Riparin II-type benzamides as novel antibiofilm agents against dermatophytes: chemical synthesis, in vitro, ex vivo and in silico evaluation.

BACKGROUND: The ability of dermatophytes to develop biofilms in host tissues confers physical and biochemical resistance to antifungal drugs. Therefore, research to find new compounds against dermatophyte biofilm is crucial. OBJECTIVES: To evaluate the antifungal activity of riparin II (RIP2), nor-riparin II (NOR2) and dinor-riparin II (DINOR2) against Trichophyton rubrum, Microsporum canis and Nannizzia gypsea strains. METHODS: Initially, we determined the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of benzamides. We evaluated the inhibitory effects on the development of dermatophyte biofilms using in vitro and ex vivo models. Finally, we built three-dimensional models of the sulphite pump Ssu1 to investigate the interactions with the benzamides by molecular docking. RESULTS: RIP2 showed a broad spectrum of activity against T. rubrum, M. canis and N. gypsea, whereas NOR2 and DINOR2 were more selective. Furthermore, the shortening of the carbon chain from RIP2 benzamide to NOR2 and DINOR2 homologs caused a decrease in the MIC values. The benzamides reduced biofilm production and viability in vitro (P < 0.05) at MIC. This result was similar ex vivo in human nail fragments tests, but NOR2 and DINOR2 showed significant results at 2xMIC (P < 0.05). We constructed a model of the Ssu1 protein for each dermatophyte with high similarity. Molecular docking showed that the benzamides obtained higher binding energy values than ciclopirox. CONCLUSIONS: Our study shows the antibiofilm potential for riparin II-type benzamides as new drugs targeting dermatophytes by inhibiting the Ssu1 protein.

It was not possible to detect BRAF V600E mutation in circulating cell-free DNA from patients with ameloblastoma: A diagnostic accuracy study.

BACKGROUND: The objective of this study is to evaluate the diagnostic accuracy of plasma-based liquid biopsy for the detection of the BRAF V600E mutation in circulating cell-free DNA from patients with ameloblastoma. METHODS: This is a prospective diagnostic accuracy study conducted based on the Standards for Reporting Diagnostic Accuracy recommendations. The index test was the plasma-based liquid biopsy, whereas the reference standard was the conventional tissue biopsy. The target condition was the detection of BRAF V600E mutation. The study population consisted of individuals with ameloblastoma recruited from three tertiary hospitals from Brazil. A negative control group composed of three individuals with confirmed wild-type BRAF lesions were included. The participants underwent plasma circulating cell-free DNA and tumor tissue DNA isolation, and both were submitted to using competitive allele-specific TaqMan™ real-time polymerase chain reaction technology mutation detection assays. Sensitivity and specificity measures and positive and negative predictive values were calculated. RESULTS: Twelve patients with conventional ameloblastoma were included. BRAF V600E mutation was detected in 11/12 (91.66%) ameloblastoma tissue samples. However, the mutation was not detected in any of the plasma-based liquid biopsy circulating cell-free DNA samples in both ameloblastomas and negative control group. The sensitivity and specificity of plasma-based liquid biopsy for the detection of the BRAF V600E mutation in circulating cell-free DNA was 0.0 and 1.0, respectively. The agreement between index test and reference standard results was 26.66%. CONCLUSION: Plasma-based liquid biopsy does not seem to be an accurate method for the detection of the BRAF V600E mutation in circulating circulating cell-free DNA from patients with ameloblastoma, regardless of tumor size, anatomic location, recurrence status, and other clinicopathological features.

Gelatin methacryloyl hydrogel with and without dental pulp stem cells for TMJ regeneration: An in vivo study in rabbits.

