A homozygous AP3D1 missense variant in patients with sensorineural hearing loss as the leading manifestation.

Loss-of-function variants in AP3D1 have been linked to Hermansky-Pudlak syndrome (HPS) 10, a severe multisystem disorder characterized by oculocutaneous albinism, immunodeficiency, neurodevelopmental delay, hearing loss (HL), and neurological abnormalities, fatal in early childhood. Here, we report a consanguineous family who presented with presumably isolated autosomal recessive (AR) HL. Whole-exome sequencing was performed on all core family members, and selected patients were screened using array-based copy-number analysis and karyotyping. Candidate variants were validated by Sanger sequencing and assessed in silico. A homozygous, likely pathogenic p.V711I missense variant in AP3D1 segregated with the HL. The family was characterized by thorough medical and laboratory examination. The HL was consistent across patients and accompanied by neurological manifestations in two brothers. The sole female patient was diagnosed with premature ovarian failure. Further findings, including mild neutropenia and reduced NK-cell cytotoxicity in some as well as brain alterations in all homozygous patients, were reminiscent of HPS10, though milder and lacking the characteristic albinism. Previously unrecognized, milder, isolated HL was identified in all heterozygous carriers. A protein model indicates that the variant interferes with protein-protein interactions. These results suggest that a missense variant alters inner-ear-specific functions leading to HL with mild HPS10-like symptoms of variable penetrance. Milder HL in heterozygous carriers may point towards semi-dominant inheritance of this trait. Since all previously reported HPS10 cases were pediatric, it is unknown whether the observed primary ovarian insufficiency recapitulates the subfertility in Ap3d1-deficient mice.

MRI surveillance after translabyrinthine vestibular schwannoma resection and cochlear implantation: is it feasible?

PURPOSE: Cochlear implantation in patients with vestibular schwannomas is of increasing importance and interest. Two remaining challenges are the assessment of conduction of the cochlear nerve and the possibility of postoperative surveillance with magnetic resonance imaging. The aim of the current study was to assess follow-up imaging and determine the visibility of the internal auditory canal after vestibular schwannoma resection and cochlear implantation as well as in patients with persistent vestibular schwannomas and cochlear implants in place. Visibility of the internal auditory canal, cerebellopontine angle, and labyrinth were evaluated and graded. METHODS: For this retrospective study, 15 MR examinations of 13 patients after translabyrinthine vestibular schwannoma resection and ipsilateral cochlear implantation were included. All patients had been implanted with an MED-EL cochlear implant. Magnetic resonance imaging was carried out on a 1.5T device. All patients were prepped according to the manufacturer's recommendations. RESULTS: All 15 examinations were carried out without any adverse event during imaging, such as pain, magnet dislocation, or malfunction. The internal auditory canal and the cerebellopontine angle were sufficiently visible in all cases to allow for vestibular schwannoma follow-up. CONCLUSION: Magnetic resonance imaging surveillance of the internal auditory canal following vestibular schwannoma resection and cochlear implantation is feasible and safe with modern implants with a 1.5T magnetic resonance imaging device using metal artifact reduction sequences. Necessary follow-up imaging should not be a contraindication for cochlear implantation in patients with vestibular schwannomas.

The challenging diagnosis and follow-up of skull base osteomyelitis in clinical practice.

PURPOSE: The disease activity of skull base osteomyelitis can be challenging to assess by means of conventional imaging methods and renders monitoring of the disease difficult, especially in areas with restricted access to nuclear medicine imaging. Here, we provide clinically relevant data on the management of skull base osteomyelitis including assessment, treatment, and follow-up strategies with regards to the role of imaging. METHOD: A chart review was performed including 30 patients treated for SBO from 1993 to 2015. Clinical findings, treatment procedures, and complication rates were assessed. Special attention was paid to imaging procedures. RESULTS: The overall mortality rate was 36.7% and increased to 45% when cranial nerve palsies were present. An initial computed tomography (CT) scan was performed in all patients, MRI in 60% and nuclear imaging in 33%. CT scans failed to detect progression or regression in up to 80% after four to nine months. MRI examinations could reveal changes at a higher rate compared to CT. Nuclear medicine functional imaging was most likely to assess disease activity. CONCLUSION: A combination of different imaging modalities is recommended for diagnosing SBO. For the follow-up, MRI is preferable to CT as changes can be detected more readily with MRI. If available, nuclear medicine imaging should guide the decision of treatment discontinuation.

