[Teeth and oral cavity at the heart of systemic health]. / Les dents et le milieu buccal au cœur de la santé globale.

Research into the interrelationships between oral and systemic diseases has been growing exponentially for over 20 years. Teeth and their supporting tissues can be affected by pathologies, particularly infectious ones, the consequences of which are felt locally in the oral cavity and at a distance in the body. Oral diseases frequently lead to the maintenance of an inflammatory state in oral bones and mucosa, which complicates the treatment of systemic inflammatory pathologies. The aim of this review is to take stock of current knowledge concerning the interrelationships that may exist between the oral environment and other organs, in both adults and children.

Title: Les dents et le milieu buccal au cœur de la santé globale. Abstract: La recherche autour des interrelations existant entre les maladies orales et les maladies systémiques connaît une croissance exponentielle depuis plus de vingt ans. Les dents et leurs tissus de soutien peuvent être atteints de maladies, notamment infectieuses, dont les conséquences se font ressentir localement, dans la cavité buccale, mais aussi à distance dans l'organisme. Ces maladies conduisent fréquemment à l'entretien d'un état inflammatoire dans la cavité orale qui complique les traitements de maladies inflammatoires systémiques. L'objectif de cette revue est de dresser un état des lieux des connaissances actuelles concernant les interrelations qui peuvent exister, chez l'adulte comme chez l'enfant.

AKI treated with kidney replacement therapy in critically Ill allogeneic hematopoietic stem cell transplant recipients.

Acute kidney injury (AKI) is a frequent complication following allogeneic hematopoietic stem cell transplantation (allo-HSCT), but few studies have focused on AKI treated with kidney replacement therapy (AKI-KRT), particularly among critically ill patients. We investigated the incidence, risk factors, and 90-day mortality associated with AKI-KRT in 529 critically ill adult allo-HSCT recipients admitted to the ICU within 1-year post-transplant at two academic medical centers between 2011 and 2021. AKI-KRT occurred in 111 of the 529 patients (21.0%). Lower baseline eGFR, veno-occlusive disease, thrombotic microangiopathy, admission to an ICU within 90 days post-transplant, and receipt of invasive mechanical ventilation (IMV), total bilirubin ≥5.0 mg/dl, and arterial pH <7.40 on ICU admission were each associated with a higher risk of AKI-KRT. Of the 111 patients with AKI-KRT, 97 (87.4%) died within 90 days. Ninety-day mortality was 100% in each of the following subgroups: serum albumin ≤2.0 g/dl, total bilirubin ≥7.0 mg/dl, arterial pH ≤7.20, IMV with moderate-to-severe hypoxemia, and ≥3 vasopressors/inotropes at KRT initiation. AKI-KRT was associated with a 6.59-fold higher adjusted 90-day mortality in critically ill allo-HSCT vs. non-transplanted patients. Short-term mortality remains exceptionally high among critically ill allo-HSCT patients with AKI-KRT, highlighting the importance of multidisciplinary discussions prior to KRT initiation.

Development of a sensitive real-time quaking-induced conversion (RT-QuIC) assay for application in prion-infected blood.

Efforts to prevent human-to-human transmission of variant Creutzfeldt-Jakob disease (vCJD) by contaminated blood would be aided by the development of a sensitive diagnostic test that could be routinely used to screen blood donations. As blood samples from vCJD patients are extremely rare, here we describe the optimisation of real-time quaking-induced conversion (RT-QuIC) for detection of PrPSc (misfolded prion protein, a marker of prion infection) in blood samples from an established large animal model of vCJD, sheep experimentally infected with bovine spongiform encephalopathy (BSE). Comparative endpoint titration experiments with RT-QuIC, miniaturized bead protein misfolding cyclic amplification (mb-PMCA) and intracerebral inoculation of a transgenic mouse line expressing sheep PrP (tgOvARQ), demonstrated highly sensitive detection of PrPSc by RT-QuIC in a reference sheep brain homogenate. Upon addition of a capture step with iron oxide beads, the RT-QuIC assay was able to detect PrPSc in whole blood samples from BSE-infected sheep up to two years before disease onset. Both RT-QuIC and mb-PMCA also demonstrated sensitive detection of PrPSc in a reference vCJD-infected human brain homogenate, suggesting that either assay may be suitable for application to human blood samples. Our results support the further development and evaluation of RT-QuIC as a diagnostic or screening test for vCJD.

