection, Radiographic evidence of maintained periradicular health, Continued root development, Success, Functional tooth, Need for further intervention, and Adverse events/Complications. COS-ENDO is an important step in standardizing outcome reporting in endodontics, ensuring consistent reporting and enhancing research utility. Further efforts are needed to establish optimal measurement methods.

Development of a Core Outcome Set in Endodontics (COS-ENDO). Part 2: COS-ENDO for Studies of Nonsurgical Root Canal Treatment and Retreatment in Permanent Teeth.

Methodological heterogeneity and reporting bias complicate interpreting endodontic outcomes. Supported by the American Association of Endodontists (AAE) and its Foundation, this study developed the Core Outcome Set in Endodontics (COS-ENDO) to standardize reporting for studies of Nonsurgical Root Canal Treatment/Retreatment, Surgical Endodontics, Vital Pulp Therapy, Apexification, and Regenerative Endodontics. This manuscript, Part 2 of a 5-part series, focuses on COS-ENDO for Nonsurgical Root Canal Treatment/Retreatment, while other parts address the remaining treatments. Outcomes were identified through scoping reviews, a qualitative study with patients, and a web-based survey of AAE practicing members. In a two-round Delphi survey, clinicians, patients, and researchers rated outcomes on a 9-point scale. Ratings were assessed against consensus criteria, and a virtual meeting finalized COS-ENDO. Of the 97 invited participants to Round 1, 77 registered, and 73 (24 Academicians/Researchers, 26 Clinicians, and 23 Patients (or their parents/caregivers) assessed 39 outcomes, with 18 excluded. The remaining outcomes-7 achieving consensus for inclusion and 14 lacking consensus-advanced to Round 2 for re-rating by 70 participants. This resulted in 9 outcomes achieving consensus for inclusion, and 12 lacking consensus. In the final meeting, 16 participants finalized the COS-ENDO for Nonsurgical Root Canal Treatment/Retreatment, including Tooth survival, Pain, Signs of infection, Radiographic evidence of periradicular healing, Success, Functional tooth, Need for further intervention, and Adverse events/Complications. COS-ENDO is an important step in standardizing outcome reporting in endodontics, ensuring consistent reporting and enhancing research utility. Further efforts are needed to establish optimal measurement methods.

Development of a Core Outcome Set for Endodontics (COS-ENDO). Part 3: COS-ENDO for Studies of Surgical Endodontics in Permanent Teeth.

Methodological heterogeneity and reporting bias complicate interpreting endodontic outcomes. Supported by the American Association of Endodontists (AAE) and its Foundation, this study developed the Core Outcome Set in Endodontics (COS-ENDO) to standardize reporting for studies of Nonsurgical Root Canal Treatment/Retreatment, Surgical Endodontics, Vital Pulp Therapy, Apexification, and Regenerative Endodontics. This manuscript, Part 3 of a 5-part series, focuses on COS-ENDO for Surgical Endodontics, while other parts address the remaining treatments. Outcomes were identified through a scoping review, a qualitative study with patients, and a web-based survey of AAE practicing members. In a two-round Delphi survey, clinicians, patients, and researchers rated outcomes on a 9-point scale. Ratings were assessed against consensus criteria, and a virtual meeting finalized COS-ENDO. Of the 97 invited participants to Round 1, 77 registered, and 73 (24 Academicians/Researchers, 26 Clinicians, and 23 Patients or their parents/caregivers) assessed 46 outcomes, with 17 excluded. The remaining outcomes-7 achieving consensus for inclusion and 22 lacking consensus-advanced to Round 2 for re-rating by 70 participants. This resulted in 1 outcome achieving consensus for exclusion, 10 for inclusion, and 18 lacking consensus. In the final meeting, 16 participants finalized the COS-ENDO for Surgical Endodontics, including Tooth survival, Pain, Signs of infection, Radiographic evidence of periradicular healing, Success, Functional tooth, Need for further intervention, and Adverse events/Complications. COS-ENDO is an important step in standardizing outcome reporting in endodontics, ensuring consistent reporting and enhancing research utility. Further efforts are needed to establish optimal measurement methods.

Development of a Core Outcome Set in Endodontics (COS-ENDO): Part 1 - General Methods for Developing COS-ENDO for Studies of Nonsurgical Root Canal Treatment, Retreatment, Surgical Endodontics, Vital Pulp Therapy, Apexification, and Regenerative Endodontics in Permanent Teeth.

