Retreatment with HBV siRNA Results in Additional Reduction in HBV Antigenemia and Immune Stimulation in the AAV-HBV Mouse Model.

BACKGROUND AND AIMS: Treatment with siRNAs that target HBV has demonstrated robust declines in HBV antigens. This effect is also observed in the AAV-HBV mouse model, which was used to investigate if two cycles of GalNAc-HBV-siRNA treatment could induce deeper declines in HBsAg levels or prevent rebound, and to provide insights into the liver immune microenvironment. METHODS: C57Bl/6 mice were transduced with one of two different titers of AAV-HBV for 28 days, resulting in stable levels of HBsAg of about 103 or 105 IU/mL. Mice were treated for 12 weeks (four doses q3wk) per cycle with 3 mg/kg of siRNA-targeting HBV or an irrelevant sequence either once (single treatment) or twice (retreatment) with an 8-week treatment pause in between. Blood was collected to evaluate viral parameters. Nine weeks after the last treatment, liver samples were collected to perform phenotyping, bulk RNA-sequencing, and immunohistochemistry. RESULTS: Independent of HBsAg baseline levels, treatment with HBV-siRNA induced a rapid decline in HBsAg levels, which then plateaued before gradually rebounding 12 weeks after treatment stopped. A second cycle of HBV-siRNA treatment induced a further decline in HBsAg levels in serum and the liver, reaching undetectable levels and preventing rebound when baseline levels were 103 IU/mL. This was accompanied with a significant increase in inflammatory macrophages in the liver and significant upregulation of regulatory T-cells and T-cells expressing immune checkpoint receptors. CONCLUSIONS: Retreatment induced an additional decline in HBsAg levels, reaching undetectable levels when baseline HBsAg levels were 3log10 or less. This correlated with T-cell activation and upregulation of Trem2.

[Clear aligner in orthodontic retreatment].

Improper diagnosis and design, misusing orthodontic technique, relapse after orthodontic treatment, and poor patient compliance may lead to treatment failure, requiring orthodontic retreatment. While in such cases, patients usually have already had their teeth extracted, or are with periodontal, joint, and other dental problems, which often require multidisciplinary treatment. The retreatment of orthodontic patients is difficult, and the treatment options are limited. The characteristics of clear aligner treatment, such as comfortable and beautiful appearance, high degree of digital precision, and personalized tooth arrangement to simulate the final outcome, make it popular in the orthodontic retreatment. This article discusses and summarizes the details of orthodontic design, case monitoring, and the application of clear aligner in orthodontic retreatment of failed cases. Before starting treatment, the difficulty assessment tool (clear aligner treatment complexity assessment tool) can be used to evaluate the difficulty of clear aligner treatment. Orthodontists are recommended to treat orthodontic patients with clear aligners within their ability to avoid treatment failure. The key to the success of the extraction case treatment with clear aligner is to make the correct diagnosis and select the right cases. In the treatment planning, attention should be paid to the restoration of anterior tooth torque, making good use of molar distalization to obtain the space, vertical control, and improving posterior tooth relationship. Proper selection of cases and reasonable design in clear aligner treatment are expected to obtain tooth alignment, good intercuspation, normal overbite and overjet, periodontal health, parallel roots, and to achieve the goal of aesthetic, functional, stable, and healthy orthodontic treatment.

Long-term functional outcomes and surgical retreatment after thulium laser enucleation of the prostate: A 10-year follow-up study.

