Retreatability of NeoSEALER Flo obturated with warm vertical compaction versus single-cone technique using two different retreatment systems.

Aim: The aim of this study was to compare the retreatability of NeoSEALER Flo obturated with warm vertical compaction (WVC) and single-cone (SC) techniques using two different retreatment systems. Materials and Methods: Thirty-two root canals were shaped and obturated with NeoSEALER Flo either in an SC obturation technique or a WVC technique. Samples were retreated using ProTaper retreatment or EdgeFile XR retreatment system. The percentage of remaining debris after retreatment was analyzed under a scanning electron microscope using ImageJ software. The time taken to reach full working length (WL) and induce patency was recorded. Statistical Analysis: Statistical analysis was performed using an unpaired t-test and a one-way analysis of variance test. Results: The percentage of remaining debris after retreatment was significantly higher in the SC technique than in the WVC technique, regardless of the retreatment system used. EdgeFile XR system removed more filling material than the ProTaper retreatment system, regardless of the obturation technique. The apical region showed significantly higher remaining debris than other regions in all groups. The WL and patency were achieved faster in the SC group, while in the WVC group, the EdgeFile XR system was faster. Conclusions: The WVC technique showed better retrieval of the filling material; however, a longer time was taken for retreatment. EdgeFile XR system performed better in removing filling materials from inside the canals.

Retreatment with immunotherapy in a patient with hepatocellular carcinoma who received immune checkpoint inhibitors after primary curative treatment: a case report.

Hepatocellular carcinoma (HCC) presents a malignant pathology known for its high early recurrence rate following curative treatment, significantly impacting patient prognosis. Currently, effective strategies to mitigate early HCC recurrence remain undetermined. In this report, we document a case of HCC managed with curative radiofrequency ablation (RFA), particularly in a patient facing a high risk of early recurrence due to a substantial tumor size. In an effort to forestall recurrence, immune checkpoint inhibitors (ICIs) were preemptively administered for 6 months post-RFA. Despite this, early recurrence ensued upon ICIs cessation. Traditionally, the approach to advanced HCC has been conservative, yet recent years have seen promising outcomes with ICIs in advanced HCC. However, research on ICIs retreatment is limited. In the short term, this patient experienced widespread metastases post-ICIs discontinuation, yet exhibited prompt regression upon ICIs reinitiation. Notably, this represents the initial documented instance of employing ICIs to forestall recurrence subsequent to curative RFA in HCC. Following ICIs discontinuation, diffuse recurrence with multiple metastases emerged, with successful resolution upon ICIs retreatment.

Comparative Evaluation of Debris Expulsion Beyond Apex During Re-root Canal Treatment by Utilizing Two Re-treatment Rotary Files and Two Reciprocating Files: An In-Vitro Study.

AIM: This study aimed to assess and compare debris quality expelled beyond the apex during re-treatment using two reciprocating and two re-treatment rotary files. MATERIALS AND METHODS: A total of 80 healthy human mandibular premolars excised for orthodontic therapy were selected. Distilled water was used to sterilize the teeth before they were preserved. The canals were widened and coronal access was created so that the F2 ProTaper universal system could be used. For the obturation, we utilized gutta-percha cones and AH plus sealant. All samples were cone-beam computed tomography (CBCT) recorded. Teeth were separated into four groups (n=20); Group 1: ProTaper re-treatment, Group 2: Mtwo re-treatment, Group 3: WaveOne gold, and Group 4: Reciproc. The re-instrumented process included collecting the extruded debris in Eppendorf tubes and then drying it off by evaporating the distilled water. The weight of the tube with debris was subtracted from the weight of the tube without debris to get the dry debris weight. Post-retreatment CBCT was recorded for all samples. Mean apical debris extrusion values were obtained, after which necessary statistical analysis was obtained using SPSS Statistics, version 21 (IBM Corp., Armonk, NY) to obtain the results. A one-way analysis of variance (ANOVA) and the student t-test were utilized for statistical analysis to compare the different experimental groups. Post-hoc Bonferroni tests were used to compare several groups. RESULT: No statistical difference (p>0.05) was identified in the filler material that was left over across all groups. The reciprocating files discharged more material compared with re-treatment file systems. CONCLUSION: The Reciproc files expelled more waste than WaveOne gold, ProTaper re-treatment, and Mtwo re-treatment file systems. Reciprocating file systems showed better cleaning efficiency compared to the re-treatment file systems.