Software-based risk stratification of pulmonary adenocarcinomas manifesting as pure ground glass nodules on computed tomography.

OBJECTIVES: To assess the performance of the "Computer-Aided Nodule Assessment and Risk Yield" (CANARY) software in the differentiation and risk assessment of histological subtypes of lung adenocarcinomas manifesting as pure ground glass nodules on computed tomography (CT). METHODS: 64 surgically resected and histologically proven adenocarcinomas manifesting as pure ground-glass nodules on CT were assessed using CANARY software, which classifies voxel-densities into three risk components (low, intermediate, and high risk). Differences in risk components between histological adenocarcinoma subtypes were analysed. To determine the optimal threshold reflecting the presence of an invasive focus, sensitivity, specificity, negative predictive value, and positive predictive value were calculated. RESULTS: 28/64 (44%) were adenocarcinomas in situ (AIS); 26/64 (41%) were minimally invasive adenocarcinomas (MIA); and 10/64 (16%) were invasive ACs (IAC). The software showed significant differences in risk components between histological subtypes (P<0.001-0.003). A relative volume of 45% or less of low-risk components was associated with histological invasiveness (specificity 100%, positive predictive value 100%). CONCLUSIONS: CANARY-based risk assessment of ACs manifesting as pure ground glass nodules on CT allows the differentiation of their histological subtypes. A threshold of 45% of low-risk components reflects invasiveness in these groups. KEY POINTS: • CANARY-based risk assessment allows the differentiation of their histological subtypes. • 45% or less of low-risk component reflects histological invasiveness. • CANARY has potential role in suspected adenocarcinomas manifesting as pure ground-glass nodules.

Normal mandibular growth and diagnosis of micrognathia at prenatal MRI.

OBJECTIVE: The aim of this article is to present reference data for fetal mandibular growth on magnetic resonance imaging, enabling the diagnosis of micrognathia. METHODS: Retrospectively, on 355 magnetic resonance scans of apparently facially normal fetuses [gestational age (GA), 20-36 weeks], mandibular anterior-posterior diameter (APD = mandibular size), inferior facial angle (IFA = mandibular position), and jaw index (APD normalized to biparietal diameter) were correlated with GA by Pearson correlation. APD-age relationship was modeled. A receding chin was subjectively determined. Ten fetuses with mandibular anomalies were compared with normal fetuses. RESULTS: For GA, APD showed high correlation (r = 0.850; P < 0.001), IFA (r = 0.086; P = 0.119) no correlation, and jaw index (r = -0.139; P = 0.018) weak correlation. APD-age relationship was expressed by the following: APD = 0.281 + 0.989 * GA (r(2) = 0.723). A receding chin was identified in 7/10 abnormal fetuses. APD, IFA, and jaw index of abnormal and normal fetuses were significantly different (P < 0.001). In 10/10 abnormal fetuses, IFA was <50.0°; in 7/10, jaw index was less than the fifth percentile (micrognathia); in 3/10, jaw index was at low normal range (retrognathia). CONCLUSIONS: Subjective identification of micrognathia may be limited. Reference data provide quantitative evaluation of mandibular size and position. An IFA <50° reflects micrognathia or retrognathia; a jaw index less than the fifth percentile suggests micrognathia.

Stress matters! Psychophysiological and emotional loadings of pregnant women undergoing fetal magnetic resonance imaging.

