Bioengineered tooth emulation systems for regenerative and pharmacological purposes

Genetic conditions, traumatic injuries, carious lesions and periodontal diseases are all responsible for dental pathologies. The current clinical approaches are based on the substitution of damaged dental tissues with inert materials, which, however, do not ensure full physiological recovery of the teeth. Different populations of dental mesenchymal stem cells have been isolated from dental tissues and several attempts have already been made at using these stem cells for the regeneration of human dental tissues. Despite encouraging progresses, dental regenerative therapies are very far from any clinical applications. This is tightly connected with the absence of proper platforms that would model and faithfully mimic human dental tissues in their complexity. Therefore, in the last decades, many efforts have been dedicated for the development of innovative systems capable of emulating human tooth physiology in vitro. This review focuses on the use of in vitro culture systems, such as bioreactors and "organ-on-a-chip" microfluidic devices, for the modelling of human dental tissues and their potential use for dental regeneration and drug testing

Diagnostic testing for SARS-CoV-2 infection in HHT patients: nasopharyngeal versus oropharyngeal swab

On March 11, 2020, WHO has defined the novel coronavirus disease SARS-CoV-2 (COVID-19) outbreak as a pandemic that still today continues to affect much of the world. Among the reasons for the rapid spread of SARS-CoV-2 infection, there is the role of asymptomatic or minimally symptomatic carriers. Therefore diagnostic testing is central to contain the global pandemic. Up to now real-time reverse transcriptase polymerase chain reaction-based molecular assays for detecting SARS-CoV-2 in respiratory specimens is the current reference standard for COVID-19 diagnosis. Based on current knowledge regarding the sensitivity of the molecular test, the highest positive detection rate is from lower respiratory tract specimens; alternatively it is possible to perform a nasopharyngeal or oropharyngeal swab. Nasopharyngeal swab is the preferred choice for SARS-CoV-2 testing since it seems to have a greater sensitivity; however the procedure is not always free of complications and an epistaxis can occur. Among patients with greatest risk of massive nosebleed there are HHT patients. Hereditary hemorrhagic telangiectasia is an autosomal dominant disease that leads to multiregional mucocutanous telangiectases and visceral arteriovenous malformations. Clinically, the presence of telangiectases in nasal mucosa is the cause of recurrent epistaxis. In HHT patients the execution of the nasopharyngeal swab can determine from little or no consequences to a massive epistaxis leading to the necessity of nasal packing generally followed by hospital admission. In HHT patients undergoing a diagnostic test to evaluate the SARS-CoV-2 infection status, especially in those patients with frequent epistaxis with a history of anemia and repeated hospitalizations, it is therefore advisable to perform an oropharyngeal swab. This, compared to the nasopharyngeal swab, exposes to a lower risk of severe nosebleeds related treatments, such as blood transfusions or invasive procedures. According to the risk-benefit assessment and based on our experience, we consider that, despite a lower diagnostic sensitivity, oropharyngeal swab is preferable to nasopharyngeal swab for the diagnosis of SARS CoV-2 infection in patients with HHT

The effects of ageing on dental pulp stem cells, the tooth longevity elixir

Stem cells are essential for tissue homeostasis and regeneration throughout the lifespan of multicellular rganisms. The decline in stem cell function during advanced age is associated with a reduced regenerative potential of tissues that leads to an increased frequency of diseases. Age-related changes also occur in the dental pulp tissue that represents a reliable model tissue, with high regenerative capability, for studying senescence mechanisms. However, little information is available concerning the effects of ageing on dental stem-cell function. In this mini-review, recent data on how the molecular and functional alterations that accumulate in stem cell populations during ageing result in modifications of dental pulp physiology are discussed. Changes that accumulate during ageing such as how reduction of pulp chamber volume, decreased vascular supply and modifications to the stem cell niches affect stem cell functions and, therefore, dental pulp regenerative potential in response to various stressful agents. Dental pulp cells from aged individuals are still metabolically active and secrete pro-inflammatory and matrix-degrading molecules. Furthermore, miRNAs and exosomes derived from dental pulp stem cells constitute an attractive source of nanovesicles for the treatment of age-related dental pathologies. Further investigation of the epigenetic alterations in dental pulp stem cells, accumulating during ageing, might reveal crucial information for potential stem cell-based therapeutic approaches in the elderly