Obesity Is Associated with the Severity of Periodontal Inflammation Due to a Specific Signature of Subgingival Microbiota.

The aim of this study was to analyze the link between periodontal microbiota and obesity in humans. We conducted a cohort study including 45 subjects with periodontitis divided into two groups: normo-weighted subjects with a body mass index (BMI) between 20 and 25 kg/m2 (n = 34) and obese subjects with a BMI > 30 kg/m2 (n = 11). Our results showed that obesity was associated with significantly more severe gingival inflammation according to Periodontal Inflamed Surface Area (PISA index). Periodontal microbiota taxonomic analysis showed that the obese (OB) subjects with periodontitis were characterized by a specific signature of subgingival microbiota with an increase in Gram-positive bacteria in periodontal pockets, associated with a decrease in microbiota diversity compared to that of normo-weighted subjects with periodontitis. Finally, periodontal treatment response was less effective in OB subjects with persisting periodontal inflammation, reflecting a still unstable periodontal condition and a risk of recurrence. To our knowledge, this study is the first exploring both salivary and subgingival microbiota of OB subjects. Considering that OB subjects are at higher periodontal risk, this could lead to more personalized preventive or therapeutic strategies for obese patients regarding periodontitis through the specific management of oral microbiota of obese patients.

The Role of Dysbiotic Oral Microbiota in Cardiometabolic Diseases: A Narrative Review.

Over the past decade, there have been significant advancements in the high-flow analysis of "omics," shedding light on the relationship between the microbiota and the host. However, the full recognition of this relationship and its implications in cardiometabolic diseases are still underway, despite advancements in understanding the pathophysiology of these conditions. Cardiometabolic diseases, which include a range of conditions from insulin resistance to cardiovascular disease and type 2 diabetes, continue to be the leading cause of mortality worldwide, with a persistently high morbidity rate. While the link between the intestinal microbiota and cardiometabolic risks has been extensively explored, the role of the oral microbiota, the second-largest microbiota in the human body, and specifically the dysbiosis of this microbiota in causing these complications, remains incompletely defined. This review aims to examine the association between the oral microbiota and cardiometabolic diseases, focusing on the dysbiosis of the oral microbiota, particularly in periodontal disease. Additionally, we will dive into the mechanistic aspects of this dysbiosis that contribute to the development of these complications. Finally, we will discuss potential prevention and treatment strategies, including the use of prebiotics, probiotics, and other interventions.

Oral and periodontal assessment at the first trimester of pregnancy: The PERISCOPE longitudinal study.

INTRODUCTION: Periodontal diseases (gingivitis and periodontitis) are chronic non-communicable inflammatory diseases. The risk of developing gingivitis and periodontitis increases during pregnancy. Also, periodontitis increases the risk of developing adverse pregnancy outcomes such as preterm birth and preeclampsia. Early diagnosis of adverse pregnancy outcomes is essential and periodontitis could be an early sign to take into consideration. MATERIAL AND METHODS: We conducted a longitudinal observational study (PERISCOPE study: CNIL, no. 1 967 084 v 0; CER, no. 01-0416) on 121 pregnant women in the first trimester to determine their oral and periodontal health status. We explored the relations between oral and periodontal health status and sociodemographic and behavior characteristics, as well as their course and outcome of pregnancy. RESULTS: A total of 47.1% of the women had periodontitis, of which only 66.7% presented clinical manifestations associated with the disease such as gingival bleeding. These women had a poorer oral and periodontal health, and a higher body mass index, and more of them developed gestational diabetes during the course of pregnancy. The remaining 33.3% showed only discreet and isolated inflammatory signs and, unless thoroughly examined, would have gone undiagnosed for periodontitis. Interestingly these women were more often primiparous, still active professionally and had had a recent oral examination. CONCLUSIONS: The PERISCOPE study is one of the few studies that reports the oral and periodontal health status of pregnant women in the first trimester. Furthermore, the results highlight the need for early oral and periodontal assessment and treatment, even in the absence of exterior clinical signs, in order to prevent periodontal disease aggravation and also, by reducing low grade systemic inflammation, possibly adverse pregnancy outcomes.

