Alessandro Acocella

Background and objectives: Although it is very uncommon, medication-induced osteonecrosis of the jaw (also known as MRONJ) can have serious consequences. Traditionally, this adverse event has been recognised in patients who were treated with bisphosphonate (BP) drugs. Nevertheless, in recent years, it has been established that individuals having treatment with various types of medications, such as a receptor activator of nuclear factor kappa-Β ligand inhibitor (denosumab) and antiangiogenic agents, have had the same issue. The purpose of this research is to determine if the application of human amniotic membrane (hAM) may be used as a therapy for MRONJ. Material and Methods: A multi-source database (MEDLINE, EMBASE, AMED, and CENTRAL) systematic search was performed. The major objective of this study is to obtain an understanding of the efficacy of hAM when it is employed as a treatment modality for MRONJ. The protocol of this review was registered in the INPLASY register under the number NPLASY202330010. Results: The authors were able to include a total of five studies for the quality analysis, whereas for the quantity evaluation, only four studies were eligible. A total of 91 patients were considered for the investigation. After treatment with human amniotic membrane (hAM), a recurrence of osteonecrosis was observed in n = 6 cases (8.8%). The combined efficacy of surgical therapy and the use of hAM resulted in an overall success rate of 91.2%. Intraoperative complications were only documented in one article, and they were mostly caused by the positioning of the hAM, which led to wound breakdown at the surgical site. Conclusions: Based on the small amount of data and low-quality research included in this study, using human amniotic membranes to treat MRONJ might represent a feasible option. Nevertheless, further studies with a wider patient population are required to understand the long-term impacts.

Background: Antiresorptive and antiangiogenic medications can cause a serious adverse effect known as medication-related osteonecrosis of the jaw (MRONJ). In recent years, a new trend of research has emerged emphasizing the potential relation of MRONJ and genetic predisposition. Current evidence-based science of this adverse reaction is associated with poorly performed studies. Additionally, MRONJ research has recently observed a new trend of studies orientated towards the misuse of reviews. This quality meta-review intends to summarize the results of all systematic reviews and meta-analyses that have been published on MRONJ in relation to genetic and pharmacogenomics risk factors. Methods: The research study protocol was registered into the database of the International Network for the Registration of Systematic Reviews and Meta-Analyses (INPLASY) INPLASY202230002. A comprehensive search across several databases (PubMed, EMBASE, MEDLINE, and CINAHL) was conducted to locate multi-language papers published between January 2003 and November 2022. Data were collected from relevant research studies and appraised in accordance with the precise outcomes described in this evaluation. Results: Only five systematic reviews and meta-analyses were analysed in this meta-review. All the reviews included in this research presented qualities mistakes and shortcomings. Two quality assessment tools (Confidence in Evidence from Reviews of Qualitative research (CERQual) and Assessment of Multiple Systematic Reviews 2 (AMSTAR-2)) were used to evaluate each study included in this research. Conclusions: The data evaluated by this meta-review confirmed the poor-quality secondary research underpinning the genetic/pharmacogenomics aspect of MRONJ. Moreover, this study highlighted the many flaws of the current published systematic and meta-analysis studies published so far.

Background: Osteonecrosis of the jaw (ONJ) is a condition affecting patients exposed to medications used to treat benign and malignant conditions of bone tissue. Many studies have highlighted that ONJ is a severe condition, which is very challenging to manage, especially in individuals with oncologic disease. The aim of this umbrella review is to analyze all available interventional and non-interventional systematic reviews published on medication-related osteonecrosis of the jaw (MRONJ) and summarize this evidence. Material and methods: A multi-database search (PubMed, MEDLINE, EMBASE and CINAHL) was performed to identify related multi-language papers published from January 2003 until June 2021. An additional manual search was also performed in systematic review registries (PROSPERO, INPLASY, JBI and OFS) to identify possible missing reviews. Data were extracted from relevant papers and analyzed according to the outcomes selected in this review. Results: The search generated 25 systematic reviews eligible for the analysis. The total number of patients included in the analysis was 80,840. Of the reviews, 64% (n = 16) were non-interventional and 36% (n = 9) were interventional. Study designs included case series 20.50% (n = 140), retrospective cohort studies 12.30% (n = 84) and case reports 12.20% (n = 83). It was unclear what study design was used for 277 studies included in the 25 systematic reviews. Conclusions: The data reviewed confirmed that the knowledge underpinning MRONJ in the last 20 years is still based on weak evidence. This umbrella review highlighted a widespread low-level quality of studies and many poorly designed reviews.

