Initial Lesion Research Articles

A Phase 1 Trial of OPB-111077 in Combination with Bendamustine (B) and Rituximab (R) in Patients with Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL): Preliminary Results of Dose-Escalation Stage

Background OPB-111077, a first-in-class small molecule, is an orally available antitumor agent with an inhibitory effect on mitochondrial oxidative phosphorylation (OXPHOS). OPB-111077 inhibits mitochondrial respiratory chain complex I, which leads to inhibition of energy production and activation of the AMPK-mTOR energy stress sensor pathway, as well as inhibition of the signal transducer and activator of transcription (STAT) 3 pathway. In non-clinical studies using cultured cells and murine xenograft models, OPB-111077 showed antitumor effects in a variety of tumor cell lines, including hematological and solid tumors, and OPB-111077 in combination with an alkylating agent has a potential synergistic antitumor effect for malignant lymphoma. Here we report the preliminary results from the dose-escalation (DE) stage of an ongoing phase 1 trial (NCT04049825) of OPB-111077 in combination with bendamustine (B) and rituximab (R) in patients with relapsed or refractory (R/R) diffuse large B-cell lymphoma (DLBCL). Method This trial is composed of 2 stages. OPB-111077 is administered in combination with B in a DE stage and with B and R in a dose-expansion (EX) stage. The DE stage uses a 3+3 design. The objectives of the DE stage are to evaluate the tolerability and safety of OPB-111077 in combination with B and to determine the recommended dose for the EX stage based on dose-limiting toxicity (DLT). A secondary objective is to evaluate efficacy. Response assessment is based on IWG Lugano response criteria for non-Hodgkin lymphoma (NHL) (2014). Key eligibility criteria include age 20 to 80 years (inclusive), at least initial standard treatment, measurable lesions, and Eastern Cooperative Oncology Group performance status score of 0 or 1. OPB-111077 is orally administered once daily on Days 3 to 6, Days 10 to 13, and Days 17 to 20 of each cycle. The duration of each cycle is 21 days, except for Cycle 1, which is 23 days. The dose in the first cohort is 200 mg/day, increasing as appropriate to 400 mg/day in Cohort 2 and then to 600 mg/day in Cohort 3. B is administered intravenously at 120 (or 90) mg/m 2 once daily on Days 1 and 2 of each cycle for up to 6 cycles. Results As of 31 Jan 2023, 16 patients had been treated with OPB-111077 + B (120 mg/m 2) at OPB-111077 doses of 200 mg (Cohort 1, n = 3), 400 mg (Cohort 2, n = 6), and 600 mg (Cohort 3, n = 7). Patients had received 1 to 6 prior lines of chemotherapy, median age was 70.0 (range 54 - 79) years, and 56.3% were male. Median treatment duration was 69.0 days. No DLT was observed in Cohort 1 or in the first 3 patients in Cohort 2. In Cohort 3, 2 patients experienced DLTs of neutropenia (grade 4) and neutropenia (grade 3, dose interruption of ≥21 consecutive days), respectively. As the Efficacy and Safety Evaluation Committee (ESEC) judged the OPB-111077 600-mg dose to be intolerable, in accordance with the scheme for the DE stage, new 3 patients were added to Cohort 2. One of the 6 patients in Cohort 2 experienced DLTs of anorexia (grade 3) and neutropenia (grade 4, dose interruption of ≥21 consecutive days). Based on the ESEC's recommendation, the recommended dose for the EX stage was set at OPB-111077 400 mg + B 120 mg/m 2. The most common (≥90%) treatment-related adverse events of any grade were lymphopenia (93.8%, grade 3: ≥93.8%), leukopenia (93.8%, grade 3: ≥81.3%), and nausea (93.8%, grade 3: ≥18.8%). The overall response rate [complete response (CR) + partial response (PR)] and CR rate were respectively 62.5% and 43.8%. Median progression-free survival was 257.0 days. Conclusion OPB-111077 400 mg + B 120 mg/m 2 combination treatment showed a tolerable safety profile. The preliminary data are encouraging, especially regarding the efficacy of OPB-111077 combination treatment, including CR in patients with DLBCL. The DE stage of the trial is still ongoing and the EX stage, which will evaluate the safety and efficacy of OPB-111077 in combination with B + R, is now recruiting.

