OCEANIA: real-world study of ovarian cancer treatment patterns across multiple lines of therapy in Argentina and Brazil.

Aim: To evaluate real-world data on treatment patterns in Argentina and Brazil in patients with ovarian cancer. Methods: This study evaluated de-identified antineoplastic exposure data from a private healthcare provider in Argentina and health claims database (Orizon) in Brazil from 2010 to 2019 and 2015 to 2020, respectively. Results: Platinum-based chemotherapy was the most common first-line therapy (Argentina: n =311 [87.6%]; Brazil: n = 1142 [79.3%]). The proportion of patients receiving platinum-based chemotherapy declined across both populations from first- to second-line, while use of non-platinum-based, targeted, and hormone therapies increased. Duration of platinum-based treatment and time to next treatment decreased from first- to fourth-line. Conclusion: There is an unmet need for effective therapies that can prolong time to next treatment in ovarian cancer in Argentina and Brazil.

[Box: see text].

A mixture of mesotrione and atrazine harms adults and larvae of the predatory wasp Polistes satan.

Herbicides have been intensively used for weed control, raising concerns about their potentially adverse effects on non-target organisms. Research on the effects of these common agrochemicals on beneficial insects and the ecosystem services they provide (e.g., predation and pollination) is scarce. Therefore, we tested whether a commercial formulation comprising a mixture of mesotrione and atrazine was detrimental to adult females and larvae of the Neotropical predatory social wasp Polistes satan, which is an effective natural enemy of crop pests. Wasps were individually fed syrups contaminated with different concentrations of the herbicide above and below the maximum label rate (MLR = 12 mL/L). Survival was assessed. The locomotor activity, immune response, and midgut morphology of adults as well as the immune response of the larvae were also studied. Herbicide concentrations far above the MLR (12, 40, and 100 times) caused adult mortality, whereas lower concentrations (0.5, 1, and 6 times) did not. Herbicide exposure at 0.5 to 12 times the MLR increased adult activity. Adult exposure at 0.1 or 0.5 times the MLR did not affect melanotic encapsulation of foreign bodies but led to changes in the morphology of the midgut epithelium and peritrophic matrix. In larvae, the ingestion of herbicide at 0.1 or 0.2 times the MLR (corresponding to 9.6 and 19.2 ng of herbicide per individual) did not cause mortality but decreased their melanization-encapsulation response. Increased locomotor activity in herbicide-exposed adults can affect their foraging activity. The altered midgut morphology of adults coupled with the decreased immune response in larvae caused by herbicide exposure at realistic concentrations can increase the susceptibility of wasps to infections. Therefore, herbicides are toxic to predatory wasps.

Blood-based multi-cancer detection: A state-of-the-art update.

The early detection of cancer is a key goal of the National Cancer Plan formally released by the National Institutes of Health's (NIH) National Cancer Institute (NCI) in April 2023. To support this effort, many laboratories and vendors are developing multi-cancer detection (MCD) assays that interrogate blood and other bodily fluids for cancer-related biomarkers, most commonly circulating tumor DNA (ctDNA). While this approach holds promise for non-invasively detecting early signals of multiple different cancers and potentially reducing cancer-related mortality, there is a dearth of prospective clinical data to inform the deployment of MCD assays for cancer screening in the general adult population. In this review we highlight differing technologies that underpin various MCD assays in clinical development, the importance of achieving adequate performance specifications for MCD assays, ongoing clinical studies investigating the utility of MCD assays in cancer screening and detection, and efforts by the NCI's Division of Cancer Prevention (DCP) to establish a network infrastructure that has the capacity to comprehensively address the scientific and logistical challenges of evaluating blood-based MCD approaches and other cancer screening tools.

Accuracy of static computer-aided implant surgery (S-CAIS) using CAD-CAM surgical templates fabricated from different additive manufacturing technologies.