The role of the osteoplastic flap in the endoscopic era : a retrospective multicentre experience on revision surgery

Objective. To retrospectively review the experience of five tertiary-care university hospitals on frontal sinus revision surgery with osteoplastic flap (OPF). Methods. Descriptive analysis of patients who underwent frontal sinus surgery with OPF after one or more endoscopic procedures for benign and inflammatory pathologies from 2000 to 2022. Clinical charts were reviewed for demographics, indications, clinical presen-tation, previous frontal procedures, OPF technique and outcomes. Results. Of the 124 patients who underwent an OPF procedure, 33 met inclusion criteria. With a mean of 2.1 previous endoscopic surgeries, Draf III was the most common former procedure. In 30 (91%) cases OPF was part of a combined procedure. The most common indications were inverted papilloma (61%), mucocele (9%) and chronic rhinosinusitis (6%). Frontal outflow stenosis (36%) and mucocele (9%) were the most frequent complications observed. Improvement of overall symptoms and patient satisfaction after the OPF procedure were recorded. Conclusions. Even in the endoscopic era, OPF still represents a paramount procedure that should be included in the rhino-surgeon’s armamentarium, in particular in patients with challenging pathologies and anatomy when previous endoscopic endonasal attempts have failed

Interventional sialendoscopy for radioiodine-induced sialadenitis: quo vadis?

La tossicità delle ghiandole salivari rappresenta un noto effetto indesiderato dello iodio radioattivo (I) utilizzato per il trattamento di neoplasie tiroidee, con una prevalenza che varia dal 2% al 67% della popolazione esposta. Recentemente, la scialoendoscopia è stata introdotta come un interessante strumento diagnostico e terapeutico per la gestione dei pazienti affetti da scialoadenite radioiodio-indotta non responsiva ai trattamenti medici standard. Lobiettivo della presente revisione è stato valutare linfluenza di questa procedura sulla storia clinica di pazienti affetti da scialoadenite conseguente a trattamento con radioiodio. Complessivamente, la revisione ha incluso 8 studi, 122 pazienti e 264 scialoendoscopie. Le stenosi duttali ed i tappi mucosi hanno rappresentato l85.7% dei reperti endoscopici, sostenendo il ruolo dellostruzione duttale nella fisiopatologia della scialoadenite da radioiodio. Circa l89.3% dei pazienti riportarono una risoluzione parziale o completa degli episodi di scialoadenite ricorrente, senza complicanze post-operatorie maggiori. Un solo caso è stato sottoposto a parotidectomia per fallimento del trattamento scialoendoscopico e persistenza dei sintomi. Tuttavia, i risultati della letteratura riguardarono principalmente valutazioni soggettive e solamente in due esperienze cliniche furono prese in considerazione misure oggettive con risultati discordanti. La xerostomia fu analizzata in pochi studi, con benefici differenti rispetto ai sintomi ostruttivi. La tempistica ideale per la videoendoscopia delle ghiandole salivari necessita di ulteriori analisi, al fine di definire la miglior gestione delle scialoadeniti ostruttive radioiodio-indotte

Characterization of epidemiological distribution and outcome of COVID-19 in patients with hereditary hemorrhagic telangiectasia: a nationwide retrospective multi-centre study during first wave in Italy

