Positional assessment of lower third molar and mandibular canal using explainable artificial intelligence.

OBJECTIVE: The aim of this study is to automatically assess the positional relationship between lower third molars (M3i) and the mandibular canal (MC) based on the panoramic radiograph(s) (PR(s)). MATERIAL AND METHODS: A total of 1444 M3s were manually annotated and labeled on 863 PRs as a reference. A deep-learning approach, based on MobileNet-V2 combination with a skeletonization algorithm and a signed distance method, was trained and validated on 733 PRs with 1227 M3s to classify the positional relationship between M3i and MC into three categories. Subsequently, the trained algorithm was applied to a test set consisting of 130 PRs (217 M3s). Accuracy, precision, sensitivity, specificity, negative predictive value, and F1-score were calculated. RESULTS: The proposed method achieved a weighted accuracy of 0.951, precision of 0.943, sensitivity of 0.941, specificity of 0.800, negative predictive value of 0.865 and an F1-score of 0.938. CONCLUSION: AI-enhanced assessment of PRs can objectively, accurately, and reproducibly determine the positional relationship between M3i and MC. CLINICAL SIGNIFICANCE: The use of such an explainable AI system can assist clinicians in the intuitive positional assessment of lower third molars and mandibular canals. Further research is required to automatically assess the risk of alveolar nerve injury on panoramic radiographs.

[Myocardial Infarction and resuscitation of an adolescent: consequences of an unexplained disease]. / Myocardinfarct en reanimatie bij een adolescent.

BACKGROUND: Morbus Kawasaki is defined by unexplained fever combined with at least 4 out of 5 classic symptoms: bilateral conjunctivitis, polymorphic exanthema, strawberry tongue and red swollen lips, extremity changes and cervical lymphadenopathy. However, these symptoms do not always occur completely or simultaneously. CASE DESCRIPTION: An 18-year old man was admitted after an out of hospital cardiac arrest caused by an occluded aneurysmatic LAD, which was treated with a percutanious coronary intervention. Coronary angiogram however also revealed coronary aneurysms of all coronaries, identifying an episode of unexplained fever and vasculitis 4 years prior as Morbus Kawasaki. CONCLUSION: Echocardiogram, CTA and MRA can reveal coronary malformations and thus identify M. Kawasaki when there is an incomplete M. Kawasaki. An early diagnosis and treatment with high dose aspirin and intravenous immunoglobulines is essential to reduce the risk of cardiovascular complications later in life.

Author Correction: One-year postoperative skeletal stability of 3D planned bimaxillary osteotomies: maxilla-first versus mandible-first surgery.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

COVID-19: Technology-Supported Remote Assessment of Pediatric Asthma at Home.

The COVID-19 crisis has pressured hospital-based care for children with high-risk asthma as they have become deprived of regular clinical evaluations. However, COVID-19 also provided important lessons about implementing novel directions for care. Personalized eHealth technology, tailored to the individual and the healthcare system, could substitute elements of hospital care and facilitate early and appropriate medical anticipation in response to imminent loss of control. This perspective article discusses new approaches to the clinical, organizational, and scientific aspects of the use of eHealth technology in pediatric asthma care in times of COVID-19, as illustrated by a case report of an acute asthma exacerbation possibly caused by COVID-19 infection.

One-year postoperative skeletal stability of 3D planned bimaxillary osteotomies: maxilla-first versus mandible-first surgery.

Orthognathic surgery is carried out to correct jaw deformities and to improve facial aesthetics. However, controversy surrounds whether the maxilla- or mandible-first surgery approach leads to better surgical outcomes. In our previous study, we have shown that in most instances, the maxilla-first surgical approach yielded closer concordance with the 3D virtual treatment plan than a mandibular-first procedure. However, the post-operative stability of each approach has not been investigated. Therefore, this one-year follow-up study was set-up and investigated the postoperative skeletal stability of the 3D planned translations and rotations after either the maxilla- or mandible-first surgery. In total, 106 patients who underwent bimaxillary surgery and had an individualized 3D virtual operation plans, received either maxilla-first (n = 53) or mandible-first (n = 53) surgery. 3D printed interocclusal splints were used during surgery to position the jaws. One year postoperatively a cone-beam computed tomography (CBCT) scan was made to assess the effects using the OrthoGnathicAnalyser. The mean sagittal, vertical and transverse relapse was less than 1.8 mm and no significant differences were found in relapse between the maxilla-first or the mandibular-first surgical procedure. Overall, this study shows that 3D virtual planning in combination with an optimised sequencing of osteotomies provides predictable long-term results in bimaxillary surgery.

Human buccal epithelium acquires microbial hyporesponsiveness at birth, a role for secretory leukocyte protease inhibitor.