Comparative evaluation of incidence of dentinal defects after root canal preparation using three different endodontic retreatment systems - An in vitro study.

Context: Safe and efficient removal of all root filling materials from the root canal system without compromising radicular dentin structure is essential for optimal nonsurgical retreatment. Aims: The aim of this study was to evaluate and compare the incidence of dentinal defects caused during root canal filling removal using conventional, rotary, and reciprocating retreatment file systems. Settings and Design: A detailed protocol explaining purpose and procedures of the study was submitted to the Institutional Ethics Committee and ethical clearance obtained. Subjects and Methods: Sixty human maxillary permanent central incisors were collected and decoronated to 12-mm standardized length. The canals prepared up to a master apical file size F3 with Protaper hand files, obturated using AH plus sealer, examined under the stereomicroscope (×40 magnification): Group I: Control (n = 15), Group II: Conventional (n = 15), Group III: Protaper Universal Retreatment Files (n = 15), and Group IV: Reciproc Blue (n = 15). After instrumentation, teeth were sectioned at 3, 6, and 9 mm from the apex to evaluate the presence of dentinal defects under the stereomicroscope. Statistical Analysis Used: Statistics were performed using the SPSS, version, 25 (SPSS Inc., Chicago, IL, USA). Initially, normality test was done using the Shapiro-Wilk test and data were not normally distributed followed by Kruskal-Wallis test. P < 0.05 is considered statistically significant. Results: Maximum percentage increase in dentinal defects was observed in Protaper Universal Retreatment Files followed by Conventional method and Reciproc Blue. Conclusions: Significantly Reciproc Blue reduced the incidence of dentinal defects after root canal preparation.

Comparative Analysis of the Efficacy of Various Retreatment File Systems in the Removal of Gutta-Percha in Retreatment Cases and Time Taken During the Procedure: An In Vitro Cone Beam CT Study.

Background Removing gutta-percha manually can be a challenging task, especially when addressing densely packed root-filling material, particularly in cases where resin-based sealers are employed for obturation. The use of nickel-titanium (NiTi) rotary instruments not only effectively shapes the root canal but also efficiently removes the endodontic filling from the curved canal during retreatment. Hence, incorporating rotary NiTi instruments in retreatment cases can alleviate fatigue for both patients and operators. Objectives This study aims to compare the efficacy of Neo-Endo retreatment files, R-Endo retreatment files, and K and H files in the removal of endodontic filling material. Additionally, the remnants of gutta-percha in root canals are evaluated using cone beam computed tomography (CBCT). Materials and methods A total of 60 extracted first maxillary molar teeth were selected for this study. Canal preparation was conducted using the step-back method up to an apical size of 40 K-file. The obturation process involved the use of gutta-percha points and AH Plus sealer in a lateral compaction technique. Post-operative CBCT scans were taken. The samples were randomly divided according to the retreatment files used: group I included Neo-Endo retreatment files, group II included R-Endo retreatment files, and group III included conventional K-files and Hedstroem files (H-Files). The retreatment procedure was considered complete when the last instrument easily reached the working-length range and was physically clean. A stopwatch was used to record the time taken by each file to remove the obturating material. T1 represented the total time (including irrigation and change of file) required to reach the apex, while T2 indicated the complete removal of materials from the canal with the last instrument. The overall time recorded (TT) was calculated as T1 + T2. The removal process was analyzed with CBCT scans. Results The Neo-Endo retreatment files removed the filling materials better and more quickly than the other files. Conclusions Despite the presence of residual filling material in all samples, the Neo-Endo retreatment files left the least amount of residual filling material and achieved the shortest completion time.

Successful Management of a Rare Distant Endodontic Lesion: A Case Report.

