PoCOsteo: generic novel platform for bone turnover marker measurement & monitoring.

Despite the increasing efforts in improving bone health assessments, current diagnostics suffer from critical shortcomings. The present article therefore describes a multiplex label-free immunosensor designed and validated for the assessment of two bone turnover markers (BTMs), namely beta isomerized C-terminal telopeptide of type I collagen (CTx) and Procollagen I Intact N-Terminal (PINP), the combination of which is needed to illustrate an accurate overview of bone health. The immunosensor was then tested outside and inside of a microsystem, with the aim of becoming compatible with a point of care system fabricated for automated assessment of these biomarkers later-on at patient side. Custom-made monoclonal antibodies were specifically designed for this purpose in order to guarantee the selectivity of the immunosensor. In the final platform, a finger prick blood sample is introduced into the microfluidic manifolds without any need for sample preparation step, making the tool suitable for near patient and outside of the central laboratory applications. The platform was exploited in 30 real blood samples with the results validated using electrochemiluminescence immunoassay. The results revealed the platform was capable of measuring the target analyte with high sensitivity and beyond the recommended clinical reference range for each biomarker (CTx: 104-1028 ng L-1 and PINP: 16-96 µg L-1, correspondingly). They also showed the platform to have a limit of detection of 15 (ng L-1) and 0.66 (µg L-1), a limit of quantification of 49 (ng L-1) and 2.21 (µg L-1), and an inter- and intra-assay coefficient of variance of 5.39-6.97% and 6.81-5.37%, for CTx and PINP respectively, which is comparable with the gold standard. The main advantage of the platform over the state-of-the art was the capability of providing the results for two markers recommended for assessing bone health within 15 minutes and without the need for skilled personnel or costly infrastructure.

Brazilian Society of Otology task force - Vestibular Schwannoma ‒ evaluation and treatment.

OBJECTIVE: To review the literature on the diagnosis and treatment of vestibular schwannoma. METHODS: Task force members were educated on knowledge synthesis methods, including electronic database search, review and selection of relevant citations, and critical appraisal of selected studies. Articles written in English or Portuguese on vestibular schwannoma were eligible for inclusion. The American College of Physicians' guideline grading system and the American Thyroid Association's guideline criteria were used for critical appraisal of evidence and recommendations for therapeutic interventions. RESULTS: The topics were divided into 2 parts: (1) Diagnosis - audiologic, electrophysiologic tests, and imaging; (2) Treatment - wait and scan protocols, surgery, radiosurgery/radiotherapy, and systemic therapy. CONCLUSIONS: Decision making in VS treatment has become more challenging. MRI can diagnose increasingly smaller tumors, which has disastrous consequences for the patients and their families. It is important to develop an individualized approach for each case, which highly depends on the experience of each surgical team.

Aquaporins Transcripts with Potential Prognostic Value in Pancreatic Cancer.

Pancreatic cancer is anticipated to be the second leading cause of cancer-related death by 2030. Aquaporins (AQPs), a family of water channel proteins, have been linked to carcinogenesis. The aim of this study was to determine AQP gene expression in pancreatic cancer tissues and to validate aquaporins as possible diagnosis and/or prognosis genes. The relative gene expression levels of AQP1, AQP3, AQP5, and AQP9 were analyzed using real-time quantitative PCR (RT-qPCR) in 24 paired pancreatic tumors and adjacent healthy tissues according to variables such as age, gender, and tumor invasiveness and aggressiveness. AQPs transcripts were detected in both healthy and tumor tissues. While AQP1 was downregulated in the tumor samples, AQP3 was particularly overexpressed in low-grade invasive tumors. Interestingly, most of the strong positive Pearson correlation coefficients found between AQPs in healthy tissues were lost when analyzing the tumor tissues, suggesting disruption of the coordinated AQP-gene expression in pancreatic cancer.

Frequency of CDH1, CTNNA1 and CTNND1 Germline Variants in Families with Diffuse and Mixed Gastric Cancer.

