Biochemical analysis of the articular disc of the temporomandibular joint with magnetic resonance T2 mapping: a feasibility study

Objectives

Symptoms of temporomandibular joint (TMJ) dysfunction can seriously compromise patients' quality of life. The aim of our study was to use magnetic resonance imaging (MRI) T2 mapping of the articular disc to determine whether T2 mapping of the TMJ disc is feasible in routine clinical imaging and to assess the normal T2 relaxation time distribution within the TMJ.

Methods

Included were ten asymptomatic volunteers without pain, any mouth-opening limitations, or any clicking phenomena. MR imaging was performed on a 3-T MR scanner using a flexible, dedicated, eight-channel multielement coil. T2 mapping was performed in the oblique sagittal plane. The regions of interest (ROIs) for the T2 relaxation time maps of the disc were selected manually.

Results

The mean values for ROIs ranged between 22.4 and 28.8 ms, and the mean for all ROIs was 26.0?±?5.0 ms. Intraclass correlation (ICC) for interobserver variability was 0.698, and ICC for intraobserver variability was 0.861. There was no statistically significant difference between raters (p?=?0.091) or sides (p?=?0.810).

Conclusion

The T2 mapping technique enables ultrastructural analysis of the composition of TMJ disc. This biochemical technique is feasible in vivo, as shown in our study, when a high-field (3 T) MR and a dedicated TMJ coil are used.

Clinical relevance

T2 mapping as a biochemical technique, together with morphological MRI, may help to gain more insights into the physiology and into the pathophysiology of the articular disc in the TMJ noninvasively and in vivo.     

Validity of the 3D VECTRA photogrammetric surface imaging system for cranio-maxillofacial anthropometric measurements

Purpose

The use of three-dimensional (3D) photography for anthropometric measurements is of increasing interest, especially in the cranio-maxillofacial field. Before standard implementation, accurate determination of the precision and accuracy of each system is mandatory.

Methods

A mannequin head was labelled with 52 landmarks, and 28 three-dimensional images were taken using a commercially available five-pod 3D photosystem (3D VECTRA; Canfield, Fairfield, NJ) in different head positions. Distances between the landmarks were measured manually using a conventional calliper and compared with the digitally calculated distances acquired from labelling by two independent observers. The experimental set-up accounted for clinical circumstances by varying the positioning (vertical, horizontal, sagittal) of the phantom.

Results

In the entire calliper measurement data set (n?=?410), a significant difference (p?=?0.02) between the directly measured and corresponding virtually calculated distances was found. The mean aberration between both modalities covering all data was 7.96 mm. No differences (p?=?0.94) between the two groups were found using a cut-off of 10 % (leaving n?=?369 distances) due to considerable errors in direct measurements and the necessary manual data translation. The mean diversity of both measurement modalities after cut-off was 1.33 mm (maximum, 6.70 mm). Inter-observer analysis of all 1,326 distances showed no difference (p?=?0.99; maximal difference, 0.58 mm) in the digital measurements.

Conclusion

The precision and accuracy of this five-pod 3D photosystem suggests its suitability for clinical applications, particularly anthropometric studies. Three-hundred-and-sixty degree surface-contour mapping of the craniofacial region within milliseconds is particularly useful in paediatric patients. Proper patient positioning is essential for high-quality imaging.     

Low dietary adherence after a positive food challenge in food allergic adults

BackgroundAfter a positive food challenge (FC), patients receive dietary advice regarding avoidance of the culprit food. We examined the frequency and variables associated with dietary adherence after a positive FC in adults.MethodsIn this prospective daily practice study, adults with a positive FC were included. After every FC, dietary advice was given consisting of three options: (1) strict avoidance, (2) avoidance but products with precautionary allergen labelling (PAL) allowed and (3) (small) amounts allowed. Questionnaires about dietary adherence and associated variables were completed prior to and 6 months after the FC(s).Results41 patients (with 58 positive FCs) were included. Overall, patients adhered to the advised diet after 31% of the FCs. After 33 FCs, the advice was strict avoidance, whereof 82% followed a less strict diet. After 16 FCs, the advice was avoidance but products with PAL allowed, whereof 19% followed a less strict and 25% a stricter diet. In 9 FCs with the least strict advice, “(small) amounts allowed’’, 67% followed a stricter diet. Three variables were associated with adherence: misremembering dietary advice, impaired health‐related quality of life (HRQL) on domain “Emotional impact’’ and the need for dietary change after the FC.ConclusionAfter one third of the positive FCs, patients adhered to the dietary advice. Variables associated with adherence were misremembering dietary advice, impaired HRQL on domain “Emotional impact’’ and the need for dietary change after the FC. It seems important that healthcare professionals should more frequently apply adherence‐enhancing strategies to improve dietary adherence.     

