Efficacy of antimalarials in oral lichen planus: A systematic review.

OBJECTIVE: To evaluate whether hydroxychloroquine (HCQ) or chloroquine (CQ) are effective for the treatment of oral lichen planus (OLP). MATERIALS AND METHODS: A literature search was conducted in four databases. Clinical studies investigating the effect of HCQ/CQ in patients with OLP were included. RESULTS: Eleven studies were included. Four were RCTs and seven quasi-experimental studies. The studies included 390 patients diagnosed with OLP, of which 326 and 7 received HCQ and CQ, respectively. 46 patients received topical dexamethasone, 5 placebo and 6 griseofulvin as controls. Five studies assessed pain, and all of them obtained pain reduction with the use of HCQ. Six studies reported objective clinical improvement of OLP with the use of HCQ. Five studies that used a subjective scale obtained that 24%-100% of the patients achieved a complete/almost complete improvement of OLP lesions and its symptomatology. The most frequent side effects were vision problems, gastric discomfort, rash, nauseas, headaches, skin pigmentation, and elevated kidney function. 17 patients had to withdraw from the studies. CONCLUSIONS: Current evidence is scarce to confirm HCQ as a therapeutic option for OLP. More RCTs are needed to compare its efficacy with topical corticosteroids and to evaluate whether HCQ reduces relapses of OLP.

Regeneration of periodontal intrabony defects using platelet-rich fibrin (PRF): a systematic review and network meta-analysis.

One of the most promising approaches to correct periodontal bone defects and achieve periodontal regeneration is platelet-rich fibrin (PRF). This systematic review and meta-analysis aimed to evaluate the regeneration of periodontal bone defects using PRF compared to other regenerative treatments. The data search and retrieval process followed the PRISMA guidelines. An electronic search of MEDLINE, Cochrane, and PubMed databases was performed, selecting exclusively randomized clinical trials where the following were measured: probing depth reduction (PD), clinical attachment level gain (CAL), and radiographic bone fill (RBF). Out of 284 selected articles, 32 were chosen based on inclusion criteria. The use of platelet-rich fibrin (PRF) + open flap debridement (OFD), PRF + metformin, PRF + platelet-rich plasma (PRP), and PRF + OFD/bone graft (BG) significantly reduced PD and improved CAL and RBF. However, the combination of PRF + BG, PRF + metformin, and PRF + STATINS reduced CAL. The intervention of PRF combined with different treatments such as metformin, OFD, PRP, BG, and STATINS has a significant impact on improving PD and CAL. The use of PRF significantly improved the regeneration of periodontal bone defects compared to other treatments.

Parents' perspectives on dental team as advisors to promote HPV vaccination among Spanish adolescents.

PURPOSE: Human papillomavirus (HPV) is a prevalent sexually transmitted infection responsible for many anogenital and oropharyngeal cancers. Dental care providers have the potential to influence vaccine uptake, yet little is known about how patients perceive their role in HPV education and prevention. METHODS: Parents of adolescents aged 9 to 17 years (n = 375) were recruited from Valdeorras District Hospital (Galicia, Spain) to investigate parents' attitudes concerning the involvement of dental care providers in discussions related to HPV. A survey was distributed to the participants, and 343 (91.5%) were included in the analysis. RESULTS: In general, nearly half of the parents reported feeling comfortable regarding discussing HPV with their dentist. Participants described more comfort with dentists than with dental hygienists. Parents' comfort levels were influenced by various social determinants of health, including education level, marital status, geographic origin, and child vaccination status (p > 0.05). CONCLUSION: Parents reported varying comfort levels when discussing HPV and its vaccine with dental professionals, displaying a preference for dentists. Dental settings have the potential to promote vaccination, but the existence of ongoing barriers needs to be addressed.

Effect of auxiliary geometric devices on the accuracy of intraoral scans in full-arch implant-supported rehabilitations: An in vitro study.