Effect of photodynamic therapy on the healing of periapical lesions after root canal retreatment: 1-year follow up randomized clinical trial

BackgroundThe aim of this randomized clinical trial was to evaluate the effects of photodynamic therapy (PDT) after traditional activated final irrigation protocol (ultrasonically activated irrigation, UAI) on periapical lesion healing after single–visit root canal retreatment. MethodsWe included 36 patients with asymptomatic chronic apical periodontitis with periapical lesions larger than 5 mm and teeth sensitive to percussion and palpation, who had previous root canal treatment. All patients who signed informed consent underwent cone-beam computed tomography (CBCT) to determine and calculate the preoperative volume of the periapical lesion. Patients were randomly distributed into two groups according to the final disinfection protocol: Group 1; UAI (NaOCl, EDTA, and NaOCl), Group 2; UAI + PDT. All patients underwent single-visit root canal retreatment using rotary instrumentation and standardized irrigation (3 %NaOCl) by the same endodontist. The root canals were filled with epoxy resin-based sealer and single-cone gutta-percha, followed by control radiography. After one year, a new CBCT scan of the teeth was performed to calculate the reduction in the initial periapical lesion as a measure of periapical healing. For the statistical analysis, the chi-square test variants, Fisher's exact test and the Fisher-Freeman-Halton test were used at the level of significance set at 5 %. ResultsThere were no significant differences between the groups in terms of age, sex, preoperative and postoperative lesion volume (p > 0.05), and reduction of periapical lesion volume (median, 86.98 % for UAI and 79.72 % for UAI+PDT) (p = 0.970). Additional use of PDT after UAI did not contribute to the healing of periapical lesions. ConclusionThe UAI and UAI+PDT protocols had equal effects on healing of periapical lesion.

Prognosis of patients with recurrent nonsmall cell lung cancer who received the best supportive care alone

Background and objectivesThe development of treatments for non-small cell lung cancer (NSCLC) has remarkably progressed. Various treatment options are available for patients with postoperative NSCLC recurrence. However, some patients receive only the best supportive care (BSC) owing to their general condition and wishes, and their prognosis and associated factors remain unclear. We aimed to clarify the survival and prognostic factors in patients with recurring NSCLC who only received BSC. MethodsThis study included 903 patients who underwent complete resection with lobectomy or more invasive resection and systematic lymph node dissection for NSCLC at the Kitasato University Hospital between 2004 and 2015; a total of 270 patients experienced recurrence. Of them, 49 patients received BSC only. We determined the overall survival (OS) and post-recurrence survival (PRS), as well as the associated prognostic factors. ResultsPatients who received BSC alone had a median survival time of 4 (0–86) months after recurrence. The 5-year OS rate was 32.7%; the PRS rates were 11.0% and 6.6% at 3 and 5 years, respectively. The multivariate analyses showed that the number of initial recurrent lesions (one or two), time to recurrence (>1 year), and performance status (0–1) were favorable prognostic factors for PRS. ConclusionGood performance status was a prognostic factor in patients with recurrence as it affects the treatment choice; however, it was also a prognostic factor in those who received the best supportive care alone. To select the appropriate treatment methods, highly accurate prognostic prediction is necessary.

Prediction of therapeutic intensity level from automatic multiclass segmentation of traumatic brain injury lesions on CT-scans

The prediction of the therapeutic intensity level (TIL) for severe traumatic brain injury (TBI) patients at the early phase of intensive care unit (ICU) remains challenging. Computed tomography images are still manually quantified and then underexploited. In this study, we develop an artificial intelligence-based tool to segment brain lesions on admission CT-scan and predict TIL within the first week in the ICU. A cohort of 29 head injured patients (87 CT-scans; Dataset1) was used to localize (using a structural atlas), segment (manually or automatically with or without transfer learning) 4 or 7 types of lesions and use these metrics to train classifiers, evaluated with AUC on a nested cross-validation, to predict requirements for TIL sum of 11 points or more during the 8 first days in ICU. The validation of the performances of both segmentation and classification tasks was done with Dice and accuracy scores on a sub-dataset of Dataset1 (internal validation) and an external dataset of 12 TBI patients (12 CT-scans; Dataset2). Automatic 4-class segmentation (without transfer learning) was not able to correctly predict the apparition of a day of extreme TIL (AUC = 60 ± 23%). In contrast, manual quantification of volumes of 7 lesions and their spatial location provided a significantly better prediction power (AUC = 89 ± 17%). Transfer learning significantly improved the automatic 4-class segmentation (DICE scores 0.63 vs 0.34) and trained more efficiently a 7-class convolutional neural network (DICE = 0.64). Both validations showed that segmentations based on transfer learning were able to predict extreme TIL with better or equivalent accuracy (83%) as those made with manual segmentations. Our automatic characterization (volume, type and spatial location) of initial brain lesions observed on CT-scan, publicly available on a dedicated computing platform, could predict requirements for high TIL during the first 8 days after severe TBI. Transfer learning strategies may improve the accuracy of CNN-based segmentation models.Trial registrations Radiomic-TBI cohort; NCT04058379, first posted: 15 august 2019; Radioxy-TC cohort; Health Data Hub index F20220207212747, first posted: 7 February 2022.