The current case report aims to document a rare presentation of a distant odontogenic lesion of a 35-year-old male patient with mild clinical discomfort in the mandibular right first molar; exploring the diagnostic and therapeutic intricacies of an uncommon distant endodontic pathosis ultimately resolved through meticulous nonsurgical retreatment. Despite a normal oral examination, diagnostic radiography revealed a suboptimal root canal treatment and apical lesions surrounding mesial- and distal-root apices; including a distinct radiolucency beneath the apex of the second mandibular molar discovered through panoramic radiography, and confirmed via cone-beam computed tomography. In addition, the computed tomography disclosed a previously unreported and unusually large endodontic lesion that extended toward the mandibular canal; highlighting a necessity for the continued exploration of a unique endodontic presentation. A nonsurgical endodontic retreatment led to a remarkable reduction in the radiolucent lesions within one year; emphasizing the significance of comprehensive diagnostic approaches and individualized treatments.

Predicting early endodontic treatment failure following primary root canal treatment.

BACKGROUND: Understanding when and why endodontic treatments fail could help clinicians make prognoses and thus improve treatment outcomes. This study was aimed to assess potential predictors of early endodontic treatment failure. We explored factors contributing to the failure of initial root canal treatment were explored, with a specific emphasis on evaluating the influence of the time elapsed since the initial treatment. METHODS: This retrospective cohort study enrolled 1262 patients who sought endodontic treatment at our department and 175 patients were included for analysis. Potential causes of endodontic treatment failure were investigated, such as inadequate obturation quality, inadequate coronal status, the presence of additional untreated canals, anatomical complexity, instrument separation, iatrogenic perforation, cracks, and endodontic-periodontal lesions. The patients were divided into "short-term" and "long-term" groups depending on the time that had passed since the initial treatment (i.e., < 5 and > 10 years, respectively). The causes of failure in the short-term and long-term group were analyzed and compared using logistic regression analyses. Subgroup analysis was performed according to the number of years since the initial treatment in the short-term group to further investigate the association between the time and cause of failure (i.e., < 1, 2, 3, and 4 years, respectively). RESULTS: Untreated additional canals were present in 21.7% of all cases, and in 36.9 and 6.4% of cases in the short-term and long-term groups, respectively. Multivariable analysis showed that the presence of untreated additional canals was significantly associated with short-term compared to long-term failure. Untreated additional canals were also associated with endodontic failure within 1, 2, 3, and 4 years. CONCLUSIONS: The presence of untreated additional canals was a predictor of endodontic failure within 5 years following initial root canal treatment. To optimize long-term prognosis, it is important to detect and treat all root canals during the initial treatment.

To flare or not to flare: patients' and rheumatologists' perceptions on the on-flare retreatment strategy of rituximab in rheumatoid arthritis.

Background: Several retreatment strategies exist for rituximab in rheumatoid arthritis (RA). In some countries, reimbursement criteria require a loss of disease control for rituximab retreatment. Understanding the patients' and rheumatologists' perceptions regarding this retreatment strategy would be informative in identifying the optimal treatment administration schedule. Objectives: This study aimed to uncover patients' and rheumatologists' perceptions regarding retreatment strategies of rituximab. Design: Qualitative study - semi-structured interviews. Methods: Patients with RA, treated with rituximab, and rheumatologists were invited to participate in a qualitative study consisting of individual, in-depth, semi-structured interviews. Interviews were analysed according to the Qualitative Analysis Guide of Leuven. Results: A total of 16 patients and 13 rheumatologists were interviewed. Benefits (e.g. decreased risk of overtreatment, cost savings and long-lasting effectiveness of rituximab) and barriers (e.g. fluctuating disease activity, slow mode of action and increased glucocorticoid use) of on-flare retreatment were identified. To effectively treat on-flare, flares must first be identified timely. Both stakeholder groups acknowledged that patients are capable of recognizing flares. However, the patient's ability to discriminate between inflammatory and other types of pain was perceived as difficult. Furthermore, patients and rheumatologists stressed that patients must timely seek professional help in case of a flare, followed by a swift response from the rheumatologists. Remarkably, retreatment was approached in various ways among rheumatologists, and not always adhering strictly to the on-flare reimbursement criteria. Conclusion: This study revealed that both stakeholder groups perceived the heterogeneity in recognition of and reaction to a flare as important in influencing the effectiveness of the on-flare retreatment strategy. Moreover, this study identified the benefits and barriers of treating on-flare, which could be informative for daily practice decisions.