OBJECTIVE: Repetitive interaction with microbial stimuli renders epithelial cells (ECs) hyporesponsive to microbial stimulation. Previously, we have reported that buccal ECs from a subset of paediatric patients with Crohn's disease are not hyporesponsive and spontaneously released chemokines. We now aimed to identify kinetics and mechanisms of acquisition of hyporesponsiveness to microbial stimulation using primary human buccal epithelium. DESIGN: Buccal ECs collected directly after birth and in later stages of life were investigated. Chemokine release and regulatory signalling pathways were studied using primary buccal ECs and the buccal EC line TR146. Findings were extended to the intestinal mucosa using murine model systems. RESULTS: Directly after birth, primary human buccal ECs spontaneously produced the chemokine CXCL-8 and were responsive to microbial stimuli. Within the first weeks of life, these ECs attained hyporesponsiveness, associated with inactivation of the NF-κB pathway and upregulation of the novel NF-κB inhibitor SLPI but no other known NF-κB inhibitors. SLPI protein was abundant in the cytoplasm and the nucleus of hyporesponsive buccal ECs. Knock-down of SLPI in TR146-buccal ECs induced loss of hyporesponsiveness with increased NF-κB activation and subsequent chemokine release. This regulatory mechanism extended to the intestine, as colonisation of germfree mice elicited SLPI expression in small intestine and colon. Moreover, SLPI-deficient mice had increased chemokine expression in small intestinal and colonic ECs. CONCLUSIONS: We identify SLPI as a new player in acquisition of microbial hyporesponsiveness by buccal and intestinal epithelium in the first weeks after microbial colonisation.

Gene expression analysis of peripheral cells for subclassification of pediatric inflammatory bowel disease in remission.

OBJECTIVE: In current clinical practice, optimal treatment of inflammatory bowel disease (IBD) aims at the induction and maintenance of clinical remission. Clinical remission is apparent when laboratory markers of inflammation are normal and clinical symptoms are absent. However, sub-clinical inflammation can still be present. A detailed analysis of the immune status during this inactive state of disease may provide a useful tool to categorize patients with clinical remission into subsets with variable states of immune activation. DESIGN: By using Affymetrix GeneChips, we analysed RNA gene expression profiles of peripheral blood leukocytes from pediatric IBD patients in clinical remission and controls. We performed (un)supervised clustering analysis of IBD-associated genes and applied Ingenuity® pathway software to identify specific molecular profiles between patients. RESULTS: Pediatric IBD patients with disease in clinical remission display heterogeneously distributed gene expression profiles that are significantly distinct from controls. We identified three clusters of IBD patients, each displaying specific expression profiles of IBD-associated genes. CONCLUSION: The expression of immune- and IBD-associated genes in peripheral blood leukocytes from pediatric IBD patients in clinical remission was different from healthy controls, indicating that sub-clinical immune mechanisms are still active during remission. As such, RNA profiling of peripheral blood may allow for non-invasive patient subclassification and new perspectives in treatment regimes of IBD patients in the future.

T-cell regulation of neutrophil infiltrate at the early stages of a murine colitis model.

BACKGROUND: T-cells are a main target for antiinflammatory drugs in inflammatory bowel disease. As the innate immune system is also implicated in the pathogenesis of these diseases, T-cell suppressors may not only inhibit T-cell-dependent production of proinflammatory mediators but also affect innate immune cell function. Specifically, these drugs may impair innate immune cell recruitment and activation through inhibition of T-cells or act independent of T-cell modulation. We explored the extent of immune modulation by the T-cell inhibitor tacrolimus in a murine colitis model. METHODS: We assessed the effects of tacrolimus on trinitro-benzene sulphonic acid (TNBS) colitis in wildtype and Rag2-deficient mice. The severity of colitis was assessed by means of histological scores and weight loss. We further characterized the inflammation using immunohistochemistry and by analysis of isolated intestinal leukocytes at various stages of disease. RESULTS: Tacrolimus-treated wildtype mice were less sensitive to colitis and had fewer activated T-cells. Inhibition of T-cell function was associated with strongly diminished recruitment of infiltrating neutrophils in the colon at the early stages of this model. In agreement, immunohistochemistry demonstrated that tacrolimus inhibited production of the neutrophil chemoattractants CXCL1 and CXCL2. Rag2-deficient mice displayed an enhanced baseline level of lamina propria neutrophils that was moderately increased in TNBS colitis and remained unaffected by tacrolimus. CONCLUSIONS: Both the innate and the adaptive mucosal immune system contribute to TNBS colitis. Tacrolimus suppresses colitis directly through inhibition of T-cell activation and by suppression of T-cell-mediated recruitment of neutrophils.

Role of the innate immune system in the pathogenesis of inflammatory bowel disease.

Crohn disease and ulcerative colitis are chronic inflammatory diseases of the intestinal tract commonly denoted as inflammatory bowel diseases. It has been proposed that these diseases result from aberrant mucosal immune responses to nonpathogenic microbial residents of the intestines. Recently, it was established that continuous interactions between the innate and the adaptive intestinal immune cells and the microbiota are directly involved in maintaining the physiological noninflammatory state of the intestinal mucosa. In light of the complexity of this mucosal homeostasis, it is astonishing that the inflammatory bowel diseases are relatively rare. Recently, altered functions of the innate immune system have been identified. As such, both hyperresponsiveness and hyporesponsiveness of innate cells have been implicated in the pathogenesis of inflammatory bowel diseases.