MRI Criteria for Healing at 1 Year After Repair of a Traumatic Meniscal Tear

Background: Meniscal repair for a traumatic meniscal tear is increasingly used to preserve the meniscus. Interpreting postoperative magnetic resonance imaging (MRI) scans remains challenging, especially in symptomatic patients. There is a lack of reliable MRI criteria to affirm the healed character of a traumatic meniscal injury repair. Purpose: To identify relevant MRI criteria for meniscal healing after meniscal repair. Study Design: Case series; Level of evidence, 4. Methods: We prospectively included all patients with a traumatic meniscal injury who underwent either an isolated meniscal repair or a repair during a concomitant anterior cruciate ligament reconstruction. A standardized preoperative and postoperative clinical evaluation was performed, along with collection of functional scores—Knee injury and Osteoarthritis Outcome Score, International Knee Documentation Committee, Lysholm Score, and 36-Item Short Form Health Survey. An MRI scan was performed 1 year postoperatively and compared with the preoperative MRI scan. The following MRI aspects were analyzed: variation of morphology and fat-saturated (FS) T2 intensity signal and pre- and postoperative tear diastasis measurement. Results: Fifty patients (age, mean ± SD, 28.7 ± 8.5 years [range, 16-45 years]) who were 1 year postoperative were included. All patients were considered clinically healed had the same MRI characteristics. A signal change (FS T2) was observed from a high signal intensity fluid to a nonfluid moderate signal intensity. The morphology of the lesion was more complex: from the initial lesion, line ramifications appeared, creating the appearance of tree branches. The tear diastasis decreased (from 2.3 ± 0.5 mm [range, 1.3-3.5] to 1.1 ± 0.28 mm [range, 0.5-1.5]). Conclusion: MRI criteria confirming meniscal healing after traumatic meniscal repair at 1 year were identified: a change in the intrameniscal signal becoming nonfluid and moderate in intensity; a reduction in tear diastasis to <1.5 mm; and a change in the signal morphology of the repaired meniscus.

BIOM-39. GENETIC VARIANTS ASSOCIATED WITH DISTANT RECURRENCE IN GLIOBLASTOMA PATIENTS TREATED WITH STANDARD THERAPY

Abstract Infiltrative growth is a hallmark of glioblastoma and is a major factor in therapeutic failure. Genetic variants predictive of distant recurrence may serve as novel treatment targets. The aim is to identify genetic variants associated with distance recurrence in glioblastoma patients. METHODS: From a prospective cohort of consecutive, non-selected glioblastoma patients administered standard therapy between 2016-2021 at Rigshospitalet, all patients with a genomic tumor profile were included. Distant recurrence was defined as a new contrast-enhancing tumor &amp;gt; 2 cm from the initial lesion. Tumor tissue was analyzed by RNA- and DNA-sequencing (WES or WGS). Genetic variants were defined as pathogenic and likely-pathogenic variants based on genomic reports. Predefined candidate biomarkers included: i) the most common genetic variants in the cohort (mutational frequency &amp;gt; 2%), ii) the number of reported variants per sample, and iii) groups of genetic variants according to the common signaling pathways. Candidates were screened for association with time to distant recurrence using univariate Cox regression analysis. Biomarkers with p &amp;lt; 0.20 were considered for multivariate analysis adjusted for known prognostic factors with death as the competing risk. RESULTS: A total of 236 patients were included, and 208 patients (88%) were evaluable for recurrence pattern. Distant recurrence was observed in 40 patients (19%). Patients with distant and local recurrence showed no difference in progression-free survival (p = 0.58), while distant recurrence tended to have a poor overall survival (OS, p = 0.09). The OS from time of first recurrence was significantly poorer for patients with distant recurrence compared to local recurrence (p = 0.01) with a median OS of 7.2 months (95%CI: 5.9-8.5) and 10.9 months (95%CI: 9.8-12). The median frequency of called gene variants was 4 (range 0-11) per sample. CONCLUSION: Patients with distant recurrence have a poor prognosis. Final analyses will be presented.

