Medico-legal considerations in immediate loading implantology: risks, responsibilities, and best practices.

The field of immediate loading implantology has grown rapidly, offering quicker solutions for prosthetic rehabilitation. However, the complexity of this technique raises significant medico-legal concerns regarding patient safety, treatment planning, and professional liability. These issues are particularly relevant in elective procedures where failure could lead to litigation. A comprehensive review of current literature, including clinical studies, legal rulings, and malpractice claims, was conducted to assess the legal implications of immediate loading implantology. The analysis focused on professional liability, patient consent, and complications during treatment. The evidence indicates that a high standard of care, including detailed preoperative planning, risk assessment, and clear patient communication, is essential in minimizing legal risks. Malpractice claims often arise from inadequate patient information or failure to follow established protocols. Proper documentation of informed consent and adherence to evidence-based dentistry (EBD) guidelines are crucial to protect both patients and practitioners. Immediate loading implantology offers numerous benefits, but it requires meticulous planning and patient management to avoid medico-legal issues. Ensuring comprehensive patient consent and following evidence-based practices are key to reducing professional liability and improving outcomes. Further studies should explore standardized protocols for reducing complications and legal disputes in implantology.

Biomechanical considerations of chemical structure and biosafety of current ceramic biomaterials for dentistry: review and outlook of the current state of the art.

Biomaterial refers to any material, non-pharmaceutical or combination of substances of synthetic or natural origin used for any period independently or as part of a system for the purpose of healing, assisting the growth or replacement of tissues, organs or functions of the body. It is an unsustainable material that interacts with biological systems. Before being produced a biomaterial goes through a sequence of steps, which includes: 1) the definition of the problem that the material will be called to solve (treatment, replacement of the instrument, aesthetic reasons); 2) design of the device, composition and control of materials (mechanical properties, toxicity, biological response, corrosion resistance, interaction with proteins, cells and tissues), manufacture, sterilization and standardization; 3) control of the device (in experimental animals, in vitro) clinical studies, studies; and 4) monitor its long-term use in vivo, in vitro and in patients. Research for ceramic materials is evolving and because they can be porous or glassy, they find applications in medicine and biotechnology, as they can be used as fillers, covering materials and scaffolds. Therefore, ceramic biomaterials are widely used not only in the field of orthopedic and maxillofacial surgery but also in dentistry as for dental prostheses. Materials monitoring technologies allow us to monitor the three-dimensional development in space, as well as imperfections or micro-cracks in the ceramic.

Assessment of psychological status by a comprehensive approach in thyroid cancer patients undergoing radionuclide therapy: A feasibility study.

This feasibility study evaluated the psychological status of patients with differentiated thyroid cancer (DTC) before, during, and 40 days after administration of I-131 radionuclide therapy (RAI). We investigated the appropriateness of providing patient a comprehensive psychological assessment in an isolation ward. Thirty consecutive patients (Study Group; SG) who received RAI were enrolled. The tools used were the Hospital Anxiety and Depression Scale (HADS) at three different moments, and the Coping Responses Inventory (CRI) at baseline for each patient. A supportive approach was also implemented. Data were collected at the first specialist visit, at the day of admission, and at 40 days follow-up visit. A matched cohort of patients (Control Group; CG), who did not receive psycho-oncological counseling, was retrospectively studied only about their medical needs and requests. Staff exposure to radiation was also compared during SG and CG hospitalization, to assess a possible reduction of radiological risk for them. A significant difference between the basal, intermediate, and final psychological status was observed (p < 0.0001), which was found to be irrespective of the induced hypothyroidism. Patients showed a significant worsening of their status in terms of anxiety and depression after the consent, but it improved 40 days after treatment. Repeated measures analysis showed a similar trend in patients' psychological status over this period. At hospital discharge, patients showed indirect signs of increased well-being. CG required more nursing and medical interventions. Staff exposure was significantly lower during hospitalization of SG as compared to CG. This study demonstrates that timed psychological evaluation and appropriate support may help to reduce anxiety and depression of patients receiving a diagnosis of cancer and undergoing RAI. Moreover, an improvement of workplace safety was recorded.

Factors and management techniques in odontogenic keratocysts: a systematic review.

