The provision of dental extractions in patients with established or a history of medication-related osteonecrosis of the jaw.

Patients with existing or a history of medication-related osteonecrosis of the jaw (MRONJ) are considered to be at a higher risk of further developing MRONJ, particularly if dental extractions are necessary. It is assumed that their underlying risk factors predispose them to developing MRONJ and they are allocated into an 'elevated risk group'. There is no evidence to quantify this risk level; however, it has led to an avoidance of dental extractions in this cohort. However, avoidance of dental extractions is not a realistic treatment option to prevent MRONJ and there is emerging evidence that inflammatory dental disease, such as peri-apical pathology or periodontal disease, can trigger the pathogenesis of MRONJ. The current case series retrospectively reviewed 28 patients with existing or a history of MRONJ who underwent dental extractions (n = 65) via our departmental protocol, which includes elective circumferential socket alveoplasty and primary closure. Our outcomes show that MRONJ did not develop at the new extraction site, with a post-operative review period of at least six months. These results provide promising evidence that dental extractions can be performed in this group of patients with <1% risk of developing MRONJ at the new surgical site, if appropriate measures are undertaken.

An institutional protocol including socket alveoplasty and primary closure following dental extractions for patients with an elevated risk of developing medication-related osteonecrosis of the jaw.

Background The purpose of this study was to evaluate the outcomes of alveoplasty and primary closure following dental extractions in patients with an elevated medication-related osteonecrosis of the jaw (MRONJ) risk.Study design A retrospective review of 46 patients with an elevated MRONJ risk was conducted. This included a total of 124 teeth extracted, due to unrestorable caries (n = 46; 37%) and peri-apical pathology (n = 44; 35%).Results Our results showed 0% (n = 0) of patients in our cohort developed MRONJ post-operatively. Most patients were being treated with intravenous zoledronic acid for breast cancer (n = 23; 50%), with an average of 15 doses (range 1-72).Conclusions This study supports the use of alveoplasty and primary closure for patients with an elevated MRONJ risk. The authors highlight the importance of pre-operative cone beam computed tomography imaging, optimisation of immune status, post-operative prophylactic antibiotics, and the delay of bone modifying agents recommencement as influential factors in mitigating risk and favouring successful outcomes.

Comparison of deep-learning multimodality data fusion strategies in mandibular osteoradionecrosis NTCP modelling using clinical variables and radiation dose distribution volumes.

Objective.Normal tissue complication probability (NTCP) modelling is rapidly embracing deep learning (DL) methods, acknowledging the importance of spatial dose information. Finding effective ways to combine information from radiation dose distribution maps (dosiomics) and clinical data involves technical challenges and requires domain knowledge. We propose different multi-modality data fusion strategies to facilitate future DL-based NTCP studies.Approach.Early, joint and late DL multi-modality fusion strategies were compared using clinical and mandibular radiation dose distribution volumes. These were contrasted with single-modality models: a random forest trained on non-image data (clinical, demographic and dose-volume metrics) and a 3D DenseNet-40 trained on image data (mandibular dose distribution maps). The study involved a matched cohort of 92 osteoradionecrosis cases and 92 controls from a single institution.Main results.The late fusion model exhibited superior discrimination and calibration performance, while the join fusion achieved a more balanced distribution of the predicted probabilities. Discrimination performance did not significantly differ between strategies. Late fusion, though less technically complex, lacks crucial inter-modality interactions for NTCP modelling. In contrast, joint fusion, despite its complexity, resulted in a single network training process which included intra- and inter-modality interactions in its model parameter optimisation.Significance.This study is a pioneering effort in comparing different strategies for including image data into DL-based NTCP models in combination with lower dimensional data such as clinical variables. The discrimination performance of such multi-modality NTCP models and the choice of fusion strategy will depend on the distribution and quality of both types of data. Multiple data fusion strategies should be compared and reported in multi-modality NTCP modelling using DL.

Combined central and peripheral demyelination in two siblings, immune mediated or genetic?

