Activity of venetoclax in patients with relapsed or refractory chronic lymphocytic leukaemia: analysis of the VENICE-1 multicentre, open-label, single-arm, phase 3b trial.

BACKGROUND: Most patients with chronic lymphocytic leukaemia progress after treatment or retreatment with targeted therapy or chemoimmunotherapy and have limited subsequent treatment options. Response levels to the single-agent venetoclax in the relapsed setting is unknown. We aimed to assess venetoclax activity in patients with or without previous B-cell receptor-associated kinase inhibitor (BCRi) treatment. METHODS: This multicentre, open-label, single-arm, phase 3b trial (VENICE-1) assessed activity and safety of venetoclax monotherapy in adults with relapsed or refractory chronic lymphocytic leukaemia, stratified by previous exposure to a BCRi. Eligible participants were aged 18 years or older with previously treated relapsed or refractory chronic lymphocytic leukaemia. Presence of del(17p) or TP53 aberrations and previous BCRi treatment were permitted. Patients received 5-week ramp-up to 400 mg of oral venetoclax once daily and were treated for up to 108 weeks, with 2 years follow-up after discontinuation, or optional extended access. The primary activity endpoint was complete remission rate (complete remission or complete remission with incomplete marrow recovery) in BCRi-naive patients. Analyses used the intent-to-treat (ie, all enrolled patients, which coincided with those who received at least one dose of venetoclax). This study was registered with ClinicalTrials.gov, NCT02756611, and is complete. FINDINGS: Between June 22, 2016, and March 11, 2022, we enrolled 258 patients with relapsed or refractory chronic lymphocytic leukaemia (180 [70%] were male; 252 [98%] were White; 191 were BCRi-naive and 67 were BCRi-pretreated). Median follow-up in the overall cohort was 49·5 months (IQR 47·2-54·1), 49·2 months (47·2-53·2) in the BCRi-naive group, and 49·7 months (47·4-54·3) in the BCRi-pretreated group. Of 191 BCRi-naive patients, 66 (35%; 95% CI 27·8-41·8) had complete remission or complete remission with incomplete marrow recovery. 18 (27%; 95% CI 16·8-39·1) of 67 patients in the BCRi-pretreated group had complete remission or complete remission with incomplete marrow recovery. Grade 3 or worse treatment-emergent adverse events were reported in 203 (79%) and serious adverse events were reported in 136 (53%) of 258 patients in the overall cohort. The most common treatment-emergent adverse event was neutropenia (96 [37%]) and the most common and serious adverse event was pneumonia (21 [8%]). There were 13 (5%) deaths reported due to adverse events; one of these deaths (autoimmune haemolytic anaemia) was possibly related to venetoclax. No new safety signals were identified. INTERPRETATION: These data demonstrate deep and durable responses with venetoclax monotherapy in patients with relapsed or refractory chronic lymphocytic leukaemia, including BCRi-pretreated patients, suggesting that venetoclax monotherapy is an effective strategy for treating BCRi-naive and BCRi-pretreated patients. FUNDING: AbbVie.

MRI compatibility of orthodontic brackets and wires: systematic review article.

BACKGROUND: Before the magnetic resonance imaging (MRI) examination fixed orthodontic devices, such as brackets and wires, cause challenges not only for the orthodontist but also for the radiologist. Essentially, the MRI-safe scan of the fixed orthodontic tools requires a proper guideline in clinical practice. Therefore, this systematic review aimed to examine all aspects of MRI-safe scan, including artifact, thermal, and debonding effects, to identify any existing gaps in knowledge in this regard and develop an evidence-based protocol. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) statement was used in this study. The clinical question in "PIO" format was: "Does MRI examination influence the temperature of the orthodontic devices, the size of artifacts, and the debonding force in patients who have fixed orthodontic bracket and/or wire?" The search process was carried out in PubMed, PubMed Central, Scopus, and Google Scholar databases. The search resulted in 1310 articles. After selection according to the eligibility criteria, 18 studies were analyzed by two reviewers. The risk of bias was determined using the Quality In Prognosis Studies tool. RESULTS: Out of the eligible 18 studies, 10 articles examined the heating effect, 6 were about the debonding effect, and 11 measured the size of artifact regarding brackets and wires. Considering the quality assessment, the overall levels of evidence were high and medium. The published studies showed that heating and debonding effects during MRI exposure were not hazardous for patients. As some wires revealed higher temperature changes, it is suggested to remove the wire or insert a spacer between the appliances and the oral mucosa. Based on the material, ceramic and plastic brackets caused no relevant artifact and were MRI-safe. Stainless steel brackets and wires resulted in susceptibility artifacts in the orofacial region and could cause distortion in the frontal lobe, orbits, and pituitary gland. The retainer wires showed no relevant artifact. CONCLUSIONS: In conclusion, the thermal and debonding effects of the fixed orthodontic brackets and wires were irrelevant or resoluble; however, the size of the artifacts was clinically relevant and determined most significantly the feasibility of fixed brackets and wires in MRI examination.