The most well-characterized hereditary form of gastric cancer is hereditary diffuse gastric cancer (HDGC), an autosomal dominant syndrome characterized by an increased risk of diffuse gastric and lobular breast cancer. HDGC is predominantly caused by germline pathogenic variants in the CDH1 gene, and more rarely in the CTNNA1 gene. Furthermore, the International Gastric Cancer Linkage Consortium (IGCLC) guidelines do not clarify whether or not mixed gastric cancer (with a diffuse component) should be considered in the HDGC genetic testing criteria. We aimed to evaluate the contribution of CTNNA1 and CTNND1 germline variants to HDGC. Additionally, we also intended to compare the frequencies of CDH1 and CTNNA1 (and eventually CTNND1) germline variants between patients with diffuse and mixed gastric carcinomas to evaluate if genetic testing for these genes should or should not be considered in patients with the latter. We analyzed the CDH1 gene in 67 cases affected with early-onset/familial mixed gastric carcinomas and the CTNNA1 and CTNND1 genes in 208 cases with diffuse or mixed gastric cancer who had tested negative for CDH1 pathogenic germline variants. A deleterious CTNNA1 germline variant was found in 0.7% (1/141) of diffuse gastric cancer patients meeting the 2020 IGCLC criteria, as compared to the rate of 2.8% of CDH1 deleterious variants found by us in this setting. No deleterious variants were found in CTNND1, but six variants of uncertain significance were identified in this gene. We did not find any pathogenic CDH1, CTNNA1 or CTNND1 variant in index patients with early-onset/familial mixed gastric cancer, so there is no evidence that supports including this tumor type in the testing criteria for germline variants in these genes. The role of the CTNND1 gene in inherited gastric cancer predisposition is still unclear.

Tissue-Specific Variation in Aquaporins and Cytokines Transcriptional Profiles in Piglets being LPS Challenged.

BACKGROUND: Lipopolysaccharide (LPS), an effective stimulator of the immune system, has been widely applied in an experimental pig model for human sepsis. Aquaporins (AQPs), a family of small integral membrane proteins responsible for facilitating water fluxes through the cell membrane, offer potential promising drug targets for sepsis treatment due to their role in water balance and inflammation. METHODS: In order to investigate the potential effect of a dietary amino acid mixture supplementation on LPS-challenged weaned piglets, a total of 30, 28-day-old, males were randomly allocated to 1 of 3 dietary treatments for a 5-week period, with 10 animals in each: diet 1 was a control (CTL) treatment; diet 2 was LPS treatment, where the piglets were intraperitoneally administered LPS (at 25 µg/kg body weight); diet 3 was LPS + cocktail treatment, where the piglets were intraperitoneally administered LPS and fed a diet supplemented with a mixture of arginine, branched-chain amino acids (BCAA, leucine, valine, and isoleucine), and cystine. Key organs that control sepsis were collected and processed by real time quantitative PCR (RT-qPCR) for the AQPs and cytokines transcriptional profiles. RESULTS: Minor variations were detected for AQPs and inflammatory markers mRNA levels, upon the dependence of LPS or the amino acid cocktail suggesting the piglets' immune recovery. Using a discriminant analysis tool, we report for the first time, a tissue-specific variation in AQPs and cytokines transcriptional profiles that clearly distinguish the small intestine and the kidney from the liver and the spleen. CONCLUSIONS: This study provides a novel insight into the gene expression signature of AQPs and cytokines in the functional physiology of each organ in piglets.

Development of a QCM-based biosensor for the detection of non-small cell lung cancer biomarkers in liquid biopsies.

Lung cancer is the main malignant cancer reported worldwide, with one of the lowest survival rates. Deletions in the Epidermal Growth Factor Receptor (EGFR) gene are often associated with non-small cell lung cancer (NSCLC), a common subtype of lung cancer. The detection of such mutations provides key information for the diagnosis and treatment of the disease; therefore, the early screening of such biomarkers is of vital importance. The need for fast, reliable, and early detection means applied to NSCLC has led to the development of highly sensitive devices that can detect cancer-associated mutations. Such devices, known as biosensors, are a promising alternative to more conventional detection methods and can potentially alter the way cancer is diagnosed and treated. In this study, we report the development of a DNA-based biosensor, namely a quartz crystal microbalance (QCM), applied to the detection of NSCLC, from liquid biopsies samples. The detection, as is the case of most DNA biosensors, is based on the hybridization between the NSCLC-specific probe and the sample DNA (containing specific mutations associated with NSCLC). The surface functionalization was performed with a blocking agent (dithiothreitol) and thiolated-ssDNA strands. The biosensor was able to detect specific DNA sequences in both synthetic and real samples. Aspects such as reutilization and regeneration of the QCM electrode were also studied.

