"A conservative technique for fractured implant abutment screw retrieval on an internal connection implant: proof of concept (PoC)".

INTRODUCTION: Broken screw removal from the implant connection is a common but challenging process. Several proposed methods and technical solutions may result in unsuccessful removal; thus, a novel, more conservative, risk-free method is proposed as a first attempt. DESCRIPTION OF THE CASE: The proposal is to use a silicon restoration holder to be twisted counterclockwise on the dried surface of the broken fragment inside the implant connection. This method, within the limitations of a minimal case series, yielded 100% results; however, despite previous attempts with less con- servative techniques, this approach showed no efficacy. CONCLUSION: This article aims to promote the use of silicon restoration holders as a minimally invasive first attempt at broken screw retrieval treatment before considering other options.

The "great imitator": IgG4-related disease of the oral cavity. Two case reports and scoping review.

This study aimed to review the lesser-known intraoral manifestations of immunoglobulin G4-related disease (IgG4-RD). In this paper we report an unprecedented case of oral IgG4-RD mimicking angiolymphoid hyperplasia with eosinophilia (ALHE), and another case presenting as plasma cell gingivitis. We then performed a scoping review of published cases of IgG4-RD involving the oral cavity. The following data were collected for each case: age, sex, intraoral site(s) involved, clinical appearance, imaging features, serum IgG4 values, histopathology, treatment, and follow-up duration. Fifty-one cases of oral IgG4-RD were published in literature. The hard palate and jaw bones were the two main locations reported, while the histological identification of a IgG4/IgG plasma cells ratio ≥40% was fundamental for diagnosis. Conversely, the pathological features of storiform fibrosis and obliterative phlebitis were not common. Future reports regarding oral IgG4-RD should report clear adherence to the recognized international diagnostic criteria of the disease.

Ten Years of Experience With a Telemedicine Platform Dedicated to Health Care Personnel: Implementation Report.

BACKGROUND: Telemedicine, a term that encompasses several applications and tasks, generally involves the remote management and treatment of patients by physicians. It is known as transversal telemedicine when practiced among health care professionals (HCPs). OBJECTIVE: We describe the experience of implementing our telemedicine Eumeda platform for HCPs over the last 10 years. METHODS: A web-based informatics platform was developed that had continuously updated hypertext created using advanced technology and the following features: security, data insertion, dedicated software for image analysis, and the ability to export data for statistical surveys. Customizable files called "modules" were designed and built for different fields of medicine, mainly in the ophthalmology subspecialty. Each module was used by HCPs with different authorization profiles. IMPLEMENTATION (RESULTS): Twelve representative modules for different projects are presented in this manuscript. These modules evolved over time, with varying degrees of interconnectivity, including the participation of a number of centers in 19 cities across Italy. The number of HCP operators involved in each single module ranged from 6 to 114 (average 21.8, SD 28.5). Data related to 2574 participants were inserted across all the modules. The average percentage of completed text/image fields in the 12 modules was 65.7%. All modules were evaluated in terms of access, acceptability, and medical efficacy. In their final evaluation, the participants judged the modules to be useful and efficient for clinical use. CONCLUSIONS: Our results demonstrate the usefulness of the telemedicine platform for HCPs in terms of improved knowledge in medicine, patient care, scientific research, teaching, and the choice of therapies. It would be useful to start similar projects across various health care fields, considering that in the near future medicine as we know it will completely change.

Anxiety and depression in keratotic oral lichen planus: a multicentric study from the SIPMO.