Efficacy of late concurrent hypofractionated radiotherapy in advanced melanoma patients failing anti-PD-1 monotherapy

Advanced melanoma patients who failed anti-PD-1 therapy have limited options. We analyzed a cohort of 133 advanced melanoma patients receiving anti-PD-1 monotherapy in a referral center between April 2015 and December 2017, and included the 26 patients with confirmed progressive (PD) or stable disease who received additional radiotherapy with an unmodified anti-PD-1 mAb regimen. Tumor evaluations were done on radiated and nonradiated (RECIST 1.1) lesions, with abscopal effect defined as a partial (PR) or complete response (CR) outside radiated fields. Primary endpoint was the CR + PR rate in radiated + nonradiated lesions. Secondary endpoints were progression-free survival (PFS), melanoma-specific survival (MSS) and safety. First late radiotherapy, consisting of hypofractionated radiotherapy (3–5 sessions, 20–26 Gy), standard palliative radiotherapy or brain radiosurgery was begun after a median of 6.3 months of anti-PD-1 in 23, 2 and 1 patient(s), respectively. Best response was 8 (31%) CR, 2 (8%) profound PR allowing surgical resection of remaining metastases and 16 (62%) PD. Abscopal effect was seen in 35% of patients. Median PFS and MSS since anti-PD-1 initiation was 15.2 [95% CI: 8.0 not achieved (na)] and 35.3 [95% CI: 18.5 na] months, respectively. PFS curves seemed to achieve a plateau. We discontinued anti-PD-1 therapy in 9/10 of patients with no residual evaluable disease and observed one relapse after a median of 10 months off anti-PD1-therapy. No unusual adverse event was recorded. Limitations of the study include its retrospective nature and limited size. Hypofractionated radiotherapy may enhance anti-PD1 monotherapy efficacy in patients who previously failed anti-PD-1 therapy. Controlled studies are needed.     

Prognostic impact of distinct genetic entities in pediatric diffuse glioma WHO-grade II—Report from the German/Swiss SIOP-LGG 2004 cohort

Reports on pediatric low-grade diffuse glioma WHO-grade II (DG2) suggest an impaired survival rate, but lack conclusive results for genetically defined DG2-entities. We analyzed the natural history, treatment and prognosis of DG2 and investigated which genetically defined sub-entities proved unfavorable for survival. Within the prospectively registered, population-based German/Swiss SIOP-LGG 2004 cohort 100 patients (age 0.8-17.8 years, 4% neurofibromatosis [NF1]) were diagnosed with a DG2. Following biopsy (41%) or variable extent of resection (59%), 65 patients received no adjuvant treatment. Radiologic progression or severe neurologic symptoms prompted chemotherapy (n = 18) or radiotherapy (n = 17). Multiple lines of salvage treatment were necessary for 19/35 patients. Five years event-free survival dropped to 0.44, while 5 years overall survival was 0.90 (median observation time 8.3 years). Extensive genetic profiling of 65/100 DG2 identified Histone3-K27M-mutation in 4, IDH1-mutation in 11, BRAF-V600-mutation in 12, KIAA1549-BRAF-fusions in 6 patients, while the remaining 32 tumor tissues did not show alterations of these genes. Progression to malignant glioma occurred in 12 cases of all genetically defined subgroups within a range of 0.5 to 10.8 years, except for tumors carrying KIAA1549-BRAF-fusions. Histone3-K27M-mutant tumors proved uniformly fatal within 0.6 to 2.4 years. The current LGG treatment strategy seems appropriate for all DG2-entities, with the exemption of Histone3-K27M-mutant tumors that require a HGG-related treatment strategy. Our data confirm the importance to genetically define pediatric low-grade diffuse gliomas for proper treatment decisions and risk assessment.     