BACKGROUND: To evaluate the 10-year functional outcomes (primary) and frequency and predictors of BPH surgical retreatment (secondary) after ThuLEP. MATERIALS AND METHODS: A single-center retrospective analysis of consecutive patients undergoing ThuLEP between 2010 and 2013 was performed. Inclusion criteria were: age ≥ 40 years, prostate volume (PV) ≥ 80 mL, International Prostate Symptom Score (IPSS)-Total score ≥ 8 points. IPSS-Total score was the primary outcome, and BPH surgical retreatment rate was the secondary outcome. Paired t-test, McNemar test, and Wilcoxon signed-rank test were used to compare variables. Logistic regression analysis was performed to evaluate predictors of surgical retreatment. RESULTS: A total of 410 patients with a mean ±SD age of 63.9 ± 9.7 years and a PV of 115.6 ± 28.6 mL were included. Mean ±SD follow-up was 108.2 ± 29.6 months. IPSS-Total score was significantly improved at 1 year compared to baseline (23.3 ± 4.7 vs. 10.3 ± 3.8; p<0.001). It was similar after 5 years (10.5 ± 3.6 vs. 10.7 ± 5.0; p=0.161), with a significant worsening at 10 years (10.3 ±4.8 vs. 13.8 ±4.5; p=0.042) but remaining statistically and clinically better than baseline (13.8 ±4.5 vs. 22.1 ±4.3; p<0.001). After 10 years, 21 (5.9%) patients had undergone BPH reoperation. Baseline PV (adjusted OR 1.27, 95% CI 1.09-1.41; p<0.001) and time from BPH surgery (adjusted OR 1.32, 95% CI 1.15-1.43; p<0.001) were predictors of BPH surgical retreatment. CONCLUSIONS: ThuLEP is associated with optimal functional outcomes and a low frequency of BPH surgical retreatment in the long-term. Baseline PV and time from surgery were predictors of BPH reoperation.

Managing Endodontic Complications: The Pathophysiology and Treatment of Flare-ups.

At its core, endodontics is a specialty centered on saving patients' teeth. Nonsurgical root canal therapy and nonsurgical retreatment, arguably the "bread and butter" of endodontics, not only facilitate the preservation of the natural dentition, but in many cases, alleviate pain. Most patients arrive for endodontic treatment expecting symptom relief. A small percentage of these patients, however, experience just the opposite. Within 48 to 72 hours, these select patients experience worsening symptoms, including swelling and pain, and may wonder what mishaps may have occurred during their treatment. These symptom exacerbations are referred to as endodontic flare-ups and are well-documented in the literature. In most cases their occurrence does not reflect a lack of practitioner judgment or skill, but rather a biologic event resulting from a shift in the delicate balance of the bacterial communities and inflammatory events at the periapex. This article reviews the pathophysiology and treatment of endodontic flare-ups, thereby informing patient communication strategies surrounding these events, to preserve both the teeth in question as well as patient relationships.

Expert consensus on difficulty assessment of endodontic therapy.

Endodontic diseases are a kind of chronic infectious oral disease. Common endodontic treatment concepts are based on the removal of inflamed or necrotic pulp tissue and the replacement by gutta-percha. However, it is very essential for endodontic treatment to debride the root canal system and prevent the root canal system from bacterial reinfection after root canal therapy (RCT). Recent research, encompassing bacterial etiology and advanced imaging techniques, contributes to our understanding of the root canal system's anatomy intricacies and the technique sensitivity of RCT. Success in RCT hinges on factors like patients, infection severity, root canal anatomy, and treatment techniques. Therefore, improving disease management is a key issue to combat endodontic diseases and cure periapical lesions. The clinical difficulty assessment system of RCT is established based on patient conditions, tooth conditions, root canal configuration, and root canal needing retreatment, and emphasizes pre-treatment risk assessment for optimal outcomes. The findings suggest that the presence of risk factors may correlate with the challenge of achieving the high standard required for RCT. These insights contribute not only to improve education but also aid practitioners in treatment planning and referral decision-making within the field of endodontics.

Comparing reactivation and retreatment for three doses of bevacizumab in type 1 retinopathy of prematurity.