OBJECTIVES: Oral lichen planus with exclusive keratotic reticular, papular, and/or plaque-like lesions (K-OLP) is a clinical pattern of OLP that may be associated with a complex symptomatology and psychological alteration. The aim of the study was to evaluate the prevalence of anxiety (A) and depression (D) in patients with K-OLP, analyzing the potential predictors which can affect mental health status. METHODS: Three hundred K-OLP patients versus 300 healthy controls (HC) were recruited in 15 Italian universities. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), and Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A) were administered. RESULTS: The K-OLP patients showed statistically higher scores in the NRS, T-PRI, HAM-D, and HAM-A compared with the HC (p-value < 0.001**). A and D were found in 158 (52.7%) and 148 (49.3%) K-OLP patients. Strong linear correlations were identified between HAM-A, HAM-D, NRS, T-PRI, and employment status and between HAM-D, HAM-A, NRS, T-PRI, employment status, and female gender. Multivariate logistic regression revealed that HAM-D and HAM-A showed the greatest increase in the R2 value for A and D in the K-OLP patients, respectively (DR2 = 55.5% p-value < 0.001**; DR2 = 56.5% p-value < 0.001**). CONCLUSIONS: The prevalence of A and D is higher in the K-OLP patients compared with the HC, also found in K-OLP subjects without pain, suggesting that the processing of pain may be in a certain way independent of the processing of mood. CLINICAL RELEVANCE: Mood disorders and pain assessment should be carefully performed in relation to K-OLP to obtain a complete analysis of the patients.

Mucosal immune response after the booster dose of the BNT162b2 COVID-19 vaccine.

BACKGROUND: To date, only a few studies reported data regarding the development of mucosal immune response after the BNT162b2-booster vaccination. METHODS: Samples of both serum and saliva of 50 healthcare workers were collected at the day of the booster dose (T3) and after two weeks (T4). Anti-S1-protein IgG and IgA antibody titres and the neutralizing antibodies against the Wuhan wild-type Receptor-Binding Domain in both serum and saliva were measured by quantitative and competitive ELISA, respectively. Data were compared with those recorded after the primary vaccination cycle (T2). Neutralizing antibodies against the variants of concern were measured in those individuals with anti-Wuhan neutralizing antibodies in their saliva. FINDINGS: After eight months from the second dose, IgG decreased in both serum (T2GMC: 23,838.5 ng/ml; T3GMC: 1473.8 ng/ml) and saliva (T2GMC: 12.9 ng/ml; T3GMC: 0.3 ng/ml). Consistently, serum IgA decreased (T2GMC: 48.6 ng/ml; T3GMC: 6.4 ng/ml); however, salivary IgA showed a different behaviour and increased (T2GMC: 0.06 ng/ml; T3GMC: 0.41 ng/ml), indicating a delayed activation of mucosal immunity. The booster elicited higher titres of both IgG and IgA when compared with the primary cycle, in both serum (IgG T4GMC: 98,493.9 ng/ml; IgA T4GMC: 187.5 ng/ml) and saliva (IgG T4GMC: 21.9 ng/ml; IgA T4GMC: 0.65 ng/ml). Moreover, the booster re-established the neutralizing activity in the serum of all individuals, not only against the Wuhan wild-type antigen (N = 50; INH: 91.6%) but also against the variants (Delta INH: 91.3%; Delta Plus INH: 89.8%; Omicron BA.1 INH: 85.1%). By contrast, the salivary neutralizing activity was high against the Wuhan antigen in 72% of individuals (N = 36, INH: 62.2%), but decreased against the variants, especially against the Omicron BA.1 variant (Delta N = 27, INH: 43.1%; Delta Plus N = 24, INH: 35.2%; Omicron BA.1 N = 4; INH: 4.7%). This was suggestive for a different behaviour of systemic immunity observed in serum with respect to mucosal immunity described in saliva (Wald chi-square test, 3 df of interaction between variants and sample type = 308.2, p < 0.0001). INTERPRETATION: The BNT162b2-booster vaccination elicits a strong systemic immune response but fails in activating an effective mucosal immunity against the Omicron BA.1 variant. FUNDING: This work was funded by the Department of Medicine and Surgery, University of Insubria, and supported by Fondazione Umberto Veronesi (COVID-19 Insieme per la ricerca di tutti, 2020), Italy.

TTV viral load as a predictor of antibody response to SARS COV-2 vaccination.

The measure of torquetenovirus (TTV) viremia is widely recognized as an optimal biomarker of an individual immune status. In the context of COVID-19, the predictive role of TTV load with regard to vaccine response has also been demonstrated, suggesting other intriguing applications for this widespread anellovirus.

