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 (IP 3 ) receptor (IP 3 R)-mediated Ca 2+ -signaling. A peptide tool (Bcl-2/IP 3 R Disruptor-2; BIRD-2) was developed to abrogate the interaction of Bcl-2 with IP 3 Rs 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 IP 3 R2 were sensitive to BIRD-2. Here, we report that BIRD-2-induced cell death in DLBCL cells does not only depend on high IP 3 R2-expression levels, but also on constitutive IP 3 signaling, downstream of the tonically active B-cell receptor. The basal Ca 2+ level in SU-DHL-4 DLBCL cells was significantly elevated due to the constitutive IP 3 production. This constitutive IP 3 signaling fulfilled a prosurvival role, since inhibition of phospholipase C (PLC) using U73122 (2.5 µM) caused cell death in SU-DHL-4 cells. Milder inhibition of IP 3 signaling using a lower U73122 concentration (1 µM) or expression of an IP 3 sponge suppressed both BIRD-2-induced Ca 2+ elevation and apoptosis in SU-DHL-4 cells. Basal PLC/IP 3 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 IP 3 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 IP 3 R activity. BIRD-2 seems to switch constitutive IP 3 signaling from pro-survival into pro-death, presenting a plausible therapeutic strategy.

The best known café-au-lait syndrome is neurofibromatosis type 1 (NF1). Legius syndrome (LS) is another, rarer syndrome with café-au-lait macules (CALMs). In young patients their clinical picture is often indistinguishable. We investigated the presence of choroidal abnormalities in syndromes with CALMs as a candidate tool for a more efficient diagnosis. Thirty-four patients with NF1 (14 with a truncating mutation, 14 with a non-truncating mutation and 6 with unknown mutation) and 11 patients with LS. All patients underwent an ophthalmological examination. Infrared images were performed. Choroidal nodules were diagnosed in 65% of the NF1 group. About 71% of NF1 patients with a truncating mutation and 50% of patients with a non-truncating mutation were found to have nodules. Choroidal nodules were seen in 18% of the LS patients, never more than one nodule/eye was detected in this group. Choroidal nodules are more abundantly present in NF1 genotypes with truncating mutations. In contrast, the number of choroidal nodules in LS is comparable with their presence in healthy individuals. Especially at an early age, when the clinical picture is incomplete, the detection of choroidal nodules is of diagnostic value, and helps in an appropriate genetic counselling and follow-up. These results support the suggestion to include choroidal nodules to the diagnostic criteria for NF1.

Study Design: Retrospective study. Objective: Zygomaticomaxillary complex (ZMC) fractures are common facial injuries with heterogeneity regarding aetiologies, fracture types, infraorbital nerve (ION) involvement, and treatment methods. The aim of this study was to identify associations between aetiologies, fracture types, and neurological complications. Additionally, treatment methods and recovery time were investigated. Methods: Medical files of 272 patients with unilateral and bilateral ZMC fractures were reviewed, whose cases were managed from January 2014 to January 2019 at the Department of Oral and Maxillofacial Surgery, University hospitals Leuven, Belgium. History of ION sensory dysfunction and facial nerve motoric dysfunction were noted during follow-up. Results: ION hypoaesthesia incidence was 37.3%, with the main causes being fall accidents, road traffic accidents, and interpersonal violence. Significant predictors of ION hypoaesthesia were Zingg type B fractures ( P = 0.003), fracture line course through the infraorbital canal ( P < .001), orbital floor fracture ( P < 0.001), and ZMC dislocation or mobility ( P = 0.001). Conclusion: Of all ZMC fractures, 37.3% exhibited ION hypoaesthesia. Only ZMC Zingg type B fractures (74.0%) were significantly more associated with ION hypoaesthesia. ION hypoesthesia was more likely (OR = 2.707) when the fracture line course ran through the infraorbital canal, and was less dependent on the degree of displacement. Neuropathic pain symptoms developed after ZMC fractures in 2.2% patients, posing a treatment challenge. Neuropathic pain symptoms were slightly more common among women, and were associated only with type B or C fractures. No other parameters were found to predict the outcome of this post-traumatic neuropathic pain condition.

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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.