NMDA glutamate receptor antagonist MK-801 induces proteome changes in adult human brain slices which are partially counteracted by haloperidol and clozapine.

Deciphering the molecular pathways associated with N-methyl-D-aspartate receptor (NMDAr) hypofunction and its interaction with antipsychotics is necessary to advance our understanding of the basis of schizophrenia, as well as our capacity to treat this disease. In this regard, the development of human brain-derived models that are amenable to studying the neurobiology of schizophrenia may contribute to filling the gaps left by the widely employed animal models. Here, we assessed the proteomic changes induced by the NMDA glutamate receptor antagonist MK-801 on human brain slice cultures obtained from adult donors submitted to respective neurosurgery. Initially, we demonstrated that MK-801 diminishes NMDA glutamate receptor signaling in human brain slices in culture. Next, using mass-spectrometry-based proteomics and systems biology in silico analyses, we found that MK-801 led to alterations in proteins related to several pathways previously associated with schizophrenia pathophysiology, including ephrin, opioid, melatonin, sirtuin signaling, interleukin 8, endocannabinoid, and synaptic vesicle cycle. We also evaluated the impact of both typical and atypical antipsychotics on MK-801-induced proteome changes. Interestingly, the atypical antipsychotic clozapine showed a more significant capacity to counteract the protein alterations induced by NMDAr hypofunction than haloperidol. Finally, using our dataset, we identified potential modulators of the MK-801-induced proteome changes, which may be considered promising targets to treat NMDAr hypofunction in schizophrenia. This dataset is publicly available and may be helpful in further studies aimed at evaluating the effects of MK-801 and antipsychotics in the human brain.

Human brain dynamics dissociate early perceptual and late motor-related stages of affordance processing.

Affordances, the opportunities for action offered by the environment to an agent, are vital for meaningful behaviour and exist in every interaction with the environment. There is an ongoing debate in the field about whether the perception of affordances is an automated process. Some studies suggest that affordance perception is an automated process that is independent from the visual context and bodily interaction with the environment, whereas others argue that it is modulated by the visual and motor context in which affordances are perceived. The present paper aims to resolve this debate by examining affordance automaticity from the perspective of sensorimotor time windows. To investigate the impact of different forms of bodily interactions with an environment, that is, the movement context (physical vs. joystick movement), we replicated a previous study on affordance perception in which participants actively moved through differently wide doors in an immersive 3D virtual environment. In the present study, we displayed the same environment on a 2D screen with participants moving through doors of different widths using the keys on a standard keyboard. We compared components of the event-related potential (ERP) from the continuously recorded electroencephalogram (EEG) that were previously reported to be related to affordance perception of architectural transitions (passable and impassable doors). Comparing early sensory and later motor-related ERPs, our study replicated ERPs reflecting early affordance perception but found differences in later motor-related components. These results indicate a shift from automated perception of affordances during early sensorimotor time windows to movement context dependence of affordance perception at later stages, suggesting that affordance perception is a dynamic and flexible process that changes over sensorimotor stages.

Computed tomography versus ultrasound for the diagnosis of acute cholecystitis: a systematic review and meta-analysis.