Detection of Torquetenovirus and Redondovirus DNA in Saliva Samples from SARS-CoV-2-Positive and -Negative Subjects.

OBJECTIVES: Torquetenovirus (TTV) and Redondovirus (ReDoV) are the most prevalent viruses found in the human respiratory virome in viral metagenomics studies. A large-scale epidemiological study was performed to investigate their prevalence and loads in saliva samples according to SARS-CoV-2 status. METHODS: Saliva samples from 448 individuals (73% SARS-CoV-2 negative and 27% SARS-CoV-2 positive) aged 23-88 years were tested. SARS-CoV-2 and TTV were determined in saliva by specific qualitative and quantitative real-time PCRs, respectively. A sub-cohort of 377 subjects was additionally tested for the presence and load of ReDoV in saliva, and a different sub-cohort of 120 subjects for which paired saliva and plasma samples were available was tested for TTV and ReDoV viremia at the same timepoints as saliva. RESULTS: TTV in saliva was 72% prevalent in the entire cohort, at a mean DNA load of 4.6 log copies/mL, with no difference regardless of SARS-CoV-2 status. ReDoV was found in saliva from 61% of the entire cohort and was more prevalent in the SARS-CoV-2-negative subgroup (65% vs. 52%, respectively). In saliva, the total mean load of ReDoV was very similar to the one of TTV, with a value of 4.4 log copies/mL. The mean viral loads in subjects infected with a single virus, namely, those infected with TTV or ReDoV alone, was lower than in dually infected samples, and Tukey's multiple-comparison test showed that ReDoV single-infected samples resulted in the only true outlier (p = 0.004). Differently from TTV, ReDoV was not detected in any blood samples. CONCLUSIONS: This study establishes the prevalence and mean value of TTV and ReDoV in saliva samples and demonstrates the existence of differences between these two components of the human virome.

Impact of Smoking Habit on Peri-Implant Indicators following Different Therapies: A Systematic Review.

Peri-implant disease and its treatment is becoming a major concern for clinicians as the number of implants placed each year is rising. Smoking is a common habit, and it is associated with an increased risk of developing peri-implant disease. The role of smoking in the response to peri-implant treatment has never been investigated. Searches were conducted in electronic databases to screen articles published until August 2021. The included studies had at least two groups of patients: peri-implant disease only or peri-implant disease and smoking status. Outcomes of interest included plaque index (PI), probing depth (PD), bleeding on probing (BoP), radiographic crestal bone loss (CBL), and analysis of peri-implant sulcular fluid. Seven hundred and forty-nine articles were found in the databases, only 71 articles potentially qualified. A total of seven studies with a minimum follow-up of six months were included. There is no homogeneity in the diagnosis, smoker definition and treatment proposed. All surgical and non-surgical treatment have statistically significantly different outcomes in smokers and nonsmokers. Recognizing this study's limitations, we conclude that smoking might play a significant role on the outcome of peri-implant disease treatment. None of the proposed treatments appear to be significantly more effective.

Safety and immunogenicity of synchronous COVID19 and influenza vaccination.

Given the ongoing COVID19 pandemic, the decline in serological response since dose 2, and the upcoming flu season, COVID19 vaccines will increasingly be administered in combination with vaccines against seasonal pathogens. It is of interest to confirm that concurrent vaccination against influenzavirus has no negative impact on serological response to SARS CoV-2. Anti-Spike IgG and Anti-Receptor Binding Domain (RBD) Neutralizing Antibodies (NAb) in serum  was assessed in 64 immunocompetent healthcare workers (HCW) before and 14 days post the third dose of BNT162b2 vaccine (Comirnaty®, Pfizer/BioNTech) or BNT162b2 plus quadrivalent flu vaccine (Vaxigript Tetra ®Sanofi Pasteur) on the same day. We report here safety and efficacy of combined BNT162b2 and flu vaccine in 64 healthcare workers at a single institution. No differences were found in adverse events or anti-Spike antibody levels.