NIMG-02. ADVERSE RADIATION EFFECT VERSUS TUMOR PROGRESSION FOLLOWING STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES: IMPLICATIONS OF RADIOGRAPHIC UNCERTAINTY

Abstract Despite efforts from RANO to standardize treatment response reporting, adverse radiation effect (ARE) following stereotactic radiosurgery (SRS) for brain metastases (BM) remains challenging to distinguish from tumor progression (TP) due to radiographic uncertainty (RU), often necessitating serial imaging until definitive diagnosis (DD) is resolved. We characterized management and implications of RU after BM irradiation for multiple primary tumor histologies. We identified 138 BM cases reviewed at our multi-disciplinary SRS Tumor Board (TB) for RU of ARE versus TP on MRI following SRS between 2015-2022. Target diameter (mm), histology, location, and SRS dose (Gy) on initial treatment and lesion diameter, associated symptoms, and supportive medications at the time of TB presentation were extracted from the medical record. Final lesion etiology, use of any intervention, and neurologic deficits upon DD were documented. Time from RU to DD was calculated. Median time from SRS to initial RU was 11.3 months (IQR 5.5-18.2). Median RU lesion diameter was 14.0 (IQR 8.0-20.0). At the time of RU, 43% of patients were symptomatic, 28% and 4% requiring steroids and bevacizumab, respectively. Time to DD following RU was &amp;gt; 6 and 12 months in 28% and 8% of patients, respectively (maximum 47 months). Median lesion diameter at DD was 16.0 mm (IQR 10.3-24.0). Most (54%) had a DD of ARE, while 41% had TP; 23% and 77% were diagnosed pathologically and radiographically, respectively. Upon DD, 41% underwent local intervention with surgery and/or re-irradiation and 25% had a new neurologic deficit, including weakness (7%), ataxia (5%), and aphasia (4%). In an interdisciplinary setting, it took &amp;gt; 6 months to reach a DD after RU in &amp;gt; 25% of patients previously irradiated for BM. Diagnostic uncertainty and delay may lead to sub-optimal outcomes and symptom burden. Improved characterization of post-SRS imaging findings is needed in this population.

Significance of the auditory meatus inferior wall cartilage in the surgical treatment of congenital first branchial cleft anomalies in children

ObjectiveTo investigate the clinical significance of the inferior wall cartilage of the auditory meatus in surgical treatment of congenital first branchial cleft anomalies (CFBCAs) in children.MethodsTwenty children diagnosed with CFBCAs...

The pathology of canine mammary candidiasis with embolic dissemination in a dog

Candidiasis is a fungal disease caused by Candida albicans or other members of the genus Candida. Descriptions of candidiasis are comparatively reduced in veterinary relative to human medicine, with no cases of mammary candidiasis being identified in pet animals. This report presents the cytological, pathological, and molecular findings of mammary candidiasis with embolic dissemination in a postpartum dog. A 1-year-old, female Shih-tzu dog that had recently given birth was admitted to a veterinary teaching hospital in Southern Brazil after repeated episodes of intermittent mammary disease and a neurological syndrome. The dog was euthanized due to worsened clinical status and poor prognosis despite adequate clinical therapy and was submitted for routine post-mortem evaluation to determine the cause of the neurological manifestations. Cytological analysis of purulent mastitis identified intralesional fungal hyphae. Gross evaluation revealed multiple masses within the kidneys, liver, myocardium, pancreas, and brain. Routine histopathology and histochemistry identified fungal nephritis, hepatitis, myocarditis, pancreatitis, and encephalitis associated with intralesional fungal hyphae, frequently with fungal emboli and vasculitis. Pure cultures of C. albicans were obtained from fragments of the masses observed at the myocardium and kidneys, with the typical germ tube of C. albicans being identified by microscopic evaluation. A PCR assay that targeted the ITS1 and 4 generic regions of fungi, amplified the desired amplicon, and direct sequencing confirmed C. albicans. Immunohistochemical and molecular assays designed to identify common infectious disease pathogens of dogs did not confirm the participation of canine distemper virus, canine parvovirus, or canine adenovirus in the target tissues of this dog. These findings suggest that this dog suffered an initial cutaneous lesion, that probably served as portal of entry to the mammary gland, resulting in mammary candidiasis with subsequent embolic dissemination to multiple organs. This report represent the first description of mammary candidiasis in pet animals and probably one of the few pathological descriptions of mammary candidiasis in domestic animals. In this case, the cause of the fungal infection was probably associated with factors intrinsic to abdominal surgery, pregnancy, and the utilization of antibiotics.