OBJECTIVES: Odontogenic keratocysts exhibit frequent recurrence, distinctive histopathological traits, a tendency towards aggressive clinical behavior, and a potential linkage to the nevoid basal cell carcinoma syndrome. The aim of this systematic review is to compile insights concerning the control of this condition and assess the effectiveness of various treatment approaches in reducing the likelihood of recurrence. MATERIALS AND METHODS: The following systematic review adhered to the PRISMA guidelines. The systematic revision was registered on PROSPERO and  structured around the questions related to the population, intervention, control, outcome and study design (PICOS). RESULTS: After conducting a search on the PubMed database, we initially identified 944 records. After using end-note software to remove duplicate entries, results totally with 462 distinct records. A thorough review of the titles and abstracts of these articles led to the selection of 50 papers for in-depth examination. Ultimately, following the application of our eligibility criteria, we incorporated 11 articles into our primary outcome analysis. CONCLUSION: Among the studies examined, the most common location for these lesions was found to be in the area of the mandibular ramus and the posterior region of the mandible. In cases where the exact location wasn't specified, the mandible emerged as the predominant site. When we considered the characteristics of these lesions in studies that mentioned locularity, most were described as unilocular in two studies, while in two other studies, the prevalence of multilocular lesions was observed. Risk factors associated with keratocyst recurrence include younger patient age, the presence of multilocular lesions, larger lesion size, and a longer anteroposterior dimension. Certain treatment methods have demonstrated a lack of relapses. These include the use of 5-fluorouracil, marsupialization, enucleation with peripheral ostectomy or resection, enucleation and curettage, as well as resection without creating continuity defects. However, it is important to note that further research is essential. Prospective studies and randomized trials are needed to collect more comprehensive evidence regarding the effectiveness of various treatment approaches and follow-up protocols for managing odontogenic keratocysts. CLINICAL RELEVANCE: Odontogenic keratocysts still enter into differential diagnoses with other lesions that affect the jaw bones such as ameloblastama and other tumor forms, furthermore it is not free from recurrence, therefore the therapeutic approach to the lesion aimed at its elimination can influence both the possible recurrence and complications, knowledge of the surgical methods that offer the most predictable and clinically relevant result for the management of follow-up and recurrences.

Challenging Axillary Lymph Nodes on PET/CT in Cancer Patients throughout COVID-19 Vaccination Era.

BACKGROUND: The unexpected detection of axillary lymphadenopathy (AxL) in cancer patients (pts) represents a real concern during the COVID-19 vaccination era. Benign reactions may take place after vaccine inoculation, which can mislead image interpretation in patients undergoing F-18-FDG, F-18-Choline, and Ga-68-DOTATOC PET/CT. They may also mimic loco-regional metastases or disease. We assessed PET/CT findings after COVID-19 first dose vaccination in cancer patients and the impact on their disease course management. METHODS: We evaluated 333 patients undergoing PET/CT (257 F-18-FDG, 54 F-18-Choline, and 23 Ga-68 DOTATOC) scans after the first vaccination with mRNA vaccine (Pfizer-BioNTech) (study group; SG). The uptake index (SUVmax) of suspected AxL was defined as significant when the ratio was > 1.5 as compared to the contralateral lymph nodes. Besides, co-registered CT (Co-CT) features of target lymph nodes were evaluated. Nodes with aggregate imaging positivity were further investigated. RESULTS: Overall, the prevalence of apparently positive lymph nodes on PET scans was 17.1% during the vaccination period. 107 pts of the same setting, who had undergone PET/CT before the COVID-19 pandemic, represented the control group (CG). Only 3 patients of CG showed reactive lymph nodes with a prevalence of 2.8% (p < 0.001 as compared to the vaccination period). 84.2% of SG patients exhibited benign characteristics on co-CT images and only 9 pts needed thorough appraisal. CONCLUSION: The correct interpretation of images is crucial to avoid unnecessary treatments and invasive procedures in vaccinated cancer pts. A detailed anamnestic interview and the analysis of lymph nodes' CT characteristics, after performing PET/CT, may help to clear any misleading diagnosis.

Investigation of the presence of Non-carious cervical lesions (NCCLs) in ancient adult skulls: analyzing data from prehistoric and historical samples through a systematic review and meta-analysis.