PURPOSE: To determine timing and rates of reactivation and retreatment of type 1 retinopathy of prematurity (ROP) after treatment with either 0.125 mg, 0.250 mg, or 0.500 mg of intravitreal bevacizumab (IVB). METHODS: Retrospective data, including demographic information, past medical history, and ROP characteristics were analyzed for babies with type 1 ROP treated with IVB at Riley Hospital for Children for the perioed 2014-2021. RESULTS: A total of 84 patients met inclusion criteria: 29 patients received 0.125 mg of IVB; 39, 0.250 mg; and 16, 0.500 mg. Of the 84, 67 (80%) had additional laser treatment because of late reactivation (n = 52) or persistent avascular retina (PAR) (n = 15). Subsequent laser treatment was more common with lower doses: 0.125 mg (n = 27 [93%]); 0.250 mg (n = 31 [80%]); 0.500 mg (n = 9 [57%]) (P = 0.012). There was no difference between groups with regard to reason for subsequent laser treatment (reactivation vs PAR). The 0.125 mg group required retreatment because of reactivation 3.8 weeks sooner than the other dosing groups (P = 0.047). CONCLUSIONS: The outcomes comparing three doses of IVB for severe ROP showed a difference in the timing of secondary treatment, with the lower dosing group requiring laser for reactivation earlier.

Retreatment of symptomatic chronic bronchitis with bronchial rheoplasty.

A man in his early 70s with a long-standing history of chronic bronchitis presented to our department 3 years ago with debilitating chronic cough and excessive sputum production. He had no previous diagnosis of chronic obstructive pulmonary disease and without evidence of severe respiratory tract infections. Due to his symptom burden and impairments in daily activities, the patient was considered to be an appropriate candidate for bronchial rheoplasty, a novel endoscopic treatment for patients with chronic bronchitis. The patient responded well to bilateral treatment but then experienced symptom recurrence roughly 14 months after completing the initial treatment. In the absence of an alternative explanation for the return of these symptoms, he then underwent uneventful retreatment. The patient, again, reported significant symptom improvement and no adverse effects since retreatment. While further studies are necessary to assess the safety and efficacy of retreatment, the findings from this case are encouraging.

Balloon dilation for the treatment of male urethral strictures: a systematic review and meta-analysis.

OBJECTIVE: The use of minimally invasive endoluminal treatment for urethral strictures has been a subject for debate for several decades. The aim of this study was to review and discuss the safety, efficacy and factors influencing the clinical application of balloon dilation for the treatment of male urethral strictures. DESIGN: Systematic review and meta-analysis. DATA SOURCES: Embase, Medline, Web of Science, Cochrane Library and Scopus were searched for publications published before 17 July 2022. STUDY SELECTION: Two independent researchers screened and assessed the results, and all clinical studies on balloon dilation for the treatment of urethral strictures in men were included. DATA EXTRACTION AND SYNTHESIS: The success rate, rate of adverse events, International Prostate Symptom Scores, maximum uroflow (Qmax) and postvoid residual urine volume were the main outcomes. Stata V.14.0 was used for statistical analysis. RESULTS: Fifteen studies with 715 patients were ultimately included in this systematic review. The pooled results of eight studies showed that the reported success rate of simple balloon dilation for male urethral strictures was 67.07% (95% confidence interval [CI]: 55.92% to 77.36%). The maximum urinary flow rate at 3 months (risk ratio [RR]= 2.6510, 95% CI: 1.0681 to 4.2338, p<0.01) and the maximum urinary flow rate at 1 year (RR= 1.6637, 95% CI: 1.1837 to 2.1437, p<0.05) were significantly different after dilation. There is insufficient evidence to suggest that balloon dilation is superior to optical internal urethrotomy or direct visual internal urethrotomy (DVIU) (RR= 1.4754, 95% CI: 0.7306 to 2.9793, p=0.278). CONCLUSION: Balloon dilation may be an intermediate step before urethroplasty and is a promising alternative therapy to simple dilation and DVIU. The balloon is a promising drug delivery tool, and paclitaxel drug-coated balloon dilation is effective in reducing retreatment rates in patients with recurrent anterior urethral strictures. The aetiology, location, length, previous treatment of urethral stricture may be associated with the efficacy of balloon dilation. PROSPERO REGISTRATION NUMBER: CRD42022334403.

Elevated risk of recurrence and retreatment for silent pituitary adenomas.

