Constitutive IP₃ signaling underlies the sensitivity of B-cell cancers to the Bcl-2/IP₃ receptor disruptor BIRD-2

Anti-apoptotic Bcl-2 proteins are upregulated in different cancers, including diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL), enabling survival by inhibiting pro-apoptotic Bcl-2-family members and inositol 1,4,5-trisphosphate (IP3) receptor (IP3R)-mediated Ca2+-signaling. A peptide tool (Bcl-2/IP3R Disruptor-2; BIRD-2) was developed to abrogate the interaction of Bcl-2 with IP3Rs by targeting Bcl-2′s BH4 domain. BIRD-2 triggers cell death in primary CLL cells and in DLBCL cell lines. Particularly, DLBCL cells with high levels of IP3R2 were sensitive to BIRD-2. Here, we report that BIRD-2-induced cell death in DLBCL cells does not only depend on high IP3R2-expression levels, but also on constitutive IP3 signaling, downstream of the tonically active B-cell receptor. The basal Ca2+ level in SU-DHL-4 DLBCL cells was significantly elevated due to the constitutive IP3 production. This constitutive IP3 signaling fulfilled a pro-survival role, since inhibition of phospholipase C (PLC) using U73122 (2.5 µM) caused cell death in SU-DHL-4 cells. Milder inhibition of IP3 signaling using a lower U73122 concentration (1 µM) or expression of an IP3 sponge suppressed both BIRD-2-induced Ca2+ elevation and apoptosis in SU-DHL-4 cells. Basal PLC/IP3 signaling also fulfilled a pro-survival role in other DLBCL cell lines, including Karpas 422, RI-1 and SU-DHL-6 cells, whereas PLC inhibition protected these cells against BIRD-2-evoked apoptosis. Finally, U73122 treatment also suppressed BIRD-2-induced cell death in primary CLL, both in unsupported systems and in co-cultures with CD40L-expressing fibroblasts. Thus, constitutive IP3 signaling in lymphoma and leukemia cells is not only important for cancer cell survival, but also represents a vulnerability, rendering cancer cells dependent on Bcl-2 to limit IP3R activity. BIRD-2 seems to switch constitutive IP3 signaling from pro-survival into pro-death, presenting a plausible therapeutic strategy

Manual versus rigid intraoperative maxillo-mandibular fixation in the surgical management of mandibular fractures:A European prospective analysis

Purpose: Intraoperative stabilisation of bony fragments with maxillo-mandibular fixation (MMF) is an essential step in the surgical treatment of mandibular fractures that are treated with open reduction and internal fixation (ORIF). The MMF can be performed with or without wire-based methods, rigid or manual MMF, respectively. The aim of this study was to compare the use of manual versus rigid MMF, in terms of occlusal outcomes and infective complications. Materials and methods: This multi-centric prospective study involved 12 European maxillofacial centres and included adult patients (age ≥16 years) with mandibular fractures treated with ORIF. The following data were collected: age, gender, pre-trauma dental status (dentate or partially dentate), cause of injury, fracture site, associated facial fractures, surgical approach, modality of intraoperative MMF (manual or rigid), outcome (minor/major malocclusions and infective complications) and revision surgeries. The main outcome was malocclusion at 6 weeks after surgery. Results: Between May 1, 2021 and April 30, 2022, 319 patients-257 males and 62 females (median age, 28 years)-with mandibular fractures (185 single, 116 double and 18 triple fractures) were hospitalised and treated with ORIF. Intraoperative MMF was performed manually on 112 (35%) patients and with rigid MMF on 207 (65%) patients. The study variables did not differ significantly between the two groups, except for age. Minor occlusion disturbances were observed in 4 (3.6%) patients in the manual MMF group and in 10 (4.8%) patients in the rigid MMF group (p &gt; .05). In the rigid MMF group, only one case of major malocclusion required a revision surgery. Infective complications involved 3.6% and 5.8% of patients in the manual and rigid MMF group, respectively (p &gt; .05). Conclusion: Intraoperative MMF was performed manually in nearly one third of the patients, with wide variability among the centres and no difference observed in terms of number, site and displacement of fractures. No significant difference was found in terms of postoperative malocclusion among patients treated with manual or rigid MMF. This suggests that both techniques were equally effective in providing intraoperative MMF.</p