Concurrent finding of Breast cancer and axillary Lymph nodes in Receptor Positive Patients

Background and Objectives: The most frequent site of disease involvement in breast cancer that has progressed from the initial lesion is the axillary lymph nodes (ALN). There are still no reliable ways to anticipate ALN status prior to surgery, despite sentinel node biopsy being a reliable means of managing ALN. Materials and Methods: This was a retrospective study of female patients with invasive breast cancer at Tertiary care hospital between January 2020 and January 2023. The clinical data and tumor character­istics for all invasive breast cancers (425) had been collected in breast cancer database. This study was approved by the institu­tional review board and ethics committee. Breast cancer patients who had undergone surgery were identified. The exclusion criteria were: 1) ductal carcinoma in situ; 2) neoadjuvant therapy; 3) bilateral invasive breast cancer; and 4) patients without breast-conserving surgery with ALND or sentinel lymph node sampling or modified radical mastectomy. SVM was used for analysis. Results: Of these, 242 patients had positive ALNM. The mean tumor size was 24.4 mm (SD=1.5); 38% of the patients had T1 tumors (＜20 mm), followed by 52% with T2 tumors and 10% with T3 tumors. The histology grade was predominantly grade II (57%), with 28% grade III and 15% grade I tumors. Lymph vascular invasion was found in 200 patients (47%). The ER/PR/HER2 profile showed 270 patients (63.5%) had luminal A type tumors, followed by 16.5% with triple-negative tumors, 13.1% with luminal B type tumors, and 6.9% with HER2-positive tumors. A higher AUC value indicated a better diagnostic perfor­mance. The AUC value of this study was 0.754 by SVM. Conclusion: It is possible to forecast ALN status using a model that is just dependent on clinically common pathologic data derived from the source tumor. This could support the surgeon's decision-making for ALN management and breast cancer counseling.

Comparison of bleomycin polidocanol foam vs electrochemotherapy combined with polidocanol foam for treatment of venous malformations

ObjectiveThis study aims to investigate the difference in safety and efficacy between two treatments for venous malformations (VMs), electrochemotherapy combined with polidocanol foam (ECP) and bleomycin polidocanol foam (BPF), providing alternative therapies for VMs. MethodsWe conducted a retrospective review of 152 patients with VMs treated with ECP and BPF. Pre- and post-treatment magnetic resonance images (MRIs) were collected, and clinical follow-up assessments were performed. Imaging results were used to calculate lesion volume changes. Clinical outcomes included changes in pain and improvements in perceived swelling. Patients were followed up at 1 week and 6 months after surgery. All emerging complications were documented in detail. ResultsOf the 152 patients, 87 (57.2%) received BPF treatment, and 65 (42.8%) received ECP treatment. The most common location of VMs was the lower extremities (92/152; 60.2%), and the most common symptom was pain (108/152; 71.1%). Forty-three patients had previously undergone therapy in the BPF group (43/87; 49.4%), whereas 30 patients had received prior treatment in the ECP group (30/65; 46.2%). The study found that the percentage of lesion volume reduction in the BPF group was not significantly different from that in the ECP group (75.00% ± 17.85% vs 74.69% ± 8.48%; P = .899). ECP was more effective when the initial lesion volume was greater than 30 mL (67.66% ± 12.34% vs 73.47% ± 8.00%; P = .048). Patients treated with BPF had significantly less posttreatment pain than those treated with ECP, in different baseline lesion size. In the overall sample, pain relief was significantly higher in the BPF group than in the ECP group (4.21 ± 1.19 vs 3.57 ± 0.76; P = .002). However, there was no difference in pain relief between the two groups for the treatment of initially large VMs (4.20 ± 0.94 vs 3.70 ± 0.87; P = .113). The ECP group was significantly more likely to develop hyperpigmentation (5/87; 5.75% vs 11/65; 16.92%; P = .026) and swelling (9/87; 10.34% vs 16/65; 24.62%; P = .019) 1 week after surgery than the BPF group. ConclusionsOur study demonstrates that both BPF and ECP are effective treatments for VMs, with BPF being a safer option. ECP is a better choice for patients with the initial lesion volume greater than 30 mL, but it is more likely to lead to early swelling and hyperpigmentation.