STATEMENT OF PROBLEM: Different 3D printers are available for guided implant surgery, but studies that evaluate their source of errors and their cost-effectiveness are lacking. PURPOSE: The purpose of this in vitro study was to compare the accuracy of different 3-dimensional (3D) printed surgical templates made using different additive manufacturing technologies and to evaluate the effect of implant location on the accuracy of fully guided implant placement. MATERIAL AND METHODS: Fifty partially edentulous maxillary typodonts with edentulous sites in the right second premolar (SP), right lateral incisor (LI), left central incisor (CI), and left first molar (FM) locations were scanned and printed from the standard tessellation language (STL) datasets. The study compared 5 groups for the fabrication of implant surgical templates: Varseo S-Bego (Bego), Polyjet-Stratasys (Poly), Low Force Stereolithography-FormLabs (LFS), P30+-Straumann (P30), and M2-Carbon (M2). After fully guided implant placement, the typodont was scanned, and the 3D implant positions were compared with the master model by superimposing the STL files. Descriptive statistics were calculated for groups and subgroups, and comparisons among the groups and subgroups were conducted via 2-way mixed analysis of variance, Tukey honest significant difference, and post hoc Bonferroni tests (α=.05). RESULTS: The results were site specific and not consistent within each group. For angle deviation, the within-group analysis for P30 demonstrated significantly lower values for implants positioned at site SP (1.4 ±0.8 degrees) than for sites LI (2.3 ±0.7 degrees; P=.001) and CI (2.3 ±0.8 degrees; P=.007). For 3D offset at base for implant CI, LFS was significantly higher than Bego (P=.002), Poly (P=.035), or M2 (P=.001); P30 was also significantly higher than Bego (P=.014) and M2 (P=.006). LFS had a significantly higher 3D offset at the tip than Bego (P=.001) and M2 (P=.022) for implant CI. CONCLUSIONS: The choice of 3D printer seemed to influence fully guided implant surgery in terms of the final implant position compared with initial implant planning. However, although statistically significant differences were present across groups, all additive manufacturing technologies were within clinically acceptable values.

Frequent Telomerase Reverse Transcriptase Promoter and Fibroblast Growth Factor Receptor 3 Mutations Support the Precursor Nature of Papillary Urothelial Hyperplasia of the Urinary Bladder.

The precursor nature of papillary urothelial hyperplasia of the urinary bladder is uncertain. In this study, we investigated the telomerase reverse transcriptase (TERT) promoter and fibroblast growth factor receptor 3 (FGFR3) mutations in 82 patients with papillary urothelial hyperplasia lesions. Thirty-eight patients presented with papillary urothelial hyperplasia and concurrent noninvasive papillary urothelial carcinoma, and 44 patients presented with de novo papillary urothelial hyperplasia. The prevalence of the TERT promoter and FGFR3 mutations is compared between de novo papillary urothelial hyperplasia and those with concurrent papillary urothelial carcinoma. Mutational concordance between papillary urothelial hyperplasia and concurrent carcinoma was also compared. The TERT promoter mutations were detected in 44% (36/82) of papillary urothelial hyperplasia, including 23 (23/38, 61%) papillary urothelial hyperplasia with urothelial carcinoma and 13 (13/44, 29%) de novo papillary urothelial hyperplasia. The overall concordance of TERT promoter mutation status between papillary urothelial hyperplasia and concurrent urothelial carcinoma was 76%. The overall FGFR3 mutation rate of papillary urothelial hyperplasia was 23% (19/82). FGFR3 mutations were detected in 11 patients with papillary urothelial hyperplasia and concurrent urothelial carcinoma (11/38, 29%) and 8 patients with de novo papillary urothelial hyperplasia (8/44, 18%). Identical FGFR3 mutation status was detected in both papillary urothelial hyperplasia and urothelial carcinoma components in all 11 patients with FGFR3 mutations. Our findings provide strong evidence of a genetic association between papillary urothelial hyperplasia and urothelial carcinoma. High frequency of TERT promoter and FGFR3 mutations suggests the precursor role of papillary urothelial hyperplasia in urothelial carcinogenesis.

Clinical features of patients with MTAP-deleted bladder cancer.