Methodological heterogeneity and reporting bias complicate interpreting endodontic outcomes. Supported by the American Association of Endodontists (AAE) and its Foundation, this study developed the Core Outcome Set in Endodontics (COS-ENDO) to standardize reporting for studies of Nonsurgical Root Canal Treatment/Retreatment, Surgical Endodontics, Vital Pulp Therapy, Apexification, and Regenerative Endodontics. This manuscript, the first in a 5-part series, outlines the methods for developing COS-ENDO, with detailed findings for each treatment presented in subsequent parts. Outcomes were identified through scoping reviews, a qualitative study with patients, and a web-based survey of AAE practicing members. In a two-round Delphi survey, clinicians, patients, and researchers rated outcomes on a 9-point scale. Ratings were assessed against consensus criteria, and a virtual meeting finalized COS-ENDO. Of the 97 invited participants to Round 1, 77 (79%) registered, and 73 (95%) completed the survey, including 24 Academicians/Researchers, 26 Clinicians, and 23 Patients (or their caregivers/parents). They rated 64 outcomes, totaling 182 occurrences across treatments: 39 for Nonsurgical Root Canal Treatment/Retreatment, 46 for Surgical Endodontics, 46 for Vital Pulp Therapy, and 51 for Apexification/Regenerative Endodontics. The outcomes that achieved consensus for inclusion and those lacking consensus (either for inclusion or exclusion) advanced to Round 2 for re-rating by 70 participants. During the final consensus meeting, 16 participants discussed the outcomes and finalized the COS-ENDO. COS-ENDO is an important step toward standardizing outcome reporting in endodontics. Its implementation will ensure consistent reporting, enhancing research utility and evidence synthesis. Further efforts are needed to establish optimal measurement methods.

Development of a Core Outcome Set for Endodontics (COS-ENDO). Part 5: COS-ENDO for Studies of Apexification and Regenerative Endodontics in Permanent Teeth.

Methodological heterogeneity and reporting bias complicate interpreting endodontic outcomes. Supported by the American Association of Endodontists (AAE) and its Foundation, this study developed the Core Outcome Set in Endodontics (COS-ENDO) to standardize reporting for studies of Nonsurgical Root Canal Treatment/Retreatment, Surgical Endodontics, Vital Pulp Therapy, Apexification, and Regenerative Endodontics. This manuscript, the last in a 5-part series, focuses on COS-ENDO for Apexification and Regenerative Endodontics, while other parts address the remaining treatments. Outcomes were identified through scoping reviews and a web-based survey of AAE practicing members. In a two-round Delphi survey, clinicians, patients, and researchers rated outcomes on a 9-point scale. Ratings were assessed against consensus criteria, and a virtual meeting finalized COS-ENDO. Of the 97 invited participants to Round 1, 77 registered, and 73 (24 Academicians/Researchers, 26 Clinicians, and 23 Patients or their parents/caregivers) assessed 51 outcomes, with 18 excluded. The remaining outcomes-7 achieving consensus for inclusion and 26 lacking consensus-advanced to Round 2 for re-rating by 70 participants. This resulted in 14 outcome achieving consensus for inclusion, and 19 lacking consensus. In the final meeting, 16 participants finalized the COS-ENDO for Apexification and Regenerative Endodontics, including Tooth survival, Pain, Signs of infection, Radiographic evidence of periradicular healing, Continued root development, Success, Functional tooth, Need for further intervention, and Adverse events/Complications. COS-ENDO is an important step in standardizing outcome reporting in endodontics, ensuring consistent reporting and enhancing research utility. Further efforts are needed to establish optimal measurement methods.

Cardiovascular and Metabolic Effects of Alternative Therapies in Menopause: A Comprehensive Review