Intraductal papillary neoplasm of the bile duct: The new frontier of biliary pathology.

Intraductal papillary neoplasms of the bile duct (IPNBs) represent a rare variant of biliary tumors characterized by a papillary growth within the bile duct lumen. Since their first description in 2001, several classifications have been proposed, mainly based on histopathological, radiological and clinical features, although no specific guidelines addressing their management have been developed. Bile duct neoplasms generally develop through a multistep process, involving different precursor pathways, ranging from the initial lesion, detectable only microscopically, i.e. biliary intraepithelial neoplasia, to the distinctive grades of IPNB until the final stage represented by invasive cholangiocarcinoma. Complex and advanced investigations, mainly relying on magnetic resonance imaging (MRI) and cholangioscopy, are required to reach a correct diagnosis and to define an adequate bile duct mapping, which supports proper treatment. The recently introduced subclassifications of types 1 and 2 highlight the histopathological and clinical aspects of IPNB, as well as their natural evolution with a particular focus on prognosis and survival. Aggressive surgical resection, including hepatectomy, pancreaticoduodenectomy or both, represents the treatment of choice, yielding optimal results in terms of survival, although several endoscopic approaches have been described. IPNBs are newly recognized preinvasive neoplasms of the bile duct with high malignant potential. The novel subclassification of types 1 and 2 defines the histological and clinical aspects, prognosis and survival. Diagnosis is mainly based on MRI and cholangioscopy. Surgical resection represents the mainstay of treatment, although endoscopic resection is currently applied to nonsurgically fit patients. New frontiers in genetic research have identified the processes underlying the carcinogenesis of IPNB, to identify targeted therapies.

Remineralization effect of NaF, NaF with TCP, NaF with CPP-ACP and NaF with CXP varnishes on newly erupted first permanent molars: A randomized controlled trial.

The aim of this study was to evaluate the remineralization effect of NaF, NaF with TCP, NaF with CPP-ACP and NaF with CXP varnishes on newly erupted first permanent molars using laser fluorescence (LF) method. The study was a randomized, double-blind, controlled trial with four parallel groups. The study was carried out in 48 high caries-risk children (DMFS >8), aged 6-7 years with newly erupted permanent first molars (initial lesion with 13 < LF value<30). A total of 140 teeth were divided randomly into four groups (n = 35): G1.Duraphat Varnish containing 5% NaF, G2. Clinpro™ White Varnish containing 5% NaF with TCP, G3.Embrace™ Varnish containing 5% NaF with CXP, G4. MI Varnish containing 5% NaF with CPP-ACP. All dental treatments of the patients were completed before the varnish application. The varnishes were applied to the targeted teeth at baseline, 1 and 3 months. Patients were called for follow-up appointments at 1, 3 and 6 months, and LF scanning was used to monitor mineralization changes. Data were analysed statistically by Wilcoxon signed-rank and Mann-Whitney U-tests. In total, 40 children (122 teeth) completed the trial. At the end of 6 months, the amount of reduction in LF values (indicating remineralization) are as follows: NaF with CXP(6.87 ± 4.32) < NaF with TCP(7.36 ± 7.05) < NaF(7.40 ± 7.03) < NaF with CPP-ACP(8.33 ± 4.90). All of the varnishes resulted in significant decrease in LF measurements and there was no significant difference between control (NaF alone) group and other groups. Only MI varnish had a significantly greater remineralization effect than Embrace™ Varnish (p < 0.05). As a non-invasive approach, CPP-ACP, TCP and CXP containing NaF varnishes have the potential to remineralize initial caries lesions on permanent first molars in high caries-risk children.

The Role of Vitamin A, Vitamin C and Vitamin E for Chemoprevention of Oral Leukoplakia