Cranial osteomyelitis 7 years after orbital exenteration and orbital implants: A cascade of problems with a good final outcome

Cranial osteomyelitis is an uncommon, but important entity, particularly when misdiagnosed. This case report describes a 73-year-old woman with a history of basal cell carcinoma in her right eyebrow. After treatment with surgery and radiotherapy, two years later, she had undergone another operation for reconstruction and orbital implants. The present study describes imaging aspects, treatment options, and follow-up of an incident that occurred seven years after reconstruction. The patient visited the emergency department, due to a deep infection around the orbital implants. We detected early cranial osteomyelitis, but treatment was followed by a cascade of problems. After two months, she presented with exposed osteosynthesis material. Two months after removal of the material, she was diagnosed with supraorbital osteoradionecrosis. Subsequent treatment with antibiotics, debridement, and a transposition flap provided a successful final outcome. Keywords: Cranial osteomyelitis, Osteoradionecrosis, Hyperbaric oxygen, Leukocyte and Platelet Rich Fibrin, Orbital implants, Basal cell carcinom

Condylar Fractures: An Argument for Conservative Treatment

Introduction: The treatment of mandibular condyle fractures remains a controversial topic in maxillofacial surgery. No uniform treatment protocol is currently available. Purpose: We performed a retrospective monocentric cohort study of patients with condylar fractures and their treatment, including long-term follow-up by telephone, followed by a short review of the literature. Patients and Methods: The available data on condylar fractures presenting at Leuven University Hospitals between January 1, 2009, and December 31, 2015, were analyzed. Cause, age, sex, fracture level, degree of displacement, associated facial fractures, malocclusion, type of treatment, and complications were noted. Follow-up by telephone was performed after an average 261 weeks for the conservative group. Results: A total of 109 condylar fractures were observed with a male/female ratio of 1.14:1. Most fractures were subcondylar, unilateral, displaced, caused by road traffic accidents, and treated conservatively. Discussion: In children and intracapsular fractures, conservative management remains the first choice. Maxillomandibular fixation should be used sparingly in children and for as short a time as possible. Some patients indicated for surgery can still have acceptable results if treated conservatively.status: publishe

A time-driven activity-based costing approach for identifying variability in costs of childbirth between and within types of delivery

Background: Recently, time-driven activity-based costing (TDABC) is put forward as an alternative, more accurate costing method to calculate the cost of a medical treatment because it allows the assignment of costs directly to patients. The objective of this paper is the application of a time-driven activity-based method in order to estimate the cost of childbirth at a maternal department. Moreover, this study shows how this costing method can be used to outline how childbirth costs vary according to considered patient and disease characteristics. Through the use of process mapping, TDABC allows to exactly identify which activities and corresponding resources are impacted by these characteristics, leading to a more detailed understanding of childbirth cost. Methods: A prospective cohort study design is performed in a maternity department. Process maps were developed for two types of childbirth, vaginal delivery (VD) and caesarean section (CS). Costs were obtained from the financial department and capacity cost rates were calculated accordingly. Results: Overall, the cost of childbirth equals €1894,12 and is mainly driven by personnel costs (89,0%). Monitoring after birth is the most expensive activity on the pathway, costing €1149,70. Significant cost variations between type of delivery were found, with VD costing €1808,66 compared to €2463,98 for a CS. Prolonged clinical visit (+ 33,3 min) and monitoring (+ 775,2 min) in CS were the main contributors to this cost difference. Within each delivery type, age, parity, number of gestation weeks and education attainment were found to drive cost variations. In particular, for VD an age > 25 years, nulliparous, gestation weeks > 40 weeks and higher education attainment were associated with higher costs. Similar results were found within CS for age, parity and number of gestation weeks. Conclusions: TDABC is a valuable approach to measure and understand the variability in costs of childbirth and its associated drivers over the full care cycle. Accordingly, these findings can inform health care providers, managers and regulators on process improvements and cost containment initiatives.