OBJECTIVES: The aim of the present in vitro study was to evaluate the effect of a novel auxiliary geometric device (AGD) on the accuracy of full-arch scans captured with 3 different intraoral scanners (IOS). METHODS: An edentulous maxillary model with four internal connection implant replicas was scanned using 3 different IOS: iTero Element 5D (ITERO) (Align Technology, Tempe, AZ, USA), Trios 4 (TRIOS) (3Shape A/S, Copenhagen, Denmark), and Carestream 3700 (CS) (Carestream Dental, Atlanta, USA). Thirty-six scans were taken with each IOS, 18 with the AGD in place, and 18 without the AGD. A digital master model was created using an industrial optical scanner (ATOS compact Scan 5M, GOM GmbH, Braunschweig, Germany). The master and IOS models were aligned using the scan bodies as a reference area. A surface comparison was performed, and deviation labels were exported for each scan body to evaluate the linear and angular deviation. Total body, platform and angular deviations were measured. RESULTS: The use of AGD resulted in a statistically significant increase of angular deviation: 0.87° (SD=0.21) in the AGD group versus 0.64° (SD=0.46) in the no AGD group (p-value=0.005). The difference between the AGD and no AGD groups was not statistically significant for total body and platform deviation values (p-value=0.051 and 0.302 respectively). Using AGD, ITERO showed a statistically significant increase in angular deviation (mean difference=-0.46 µm, p-value=0.002) and a decrease in mean platform deviation (mean difference=63.19 µm, p-value<0.001). No statistically significant differences were found for the other IOS. CONCLUSIONS: The use of AGD did not add benefit on CS and TRIOS. On ITERO, there was an improvement in platform deviation, that was outweighed by the worsening of the angular deviation. CLINICAL SIGNIFICANCE: In vitro data suggest that intraoral scans can be successfully used in full-arch cases. The use of AGD has no additional benefit on CS and TRIOS. On ITERO there was an improvement in platform deviation that was outweighed by the worsening of the angular deviation. Translational application to clinical practice deserves further investigation, taking into account patient-related and anatomical variables.

Oral lichen planus in children: A systematic review / Liquen plano oral en niños: una revisión sistemática

Background: Oral Lichen Planus is a common chronic inflammatory disease of the oral mucosa. The prevalencein adults ranges between 0.5% and 2%, while in children is reported to be about 0,03%. Clinical features of OralLichen Planus could be variable in both adults and children, ranging from painless white hyperkeratotic lesions topainful erythematous atrophic ones.Actually, there are no systematic reviews in the literature on OLP in children, whereby this paper aims to sum-marize all the pathophysiological aspects and identify all cases described in the literature of Oral Lichen Planusin children, reporting their clinical characteristics.Material and Methods: A systematic review of the literature was performed in online databases including PubMed,Scopus, Web of Science, Science Direct, EMBASE. In addition, in order to identify reports not otherwise identifi-able, an analysis of the gray literature was performed on google scholar and in Open Gray.Results: By literature analysis, it emerged that most cases were reported from India. The mean age at time of diag-nosis of the disease was 11 years, ranging from 3 to 17 years. The most frequent pattern was the reticular patternfollowed by plaque-like, erosive, atrophic, sclerosus, and bullous. The buccal mucosa was the most involved oralsite, followed by the tongue, lips and gingiva.Conclusions: Although Oral Lichen Planus in children is rare, it may cause oral discomfort and need to be dif-ferentiated from other oral white lesions and/or chronic ulcers.(AU)

Dietary Polyphenols against Oxidative Stress in Head and Neck Cancer: What's New, What's Next.

Head and neck cancers (HNC) are a worldwide health problem, accounting for over 5% of all types of cancers. Their varied nature makes it sometimes difficult to find clear explanations for the molecular mechanisms that underline their onset and development. While chemio- and radiotherapy are clearly not to be dismissed, we cannot undervalue the effect that polyphenols - especially dietary polyphenols - can have in helping us to cope with this medical emergency. By influencing several different proteins involved in numerous different metabolic pathways, polyphenols can have a broad spectrum of biological action and can hopefully act synergistically to tackle down head and neck cancer. Moreover, being natural molecules, polyphenols does not present any side effects and can even enhance drugs efficacy, making our clinical therapy against head and neck cancer more and more effective. Certainly, oxidative stress plays an important role, altering several molecular pathways, lowering the body's defenses, and ultimately helping to create a microenvironment conducive to the appearance and development of the tumor. In this regard, the regular and constant intake of foods rich in polyphenols can help counteract the onset of oxidative stress, improving the health of the general population. In this review, we highlight the role of polyphenols in managing oxidative stress, with such positive effects that they can be considered new tools to use in our anti-head and neck cancer strategy.