Introduction: Oral leukoplakia is a prevalent oral mucosal lesion known to undergo malignant transformation, posing a significant public health concern worldwide, primarily attributable to tobacco use. This study aims to investigate the potential preventive effects of vitamins A, C, and E on oral leukoplakia. We conducted a cross-sectional study at the Department of Oral &amp; Maxillofacial Surgery, Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh, over a one-year period from March 2017 to March 2018. Methods: Study Population: We enrolled a total of 43 patients diagnosed with oral leukoplakia attending the Outpatient Department (OPD) of the Oral &amp; Maxillofacial Surgery Department. Data Collection: Patients were assessed at 6, 12, and 24-week intervals, during which data were collected using standardized data sheets. Lesion size was measured in square centimeters, and lesion color was recorded through photography. Adverse drug reactions were monitored based on patient complaints during follow-up. Histopathological Evaluation: Histopathological evaluations were performed both before the study and at the conclusion of the study to assess any changes in tissue characteristics. Outcome Variables: The primary outcome variables of interest were clinical response, histopathological findings, and complications associated with the treatment. Results: The study population had a mean age of 44.95±10.42 years, with an age range from 22 to 60 years. The male-to-female ratio was 1.3:1. The average duration of the lesions was 14.81±4.82 months, with a range of 6 to 24 months. Lesions were most commonly located in the right buccal mucosa (41.9%), followed by the left buccal mucosa (27.4%). The mean initial lesion size was 4.08±1.95 cm², ranging from 1 to 8 cm². After 24 weeks, 11.63% of patients showed complete improvement. All patients initially presented with white lesions, with a reduction to 97.7% after 6 weeks, 88.4% after 12 weeks, and 69.8% after 24 weeks. Mild adverse drug reactions were reported in 11.7% of patients after 6 weeks and 2.3% after 12 and 24 weeks. Complete remission was observed in 11.6% of patients, and moderate improvement (41–90%) in 37.3%. Notably, one-third of patients experienced a significant color change in their lesions, and adverse drug reactions decreased during subsequent follow-up. Conclusion: This cross-sectional study indicates potential benefits of Vitamin A, Vitamin C, and Vitamin E in mitigating oral leukoplakia symptoms, such as reduced lesion size and color improvement, with fewer adverse reactions observed. However, larger, controlled trials are necessary to establish the definitive efficacy of this vitamin combination. Update Dent. Coll. j: 2023; 13(2): 23-29

Evaluation of experimental resin infiltrant containing nanohydroxyapatite on color stability and microhardness in demineralized enamel.

The aim of the study was to evaluate the effect of the addition of 10% nanohydroxyapatite in an experimental resin infiltrant on color stability and mineral loss. Bovine enamel blocks were randomized into five groups (n = 27/group): SE (sound enamel); ICL (initial caries lesion); I (Icon®); E (experimental infiltrant); EH (experimental infiltrant containing 10% nanohydroxyapatite). Color evaluation (n = 15) was performed and CIEL*a*b* values were obtained at points T0 (baseline), T1 (14days immersed on coffee solution), and T2 (28days immersed) and data were calculated ∆E00, ∆WID, ∆L*, ∆a*, and ∆b*. Cross-sectional microhardness (n = 12) was performed and lesion area (∆S) was calculated. Images were obtained with polarized light optical microscopy at 40 × magnification (n = 5). In color stability results, there was significant difference between time (14 and 28days); ICL demonstrated significant difference among treated groups in all measures (∆L*, ∆a*, ∆b*, ∆E00, ∆WID) regardless of time; I and E demonstrated similar behavior on those measures and EH differed from I in ∆L*. For ∆S, ICL group showed a significant difference compared to I and EH groups, but did not differ from E. The nanohydroxyapatite incorporation suggested an effective mineral recovery on initial caries lesion in depth; however, it showed high color variation, such as Icon. In terms of ∆S, I and EH had lower mineral loss, suggesting a reinforcement on initial caries lesion. Commercial and experimental infiltrants containing nanohydroxyapatite present low color stability and might reinforce mineral in initial caries lesion.

Evaluation of Physicochemical Properties of a Hydroxyapatite Polymer Nanocomposite for Use in Fused Filament Fabrication.

Over the last decade, there has been an increasing interest in the use of bioceramics for biomedical purposes. Bioceramics, specifically those made of calcium phosphate, are commonly used in dental and orthopaedic applications. In this context, hydroxyapatite (HA) is considered a viable option for hard tissue engineering applications given its compositional similarity to bioapatite. However, owing to their poor mechanobiology and biodegradability, traditional HA-based composites have limited utilisation possibilities in bone, cartilage and dental applications. Therefore, the efficiency of nano HA (nHA) has been explored to address these limitations. nHA has shown excellent remineralising effects on initial enamel lesions and is widely used as an additive for improving existing dental materials. Furthermore, three-dimensional printing (3DP) or fused deposition modelling that can be used for creating dental and hard tissue scaffolds tailored to each patient's specific anatomy has attracted considerable interest. However, the materials used for producing hard tissue with 3DP are still limited. Therefore, the current study aimed to develop a hybrid polymer nanocomposite composed of nHA, nanoclay (NC) and polylactic acid (PLA) that was suitable for 3DP. The nHA polymer nanocomposites were extruded into filaments and their physiochemical properties were evaluated. The results showed that the addition of nHA and NC to the PLA matrix significantly increased the water absorption and contact angle. In addition, the hardness increased from 1.04 to 1.25 times with the incorporation of nHA. In sum, the nHA-NC-reinforced PLA could be used as 3DP filaments to generate bone and dental scaffolds, and further studies are needed on the biocompatibility of this material.