PURPOSE: Pituitary adenomas are the most common tumor of the pituitary gland and comprise nearly 15% of all intracranial masses. These tumors are stratified into functional or silent categories based on their pattern of hormone expression and secretion. Preliminary evidence supports differential clinical outcomes between some functional pituitary adenoma (FPA) subtypes and silent pituitary adenoma (SPA) subtypes. METHODS: We collected and analyzed the medical records of all patients undergoing resection of SPAs or FPAs from a single high-volume neurosurgeon between 2007 and 2018 at Brigham and Women's Hospital. Descriptive statistics and the Mantel-Cox log-rank test were used to identify differences in outcomes between these cohorts, and multivariate logistic regression was used to identify predictors of radiographic recurrence for SPAs. RESULTS: Our cohort included 88 SPAs and 200 FPAs. The majority of patients in both cohorts were female (48.9% of SPAs and 63.5% of FPAs). SPAs were larger in median diameter than FPAs (2.1 cm vs. 1.2 cm, p < 0.001). The most frequent subtypes of SPA were gonadotrophs (55.7%) and corticotrophs (30.7%). Gross total resection (GTR) was achieved in 70.1% of SPA resections and 86.0% of FPA resections (p < 0.001). SPAs had a higher likelihood of recurring (hazard ratio [HR] 3.2, 95% confidence interval [95%CI] 1.6-7.2) and a higher likelihood of requiring retreatment for recurrence (HR 2.5; 95%CI 1.0-6.1). Subset analyses revealed that recurrence and retreatment were more both likely for subtotally resected SPAs than subtotally resected FPAs, but this pattern was not observed in SPAs and FPAs after GTR. Among SPAs, recurrence was associated with STR (odds ratio [OR] 9.3; 95%CI 1.4-64.0) and younger age (OR 0.92 per year; 95%CI 0.88-0.98) in multivariable analysis. Of SPAs that recurred, 12 of 19 (63.2%) were retreated with repeat surgery (n = 11) or radiosurgery (n = 1), while the remainder were observed (n = 7).There were similar rates of recurrence across different SPA subtypes. CONCLUSION: Patients undergoing resection of SPAs should be closely monitored for disease recurrence through more frequent clinical follow-up and diagnostic imaging than other adenomas, particularly among patients with STR and younger patients. Several patients can be observed after radiographic recurrence, and the decision to retreat should be individualized. Longitudinal clinical follow-up of SPAs, including an assessment of symptoms, endocrine function, and imaging remains critical.

Enhanced durability and evolution of retreatment criteria of intravitreal antivascular endothelial growth factor agents for diabetic macular edema.

PURPOSE OF REVIEW: The increasing prevalence of diabetic macular edema (DME) necessitates an updated review of treatment modalities. While the shift from laser to anti-vascular endothelial growth factor (anti-VEGF) therapy has transformed patient outcomes, benefits of these agents are not fully realized in real-world implementation relative to the setting of controlled clinical trials. This review outlines the evolution of intravitreal anti-VEGF treatment extension protocols for DME that reflect efforts to address treatment adherence challenges while optimizing visual outcomes. RECENT FINDINGS: Recent studies highlight the efficacy of extended-interval dosing with anti-VEGF agents in managing DME. Trials such as RISE/RIDE, VISTA/VIVID, and LUCIDATE have established the foundation of these regimens by demonstrating sustained visual gains with continuous treatment. However, newer trials including PROTOCOL T, KESTREL/KITE, YOSEMITE/RHINE, and PHOTON have furthered this concept, revealing that less frequent dosing of various anti-VEGF agents can maintain similar visual acuity and anatomical outcomes to traditional monthly injections. SUMMARY: The reviewed findings suggest a paradigm shift in DME treatment toward less frequent anti-VEGF injections. This has significant implications for clinical practice, potentially leading to greater adherence to treatment regimens and sustained visual function in patients, while minimizing treatment burden and healthcare costs. Further investigation into the long-term effects of extended dosing intervals is required.

Exploration of genetic characterization in hyperprogressive disease after immunotherapy retreatment in a patient with LCNEC: A case report.