OBJECTIVES: Some patients undergo both computed tomography (CT) and ultrasound (US) sequentially as part of the same evaluation for acute cholecystitis (AC). Our goal was to perform a systematic review and meta-analysis comparing the diagnostic performance of US and CT in the diagnosis of AC. MATERIALS AND METHODS: Databases were searched for relevant published studies through November 2023. The primary objective was to compare the head-to-head performance of US and CT using surgical intervention or clinical follow-up as the reference standard. For the secondary analysis, all individual US and CT studies were analyzed. The pooled sensitivities, specificities, and areas under the curve (AUCs) were determined along with 95% confidence intervals (CIs). The prevalence of imaging findings was also evaluated. RESULTS: Sixty-four studies met the inclusion criteria. In the primary analysis of head-to-head studies (n = 5), CT had a pooled sensitivity of 83.9% (95% CI, 78.4-88.2%) versus 79.0% (95% CI, 68.8-86.6%) of US (p = 0.44). The pooled specificity of CT was 94% (95% CI, 82.0-98.0%) versus 93.6% (95% CI, 79.4-98.2%) of US (p = 0.85). The concordance of positive or negative test between both modalities was 82.3% (95% CI, 72.1-89.4%). US and CT led to a positive change in management in only 4 to 8% of cases, respectively, when ordered sequentially after the other test. CONCLUSION: The diagnostic performance of CT is comparable to US for the diagnosis of acute cholecystitis, with a high rate of concordance between the two modalities. CLINICAL RELEVANCE STATEMENT: A subsequent US after a positive or negative CT for suspected acute cholecystitis may be unnecessary in most cases. KEY POINTS: When there is clinical suspicion of acute cholecystitis, patients will often undergo both CT and US. CT has similar sensitivity and specificity compared to US for the diagnosis of acute cholecystitis. The concordance rate between CT and US for the diagnosis of acute cholecystitis is 82.3%.

Effect of photobiomodulation with different wavelengths on periodontal repair in non-hyperglycemic and hyperglycemic rats.

BACKGROUND: Hyperglycemic conditions is associated with more severe periodontitis and poorer outcomes after nonsurgical periodontal treatment (NPT). Then, these patients are candidates for adjunctive therapy associated with NPT. This study evaluates the effect of photobiomodulation (PBMT) at different wavelengths on periodontal repair in non-hyperglycemic/hyperglycemic animals. MATERIALS AND METHODS: Sixty-four rats were submitted to induction of periodontitis by ligatures. Hyperglycemia was induced in half of these animals, whereas the other half remained non-hyperglycemic. The animals were subdivided into 4 groups according to the PBMT protocol applied at the time of ligature removal (n = 8): CTR: Without PBMT; IRL: PBMT with infrared laser (808 nm); RL: PBMT with red laser (660 nm); and RL-IRL: PBMT with red (660 nm) and infrared laser (808 nm). After a period of 7 days, the animals were euthanized. The parameters assessed by microtomography were the bone volume relative to total tissue volume (BV/TV%), distance from the cemento-enamel junction to the top of the bone crest (CEJ-CB), trabecular thickness, space between trabeculae, and number of trabeculae. Additionally, the percentage of inflammatory cells, blood vessels, and connective tissue matrix were assessed by histomorphometric analysis. RESULTS: PBMT reduced bone loss and increased trabecular density in hyperglycemic animals (p < .05), with RL being more effective in reducing linear bone loss (CEJ-CB), whereas RL-IRL was more effective in maintaining BV/TV%. PBMT reduced blood vessels and increased the connective tissue component in hyperglycemic animals (p < .05). RL-IRL reduced inflammatory cells regardless of the systemic condition of the animal (p < .05). CONCLUSION: PBMT (RL, RL-IRL) improves the repair of periodontal tissues in hyperglycemic animals.

Molecular overlaps of neurological manifestations of COVID-19 and schizophrenia from a proteomic perspective.