BACKGROUND: In the last decade, tissue-engineering strategies for regenerating the temporomandibular joint (TMJ) have been investigated. This may be a promising strategy for the minimally invasive restoration of joint integrity. OBJECTIVES: To evaluate whether dental pulp stem cells (DPSCs) loaded in a light-occured hydrogel made of gelatin methacryloyl (GelMA) enhance the regeneration of osteochondral defects in the rabbit TMJ. MATERIALS AND METHODS: Defects were filled with GelMA alone (control group; n = 4) or filled with GelMA loaded with rabbit DPSCs (experimental group; n = 4), In one group, the TMJ capsule was opened without creating a defect (sham group; n = 2). The following micro-CT parameters were analysed: bone volume to total volume ratio (BV/TV%) and bone mineral density (BMD). Histological evaluation was performed to assess cartilage regeneration features. A semi-quantitative scoring system was also used to evaluate the defects. RESULTS: All groups had no statistical difference regarding the micro-CT parameters. The highest mean healing score was found for the experimental group. After 4 weeks, there were no signs of hydrogel in either group or no signs of inflammation in the adjacent tissues. The tissue formed in the defect was dense fibrous connective tissue. CONCLUSION: Adding DPSCs to GelMA did not provide a regenerative enhancement in TMJ osteochondral defects. This resulted in similar micro-CT parameters after 4 weeks of healing, with improved signs of subchondral bone regeneration but no cartilage regeneration.

Does BRAF V600E mutation affect recurrence rate of ameloblastomas? Systematic review and meta-analysis.

OBJECTIVE: The objective of this systematic review with meta-analysis was to critically evaluate the available data on the association of the BRAF V600E mutation and recurrence rate of ameloblastomas. MATERIALS AND METHODS: This systematic review was registered in Prospero (CRD42020183645) and performed based on the PRISMA statement. A comprehensive search in PubMed, Web of Science, Scopus and Cochrane Library databases was performed in order to answer the question "Does BRAF V600E mutation affect recurrence rate of ameloblastomas?" Methodological quality and risk of bias of the selected studies were assessed with JBI Critical Appraise Tool. Meta-analysis of quantitative data was conducted with RevMan 5.3 and Jamovi 2.3. RESULTS: The initial search identified 302 articles, and 21 met the inclusion criteria. A total of 855 subjects with ameloblastoma were included in the analysis. The pooled measures for frequency of BRAF V600E mutation was 65.30% (95% CI: 0.56-0.75; p < .001; I2 = 90.85%; τ = 0.205; p < .001), and the pooled recurrence rate was 25.30% (95% CI: 0.19-0.31; p < .001; I2 = 79.44%; τ = 0.118; p < .001). No differences in recurrence rate were observed between the BRAF V600E and wild type BRAF ameloblastomas, with a pooled Odds Ratio of 0.93 (95% CI: 0.56-1.54; p = .78; I2 = 31%; p = .09). CONCLUSIONS: BRAF V600E mutation is a frequent event in ameloblastomas, but does not increase nor reduce its recurrence rate, and thus have a limited value in predicting its prognosis.

Diagnostic accuracy of immunohistochemistry compared with molecular tests for detection of BRAF V600E mutation in ameloblastomas: Systematic review and meta-analysis.

OBJECTIVE: The objective of this systematic review with meta-analysis was to critically evaluate the available data on sensitivity and specificity of IHC compared with molecular tests in the detection of BRAF V600E mutation in ameloblastomas. MATERIALS AND METHODS: This systematic review was performed based on the PRISMA statement and registered in Prospero (CRD42021259117). PubMed, Web of Science, Scopus, and Cochrane Library databases were searched for observational studies to answer the question "What is the diagnostic accuracy of immunohistochemistry compared with molecular tests for the diagnosis of BRAF V600E mutation in ameloblastomas?". Methodological quality and risk of bias assessment of the selected studies were based on the QUADAS-2. Meta-analysis based on hierarchical SROC curve model and summary measures for sensitivity and specificity were computed. RESULTS: A total of 226 records were found, but only 05 articles met the inclusion criteria, with 277 FFPE specimens of ameloblastoma included in the quantitative analysis. The sensitivity of the IHC compared to molecular tests ranged from 0.71 to 1.00, while all of the included studies showed perfect specificity (1.00). Pooled measures for sensitivity and specificity were 0.95 [95% CI 0.89, 1.00] and 1.00 [95% CI 0.95, 1.00], respectively. The diagnostic odds ratio was 4.05, and the AUC for SROC curve was calculated as 0.979. CONCLUSIONS: BRAF V600E-specific IHC using VE1 antibody showed extremely high sensitivity and specificity when compared with molecular tests in the detection of the mutation in ameloblastomas.