Evaluation of Remineralization Potential of Preventive Regimen Containing Herbal-Based Compared to Fluoride-Based Toothpastes in High Caries Risk Patients with Initial Carious Lesions: A Randomized Clinical Trial

Evaluation of Remineralization Potential of Preventive Regimen Containing Herbal-Based Compared to Fluoride-Based Toothpastes in High Caries Risk Patients with Initial Carious Lesions: A Randomized Clinical Trial

Remineralization Efficacy Of Gum Arabic Varnish Vs Fluoride Varnish And Cpp-Acp With Fluoride Based Varnish In Initial Carious Lesions Over 6 Months Follow Up: A Randomized Controlled Clinical Trial

Remineralization Efficacy Of Gum Arabic Varnish Vs Fluoride Varnish And Cpp-Acp With Fluoride Based Varnish In Initial Carious Lesions Over 6 Months Follow Up: A Randomized Controlled Clinical Trial

Distribution and Failure Patterns of Primary Central Nervous System Lymphoma Related to Hippocampus

Hippocampus (HC) injury by conventional whole brain radiotherapy (C-WBRT) contributes to the neurocognitive decline in primary central nervous system lymphoma (PCNSL). Hippocampal avoidance (HA-WBRT) could minimize neurocognitive impairment by reducing the radiation dose to HC. However, its feasibility in PCNSL has not been examined regarding the incidence of HC involvement and failures. In this retrospective study, we assessed the risk of hippocampal area involvement at diagnosis and after treatments in PCNSL patients. We identified 278 immunocompetent PCNSL patients diagnosed between 2000 and 2020. After high dose methotrexate-based induction chemotherapy, patients were observed or given consolidation therapy including RT, cytarabine alone, or autologous stem cell transplantation (ASCT). HC was contoured on T1 MRI image and expanded with a 5mm margin, generating hippocampal avoidance region (HAR). The extent of initial and recurrent lesions was evaluated using pre-induction and post-consolidation T1 contrast-enhanced MRI images. HC failure was defined as recurrence or progression at HAR and those who progressed after induction were excluded. The median follow up was 38.7 months (3.1-239.4). Of 278 patients diagnosed with PCNSL, 39.9% of them had initial lesions at HAR (Figure 1a). After induction therapy, 212 evaluable patients received following treatments: RT (n = 145, 68.4%) consisting of C-WBRT (n = 114), HA-WBRT (n = 23), and focal RT (n = 8), observation (n = 38, 17.9%), cytarabine only (24, 11.3%), and ASCT (n = 5, 2.4%). Intracranial failures occurred in 47.6% (n = 101) of patients, with 33.7% (n = 34) of them in HAR (Figure 1b). The multivariate analysis identified multifocal disease (HR 3.86, 95% CI 1.15-9.73, p = 0.004) as the only factor associated with the risk of HC failure. Those with unifocal lesion outside HAR showed the lowest HC failure rate, 7.0%, while the highest HC failure rate, 25.4% was observed in the subgroup with multifocal disease within HAR at diagnosis (Figure 2a). In the lowest risk group (unifocal lesion outside HAR, n = 66), C-WBRT was not significantly associated with HC failure (HR 0.57, CI 0.09-3.33, P = .572, Figure 2b) or intracranial failure (HR 0.88, CI 0.40-1.91, P = .748). Our data suggest the HA-WBRT could be explored in patients whose lesion is unifocal and located outside HAR. For patients without initial HAR involvement, hippocampal including WBRT did not significantly change HC failure. Further prospective study will be warranted to assess the feasibility of HA-WBRT in the subgroup with low risk of HC failure.

Longitudinal radiological follow-up of individual level non-ischemic cerebral enhancing lesions following endovascular aneurysm treatment

BackgroundNon-ischemic cerebral enhancing (NICE) lesions following aneurysm endovascular therapy are exceptionally rare, with unknown longitudinal evolution.ObjectiveTo evaluate the radiological behavior of individual NICE lesions over time.MethodsPatients included in a retrospective...