We report unusual cases of combined central and peripheral demyelination in two siblings related to pregnancy, each presenting with progressive tetraparesis and cranial nerve palsies. The elder sister had a relapsing-remitting course with optic nerve dysfunction and died during a relapse from respiratory insufficiency. The younger sister presented with disorientation and acute-onset limb and facial weakness. She responded well to corticosteroid therapy. Their clinical presentation, response to immunomodulatory therapy, nerve conduction studies, cerebrospinal fluid and histology supported an acquired demyelinating cause. Whole-exome sequencing identified variants in two genes not previously linked to this clinical phenotype. Serological tests for antibody-mediated demyelination were negative. Despite the undefined pathogenesis, these cases provide a platform to explore the confluence of genetic, immune and environmental factors in the context of acquired demyelination. We discuss the differential diagnosis and a diagnostic approach to such cases from the perspectives of neuroimmunology and neurogenetics.

Initial evaluation of a technologyenabled change in delivery of the dementia service during COVID-19 in North Warwickshire.

BACKGROUND: Remote monitoring technologies show potential to help health professionals deliver preventative interventions which can avoid hospital admissions and allow patients to remain in a home setting. AIMS: To assess whether an Internet of Things (IoT) driven remote monitoring technology, used in the care pathway of community dementia patients in North Warwickshire improved access to care for patients and cost effectiveness. METHOD: Patient level changes to anonymised retrospective healthcare utilisation data were analysed alongside costs. RESULTS: Urgent care decreased following use of an IoT driven remote monitoring technology; one preventative intervention avoided an average of three urgent interventions. A Chi-Square test showing this change as significant. Estimates show annualised service activity avoidance of £201,583 for the cohort; £8764 per patient. CONCLUSIONS: IoT driven remote monitoring had a positive impact on health utilisation and cost avoidance. Future expansion of the cohort will allow for validation of the results and consider the impact of the technology on patient health outcomes and staff workflows.

Clinical status of established MRONJ in oncology patients continuing bone-modifying agents.

The continuation of bone-modifying agents (BMAs) in patients with established medication-related osteonecrosis of the jaw (MRONJ) is a common concern among dentists and oncologists. There is little evidence supporting or refuting the continued use of BMAs or drug holidays and their impact on established MRONJ. This paper evaluates the outcome of continued BMAs use on the patient's MRONJ status. A retrospective review of 29 oncology patients undergoing active cancer care for either metastatic disease or multiple myeloma was conducted. Data on demographics, oncological status, BMA history and MRONJ status were collected. In total, 90% of patients were judged to have healed or stable MRONJ while continuing BMAs. Most patients (69%) continued the same BMA regime (three- or four-weekly) that they were on before developing MRONJ. The average number of BMAs doses received after an MRONJ diagnosis was 12 (range 1-48). Three patients (10.3%) were found to have MRONJ progression, with two patients developing new sites of necrosis. This real-world dataset suggests that the majority of MRONJ cases remain stable and will not worsen with the continuation of BMAs.

The effectiveness of autologous platelet concentrates in prevention and treatment of medication-related osteonecrosis of the jaws: A systematic review.

The systematic review aims to answer the PICOS question: "Are the autologous platelet concentrates (APCs) an effective strategy in prevention and/or treatment of patients at risk of/affected by medication-related osteonecrosis of the jaws (MRONJ)?". A literature search was conducted via PubMed, MEDLINE, EMBASE, and CINAHL (January 2006 - September 2023). 30 articles were included, evaluating preventive (n = 8*) and treatment strategies (n = 23*). The risk of bias and quality of studies were assessed utilising ROB-2, ROBIN-1 and GRADE criteria. Meta-analysis was undertaken for eligible studies. The application of APCs demonstrated a statistically significant effectiveness in prevention of MRONJ in 86.13% (p < 0.001) but failed to achieve the same level of certainty in treatment of established MRONJ in 83.4% (p = 0.08). High levels of bias were identified; thus, the results should be interpreted with caution. More high quality prospective randomised controlled trials are needed to further evaluate the effectiveness of APCs in management of MRONJ.