Effect of Laminaria digitata dietary inclusion and CAZyme supplementation on blood cells, serum metabolites and hepatic lipids and minerals of weaned piglets.

Seaweeds, such as Laminaria digitata, are a sustainable alternative to conventional feedstuffs for weaned piglet diets, improving their health and mitigating environmental impacts. L. digitata has a complex cell wall that can be difficult for monogastrics to digest. However, carbohydrate-active enzymes (CAZymes) such as Rovabio® Excel AP and alginate lyase can help break down these polysaccharides and render intracellular nutrients more accessible. This study aimed to evaluate the impact of 10% L. digitata feed inclusion and CAZyme supplementation on piglet blood cells, serum metabolites, liver lipid and mineral profiles. Forty weaned piglets were randomly assigned to one of four diets (n = 10 each): a control diet, 10% L. digitata (LA), 10% L. digitata + 0.005% Rovabio® Excel AP (LAR), and 10% L. digitata + 0.01% alginate lyase (LAL). After two weeks of trial, animals were slaughtered and liver and blood serum samples taken for analysis. The results showed that the LA and LAL diets increased blood lymphocytes, IgG and IgM, and decreased serum lipids, improving both cellular and humoral immune response and cardiovascular health. Dietary CAZymes reversed the anti-inflammatory and hematopoietic effects. Additionally, cortisol levels were reduced with seaweed inclusion compared to the control diet (P < 0.001). In the liver, total n-3 PUFA and n-6/n-3 ratio were increased and decreased, respectively, due to eicosapentaenoic acid and α-linolenic acid accumulation (P < 0.001). However, total liver mineral content was incorporated to a lesser extent with the combined seaweed and enzyme diets (P < 0.001), potentially indicating a negative effect on mineral bioavailability. Overall, results suggest that a 10% L. digitata inclusion can effectively improve piglet health by reducing stress during weaning, without the need for dietary CAZymes.

pH-Responsive Hybrid Nanoassemblies for Cancer Treatment: Formulation Development, Optimization, and In Vitro Therapeutic Performance.

Current needs for increased drug delivery carrier efficacy and specificity in cancer necessitate the adoption of intelligent materials that respond to environmental stimuli. Therefore, we developed and optimized pH-triggered drug delivery nanoassemblies that exhibit an increased release of doxorubicin (DOX) in acidic conditions typical of cancer tissues and endosomal vesicles (pH 5.5) while exhibiting significantly lower release under normal physiological conditions (pH 7.5), indicating the potential to reduce cytotoxicity in healthy cells. The hybrid (polymeric/lipid) composition of the lyotropic non-lamellar liquid crystalline (LNLCs) nanoassemblies demonstrated high encapsulation efficiency of the drug (>90%) and high drug loading content (>7%) with colloidal stability lasting at least 4 weeks. Confocal microscopy revealed cancer cellular uptake and DOX-loaded LNLCs accumulation near the nucleus of human hepatocellular carcinoma cells, with a large number of cells appearing to be in apoptosis. DOX-loaded LNLCs have also shown higher citotoxicity in cancer cell lines (MDA-MB 231 and HepG2 cell lines after 24 h and in NCI-H1299 cell line after 48 h) when compared to free drug. After 24 h, free DOX was found to have higher cytotoxicity than DOX-loaded LNLCs and empty LNLCs in the normal cell line. Overall, the results demonstrate that DOX-loaded LNLCs have the potential to be explored in cancer therapy.

A three-dimensionally printed otological model for cholesteatoma mastoidectomy training.