The Impact of Citric Acid Solution on Hydraulic Calcium Silicate-Based Sealers and Root Dentin: A Preliminary Assessment.

Hydraulic calcium silicate-based (HCS) sealers have recently gained tremendous popularity due to their unique properties. However, their removal during endodontic retreatment is challenging. The solvent, which could chemically deteriorate the material, would be highly desirable for endodontic retreatment procedures. This preliminary study assessed the interplay and dissolving capability of 10% and 20% citric acid, compared to 17% EDTA, on commonly used HCS sealers (AH Plus Bioceramic Sealer, Bio-C Sealer, BioRoot RCS, TotalFill BC Sealer), and evaluated the potential impact of these solutions on root dentin structure. The interaction between tested sealers and irrigating solutions was photographed, and solubility-related mass changes were determined. The surface morphology of treated filling materials and dentin was evaluated using a scanning electron microscope (SEM). One-way analysis of variance (ANOVA) along with Tukey's test were used to detect the statistically significant differences among groups at the confidence level of 0.95. Intense gas release was observed during the interaction of HCS materials and citric acid, with no evidently visible "bubbling" after the immersion in EDTA. The mass loss of HCS sealers equally confirmed the significantly higher dissolving characteristics of 10% and 20% citric acid solutions compared to EDTA. The surface structural changes, associated with pore and crack formation, were mainly seen for HCS sealers exposed to citric acid. Meanwhile, no severe erosion was detected for dentin after root canal preparation with 10% and 20% citric acid solutions. These findings demonstrate that citric acid has the potential to dissolve HCS sealers with minimal or no negative impact on root dentin, suggesting citric acid as a solvent for HCS sealers in endodontic retreatment procedures.

Efficacy and safety of intravenous immunoglobulin retreatment amongst Guillain-Barré syndrome patients who poorly responded to initial IVIG cycle: a systematic review.

INTRODUCTION: Small cross-sectional studies and case reports observed improvement after administration of second IVIG dose (SID) amongst Guillain-Barré Syndrome (GBS) patients not responsive to initial IVIG cycle. Nevertheless, recent clinical trial and larger observational studies did not find any positive effects of SID. Instead, an increased risk of thromboembolism and mortality was noted. The conclusions of these studies however were not robust as confounding and selection bias were present. METHODOLOGY: Two neurologists conducted the search process (KBA and MBP) using the following terms in Medline: [(" Guillain-Barré Syndrome"[MeSH Terms] or GBS or Acute Motor Axonal Neuropathy or Acute Motor Axonal Neuropathy or Acute Inflammatory Demyelinating Polyneuropathy) AND (Poorly Responsive or Poor Prognosis or Progressive)] AND [("Intravenous Immunoglobulin"[MeSH Terms] or IVIG or IGIV) AND (second dose or retreatment or SID)]. RESULTS: Only 7 articles were included in this review. In terms of primary outcomes, although the cross-sectional study found improvement in GBS DS score at 4 weeks (Median GBS DS: 3 vs 5, p = 0.033) and the 2 case series observed improvement after SID, no significant differences between the control and intervention groups were found in the cohort [Early SIV OR: 0.7 (95% CI 0.16-3.04), Late SIV OR: 0.66 (CI: 0.18-2.5)] and clinical trial studies (Adjusted OR: 1.4 (95% CI:0.6-3.3, p = 0.45). Moreover, 4 patients who died in the clinical trial were from the intervention group. CONCLUSION: Based on studies with research designs of higher quality, SID is not effective in the management of GBS patients who poorly responded to initial IVIG. Nevertheless, an adequately powered, randomized, double-blinded, placebo-controlled clinical trial, using GBS-DS of 3 and above after first IVIG dose should be done to effectively establish the efficacy and safety of SID as intervention for this cohort of patients.

Incidence of Middle Mesial Canals in Mandibular Molars during Root Canal Treatment and Nonsurgical Retreatment.