Where do you live? North versus Central-South differences in relation to Italian patients with oral lichen planus: a cross-sectional study from the SIPMO (Italian Society of Oral Pathology and Medicine).

BACKGROUND: Oral lichen planus (OLP) is an immune-mediated inflammatory chronic disease of the oral mucosa, with different patterns of clinical manifestations which range from keratotic manifestations (K-OLP) to predominantly non-keratotic lesions (nK-OLP). The aim of the study was to analyze the differences in the clinical, psychological profile and symptoms between Italian patients of the North and Central-South with K-OLP and nK-OLP. METHODS: 270 K-OLP and 270 nK-OLP patients were recruited in 15 Italian universities. The Numeric Rating Scale (NRS), Total Pain Rating Index (T-PRI), Hamilton Rating Scales for Depression and for Anxiety (HAM-D and HAM-A), Pittsburgh Sleep Quality Index (PSQI), and Epworth Sleepiness Scale (ESS) were administered. RESULTS: The Central-South K-OLP (CS-K-OLP) patients reported a higher frequency of pain/burning compared with the K-OLP patients of the North (N-K-OLP) with higher scores in the NRS and T-PRI (p value < 0.001**). The CS-K-OLP and the CS-nK-OLP patients showed higher scores in the HAM-D, HAM-A, PSQI and ESS compared with the Northern patients (p value < 0.001**). Multivariate logistic regression revealed that the NRS and T-PRI showed the greatest increase in the R2 value for the CS-K-OLP (DR2 = 9.6%; p value < 0.001**; DR2 = 9.7% p value < 0.001**; respectively) and that the oral symptoms (globus, itching and intraoral foreign body sensation) and PSQI showed the greatest increase in the R2 value for the CS-nK-OLP (DR2 = 5.6%; p value < 0.001**; DR2 = 4.5% p value < 0.001** respectively). CONCLUSIONS: Pain and mood disorders are predominant in patients with OLP in the Central-South of Italy. Clinicians should consider that the geographical living area may explain the differences in oral symptoms and psychological profile in OLP.

Macular Holes: Main Clinical Presentations, Diagnosis, and Therapies.

Macular holes are a spectrum of retinal diseases that comprehends full-thickness macular holes (FTMHs), refractory/recurrent macular holes, lamellar macular holes (LMHs), myopic macular holes (MMHs), traumatic macular holes, and macular holes secondary to other retinal pathologies or injuries. There are various classifications of the subtypes of macular hole, and only in recent times researchers defined a common nomenclature, especially thanks to the evolution in retinal imaging, offered by new instruments like the swept-source OCT. The proposed therapies for macular holes are different and range from a "wait-and-see" approach to the vitrectomy, with different results in each subtype of macular hole. This narrative review has the purpose to investigate the available evidence in literature to give a summary of the knowledge about these retinal pathologies.

Immune-Mediated Mechanisms in Patients Testing Positive for SARS-CoV-2: Protocol for a Multianalysis Study.