Background: Medication-related osteonecrosis of the jaw (MRONJ) can be a life changing iatrogenic complication of antiresorptive and antiangiogenic drug therapy. It is most often associated with high doses of these medications that are used to prevent skeletal-related events in patients with cancer and bone pathologies. Unfortunately, managing MRONJ lesions has proven difficult and remains a major challenge for clinicians. Due to the lack of efficacy in treating MRONJ by surgical modalities (local debridement and free flap reconstruction), the nonsurgical management of MRONJ is still advocated to aid healing or avoid disease progression. The aim of this systematic review is to identify, analyse and understand the published evidence related to the success of oxygen therapies such as ozone (OT) and hyperbaric oxygen (HBO) in treating MRONJ. Material and methods: A multi-database (PubMed, MEDLINE, EMBASE, CINAHL and Cochrane CENTRAL) systematic search was performed by three authors. The identified articles were independently assessed for their risk of bias. Any type of study evaluating humans treated with antiresorptive and antiangiogenic drugs were considered. The aim is primarily to evaluate the success of OT and HBO in resolving MRONJ and secondarily to identify any improvements in quality of life (QoL), rate of complications, time-to-event and severity of side effects related to these treatments. Results: In total, just 13 studies were eligible for analysis. A pooled total of 313 patients (HBO group n = 82; OT group n = 231) described in these studies have shown good tolerance for oxygen therapies. Complete resolution of MRONJ was reported in 44.58% of OT patients but only 5.17% of the HBO group. Progression of MRONJ was reported only in the HBO studies in 10.34% of cases (6 patients). The quality of evidence was low or very low in all studies. This was due to limitations in how the studies were designed, run and reported. Conclusions: Based on the limited data available, it is difficult to suggest OT is better or worse than HBO or whether it is better than a placebo. As the level of evidence available is low, this necessitates larger well-designed trials to justify these interventions for patients affected by MRONJ.

Gorlin-Goltz Syndrome (Nevoid Basal Cell Carcinoma Syndrome) is a well-known disorder with distinctive symptoms, which are studied since the 1960s. This is an hereditary disease, with autosomal dominant trait, characterised by high penetration and variable expressivity. Only recently it has been ascertained that it is caused by the aberration of the long arm of the chromosome 9q22.3, mapped specifically in the area of Patched gene (PTCH). In particular, the PTCH gene is important both for embryonic structuring and cellular cycle, therefore, its mutation represents a key event for the development of the disease. From a clinical point of view, the syndrome requires a multidisciplinary approach meaning that a successful treatment needs the simultaneous co-operation of different specialists. Thus, a correct treatment entails the following steps: an early detection of the disease, an extended family history and a careful evaluation of symptoms. The aim of this article was to highlight the main pathologic and genetic features of Gorlin-Goltz Syndrome, its outbreak frequency and the main characteristics of the population clusters it is more likely to hit. Furthermore, due to the predisposition of the disease to relapse, a constant clinical follow-up combined with a correct treatment are important.