OBJECTIVES: Historically, the prevalence of caries has undergone significant changes, particularly increasing with the industrialization of sugar consumption. When examining ancient populations, lower caries rates are discovered, attributed in part to dietary factors. These populations consumed abrasive foods, leading to occlusal wear and reduced non-axial occlusal forces, potentially influencing Non-Carious Cervical Lesions (NCCLs). Although some attribute NCCLs to abfraction, the mechanism remains debated. This systematic review aims to evaluate the presence of NCCLs in ancient populations, shedding light on the factors contributing to their occurrence. MATERIALS AND METHODS: The present systematic review was registered on PROSPERO, and the manuscript was prepared following PRISMA guidelines. RESULTS: After the literature search and article screening, data from 6 studies were included in the meta-analysis, with only 2 reporting NCCLs in ancient skulls, encopassing 17 subjects in 805 examined skulls, suggesting their presence even before the widespread use of toothbrushes. This finding indicates a potential etiopathogenic mechanism linked to abfraction, but the cause is complex and involves abrasive and erosive factors closely tied to dietary habits. CONCLUSIONS: In summary, NCCLs were present in ancient populations, albeit with a much lower prevalence. Their occurrence cannot be solely attributed to wear mechanisms but must be connected to abrasive factors related to diet or practices with religious and cultural significance, such as the use of labrets. CLINICAL RELEVANCE: Th the knowledge of NCCLs presence in acient sculls is crucial today for better understand the associated risk factors. In this context, the analysis of ancient skulls allows us to discern the role that tooth brushing and diet played in the formation of NCCLs, over the past century.

Dentistry in the centuries: a historical overview.

The began of the dentistry as medicine's concept has a long history dating back to 7000 BCE, making it one of the earliest medical specialties. In its early days, dental diseases were often attributed to supernatural causes like "evil spirits" and "tooth worms." However, today, dentistry leverages cutting-edge technologies, including artificial intelligence, for diagnosis and treatment. This journey reflects the remarkable progress made in the field. Despite these advancements, there is still room for improvement in integrating dental knowledge and skills with medical science and engineering backgrounds. Bridging these disciplines could lead to even greater advancements in the diagnosis and maintenance of oral health. Thus, over time, it has transformed from a primitive form of medicine into a modern field that emphasizes preventative dental care, advanced diagnostics, and state-of-the-art treatment.

The Role of Temporomandibular Joint Arthroscopy for Diagnosis and Surgical Management of Synovial Chondromatosis.

OBJECTIVE: We report the experience of our maxillo-facial surgery unit into the diagnostic and the therapeutic role of arthroscopy of temporomandibular joint (TMJ) synovial chondromatosis (SC). MATERIALS AND METHODS: A series of sixteen patients with an imaging, arthroscopical, and histological diagnosis of SC treated with arthroscopy was selected. The surgeries were conducted in the Department of Maxillo-facial surgery, Academic hospital of Udine, from January 2016 to December 2022. Medical history, clinical examination, imaging, arthroscopical, and histological characteristics were recorded and then reviewed and discussed. RESULTS: Clinical improvement, both in pain and in maximum incisal opening (MIO), were noticed in whole patients. Histologically, according to Milgram's classification, the sample was fairly homogeneous. Arthroscopic treatment was successful in 87.5% of the patients. Only two cases of SC relapse were registered and were then submitted to open surgery to perform a total sinovectomy. The data collected were used to develop an SC classification proposal based on clinical, radiological (magnetic resonance imaging), arthroscopical, and histopathological characteristics. CONCLUSIONS: TMJ arthroscopy must be considered the first line of treatment for SC, leaving open surgery to relapses cases and those cases with extraarticular extension. A univocal classification is essential to best stage and prognostically characterise this pathology.

Efficacy of Systematic Early-Second-Trimester Ultrasound Screening for Facial Anomalies: A Comparison between Prenatal Ultrasound and Postmortem Findings.