PURPOSE: To relate the creation and expert validation (face and content validity) of an affordable three-dimensional (3-D) printed model of temporal bones with chronic otitis media with cholesteatoma (COMC) as a simulator for mastoidectomy. METHODS: We performed computed tomography (CT) of the temporal bones of a patient with COMC followed at the University of São Paulo (USP) Hospital with 3-D Slicer to create a 3-D model of the affected bone using light-curing resin and silicone (cholesteatoma). The final 3-D printed images were scored by 10 otologists using a customized version of the Michigan Standard Simulation Scale Experience (MiSSES). Internal consistency and inter-rater reliability were assessed using Cronbach's α and intraclass correlations. RESULTS: Otologists consistently scored the model positively for fidelity, educational value, reactions, and the overall model quality. Nine otologists agreed that the model was a good educational device for surgical training of COMC. All experts deemed the model ready-or nearly ready-for use. The final cost of the model, including raw materials and manufacturing, was 120 USD. CONCLUSIONS: Using 3-D printing technology, we created the first anatomically accurate, low-cost, disease-reproducing 3-D model of temporal bones for mastoidectomy training for cholesteatoma.

Brazilian Society of Otology task force - Vestibular Schwannoma - evaluation and treatment

Abstract Objective: To review the literature on the diagnosis and treatment of vestibular schwannoma. Methods: Task force members were educated on knowledge synthesis methods, including electronic database search, review and selection of relevant citations, and critical appraisal of selected studies. Articles written in English or Portuguese on vestibular schwannoma were eligible for inclusion. The American College of Physicians' guideline grading system and the American Thyroid Association's guideline criteria were used for critical appraisal of evidence and recommendations for therapeutic interventions. Results: The topics were divided into 2 parts: (1) Diagnosis - audiologic, electrophysiologic tests, and imaging; (2) Treatment - wait and scan protocols, surgery, radiosurgery/radiotherapy, and systemic therapy. Conclusions: Decision making in VS treatment has become more challenging. MRI can diagnose increasingly smaller tumors, which has disastrous consequences for the patients and their families. It is important to develop an individualized approach for each case, which highly depends on the experience of each surgical team.

Sexually-transmitted monkeypox: report of two cases

Abstract Monkeypox is an emerging infection that has spread to all continents since May 2022. It is caused by the zoonotic monkeypox virus, consisting of double-stranded DNA, belonging to the Orthopoxvirus genus of the Poxviridae family, which has high transmissibility, especially by contact with the skin, favoring its sexual transmission. This case report describes a same-sex male couple, both aged 28 years old, without comorbidities. In the index case, perioral and penile lesions started ten days before the consultation, with rapid progression and a high fever that started eight days after the appearance of the lesions. In the second case, the perioral lesions started three days after the partner; however, he remained afebrile. Both were isolated, treated with symptomatic measures, and, after ulceration, the lesions completely regressed in 14 days. Dermatologists should be aware of manifestations of monkeypox, which may include vesiculopustular lesions in areas of sexual contact, as well as oligosymptomatic cases or cases with few skin lesions.

Detailed bladder cancer immunoprofiling reveals new clues for immunotherapeutic strategies.

Objectives: Bladder cancer (BlCa) is the tenth most frequent malignancy worldwide and the costliest to treat and monitor. Muscle-invasive BlCa (MIBC) has a dismal prognosis, entailing the need for alternative therapies for the standard radical cystectomy. Checkpoint blockade immunotherapy has been approved for high-grade non-muscle-invasive BlCa (HG NMIBC) and metastatic disease, but its effectiveness in localised MIBC remains under scrutiny. Herein, we sought to characterise and compare the immune infiltrate of HG NMIBC and MIBC samples, including ICOS expression, a targetable immune checkpoint associated with regulatory T cell(Tregs)-mediated immunosuppression. Methods: Immunohistochemistry for CD83, CD20, CD68, CD163, CD3, CD8, CD4, FoxP3/ICOS and PD-L1 was performed in HG NMIBC and MIBC samples (n = 206), and positive staining was quantified in the peritumoral and/or intratumoral tissue compartments with QuPath imaging software. Results: CD20+ B cells, CD68+ and CD163+ tumor-associated macrophages were significantly increased in MIBCs and associated with poor prognosis. In turn, higher infiltration of T cells was associated with prolonged survival, with exception of the CD4+ helper subset. Intratumoral expression of CD3 and CD8 was independent prognostic factors for increased disease-free survival (DFS) in multivariable analysis. Remarkably, Tregs (FoxP3+/FoxP3+ICOS+) were found differentially distributed between tissue compartments. PD-L1 immunoexpression independently predicted a shorter DFS and associated with higher infiltration of FoxP3+ICOS+ Tregs. Conclusions: Immune infiltrates of HG NMIBC and MIBC display significant differences that may help selecting patients for immunotherapies. Considering ICOS immunoexpression results, it might constitute a relevant therapeutic target, eventually in combination with anti-PD-1/PD-L1 therapies, for certain BlCa patient subsets.