COVID-19, a complex multisystem disorder affecting the central nervous system, can also have psychiatric sequelae. In addition, clinical evidence indicates that a diagnosis of a schizophrenia spectrum disorder is a risk factor for mortality in patients with COVID-19. In this study, we aimed to explore brain-specific molecular aspects of COVID-19 by using a proteomic approach. We analyzed the brain proteome of fatal COVID-19 cases and compared it with differentially regulated proteins found in postmortem schizophrenia brains. The COVID-19 proteomic dataset revealed a strong enrichment of proteins expressed by glial and neuronal cells and processes related to diseases with a psychiatric and neurodegenerative component. Specifically, the COVID-19 brain proteome enriches processes that are hallmark features of schizophrenia. Furthermore, we identified shared and distinct molecular pathways affected in both conditions. We found that brain ageing processes are likely present in both COVID-19 and schizophrenia, albeit possibly driven by distinct processes. In addition, alterations in brain cell metabolism were observed, with schizophrenia primarily impacting amino acid metabolism and COVID-19 predominantly affecting carbohydrate metabolism. The enrichment of metabolic pathways associated with astrocytic components in both conditions suggests the involvement of this cell type in the pathogenesis. Both COVID-19 and schizophrenia influenced neurotransmitter systems, but with distinct impacts. Future studies exploring the underlying mechanisms linking brain ageing and metabolic dysregulation may provide valuable insights into the complex pathophysiology of these conditions and the increased vulnerability of schizophrenia patients to severe outcomes.

Ontogeny of daily rhythms in the expression of metabolic factors in Nile tilapia (Oreochromis niloticus) kept at two different temperature regimes: Thermocycle and constant temperature.

The daily variations of temperature are one of the main synchronizers of the circadian rhythms. In addition, water temperature influences the embryonic and larval development of fish and directly affects their metabolic processes. The application of thermocycles to fish larvae has been reported to improve growth and the maturation of the digestive system, but their effects on metabolism are poorly understood. The aim of the present study was to evaluate the effect of two different temperature regimes, cycling versus constant, on the daily rhythms of metabolic factors of Nile tilapia (Oreochromis niloticus) larvae. For this purpose, fertilized eggs were divided into two groups: one reared in a 31 °C:25 °C day:night thermocycle (TCY) and another group maintained in a constant 28 °C temperature (CTE). The photoperiod was set to a 12:12 h light/dark cycle. Samples were collected every 4 h during a 24-h cycle on days 4, 8 and 13 post fertilization (dpf). The expression levels of alanine aminotransferase (alt), aspartate aminotransferase (ast), malic enzyme, glucose-6-phosphate dehydrogenase (g6pd), phosphofructokinase (pfk) and pyruvate kinase (pk) were analyzed by qPCR. Results showed that, in 13 dpf animals, most of the genes analyzed (alt, ast, malic, g6pd and pfk) showed daily rhythms in TCY, but not in the group kept at constant temperature, with most acrophases detected during the feeding period. An increase in nutrient metabolism around feeding time can improve food utilization and thus increase larval performance. Therefore, the use of thermocycles is recommended for tilapia larviculture.

Assessing bone formation on hydrophilic and hydrophobic implant surfaces in a murine model treated with bisphosphonates.

OBJECTIVE: To evaluate the osseointegration of implants with hydrophobic (HFB) and hydrophilic (HFL) surfaces in a murine model of high-dose bisphosphonates (BPs). MATERIALS AND METHODS: Sixty-four rats were randomly allocated into four groups: control group with HFB implants (CG-HFB), control group with HFL implants (CG-HFL), BP group with HFB implants (BP-HFB), and BP group with HFL implants (BP-HFL). Animals were euthanized after 15 and 45 days (n=8). The dependent variables assessed were the removal torque (biomechanical analysis), the bone volume around the implants (%BV/TV) (microtomographic analysis), the bone-implant contact (%BIC), the bone between the threads (%BBT) (histomorphometric analysis), and the expression of bone metabolism markers (immunohistochemistry analysis). RESULTS: The CG-HFL and BP-HFL groups presented higher removal torque than the CG-HFB and BP-HFB implants. The %BIC of the CG-HFL surfaces was slightly higher than that of the CG-HFB implants. The BP-HFB and BP-HFL groups presented a higher %BIC than that of the CG-HFB and CG-HFL groups (p<0.001). BP therapy also increased the %BBT at both implant surfaces. Higher levels of ALP were observed in the matrix region of bone tissue on the HFL surfaces than on the HFB surfaces. CONCLUSION: Both surfaces enable osseointegration in rats under BP therapy. CLINICAL RELEVANCE: The study demonstrates that hydrophobic (HFB) and hydrophilic (HFL) implant surfaces can promote osseointegration in rats undergoing bisphosphonate therapy. The HFL surfaces exhibited improved biomechanical performance, higher bone-implant contact, and increased bone volume, suggesting their potential clinical relevance for implant success in individuals on bisphosphonate treatment.