Pyrosequencing Analysis of O-6-Methylguanine-DNA Methyltransferase Methylation at Different Cut-Offs of Positivity Associated with Treatment Response and Disease-Specific Survival in Isocitrate Dehydrogenase-Wildtype Grade 4 Glioblastoma.

The O-6-methylguanine-DNA methyltransferase (MGMT) gene is a critical guardian of genomic integrity. MGMT methylation in diffuse gliomas serves as an important determinant of patients' prognostic outcomes, more specifically in glioblastomas (GBMs). In GBMs, the absence of MGMT methylation, known as MGMT promoter unmethylation, often translates into a more challenging clinical scenario, tending to present resistance to chemotherapy and a worse prognosis. A pyrosequencing (PSQ) technique was used to analyze MGMT methylation status at different cut-offs (5%, 9%, and 11%) in a sample of 78 patients diagnosed with IDH-wildtype grade 4 GBM. A retrospective analysis was provided to collect clinicopathological and prognostic data. A statistical analysis was used to establish an association between methylation status and treatment response (TR) and disease-specific survival (DSS). The patients with methylated MGMT status experienced progressive disease rates of 84.6%, 80%, and 78.4% at the respective cut-offs of 5%, 9%, and 11%. The number was considerably higher when considering unmethylated patients, as all patients (100%), regardless of the cut-off, presented progressive disease. Regarding disease-specific survival (DSS), the Hazard Ratio (HR) was HR = 0.74 (0.45-1.24; p = 0.251); HR = 0.82 (0.51-1.33; p = 0.425); and HR = 0.79 (0.49-1.29; p = 0.350), respectively. Our study concludes that there is an association between MGMT unmethylation and worse TR and DSS. The 9% cut-off demonstrated a greater potential for patient survival as a function of time, which may shed light on the future need for standardization of MGMT methylation positivity parameters in PSQ.

Recurrence and survival for patients with thyroid carcinoma in the pediatric age group in the Emirate of Abu Dhabi: retrospective analysis of a multicentre cohort.

OBJECTIVES: Pediatric thyroid cancer represents 2.3 % of thyroid cancers, and its long-term outcome data are sparse. There have not been studies in the UAE delineating its epidemiology, clinical and histological characteristics, and follow-up outcomes. We aimed to evaluate the clinical-pathological behavior, recurrence and survival rates in pediatrics with all types of thyroid cancer in the UAE. METHODS: Multicentre retrospective chart review analysis of pediatric patients with thyroid carcinoma from January 2010 to December 2020 in Abu Dhabi, UAE. RESULTS: Thirty-four patients were included, 85 % being females. Papillary thyroid carcinoma (PTC) was the commonest type of thyroid cancer (88 %) vs. follicular thyroid carcinoma (FTC) (11.8 %). Almost half of our patients had a multifocal disease, 26 % had lymphovascular invasion (LVI), and 21 % had extrathyroidal extension (ETE). There were no mortalities during follow-up. 85 % of patients exhibited complete remission, while 15 % of patients showed evidence of progressive residual or recurrent disease. One patient had metastasis to lymph nodes and lungs. CONCLUSIONS: There were similar trends of incidence, sex prevalence, and histopathological patterns as the ones observed internationally. Potential risk factors in our population include a family history of thyroid cancer and obesity. The lower rate of ETE, LVI, metastasis, and recurrence indicates a possibly less aggressive disease.

Anti-LGALS3BP antibody-drug conjugate treatment induces durable and potent antitumor response in a preclinical model of adenoid cystic carcinoma.