Grape By-Products as Feedstuff for Pig and Poultry Production.

Grape by-products are exceptional options for replacement of conventional and unsustainable feed sources, since large amounts are generated every year from the winery industry. However, the majority is wasted with severe environmental and economic consequences. The present review aimed to evaluate the effects of grape by-products on pig and poultry growth performance. The most recent literature was reviewed using ScienceDirect and PubMed databases and the results of a total of 16 and 38 papers for pigs and poultry, respectively, were assessed. Fewer studies are documented for pig, but the incorporation of grape by-products up to 9% feed led to an improvement in growth performance with an increase in average daily gain. Conversely, lower levels (<3% feed) are needed to achieve these results in poultry. The beneficial effects of grape by-products on animal performance are mainly due to their antioxidant, antimicrobial, and gut morphology modulator properties, but their high level of cell wall lignification and content of polyphenolic compounds (e.g., tannin) limits nutrient digestion and absorption by monogastric animals. The use of exogenous enzymes or mechanical/chemical processes can provide additional nutritional value to these products by improving nutrient bioavailability. Overall, the valorization of grape by-products is imperative to use them as feed alternatives and intestinal health promoters, thereby contributing to boost circular agricultural economy.

Use of Grape By-Products to Enhance Meat Quality and Nutritional Value in Monogastrics.

Grape by-products could be used in monogastric animals' nutrition to reduce feeding costs with conventional crops (e.g., maize and soybean meal) and to improve meat quality. The main grape by-products with the largest expression worldwide, particularly in the Mediterranean region, are grape pomace, grape seed, grape seed oil and grape skins. These by-products are rich sources of bioactive polyphenols, dietary fiber and polyunsaturated fatty acids (PUFA), more specifically, the beneficial n-3 PUFA, that could be transferred to pork and poultry meat. The potential biological activities, mainly associated with antimicrobial and antioxidant properties, make them putative candidates as feed supplements and/or ingredients capable of enhancing meat quality traits, such as color, lipid oxidation and shelf life. However, grape by-products face several limitations, namely, the high level of lignified cell wall and tannin content, both antinutritional compounds that limit nutrients absorption. Therefore, it is imperative to improve grape by-products' bioavailability, taking advantage of enzyme supplementation or pretreatment processes, to use them as feed alternatives contributing to boost a circular agricultural economy. The present review summarizes the current applications and challenges of using grape by-products from the agro-industrial sector in pig and poultry diets aiming at improving meat quality and nutritional value.

Altered excitatory and inhibitory neocortical circuitry leads to increased convulsive severity after pentylenetetrazol injection in an animal model of schizencephaly, but not of microgyria.