Low-Diversity Microbiota in Apical Periodontitis and High Blood Pressure Are Signatures of the Severity of Apical Lesions in Humans.

(1) Background: In developed countries, the prevalence of apical periodontitis (AP) varies from 20% to 50% for reasons that could be associated with the apical periodontitis microbiota ecology. (2) Methods: We performed a clinical study in the Odontology department of Toulouse hospital in France, to sequence the 16S rRNA gene of AP microbiota and collect clinical parameters from 94 patients. Forty-four patients were characterized with a PAI (periapical index of AP severity) score lower or equal to 3, while the others had superior scores (n = 50). (3) Results: The low diversity of granuloma microbiota is associated with the highest severity (PAI = 5) of periapical lesions (Odds Ratio 4.592, IC 95% [1.6329; 14.0728]; p = 0.001; notably, a lower relative abundance of Burkholderiaceae and a higher relative abundance of Pseudomonas and Prevotella). We also identified that high blood pressure (HBP) is associated with the increase in PAI scores. (4) Conclusions: Our data show that a low diversity of bacterial ecology of the AP is associated with severe PAI scores, suggesting a causal mechanism. Furthermore, a second risk factor was blood pressure associated with the severity of apical periodontitis.

Human liver microbiota modeling strategy at the early onset of fibrosis.

BACKGROUND: Gut microbiota is involved in the development of liver diseases such as fibrosis. We and others identified that selected sets of gut bacterial DNA and bacteria translocate to tissues, notably the liver, to establish a non-infectious tissue microbiota composed of microbial DNA and a low frequency live bacteria. However, the precise set of bacterial DNA, and thereby the corresponding taxa associated with the early stages of fibrosis need to be identified. Furthermore, to overcome the impact of different group size and patient origins we adapted innovative statistical approaches. Liver samples with low liver fibrosis scores (F0, F1, F2), to study the early stages of the disease, were collected from Romania(n = 36), Austria(n = 10), Italy(n = 19), and Spain(n = 17). The 16S rRNA gene was sequenced. We considered the frequency, sparsity, unbalanced sample size between cohorts to identify taxonomic profiles and statistical differences. RESULTS: Multivariate analyses, including adapted spectral clustering with L1-penalty fair-discriminant strategies, and predicted metagenomics were used to identify that 50% of liver taxa associated with the early stage fibrosis were Enterobacteriaceae, Pseudomonadaceae, Xanthobacteriaceae and Burkholderiaceae. The Flavobacteriaceae and Xanthobacteriaceae discriminated between F0 and F1. Predicted metagenomics analysis identified that the preQ0 biosynthesis and the potential pathways involving glucoryranose and glycogen degradation were negatively associated with liver fibrosis F1-F2 vs F0. CONCLUSIONS: Without demonstrating causality, our results suggest first a role of bacterial translocation to the liver in the progression of fibrosis, notably at the earliest stages. Second, our statistical approach can identify microbial signatures and overcome issues regarding sample size differences, the impact of environment, and sets of analyses. TRIAL REGISTRATION: TirguMECCH ROLIVER Prospective Cohort for the Identification of Liver Microbiota, registration 4065/2014. Registered 01 01 2014.

Improvement of Mucosal Lesion Diagnosis with Machine Learning Based on Medical and Semiological Data: An Observational Study.