OBJECTIVES: Adenoid cystic carcinoma (ACC) is a rare type of cancer that typically arises from glandular tissues, most commonly in the salivary glands. Although relatively rare, it represents a serious clinical issue as the management of the disease is highly complex being the only therapeutic options represented by invasive surgery and/or radiotherapy. In the present study, we have explored the potential of galectin-3 binding protein (LGALS3BP) as a novel target for antibody-drug conjugate (ADC) therapy in ACC. MATERIALS AND METHODS: RNAseq was conducted on a panel of 10 ACC patient-derived xenografts (PDX)s tissues and 6 normal salivary glands to analyze LGALS3BP gene expression. Protein expression was assessed in ACC PDX and primary tumor tissues using immunohistochemistry. Anti-LGALS3BP ADC named 1959-sss/DM4, was tested in high LGALS3BP expressing ACC PDX model ST1502B. RESULTS: RNAseq analysis revealed that LGALS3BP expression was highly expressed in ACC PDX tissues compared to normal salivary gland tissues. As evaluated by immunohistochemical analysis, LGALS3BP protein was found to be heterogeneously expressed in 10 ACC PDX and in tumor tissues derived from a cohort of 37 ACC patients. Further, treatment with 1959-sss/DM4 ADC led to durable tumor growth inhibition (TGI) in 100% of animals without observed toxicity. CONCLUSIONS: Our study provides strong evidence that LGALS3BP is a promising therapeutic target for ACC, warranting further expedited preclinical and clinical investigation.

Tumor budding is a prognostic factor in head and neck squamous cell carcinoma: A comprehensive meta-analysis and trial sequential analysis.

BACKGROUND: Mortality is linked to tumor budding (TB) in certain neoplasms. TB as a relevant histopathological feature is conditioned by tumor site, a specific study on head and neck squamous cell carcinoma (HNSCC) is needed. METHODS: A comprehensive meta-analysis was undertaken to investigate the relationship between TB and HNSCC-related outcomes. RESULTS: Overall 42 studies were included. Patients harboring high TB reported an Overall Survival (OS) Hazard Ratio (HR) of 2.63 (95% confidential interval (CI) 2.04-3.39; p-value < 0.001), Disease-free Survival (DFS) HR of 1.88 (95%CI 1.57-2.24; p-value <0.001) and Disease-specific Survival (DSS) HR of 2.14 (95%CI 1.81-2.52; p-value <0.001). Lymph Node Metastasis (LNM) studies harbored null heterogeneity and marked association with TB (Odds Ratio (OR) = 4.48, 95%CI 2.97-6.76; p-value < 0.001). Trial Sequential Analysis (TSA) supported definitive results for DSS. CONCLUSION: The study has provided compelling evidence that there is a significant association between TB and a worse prognosis for HNSCC.

Tongue Mucoceles: a retrospective clinic-pathological evaluation of 240 cases.

BACKGROUND: Minor salivary glands can be found in the ventral and anterior part of the tongue; these glands can rarely develop mucoceles that, due to their rarity and their unusual clinical appearance, may present an interesting differential diagnosis. Mucoceles appear as an exophytic, sometimes pedunculated, lesion, which is a feature that is due to the absence of a capsule; thus, the glands are right beneath the mucosa and over the muscle tissue. The aim of this article is to retrospectively present and discuss the anatomy, pathology, clinical features and therapy of several cases of Blandin-Nunh mucoceles collected from two different institutions. METHODS: A retrospective case review was carried out in two university institutions, retrieving all cases of tongue mucoceles from 1999 to today. Two oral pathologists reviewed all the slides, confirming the diagnosis. Demographic data of the patient, anatomic location and clinical appearance were retrieved from clinical charts, together with the type of surgical procedure and possible relapses. RESULTS: A total of 240 cases of tongue mucoceles were gathered from the archives: the mean age was 22 years (DS = 14,7; Range 2-83), 126 were females (52,5%, mean age 22,7 years, DS = 16,5; Range 2-83), and 114 were males (47,5%, mean age 20,9 years, DS = 12,4; Range 3-73); in all cases, a history of trauma was reported. The ventral surface was the most frequent location (224 cases - 93,3%), and in the great majority (235 cases - 97,9%), pathology revealed mucous spillage with a wall formed by fibrous connective and granulation tissue with no epithelium lining the cavity. Superficial mucocele and sclerosing sialoadenitis were the more frequent pathological variants (21 cases - 8,8%). All lesions were treated with excision and enucleation of the servicing gland. The healing was uneventful in all cases, but there were four recurrences and two cases of sensory paraesthesia of the border of the tongue, all in males, except one case of paraesthesia in a female. CONCLUSIONS: Tongue mucoceles must be differentiated from many benign and malignant lesions. For this reason, surgical removal of the lesion and of the associated gland with a pathological exam is mandatory. In fact, the anatomical location of the glands and the possible pathological variants must be considered to reach a correct diagnosis and diminish possible relapses. TRIAL REGISTRATION: CE-Muc_Ton_3/2023.