Advanced urothelial carcinoma continues to have a dismal prognosis despite several new therapies in the last 5 years. FGFR2 and FGFR3 mutations and fusions, PD-L1 expression, tumor mutational burden, and microsatellite instability are established predictive biomarkers in advanced urothelial carcinoma. Novel biomarkers can optimize the sequencing of available treatments and improve outcomes. We describe herein the clinical and pathologic features of patients with an emerging subtype of bladder cancer characterized by deletion of the gene MTAP encoding the enzyme S-Methyl-5'-thioadenosine phosphatase, a potential biomarker of response to pemetrexed. We performed a retrospective analysis of 61 patients with advanced urothelial carcinoma for whom demographics, pathologic specimens, next generation sequencing, and clinical outcomes were available. We compared the frequency of histology variants, upper tract location, pathogenic gene variants, tumor response, progression free survival (PFS) and overall survival (OS) between patients with tumors harboring MTAP deletion (MTAP-del) and wild type tumors (MTAP-WT). A propensity score matching of 5 covariates (age, gender, presence of variant histology, prior surgery, and prior non-muscle invasive bladder cancer) was calculated to compensate for disparity when comparing survival in these subgroups. Non-supervised clustering analysis of differentially expressed genes between MTAP-del and MTAP-WT urothelial carcinomas was performed. MTAP-del occurred in 19 patients (31%). Tumors with MTAP-del were characterized by higher prevalence of squamous differentiation (47.4 vs 11.9%), bone metastases (52.6 vs 23.5%) and lower frequency of upper urinary tract location (5.2% vs 26.1%). Pathway gene set enrichment analysis showed that among the genes upregulated in the MTAP-del cohort, at least 5 were linked to keratinization (FOXN1, KRT33A/B, KRT84, RPTN) possibly contributing to the higher prevalence of squamous differentiation. Alterations in the PIK3 and MAPK pathways were more frequent when MTAP was deleted. There was a trend to inferior response to chemotherapy among MTAP-del tumors, but no difference in the response to immune checkpoint inhibitors or enfortumab. Median progression free survival after first line therapy (PFS1) was 5.5 months for patients with MTAP-WT and 4.5 months for patients with MTAP-del (HR = 1.30; 95% CI, 0.64-2.63; P = 0.471). There was no difference in the time from metastatic diagnosis to death (P = 0.6346). Median OS from diagnosis of localized or de novo metastatic disease was 16 months (range 1.5-60, IQR 8-26) for patients with MTAP-del and 24.5 months (range 3-156, IQR 16-48) for patients with MTAP-WT (P = 0.0218), suggesting that time to progression to metastatic disease is shorter in MTAP-del patients. Covariates did not impact significantly overall survival on propensity score matching. In conclusion, MTAP -del occurs in approximately 30% of patients with advanced urothelial carcinoma and defines a subgroup of patients with aggressive features, such as squamous differentiation, frequent bone metastases, poor response to chemotherapy, and shorter time to progression to metastatic disease.

Clinical activity of 9-ING-41, a small molecule selective glycogen synthase kinase-3 beta (GSK-3ß) inhibitor, in refractory adult T-Cell leukemia/lymphoma.

GSK-3ß is a serine/threonine kinase implicated in tumorigenesis and chemotherapy resistance. GSK-3ß blockade downregulates the NF-κB pathway, modulates immune cell PD-1 and tumor cell PD-L1 expression, and increases CD8 + T cell and NK cell function. We report a case of adult T-cell leukemia/lymphoma (ATLL) treated with 9-ING-41, a selective GSK-3ß inhibitor in clinical development, who achieved a durable response. A 43-year-old male developed diffuse lymphadenopathy, and biopsy of axillary lymph node showed acute-type ATLL. Peripheral blood flow cytometry revealed a circulating clonal T cell population, and CSF was positive for ATLL involvement. After disease progression on the 3rd line of treatment, he started treatment with 9-ING-41 monotherapy in a clinical trial (NCT03678883). CT imaging after seven months showed a partial response. Sustained reduction of peripheral blood ATLL cells lasted 15 months. Treatment of patient-derived CD8 + T cells with 9-ING-41 increased the secretion of IFN-γ, granzyme B, and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL). In conclusion, treatment of a patient with refractory ATLL with the GSK-3ß inhibitor 9-ING-41 resulted in a prolonged response. Ongoing experiments are investigating the hypothesis that 9-ING-41-induced T cell activation and immunomodulation contributes to its clinical activity. Further clinical investigation of 9-ING-41 for treatment of ATLL is warranted.