The clinical presentation of Ludwig's angina consists in a severe expanding cellulitis causing swelling of the floor of the mouth, tongue and submandibular region, thus resulting in a possible obstruction of the airway and in a rapid progress in deep neck soft tissue infection and mediastinitis with potentially fatal consequences. Frequently, submandibular cellulitis develops from an acute infection spreading from the lower molar teeth. Mandibular fractures, traumatic laceration of the floor of the mouth, and peritonsillar abscesses are other concomitant clinical features. A case of Ludwig's angina associated with a large erupted odontoma and with a deeply impacted third molar displaced to the border of the mandible is described. The patient was affected by enlargement of submandibular space, marked face swelling causing an evident face deformity, tenderness and redness of the neck and limited movement of the neck and mouth. In the past, Ludwig's angina was frequently fatal, however aggressive surgical and medical therapy have significantly reduced the mortality rate. The reported case can be considered as important, not only because of the rarity of the odontoma eruption in the oral cavity, but mainly for the extent of the clinical manifestation of a lesion usually described in literature as asymptomatic.

If an abscess is not able to establish drainage through the skin surface or into the oral cavity, it may spread diffusely through fascial planes of the neck's soft tissue. Once the infection descends into the submandibular space, it may extend to the lateral pharyngeal space, and then to the retro-pharyngeal space. From here, it may reach the thyroid gland. The authors here describe a case of submandibular phlegmon derived from a periapical abscess of inferior premolar, which has reached the thyroid gland. The damage caused to the gland resulted in the release of a conspicuous quantity of thyroid hormones, thus causing a thyrotoxic pattern: temperature, cutaneous pallor, excessive perspiration, tremor, tiredness, weight loss, increased appetite, and tachycardia. Additionally, the gland's edema caused dysphagia and dysphonia commonly seen with thyroid gland enlargement. After dental drainage and appropriate anti-inflammatory and antibiotic therapy, administration of oral beta-blockers and corticosteroid therapy were performed to counteract thyrotoxicosis in order to prevent recurrences. Finally, a root canal was performed once the thyrotoxicosis had been resolved.

The anterior iliac crest is the harvest site preferred by many authors because of the quantity and quality of bone obtainable and the simplicity of harvesting techniques. The purpose of the present paper is to present a review of anterior iliac crest harvesting techniques and to illustrate the most serious sequelae reported in the literature. A clinical series is also presented in order to evaluate what is, in our experience, the degree of morbility connected with this donor site. We have controlled 107 patients who underwent bone harvesting from the anterior iliac crest between 1980 and 2000, investigating minor complications such as walking deficiency (immediate and long-term) the formation of seromas, haematomas, adynamic ileus and more serious complications such as retroperitoneal haemorrhages, abdominal hernias, ileus fractures, nervous lesions (immediate and long-term). From our survey it emerged that, among the major complications, incidentally rarely reported in the international literature, we found only a small percentage of cases involving damage to nervous structures. Minor complications were also limited and the only problem remains difficulty in walking after the operation which resolves fully in almost all cases. We can therefore state that the anterior iliac crest remains, to date, an excellent site for harvesting and there is no significant morbility and the surgeon has numerous techniques available for reducing the incidence of complications to the minimum.

Fractures of the zygomatic-orbito-maxillary complex (ZOM) are among the most frequent in maxillo-facial surgery. The study evaluates treatment for this type of fracture in the long-term and the sequelae linked to it. Patients who had been operated between february 1998 and november 1999 to reduce and retain ZOM fractures were subjected to check-up examination at the Maxillo-Facial Surgery Operative Unit, Florence. Cases selected had been operated via trans-oral access with incision of the superior vestibular fornix and where necessary with application of means of retention (Foley balloon and/or wire or plate-and-screw osteosynthesis). In these patients, the presence of residual deformities was evaluated together with enophthalmos, diplopia, compromised mouth opening if present, inflammation of the mucosa of the maxillary sinus, and above all incidence of sensory deficit in the distribution area of the infra-orbital nerves and the dental plexus. Particular attention was paid to evaluating tooth sensitivity on the side involved by the trauma, for any damage of the dental plexus. The most frequent sequela found in our group was lesion of the infra-orbital nerves, and a lower percentage of other sequelae such as residual deformities, enophthalmos or diplopia. Interestingly, in all cases in our series there was a significant reduction in tooth sensitivity on the side of the lesion, above all in the anterior sectors.