A catastrophic seronegative anti-phospholipid syndrome: case and literature review.

BACKGROUND: Antiphospholipid Syndrome (APS) is a multisystemic autoimmune disease characterized by arterial and venous thrombosis and / or obstetric morbidity in the presence of at least one circulating anti-phospholipid antibody. The spectrum of vascular events varies from deep venous thrombosis to catastrophic APS, a rare form characterized by acute multiorgan thrombosis and high mortality. CASE REPORT: We present the case of a 32-week pregnant woman arriving in the hospital emergency room with bilateral acute lower limb ischemia. In the obstetric evaluation, fetal death was declared. Computerized Tomography angiography showed pulmonary embolism of both pulmonary arteries, areas of splenic and right renal infarction and multiple arterial and venous thrombosis. The patient underwent urgent caesarean section and axillary-bifemoral bypass. No events registered. In the postoperative period, in an intensive care unit, treatment with rituximab and plasmapheresis were added to anticoagulant therapy. The laboratorial investigation was negative for thrombophilia and autoimmune diseases. CONCLUSION: Catastrophic APS develops quickly, with multiorgan involvement and high mortality rate. The presented case poses a multidisciplinary challenge, with the surgical approach of extra-anatomical revascularization being less invasive and guaranteeing immediate perfusion of the lower limbs. Although the serological tests were negative for anti-phospholipid antibodies, this case hardly fits into another diagnosis. Therefore, it was treated as a catastrophic APS, having shown a favorable evolution.

Surface Free Energy, Interaction, and Adsorption of Calcium and Phosphate to Enamel Treated with Trimetaphosphate and Glycerophosphate.

This study aimed to evaluate the surface (γs) and interaction (ΔGiwi) free energy and calcium (Ca2+) and phosphate (PO43-) adsorption to dental enamel treated with sodium trimetaphosphate (TMP) or calcium glycerophosphate (CaGP) that had or had not been exposed to CaPO4-containing solutions. Bovine enamel blocks (n = 192; 24 blocks/group) were treated (2 mL/block; 2 min) with TMP (0%, 1%, 3%, and 9%) and CaGP (0, 0.25, 0.5, and 1%) or exposed to a CaPO4-containing solution. The adsorption of these compounds by enamel was assessed before and after treatment. γs and ΔGiwi and their apolar (γsLW and ΔGiwiLW) and polar (γsAB and ΔGiwiAB) components and acid-base interactions (γs+/γs-) were determined by the contact angles. The data were subjected to ANOVA, followed by the Student-Newman-Keuls test (p < 0.05). The adsorption of TMP was dose dependent (p < 0.001), and it reduced γs and γsAB and increased ΔGiwiAB (ΔGiwi > 0) and γs- when compared with the group without TMP (p < 0.001). The immersion in CaPO4-containing solution increased γs and γsAB and reduced ΔGiwiAB (ΔGiwi > 0) and γs- (p < 0.001). There was a correlation between the adsorption of TMP and Ca2+ (r = 0.916; p < 0.001) and PO43- (r = 0.899; p < 0.001). The adsorption of CaGP on the enamel was dose dependent (p < 0.001), reducing γs, ΔGiwiAB (ΔGiwi < 0), γsLW, and γs- when compared to the group without CaGP (p < 0.001). When exposed to the CaPO4-containing solution, there was an increase in ΔGiwiAB (ΔGiwi > 0), γsLW, and γs- and a decrease in γsAB (p < 0.001) without adsorption of Ca2+ by enamel. It may be concluded that TMP and CaGP were adsorbed onto the enamel, producing hydrophilic and hydrophobic surfaces, respectively. TMP produces electron donor sites that induce Ca2+ adsorption, while CaGP releases Ca2+ into the medium.

Clinical and demographic characteristics of primary progressive multiple sclerosis in Argentina: Argentinean registry cohort study (RelevarEM).