Immune checkpoint inhibitors (ICIs) have emerged as a promising therapeutic option for large cell neuroendocrine carcinoma (LCNEC). However, various studies have suggested a potential risk of hyperprogressive disease (HPD) in patients receiving ICI, which might be associated with gene alterations. Here, this is the first report on an unknown primary LCNEC patient who had achieved a long-term response from ICI treatment (atezolizumab), but developed HPD after tumor progression due to receiving another ICI agent (serplulimab). The mutation region of FAT4, SMARCA4, CYLD, CTNNB1, and KIT was altered prior to serplulimab treatment compared to before atezolizumab treatment. This case suggested a potential association between these mutated genes and HPD. Patients with the aforementioned genes should caution when selecting ICI treatment. These findings required further confirmation in a larger study cohort.

The Effect of Different Obturation Techniques Using Different Root Canal Sealers on the Residual Filling Material After Retreatment Procedures.

BACKGROUND: This study aimed to compare the effect of different obturation techniques with root canal sealers on the residual filling material after retreatment using SEM. MATERIAL AND METHOD: Sixty (60) single rooted mandibular premolars were selected and instrumented with rotary files using the Mtwo system up to file size 30/.05 taper. The samples were randomly divided to two groups based on the type of sealer and three sub-groups (n=10) based on the obturating technique used. The root fillings were removed using the PTUR system files and the specimens were longitudinally sectioned while digital images were obtained from the root canals with SEM. The time required to reach working lenght were recorded. RESULTS: There was no difference in terms of the smear score when comparing both sealer and obturation technique groups in the apical third. Smear scores were significantly affected by the type of sealer and obturation technique in the medium and coronal thirds of root canals (p<0.05). Higher smear scores were obtained with GFB than AH Plus (p<0.05). The time required to reach working length with GFB was longer than AH Plus (p<0.05). CONCLUSION: Residual filling material was observed in all samples, regardless of the root canal sealer or the obturation technique used. There was a significantly lower smear scores in the AH Plus groups as compared to the GFB.

Reprint of: The Effect of Mineral Trioxide Aggregate Obturation Levels on the Outcome of Endodontic Retreatment: An Observational Study.

INTRODUCTION: No clinical studies have examined the effect of mineral trioxide aggregate (MTA) obturation levels on the outcome of endodontic retreatment. This retrospective study examined treatment outcomes in three cohorts that compared overfilling, flush filling, and underfilling after orthograde retreatment using MTA. METHODS: Two hundred fifty patients with 264 teeth diagnosed with previously treated root canals and apical periodontitis retreated in a private endodontic practice were included. All teeth received MTA obturation and the extent of the final filling level was measured in relation to the major apical foramen. After 6-month follow-ups, all nonhealing cases were treated surgically. After 24- to 72-month reviews, the effect of preoperative lesion size and the degree of MTA obturation level were assessed. Multiple linear regression and time-to-event analysis using Stata 17 software (StataCorp LLC, College Station, TX) were used to evaluate the data. RESULTS: Within the three cohorts, 99 out of 108 overfilled teeth (91.7%), 90 out of 103 flush fills (87.4%), and 10 out of 53 underfilled teeth (18.9%) healed and were successfully retreated without surgery at 48-months. When surgical outcomes were included, the combined healed proportion was 93.2%. Preoperative lesion size was found to be an important predictor for retreatment nonhealing. A 1-mm increase in lesion size at baseline resulted in an estimated 11% (95% CI 1.04, 1.18)-38% (95% CI 1.22, 1.58) increase in the risk of surgery. Compared to overfilling and flush filling, underfilling was associated with an approximately three-fold increase in requiring surgery and characterized by delayed healing. CONCLUSION: MTA obturation is a viable retreatment option for teeth with nonhealing endodontic treatment. MTA overfills or flush fillings do not adversely affect healing outcomes. However, MTA underfilling increases the chances for nonhealing and surgical intervention.

Radiographic outcome of endodontic treatment and retreatment of teeth with apical periodontitis using two different root canal irrigants. A prospective cohort study.