Screw-retained surgical guide for implant placement in terminal dentition patients with existing implants.

For patients with existing implants in need of additional implant placement, the use of the existing implants for guide fixation seems to be a logical alternative. Current options for the fabrication of surgical guides involve creating surgical guides that are mucosa-borne and/or retained by fixation pins. Since these existing techniques involve inherent inaccuracies, the fabrication of surgical guides that are screw-retained at the implant- or abutment-level would eliminate the introduction of those same fundamental inaccuracies. The purpose of the present technical report is to illustrate a step-by-step digitally planned guided implant placement protocol for terminal dentition patients with salvageable existing implants requiring full-arch implant rehabilitation. The advantages of this protocol include enhancing the accuracy of guided implant placement with screw-retention versus the traditional mucosa- or fixation pin support. Thus, this simplifies the transition from failing teeth to implants by ensuring that fixed provisionalization serves both functional and esthetic requirements. This protocol can also predictably reduce chairside time and adjustments at the surgical implant placement appointment.

Association between pre-operative complications, comorbidities, and in-hospital mortality in a hip fracture cohort: a register study in a tertiary hospital in Brazil.

PURPOSE: The incidence of hip fractures is increasing exponentially due to an aging Brazilian population. Older people had significant comorbidities which increases the risk of post-operative mortality. Our purpose was to examine the association between pre-operative infections and comorbidities on the risk of post-operative in-hospital mortality after proximal femur fracture surgery's, beyond that, to evaluate the association between comorbidities and time to surgery. METHODS: This is a population-based cohort retrospective study, using medical records of all six year consecutive surgical procedures for correction of hip fracture in a tertiary teaching Hospital in Brazil. The exclusion criteria aimed to exclusively allocate patients who had their first hip fracture secondary to low-energy trauma. Multivariate logistical regression was performed and receiver operating characteristic (ROC) curve with area under curve (AUC) to evaluate the sensitivity and specificity of the model. p-value < 0.05 was considered significant. RESULTS: Final sample was composed by 856 consecutive patients with 81 years of median and 164 patients were excluded. The median length of hospital say was five days with - l mortality at 3.6%. Significant variables for increased mortality included the presence of pre-operative infection (odds ratio (OR): 3.9(1.12-8.54), chronic obstructive pulmonary disease (COPD) (OR: 3.83(1.36-10.82)), and systemic arterial hypertension (SAH) (OR: 4.1(1.18-14.25)). Development of pre-operative infection was associated with a delay to surgery (OR: 1.1 (1.08-1.13)). CONCLUSIONS: In older people with proximal femur fracture, the presence of pre-operative infection, COPD and SAH were the strongest risk factor for post-operative in-hospital mortality. Pre-operative infection was associated with statistically significant delay to surgery.

Consumo de tabaco y alcohol y comportamientos de salud entre estudiantes de enfermería / O consumo de tabaco e álcool e os comportamentos de saúde em estudantes de enfermagen / Tobacco and alcohol consumption and health behaviors among nursing students

Objective: To evaluate the association between attitudes, health behaviors, and the use of tobacco and alcohol among nursing students. Materials and method: Exploratory, descriptive and cross-sectional study conducted with 182 undergraduate nursing students in the countryside of São Paulo, Brazil. Sociodemographic Information Form, Alcohol Use Disorders Identification Test ­ C (AUDIT-C), Fagerström Test for Nicotine Dependence (FTND), Attitudes and Health Behaviors Questionnaire (AHBQ), and Patient Health Questionnaire ­ 2 (PHQ-2) were applied. Results: More than half of the students showed appropriate health behaviors and positive attitudes. Approximately 50% of the participants had consumed alcoholic beverages in the last month. Experimental use of illicit drugs and smoking were also observed. In addition, students who reported excessive alcohol use presented a deficit in self-care. Conclusions: The precariousness in health attitudes and behaviors identified in this study was associated with various patterns of psychoactive substance use. Thus, the results indicate the need for interventions aimed at promoting well-being and a healthy lifestyle in the university environment.