INTRODUCTION Menopause is associated with significant hormonal changes that increase cardiovascular and metabolic risks, including dyslipidemia, insulin resistance, and hypertension. Hormone replacement therapy (HRT) has traditionally been used to mitigate these risks; however, concerns regarding adverse effects have led to a growing interest in alternative therapies such as phytoestrogens, dietary modifications, exercise, and mind-body interventions. These approaches aim to provide symptom relief and cardiometabolic benefits without the potential risks associated with hormonal treatments. OBJETIVE To evaluate the cardiovascular and metabolic impacts of alternative therapies in menopausal women, providing an evidence-based perspective on their effectiveness and safety. METHODS This is a narrative review which included studies in the MEDLINE – PubMed (National Library of Medicine, National Institutes of Health), COCHRANE, EMBASE and Google Scholar databases, using as descriptors: “Menopause” AND “Phytoestrogens” OR “Cardiovascular risk” OR “Metabolic syndrome” OR “Hormone replacement alternatives” in the last years. RESULTS AND DISCUSSION Studies suggest that phytoestrogens, particularly isoflavones and lignans, may improve lipid profiles and endothelial function, while plant-based diets and Mediterranean-style eating patterns have been linked to better metabolic outcomes. Regular physical activity has shown a significant impact on reducing central adiposity and improving insulin sensitivity. Additionally, acupuncture and mind-body practices, such as yoga and meditation, have demonstrated promising results in regulating autonomic function and reducing stress-related metabolic disturbances. Despite these benefits, heterogeneity in study methodologies and individual variability remain challenges in establishing standardized treatment guidelines. CONCLUSION Alternative therapies represent a promising avenue for improving cardiovascular and metabolic health in menopausal women. While they offer potential benefits, further high-quality research is required to determine optimal interventions, dosages, and long-term effects. A multidisciplinary approach that integrates lifestyle modifications and individualized treatment plans is essential to optimizing health outcomes and ensuring evidence-based recommendations for menopausal care.

Breathing in virtual reality for promoting mental health: a scoping review

Breathing techniques have long been recognized as effective strategies for promoting mental health-related outcomes such as relaxation and emotional regulation. Virtual reality (VR), with its immersion and interactivity, offers the possibility to amplify the effectiveness of breathing techniques in promoting mental health. Recently, there has been an increasing use of VR to support breathing, although a formal summary of this integration is lacking. Following the PRISMA-ScR reporting guidelines, this scoping review aims to investigate the integration of breathing techniques and VR experiences and examine their potential effects on mental health-related outcomes. The synthesis of the reviewed studies (n = 18) reveals that different VR experiences can be used to strengthen breathing techniques. VR can, for example, reduce distractions and enhance focus during breathing exercises, provide direct, real-time feedback on the practice, and be used to create personalized environments, allowing users to train their breathing techniques in various contexts, from calming virtual nature settings to safe environments for practicing breathing skills that can be applied to real-life situations. Furthermore, this scoping review reveals the positive effects of VR-based breathing interventions on reducing clinical symptoms and increasing well-being and physical health outcomes. Overall, while acknowledging some methodological heterogeneity in the existing studies, the findings demonstrate the unique and promising potential of integrating breathing techniques with VR experiences. Future research is recommended to understand long-term effects, user experience, and the potential customization of interventions for diverse clinical and well-being contexts.

The co-occurrence of functional neurological disorder and autism spectrum disorder: a systematic literature review and meta-analysis

ABSTRACT Background Recent studies reveal increasing interest in the link between Autism Spectrum Disorder (ASD) and Functional Neurological Disorder (FND), prompting a systematic review and meta-analysis of their co-occurrence. Method The review covered a comprehensive literature search across multiple databases up to November 2024, focusing on peer-reviewed studies of ASD and FND co-occurrence. Twenty-four studies qualified for inclusion. Results The study included 11,324 participants, predominantly female (73.4%). It estimated the proportion of ASD in FND populations to be 0.10 (95% CI: 0.07–0.15), with significant heterogeneity (I² = 97%, p < 0.01). Subgroup analysis showed variation among different age groups and diagnoses. The proportion of ASD was 0.09 in adults and 0.10 in children with FND, 0.15 in adults and 0.19 in children with Functional Tic-Like Behaviours (FTLB), and 0.07 in children with Functional Seizures (FS). Conclusion Many studies have reported the co-occurrence of ASD in FND, suggesting a higher-than-expected rate of 10%. Emerging themes exploring the overlapping determinants of FND and ASD, are discussed. However, the significance of this correlation and the overlapping determinants that might explain it, require further research due to the heterogeneity in methodologies, settings, conditions studied and findings. The presence of publication bias warrants cautious interpretation of the results.