AIM: The aim of this prospective cohort study was to compare the radiographic outcome of endodontic treatment and retreatment of teeth with apical periodontitis using either 1% sodium hypochlorite (NaOCl) or 2% chlorhexidine digluconate (CHX) for root canal irrigation. MATERIALS AND METHODS: In the years from 2013 to 2015 standard irrigation varied by semester between NaOCl and CHX at the Department of Endodontics at the Faculty of Dentistry. During that time, 912 teeth received treatment for apical periodontitis in 744 patients, of whom 532 responded to the request for a 1-year follow-up. Only one tooth per person (the most distally located) were included; 285 teeth treated with NaOCl and 247 with CHX. One hundred cases were then randomly sampled from each irrigation group and analysed for outcome by periapical index (PAI) scoring using criteria for success, uncertain and failure. Clinical and other radiographic parameters were scored or recorded and analysed for associations with radiographic outcome using chi-square, ANOVA and regression analyses. RESULTS: Success rates (PAI score 1 or 2 at control) were nearly identical for the two irrigation liquids. The use of irrigating solution also did not significantly influence the outcome in chi-square analyses of subgroups of teeth or regression analyses with other variables included. Ordinal regression analysis established that preoperative lesion size or preoperative PAI score were significantly associated with outcome, and teeth in the mandible had significantly better outcomes than in the maxilla. CONCLUSIONS: No significant differences in the radiographic outcome using either 1% NaOCl or 2% CHX as irrigants were found. The outcome was better for teeth with small lesions or lower PAI scores at completion of treatment and for mandibular teeth.

Neurosurgical clipping versus endovascular coiling for patients with ruptured anterior circulation aneurysms: A systematic review and meta-analysis.

To compare the safety and efficacy of clipping and coiling in patients with ruptured anterior circulation aneurysms. A systematic search of four databases (PubMed, Web of Science, Cochrane Library, and Embase) was conducted to identify comparative articles on endovascular coiling and surgical clipping in patients with ruptured anterior circulation aneurysms. Meta-analyses were conducted using random-effects models. Nineteen studies, including 1983 patients, were included. The meta-analysis showed that neurosurgical clipping was associated with a lower incidence of retreatment (OR:0.28, 95% CI (0.11, 0.70), P = 0.006) than endovascular coiling, which seemed to be a result of incomplete occlusion (OR:0.22, 95% CI (0.11, 0.45), P < 0.001). Neurosurgical clipping was associated with lower mortality (OR:0.45, 95% CI (0.25, 0.82), P = 0.009) at short-term follow-up than endovascular coiling. However, neurosurgical clipping showed a higher incidence of ischemic infarction (OR:2.28, 95% CI (1.44, 3.63), P < 0.001) and a longer length of stay (LOS) (WMD:6.12, 95% CI (4.19, 8.04), P < 0.001) after surgery than endovascular coiling. Furthermore, the pooled results showed no statistically significant differences between the two groups regarding poor outcome, long-term mortality, rebleeding, vasospasm, and hydrocephalus. Evidence from this systematic review illustrates that neurosurgical clipping may be superior to endovascular coiling for ruptured anterior circulation aneurysms. Large-scale RCTs should be conducted to verify these outcomes and provide results according to patient status.

Influence of larval growth and habitat shading on retreatment frequencies of biolarvicides against malaria vectors.