INTRODUCTION: Large-scale clinical studies on the incidence of middle mesial canals (MMCs) in nonsurgical root canal treatment (RCT) and retreatment of mandibular molars are lacking. The primary aim of this observational study was to determine the incidence of MMCs in mandibular first and second molars that received RCT or nonsurgical retreatment (NSRetx). The secondary aim was to determine factors associated with incidence of MMCs. METHODS: Included were 3018 mandibular molars that received RCT (n = 1624) or NSRetx (n = 1394) by 3 endodontists in a private practice. Demographic and procedural data were collected. Bivariate and multivariable (Poisson regression model) analyses were performed. RESULTS: Incidence of MMCs was 8.8% (n = 267). Although the bivariate analysis showed that NSRetx was significantly associated with incidence of MMCs, this association did not reach the threshold for statistical significance after controlling for all covariates (P = .07). Multivariable analysis on the entire cohort showed that incidence of MMCs was significantly associated with younger age (risk ratio [RR] = 1.62; 95% confidence interval [CI], 1.28-2.06), male gender (RR = 1.48; 95% CI, 1.18-1.85), preoperative cone-beam computed tomography (CBCT) (RR = 1.48; 95% CI, 1.17-1.89), and first molar (RR = 2.30; 95% CI:1.74-3.05). Subgroup multivariable analyses revealed that incidence of MMCs was associated with male gender only in the RCT group (RR = 2.26; 95% CI, 1.55-3.30) but not in the NSRetx group (RR = 1.11; 95% CI, 0.82, 1.50); and with preoperative CBCT only in the NSRetx group (RR = 1.78; 95% CI, 1.28, 2.50) but not in the RCT group (RR = 1.10; 95% CI, 0.71, 1.69). Associations with younger age and first molar remained unchanged. CONCLUSIONS: Overall incidence of MMCs was 8.8%. Incidence of MMCs was significantly higher in younger patients and in mandibular first molars but was not associated with the type of treatment.

Analysis of retreatment with monoclonal antibodies in chronic/episodic migraine: Real world data.

OBJECTIVE: To analyze the response to retreatment in patients with chronic/episodic migraine who discontinued therapy with erenumab/fremanezumab after 1 year of treatment. METHODS: Observational, retrospective, single-center, multidisciplinary study in patients with chronic/episodic migraine who received therapy with erenumab/fremanezumab for at least 1 year and discontinued it after achieving an adequate response (optimization). The evaluation of the response after retreatment included the following variables: DMM, MIDAS, and HIT-6 scales at the beginning of retreatment and 3 months later. The response was evaluated in different subgroups (episodic/chronic, erenumab/fremanezumab, and time until retreatment). RESULTS: 48 patients were included. 70.8% (n=34) required retreatment with mAb, with a median of 3.9 (2.9-6.4) months until reintroduction. Clinical response after retreatment was achieved in 67.6% (n=23) of patients. No statistically significant differences were found in the analyzed subgroups. CONCLUSION: Interruption of treatment with erenumab/fremanezumab for chronic/episodic migraine produces a clinical worsening of the disease requiring retreatment in most cases, approximately after 4 months. Two out of three patients respond positively after restarting monoclonal therapy. This response does not appear to be related to the type of migraine, the specific monoclonal antibody prescribed, or the time to retreatment.

Fluorescence intensity of composite resin for direct veneer removal using a fluorescence-aided identification technique.

OBJECTIVES: This laboratory study evaluated the influence of the fluorescence intensity of composite resins on additional tooth wear and the presence of restorative material in different dental thirds during the retreatment of direct veneers. MATERIALS AND METHODS: The crown dimensions of 60 bovine incisors were reduced to 10 × 8 mm. The teeth were classified according to the fluorescence intensity of the composites: low (LOW) (TPH Spectra), medium (MED) (Opallis), and high (HIGH) (Essentia) groups. The teeth were divided according to the removal methods: conventional (CON) and fluorescence-aided identification technique (FIT). The specimens were scanned (T0), received veneer preparation, and scanned again (T1). After restorations, the composites were removed and the teeth were scanned (T2). Measurement assessments between T1 and T2 were performed to determine additional wear, presence of residual areas, and the average between additional wear and the presence of residual areas. Kruskal Wallis, Mann-Whitney, Friedman, 2-way ANOVA, and post-Tukey tests were performed (α < 0.05). RESULTS: The comparison of composite resins indicated a smaller area of additional wear and greater residue presence in the HIGH group than the LOW group for both techniques in the cervical third. Regarding removal methods, the FIT produced greater additional wear than the CON method for the LOW and MED groups in the middle and cervical thirds. The incisal third exhibited greater additional wear than the other thirds. CONCLUSIONS: Composite resins with high fluorescence intensity removed using FIT had less tooth wear. The incisal third was the most affected area for direct veneer removal procedures. CLINICAL SIGNIFICANCE: A FIT has been proposed for composite resin removal; however, the different fluorescence intensities of composite resins can influence tooth wear caused during this procedure.