[Planning options of reconstructive and orthognathic operation by means of three-dimensional imaging]. / Arcrekonstrukciós és orthognath mutétek tervezési lehetoségei háromdimenziós képalkotói módszerekkel.

We summarize up-to-date planning technics of orthognathic and reconstructive surgery operation which appeared with three-dimensional imaging, using literature data and some clinical examples. In many cases, orthognathic and reconstructive operations mean the only treatment of facial deformity caused by tumour, traumatic injury or congenital anomaly. In this field, radiology plays an important role not only in the diagnosis but also in the planning of the treatment. With the appearance of cone-beam computed tomography (CBCT), the previously used two-dimensional cephalometric analysis on lateral cephalogram was changed for three-dimensional cephalometric measurements. The first step of the adaptation was the lateral and frontal x-ray images generated from the CBCT database and later the volume rendered surface and segmentation technics provided the moving of the facial bones in three dimensions which meant virtual surgical planning. With the development of CAD/CAM technic and the three-dimensional printing, many opportunities became available, such as preoperative bending splints and plates and printed surgical model for the tangible planning. The progress of imaging facilitated the individual, accurate, and reliable planning which significantly determines the success of the treatment. Orv Hetil. 2018; 159(39): 1584-1592.

Landmark-based midsagittal plane analysis in patients with facial symmetry and asymmetry based on CBCT analysis tomography.

PURPOSE: Reconstruction of the facial midplane is relevant in anthropometry, orthodontics, maxillofacial surgery, and the accurate measurement of symmetry deviation is relevant in many fields of medicine especially when planning surgical treatment. In the literature, three different means of midplane generation have been published; however, there is currently no consensus regarding the approach to use. Morphometric methods are used to determine the true midsagittal plane (MSP), but its use in clinical practice is difficult. A regression plane based on N­ANS-PNS landmarks reportedly approximates the morphometric MSP. As these points are vulnerable, we investigated which combination of landmarks can be substituted in symmetric and asymmetric faces. PATIENTS AND METHODS: Thirty symmetric and 30 asymmetric faces were analyzed on cone-beam computed tomography scans. A total of 50 regression planes were generated based on three unpaired landmarks and 35 regression planes were generated based the midpoints of paired landmarks. The Na-ANS-PNS plane was used as reference plane, and the mean angle between it and each generated MSP was calculated. The differences from the reference plane were compared by t­test between the groups. RESULTS: In the symmetric group, 86% of angles deviated by <5° using unpaired points, whereby 74% of angles deviated by <5° for paired points. Between the two groups 50% of planes from midline points, and 77% of planes from paired points were significantly different. All planes deviated more in the asymmetric group. CONCLUSIONS: The N­ANS-PNS reference plane can be substituted with the following combinations: ANS-G-Ba, ANS-G-S, ANS-S-De, PNS-G-Ba, PNS-S-Ba, PNS-ANS-G, and PNS-N-Ba.

Lower face cephalometry based on quadrilateral analysis with cone-beam computed tomography: a clinical pilot study.

OBJECTIVE: As most orthognathic surgeries focus on the lower face, the aim of this study was to transfer previously developed two-dimensional cephalometry-which is useful for surgeons in the orthognathic surgery of the lower face-to three-dimensional (3D) cephalometry by using cone-beam computed tomography (CBCT). We selected the quadrilateral lower face analysis developed by the surgeon Di Paolo, who focused only for the lower face and mentioned that data in millimeters are more easy to use than angles for surgeons. Additionally, we wanted to create a 3D lower face analysis approach based on quadrilateral analysis and establish a reference table for surgical planning. STUDY DESIGN: Three investigators assigned 16 landmarks on CBCT images from 30 patients with normocclusion. Intra-class correlation coefficients (ICCs) and standard deviations (SDs) were calculated according to each landmark. The maxillary and mandibular lengths and widths and the anterior and posterior lower facial heights (ALFH and PLFH) are presented as means and SDs. The asymmetry of the face was calculated with paired t test, and the coherence of the lower face was assessed with correlation coefficients (r) and regression models. RESULTS: The ICCs were ≥0.90, and the SDs of the landmarks were lower than 1.00 mm, except for the J-point, which was located at the junction of the anterior border of the ramus and the corpus of the mandible. The SDs of linear measurements were 3.06-5.20 mm, and there was no significant facial asymmetry. The r among the structures was greater than 0.3 in 13 of 15 assessments. Based on these values, we could establish a floating norm of the lower face using the following five regressions: one linear regression for the mandibular length, two quadratic models for the ALFH and PLFH, and two multivariate regressions for the posterior widths of the maxillae and mandible. CONCLUSION: The adaptation of quadrilateral analysis can provide accurate 3D characterization of the morphology of the lower face and the floating norm based on millimeter values, which is practical for surgeons. As the 3D extension of quadrilateral analysis could provide references of the lower face, which might be an accurate 3D approach for presurgical planning, the further investigation in bigger sample would be relevant in the practice.