Objetivo: evaluar la asociación entre las actitudes, los comportamientos de salud y el uso de tabaco y alcohol entre un grupo de estudiantes de enfermería. Materiales y método: estudio exploratorio, descriptivo y transversal realizado con 182 estudiantes de pregrado en enfermería en São Paulo, Brasil. Se aplicaron los siguientes instrumentos: Formulario de Información Sociodemográfica, Prueba de Identificación de Trastornos Derivados del Consumo de Alcohol ­ C (AUDIT-C), Test de Fagerström para Adicción a la Nicotina (FTND), Cuestionario sobre Actitudes y Conductas de Salud (CACS) y Cuestionario de Salud del Paciente ­ 2 (PHQ-2). Resultados: más de la mitad de los estudiantes mostraron comportamientos de salud apropiados y actitudes positivas. Aproximadamente 50 % de los participantes había consumido bebidas alcohólicas en el último mes. También se observó el uso experimental de drogas ilícitas y tabaco. Además, los estudiantes que reportaron el consumo excesivo de alcohol presentaron un déficit en el autocuidado. Conclusiones: la precariedad en las actitudes y los comportamientos de salud identificados en este estudio fue asociada con diversos patrones de uso de sustancias psicoactivas. Los resultados señalan la necesidad de intervenciones destinadas a promover el bienestar y un estilo de vida saludable en el ámbito universitario.

Objetivo: avaliar a associação entre as atitudes, os comportamentos de saúde e o uso de tabaco e álcool num grupo de estudantes de enfermagen. Materiais e método: estudo exploratório, descritivo e transversal realizado com 182 estudantes de graduação em enfermagem em São Paulo, Brasil. Foram aplicados os seguintes instrumentos: Formulário de Informação Sociodemográfica, Teste de Identificação de Transtornos Derivados do Consumo de Álcool-C (AUDIT-C), Teste de Fagerström para a Dependência de Nicotina (FTND), Questionário sobre Atitudes e Condutas de Saúde (CACS) e Questionário de Saúde do Paciente-2 (PHQ-2). Resultados: mais da metade dos estudantes mostraram comportamentos de saúde apropriados e atitudes positivas. Aproximadamente 50 % dos participantes tinham consumido bebidas alcoólicas no último mês. Também foi observado o uso experimental de drogas ilícitas e tabaco. Além disso, os estudantes que relataram o consumo excessivo de álcool apresentaram um déficit no autocuidado. Conclusões: a precariedade nas atitudes e comportamentos de saúde identificados neste estudo foi associada com diversos padrões de uso de substâncias psicoativas. Os resultados indicam a necessidade de intervenções destinadas a promover o bem-estar e um estilo de vida saudável no contexto universitário.

The Use of Surgical Splints in Orthognathic Surgery: A Bibliometric Study.

Introduction Orthognathic surgeries require the use of surgical splints (SS) to stabilize the occlusion and the segments fixed with plates and screws. Technological advances in the field of computing and the possibility of generating three-dimensional (3D) images have brought different possibilities for making SS, which has generated greater predictability and customization of surgical plans. The bibliometric study can have a qualitative character through the scope of articles in a certain area of knowledge. It is a selection process that can track a topic or scientific production. Methods The present study aimed to carry out a bibliometric literature review, in order to assess the evolution of the use of SS and the different planning protocols in orthognathic surgery. The Scopus database was used, with the terms "splint" and "orthognathic surgery." Results A total of 331 articles were found. These were exported to Rayyan for application of the inclusion and exclusion criteria and selection of articles. A total of 76 references were selected and exported to the VOSviewer application for the analysis of bibliometric data. Conclusions Orthognathic surgery was initially not associated with any computerized technological resource; however, it underwent updates between the years 2010 to 2012. These advances allowed surgical planning to become faster, cheaper, and more accurate.