Despite artificial intelligence used in skin dermatology diagnosis is booming, application in oral pathology remains to be developed. Early diagnosis and therefore early management, remain key points in the successful management of oral mucosa cancers. The objective was to develop and evaluate a machine learning algorithm that allows the prediction of oral mucosa lesions diagnosis. This cohort study included patients followed between January 2015 and December 2020 in the oral mucosal pathology consultation of the Toulouse University Hospital. Photographs and demographic and medical data were collected from each patient to constitute clinical cases. A machine learning model was then developed and optimized and compared to 5 models classically used in the field. A total of 299 patients representing 1242 records of oral mucosa lesions were used to train and evaluate machine learning models. Our model reached a mean accuracy of 0.84 for diagnostic prediction. The specificity and sensitivity range from 0.89 to 1.00 and 0.72 to 0.92, respectively. The other models were proven to be less efficient in performing this task. These results suggest the utility of machine learning-based tools in diagnosing oral mucosal lesions with high accuracy. Moreover, the results of this study confirm that the consideration of clinical data and medical history, in addition to the lesion itself, appears to play an important role.

Perioperative management of lithium in the patient undergoing pituitary surgery: a case report.

Lithium is a psychotropic drug used primarily in the treatment of bipolar disorder. It is renally excreted and characteristically causes nephrogenic diabetes insipidus as an adverse drug reaction. Lithium also requires serum level monitoring as there is a narrow therapeutic window and untreated toxicity can result in neurological sequelae including drowsiness, coma, seizures, and ultimately death. We present the case of a 65-year old man admitted for pituitary surgery complicated by post-operative difficult fluid management and subsequent lithium toxicity. We highlight this rare situation and the need to be vigilant in the peri-operative period with any patients on lithium who undergo pituitary surgery.

Developing the Next Generation of Leaders in Health Policy and Management: Lessons From an Undergraduate Student-Led Organization.

As health care continues to evolve, training the next generation of healthcare leaders is more important than ever. However, many university undergraduate students are not directly exposed to topics such as health policy and management within their coursework or co-curricular engagements. At Duke University, we developed the Student Collaborative on Health Policy (SCOHP) as an inter-disciplinary health policy hub that offers opportunities for learning, engagement, and leadership in the healthcare-related fields for students of all academic backgrounds. We see opportunity for similar student-led groups to be established by student leaders at other institutions, increasing interaction with experts, mentorship and the accessibility of experiential education, service, and leadership in the health care sector.

Relationship Between Clinical Features and the Arc and Length of Dehiscence in SCDS: A Single Center Review of 42 Cases.

INTRODUCTION: Superior canal dehiscence syndrome (SCDS) is a rare disorder characterized by an array of audiovestibular symptoms due to a dehiscence of bone overlying the superior semicircular canal (SSC). In the presence of debilitating symptoms, surgical management, to plug or resurface the SCC is performed. Although computed tomography (CT) may overestimate the size or presence of a dehiscence due to a partial volume effect, it remains an invaluable diagnostic tool. OBJECTIVES: To assess for correlation between the arc and length of dehiscence and clinical symptomology. METHOD: A single-center, single-operator retrospective analysis of 42 patients who underwent trans mastoid plugging of SCC with confirmed radiological dehiscence of their SSC between January 2008 and July 2019 was undertaken. Patients were assessed based on seven predefined clinical symptoms. Length and arc of dehiscence's were evaluated by means of high resolution (0.5 mm) CT (HRCT), using multiplanar reconstruction (MPR). Receiver operating characteristics (ROC), and more specifically the area under the ROC curve (AUROC) were used to assess for statistical significance. RESULTS: Our results demonstrate overall very little correlation between the arc and size of the dehiscence and symptoms. The only statistically significant correlation we found was between length of dehiscence and the presence of aural fullness. CONCLUSION: SCDS is a debilitating condition with an array of symptoms on presentation. While dehiscence length demonstrated a correlation with aural fullness, no other symptomology in patients with radiologically evident SCDS demonstrated a statistically significant correlation either against the length or arc of dehiscence.

From Child to Adulthood, a Multidisciplinary Approach of Multiple Microdontia Associated with Hypodontia: Case Report Relating a 15 Year-Long Management and Follow-Up.