[Di Paolo's cephalometrical analysis of lower face by means of Cone-Beam CT]. / Az alsó archarmad Di Paolo-féle vizsgálata Cone-Beam CT adatállományon.

OBJECT: 3D cephalometry is often the only way to set up accurate diagnosis and treatment plan in the field of reconstructive surgery. In these cases complement exposures are needed beyond common cephalograms with higher accuracy than conventional Cone-Beam CT. Consequently the aim of our study was to perform a complex 3D cephalometry. As the first step of this approach, was the 3D adaptation of DiPaolo's Quadrilateral technique, and to determine norms of references in lower face by means of CBCT. METHOD: Thirty non-orthodontic CBCT scans were selected for the digitalization. The most important inclusion criteria was Class I occlusion. Locations of 55 landmarks were signed three times by three observers by means of Cranio Viewer software. RESULTS: However Quadrilateral analysis contains only millimetric values we also integrate angles in the 3D version to determine the width of maxilla and mandible. In the 2D examination--where landmarks were projected to the middle plane. The SDs of the lengths were between 2,66 mm and 5,20 mm. The ratios of normodivergent lower face were significant different from the one by DiPaolo. In 3D adaptation there were no significant differences between the measurements of the two sides (p ≥ 0.05). We found mostly strong and significant correlations between each anatomical structure except of angles. CONCLUSION: Creation of 3D Quadrilateral cephalometry by means of strong correlation and norms of Class I occlusion provide a practical, reliable method to measure also the transversal asymmetry of lower face which is necessary part of 3D cephalometry.

Measurements of orbital volume using cone-beam computed tomography in eye movement abnormalities.

PURPOSE: To measure the orbital volume in adult patients with unilateral eye movement abnormalities originating in childhood. METHODS: Cone-beam computed tomography was performed in 2 patients with eye movement abnormalities. A 28-year-old woman was treated because of right divergent squint originating at 8 years of age after penetrating corneal trauma. A 38-year-old man was examined because of abnormal head posture caused by left superior oblique underaction originating at 6 years of age. Orbital scans were analyzed with Cranioviewer 3D craniofacial cephalometric program. We measured bony orbital area in 6 slices (in ventro-dorsal direction per 4.8 mm) in every orbit on coronal scans. RESULTS: The volume was more in the orbit with unilateral divergent squint and less in the orbit with unilateral superior oblique underaction compared to the contralateral orbital volume measurements. CONCLUSION: Cranioviewer 3D craniofacial cephalometric program is suitable for volumetric analysis of the bony orbit on cone-beam computed tomography files. The development of the orbit can be influenced by extraocular muscle movements.

Measurement of orbital volume after enucleation and orbital implantation.

INTRODUCTION: This article reports experience relating to the measurement of orbital volume by means of cone beam computed tomography (CBCT) and Cranioviewer program software in patients who have undergone enucleation and orbital implantation. PATIENTS AND METHODS: CBCT scans were made in 30 cases, 10 of which were later excluded because of various technical problems. The study group therefore consisted of 20 patients (8 men and 12 women). The longest follow-up time was 7 years, and the shortest was 1 year. In all 20 cases, the orbital volume was measured with Cranioviewer orbital program software. Slices were made in the ventrodorsal direction at 4.8 mm intervals in the frontal plane, in both bony orbits (both that containing the orbital implant and the healthy one). Similar measurements were made in 20 patients with various dental problems. CBCT scans were recorded for the facial region of the skull, containing the orbital region. The Cranioviewer program can colour the area of the slices red, and it automatically measures the area in mm. RESULTS: In 5 of the 20 cases, the first 4 or all 5 slices revealed that the volume of the operated orbit was significantly smaller than that of the healthy orbit, in 12 cases only from 1 to 3 of the slices indicated such a significant difference, and in 3 cases no differences were observed between the orbits. In the control group of patients with various dental problems, there was no significant difference between the two healthy orbits. The accuracy of the volume measurements was assessed statistically by means of the paired samples t-test. SUMMARY: To date, no appropriate method is avaliable for exact measurement of the bony orbital volume, which would be of particular importance in orbital injury reconstruction. However, the use of CBCT scans and Cranioviewer orbital program software appears to offer a reliable method for the measurement of changes in orbital volume.

[Distractios osteogenesis in maxillofacial surgery]. / Distractios osteogenesis a maxillofaciális sebészetben.

For more than one decade the extremity surgery already used distraction osteogenesis. This new therapy in the region of the maxillofacial surgery (in the case of malformation of the maxilla and mandible) was adapted from the extremity surgeons. The authors summarized and classified the methods and history of the osteodistraction surgery based on literature. The indication fields, the used protocols and the most common distractor types are listed. The authors emphasized the multidisciplinary feature of the therapies, underlined the leading role of the orthodontist. With presenting their own two mandible distraction case reports they introduced the practical use of the distractors while using intra- and extraoral devices. They also emphasized the difficulties and failure opportunities. Their aim was to make suggestions for the further development of this method in our country.