Second-trimester 2D ultrasound (US) assessment of the fetal anatomy, as proposed by worldwide guidelines, allows detecting the majority of fetal malformation. However, the detection rates of fetal facial anomalies seem to still be low, mostly in cases of isolated facial malformation. The purpose of this research was to assess and analyze the concordance between the antenatal imaging findings from second-trimester US screening and the results of fetal postmortem autopsy. Between January 2010 and January 2020, there were 43 cases where fetuses with prenatal ultrasound diagnosis of a face abnormality, associated or not with a genetic syndrome or chromosomal disorder, following intrauterine death (IUD) or termination of pregnancy (TOP) after the 13 weeks of pregnancy, underwent autopsy in the Pathological Anatomy section of Bari Polyclinic specializing in feto-placental autopsies. The diagnosis of the fetal facial defects at ultrasound was compared with the findings at autopsy in all cases. A very high level of agreement between prenatal ultrasound and autopsy findings was found for facial abnormalities associated with genetic syndromes or numerical abnormality of chromosomes. A lower level of concordance was instead found in isolated facial defects or those associated with other organ anomalies, but not associated with genetic syndrome or numerical chromosome anomaly. A detailed examination of aborted fetuses led to successful quality control of early-second-trimester ultrasound detection of facial anomalies; however, it was less accurate for the isolated ones. It is, thus, reasonable to propose a systematic early-second-trimester prenatal ultrasound screening for facial anatomy by operators specialized in fetal medicine field, using 2D, 3D, and 4D techniques (two-, three-, and four-dimensional ultrasound).

Radiographic marginal bone level evaluation around two different tissue-level implant systems: a one-year prospective study.

BACKGROUND: Marginal bone loss, is a frequently reported variable in the evaluation of dental implants. The primary objective of this study was to evaluate radiographic marginal bone level changes around the two different tissue-level implant systems placed adjacently in the posterior maxilla or mandible. The influence of implant macro-geometry and vertical soft tissue thickness on marginal bone loss were also evaluated. METHODS: Seven patients were included in the study and a total of 18 implants were analyzed. Each patient received two different implants placed adjacently in the maxilla or the mandible. The implants used in our study were either Straumann® SP cylindrical implants or JD Octa® tapered implants. During the surgery, vertical soft-tissue thickness was measured with a periodontal probe placed on the top of the bony crest and in the center of the future implant site. Healing abutments were then seated. Three months following implant placement, impressions were taken, and screw-retained metal ceramic prostheses were delivered. Standardized intraoral radiographs were taken immediately after implant placement and one year following implant loading in order to assess marginal bone level changes. RESULTS: Results showed a mean marginal bone loss of 0.55±0.5 mm for Straumann® SP implants and 0.39±0.49 mm for JD Octa® implants after one year of loading and the difference was not statistically significant between the two systems. A statistically significant correlation was found between soft tissue thickness and marginal bone loss; in sites with thin mucosal tissues (≤2 mm), there was significantly greater bone loss compared to sites with thick, soft tissues (> 2 mm) in both implants. CONCLUSIONS: Radiographic marginal bone loss was not statistically different between the two implant systems at the one-year examination period. Moreover, vertical soft tissue thickness influenced marginal bone loss regardless of the implant system used.

Is the Non-Coding RNA miR-195 a Biodynamic Marker in the Pathogenesis of Head and Neck Squamous Cell Carcinoma? A Prognostic Meta-Analysis.

Head and neck squamous cell carcinoma (HNSCC) represents a heterogeneous group of neoplasms whose histological derivation comes from the mucous membranes lining the epithelium: the oral cavity, the larynx, the hypopharynx, the nasopharynx, and the oropharynx. The etiopathogenetic mechanisms involving tumor genesis including the alteration of cell proliferation, apoptosis, invasion, migration, and death may involve alterations in the expression of microRNA (miR). To date there have been no systematic reviews with meta-analysis conducted specifically on the role of miR-195 in HNSCC; therefore, our hypothesis was to evaluate if the aberrant expression of miR-195 in HNSCC tissues may represent a prognostic biomarker of survival through the hazard ratio (HR) and relative risk (RR) analysis. The systematic review was designed according to the PRISMA indications; in total, three electronic databases were consulted (PubMed, Scopus, Cochrane Central Trial) including Google Scholar and the gray literature, and a combination of keywords was used such as miR-195 AND HNSCC, microRNA AND HNSCC and miR-195. The meta-analysis and trial sequential analysis were performed using RevMan 5.41 software and TSA software (Cochrane Collaboration, Copenhagen, Denmark). This search identified 1592 articles and, at the end of the selection process, three articles were included. The results of the meta-analysis reported an aggregated risk ratio for overall survival (OS) between the expression of miR-195 at the highest and lowest of 0.36 and 6, respectively, 95% CI: [0.25, 0.51]. Heterogeneity was evaluated through Chi2 = 0.05 df = 2 (p = 0.98) and the Higgins index I2 = 0%. The test for the overall effect was Z = 5.77 (p < 0.00001). The forest plot was in favor of higher OS in patients with high miR-195 expression.