Digital Workflow in Implant Treatment Planning For Terminal Dentition Patients.

Treatment planning for the transition of patients from terminal dentition to full-arch implant rehabilitation poses challenges. Such challenges pertain to achieving the new orientation of the occlusal and esthetic plane as well as the change of vertical dimension of occlusion (VDO), while the fixed provisionalization using a digital workflow still tends to be considered complex and hard to perform. This article illustrates step-by-step the utilization of a digital workflow protocol in the treatment planning for rehabilitation of terminal dentition patients, simplifying the smile design and ensuring that fixed provisionalization serves both functional and esthetic requirements. This protocol includes facially driven, three-dimensional (3D) digital smile design and chairside mock-up restoration workflows that enable prosthetically driven assessment prior to implant treatment planning and 3D printing of surgical templates and prefabricated interim prostheses, which can predictably reduce chairside time and adjustments at the surgical and fixed provisionalization appointment.

Periodontal plastic surgery for esthetic crown lengthening by using data merging and a CAD-CAM surgical guide.

This article introduced a digital workflow by using data merging and a computer-aided design and computer-aided manufacturing (CAD-CAM) milled surgical guide for an esthetic crown lengthening procedure. The superimposition of intraoral scanning, digital photographs, cone beam computed tomography, and a CAD-CAM surgical guide should increase the predictability of esthetic crown lengthening surgery.

A comparative retrospective study of different surgical guide designs for static computer-assisted implant surgery in posterior single edentulous sites.

AIM: The aim of this retrospective clinical study was to compare the accuracy of static Computer-assisted implant surgery (sCAIS) in posterior single edentulous patients using different surgical guide designs. MATERIALS AND METHODS: Thirty-seven partially edentulous patients with a total of 54 implants were included in the study. Seventeen implants were included in Group 1-Unbounded Tooth-Mucosa Supported; 18 implants in Group 2-Unbounded Tooth Supported; and 19 implants in Group 3 (Control)-Bounded Tooth Supported. All partially edentulous patients were treated with fully guided implant surgery using the corresponding surgical guide. Discrepancies between the pre-planned and post-operative implant position were evaluated. RESULTS: The mean angular deviation ± standard deviation (SD) was 2.91 ± 1.56°, 3.33 ± 1.72° and 2.25 ± 1.13° for Groups 1, 2, and 3, respectively. The mean ± SD 3D offset at base was 0.66 ± 0.29 mm, 0.77 ± 0.24 mm, and 0.49 ± 0.22 mm; and 3D offset at tip was 0.84 ± 0.45 mm, 1.07 ± 0.38 mm, and 0.75 ± 0.25 mm for Groups 1, 2, and 3, respectively. No statistically significant differences between groups were found for angular deviation. There were statistically significant differences between Groups 2 and 3 for 3D offset at base (p = .002) and 3D offset at tip (p = .010). CONCLUSIONS: Different surgical guide designs for posterior single edentulous areas appear to be associated with the accuracy level of sCAIS. In unbounded sites, having additional posterior attached soft tissue support is preferable.

Accuracy of Different Surgical Guide Designs for Static Computer-Assisted Implant Surgery: An In Vitro Study.

The aims of this study were to evaluate the effect of (1) the different surgical guide designs and (2) implant placement location on the accuracy of fully guided implant placement in single edentulous sites using an in vitro study model. Forty-five partially edentulous models were scanned and divided into 3 groups: group 1, tooth-supported full-arch surgical guide; group 2, 3 different tooth-supported shortened surgical guides (SSGs); and group 3, tooth-supported full-arch surgical guide with a crossbar. All surgical guides were printed and used for fully guided implant placement. A total of 180 implants (60 per group) were placed, and scan bodies were positioned on all models, and postoperative surface scan files (STL) files were obtained. Superimposition of preoperative and postoperative STL files was performed, and the accuracy of implant position was evaluated. The interaction between group and implant location was statistically significant for angle, 3D offset at the base, and at the tip (P < .001). The post-hoc tests showed a statistically significantly higher deviation for group 2 compared to group 3 for all outcomes for implants #4 (P < .05) and #7 (P < .05). There was also a statistically significant difference in all outcomes between groups 1 and 3 for implant #7 (P < .05). All surgical guide designs presented satisfactory performance with clinically acceptable levels of deviation. However, SSGs presented higher accuracy for guided implant placement in a single-edentulous site, whereas a full-arch surgical guide with a crossbar presented superior outcomes when 2 or more guided implants were placed simultaneously.