BACKGROUND: Primary progressive multiple sclerosis (PPMS) is an infrequent clinical form of multiple sclerosis (MS). Scarce information is available about PPMS in Latin America. The aim of this work is to describe the clinical and demographic characteristics of PPMS patients in Argentina. MATERIAL AND METHODS: RelevarEM is a longitudinal, strictly observational registry in Argentina. Clinical and epidemiological data from PPMS patients were described. RESULTS: There were 144 cases of PPMS. They represented 7% of MS patients. The mean age was 44.1 years. The female:male ratio was 1.08. The mean Expanded Disability Status Scale (EDSS) score was 5.5 and the mean disease evolution time was 10.6 years. Oligoclonal bands were found in 72.9%. At the time of diagnosis, magnetic resonance imaging showed spinal cord lesions in 82.6% and contrast-enhancing brain lesions in 18.1% of patients. Almost one third of patients were treated with a disease-modifying drug, and ocrelizumab was the most frequently used (55.8%). CONCLUSIONS: PPMS is an infrequent subtype of MS and its recognition is of the highest importance as it has its own evolution, treatment, and prognosis. The importance of our research resides in providing local data and contributing to a better understanding of PPMS and its treatment in Latin America.

Multiple sclerosis and neuromyelitis optica spectrum disorders in Argentina: comparing baseline data from the Argentinean MS Registry (RelevarEM).

The objective of this study was to describe and compare the baseline epidemiological data of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD) patients included in RelevarEM (Clinical Trials registry number NCT03375177). METHODS: RelevarEM is a longitudinal, strictly observational MS and NMOSD registry in Argentina. Epidemiological and comorbidity data from MS and NMOSD patients were described and compared. For comorbidities, the Charlson comorbidity index (CCI) was used to calculate the burden at entry. CCI was stratified in 0 and ≥ 1 and described for the entire cohort. RESULTS: A total of 1588 and 75 MS and NMOSD patients (respectively) were included. For MS patients, the mean age was 42 ± 7 years, female sex 65.3%, mean EDSS 2, and mean disease duration 8 ± 6 years. In NMOSD, the mean age was 40 ± 7 years, female sex 78.7%, mean disease duration 5 ± 3.5 years, and mean EDSS 2.5. The most frequent MS phenotype was RRMS in 82.4%. In MS, the CCI was 0 in 85.8.2% while ≥ 1 was in 14.2% of patients. Regarding phenotype stratification, CCI ≥ 1 was 3.9% in CIS, 13.5% in RRMS, 28.7% in SPMS, and 17.4% in PPMS (p < 0.001 between groups). In NMOSD, the CCI was 0 in 64% while ≥ 1 was in 36%. The MS/NMOSD ratio found was 21/1. CONCLUSIONS: This is the first analysis of the longitudinal Argentinean registry of MS and NMOSD describing and comparing conditions that contributes to provide reliable real-world data in the country.

Is Single-Puncture TMJ Arthrocentesis Superior to the Double-Puncture Technique for the Improvement of Outcomes in Patients With TMDs?

PURPOSE: Arthrocentesis is a common treatment for temporomandibular joint disorders. Although modifications of the standard double-puncture technique have been described, no consensus has been reached regarding which is the best. The aim of the present study was to compare the outcomes of the single- and double-puncture arthrocentesis techniques (SPT and DPT, respectively). MATERIALS AND METHODS: A systematic review following the PRISMA (preferred reporting items for systematic reviews and meta-analyses) guidelines was performed. Two independent reviewers conducted electronic searches in the MEDLINE/PubMed, Cochrane Library, and Scopus databases for relevant studies reported up to January 2019. Studies comparing type I SPT (only 1 cannula) or type II SPT (2 soldered cannulas) to conventional DPT were considered. Data regarding the maximal mouth opening (MMO), joint pain, and operative time were extracted for the meta-analysis. In the case of statistically significant heterogeneity (P < .10), a random effects model was used to assess the significance of the treatment effects. Otherwise, a fixed effects model was used. The included randomized controlled trials (RCTs) were assessed for methodologic quality using the Cochrane Collaboration tool. RESULTS: Nine studies were included for qualitative synthesis. Two were suitable for quantitative synthesis per outcome. The meta-analysis did not find any differences between SPT and DPT in relation to the MMO. However, in relation to joint pain, the results slightly favored the use of DPT. No differences in operative time were found between type I SPT and DPT (P = .49). CONCLUSIONS: The present study found no differences between the SPT and DPT in relation to the MMO, and no difference was found in operative time between the DPT and type I SPT. Because of the heterogeneity between studies, it might be interesting to conduct more homogeneous RCTs to elucidate which technique results in better clinical outcomes.