Fresh-frozen allogeneic bone blocks grafts for alveolar ridge augmentation: Biological and clinical aspects.

The possibilities for oral bone regeneration procedures vary depending on the type of bone defect to be treated, which in turn dictate the type of graft to be used. Atrophic alveolar ridges are non-contained defects and pose a challenging defect morphology for bone regeneration/augmentation. Successful results are regularly obtained with the use of particulate grafts in combination with barrier membranes. In cases of very narrow ridges with need of larger amount of bone augmentation, block grafts are often used. Fresh-frozen allogeneic bone block grafts have been proposed as an alternative to autogenous (AT) bone blocks. Based on a systematic appraisal of pre-clinical in vivo studies and clinical trials including a direct comparison of fresh-frozen bone (FFB) blocks versus AT bone blocks it can be concluded that a FFB block graft: (a) cannot be considered as a reliable replacement of a AT bone block, and (b) should only be considered in cases where the amount of necessary augmentation-in a lateral direction-is relatively limited, so that the main portion of the body of the implant lies within the inner (i.e., the vital) aspect of the block.

Rewilding psychology.

Some commentators have recently argued that scientific psychology is overly reliant on artificial laboratory-based activities and that it undervalues field-based investigations. However, it remains unclear how a field-based programme of psychological research might be organized in a scalable way. We examine and compare two existing field-based approaches: Roger Barker's behaviour settings programme and Edwin Hutchins's distributed cognition programme. Both programmes prioritize observational work, and both reject the individual as the unit of analysis in favour of a community-scale unit. However, whereas the behaviour settings programme is concerned with structural properties of community life, distributed cognition is concerned more narrowly with the functional analysis of expert team performance. We discuss how these programmes can inform a future community-scale approach to studying psychology in the wild. We conclude that the two programmes are proof of concept of the possibility of a scientific psychology that rejects methodological individualism. This article is part of the theme issue 'People, places, things and communities: expanding behaviour settings theory in the twenty-first century'.

Depicting the molecular features of suicidal behavior: a review from an "omics" perspective.

Background Suicide is one of the leading global causes of death. Behavior patterns from suicide ideation to completion are complex, involving multiple risk factors. Advances in technologies and large-scale bioinformatic tools are changing how we approach biomedical problems. The "omics" field may provide new knowledge about suicidal behavior to improve identification of relevant biological pathways associated with suicidal behavior. Methods We reviewed transcriptomic, proteomic, and metabolomic studies conducted in blood and post-mortem brains from individuals who experienced suicide or suicidal behavior. Omics data were combined using systems biology in silico, aiming at identifying major biological mechanisms and key molecules associated with suicide. Results Post-mortem samples of suicide completers indicate major dysregulations in pathways associated with glial cells (astrocytes and microglia), neurotransmission (GABAergic and glutamatergic systems), neuroplasticity and cell survivor, immune responses and energy homeostasis. In the periphery, studies found alterations in molecules involved in immune responses, polyamines, lipid transport, energy homeostasis, and amino and nucleic acid metabolism. Limitations We included only exploratory, non-hypothesis-driven studies; most studies only included one brain region and whole tissue analysis, and focused on suicide completers who were white males with almost none confounding factors. Conclusions We can highlight the importance of synaptic function, especially the balance between the inhibitory and excitatory synapses, and mechanisms associated with neuroplasticity, common pathways associated with psychiatric disorders. However, some of the pathways highlighted in this review, such as transcriptional factors associated with RNA splicing, formation of cortical connections, and gliogenesis, point to mechanisms that still need to be explored.