The Role of BCL-2 Proteins in the Development of Castration-resistant Prostate Cancer and Emerging Therapeutic Strategies.

The development of androgen resistance in advanced prostate cancer remains a challenging clinical problem. Because androgen deprivation therapy constitutes the backbone of first-line treatments for metastatic prostate cancer, the phenotypic switch from an androgen-dependent to an androgen-independent growth state limits the treatment options for these patients. This critical change from an androgen-dependent to an androgen-independent growth state can be regulated by the B-cell lymphoma gene 2 (BCL-2) family of apoptotic proteins. While the roles of BCL-2 protein family members in the carcinogenesis of prostate cancer have been well-studied, emerging data also delineates their modulation of disease progression to castration-resistant prostate cancer (CRPC). Over the past 2 decades, investigators have sought to describe the mechanisms that underpin this development at the molecular level, yet no recent literature has consolidated these findings in a dedicated review. As new classes of BCL-2 family inhibitors are finding indications for other cancer types, it is time to evaluate how such agents might find stable footing for the treatment of CRPC. Several trials to date have investigated BCL-2 inhibitors as therapeutic agents for CRPC. These therapies include selective BCL-2 inhibitors, pan-BCL-2 inhibitors, and novel inhibitors of MCL-1 and BCL-XL. This review details the research regarding the role of BCL-2 family members in the pathogenesis of prostate cancer and contextualizes these findings within the contemporary landscape of prostate cancer treatment.

p53 Expression, Programmed Death Ligand 1, and Risk Factors in Urinary Tract Small Cell Carcinoma.

Introduction: Small cell carcinoma of the urinary tract (SCCUT) is a rare finding with poor clinical course. This study sheds light on the molecular subtype and identifies risk factors in patients diagnosed with SCCUT. Methods: Immunohistochemical expression of immunotherapy target programmed death ligand 1 (PD-L1) and luminal (GATA3), basal (p63), and p53 markers are assessed in patients diagnosed with SCCUT. Univariate analysis identified risk factors. Overall survival (OS) is computed using the Kaplan-Meier method. Results: Tissue was available for 70.2% (33/47). All showed a high PD-L1 expression phenotype. p53 is seen in 93.9% (31/33), mostly as overexpression, GATA3 in 45.5% (15/33), and p63 in 57.6% (19/33). For the entire cohort (n = 47), 1-year survival was 59.6%, and the median OS was 17 months. Univariate analysis shows that chemotherapy [hazard ratio (HR) = 0.29, 95% confidence interval (CI) = 0.14-0.61, p = 0.001], radical surgery (HR = 0.37, 95% CI = 0.18-0.76, p = 0.007), and diagnosis of non-pure SCCUT (HR = 0.44, 95% CI = 0.22-0.86, p = 0.02) are favorable prognostic features. Metastasis had negative associations with survival (HR = 2.1, 95% CI = 1.1-4.2, p = 0.03). Conclusions: In this series, pure and mixed SCCUT are characterized by p53 overexpression and a high PD-L1 phenotype. Histology of non-pure SCCUT is a positive prognosticator, and radical cystectomy or chemotherapy can improve OS. These findings demonstrate that SCCUT may be eligible for PD-L1 immunotherapy.

Complete Digital Workflow for Mandibular Full-Arch Implant Rehabilitation in 3 Appointments.