Pembrolizumab related osteonecrosis of the jaw.

Medication related osteonecrosis of the jaw (MRONJ) is a serious complication with potential implications on patients' ongoing medical care. This case report describes a case of MRONJ from pembrolizumab; a novel immune checkpoint inhibitor drug.

Pre-existing medication-related osteonecrosis of the jaw before dental extraction.

Medication-related osteonecrosis of the jaw (MRONJ) is a severe adverse event, most commonly associated with dental extractions as a predisposing event. However, it is possible that established MRONJ may be existent before dental extractions and is mistaken for odontogenic disease. The provision of a dental extraction will lead to clinically obvious MRONJ with the cause being attributed to tooth removal. We present a case series of ten patients with pre-existing necrosis of the jaw before dental extraction.Retrospective data were collected on ten patients who presented to the oral surgery department between 2017-2021, diagnosed with pre-existing necrosis. A diagnosis of pre-existing MRONJ was made based on the identification of necrotic bone clinically, either with plain film or cone beam computed tomography (CBCT). Patients with pre-existing necrosis presented with a range of symptoms, including pain, swelling and tooth mobility. Plain film imaging revealed a variety of findings, including periapical radiolucency, periodontal ligament widening and bone loss. CBCT imaging confirmed a necrotic pattern of bone destruction confirming a diagnosis of pre-existing MRONJ.There is increasing evidence to suggest that local inflammation can be a predisposing factor for MRONJ development as opposed to surgical intervention. This case series provides early insight into the presentation of pre-existing MRONJ.

The continuation of oral anticoagulation and antiplatelet therapy for dento-alveolar surgery: a service evaluation.

Background Patients taking oral anticoagulants (OACs) and oral antiplatelets (OAPs) have a risk of post-operative bleeding when dental extractions are required. Guidance exists to assist dental practitioners on how best to clinically manage these patients, but this is based upon low-quality evidence. The current service evaluation provides real world clinical data when these drugs are not discontinued for oral surgery procedures.Materials and methods All OACs and OAPs were continued and patients requiring dental extractions had local haemostatic measures (local anaesthesia with adrenaline, socket packing with haemostat and resorbable sutures). All patients were offered a follow-up via a telephone clinic service after surgery to assess any post-operative bleeding.Results A total of 439 patients underwent 513 surgical episodes, equating to 1,001 dental extractions. Overall, 412 (95.9%) patients reported no post-operative bleeding complications. A total of 18 (4.1%) patients reported post-operative bleeding requiring further intervention. All but two patients were managed with local haemostatic measures, and no patient required hospital admission. For the single novel OAC cohort of patients, 8/185 (4.3%) procedures had post-operative bleeding.Conclusion This current service evaluation highlights that the risk of significant or life-threatening bleeding following dental extraction when OACs or OAPs are continued remains rare.

Prediction of postpartum prediabetes by machine learning methods in women with gestational diabetes mellitus.

Early onset of type 2 diabetes and cardiovascular disease are common complications for women diagnosed with gestational diabetes. Prediabetes refers to a condition in which blood glucose levels are higher than normal, but not yet high enough to be diagnosed as type 2 diabetes. Currently, there is no accurate way of knowing which women with gestational diabetes are likely to develop postpartum prediabetes. This study aims to predict the risk of postpartum prediabetes in women diagnosed with gestational diabetes. Our sparse logistic regression approach selects only two variables - antenatal fasting glucose at OGTT and HbA1c soon after the diagnosis of GDM - as relevant, but gives an area under the receiver operating characteristic curve of 0.72, outperforming all other methods. We envision this to be a practical solution, which coupled with a targeted follow-up of high-risk women, could yield better cardiometabolic outcomes in women with a history of GDM.

Percutaneous approach for reducing outflow tract obstruction in hypertrophic obstructive cardiomyopathy.