Effective larviciding for malaria control requires detailed studies of larvicide efficacies, aquatic habitat characteristics, and life history traits of target vectors. Mosquitoes with brief larval phases present narrower timeframes for biolarvicidal effects than mosquitoes with extended periods. We evaluated two biolarvicides, VectoBac (Bacillus thuringiensis israelensis (Bti)) and VectoMax (Bti and Bacillus sphaericus) against Anopheles funestus and Anopheles arabiensis in shaded and unshaded habitats; and explored how larval development might influence retreatment intervals. These tests were done in semi-natural habitats using field-collected larvae, with untreated habitats as controls. Additionally, larval development was assessed in semi-natural and natural habitats in rural Tanzania, by sampling daily and recording larval developmental stages. Both biolarvicides reduced larval densities of both species by >98% within 72 h. Efficacy lasted one week in sun-exposed habitats but remained >50% for two weeks in shaded habitats. An. funestus spent up to two weeks before pupating (13.2(10.4-16.0) days in semi-natural; 10.0(6.6-13.5) in natural habitats), while An. arabiensis required slightly over one week (8.2 (5.8-10.6) days in semi-natural; 8.3 (5.0-11.6) in natural habitats). The findings suggest that weekly larviciding, which is essential for An. arabiensis might be more effective for An. funestus whose prolonged aquatic growth allows for repeated exposures. Additionally, the longer residual effect of biolarvicides in shaded habitats indicates they may require less frequent treatments compared to sun-exposed areas.

Outcome of Contemporary Nonsurgical Endodontic Retreatment: A Systematic Review of Randomized Controlled Trials and Cohort Studies.

INTRODUCTION: The success rates of NS-ReTx have varied across decades of prior research. Nonetheless, recent endodontic advances have substantially enhanced case management. This systematic review aimed to identify rigorous studies on contemporary NS-ReTx, investigating both periapical healing-evaluated strictly for complete resolution or loosely for size reduction of periapical radiolucency-and success, denoting clinical normalcy combined with periapical healing. METHODS: We systematically searched MEDLINE, Embase, Web of Science, the Cochrane Library, and gray literature from January 1988 to December 2022. Article selection and data extraction were independently conducted by 3 reviewers. Selected studies underwent risk of bias assessment, and evidence quality using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Meta-analysis and meta-regression established pooled outcome rates, 95% confidence intervals (CIs), and significant clinical prognostic factors (P < .05). RESULTS: Twenty-nine articles were included. Pooled periapical healing rates using strict and loose criteria were 78.8% (95% CI: 75.2-82.4) and 87.5% (95% CI: 83.8-91.2), respectively. Pooled success rates using strict and loose criteria were 78.0% (95% CI: 74.9-81.2) and 86.4% (95% CI: 82.6-90.1), respectively. Meta-regression analyses revealed significant influences on NS-ReTx outcomes (P < .05), including periapical status, lesion size, apical root filling extent, and follow-up duration. CONCLUSIONS: Contemporary NS-ReTx shows encouraging outcomes, achieving periapical healing and success rates ranging from approximately 78% (strict criteria) to 87% (loose criteria). The absence of or smaller preoperative lesions, adequate root filling length, and extended follow-ups significantly improve NS-ReTx outcomes. Integrating these factors into treatment planning is pivotal for optimizing the outcome of NS-ReTx.

Effective retreatment with osimertinib in CNS-relapsed epidermal growth factor receptor-mutant non-small cell lung cancer patient following resection and adjuvant osimertinib.

For years, adjuvant chemotherapy has been the only standard treatment for resected non-small cell lung cancer patients (NSCLC), offering a dismal survival improvement at 5 years. Following the outstanding results of the recent ADAURA trial, osimertinib has become a new standard treatment for resected epidermal growth factor receptor (EGFR)-mutant non-squamous NSCLC, regardless of the administration of chemotherapy. For patients whose disease relapses after completion of the adjuvant therapy, there is no consensus about the optimal treatment. Herein, we report the case of a 74-year-old woman diagnosed with stage IIIA non-squamous NSCLC, harboring the EGFR p.L858R mutation. After complete tumor resection, the patient received adjuvant chemotherapy with cisplatin and vinorelbine, followed by osimertinib 80 mg daily for 3 years within the ADAURA trial. Brain disease relapse was documented 18 months after treatment completion by computed tomography scans. The patient was then retreated with osimertinib obtaining a deep intracranial partial response, which is still lasting after 21 months. The retreatment with osimertinib in patients whose disease relapsed following adjuvant therapy with the third-generation EGFR inhibitor might be a valid option, especially in patients with intracranial disease relapse. Studies are warranted to confirm this finding and to define the impact of the disease-free interval in this regard.