BACKGROUND: The novel coronavirus has a high mortality rate (over 1% for patients older than 50 years). This can only be partially ascribed to other comorbidities. A possible explanation is a factor that assures a prompt response to SARS-CoV-2 in younger people, independent from the novelty of the virus itself. A factor is believed to stimulate the immune system and provide immunity against more antigens. The only external stimulation received by healthy people is vaccination (eg, the diphtheria, tetanus, and pertussis [DTP] vaccine). One hypothesis is that vaccination helps develop specific immunity but generates sprouting immunity against antigens in transit. The underlying immunological phenomena are the "bystander effect" and "trained immunity." The developed immunity gives protection for years until it naturally fades out. After the fifth decade of life, the immune system is almost incompetent when a viral infection occurs, and thus, at this stage, the novel coronavirus can enter the body and cause acute respiratory distress syndrome. OBJECTIVE: The initial aim is to demonstrate that blood monocytes and natural killer cells show overpowering hyperactivity, while CD4+ and CD8+ T cells experience impediments to their defensive functions in patients with severe SARS-CoV-2 infection. The secondary objectives are to correlate clinical data and vaccination history with laboratory immune patterns in order to identify protective factors. Subsequently, we are also interested in characterizing the phenotypes and state of the degree of activation of peripheral blood mononuclear cells, including monocytes, natural killer cells, and CD4+ and CD8+ T cells, in healthy subjects vaccinated with the Pfizer vaccine. METHODS: Data will be collected using the following 3 approaches: (1) an experimental analysis to study the innate immune response and to identify genetic profiles; (2) an epidemiological analysis to identify the patients' vaccination history; and (3) a clinical analysis to detect the immunological profile. RESULTS: The protocol was approved by the Ethics Committee on April 16, 2020, and the study started on April 27, 2020. As of February 2021, enrollment has been completed. Immunological analysis is ongoing, and we expect to complete this analysis by December 2022. CONCLUSIONS: We will recognize different populations of patients, each one with a specific immunological pattern in terms of cytokines, soluble factor serum levels, and immune cell activity. Anamnestic data, such as preceding vaccinations and comorbidities, biochemical findings like lymphocyte immunophenotyping, and pre-existing persistent cytomegalovirus infection, allow depicting the risk profile of severe COVID-19. Proof of the roles of these immunological phenomena in the development of COVID-19 can be the basis for the implementation of therapeutic immunomodulatory treatments. TRIAL REGISTRATION: ClinicalTrials.gov NCT04375176; https://clinicaltrials.gov/ct2/show/NCT04375176. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/29892.

Assessment of sleep disturbance in oral lichen planus and validation of PSQI: A case-control multicenter study from the SIPMO (Italian Society of Oral Pathology and Medicine).

BACKGROUND: The wellbeing of oral lichen planus patients (OLPs) may be strongly influenced by a poor quality of sleep (QoS) and psychological impairment. The aims were to analyze the prevalence of sleep disturbance, anxiety, and depression in OLPs and to validate the Pittsburgh Sleep Quality Index (PSQI) in OLPs. METHODS: Three hundred keratotic OLPs (K-OLPs), 300 with predominant non-keratotic OLP (nK-OLPs), and 300 controls were recruited in 15 Italian universities. The PSQI, Epworth Sleepiness Scale (ESS), Hamilton Rating Scales for Depression and Anxiety (HAM-D and HAM-A), Numeric Rating Scale (NRS), and Total Pain Rating Index (T-PRI) were administered. RESULTS: Oral lichen planus patients had statistically higher scores than the controls in the majority of the PSQI sub-items (p-values < 0.001**). Moreover, OLPs had higher scores in the HAM-D, HAM-A, NRS, and T-PRI (p-values < 0.001**). No differences in the PSQI sub-items' scores were found between the K-OLPs and nK-OLPs, although nK-OLPs suffered from higher levels of anxiety, depression, and pain (p-values: HAM-A, 0.007**, HAM-D, 0.009**, NRS, <0.001**, T-PRI, <0.001**). The female gender, anxiety, depression (p-value: 0.007**, 0.001**, 0.020*) and the intensity of pain, anxiety, and depression (p-value: 0.006**, <0.001**, 0.014*) were independent predictors of poor sleep (PSQI > 5) in K-OLPs and nK-OLPs, respectively. The PSQI's validation demonstrated good internal consistency and reliability of both the total and subscale of the PSQI. CONCLUSIONS: The OLPs reported an overall impaired QoS, which seemed to be an independent parameter according to the regression analysis. Hence, clinicians should assess QoS in OLPs and treat sleep disturbances in order to improve OLPs management.

Chronic mechanical trauma/irritation and oral carcinoma: A systematic review showing low evidence to support an association.