BACKGROUND: While the application of fetal MRI in high-risk pregnant women is steadily rising, little is known about the psychological consequences of this procedure. The aim of the present study was to investigate emotional and psychophysiological reactions of females undergoing fetal MRI. METHODS: Sixty women (17-44 ys), assigned for fetal MRI, were included. Affective state was assessed by standardized measures of anxiety, emotional states and depressive symptoms. Stress coping strategies were assessed using a self-report questionnaire. Stress responses were determined using skin conductance levels (SCL) during fetal MRI as well as measurement of salivary cortisol levels immediately before and after fetal MRI. RESULTS: Analysis of fast and slow physiological stress measures revealed significant differences between women with and without a supporting person accompanying them to the examination. For SCLs, lower levels of stress during MRI emerged in accompanied women. Women with well-marked stress-coping-strategies experienced lower levels of stress during the examination. Although fast and slow stress measures before and after MRI did not show significant correlations, a significant difference of SCLs pre and post examination was clearly detectable, as well as a trend of decreased cortisol levels for both time points. CONCLUSIONS: The results imply that the elevation of SCLs is an accurate instrument to assess fast stress alterations in patients during fetal MRI. Stress coping strategies and whether women are accompanied or not play an important role in the experience of anxiety and depressive symptoms. These factors should be considered especially in patients with high-risk-pregnancies to improve patient care.

Radiological follow-up of cemento-osseous dysplasia on cone-beam computed tomography.

This study investigated the natural course of cemento-osseous dysplasia (COD) on cone-beam computed tomography (CBCT). Retrospectively, 104 CBCT scans from 36 patients (mean age, 44.5 years; 33 female and three male) with mandibular COD (10 florid, seven focal, 19 periapical) were included, based upon clinico-radiological features, without complications such as infection and related surgery. Changes in maximum diameter and morphology (lytic, mixed lytic-sclerotic, sclerotic) were evaluated in 83 lesions, with a mean follow-up of 28.3 months. The occurrence of a diameter increase was assessed by time-to-event analysis; interreader agreement for diameter and morphological evaluation by intraclass correlation coefficient and weighted κ statistics, respectively. Fifteen of 83 (18.1%) lesions (eight florid, one focal, six periapical) in 10 patients increased in diameter; 12 of 83 (14.5%) lesions (five florid, seven periapical) in 11 patients changed morphologically. The median period until a diameter increase was longest (120 months) for periapical COD, and shortest (66 months) for florid COD (p = 0.023). There was high reader agreement (ICC = 0.891; weighted κ = 0.901). In conclusion, CBCT is an effective tool with which to follow-up COD. If any, the natural progress in uncomplicated COD is prolonged, which underlines its non-surgical character and aids in its long-term management.

Human long bone development in vivo: analysis of the distal femoral epimetaphysis on MR images of fetuses.

PURPOSE: To investigate human long bone development in vivo by analyzing distal femoral epimetaphyseal structures and bone morphometrics on magnetic resonance (MR) images of fetuses. MATERIALS AND METHODS: An institutional review board approved this retrospective study, and informed consent was waived. Included were 272 MR imaging examinations (April 2004-July 2011) in 253 fetuses with a mean gestational age (GA) of 26 weeks 6 days (range, 19 weeks 2 days to 35 weeks 6 days) without known musculoskeletal abnormalities. Two independent readers qualitatively analyzed epiphyseal and metaphyseal shape, secondary ossification, and the perichondrium on 1.5-T echo-planar MR images and correlated the results with the GA that was derived from previous fetal ultrasonography (US). Diaphyseal and epiphyseal morphometric measurements were correlated with GA by means of the Pearson correlation and linear regression. MR imaging measurements of diaphyseal length and US normative values were compared graphically. Interreader agreement analysis was performed with weighted κ statistics and the intraclass correlation coefficient. RESULTS: With advancing GA, the epiphyseal shape changed from spherical (r(2) = 0.664) to hemispherical with a notch (r(2) = 0.804), and the metaphyseal shape changed from flat (r(2) = 0.766) to clearly undulated (r(2) = 0.669). Secondary ossification (r(2) = 0.777) was not observed until 25 weeks 3 days. The perichondrium decreased (r(2) = 0.684) from 20 weeks onward. Correlation coefficients were 0.897 for diaphyseal length, 0.738 for epiphyseal length, and 0.801 for epiphyseal width with respect to GA. The range of measurements of diaphyseal length was larger than that of the reported US normative values. Interreader agreement was good for bone morphometrics (intraclass correlation coefficient, 0.906-0.976), and moderate for bone characteristics (weighted κ, 0.448-0.848). CONCLUSION: Prenatal MR imaging allows visualization of human bone development in vivo by means of epimetaphyseal characteristics and bone morphometrics. SUPPLEMENTAL MATERIAL: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.13112441/-/DC1.