Background: Coronavirus Disease 2019 (COVID-19) continues to have a devastating impact across the world. A number of pre-existing common clinical conditions were reported to represent risk factors for more severe COVID-19 outcomes. Hereditary Hemorrhagic Telangiectasia (HHT) is a rare vascular heritable disorders, characterized by complications secondary to visceral Arterio-Venous Malformations. The impact of HHT, as well as for many Rare Diseases (RDs) on infection susceptibility profile and clinical adverse outcome risk is an unresolved issue. Objectives: The main objectives were: to assess the clinical features and outcomes of HHT patients infected with COVID-19; to compare the relative infection risk in these patients with the Italian general population throughout the first pandemic wave; to investigate the factors potentially associated with severe COVID-19 outcome in HHT patients, and the possible impact of COVID-19 infection on HHT-related symptoms/complications. Finally, we aimed to estimate how the lockdown-associated wearing of personal protective equipment/individual protection devices could affect HHT-related telangiectasia bleeding frequency. Methods: The study is a nation-wide questionnaire-based survey, with a multi-Center retrospective cross-sectional design, addressed to the whole Italian HHT population. COVID-19 cases, occurring throughout the first pandemic wave, were collected by a questionnaire-based semi-structured interview. Only the cases ascertained by laboratory confirmation (molecular/serological) were included for epidemiological estimates. Information concerning eventual SarS-Cov-2 infection, as well as regarding HHT-related manifestations and HHT-unrelated co-morbidities were collected by the questionnaire. Prevalence data were compared to Italian general population in the same period. Results: The survey disclosed 9/296 (3.04%) COVID-19 cases, 8/9 of them being resident in Lombardy, the main epidemic epicenter. Pneumonia was reported by 4/9 patients, which prompted hospital admission and intensive care management in 2 cases. No fatal outcome was recorded. After careful refinement of epidemiological analysis, the survey evidenced overlapping infection risk in HHT compared to general population. Conclusions: COVID-19 infection profile parallels geographical distribution of epidemic foci. COVID-19 in HHT patients can lead to highly variable clinical profile, likely overlapping with that of general population. The HHT disease does not seem to involve a different approach in terms of hospital admission and access to intensive care with respect to general population

Safety of direct oral anticoagulants in patients with hereditary hemorrhagic telangiectasia

Background: Hereditary haemorrhagic telangiectasia (HHT) is a rare vascular dysplasia resulting in visceral arteriovenous malformations and smaller mucocutaneous telangiectasia. Most patients experience recurrent nosebleeds and become anaemic without iron supplementation. However, thousands may require anticoagulation for conditions such as venous thromboembolismand/or atrial fibrillation. Over decades,tolerance data has been publishedfor almost 200HHT-affected usersof warfarinand heparins, but there are no publisheddata forthe newer direct oralanticoagulants(DOACs)in HHT. Methods: To provide such data, aretrospective audit was conducted across the eight HHT centres of the European Reference Network for Rare Vascular Disorders (VASCERN),in Denmark, France, Germany, Italy, Netherlands and UK. Results: Although HHT Centreshad not specifically recommended the use of DOACs, 32treatment episodes had been initiated by other cliniciansin 28patients reviewed at the centres, at median age 65years(range 30-84). Indications were for atrial fibrillation (16 treatment episodes) and venous thromboembolism (16 episodes).The 32 treatment episodes used Apixaban (n=15), Rivaroxaban (n=14), and Dabigatran (n=3). HHT nosebleeds increased in severity in 24/32 treatment episodes (75%), leading to treatment discontinuation in 11 (34.4%). Treatment discontinuation was required for 4/15(26.7%) Apixabanepisodes and 7/14 (50%)Rivaroxaban episodes.By a 4 point scale of increasing severity,there was a trend for Rivaroxaban to be associated with a greaterbleeding riskboth including and excluding patients who had used more than one agent (age-adjusted coefficients 0.61 (95% confidence intervals 0.11, 1.20) and 0.74 (95% confidence intervals 0.12, 1.36) respectively. Associationswere maintained after adjustment for genderand treatment indication. Extreme haemorrhagic responses, worse thananything experienced previously, with individual nosebleedslasting hours requiring hospital admissions, blood transfusions and in all cases treatment discontinuation, occurred in5/14(35.7%) Rivaroxabanepisodes compared to 3/15(20%) Apixabanepisodes and published rates of ~5% for warfarin and heparin. Conclusions: Currently, conventional heparin and warfarin remain first choice anticoagulantsin HHT. If newer anticoagulants are considered,although study numbers are small, at this stage Apixaban appearsto be associated with lesser bleeding riskthan Rivaroxaban