Jacob's Disease: Case Series, Extensive Literature Review and Classification Proposal.

Jacob's disease is a rare entity consisting of the formation of a pseudojoint between an abnormal coronoid process of the mandible and the inner surface of the zygomatic bone. First described by Jacob in 1899, its diagnosis and definition have never been entirely univocal. In this paper, we present three emblematic cases and an extensive review of the literature on Jacob's disease. Given the variability observed in the presentation of the disease, we have developed a proposal for the classification, here reported.

In Vitro Mechanical Properties of a Novel Graphene-Reinforced PMMA-Based Dental Restorative Material.

Recent studies suggest that the incorporation of graphene in resin-based dental materials might enhance their mechanical properties and even decrease their degree of contraction during polymerization. The present study aimed at comparing the three-point flexural strength (FS), the compressive strength (CS), and the Vickers hardness (VH) of a CAD/CAM poly-methylmethacrylate (PMMA)-based resin, a recently introduced graphene-reinforced CAD/CAM PMMA-based resin (G-PMMA), and a conventional dental bis-acryl composite resin (BACR). No significant differences (p > 0.05) were detected among the materials in terms of flexural strength. On the other hand, a mean flexural modulus value of 9920.1 MPa was recorded in BACR group, significantly higher compared to the flexural modulus detected for G-PMMA (2670.2 MPa) and for conventional PMMA (2505.3) (p < 0.05). In terms of compressive modulus (MPa) and compressive strength (MPa), BACR was significantly stiffer than PMMA and G-PMMA. Concerning VH measurements, a significantly increased hardness emerged comparing the BACR group (VH 98.19) to both PMMA and G-PMMA groups (VH 34.16 and 34.26, respectively). Based on the finding of the present study, the graphene-reinforced (PMMA)-based polymer herein tested was not superior to the conventional PMMA and seemed not able to be considered as an alternative material for permanent restorations, at least in terms of hardness and mechanical response to compressive stress. More research on the mechanical/biological properties of G-PMMAs (and on graphene as a filler) seems still necessary to better clarify their potential as dental restorative materials.

Odontogenic-Related Head and Neck Infections: From Abscess to Mediastinitis: Our Experience, Limits, and Perspectives-A 5-Year Survey.

BACKGROUND: Head and neck infections are commonly caused by affections with an odontogenic origin. Untreated or non-responsive to treatment odontogenic infections can cause severe consequences such as localized abscesses, deep neck infections (DNI), and mediastinitis, conditions where emergency procedures such as tracheostomy or cervicotomy could be needed. METHODS: An epidemiological retrospective observational study was performed, and the objective of the investigation was to present a single-center 5-years retrospective analysis of all patients admitted to the emergency department of the hospital Policlinico Umberto I "Sapienza" with a diagnosis of odontogenic related head and neck infection, observing the epidemiological patterns, the management and the type of surgical procedure adopted to treat the affections. RESULTS: Over a 5-year period, 376,940 patients entered the emergency room of Policlinico Umberto I, "Sapienza" University of Rome, for a total of 63,632 hospitalizations. A total of 6607 patients were registered with a diagnosis of odontogenic abscess (10.38%), 151 of the patients were hospitalized, 116 of them were surgically treated (76.8%), and 6 of them (3.9%) manifested critical conditions such as sepsis and mediastinitis. CONCLUSIONS: Even today, despite the improvement of dental health education, dental affections can certainly lead to acute conditions, necessitating immediate surgical intervention.

Evaluation of qualitative and quantitative taste alterations in COVID-19.