Intraoral Approach for Surgical Treatment of Psammomatoid Juvenile Ossifying Fibroma.

Psammomatoid juvenile ossifying fibroma (PJOF) is a rare benign tumor that usually affects the paranasal sinuses, orbit, and skull. In most cases, extensive incisions are necessary for full access to the tumor site. The aim of this paper is to report a case of extensive PJOF in which an intraoral surgical approach was performed with complete excision of the tumor. A female patient, 18-year old had a deforming volume increase in the region of the left facial middle third with an approximate evolution time of 2 years. She complained of headache, epiphora in the left eye, and total obstruction of the left nostril. Extraoral examination showed facial asymmetry with dystopia, ocular proptosis, and considerable sclera exposition of the left eye. Tomography examination showed a mixed aspect lesion on the left side of the face, well delimited. The intraoral surgical approach was chosen for the excision of the lesion. Under general anesthesia and nasotracheal intubation, total resection was performed, followed by exodontia of the directly involved teeth. In the definitive histopathological examination, the diagnosis was confirmed. The patient is currently with 2 years and 6 months of postoperative follow-up and has good healing of intraoral surgical wounds and stable occlusion. Extraoral examination showed harmonic projection of the facial middle third, but still with excessive exposure of the sclera of the left eye due to the defect in the orbital floor. The surgical treatment of PJOF was possible by intraoral approach, even taking into account the limitations of the access and the complexity of the anatomy of the facial bones involved.

Suitability of Wrist External Fixator for Treatment of Mandibular Fracture.

The mandibular fracture is one of the most commonly fractures of the facial bones. In high-energy traumas, a comminuted mandible fracture may occur. The closed reduction with external fixator is an interesting alternative for these types of fractures. The aim of this article is to report the case of a patient with comminuted fracture in the right mandibular body, whose surgical treatment was the noninvasive reduction of fracture and stabilization using a Colles' wrist external fixator. After 1 year of follow-up, the patient is without complaints, with satisfactory dental occlusion, adequate contour, and mandibular alignment. External fixation with wrist orthopedic fixators adapted to the mandible provides many advantages owing to its versatility and simplicity of use. Therefore, this method should be remembered as a valid and affordable option for the treatment of complex lesions when indicated correctly.

Cervical-thoracic necrotizing fasciitis of odontogenic origin in a diabetic patient: a case report.

Necrotizing fasciitis (NF) is a severe bacterial infection with rapid and aggressive progression. The infection generally affects individuals with comorbid conditions that lead to immunologic and microvascular deficiencies. It is characterized by necrosis of tissues, mainly in the extremities, trunk, and perineum, and is rarely found in the head and neck. This case report describes the course of NF in a 55-year-old man, highlighting diagnosis, surgical treatment, drug therapy, and supportive measures. The patient, who had chronic alcoholism, systemic arterial hypertension, a smoking habit, and decompensated diabetes (glucose level of 490 mg/dL), was admitted to the hospital with a volume increase in the cervical and thoracic areas with a duration of about 7 days. He presented with fever, dyspnea, and inflammatory signs bilaterally in the submandibular, submental, and superior thoracic regions as well as severe trismus. The patient underwent a surgical procedure to drain the infectious process and to place drains. The patient developed cutaneous necrosis in the cervical and superior thoracic regions, diagnosed as NF. Surgical debridement of all affected tissue was performed. After resolution of the infection, the patient underwent skin grafting with a satisfactory outcome.