Sensibilisierungstrainings gegenüber häuslicher Gewalt für medizinisches Fachpersonal. Sind diese auch effizient?

Untersuchungen der Europäischen Union folgend, sind 33 % aller Frauen ab dem 15. Lebensjahr von häuslicher Gewalt betroffen und wenden sich bei der Suche nach Hilfe vorwiegend an das Gesundheitssystem. Das Erleben von Gewalt hat schwerwiegende Folgen nicht nur auf die psychische, sondern auch auf die körperliche Gesundheit der Betroffenen. So kommt es neben Verletzungsfolgen, u. a. zu unerklärbaren Schmerzen, gastrointestinalen Beschwerden oder Problemen im Bereich der reproduktiven Medizin. Nachdem sich viele der Betroffenen auf der Suche nach Unterstützung zuerst an das Gesundheitssystem wenden, kommt dem medizinischen Fachpersonal auch hier eine Schlüsselrolle zu, wodurch Sensibilisierungstrainings für die Berufsgruppen immer bedeutender werden. Teilnehmerinnen und Teilnehmer an Sensibilisierungstrainings gegenüber häuslicher Gewalt wurden vor und nach dem Training mit Hilfe eines Fragebogens zu ihrer empfundenen Sicherheit im Umgang mit von Gewalt betroffenen Patientinnen und Patienten befragt. Die Evaluation eines Schulungszyklus am Landeskrankenhaus Innsbruck zeigte signifikante Verbesserungen im subjektiven Sicherheitsgefühl im Umgang mit gewaltbetroffenen Patientinnen und Patienten. Ein strukturierter Aufbau der Sensibilisierungstrainings mit Basiskursen und Aufbauseminaren, sowie einem Fokus auf Beziehungsaufbau und Umgang mit Emotionen erscheint sinnvoll.     

Biasing human epidermal growth factor receptor 4 (HER4) tyrosine kinase signaling with antibodies: Induction of cell death by antibody‐dependent HER4 intracellular domain trafficking

Human epidermal growth factor receptor 4 (HER4) isoforms have oncogenic or tumor suppressor functions depending on their susceptibility to proteolytic cleavage and HER4 intracellular domain (4ICD) translocation. Here, we report that the neuregulin 1 (NRG1) tumor suppressor mechanism through the HER4 JMa/CYT1 isoform can be mimicked by the agonist anti‐HER4 Ab C6. Neuregulin 1 induced cleavage of poly(ADP‐ribose) polymerase (PARP) and sub‐G₁ DNA fragmentation, and also reduced the metabolic activity of HER3^?/HER4⁺ cervical (C‐33A) and ovarian (COV318) cancer cells. This effect was confirmed in HER4 JMa/CYT1‐, but not JMa/CYT2‐transfected BT549 triple‐negative breast cancer cells. Neuregulin 1 favored 4ICD cleavage and retention in mitochondria in JMa/CYT1‐transfected BT549 cells, leading to reactive oxygen species (ROS) production through mitochondrial depolarization. Similarly, the anti‐HER4 Ab C6, which binds to a conformational epitope located on a.a. 575‐592 and 605‐620 of HER4 domain IV, induced 4ICD cleavage and retention in mitochondria, and mimicked NRG1‐mediated effects on PARP cleavage, ROS production, and mitochondrial membrane depolarization in cancer cells. In vivo, C6 reduced growth of COV434 and HCC1187 tumor cell xenografts in nude mice. Biasing 4ICD trafficking to mitochondria with anti‐HER4 Abs to mimic NRG1 suppressor functions could be an alternative anticancer strategy.     

Multi‐tissue cytogenetic analysis for the diagnosis of mosaic Down syndrome: A case report

Less than one percent of individuals with Down syndrome exhibit mosaicism, a biological phenomenon that describes an individual who has two or more genetically distinct cell lines. The percentage of mosaicism in different tissues can impact the presence of clinical findings and hinder cytogenetic diagnosis. We report a case of mosaicism for trisomy 21 diagnosed after multi‐tissue cytogenetic analysis of peripheral blood and buccal mucosa, associated with significant intellectual disability, dysmorphic facial features, congenital heart defects, macropenis, and imperforate anus.