Ne Health: Bisphenol a and Early Puberty, a Systematic Literature Review

Objective: Investigate the relationship between BPA exposure and precocious puberty. Theoretical Framework: The theoretical framework includes studies that aim to demonstrate human contamination by BPA; highlight its toxic potential to human health and the environment; and associate BPA exposure with alterations in pubertal development (Valadares and Pfeilsticker, 2012; Castro-Correia and Fontoura, 2015; Sonnenschein and Soto, 2010, among others). Method: The methodology adopted for this research comprises a systematic literature review, analyzing experimental, epidemiological, and clinical studies available in databases such as PubMed, Scopus, and Web of Science. Results and Discussion: The results revealed a positive correlation between BPA exposure and alterations in pubertal development, particularly in girls, with evidence pointing to the influence of this compound in accelerating sexual maturation. However, the methodological heterogeneity of the studies and the lack of consensus on the exact biological mechanisms indicate the need for more robust research. Research Implications: This study contributes to the literature by demonstrating that BPA exposure may be a risk factor for precocious puberty, highlighting the importance of stricter regulatory policies and additional investigations to confirm and clarify this association. Originality/Value: This study significantly contributes to the literature by gathering and synthesizing available evidence on the relationship between bisphenol A (BPA) exposure and precocious puberty. It provides a comprehensive overview of the experimental, epidemiological, and clinical data, highlighting the potential of BPA as an environmental risk factor for alterations in pubertal development, particularly in girls.Furthermore, the article identifies critical gaps in scientific knowledge, such as the lack of consensus on the exact biological mechanisms through which BPA accelerates sexual maturation and the methodological heterogeneity present in the analyzed studies. This critical approach reinforces the need for future research that is more robust and methodologically consistent. Finally, by emphasizing the importance of stricter regulatory policies to minimize BPA exposure, the study also contributes to a public health agenda, pointing to pathways for interventions that can mitigate the impacts of this endocrine disruptor on human health and the environment.

Virtual Biopsy for the Prediction of MGMT Promoter Methylation in Gliomas: A Comprehensive Review of Radiomics and Deep Learning Approaches Applied to MRI

Background/Objectives: The methylation status of the O6-methylguanine-DNA methyltransferase (MGMT) promoter in gliomas has emerged as a critical biomarker for prognosis and treatment response. Conventional methods for assessing MGMT promoter methylation, such as methylation-specific PCR, are invasive and require tissue sampling. Methods: A comprehensive literature search was performed in compliance with the updated PRISMA 2020 guidelines within electronic databases MEDLINE/PubMed, Scopus, and IEEE Xplore. Search terms, including “MGMT”, “methylation”, “glioma”, “glioblastoma”, “machine learning”, “deep learning”, and “radiomics”, were adopted in various MeSH combinations. Original studies in the English, Italian, German, and French languages were considered for inclusion. Results: This review analyzed 34 studies conducted in the last six years, focusing on assessing MGMT methylation status using radiomics (RD), deep learning (DL), or combined approaches. These studies utilized radiological data from the public (e.g., BraTS, TCGA) and private institutional datasets. Sixteen studies focused exclusively on glioblastoma (GBM), while others included low- and high-grade gliomas. Twenty-seven studies reported diagnostic accuracy, with fourteen achieving values above 80%. The combined use of DL and RD generally resulted in higher accuracy, sensitivity, and specificity, although some studies reported lower minimum accuracy compared to studies using a single model. Conclusions: The integration of RD and DL offers a powerful, non-invasive tool for precisely recognizing MGMT promoter methylation status in gliomas, paving the way for enhanced personalized medicine in neuro-oncology. The heterogeneity of study populations, data sources, and methodologies reflected the complexity of the pipeline and machine learning algorithms, which may require general standardization to be implemented in clinical practice.

P1284 Prevalence of immune-mediated extraintestinal manifestations in paediatric Inflammatory Bowel Disease: a systematic review and meta-analysis