Oral rehabilitation of patients presenting multiple microdontia is a real therapeutic challenge. These alterations in size, often associated with other dental anomalies, have aesthetic and functional repercussions for patients and can lead to significant psycho-social consequences. We report here the case of an 11-year-old patient with bilateral sectorial microdontia and agenesis of teeth numbers 13 and 23. She also presented staturo-ponderal delay and a history of acute coronary syndrome with a lower coronary occlusion of unknown aetiology. At first, additive coronoplasties and an orthodontically retained interim prosthesis answered the aesthetic and functional need during childhood and adolescence. Once she reached adulthood, a multidisciplinary meeting was conducted and a treatment plan was established. The decision was made to rehabilitate the upper arch with a permanent bridge and the lower arch with indirect adhesive restorations. This solution solved the problem of the bilateral lateral infraocclusions and tooth agenesis, restoring both aesthetics and function. This paper presents 15 years of management and treatment of a patient presenting multiple microdontia associated with hypodontia. Both the multidisciplinary approach and coordination between the different medical team members was essential to maintain the existing dentition while preparing, planning, and carrying out a personalized treatment plan once maxillofacial growth was complete.

Oral Microbiota: A Major Player in the Diagnosis of Systemic Diseases.

The oral cavity is host to a complex and diverse microbiota community which plays an important role in health and disease. Major oral infections, i.e., caries and periodontal diseases, are both responsible for and induced by oral microbiota dysbiosis. This dysbiosis is known to have an impact on other chronic systemic diseases, whether triggering or aggravating them, making the oral microbiota a novel target in diagnosing, following, and treating systemic diseases. In this review, we summarize the major roles that oral microbiota can play in systemic disease development and aggravation and also how novel tools can help investigate this complex ecosystem. Finally, we describe new therapeutic approaches based on oral bacterial recolonization or host modulation therapies. Collaboration in diagnosis and treatment between oral specialists and general health specialists is of key importance in bridging oral and systemic health and disease and improving patients' wellbeing.

Obesity Drives an Oral Microbiota Signature of Female Patients with Periodontitis: A Pilot Study.

The aim of this study was to analyze the link between oral microbiota and obesity in humans. We conducted a pilot study including 19 subjects with periodontitis divided into two groups: normo-weighted subjects (NWS) with a body mass index (BMI) between 20 and 25 (n = 9) and obese subjects (OS) with a BMI > 30 (n = 10). Obesity was associated with a poor oral health status characterized by an increased number of missing teeth and a higher score of periodontal-support loss associated with dysbiotic oral microbiota (39.45 ± 3.74 vs. 26.41 ± 11.21, p = 0.03 for the Chao 1 index). Oral microbiota taxonomic analysis showed that the abundance of the Capnocytophaga genus was higher (2.47% ± 3.02 vs. 0.27% ± 0.29, p = 0.04) in OS compared to NWS. Obese females (OF) were characterized by an increase in the Streptococcus genus (34.12% ± 14.29 vs. 10.55% ± 10.42, p = 0.05) compared to obese males (OM), where the Neisseria genus was increased (5.75% ± 5.03 vs. 58.05% ± 30.64, p = 0.008). These first data suggest that sex/gender is determinant in the link between oral dysbiotic microbiota and obesity in patients with periodontitis. Our results could lead to recommendations concerning therapeutic strategies for obese patients with periodontitis following the sex/gender.

How Oral Specialists Can Help Diagnose and Manage Extra-Digestive Inflammatory Bowel Disease Complications.

Identification of extra-digestive manifestations of inflammatory bowel disease (IBD) is essential. The oral cavity is a preferential site in which gingival enlargement may be one of these manifestations. We present, in this article, two original cases and a concept map that highlights the need for a close collaboration between the dental surgeon or oral specialist, the dermatologist, and the gastroenterologist. In the first case, the strictly local management of a systemic IBD oral complication, can relieve and answer the patient's complaint without modifying or disrupting the systemic treatment already implemented by the gastroenterologists. In the second case, the dental surgeon's diagnosis of gingival enlargement turns out to be the inaugural manifestation of Crohn's disease and allows early treatment of the intestinal pathology. These two cases illustrate the close link between the oral cavity and IBD. Knowledge and multidisciplinary management of these manifestations such as proposed in the concept map are essential for clinicians for the early diagnosis and the improvement of the oral and general quality of life of patients suffering from IBD.