Attitudes and practices of dentists treating HIV+ patients in the era of new antiretroviral therapy: A 12-year update.

During the first years of the HIV pandemic, the virus diffusion was responsible for discriminatory behavior from medical and dental care workers towards HIV-infected patients, as described by our research group in 2009. The aim of the current study was to provide an update on the previous data, investigating the presence of discriminatory behaviors, evaluating the level of dentists' knowledge about the virus and proposing strategies to be implemented to avoid professional exposure and cross-infections. This study was a cross-sectional, online, national survey on dentists, members of the main national dental associations (ANDI and AIO). The questionnaire was divided into four major sections, with the same structure as the questionnaire administered in 2009. The differences between groups were analyzed using the software program IBM SPSS Statistic, version 21.0. A total of 1054 dentists filled out the questionnaire completely. Among them 0.04% revealed a discriminatory attitude towards HIV-infected patients. The univariate analysis showed that discrimination towards HIV + patients was statistically associated with personal experiences and the level of fear associated with treating them (p = 0.001) and with the type of dental treatments performed (p = 0.01). This cross-sectional study revealed the persistence of dentists who still discriminate against HIV + patients, and the percentage of these dentists was only slightly lower than that in the previous survey (4.3% in the present survey vs. 4.5%). The survey also depicted other information worthy of consideration, such as a perceived ability to detect HIV + patients based on their appearance, complaints about not having received adequate training for treating HIV + individuals, and a lack of scientific knowledge about the virus. From the evidence reported by the present survey, it can be argued that universities, professional boards, and training institutions must increase their efforts in spreading correct knowledge about HIV among all dental care workers.

The Immune Cells in the Development of Oral Squamous Cell Carcinoma.

A still unresolved issue surrounding tumor formation concerns the role that the immune system plays in preventing the formation and progression of neoplasia, including oral squamous cell carcinoma (OSCC). Antitumor immunity has historically been seen as a critical barrier for cancer cells to develop, grow and spread, and this can be modulated using immunotherapies to achieve antitumor clinical responses. However, it has recently become clear that tumor-associated immunity, particularly the inflammatory microenvironment, has the paradoxical effect of enhancing tumorigenesis and progression. In this review, we discuss the multifaceted function of infiltrating immune cells in suppressing or promoting premalignancy and cancer. In particular, we report on the evidence supporting a role for T lymphocytes, dendritic cells, macrophages, and neutrophils in the development and progression of oral potentially malignant disorders (OPMD) and OSCC. We also draw attention to the clinical relevance of immune cell phenotypes and associated molecules for use as biomarkers and to the translatability of current research findings to improve classification systems and precision medicine in patients with OSCC.

LGALS3BP is a potential target of antibody-drug conjugates in oral squamous cell carcinoma.

OBJECTIVE: The aim of the present study was to evaluate the expression of intracellular and vesicular LGALS3BP in oral squamous cell carcinoma (OSCC) patients and available cell lines to explore its potential as a target for antibody-drug conjugate (ADC) therapy. METHODS: Free and vesicular LGALS3BP expression levels were evaluated in cancer tissues from a cohort of OSCC patients as well as in a panel of OSCC cell lines through immunohistochemistry, qRT-PCR, Western Blot analysis, and ELISA. RESULTS: LGALS3BP resulted in being highly expressed in the cytoplasm of tumour cells in OSCC patient tissues. A strong correlation was found between high LGALS3BP expression levels and aggressive histological features of OSCC. Biochemistry analysis performed on OSCC cell lines showed that LGALS3BP is expressed in all the tested cell lines and highly enriched in cancer-derived extracellular vesicles. Moreover, LGALS3BP high-expressing HOC621 and CAL27 OSCC cell lines showed high sensitivity to the ADC-payload DM4, with an IC50 around 0.3 nM. CONCLUSIONS: The present study highlights that LGALS3BP is highly expressed in OSCC suggesting a role as a potential diagnostic biomarker and therapeutic target for ADC-based therapy.