Abstract Background Concurrent immune-mediated extraintestinal manifestations (IM-EIMs; Table 1) are common in paediatric-onset inflammatory bowel disease (pIBD), but the overall epidemiology is unknown. This systematic review and meta-analysis aimed to summarise the prevalence and management of EIMs in pIBD. Methods MEDLINE, EMBASE and CENTRAL, clinicaltrials.gov and conference abstracts were searched up to May 6, 2024, for studies that included pIBD (2-17 years old) with secondarily diagnosed EIMs. The primary outcome included the prevalence of IM-EIMs among pIBD. Secondary outcomes included efficacy and adverse effects of treatment on EIMs. Meta-analysis included pooled proportions with DerSimonian-Laird random-effects analysis. Results The pooled proportion of IM-EIMs among pIBD was 8.4% (95% CI, 6.5-11.0%; I2=97%) among 53 eligible studies. The pooled proportion of IM-EIMs was 10.3% (95% CI, 7.3-13.8%; I2=95%) among 37 Crohn’s disease (CD) studies, compared to 11.3% (95% CI, 7.8-15.3%; I2=93%) among 39 ulcerative colitis (UC) studies. Enthesitis was the highest reported individual IM-EIM (23%, 95% CI, 4-50%; I2=94.7%) in pIBD. Arthritis was the second highest reported individual IM-EIM (8%, 95% CI, 6-10%; I2=96%) in pIBD, followed by primary sclerosing cholangitis (PSC) in UC (5%, 95% CI, 4-7%; I2=81%; Table 2). Uveitis, pyoderma gangrenosum, autoimmune hepatitis, and PSC in CD were the lowest reported IM-EIMs at 1% or less. The largest difference in reported proportions between IBD phenotypes was PSC, which was 4% higher in UC than CD. Only one eligible study described treatment response. Conclusion This meta-analysis identified that while musculoskeletal manifestations are relatively common, fewer than 5% of pIBD patients experience ophthalmological, dermatological, and hepatic IM-EIMs. There was significant methodological and statistical heterogeneity as expected for the relatively small number of individual paediatric studies and likely resulted in the large difference of pooled proportions between individual IM-EIMs. Multicentre collaborative efforts are needed to systematically describe the epidemiology and management outcomes of EIMs in pIBD in the current era of advanced therapies.

Kinematic and kinetic characteristics of individuals with coping lateral ankle sprain during landing and walking/running tasks: A systematic review with meta-analysis.

We aimed to synthesize the kinematics and kinetics during landing and walking/running tasks of ankle copers compared with patients with chronic ankle instability and controls. We systematically searched PubMed, CINAHL, SPORTDiscus, and Web of Science. Tri-planar lower extremity biomechanics (joint angle and moment at maximum and initial contact, and joint displacement) were synthesized using standard mean difference and 95% confidence intervals. We assessed methodological quality, study heterogeneity, and publication bias. We identified 13 studies. Pooled evidence indicated that copers had less inversion and eversion angles, and ankle frontal displacement during landing compared with patients with chronic ankle instability (|standard mean difference| 0.31-0.40). Copers revealed greater dorsiflexion, plantarflexion, and ankle sagittal displacement during landing and less plantarflexion moment during walking than patients with chronic ankle instability (|standard mean difference| 0.29-0.46); however, most ankle biomechanics of copers were not significantly different from those of controls. In the proximal joints, copers revealed less knee valgus angle at maximum and initial contact (|standard mean difference| 0.25-0.33); and less hip flexion angle at maximum and initial contact, hip external rotation angle and sagittal and frontal displacement during landing (standard mean difference 0.49-0.73) than patients with chronic ankle instability. Copers had less hip extension moment during walking and greater maximum hip adduction angle during landing than controls (|standard mean difference| 0.66-0.77). Our results provide insight into the lower extremity biomechanics of copers during dynamic tasks, contributing injury coping mechanisms and developing rehabilitation programs to return to sports.

The impact of demographics and positioning on the imaging features of the optic nerve sheath and ophthalmic vessels

BackgroundThere are significant discrepancies in the optic nerve sheath diameter (ONSD) reported in the literature. We aimed to determine the ultrasonographic imaging features of ONSD and ophthalmic vessels in a healthy population, using a standardized protocol, and to estimate the effect of demographics and positioning changes on imaging measurements.MethodsWe measured the mean values of the ONSD in supine and sitting position and the Doppler imaging parameters of the ophthalmic, central retinal and short posterior ciliary arteries. Inter-observer reliability was assessed using intraclass correlation coefficient (ICC). Linear regression models were fitted to predict the effect of demographic and clinical determinants on the imaging features.ResultsA total of 50 measurements were obtained for each observer. The mean ONSD was 5.9 mm and there was a mean reduction of 0.2 mm when assessed in sitting position (p < 0.001). Doppler analysis showed higher peak-systolic velocity and resistive index in the ophthalmic artery (35.6 cm/s vs. 12.0 cm/s; 0.78 vs. 0.70) compared to the central retinal artery (p < 0.001). Age, sex, heart rate and systolic blood pressure were significant determinants of the imaging features, with ONSD being larger in males (p < 0.001) and increasing with heart rate (p = 0.001). ICC estimates indicated ‘good’ inter-observer reliability of the ONSD and the ophthalmic and central retinal arteries velocities and resistance.ConclusionsOur findings suggest a significant impact of patient demographics and positioning during ultrasonography on the normal imaging features of the ONSD and ophthalmic vessels. The heterogeneity in methodology and clinical cohorts may justify previous discrepancies in the literature. These findings can assist in the interpretation of imaging features in clinical settings and in the standardization of point of care ONSD ultrasonography.