Hypertrophic obstructive cardiomyopathy (HOCM) affects approximately 1 in 500 people globally. The condition results in hypertrophy of the interventricular septum and thickening of the left ventricular wall. Surgical management to resect the thickened myocardium or septal alcohol ablation are currently considered the mainstay treatment option for HOCM refractory to pharmacological therapy. In this special report we aim to highlight the current landscape of septal mass reduction in HOCM. Next, we describe the evolving discipline of minimally invasive techniques for reducing outflow tract obstruction in patients with HOCM. We further consider future options and outline a possible percutaneous approach for septal myectomy with a novel device.

The use of liquid formulation pentoxifylline and vitamin E in both established and as a prophylaxis for dental extractions "at risk" of osteoradionecrosis.

BACKGROUND: Osteoradionecrosis (ORN) of the jaws remains one of the most debilitating complications of radiotherapy (RT) in patients with head and neck cancer (HNC). Liquid pentoxifylline and vitamin E (PVe) presents an alternative formulation to tablets for patients with dysphagia or enteric feeding. OBJECTIVE: This study aimed to assess the clinical outcomes of using a liquid formulation of PVe for both established ORN and as a prophylaxis to avoid its occurrence after dental extractions. A secondary objective was to determine patient-reported side effects in relation to the liquid formulation of PVe. STUDY DESIGN: The clinical records of 111 patients with HNC who were prescribed liquid PVe were reviewed retrospectively (66 with established ORN and 45 as prophylaxis before an invasive dental procedure). RESULTS: In established ORN, 44% healed, and 41% were stable. In the prophylaxis group, 96% of surgical sites healed completely, with 4% (n = 2) developing ORN. Most patients (89%) were able to tolerate liquid PVe. Of the 11% (n = 12) who could not tolerate this regime, the most commonly reported side effect was gastric irritation (n = 5/12), whereas no more than 1 patient reported dizziness, malaise, and bleeding. CONCLUSIONS: This retrospective review suggests that liquid PVe is efficacious for both established ORN and as a prophylaxis. Side effects reported were similar to those recognized for the tablet formulation.

Breeding and Genomic Approaches towards Development of Fusarium Wilt Resistance in Chickpea.

Chickpea is an important leguminous crop with potential to provide dietary proteins to both humans and animals. It also ameliorates soil nitrogen through biological nitrogen fixation. The crop is affected by an array of biotic and abiotic factors. Among different biotic stresses, a major fungal disease called Fusarium wilt, caused by Fusarium oxysporum f. sp. ciceris (FOC), is responsible for low productivity in chickpea. To date, eight pathogenic races of FOC (race 0, 1A, and 1B/C, 2-6) have been reported worldwide. The development of resistant cultivars using different conventional breeding methods is very time consuming and depends upon the environment. Modern technologies can improve conventional methods to solve these major constraints. Understanding the molecular response of chickpea to Fusarium wilt can help to provide effective management strategies. The identification of molecular markers closely linked to genes/QTLs has provided great potential for chickpea improvement programs. Moreover, omics approaches, including transcriptomics, metabolomics, and proteomics give scientists a vast viewpoint of functional genomics. In this review, we will discuss the integration of all available strategies and provide comprehensive knowledge about chickpea plant defense against Fusarium wilt.

Pentoxifylline and tocopherol (vitamin E) with/without clodronate for the management of osteoradionecrosis: A scoping review.

BACKGROUND: Treatment of osteoradionecrosis (ORN) is not a straightforward task, and it is unpredictable. However, a combination of pentoxifylline; an antioxidant drug, and tocopherol (vitamin E) works as a potent antifibrotic agent and have shown recently both significant and impressive results. AIMS: This scoping review aims to investigate the most prescribed regimen of pentoxifylline and tocopherol with/without clodronate for the management of ORN. METHODS: Ovid MEDLINE and EMBASE databases were used to retrieve eligible studies using planned search keywords. PROSPERO and Cohcarne library were also searched for ongoing or published systematic reviews, respectively. Included articles were grouped thematically according to the type of studies and accordingly they were summarized. RESULTS: A total of 27 articles met the inclusion criteria and included in the data analyses. All the included articles were published between 1997 and 2020. Of these 27 included studies, two were randomized control trials, two were systematic reviews, six were retrospective studies, five were observational studies, seven were narrative reviews, four were case reports, and lastly one was an in-vitro study. CONCLUSIONS: Treatment by PENTO (800 mg of pentoxifylline + 1000 IU of tocopherol) once daily for an early established ORN or PENTOCLO (PENTO regimen + 1600 mg of clodronate) once daily for the refractory/severe cases of ORN appears to be the most prescribed regimen used for the treatment of ORN using these drugs. These drugs appear safe, effective and inexpensive for the treatment of ORN.