Quantitative evaluation of contrast-enhanced ultrasound after intravenous administration of a microbubble contrast agent for differentiation of benign and malignant thyroid nodules: assessment of diagnostic accuracy.

OBJECTIVES: To investigate the diagnostic accuracy, through quantitative analysis, of contrast-enhanced ultrasound (CEUS), using a microbubble contrast agent, in the differentiation of thyroid nodules. METHODS: This prospective study enrolled 46 patients with solitary, scintigraphically non-functional thyroid nodules. These patients were scheduled for surgery and underwent preoperative CEUS with pulse-inversion harmonic imaging after intravenous microbubble contrast medium administration. Using histology as a standard of reference, time-intensity curves of benign and malignant nodules were compared by means of peak enhancement and wash-out enhancement relative to the baseline intensity using a mixed model ANOVA. ROC analysis was performed to assess the diagnostic accuracy in the differentiation of benign and malignant nodules on CEUS. RESULTS: The complete CEUS data of 42 patients (31/42 [73.8%] benign and 11/42 [26.2%] malignant nodules) revealed a significant difference (P < 0.001) in enhancement between benign and malignant nodules. Furthermore, based on ROC analysis, CEUS demonstrated sensitivity of 76.9%, specificity of 84.8% and accuracy of 82.6%. CONCLUSIONS: Quantitative analysis of CEUS using a microbubble contrast agent allows the differentiation of benign and malignant thyroid nodules and may potentially serve, in addition to grey-scale and Doppler ultrasound, as an adjunctive tool in the assessment of patients with thyroid nodules. KEY POINTS: • Contrast-enhanced ultrasound (CEUS) helps differentiate between benign and malignant thyroid nodules. • Quantitative CEUS analysis yields sensitivity of 76.9% and specificity of 84.8%. • CEUS may be a potentially useful adjunct in assessing thyroid nodules.

MR imaging of the fetal musculoskeletal system.

Magnetic resonance imaging (MRI) appears to be increasingly used, in addition to standard ultrasonography for the diagnosis of abnormalities in utero. Previous studies have recently drawn attention to the technical refinement of MRI to visualize the fetal bones and muscles. Beyond commonly used T2-weighted MRI, echoplanar, thick-slab T2-weighted and dynamic sequences, and three-dimensional MRI techniques, are about to provide new imaging insights into the normal and the pathological musculoskeletal system of the fetus. This review emphasizes the potential significance of MRI in the visualization of the fetal musculoskeletal system.

Male genital abnormalities in intrauterine growth restriction.

OBJECTIVE: Previous studies have shown a correlation between hypospadias and intrauterine growth restriction (IUGR), suggesting an association between placental insufficiency and abnormal genital development. This study sought to analyze the association of IUGR and genital abnormalities apparent on fetal magnetic resonance imaging (MRI). METHODS: This retrospective study included 22 MRI scans of 20 male fetuses between 20 and 35 weeks of gestation presenting with IUGR. On MRI, penile length and testicular descent were evaluated. Student's t-testing and analysis of covariance were used to compare MRI penile length measurements with published normative data obtained from fetal ultrasonography (US) and MRI. McNemar testing was used to evaluate testicular descent in IUGR, compared with reported fetal MRI normative data. RESULTS: The penile length in IUGR fetuses was shorter than in normal fetuses (p<0.001). Furthermore, six of 20 fetuses presented with a micropenis (2.5 SD below the mean value for age). Undescended testes were significantly more frequent in IUGR fetuses than in normal fetuses (p=0.004). CONCLUSION: Our data confirm that abnormal fetal growth may be associated with penile shortening and, potentially, also undescended testes.