Predictive value of CDKN2A/p16INK4a expression in the malignant transformation of oral potentially malignant disorders: Systematic review and meta-analysis.

BACKGROUND: Management of oral potentially malignant disorders (OPMDs) is still challenging. Despite the diagnostic ascertainment by bioptic examination, this method is poorly informative of the prognosis and subsequent malignant transformation. Prognosis is based on histological findings by grading of dysplasia. Immunohistochemical expression of p16INK4a has been investigated in different studies, with controversial results. In this scenario, we systematically revised the current evidence about p16INK4a immunohistochemical expression and the risk of malignization of OPMDs. MATERIAL AND METHODS: After a proper set of keywords combination, 5 databases were accessed and screened to select eligible studies. The protocol was previously registered on PROSPERO (Protocol ID: CRD42022355931). Data were obtained directly from the primary studies as a measure to determine the relationship between CDKN2A/P16INK4a expression and the malignant transformation of OPMDs. Heterogeneity and publication bias were investigated by different tools, such as Cochran's Q test, Galbraith plot and Egger and Begg Mazumdar's rank tests. RESULTS: Meta-analysis revealed a twofold increased risk to malignant development (RR = 2.01, 95% CI = 1.36-2.96 - I2 = 0%). Subgroup analysis did not highlight any relevant heterogeneity. Galbraith plot showed that no individual study could be considered as an important outlier. CONCLUSION: Pooled analysis showed that p16INK4a assessment may arise adjunct tool to dysplasia grading, leading to an optimized determination of the potential progression to cancer of OPMDs. The p16INK4a overexpression analysis by immunohistochemistry techniques has a multitude of virtues that may facilitate its incorporation in the day-to-day prognostic study of OPMDs.

High-risk TP53 mutations predict poor primary treatment response of patients with head and neck squamous cell carcinoma.

OBJECTIVES: Head and neck squamous cell carcinoma (HNSCC) poses a diagnostic and therapeutic challenge worldwide and is associated with a poor survival rate. Due to the variability in the efficacy of treatments for HNSCC, new predictive biomarkers of therapy outcomes are needed. Recently, we developed an algorithm that employs the mutational profile of TP53 as an independent prognostic factor in HNSCC. In this study, we investigated its role as a predictive biomarker of treatment outcomes in HNSCC patients. We also tested the usefulness of two classification systems for TP53 mutational landscapes. MATERIALS AND METHODS: Clinical and genomic data were retrieved from The Cancer Genome Atlas database. We built a multivariate stepwise backward binary regression model to assess the role of TP53 mutations in predicting therapeutic outcomes. RESULTS: Cases harbouring high-risk-of-death mutations reported an odds ratio of 3.301 for stable or progressive disease compared to wild-type cases, while no significant difference in treatment outcomes was found between cases with low-risk-of-death mutations and wild-type TP53. Our analysis found that older patients with a history of alcohol consumption had a higher risk of stable/progressive disease. CONCLUSIONS: This study improves current evidence on the role of TP53 mutations in treatment response in HNSCC patients.

Effect of the use of platelet concentrates on new bone formation in alveolar ridge preservation: a systematic review, meta-analysis, and trial sequential analysis.

OBJECTIVES: To investigate the histomorphometric changes occurring in alveolar ridge preservation (ARP) based on the use of different plasma concentrates (PCs) in randomized clinical trials (RCT). There is controversy whether the placement of PCs in ARP is effective in the formation of new bone. MATERIALS AND METHODS: A systematic review search was conducted in PubMed, Scopus, Web of Science, and Cochrane Database to answer the PICO question: In patients undergoing tooth extraction followed by ARP, do PCs alone in the post-extraction socket in comparison with spontaneous healing improve new vital bone formation percentage in histomorphometric analysis after more than 10 weeks? The risk of bias was assessed and a meta-analysis was conducted. RESULTS: Of 3809 results, 8 studies were considered suitable for inclusion. A total of 255 teeth were extracted in 250 patients. Regarding the PCs used, ARP was performed with platelet- and leukocyte-rich fibrin (L-PRF) in 120 sockets, and with pure platelet-rich plasma (P-PRP) in 31 sockets and 104 sockets were controlled. PCs improved new bone formation in ARP with respect to the spontaneous healing group (SMD = 1.77, 95%C.I. = 1.47-2.06, p-value < 000.1). There were no differences between the different PCs (L-PRF and P-PRP). CONCLUSION: The results of this meta-analysis support the efficacy of the use of PCs in new bone formation in ARP. With respect to the different types of PCs studied, no differences were observed. CLINICAL RELEVANCE: When planning implant surgery after tooth extraction, treatment with PCs should be considered for ARP. Any PC increases new bone formation compared to spontaneous healing.