The Helping Everyone Achieve Long Term Health Passport: exploring potential use of the HEALTH Passport in primary and secondary schools.

BACKGROUND: Chronic disease is a significant burden on the global population. The Helping Everyone Achieve Long Term Health (HEALTH) Passport is a paper-based approach previously utilized to help adults modify clinical risk factors through lifestyle, which may be effective in improving the long-term health of school-age children. This study investigates the feasibility of in-school use by engaging trainee teachers in primary and secondary education. METHODS: Two hundred and fifty six unique responses were collated to evaluate current teaching of the main health risk factors and HEALTH Passports specifically adapted for schools. Trainees attended workshops with pre- and post-questionnaires used to measure training efficacy and evaluate the Passports' suitability for in-school use. Narrative analysis of feedback was performed. RESULTS: Feedback received for both Passports was positive overall. Trainees highlighted the need for the Passports to be further age differentiated. Significantly increased confidence (P < 0.01) in knowledge of exercise, type 2 diabetes, weight and blood pressure was shown. Confidence in smoking, drugs and alcohol knowledge was reduced highlighting the requirement for further teacher training. CONCLUSIONS: The HEALTH Passport has potential as an intervention to improve health literacy in school-age children. Age adaptation is needed with references to weight measures removed. Emotional well-being should be focused on, and data management stringently assessed for child protection.

The clinical effect of radiotherapy on pulpal microvasculature: a systematic review.

Introduction/objectives Radiotherapy (RT) has a detrimental effect on the histomorphology of oral tissues. Patients undergoing RT are at risk of developing macrovascular and microvascular changes, which can lead to significant clinical consequences. Despite advances in RT delivery systems, radiation injury remains a modern-day clinical problem. The aim of this systematic review is to investigate the available evidence regarding the impact of RT to the dental pulp and the clinical manifestations of these effects.Data and sources A multi-database search (PubMed, Medline, Embase and CINAHL) was performed to identify related papers published from inception until November 2021. An additional manual search was performed to identify further articles. The data extracted from relevant papers were analysed according to the outcomes selected in this review.Study selection The search generated seven articles eligible for analysis with a total of 2,709 teeth included. RT dose exposure ranged from 30-71.2 Gray with a common finding that RT decreases the number of teeth responding to pulp sensibility testing.Conclusions Knowledge related to the impact of RT on dental pulp is limited and based on weak evidence and a low-level quality of studies. Future studies should incorporate exact RT doses to the teeth and use replicable pulpal testing methods. Understanding the pulpal status post-RT remains an important consideration as dental extractions should be avoided in this cohort due to the risk of osteoradionecrosis.

Osteonecrosis of the jaw in primary dental care: Recognition and referral.

Osteoradionecrosis (ORN) and medication-related osteonecrosis of the jaw (MRONJ) are uncommon conditions, however when present they have a significant impact on a patient's quality of life and are notoriously difficult to treat. With medical advances resulting in improved survival rates and increased life expectancy, it is likely that general dental practitioners (GDPs) will more frequently be involved in the oral health management of patients at risk of both ORN and MRONJ. Though management of both diseases is beyond the scope of primary care dentistry, the GDP still has a key role in the patient's overall care. It is therefore important to have a good understanding of these conditions and their consequences for dental treatment in order to provide adequate patient support. Management requires a multidisciplinary approach to treatment and as part of this GDPs are integral in prevention, early recognition and maintenance of oral health following diagnosis. This article aims to refresh the reader's knowledge regarding MRONJ and ORN and support the GDP in managing this patient group.