BACKGROUND: Chronic trauma of oral mucosa, resulting from repeated and persistent mechanical irritative action of an intraoral injury agent, has repeatedly been reported to be possibly implicated in the development of oral squamous cell carcinoma (OSCC). OBJECTIVES: The present systematic review aimed to assess whether chronic mechanical trauma can be considered a risk factor for OSCC. DATA SOURCES: PubMed, CENTRAL (Cochrane Central Register of Controlled Trials), Scopus; EMBASE, Web of Science. STUDY ELIGIBILITY CRITERIA: Cohort studies comparing OSCC incidence among subjects with/without chronic mechanical trauma or case-control or cross-sectional studies comparing chronic mechanical trauma among subjects with/without OSCC. RESULTS: Only one prospective case-control study fulfilled the inclusion criteria, but the quality of the evidence provided is not enough to define trauma as a risk factor for OSCC. The main limitation is the presence of only one case-control study at high risk of bias. In the absence of strong evidence supporting the role of trauma in OSCC, a thorough discussion on trauma and carcinogenesis has been performed. CONCLUSIONS: Available evidence does not support an active role for chronic trauma in oral carcinogenesis, neither as promoter nor as progressor factor. Prospective cohort studies able to better assess trauma in OSCC are needed.

Mucosal immune response in BNT162b2 COVID-19 vaccine recipients.

BACKGROUND: Although the BNT162b2 COVID-19 vaccine is known to induce IgG neutralizing antibodies in serum protecting against COVID-19, it has not been studied in detail whether it could generate specific immunity at mucosal sites, which represent the primary route of entry of SARS-CoV-2. METHODS: Samples of serum and saliva of 60 BNT162b2-vaccinated healthcare workers were collected at baseline, two weeks after the first dose and two weeks after the second dose. Anti-S1-protein IgG and IgA total antibodies titres and the presence of neutralizing antibodies against the Receptor Binding Domain in both serum and saliva were measured by quantitative and by competitive ELISA, respectively. FINDINGS: Complete vaccination cycle generates a high serum IgG antibody titre as a single dose in previously infected seropositive individuals. Serum IgA concentration reaches a plateau after a single dose in seropositive individuals and two vaccine doses in seronegative subjects. After the second dose IgA level was higher in seronegative than in seropositive subjects. In saliva, IgG level is almost two orders of magnitude lower than in serum, reaching the highest values after the second dose. IgA concentration remains low and increases significantly only in seropositive individuals after the second dose. Neutralizing antibody titres were much higher in serum than in saliva. INTERPRETATION: The mRNA BNT162b2 vaccination elicits a strong systemic immune response by drastically boosting neutralizing antibodies development in serum, but not in saliva, indicating that at least oral mucosal immunity is poorly activated by this vaccination protocol, thus failing in limiting virus acquisition upon its entry through this route. FUNDING: This work was funded by the Department of Medicine and Surgery, University of Insubria, and partially supported by Fondazione Umberto Veronesi (COVID-19 Insieme per la ricerca di tutti, 2020).

Performance Assessment of the LIAISON® SARS-CoV-2 Antigen Assay On Nasopharyngeal Swabs.

The SARS-CoV-2 pandemic is ongoing worldwide, causing prolonged pressure on molecular diagnostics. Viral antigen (Ag) assays have several advantages, ranging from lower cost to shorter turnaround time to detection. Given the rare occurrence of low-load viremia, antigen assays for SARSCoV-2 have focused on nasopharyngeal swab and saliva as biological matrices, but their effectiveness must be validated. We assayed here the performances of the novel quantitative Liaison® SARSCoV-2 Ag assay on 119 nasopharyngeal swabs and obtained results were compared with Hologic Panther and Abbott m2000 RT-qPCR. The Ag assay demonstrated a good correlation with viral load, shorter turnaround time, and favorable economics. The best performance was obtained in the acute phase of disease.

Symptomatic SARS-CoV-2 infections after full schedule BNT162b2 vaccination in seropositive healthcare workers: a case series from a single institution.

We report 11 cases of SARS-CoV-2 infection in healthcare workers (HCW) naïve for COVID-19 and seropositive after the second dose of the BNT162b2 mRNA vaccine. Based on voluntary-based surveillance, they tested positive for different strains of SARS-CoV-2, as Spike gene sequencing showed. Five of them reported mild symptoms. Given the risk for SARS-CoV-2 introduction from asymptomatic vaccinees, this case series suggests the need to continue nasopharyngeal screening programmes.