Effectiveness and Safety of Retreatment with 177Lu-DOTATATE in Patients with Progressive Neuroendocrine Tumors: A Retrospective Real-World Study in the United States.

Advanced neuroendocrine tumors (NETs) are associated with a poor prognosis. A regimen of 4 cycles of 177Lu-DOTATATE has been shown to improve both progression-free survival (PFS) and overall survival (OS) in patients with advanced NETs. To the best of our knowledge, this is the first study in the United States to evaluate the effectiveness and safety of additional cycles of 177Lu-DOTATATE therapy in patients with progressive NETs. Methods: This was a retrospective chart review of adults with advanced NETs. The patients had undergone initial treatment with up to 4 cycles of 177Lu-DOTATATE and, after disease progression and a period of at least 6 mo since the end of the initial treatment, were retreated with at least 1 additional cycle at a single center (2010-2020). Patient characteristics, treatment patterns, and clinical outcomes were evaluated descriptively. Response was evaluated according to RECIST 1.1; toxicity was defined using criteria from Common Terminology Criteria for Adverse Events, version 5.0. Kaplan-Meier plots were used to evaluate PFS and OS. Results: Of the 31 patients who received 177Lu-DOTATATE retreatment, 61% were male and 94% were White. Overall, patients received a median of 6 cycles (4 initial cycles and 2 retreatment cycles), and the mean administered activity was 41.9 GBq. Two patients also went on to receive additional retreatment (1 and 2 cycles, individually) after a second period of at least 6 mo and progression after retreatment. Best responses of partial response and stable disease were observed in 35% and 65% of patients after the initial treatment and 23% and 45% of patients after retreatment, respectively. The median PFS after the initial treatment was 20.2 mo and after retreatment was 9.6 mo. The median OS after the initial treatment was 42.6 mo and after retreatment was 12.6 mo. Hematologic parameters decreased significantly during both the initial treatment and retreatment but recovered such that there was little difference between the values before the initial treatment and before the retreatment. Clinically significant hematotoxicity occurred in 1 and 3 patients after the initial treatment and retreatment, respectively. No grade 3 or 4 nephrotoxicity was observed. Conclusion: Retreatment with 177Lu-DOTATATE after progression appeared to be well tolerated and offered disease control in patients with progressive NETs after initial 177Lu-DOTATATE treatment.

Removal of fiber posts using conventional versus guided endodontics: a comparative study of dentin loss and complications.

OBJECTIVES: To compare the efficacy of fiber post removal using conventional (CONV) versus guided endodontics (GE) in terms of dentin loss, residual resin material, procedural errors, and working time in vitro. MATERIAL AND METHODS: Ninety human central incisors were root-filled and scanned by micro-computed tomography (CT), then restored with fiber posts and composite. Twenty-four sets of teeth with up to four human maxillary central incisors were fabricated and divided into three groups: conventional post removal by a general dentist (CG) or endodontology specialist (CS) and guided endodontics (GE) by a general dentist, yielding 30 teeth per operator and group. After treatment, the prepared access cavities were volumetrically assessed by micro-CT. Statistical significance was evaluated by one-way analysis of variance followed by post hoc comparisons with Tukey's HSD test and Pearson's chi-squared test for independence. RESULTS: Both CONV and GE resulted in dentin loss and residual resin material. CS resulted in more dentin loss and less residual resin material than CG and GE (p < .05). All groups had some deviations from the original root canal but no perforations. The shortest working time was observed in the GE group. CONCLUSIONS: Compared to the conventional freehand technique, GE resulted in significantly less radicular dentin loss, a few deviations but no perforations. CLINICAL RELEVANCE: Guided endodontics can improve the speed and safety of fiber post removal without root perforation.