OBJECTIVE: Malformations of the polymicrogyria spectrum can be mimicked in rodents through neonatal transcranial focal cortical freeze lesions. The animals presenting the malformations present both altered synaptic events and epileptiform activity in the vicinity of the microgyrus, but the comprehension of their contribution to increased predisposition or severity of seizures require further studies. METHODS: In order to investigate these issues, we induced both microgyria and schizencephaly in 57 mice and evaluated: their convulsive susceptibility and severity after pentyleneterazol (PTZ) treatment, the quantification of their symmetric and asymmetric synapses, the morphology of their dendritic arbors, and the content of modulators of synaptogenesis, such as SPARC, gephyrin and GAP-43 within the adjacent visual cortex. RESULTS: Our results have shown that only schizencephalic animals present increased convulsive severity. Nevertheless, both microgyric and schizencephalic cortices present increased synapse number and dendritic complexity of layer IV and layer V-located neurons. Specifically, the microgyric cortex presented reduced inhibitory synapses, while the schizencephalic cortex presented increased excitatory synapses. This altered synapse number is correlated with decreased content of both the anti-synaptogenic factor SPARC and the inhibitory postsynaptic organizer gephyrin in both malformed groups. Besides, GAP-43 content and dendritic spines number are enhanced exclusively in schizencephalic cortices. SIGNIFICANCE: In conclusion, our study supports the hypothesis that the sum of synaptic alterations drives to convulsive aggravation in animals with schizencephaly, but not microgyria after PTZ treatment. These findings reveal that different malformations of cortical development should trigger epilepsy via different mechanisms, requiring further studies for development of specific therapeutic interventions.

What do Cochrane systematic reviews say about therapeutic tinnitus interventions? / O que revisões sistemáticas Cochrane dizem sobre terapêutica para zumbido?

INTRODUCTION: Tinnitus is a sound perception not related to stimulation. It can significantly impair the quality of life and its treatment is considered one significant challenge of Medicine. OBJECTIVE: To evaluate systematic reviews developed by Cochrane regarding therapeutic interventions for subjective tinnitus. METHODS: It is an overview of Cochrane systematic reviews. We searched systematic reviews on Cochrane Library. The MeSH term "tinnitus" was used for searches. Inclusion criteria involved therapeutic interventions for patients with subjective tinnitus. RESULTS: The search strategy recovered 577 citations with 14 Cochrane systematic reviews. 13 were included because they were focusing on primary tinnitus interventions. One review had no scope of analysis for tinnitus and it was excluded. 7,998 tinnitus patients were evaluated. CONCLUSION: There is a lack of evidence of the effectiveness of any intervention for tinnitus treatment, considering the studies performed so far and compiled in Cochrane systematic reviews.

INTRODUÇÃO: O zumbido é a sensação do som sem que haja estimulação ambiental. Pode prejudicar significativamente a qualidade de vida e seu tratamento é considerado um grande desafio da Medicina. OBJETIVO: Avaliar as revisões sistemáticas desenvolvidas pela Cochrane, no que concerne às intervenções terapêuticas para o zumbido subjetivo. MÉTODOS: Trata-se de overview de revisões sistemáticas Cochrane. Procedeu-se à busca por revisões sistemáticas na Cochrane Library. Foi utilizado o termo DeCS "zumbido". Os critérios de inclusão envolveram intervenções terapêuticas para pacientes com zumbido subjetivo. RESULTADOS: A estratégia de busca recuperou 577 citações e, destas, 14 revisões sistemáticas Cochrane, sendo que 13 enfocavam intervenções primárias para zumbido, sendo estas incluídas neste estudo. Uma revisão não tinha escopo de análise para zumbido e foi excluída. Foram avaliados 7.998 portadores de zumbido. CONCLUSÃO: Há carência de evidência de efetividade de qualquer intervenção, medicamentosa ou não, para tratamento do zumbido, considerando os estudos realizados até o momento e compilados em revisões sistemáticas Cochrane.

Ki67 and LSD1 Expression in Testicular Germ Cell Tumors Is Not Associated with Patient Outcome: Investigation Using a Digital Pathology Algorithm.

TGCTs represent a model of curable disease afflicting especially young men. Defining tumor biological characteristics is crucial to increase current knowledge and tailor the best clinical management. Ki67, a potential prognostic marker, still exhibits heterogenous associations with patient outcomes, thus bringing the need of corroboration with larger cohorts in clinical practice. LSD1, an epigenetic enzyme, represents a future target for epigenetic drugs that may lower treatment-associated morbidity. This study aimed to assess Ki67/LSD1 immunoexpression across all TGCT histological subtypes and correlate it with clinicopathological features. Results were compared with an in silico analysis of the TCGA database. Immunohistochemistry for Ki67 and LSD1 was carried out in a cohort of 157 TGCT tumor samples and assessed using a digital pathology algorithm. LSD1 protein expression was explored in TGCT cell lines, including ATRA-differentiated clones. There was a significant positive correlation between Ki67 and LSD1 H-scores (rs = 0.182, p = 0.037). Ki67 positivity percentage and H-score were significantly higher in non-seminomas (p = 0.0316 and 0.0113, respectively). Expression was not significantly different according to clinicopathological features, including stage, IGCCCG prognosis-based system, or relapse/progression-free survival, which was corroborated by in silico analysis. Our study, making use of digital image analysis, does not confirm the utility of these biomarkers in a daily practice cohort. Although not affecting patient outcome in our cohort, LSD1 is expressed overall in TGCTs, suggesting sensitivity to LSD1 inhibitors.