OmicScope unravels systems-level insights from quantitative proteomics data.

Shotgun proteomics analysis presents multifaceted challenges, demanding diverse tool integration for insights. Addressing this complexity, OmicScope emerges as an innovative solution for quantitative proteomics data analysis. Engineered to handle various data formats, it performs data pre-processing - including joining replicates, normalization, data imputation - and conducts differential proteomics analysis for both static and longitudinal experimental designs. Empowered by Enrichr with over 224 databases, OmicScope performs Over Representation Analysis (ORA) and Gene Set Enrichment Analysis (GSEA). Additionally, its Nebula module facilitates meta-analysis from independent datasets, providing a systems biology approach for enriched insights. Complete with a data visualization toolkit and accessible as Python package and a web application, OmicScope democratizes proteomics analysis, offering an efficient and high-quality pipeline for researchers.

Periodontal host-modulation therapy with avocado/soybean unsaponifiables in rats with arthritis.

BACKGROUND: The aim of this study was to evaluate the effect of the avocado/soybean unsaponifiables (ASU) in the treatment of induced periodontitis in rats with experimental arthritis. METHODS: Sixty rats were randomly assigned to 4 groups according to the type of treatment and the systemic condition of the animals: CTR-S: healthy animals in which saline solution (SS) was administered; ASU-S: healthy animals in which ASU (0.6 mg/kg) was administered; AR/ASU-S: animals with induced arthritis in which ASU was administered; AR-S: animals with induced arthritis in which SS was administered. Periodontitis was induced by ligatures, maintained for 15 days. Subsequently, the treatment was performed by scaling with hand instruments. The SS and ASU were administered daily by gavage until euthanasia of the animals that occurred at 7, 15 or 30 days after the scaling procedure (N.=5 animals/group). Bone resorption, inflammatory infiltrate composition, and osteoclastogenesis were assessed. RESULTS: The AR-S group had greater bone loss, smaller amounts of fibroblasts and larger amounts of inflammatory cells than all other groups. In addition, the AR-S group had greater osteoclastogenesis in relation to the healthy animal groups. CONCLUSIONS: The use of ASU improved the healing pattern after treatment for experimental periodontitis in animals with arthritis reducing the periodontal bone loss.

Supraphysiologic Testosterone Administration Impairs Late Osseointegration in Male Rats.

PURPOSE: To evaluate the effect of supraphysiologic administration of testosterone in an early and late model of implant osseointegration in rat tibiae. MATERIALS AND METHODS: A total of 40 rats were randomly allocated into four groups (n = 10/ group), which were divided according to the type of experiment and time of osseointegration: (1) vehicle (14 days), (2) testosterone (14 days), (3) vehicle (42 days), and (4) testosterone (42 days). Testosterone cypionate (7.5 mg/kg) administration started 4 weeks before implant placement, and the injections were performed daily until euthanasia. Machined-surface titanium implants (2.2 mm in diameter and 4 mm high) were placed bilaterally in the tibia of animals 28 days after the first testosterone injection. At days 14 and 42 after implant placement, euthanasia was performed and the tibiae were harvested to perform biomechanical evaluation and histomorphometric analysis of bone-to-implant contact (BIC%) and bone between the threads (BBT%). RESULTS: There was no statistical difference in the removal torque of the implants between the groups treated with the vehicle (control group) or testosterone (P > .05). At 14 days of osseointegration, the BIC% and BBT% did not differ between vehicle or testosterone groups (P > .05), while at 42 days, both the BIC% and BBT% were significantly reduced by testosterone compared to the vehicle group (P < .05). CONCLUSIONS: Testosterone cypionate in supraphysiologic dose impaired late-phase osseointegration in rat tibiae.

Chronic Chest Computed Tomography Findings Following COVID-19 Pneumonia.