A large percentage of coronavirus disease 2019 (COVID-19) patients have taste dysfunction. Interleukin 6 (IL-6) levels in mild and moderate COVID-19 patients with the type (quantitative or qualitative) of taste disorders were compared in this observational study. The 208 COVID-19 patients (118 men and 90 women) revealing only taste dysfunctions as prodromic symptoms were classified as mild and moderate patients. Survey results were used to evaluate the taste disorder. The IL-6 levels were measured using a chemiluminescence assay. Statistical analysis was conducted using the Wilcoxon rank, Welch's, and Mann-Whitney tests. The findings revealed that neither the presence of dysgeusia or phantogeusia nor the perception of sour and salty, differed statistically significantly between moderate and mild patients (P > 0.05). But between moderate and mild patients, there were statistically significant differences in how umami, bitter, sweet, and parageusia were perceived (P < 0.05). There was an impairment of multiple tastes up to ageusia in patients with high IL-6 levels. The findings demonstrated that parageusia and dysfunctions in umami, bitter, and sweet taste perception can be indicators of more severe forms of COVID-19.

Natural Bioactive Compounds against Oxidative Stress: Dietary Polyphenols Strike Back.

Oxidative stress is a major cellular and metabolic burden that can really alter cell life and become the base for disease onset and development. Many widespread pathologies can develop from an unresolved oxidative stress situation; thus, addressing this state is paramount for human health. Our antioxidant enzymes sometimes are not just enough. Fortifying our defense and the antioxidant and anti-inflammatory system can make a difference in our health: if this is attainable with our dietary habits, it could be a dream come true. Polyphenols are a fantastic tool indeed in the fight against oxidative stress: they are easy to obtain, with little cost, no side effects, and have a multitude of metabolic actions. This perspective review would shed light on polyphenol's metabolic and molecular action regarding oxidative stress to help preserve our health.

Temporomandibular Disorders as a Risk Factor for Suicidal Behavior: A Systematic Review.

BACKGROUND: Temporomandibular disorders (TMD) are a group of common musculoskeletal dysfunctions that affect the temporomandibular joint or masticatory muscles and related structures or are expressed as a clinical combination of these two factors. The etiology of TMD is multifactorial and features related to anxiety, depression and mental disorders can contribute to the predisposition, onset and progression of TMD. The ability to adapt and develop coping attitudes was reduced in patients presenting with chronic pain, while suicidal behavior (suicidal ideation, suicide attempts, and suicide completion) was increased. The objective of this review was therefore to investigate suicidal behavior in relation to TMD. METHODS: The review was performed according to the PRISMA 2020 guidelines. Six databases (PubMed, MEDLINE, EMBASE, Scopus, Ovid, and Google Scholar) were consulted through the use of keywords related to the review topic. The study is registered on PROSPERO (CRD42022320828). RESULTS: The preliminary systematic search of the literature yielded 267 records. Excluding duplicates, 15 were considered potentially relevant and kept for title and abstract analysis. Only six articles were considered admissible reporting a single exposure factor, TMD and a single outcome, suicidal behavior, although these were evaluated through different assessment tools. We found a low association of TMD with suicidal behavior in observational studies, with estimates partly provided [prevalence ratio (PR) from 1.26 to 1.35, 95% confidence intervals (CI) from 1.15 to 1.19 (lower) and from 1.37 to 1.54 (higher); and odds ratios (OR) from 1.54 to 2.56, 95% CI from 1.014 to 1.157 (lower) and 2.051 to 6.484 (higher)], a relevant sample size (n = 44,645), but a few studies included (n = 6). CONCLUSIONS: The results of the included studies showed that the prevalence data of suicidal behavior were more present in young adults with TMD, with a controversial association with gender. Suicidal behavior was also correlated and aggravated by the intensity of pain.

Congenital adrenal hyperplasia. Role of dentist in early diagnosis.

Congenital adrenal hyperplasia (CAH) is a genetic disorder characterized by an impairment of steroid synthesis due to an altered production of 21-hydroxylase enzyme. Corticoid hormones are involved in the development and functioning of many organs. The aim of the present study was to review the international literature to collect data regarding oral manifestations of CAH. A review of the literature describing oral features of patients affected by CAH was performed using electronic databases (PubMed and Scopus). The data about number of patients, form of CAH, and oral findings were extracted and analyzed. Seven studies were included in the final analysis. The principal findings reported regarded an advanced dental development observed in patients with CAH. One paper reported amelogenesis imperfecta and periodontal issues. The dentist could be the first specialist involved in the CAH syndrome diagnosis, identifying the characteristic features described above, especially for the classical simple virilizing and non-classical form.