Simultaneous dysphagia and stridor: an unreported presentation of hypocalcaemia.

Hypocalcaemia is a well-recognized complication of total thyroidectomy surgery. Patients who develop post-operative hypocalcaemia often report symptoms of neuromuscular instability including peripheral numbness and/or tingling. In severe cases, larygospasm with stridor and bronchospasm can occur. We present the first reported case in the literature, to our knowledge, of a 58-year-old male presenting with intermittent exertional stridor, dysphonia and dysphagia following thyroid surgery 2 years previously. Clinical and radiological investigations were unremarkable. Pre-operative screening for a planned panendoscopy to investigate his symptoms highlighted a profound hypocalcaemia (adjusted calcium 1.42 mmol/l). Following calcium replacement therapy, his symptoms subsided. There is an absence of literature describing both dysphagia and stridor synchronously. We not only advocate regular routine follow-up and compliance assessments for such patients but also the consideration of hypocalcaemia as a differential in any patient presenting with such symptoms following any thyroid surgery.

The Schistosoma mansoni tegumental allergen protein, SmTAL1: Binding to an IQ-motif from a voltage-gated ion channel and effects of praziquantel.

SmTAL1 is a calcium binding protein from the parasitic worm, Schistosoma mansoni. Structurally it is comprised of two domains - an N-terminal EF-hand domain and a C-terminal dynein light chain (DLC)-like domain. The protein has previously been shown to interact with the anti-schistosomal drug, praziquantel (PZQ). Here, we demonstrated that both EF-hands in the N-terminal domain are functional calcium ion binding sites. The second EF-hand appears to be more important in dictating affinity and mediating the conformational changes which occur on calcium ion binding. There is positive cooperativity between the four calcium ion binding sites in the dimeric form of SmTAL1. Both the EF-hand domain and the DLC-domain dimerise independently suggesting that both play a role in forming the SmTAL1 dimer. SmTAL1 binds non-cooperatively to PZQ and cooperatively to an IQ-motif from SmCav1B, a voltage-gated calcium channel. PZQ tends to strengthen this interaction, although the relationship is complex. These data suggest the hypothesis that SmTAL1 regulates at least one voltage-gated calcium channel and PZQ interferes with this process. This may be important in the molecular mechanism of this drug. It also suggests that compounds which bind SmTAL1, such as six from the Medicines for Malaria Box identified in this work, may represent possible leads for the discovery of novel antagonists.

The Mechanism of Action of Praziquantel: Can New Drugs Exploit Similar Mechanisms?

Praziquantel (PZQ) is the drug of choice for treating infection with worms from the genus Schistosoma. The drug is effective, cheap and has few side effects. However, despite its use in millions of patients for over 40 years its molecular mechanism of action remains elusive. Early studies demonstrated that PZQ disrupts calcium ion homeostasis in the worm and the current consensus is that it antagonises voltage-gated calcium channels. It is hypothesised that disruption of these channels results in uncontrolled calcium ion influx leading to uncontrolled muscle contraction and paralysis. However, other experimental studies have suggested a role for myosin regulatory light chains and adenosine uptake in the drug's mechanism of action. Assuming voltage-gated calcium channels do represent the main molecular target of PZQ, the precise binding site for the drug remains to be identified. Unlike other commonly used anti-parasitic drugs, there are few definitive reports of resistance to PZQ in the literature. The lack of knowledge about PZQ's molecular mechanism(s) undermines our ability to predict how resistance might arise and also hinder our attempts to develop alternative antischistosomal drugs which exploit the same target(s). Some PZQ derivatives have been identified which also kill or paralyse schistosomes in culture. However, none of these are in widespread clinical use. There is a pressing need for fundamental research into the molecular mechanism( s) of action of PZQ. Such research would enable new avenues for antischsistosomal drug discovery.