Meta-Analysis: Exclusive Enteral Nutrition in Adults With Ulcerative Colitis.

Exclusive enteral nutrition (EEN) is an established dietary therapy for Crohn's disease but its role in ulcerative colitis remains unclear. To investigate the efficacy of EEN in adults with active ulcerative colitis and compare variations in treatment protocols, safety, tolerability and adherence. We conducted a systematic search of MEDLINE, Embase, Cochrane CENTRAL, Emcare, CINAHL, Web of Science and trial registries for articles published from inception until July 21, 2024. We included all experimental and observational studies that described the use of EEN in adults with active ulcerative colitis. This review was registered on PROSPERO (CRD42022319584). Of 3273 articles screened, we included 10 studies (334 adults). Overall, there was no difference between EEN and comparator for ulcerative colitis remission induction (median follow-up 14 days, risk ratio (RR) 1.15, 95% confidence interval (CI) 0.71-1.85; 2 studies). In acute severe ulcerative colitis, there was no difference between EEN and comparator for corticosteroid failure (RR 0.76, 95% CI 0.48-1.20; 2 studies) or risk of colectomy (RR 0.88, 95% CI 0.51-1.51, n = 2 studies) during index admission. The pooled discontinuation rate was 3% (95% CI 0-10; 9 studies). There was heterogeneity in trial design, methodology and assessment of outcomes. EEN was well tolerated with low therapy discontinuation in adults with active ulcerative colitis. However, there is insufficient evidence to support the use of EEN as an adjunctive therapy to standard of care. Further, well-designed studies with reproducible methodology and endpoints are necessary to evaluate its effectiveness. PROSPERO 2022 CRD42022319584.

Artificial intelligence for early diagnosis of breast cancer in women: A systematic literature review

Breast cancer is one of the most prevalent cancers affecting women globally. Early diagnosis is crucial for effective treatment and improved survival rates. Imaging techniques such as mammography and ultrasound are widely used conventional diagnostic methods. However, these methods have limitations, including low sensitivity and specificity, especially in patients with dense breast tissue. For instance, mammograms miss approximately 20% of breast cancer cases, leading to false negatives and delayed treatment that can have fatal consequences. To address these challenges, artificial intelligence (AI)-based diagnostic tools have been developed to assist healthcare professionals in accurately detecting breast cancer. These tools work in conjunction with human radiologists to improve diagnostic outcomes. In addition, biomarkers present a promising non-invasive, more convenient alternative for the early detection of breast cancer, potentially overcoming the limitations of traditional screening methods. Various biomarkers, such as circulating tumor cells, cell-free tumor nucleic acids, and microRNAs, have shown promise in early breast cancer diagnosis. A systematic literature review is needed to consolidate ongoing efforts in molecular biology and biomedical sciences aimed at achieving early breast cancer diagnosis. One of the limitations of previously published research is the heterogeneity of methodologies, which can compromise the credibility of comparisons due to potential inaccuracies in the original data. Hence, future studies should prioritize using consistent datasets and developing robust techniques to manage missing values, outliers, and class imbalances to improve the reliability of breast cancer detection models. This literature review seeks to bridge the knowledge gap by reporting recent high-performing AI models and effective biomarkers that can serve as diagnostic tools in clinical practice.

Cost-utility of lumbar interbody fusion surgery: A systematic review.