Role of EMSE and STESS scores in the outcome evaluation of status epilepticus.

Status epilepticus (SE) is a severe neurological condition with significant morbidity and mortality. A reliable tool for prognosis is needed to take decision regarding treatment strategies. We compared 2 available prognostic scores of outcome: the Status Epilepticus Severity Score (STESS) and the Epidemiology-based Mortality score in SE (EMSE). We included 46 patients with SE evaluated out the last 5years in our hospital. We excluded patients with postanoxic encephalopathy or incomplete data. Among the 46 patients with SE, in-hospital mortality was 28%. The receiver operating characteristic (ROC) curve for predicting of death by STESS had an area under the curve (AUC) of 0.80 with cutoff point ≥4. The best EMSE variable combination to predict mortality was EMSE-AEL using an optimized cutoff point of 34 (age/etiology/loss of consciousness) with an area under the ROC of 0.79. The STESS and EMSE would be useful tools to predict in-hospital mortality in SE.

Rectus femoris muscle flap based on proximal insertion mobilization to cover a groin infected vascular graft.

The rectus femoris (RF) muscle flap, which is widely used to cover groin infected vascular grafts, is usually harvested through distal tendon division and an extensive muscle elevation and transposition into the groin wound defect. A case of a vascular prosthetic graft infection in the groin was successfully controlled after coverage with an RF flap that was harvested based on proximal portion mobilization instead of the conventional distal one. This case suggests that the RF muscle flap based on proximal insertion mobilization is a feasible, effective, technically simpler, and less invasive alternative to cover infected vascular grafts in the groin.

Temporomandibular joint disorders in skeletal class II patients referred to orthognathic surgery: A cross-sectional study.

OBJECTIVES: The aim of this study was to assess the prevalence of Temporomandibular Disorders (TMD) in subjects with skeletal class II dentofacial deformity referred for orthognathic surgery, as well as to elucidate its association with sociodemographic and psychosocial features. METHODS: This was a cross-sectional study using the Research Diagnostic Criteria for Temporomandibular Disorders. The sample comprised class II skeletal patients referred to an Oral and Maxillofacial Surgery center in the Brazilian Northeast. RESULTS: Seventy-three subjects were enrolled and completed the data collection, which consisted of a physical examination according to Axis I of the Research Diagnostic Criteria for Temporomandibular Disorders and facial analysis. Women represented 82.2% of the sample. Among the assessed subjects, 68.5% were already undergoing orthodontic treatment, and the mean overjet of patients was 6.97 mm. The prevalence of TMD in this sample was 46.6%, with muscular disorders being the most common. Patients with an anteroposterior discrepancy greater than 7 mm showed a higher occurrence of TMD (p = 0.017). CONCLUSION: This study demonstrated a high prevalence of TMD in skeletal class II patients referred for orthognathic surgery, especially in those with a pronounced overjet, being Group I (muscular disorders) and Group III (degenerative disorders) the most prevalent.

The High Capacity of Brazilian Aedes aegypti Populations to Transmit a Locally Circulating Lineage of Chikungunya Virus.

The incidence of chikungunya has dramatically surged worldwide in recent decades, imposing an expanding burden on public health. In recent years, South America, particularly Brazil, has experienced outbreaks that have ravaged populations following the rapid dissemination of the chikungunya virus (CHIKV), which was first detected in 2014. The primary vector for CHIKV transmission is the urban mosquito species Aedes aegypti, which is highly prevalent throughout Brazil. However, the impact of the locally circulating CHIKV genotypes and specific combinations of local mosquito populations on vector competence remains unexplored. Here, we experimentally analyzed and compared the infectivity and transmissibility of the CHIKV-ECSA lineage recently isolated in Brazil among four Ae. aegypti populations collected from different regions of the country. When exposed to CHIKV-infected AG129 mice for blood feeding, all the mosquito populations displayed high infection rates and dissemination efficiency. Furthermore, we observed that all the populations were highly efficient in transmitting CHIKV to a vertebrate host (naïve AG129 mice) as early as eight days post-infection. These results demonstrate the high capacity of Brazilian Ae. aegypti populations to transmit the locally circulating CHIKV-ECSA lineage. This observation could help to explain the high prevalence of the CHIKV-ECSA lineage over the Asian lineage, which was also detected in Brazil in 2014. However, further studies comparing both lineages are necessary to gain a better understanding of the vector's importance in the epidemiology of CHIKV in the Americas.