Maxillary dental arch biometry: assessment with fetal MR imaging.

OBJECTIVE: To define normal growth of the fetal maxillary dental arch using magnetic resonance imaging. METHOD: Four hundred twenty-four consecutive fetuses (18 to 37 weeks) with a morphologically normal anatomy or only minor malformations, not affecting bone growth and face anatomy were included. On axial T2-weighted images the dental arch length and width were measured. The measurements were correlated with gestational age and the biparietal diameter (BPD) of the fetal head using correlation and regression analysis. RESULTS: A linear growth relationship was observed between the dental arch length and gestational age (r = 0.86; p = < 0.0001; y = -1.85 + 0.75 × gestational age) and the dental arch width and gestational age (r = 0.92; p = < 0.0001; y = -2.19 + 1.05 × gestational age). A significant correlation was found between the dental arch length and the BPD (r = 0.903; p = < 0.0001) and the dental arch width and the BPD (r = 0.927; p = < 0.0001). The interobserver variability showed good agreement for the dental arch length (intraclass coefficient 0.981; r = 0.963) and width (intraclass coefficient 0.987; r = 0.974), respectively. CONCLUSION: We present a nomogram for the in utero assessment of the fetal dental arch. These data may help in the early detection of abnormal dental arch development.

Clubfeet and associated abnormalities on fetal magnetic resonance imaging.

OBJECTIVE: Clubfoot, or talipes equinovarus (TEV), is commonly diagnosed on prenatal ultrasound. This study sought to visualize TEV and associated abnormalities on fetal magnetic resonance imaging (MRI) compared with ultrasound. METHODS: This retrospective study included the MRI scans of 44 fetuses with TEV using postnatal assessment and autopsy as standard of reference. Isolated TEV was differentiated from complex TEV with associated abnormalities. MRI findings and previous ultrasound diagnoses were compared. RESULTS: Isolated TEV was found in 19/44 (43.2%) fetuses and complex TEV in 25/44 (56.8%). Associated abnormalities consisted of the following: central nervous system/spinal abnormalities in 13/25 (52.0%) fetuses; musculoskeletal abnormalities in 7/25 (28.0%); thoracic abnormalities in 3/25 (12.0%); a tumor in one case; and hydrops fetalis in one. Of the 44 cases, 35 (79.5%) pregnancies were delivered, and nine (20.5%) pregnancies, which were terminated, all had complex TEV. Of the 42 available ultrasound reports, additional MRI findings were made in 8/42 (19.0%) cases. MRI did not add findings in isolated TEV on ultrasound. In 4/44 (9.1%) cases, autopsy revealed additional findings compared with prenatal imaging. CONCLUSION: Fetal MRI enables differentiation between isolated and complex TEV. Isolated TEV on ultrasound may not be an MRI indication, whereas MRI may be useful in cases of complex TEV.

Triamcinolone acetonide can be detected in cerebrospinal fluid after intratympanic injection.

Intratympanically applied treatments are of increasing interest to the otologic community to treat sudden sensorineural hearing loss or vestibular disorders but also to deliver gene therapy agents, or biologics to the inner ear. Further diversion from the middle ear and perilymph to blood circulation and cerebrospinal fluid via the cochlear aqueduct are one of the limiting factors and so far not understood well enough. In this study, intratympanically applied triamcinolone acetonide was determined in cerebrospinal fluid. Additionally, perilymph was sampled through the round window membrane as well as at the lateral semicircular canal to determine drug levels. Of the twenty-one included patients, triamcinolone acetonide was quantifiable in cerebrospinal fluid in 43% at very low levels (range 0 ng/ml-6.2 ng/ml) which did not correlate with perilymph levels. Drug levels at the two different perilymph sampling sites were within a range of 13.5 ng/ml to 1180.0 ng/ml. Results suggest an equal distribution of triamcinolone acetonide to semicircular canals, which might support the use of triamcinolone acetonide as a treatment option for vestibular pathologies such as Menièrés disease. On the other hand, the distribution to cerebrospinal fluid might be limiting current approaches in gene therapy where a central distribution is unwanted.