Three-dimensional printing in otolaryngology education: a systematic review.

PURPOSE: The progressive expansion of the technology that facilitates the development of three-dimensional (3D) printing within the field of otorhinolaryngology has opened up a new study front in medicine. The objective of this study is to systematically review scientific publications describing the development of 3D models having applications in otorhinolaryngology, with emphasis on subareas with a large number of publications, as well as the countries in which the publications are concentrated. METHODS: In this literature review, specific criteria were used to search for publications on 3D models. The review considered articles published in English on the development of 3D models to teach otorhinolaryngology. The studies with presurgical purposes or without validation of the task by surgeons were excluded from this review. RESULTS: This review considered 39 articles published in 10 countries between 2012 and 2021. The works published prior to 2012 were not considered as per the inclusion criteria for the research. Among the 39 simulators selected for review, otology models comprised a total of 15 publications (38%); they were followed by rhinology, with 12 (31%); laryngology, with 8 (21%); and head and neck surgery, with 4 publications (10%). CONCLUSION: The use of 3D technology and printing is well established in the context of surgical education and simulation models. The importance of developing new technological tools to enhance 3D printing and the current limitations in obtaining appropriate animal and cadaver models signify the necessity of investing more in 3D models.

"Benefits of the pedicled osteoplastic flap as a surgical approach of mastoidectomy in cochlear implant surgery".

OBJECTIVE: To evaluate the esthetic and functional results of an osteoplastic flap for mastoid cavity closure in cochlear implant surgery. STUDY DESIGN: Double-blind, prospective, randomized clinical trial. SETTING: tertiary referral center. INTERVENTION(S): On hundred and twenty-six patients were randomized in 2 groups for cochlear implant surgery. Cases (n: 63) underwent simple mastoidectomy using an anteriorly pedicled osteoplastic flap for mastoid closure. In controls (n: 63), a traditional periosteal flap was used. Evaluation with the POSAS questionnaire was performed 1 year after surgery to assess surgical wound esthetics. Sixteen patients from each group had postoperative CT-scans and wideband tympanometry to assess mastoid aeration and middle ear absorbance. Gender and time after surgery were correlated. MAIN OUTCOME MEASURE(S): Evaluation of the quality of the surgical wound with the application of a questionnaire validated in the medical literature and translated into Portuguese language called POSAS, considering the perception of the blinded patient and doctor regarding the surgical technique proceeded. A lower POSAS score suggests better esthetics of the surgical wound. Secondary outcomes are volumetric measurement of aeration inside mastoid cavity using 3D computer tomography exam, which aims to analyze the influence of fibrocicatricial retraction in the surgical wound into the mastoid and the interference of its aeration volume in the absorption of sound in the middle ear, using the wideband tympanometry exam. RESULTS: The POSAS questionnaire in the Case group showed a lower level of local pain and itchiness, a skin color and thickness more similar to the surrounding skin and less irregularity and stiffness, with no influence from time after surgery and gender compared to the Control group. The median tomographic volume was 6.37 cc in the cases and 4.60 cc in controls. Wideband tympanometry showed general smaller sound absorbance in the Case group results, specially, at 1000 Hz frequency. No intraoperative or postoperative complications were observed with the osteoplastic flap. CONCLUSIONS: This technique is an effective and safe alternative to alleviate common problems of mastoid surgery for cochlear implantation. In addition to esthetic benefits, it has less interference in middle ear physiology of sound absorbance and less fibrous tissue into the mastoid cavity during the follow-up of more than 1 year.