Can L-PRF be helpful for delayed deep wound healing after a tracheotomy or lymph node dissection in a pN0 status?: A case report

Introduction and importance Leukocyte platelet-rich fibrin (L-PRF) is used for its ability to deliver high concentrations of autologous growth factors to host tissues, to promote tissue repair. Case presentation This report describes the case of a 48-year-old woman with tongue cancer treated surgically (pT3pN0), who experienced a delay of five weeks in the process of deep wound healing after a tracheotomy and cervical lymph node dissection that was treated with L-PRF. The patient had no risk factors for delayed wound healing, except for active preoperative smoking. Several attempts were made to stimulate bleeding and edge-to-edge closure, without conclusive results. However, five days after L-PRF placement, the subcutaneous tissues were adhering to the deep planes in both wounds. Fifteen days after L-PRF treatment, a complete wound healing was observed which allowed initiation of postoperative radiotherapy. Clinical discussion This case report questions the potential of L-PRF for patients with a pN0 status, not only in superficial wounds, but also in deep wound healing. However, the use of L-PRF for patients with a pN1 status is not recommended, given the possible presence of tumour cells in the tissues, and the activation of these tumour cells by the growth factors present in L-PRF. Conclusion This report supports the idea that L-PRF can contribute to deep soft tissue healing for patients with a pN0 status due to its positive clinical healing effects

Subperiosteal orbital abscess from odontogenic origin: A case report

INTRODUCTION: Subperiosteal orbital abcess is a rarely reported complication of odontogenic infections and can be associated visual impairment and neurological symptoms. Because of fast infection spreading, delay in diagnosis and treatment can result in permanent damage. PRESENTATION OF CASE: A 55-year old presented with a right-sided subperiosteal orbital abscess originating from a decayed first upper molar. The associated loss of vision improved only after a extraoral surgical drainage. Three years later, recurrent headaches, photobia and ptosis still persist. DISCUSSION: Our case demonstrates a rare but potentially hazardous complication of untreated dental infections. The effect of antibiotics is often overestimated, and lack of treatment may lead to serious sequelae, certainly when the orbital infection is located posterior to the orbital septum. When intraoral drainage is insufficient, the infection should be accessed extraorally. CONCLUSION: Orbital infections require a thorough clinical evaluation, including the oral cavity as dental infections may be overlooked. Dental radiograpy plays a major role. Prompt and adequate treatment is crucial in preventing further spreading of odontogenic infections.status: publishe

Diagnostic value of cone beam computed tomography in complex and compound odontomas: a systematic review and open classification matrix

Objective: Firstly, this review aims to analyse the recent literature about three-dimensional (3D) diagnostic imaging in complex and compound odontomas and compare it to two-dimensional (2D) imaging. Panoramic radiographs help to evaluate the vertical position of odontomas, and occlusal radiographs are used to evaluate the proximity to adjacent teeth. However, cone beam computed tomography (CBCT) can offer volumetric images, and therefore, a more accurate three-dimensional analysis. Secondly, this research aims to construct an open classification matrix for complex and compound odontomas for dentomaxillofacial CBCT radiology protocols based on a systematic literature review. Material and methods: Two systematic literature searches were conducted in PubMed (Medline), on 2 February 2022 concerning classification systems, and on 5 February 2022 concerning CBCT images. Results: In total, these searches revealed 391 papers by reviewing the databases mentioned above. Six articles were selected for inclusion on classification of odontomas and 13 articles were found on CBCT imaging. Consequently, the construction of an open classification matrix for compound and complex odontomas for dentomaxillofacial CBCT radiology protocols was performed using these 19 articles. Conclusions: CBCT offers a more precise position and accurate diagnosis of complex and compound odontomas compared to 2D imaging. Consequently, it enhances the detailed view of the site (multiple or unique), location (intraosseous, partially or completely extragnathic), size, extension (bony expansion, thinning or perforation cortical bone), density and type (denticulo type, particle type, denticulo-particle type, denticulo-amorphous type, amorphous tissue), relationship (with the crown or root of the definitive tooth), adjacent teeth resorption (deciduous or definitive), adjacent teeth (retention or impaction), and distance with adjacent structures (inferior alveolar nerve, sinus maxillaris), as well as adequate surgical planning. Moreover, this research presents an open classification matrix for the most complete description of compound and complex odontomas when analysing CBCT imaging.