Lumbar interbody fusion (LIF) is a common surgical intervention for treating lumbar degenerative disorders. Increasing demand has contributed to ever-increasing healthcare expenditure and economic burden. To address this, cost-utility analyses (CUAs) compare value in the context of patient outcomes. CUAs quantify health improvements using quality-adjusted life years (QALYs), allowing decision-makers to determine procedure value. While there is a growing body of literature assessing LIF value, a comprehensive synthesis of LIF CUAs is lacking. This systematic review aims to address this gap by assessing all available CUAs of LIF techniques, to support evidence-based practices that improve outcomes and promote efficient resource use. Systematic review. This study sample consisted of adult patients with lumbar degenerative conditions specifically treated with lumbar interbody fusion, including grade I or II degenerative spondylolisthesis, lumbar spinal stenosis, disc degeneration, and spondylosis, with or without low back and/or leg pain. Direct (healthcare) and indirect (non-healthcare) costs, cost sources and calculation methods, utility scores, QALY gain, cost-utility, incremental cost-effectiveness ratios, and willingness-to-pay thresholds. Outcomes were reported as median and interquartile ranges (IQR). A systematic review was conducted following PRISMA guidelines. PubMed, Web of Science, and Embase were searched from inception to October 23, 2023, for CUAs reporting QALYs and costs of LIF procedures. Relevant studies were selected and data extracted. Subgroup analyses compared minimally invasive versus open surgery and anterior versus posterior approaches. Study quality was assessed using the CHEC-Extended tool. Quantitative meta-analysis was not performed due to methodological heterogeneity. Out of 2047 identified studies, 14 met inclusion criteria. The mean CHEC-Extended score was 72.1%. Most studies reported on TLIF (n=11) and utilized EQ-5D questionnaire to calculate utility (n=9). Direct costs were sourced from institutional databases, Medicare, DRGs, Redbook, and a variety of other sources. Most indirect costs were estimated from productivity loss. TLIF demonstrated the highest median QALY gain over 1 year (0.43, IQR 0.121-0.705), while PLIF was highest over 2 years (1.33). ALIF was most favorable over 1 year ($30901/QALY) and OLIF was most favorable over 2 years ($11187/QALY). PLIF, TLIF, and LLIF exhibited similar cost-utility over 2 years ($44383, $45628, $48576/QALY). MIS was substantially favorable to OS at 1 year ($42635 vs. $226304), though similar at 2 years ($48576 vs. $45628/QALY). Anterior approach was favorable to posterior approach at 1 year ($30901.5 vs. $81038) and 2 years ($29881.9 vs. $44383). Cost-utility comparisons substantially varied and were sensitive to utility measures, study methodology, cost sourcing, and follow-up duration. This is the first systematic review to comprehensively assess CUAs of all LIF approaches in the existing literature. While certain approaches, such as ALIF and OLIF, may demonstrate favorable outcomes, these conclusions are limited by high methodological heterogeneity and a limited study pool. By addressing existing gaps in study design and reporting, future comparative cost-utility research can better inform evidence-based decision-making and optimize the value of spinal surgical care.

Integrating genetics, metabolites, and clinical characteristics in predicting cardiometabolic health outcomes using machine learning algorithms - A systematic review.

Machine learning (ML) integration of clinical, metabolite, and genetic data reveals variable results in predicting cardiometabolic health (CMH) outcomes. Therefore, we aim to (1) evaluate whether a multi-modal approach incorporating all three data types using ML algorithms can improve CMH outcome prediction compared to single-modal or paired-modal models, and (2) compare the methodologies used in existing prediction models. We systematically searched five databases from 1998 to 2024 for ML predictive modelling studies using the multi-modal approach for CMH outcomes. Risk-of-bias assessment tools were used to assess methodological quality. Study characteristics, ML algorithms, data preprocessing, evaluation methods and metrics, feature selections, and feature importance parameters were synthesized narratively to show methodological heterogeneity. Of the four included studies (3ML algorithms), three were at low risk of bias, and one was at high risk. The multi-modal approach consistently improved T2D and BP prediction compared to single-modal or paired-modal models. Genetics showed the lowest predictive performance in three studies. Logistic regression (n=2 studies) and random forest (n=1) were used in T2D studies, while XGBoost was used in one BP study. One study with missing data and variations in feature selection across all studies hindered a comprehensive comparison of feature importance. Our review emphasizes the potential improvement in T2D and BP prediction using ML algorithms with the multi-modal approach. However, further studies using diverse ML algorithms with optimized methodologies on single-modal, paired-modal, and multi-modal models are needed to gain insights into biomarker selection for predicting CMH outcomes.

Understanding Patterns of the Gut Microbiome May Contribute to the Early Detection and Prevention of Type 2 Diabetes Mellitus: A Systematic Review.