Does miR-197 Represent a Valid Prognostic Biomarker in Head and Neck Squamous Cell Carcinoma (HNSCC)? A Systematic Review and Trial Sequential Analysis.

(1) Background: Between tumors of the head and neck region, the squamous cell variant (HNSCC) is the most common and represents one of the main neoplasms affecting humans. At the base of carcinogenesis processes, there are genetic alterations whose regulation can be influenced by changes in the expression of microRNA (miR). Consequently, despite recent studies indicating miR-197 as a potential prognostic biomarker of survival for many varieties of cancer, there are currently no systematic reviews and trial sequential/bioinformatics/meta-analysis regarding the role of miR-197 in HNSCC. Our hypothesis was that with the existing literature, it is possible to clarify whether the different expressions of miR-197 in neoplastic tissues can represent a prognostic biomarker of survival in head and neck tumors. (2) Methods: The systematic review was reported following the indications of PRISMA and by consulting six electronic databases (including one register). Moreover, this review was carried out using the Kaplan-Meier plotter database portal, and hazard ratio (HR) data were extracted. Finally, a trial sequential analysis (TSA) was conducted to test the robustness of the proposed meta-analysis. (3) Results: This search identified 1119 articles and outcomes of the meta-analysis, reporting an aggregate HR for overall survival (OS) between the highest and lowest miR-197 expression of 1.01, 95% CI: [1.00, 1.02]. (4) Conclusions: We can state that, from the literature data included in the present meta-analysis, and from the TSA and bioinformatics analysis data, miR-197 does not currently represent a valid prognostic biomarker for HNSCC, although the data provided by the Kaplan-Meier plotter suggest that miR-197 can serve as a putative biomarker in short-term (5 years) survival.

Potential Role of miR-196a and miR-196b as Prognostic Biomarkers of Survival in Head and Neck Squamous Cell Carcinoma: A Systematic Review, Meta-Analysis and Trial Sequential Analysis.

The etiopathogenetic mechanisms involving tumor genesis, including alteration of cell proliferation, apoptosis, invasion, migration, and death, may lead to alterations in microRNAs (miR) expression. The hypothesis is that with the presence in the literature of recent studies conducted on miR-196a and miR-196b, it is possible to clearly determine, by aggregating the results, whether miR-196 upregulation in head and neck squamous cell carcinoma (HNSCC) tissues can represent a prognostic biomarker of survival through hazard ratio (HR) analysis. The systematic review was conducted following the indications of the PRISMA, and four electronic databases were used (Science Direct, SCOPUS, PubMed, and Cochrane Central), with the addition of gray literature. Combinations of keywords were used, such as miR-196, miR-196 AND HNSCC, microRNA AND HNSCC, LSCC AND miR-196, OSCC AND miR-196, OPSCC AND miR-196, HSCC AND miR-196. The meta-analysis and trial sequential analysis (TSA) were performed using RevMan 5.41 software and Stata 13 (StataCorp, College Station, TX, USA) with the implementation of the R 4.2 software. This search identified 1593 reports and, at the end of the selection, five articles were inserted. The results of the meta-analysis report an aggregate HR for overall survival (OS), between the highest and lowest miR-196 expression of 1.67, 95% CI: [1.16, 2.49]. In this meta-analysis, we found that the forest plot is in favor of higher OS in HNSCC patients, compared with the control, with low miR-196 expression, correlating this data with a favorable prognosis, which indicated the potential role of this miRNA in strengthening the therapy sensitiveness of the HNSCC patients. Consequently, the present systematic review places itself, together with other systematic reviews on this topic, in a key role to the finding of Phase 3 clinical trials studies, in search for a prognostic model of miR-196 for HNSCC. In conclusion, with the limitations of the meta-analysis, it can be argued that miRs of the miR-196 family could be independent prognostic biomarkers of survival for HNSCC.