Prediction of intravenous immunoglobulin retreatment in children with Kawasaki disease using models combining lymphocyte subset and cytokine profile in an East Asian cohort.

Objectives: For children with Kawasaki disease (KD) at high risk of developing coronary artery lesions and requiring retreatment with intravenous immunoglobulin (IVIG), the availability of accurate prediction models remains limited because of inconsistent variables and unsatisfactory prediction results. We aimed to construct models to predict patient's probability of IVIG retreatment combining children's individual inflammatory characteristics. Methods: Clinical manifestations and laboratory examinations of 266 children with KD were retrospectively analysed to build a development cohort data set (DC) and a validation cohort data set (VC). In the DC, binary logistic regression analyses were performed using R language. Nomograms and receiver operating curves were plotted. The concordance index (C index), net reclassification index, integrated discrimination improvement index and confusion matrix were applied to evaluate and validate the models. Results: Models_5V and _9V were established. Both contained variables including the percentages of CD8+ T cells, CD4+ T cells, CD3+ T cells, levels of interleukin (IL)-2R and CRP. Model_9V additionally included variables for IL-6, TNF-α, NT-proBNP and sex, with a C index of 0.86 (95% CI 0.79-0.92). When model_9V was compared with model_5V, the NRI and IDI were 0.15 (95% CI 0.01-0.30, P < 0.01) and 0.07 (95% CI 0.02-0.12, P < 0.01). In the VC, the sensitivity, specificity and precision of model_9V were 1, 0.875 and 0.667, while those of model_5V were 0.833, 0.875 and 0.625. Conclusion: Model_9V combined cytokine profiles and lymphocyte subsets with clinical characteristics and was superior to model_5V achieving satisfactory predictive power and providing a novel strategy early to identify patients who needed IVIG retreatment.

Successful Management of Ovarian Cancer Progressing on Olaparib by Niraparib Following Cytoreduction: A Case Report.

BACKGROUND: Polyadenosine 5'-diphosphoribose polymerase inhibitors (PARP-Is) are novel, effective agents for treating newly diagnosed epithelial ovarian cancer (EOC). However, the effect of PARP-I on the progression of recurrent EOC has not yet been determined. In particular, there is limited evidence regarding retreatment with PARP-I for recurrent EOC that has progressed on PARP-I in the short term. CASE REPORT: A 69-year-old woman with a BRCA1 mutated EOC relapsed five months after starting olaparib maintenance following neoadjuvant chemotherapy and interval debulking surgery. Although the platinum-free interval was within six months, secondary cytoreductive surgery was performed because the tumor was locoregional. Following two cycles of weekly nedaplatin, niraparib induced a complete response, and the patient maintained a progression-free status for 15 months. CONCLUSION: Even with short-term progression on PARP-I, local control combined with different platinum agents and PARP-I can be used to achieve good responses.

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.

Real-world effectiveness of voxilaprevir/velpatasvir/sofosbuvir in patients following DAA failure.