Diagnostic value of cone beam computed tomography in complex and compound odontomas: a systematic review and open classification matrix

Objective: Firstly, this review aims to analyse the recent literature about three-dimensional (3D) diagnostic imaging in complex and compound odontomas and compare it to two-dimensional (2D) imaging. Panoramic radiographs help to evaluate the vertical position of odontomas, and occlusal radiographs are used to evaluate the proximity to adjacent teeth. However, cone beam computed tomography (CBCT) can offer volumetric images, and therefore, a more accurate three-dimensional analysis. Secondly, this research aims to construct an open classification matrix for complex and compound odontomas for dentomaxillofacial CBCT radiology protocols based on a systematic literature review. Material and methods: Two systematic literature searches were conducted in PubMed (Medline), on 2 February 2022 concerning classification systems, and on 5 February 2022 concerning CBCT images. Results: In total, these searches revealed 391 papers by reviewing the databases mentioned above. Six articles were selected for inclusion on classification of odontomas and 13 articles were found on CBCT imaging. Consequently, the construction of an open classification matrix for compound and complex odontomas for dentomaxillofacial CBCT radiology protocols was performed using these 19 articles. Conclusions: CBCT offers a more precise position and accurate diagnosis of complex and compound odontomas compared to 2D imaging. Consequently, it enhances the detailed view of the site (multiple or unique), location (intraosseous, partially or completely extragnathic), size, extension (bony expansion, thinning or perforation cortical bone), density and type (denticulo type, particle type, denticulo-particle type, denticulo-amorphous type, amorphous tissue), relationship (with the crown or root of the definitive tooth), adjacent teeth resorption (deciduous or definitive), adjacent teeth (retention or impaction), and distance with adjacent structures (inferior alveolar nerve, sinus maxillaris), as well as adequate surgical planning. Moreover, this research presents an open classification matrix for the most complete description of compound and complex odontomas when analysing CBCT imaging. &nbsp;Objective: Firstly, this review aims to analyse the recent literature about three-dimensional (3D) diagnostic imaging in complex and compound odontomas and compare it to two-dimensional (2D) imaging. Panoramic radiographs help to evaluate the vertical position of odontomas, and occlusal radiographs are used to evaluate the proximity to adjacent teeth. However, cone beam computed tomography (CBCT) can offer volumetric images, and therefore, a more accurate three-dimensional analysis. Secondly, this research aims to construct an open classification matrix for complex and compound odontomas for dentomaxillofacial CBCT radiology protocols based on a systematic literature review. Material and methods: Two systematic literature searches were conducted in PubMed (Medline), on 2 February 2022 concerning classification systems, and on 5 February 2022 concerning CBCT images. Results: In total, these searches revealed 391 papers by reviewing the databases mentioned above. Six articles were selected for inclusion on classification of odontomas and 13 articles were found on CBCT imaging. Consequently, the construction of an open classification matrix for compound and complex odontomas for dentomaxillofacial CBCT radiology protocols was performed using these 19 articles. Conclusions: CBCT offers a more precise position and accurate diagnosis of complex and compound odontomas compared to 2D imaging. Consequently, it enhances the detailed view of the site (multiple or unique), location (intraosseous, partially or completely extragnathic), size, extension (bony expansion, thinning or perforation cortical bone), density and type (denticulo type, particle type, denticulo-particle type, denticulo-amorphous type, amorphous tissue), relationship (with the crown or root of the definitive tooth), adjacent teeth resorption (deciduous or definitive), adjacent teeth (retention or impaction), and distance with adjacent structures (inferior alveolar nerve, sinus maxillaris), as well as adequate surgical planning. Moreover, this research presents an open classification matrix for the most complete description of compound and complex odontomas when analysing CBCT imaging. &nbsp

Septic arthritis of the temporomandibular joint after acute otitis media in a child

Septic arthritis of the temporomandibular joint as a complication of acute otitis media is rare in the Western world. This report describes the case of a 7-year-old boy who had pain in his right ear and limited mouth opening, following the onset of acute otitis media. A contrast-enhanced computed tomography scan revealed right-sided mastoiditis and hydrops of the right temporomandibular joint, suggesting septic arthritis. Real-time PCR and microbiologic analysis identified Streptococcus pyogenes and Staphylococcus epidermidis in the joint aspirate. Treatment with arthrocentesis and antibiotics led to full recovery of temporomandibular joint function.status: publishe