Respiratory symptoms are a frequent manifestation of patients with post-acute sequela of SARS-CoV-2 (PASC), also known as long-COVID. Many cohorts of predominantly hospitalized patients have shown that a significant subset may have persistent chest computed tomography findings for more than 12 months after the acute infection. Proper understanding of the evolving long-term imaging findings and terminology is crucial for accurate imaging interpretation and patient care. The goal of this article is to review the chronic chest computed tomography findings of patients with PASC and common pitfalls.

Comparison of different dual-wavelength photobiomodulation protocols application in third molar extractions. A split-mouth randomized controlled trial.

OBJECTIVE: To compare the use of PBMT in the soft tissue and bone healing after third molar extraction using the dual-wavelength laser directly into the post-extraction alveoli (PBMT-I), or PBMT with a red laser directly into the alveoli and with an infrared laser externally on the patient's face (PBMT-IE). METHODS: Twenty patients underwent extraction of four third molars were involved in this split-mouth double-blind randomized controlled trial. The Post-extraction alveoli were treated with the following protocols: PBMT-IE: Application of a red laser directly into the alveolus, and infrared laser irradiation transcutaneously and PBMT-I: Application of dual-wavelength laser intraorally. Patients were clinically evaluated 3, 7, 14, 30, and 90 days after the surgical procedure. The analyses in this study were divided into qualitative (centered on the patient's report and on the evaluators' analysis), and quantitative analyses (measurement of the vertical and horizontal dimensions of the face with the objective of measuring post-surgical edema and radiographic analyses for evaluation of the density and structure of the newly formed bone). RESULTS: A progressive improvement was observed in all parameters evaluated in this study, however, this improvement was time dependent, with no distinct effect observed between the PBMT treatments applied. CONCLUSION: The different dual-wavelength PBMT protocols induced a similar postoperative clinical course in third molar extraction surgeries, with a reduced occurrence of complications and a good healing pattern of hard and soft tissues.

Efficacy of analgesia promoted by lidocaine and articaine in third molar extraction surgery. A split-mouth, randomized, controlled trial.

PURPOSE: The aim of this study was to compare the analgesic efficacy of 4% articaine associated with epinephrine (1:100,000), and 2% lidocaine associated with epinephrine (1:100,000) in third molar extraction surgery. METHODS: Sixty patients who underwent surgeries to extract upper and lower third molars were included in this split-mouth, double-blind, randomized, controlled trial. The groups in this study were divided according to the anesthetic solution used to provide local anesthesia during extraction of upper and lower third molars: (1) 4% articaine associated with epinephrine (1:100,000); (2) 2% lidocaine associated with epinephrine (1:100,000). The time to the beginning and end of the sensation of analgesia, pain sensation according to the VAS scale, and number of anesthetic tubes necessary for supplementation were analyzed. RESULTS: It was found that the onset time for analgesia was shorter on the side anesthetized with articaine compared to the side anesthetized with lidocaine (122.1 ± 52.90 s vs. 144.5 ± 68.85 s) (p < 0.05). In addition, the number of tubes used for anesthetic supplementation was also reduced on the articaine side compared to the lidocaine side (0.26 ± 0.48 vs. 0.50 ± 0.75) (p < 0.05). There were no differences between the anesthetic solutions in the other evaluated parameters. CONCLUSION: It can be concluded that the use of 4% articaine associated with epinephrine (1:100,000) reduced the time of onset of analgesia and the necessity for anesthetic supplementation in third molar extraction surgeries compared to the use of 2% lidocaine associated with epinephrine (1:100,000).

Survival analysis of dental implants placed in horizontally severely resorbed maxillae after reconstruction with xenogeneic graft: a case series.