The aim of this clinical report is to describe a complete digital workflow protocol for mandibular full-arch implant rehabilitation from guided surgery to definitive prosthesis in only 3 appointments. This expedited protocol allows for guided implant placement with a system of stackable surgical templates and CAD/CAM prosthodontic rehabilitation using a digital workflow. At the first appointment, a guided implant placement protocol with the stackable template concept was done followed by immediate loading with a prefabricated interim prosthesis. At the same appointment, the Double Digital Scanning (DDS) technique was used for scanning, maxillomandibular relationship registration and virtual articulation. The anchor pins from guided surgery were used as fiducial markers for DDS data superimposition. At the second appointment, the prosthesis prototype was tried-in and adjustments were made. At the third appointment, the definitive monolithic zirconia full-arch prosthesis was delivered.

Influence of zirconia crown artifacts on cone beam computed tomography scans and image superimposition of tomographic image and tooth surface scan: An in vitro study.

STATEMENT OF PROBLEM: Zirconia restorations create significant artifacts on 3D cone beam computed tomography (CBCT) imaging. Static computer-assisted implant surgery (s-CAIS) relies on the accuracy of superimposition between an intraoral surface scan and CBCT imaging. However, how the artifacts from zirconia on the tomographic image might affect the predictability of s-CAIS is unclear. PURPOSE: The purpose of this in vitro study was to evaluate the effect of zirconia crown restorations on the superimposition process for s-CAIS. MATERIAL AND METHODS: Four stone casts generated 4 groups: a control group (CG) with no crowns and 3 experimental groups with 4 (TG4), 7 (TG7), and 13 (TG13) zirconia crowns. A total of 40 CBCT scans were made for the 4 groups (n=10). All CBCTs were imported into a computer planning software program, and the casts from all 4 groups were scanned by using a high-resolution laboratory scanner. The standard tessellation language (STL) files were imported, segmented, and the 3 files superimposed for all groups. The accuracy of the superimposition was assessed, in millimeters, in 3 planes corresponding to anterior-posterior, horizontal, and vertical, as well as the overall measurement, and the results were analyzed statistically (α=.05). RESULTS: The overall analysis demonstrated statistically significant differences between all groups (P<.001), except between CG and TG4. The anterior-posterior dimension demonstrated significant differences between CG and TG7 (P<.001), CG and TG13 (P<.001), TG4 and TG7 (P=.004), and TG4 and TG13 (P=.001). For the vertical dimension analysis, significant differences were found between CG and TG7 (P=.001), CG and TG13 (P<.001), and TG4 and TG13 (P<.001). For the horizontal variable, statistically significant differences were found between CG and TG7 (P=.049), CG and TG13 (P<.001), TG4 and TG13 (P<.001), and TG7 and TG13 (P=.003). CONCLUSIONS: The accuracy of the superimposition of the images was influenced by the number of zirconia crowns, with an increased number reducing the superimposition accuracy.

Restorative Alveolar Interface Management Combined With Tunnel Technique and Connective Tissue Graft: A Conservative Approach for Root Fracture Treatment.

INTRODUCTION: The infringement of supracrestal tissue attachment by subgingival restorative margins, extensive caries, and root fractures, can compromise the periodontal health, resulting in inflammation and loss of periodontal supporting tissues. This report describes a case of a root fracture on the upper left central incisor that was successfully treated using a conservative approach, by applying the restorative alveolar interface (RAI) management combined with tunnel technique and a subepithelial connective tissue graft (SCTG). CASE PRESENTATION: A 24-year-old male patient presented with a provisional single-unit fixed prosthesis on his upper left central incisor, in function for 4 years, with the chief complaint of prosthesis discoloration. After clinical and radiographic examination, a diagnosis of root fracture was established. Following the removal of the provisional prosthesis, a full-thickness flap was elevated creating a tunnel. The elimination of the fracture line/angle, root recontouring, and planning was then performed with the aid of a conical long diamond bur and periodontal curets. Additionally, an SCTG was placed buccally into the tunnel. The final zirconia layered with E-max crown was placed 6 months after surgery. At 12- and 24-month follow-up, the periodontal tissues presented healthy aspect, no bleeding on probing, and a 4-mm probing depth. CONCLUSIONS: Surgical repositioning of the restorative margin can be an alternative and conservative treatment approach to compromised teeth with subgingival fracture line/angle. However, case selection should be carefully considered and restorability assessed as limitations might apply.