BRAF p.V600E Mutational Status Does Not Correlate with Biological Behavior in Conventional Ameloblastomas: A Disease-Free Survival Analysis.

BACKGROUND: Dysregulation of the MAPK pathway appears to exert a pivotal role in the pathogenesis of ameloblastomas, since BRAF p.V600E has been reported in over 65% of the tumors. Therefore, the purpose of this study was to investigate whether the BRAF p.V600E is related to biological behavior and disease-free survival in patients with conventional ameloblastomas. METHODS: This is a retrospective cohort study based on the STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) recommendations. The study population consisted of individuals treated for conventional ameloblastomas. Clinical, imaging, histomorphological, immunohistochemical (Ki67 and CD138/syndecan-1), and molecular BRAF p.V600E mutation analyses were performed. Bivariate statistical analysis was performed through chi-square and Fisher's exact tests. Kaplan-Meier analysis with log-rank test and Cox proportional hazards regression were used to identify predictors of disease-free survival, with a significance level of 5%. RESULTS: Forty-one individuals were included, with a male-to-female ratio of 1.15:1. BRAF p.V600E mutation was identified in 75.6% of the tumors. No association between the BRAF mutational status and other clinical, imaging, histomorphological, and immunohistochemical variables was observed. Only the initial treatment modality was significantly associated with a better prognosis in univariate (p = 0.008) and multivariate (p = 0.030) analyses, with a hazard ratio of 9.60 (95%IC = 1.24-73.89), favoring radical treatment. CONCLUSION: BRAF p.V600E mutation emerges as a prevalent molecular aberration in ameloblastomas. Nevertheless, it does not seem to significantly affect the tumor proliferative activity, CD138/syndecan-1-mediated cell adhesion, or disease-free survival outcomes.

Real-World Effectiveness and Safety of Cladribine in Multiple Sclerosis: Longitudinal Data From the Nationwide Registry in Argentina.

OBJECTIVE: The aim was to evaluate patient profiles, effectiveness and safety of cladribine (CLAD) in patients with relapsing-remitting multiple sclerosis in Argentina. METHODS: This was a substudy included in RelevarEM (MS and neuromyelitis optica registry in Argentina, NCT03375177). Patients with MS who received CLAD tablets and were followed up for at least 24 months were included. Clinical evaluations every 3 months collect information about: a) clinical relapses; b) progression of physical disability, evaluated through Expanded Disability Status Scale, and c) new lesions found in the magnetic resonance imaging. Lymphopenia was evaluated during the follow-up and defined as grade 1: absolute lymphocyte count (ALC) 800-999/µL; grade 2: ALC 500-799/µL; grade 3: ALC 200-499/µL and grade 4: ALC <200/µL. RESULTS: A total of 240 patients were included from 19 centers from Argentina. The mean annualized relapse rate during the 12-month pre-CLAD initiation was 1.19 ± 0.56 versus 0.22 ± 0.18 at month 12 and 0.19 ± 0.15 at month 24 (P < 0.001). A total of 142 (59.2%) fulfilled the criteria of disease activity during the 12 months before treatment initiation, whereas 27 (11.3%) fulfilled it at month 12 and 38 (15.8%) at month 24, P < 0.001. Regarding no evidence of disease activity (NEDA), 202 (84.2%) patients achieved NEDA status at month 12 and 185 (77%) at month 24. The most frequent incidence density of lymphopenia for course 2 observed was also for grade 1, 6.1 (95% confidence interval [CI] = 5.5-7.1). The overall incidence density of lymphopenia grade 4 was 0.1 (95% CI = 0.06-0.19). CONCLUSION: This information will help when choosing the best treatment option for Argentinean patients.