PURPOSE: To evaluate the survival rates of dental implants with a hybrid macrostructure and the surface biomimetically coated with nanohydroxyapatite, placed in horizontally atrophic maxillae previously submitted to the guided bone regeneration (GBR) procedure, associated with the use of a deproteinized bovine bone graft (DBB). METHODS: Twenty-five patients who received 196 implants were involved in this study. First, these patients were submitted to GBR procedures and maxillary sinus lift, where DBB was used as the grafting material. The dental implants were placed after a minimum period of 6 months of the grafting procedures. The patients were followed up every six months and clinical/radiographic examinations were performed to assess the implants, using the following indicators as a reference: (1) Absence of mobility; (2) Absence of pain. Data about the age, surgery time, smoking status, implant size, and time between the grafting procedure and implant placement were correlated with implant failures. RESULTS: Twelve implants failed, generating a survival rate of 94.23%. None of the variables analysed correlated with the implant failures. CONCLUSION: Implants with a hybrid macrostructure and surface biomimetically coated with nanohydroxyapatite present good survival rates in horizontally atrophic maxillae grafted with DBB.

Green tea and hyaluronic acid gel enhance fibroblast activation and improves the gingival healing post-third molar extraction.

This study evaluates the effects of a green tea (Camellia sinensis) and hyaluronic acid gel on fibroblast activity and alveolar bone repair following third molar extractions. By examining the gene expression related to cell survival, proliferation, and angiogenesis, the study bridges in vitro findings with clinical outcomes in a split-mouth randomized trial. Human fibroblasts were exposed to the treatment gel, analysing gene expression through RT-qPCR. Twenty participants undergoing bilateral third molar extractions received the test gel on one side and a placebo on the other. Assessments included patient-reported outcomes, professional evaluations, and radiographic analyses at multiple postoperative intervals. The test gel significantly enhanced AKT, CDKs, and VEGF gene expressions, indicating a positive effect on angiogenesis and cell proliferation. Clinically, it resulted in reduced exudate, swelling, and secondary interventions, with radiographs showing improved alveolar bone density after 90 days. The green tea and hyaluronic acid gel significantly improves soft tissue and bone healing post-extraction, offering a promising adjunctive therapy for enhancing postoperative recovery. This gel represents a novel adjuvant treatment option for facilitating improved healing outcomes after third molar extractions, highlighting its potential utility in clinical dental practice.

Radiofrequency ablation for ampullary neoplasia with intraductal extension after endoscopic papillectomy: Systematic review and meta-analysis.

Background and study aims Noninvasive ampullary neoplasms may be removed by surgery or endoscopy. However, given the morbidity and mortality associated with surgery, endoscopic papillectomy (EP) is the preferred approach. Radiofrequency ablation (RFA) after EP has emerged as a promising alternative therapy to avoid surgery after incomplete EP. Our goal was to evaluate the efficacy and safety of RFA for residual or recurrent lesions with intraductal extension after endoscopic papillectomy. Patients and methods The inclusion criteria include clinical trials, cohort studies, and case series evaluating patients with residual or recurrent lesions with intraductal extension after EP treated with RFA. Case reports, duplicated data, and studies with follow-up periods < 10 months were excluded. The metanalysis evaluated adverse events, surgical conversion rate, clinical success and recurrence. Results Seven studies were selected, totaling 124 patients. RFA was associated with a clinical success rate of 75.7% (95% confidence interval [CI] 65.0-88.0%; I 2 = 23.484) in a mean follow-up period < 10 months. However, the biliary stricture rate was 22.2% (95% CI 12.1-28.4%; I 2 = 61.030), 14.3% of pancreatitis (95% CI 8.8-22.3%; I 2 < 0.001), 7.0% of cholangitis (95% CI 3.3-14.5%; I 2 < 0.001), 4.0% of bleeding (95% CI 1.7-9.3%; I 2 < 0.001), and recurrence of 24.3% (95% CI 16.0-35.0%; I 2 = 23.484). Conclusions RFA is feasible and appears to be effective for managing residual or recurrent lesions with intraductal extension after EP. However, long-term follow-up and high-quality studies are required to confirm our findings.