Monkeypox: A New Challenge for Global Health System?

The COVID-19 pandemic, starting in 2020, has presented a major challenge in terms of early diagnosis and the subsequent containment and management of severe cases. The spread of viruses such as monkeypox in non-endemic countries is now creating new difficulties for healthcare professionals. Proper case definition and clinical examination are crucial for the early identification of suspected cases. For this reason, we performed a review of the literature in order to report the first signs, which are useful for healthcare providers for early case identification. Since 2022 to date, 86,930 laboratory-confirmed cases and 1051 probable cases have been reported worldwide, and of these, 116 were fatal cases and, for the first time, most of the cases were registered in countries that have not historically reported monkeypox and that lack direct or immediate epidemiological links to areas of West or Central Africa where the disease is endemic. Patients with Monkeypox experience prodromal symptoms, such as fever, fatigue, headache, muscle aches, and a rash after an incubation period of 5-21 days. The disease is usually self-limiting within 2-4 weeks but can lead to complications, such as pneumonia, encephalitis, kidney injury, and myocarditis in children, pregnant individuals, and those with weakened immune systems. The case-fatality ratio is between 1 and 10%. Today, prevention campaigns and the control of human monkeypox are the best weapons to prevent infection and stop transmission. Prevention strategies, such as avoiding contact with sick or dead animals, and the proper preparation of all foods containing animal meat or parts, should be adopted. Furthermore, close contact with infected people or contaminated materials should be avoided to prevent human-to-human transmission.

Correlation of Bcl-2 expression with prognosis and survival in patients with head and neck cancer: A systematic review and meta-analysis.

Head and neck cancer (HNC) is a growing disease, affecting more than 700.000 cases per year and ranking as the sixth most prevalent type of cancer worldwide. The impossibility of properly entering into apoptosis directly influences uncontrolled growth and consequently tumor development and progression. Bcl-2 emerged as a key regulator in the balance between cell apoptosis and proliferation in apoptosis machinery. This systematic review and meta-analysis aimed to review all published studies investigating changes in Bcl-2 protein expression assessed by immunohistochemistry (IHC) and related to prognostic and survival values of patients with HNC. After applying the inclusion and exclusion factors, we reached the number of 20 articles included in the meta-analysis. The random-effect pooled HR (CI95%) value of OS related to Bcl-2 IHC expression in tissues from HNC patients was 1.80 (CI95% 1.21-2.67) (p 0.0001) and DFS was 1.90 (CI95% 1.26-2.86 (p 0.0001). The OS value for the specific oral cavity tumors was 1.89 (1.34-2.67), while in the larynx it was 1.77 (0.62-5.06), and the DFS in the pharynx was 2.02 (1.46-2.79). The univariate and multivariate analyses of OS were respectively 1.43 (1.11-1.86) and 1.88 (1.12-3.16), while in DFS it was 1.70 (0.95-3.03) and 2.08 (1.55-2.80). The OS considering a low cut-off for Bcl-2 positivity was 1.19 (0.60-2.37) and DFS was 1.48 (0.91-2.41), while studies with a high cut-off demonstrated OS of 2.28 (1.47-3.52) and DFS of 2.77 (1.74-4.40). Our meta-analysis demonstrates that Bcl-2 protein overexpression can result in worse LNM, OS, and DFS in patients with HNC, however, it is not a reliable conclusion, due to the wide divergences between the original studies and the fact that many studies have a very high range of confidence and also a high risk of bias.