The rising burden of type 2 diabetes mellitus (T2DM) is a growing global public health problem, particularly prominent in developing countries. The early detection of T2DM and prediabetes is vital for reversing the outcome of disease, allowing early intervention. In the past decade, various microbiome-metabolome studies have attempted to address the question of whether there are any common microbial patterns that indicate either prediabetic or diabetic gut microbial signatures. Because current studies have a high methodological heterogeneity and risk of bias, we have selected studies that adhered to similar design and methodology. We performed a systematic review to assess if there were any common changes in microbiome belonging to diabetic, prediabetic and healthy individuals. The cross-sectional studies presented here collectively covered a population of 65,754 people, with 1800 in the 2TD group, 2770 in the prediabetic group and 61,184 in the control group. The overall microbial diversity scores were lower in the T2D and prediabetes cohorts in 86% of the analyzed studies. Re-programming of the microbiome is potentially one of the safest and long-lasting ways to eliminate diabetes in its early stages. The differences in the abundance of certain microbial species could serve as an early warning for a dysbiotic gut environment and could be easily modified before the onset of disease by changes in lifestyle, taking probiotics, introducing diet modifications or stimulating the vagal nerve. This review shows how metagenomic studies have and will continue to identify novel therapeutic targets (probiotics, prebiotics or targets for elimination from flora). This work clearly shows that gut microbiome intervention studies, if performed according to standard operating protocols using a predefined analytic framework (e.g., STORMS), could be combined with other similar studies, allowing broader conclusions from collating all global cohort studies efforts and eliminating the effect-size statistical insufficiency of a single study.

Liquid Biopsy and Challenge of Assay Heterogeneity for Minimal Residual Disease Assessment in Colon Cancer Treatment.

This review provides a comprehensive overview of the evolving role of minimal residual disease (MRD) for patients with Colon Cancer (CC). Currently, the standard of care for patients with non-metastatic CC is adjuvant chemotherapy (ACT) for all patients with stage III and high-risk stage II CC following surgical intervention. Despite a 5-20% improvement in long-term survival outcomes, this approach also results in a significant proportion of patients receiving ACT without any therapeutic benefit and being unnecessarily exposed to the risks of secondary side effects. This underscores an unmet clinical need for more precise stratification to distinguish patients who necessitate ACT from those who can be treated with surgery alone. By employing liquid biopsy, it is possible to discern MRD enabling the categorization of patients as MRD-positive or MRD-negative, potentially revolutionizing the management of ACT. This review aimed to examine the heterogeneity of methodologies currently available for MRD detection, encompassing the state-of-the-art technologies, their respective advantages, limitations, and the technological challenges and multi-omic approaches that can be utilized to enhance assay performance. Furthermore, a discussion was held regarding the clinical trials that employ an MRD assay focusing on the heterogeneity of the assays used. These differences in methodology, target selection, and performance risk producing inconsistent results that may not solely reflect biological/clinical differences but may be the consequence of the preferential use of particular products in studies conducted in different countries. Standardization and harmonization of MRD assays will be crucial to ensure the liquid revolution delivers reliable and clinically actionable outcomes for patients.

Standardisation of the radiological definition of supramaximal resection in glioblastoma.

Glioblastoma remains the most common and lethal primary malignant brain tumour, with high rates of recurrence and progression despite gross-total resection of the contrast-enhancing region based on T1-weighted MRI. There has been growing interest in exploring "supramaximal" resections that extend beyond contrast-enhancing borders, with initial retrospective data suggesting survival benefit, but there is currently no consensus definition. In this systematic review, we explore the evolution of supramaximal resection in glioblastoma, dissect the incongruencies in the literature regarding its definition, qualitatively appraise each definition and discuss the results of various studies that have explored its impacts on patient outcomes. MEDLINE, EMBASE, SCOPUS, Cochrane Registry of Clinical Trials and Pub-MED were systematically searched for studies of glioblastoma patients who had undergone supramaximal resection. After screening and applying eligibility criteria, 25 studies were included in the final review. Definitions were grouped according to radiological modality and visualisation adjuncts and included various extents of resection of hyperintensity visualised using T2-Fluid-Attenuated Inversion Recovery, various volumetric resections of the non-contrast enhancing region, removal of methionine-uptake areas on PET, complete removal of 5-aminolevulinic acid fluorescent tissue and lobectomies. Our systematic review identified a general trend suggesting a survival benefit from supramaximal resection compared to gross-total resection but, more importantly, demonstrated the limitations of these studies due to selection bias and substantial methodological heterogeneity. Ultimately, our findings demonstrate the need for an applicable, standardised and specific definition for supramaximal resection so that prospective studies can determine prognostically significant clinical data to guide the surgical management of glioblastoma.