Background & Aims: Voxilaprevir/velpatasvir/sofosbuvir (VOX/VEL/SOF) is highly effective for re-treatment of direct-acting antiviral (DAA)-experienced patients with chronic HCV infection. In the present study, predictors of virologic treatment response were analyzed in an integrative analysis of three large real-world cohorts. Methods: Consecutive patients re-treated with VOX/VEL/SOF after DAA failure were enrolled between 2016 and 2021 in Austria, Belgium, Germany, Italy, Spain and Switzerland. Results: A total of 746 patients were included: median age was 56 (16-88) years and 77% were male. Most patients were infected with HCV genotype 1 (56%) and 3 (32%). 86% of patients carried resistance-associated substitutions in the NS3, NS5A or NS5B regions. Overall, 95.4% (683/716) of patients achieved a sustained virologic response. Treatment effectiveness was significantly affected by advanced liver disease (p <0.001), hepatocellular carcinoma (p <0.001), higher baseline ALT levels (p = 0.02), HCV genotype 3 (p <0.001), and prior VEL/SOF treatment (p = 0.01). In a multivariate analysis, only HCV genotype 3, hepatocellular carcinoma and cirrhosis turned out to be independent predictors of treatment failure. Resistance-associated substitutions, as well as the presence of rare genotypes, did not impact treatment outcome. The effectiveness of rescue therapy with glecaprevir/pibrentasvir and SOF, with or without ribavirin, for 12 to 24 weeks was found to be high (100%). Conclusions: Infection with HCV genotype 3, the presence of liver cancer and cirrhosis are independently associated with failure of VOX/VEL/SOF re-treatment. It is unclear whether the addition of ribavirin and/or extension of treatment duration may be effective to avoid virologic relapse on VOX/VEL/SOF. However, rescue treatment with glecaprevir/pibrentasvir+SOF seems to be effective. Impact and implications: Representative data on the effectiveness of voxilaprevir/velpatasvir/sofosbuvir (VOX/VEL/SOF) in clinical practice are still scarce and the collection of a larger number of patients with difficult-to-treat cofactors including the assessment of resistance-associated substitution profiles is required before more specific recommendations for optimal re-treatment in these patients can be given. Thus, we aimed to analyze treatment effectiveness and predictors of virologic response to VOX/VEL/SOF in an integrative analysis of three large real-word cohorts. The study results, derived from a multicenter cohort consisting of 746 patients, demonstrated that re-treatment with VOX/VEL/SOF is an effective salvage therapy associated with an overall per protocol sustained virologic response rate of 95%. Hepatocellular carcinoma onset, cirrhosis and HCV genotype 3 were identified as independent negative predictors of treatment response, whereas resistance-associated substitutions, as well as rare genotypes and chimera, did not impact sustained virologic response rates following re-treatment with VOX/VEL/SOF.

Acute Care Surgery: Navigating Recent Developments, Protocols, and Challenges in the Comprehensive Management of Surgical Emergencies.

Acute care surgery (ACS) is a crucial medical field that specifically deals with the rapid treatment of surgical emergencies. This investigation encompasses the most recent progress, procedures, and obstacles in ACS, utilizing various sources such as scholarly articles, clinical trials, and expert statements. The development of ACS as a specialized field is a significant area of concentration, particularly emphasizing its contribution to improving patient care. An examination is conducted on the efficacy of contemporary triage systems and prompt response mechanisms, specifically in diminishing the incidence of illness and death rates associated with illnesses such as trauma, acute appendicitis, and obstructed viscera. The emphasis is placed on the surgical protocols and principles that form the basis of ACS. Examining regional and international approaches provides insight into the distinctions and commonalities in surgical techniques. An assessment is conducted to determine the effects of the transition to minimally invasive procedures on patient outcomes, recuperation periods, and healthcare expenses. The assessment also examines the logistical obstacles that ACS encounters, such as resource allocation and managing diverse teams. The examination focuses on the delicate equilibrium between prompt decision-making and care grounded in evidence. It also evaluates the possible contribution of technical breakthroughs such as telemedicine and AI to improving patient care and overcoming current obstacles. The topic of training and education for surgeons in ACS is of utmost importance and requires careful consideration. The evaluation evaluates the sufficiency of existing educational frameworks and the necessity of specific training to equip surgeons for the requirements of ACS. This analysis explores the current discourse surrounding the standardization of ACS training, considering its potential ramifications for the future of surgical procedures. Exploring ethical and legal problems in ACS also includes situations when prompt decision-making may clash with patient autonomy and informed consent. The significance of proficient communication with patients and their families during emergency surgical scenarios is underscored, emphasizing the necessity for ethical awareness and interpersonal aptitude. The investigation of ACS demonstrates its dynamic character, signifying notable advancements while recognizing enduring obstacles. Continual research, interdisciplinary collaboration, and policy adjustments are necessary to improve ACS procedures. This thorough investigation offers valuable insights for professionals and researchers, facilitating future progress in managing surgical crises.