Pembrolizumab plus docetaxel for the treatment of recurrent/metastatic head and neck cancer: A prospective phase I/II study.

BACKGROUND: Taxane-based checkpoint inhibitor combination therapy might improve the outcome in recurrent/metastatic (R/M) head and neck cancer (HNSCC) patients. Thus, we investigated the efficacy and safety of docetaxel (DTX) plus pembrolizumab (P) in a prospective phase I/II trial. METHODS: Platinum-resistant R/M HNSCC patients received DTX 75 mg/m^2 plus P 200 mg for up to six cycles followed by P maintenance therapy. The primary endpoint was overall response rate (ORR) and safety. Secondary endpoints comprised disease control rate (DCR), overall survival (OS) and progression free survival (PFS). RESULTS: Twenty-two patients were enrolled. Nine patients (40.9%) had a primary tumor in the oropharynx, 8 (36.4%) in the oral cavity, 3 (13.6%) in the hypopharynx and 2 (9.1%) in the larynx. The ORR was 22.7% (95% CI 10.1%-43.4%) and one (4.5%) complete response was achieved. The DCR was 54.6% (95% 34.7%-73.1%). The median PFS was 5.8 months (95% CI 2.7-11.6) and the median OS 21.3 months (95% CI 6.3-31.1). The 1-year PFS and OS rates were 27.3% and 68.2%, respectively. While the most frequent adverse event (AE) was myelosuppression, which was reported in all 22 patients, 3 (13.6%) patients experienced grade 3 febrile neutropenia. The most common immune-related AEs were grade skin rash (40.9%) and hypothyroidism (40.9%). One patient (4.5%) experienced grade 5 immune thrombocytopenia. CONCLUSION: DXT in combination with P shows promising activity accompanied with a manageable side effect profile in pre-treated R/M HNSCC patients.

Rectal preparation significantly improves prostate imaging quality: Assessment of the PI-QUAL score with visual grading characteristics.

PURPOSE: To investigate the effects of a rectal preparation regimen, that consisted of a rectal cleansing enema and an endorectal gel filling protocol, on prostate imaging quality (PI-QUAL). METHODS: Multiparametric MRI (mpMRI) was performed in 150 consecutive patients divided into two groups of 75 patients. One group received a rectal preparation with a cleansing enema and endorectal gel filling (median age 65.3 years, median PSA level 6 ng/ml). The other patient group did not receive such a preparation (median age 64 years, median PSA level 6 ng/ml). Two uroradiologists independently rated general image quality and lesion visibility on diffusion-weighted imaging (DWI), T2-weighted (T2w), and dynamic contrast-enhanced (DCE) images using a five-point ordinal scale. In addition, two uroradiologists assigned PI-QUAL scores, using the dedicated scoring sheet. Data sets were compared using visual grading characteristics (VGC) and receiver operating characteristics (ROC)/ area under the curve (AUC) analysis. RESULTS: VGC revealed significantly better general image quality for DWI (AUC R1 0.708 (0.628-0.779 CI, p < 0.001; AUC R2 0.687 (0.606-0.760 CI, p < 0.001) and lesion visibility for both readers (AUC R1 0.729 (0.607-0.831 CI, p < 0.001); AUC R2 0.714 (0.590-0.818CI, p < 0.001) in the preparation group. For T2w imaging, rectal preparation resulted in significantly better lesion visibility for both readers (R1 0.663 (0.537-0.774 CI, p = 0.014; R2 0.663 (0.537-0.774 CI, p = 0.014)). Averaged PI-QUAL scores were significantly improved with rectal preparation (AUC R3/R4 0.667, CI 0.581-0.754, p < 0.001). CONCLUSION: Rectal preparation significantly improved prostate imaging quality (PI-QUAL) and lesion visibility. Hence, a rectal preparation regimen consisting of a rectal cleansing enema and an endorectal gel filling could be considered.

DNA methylation profiles differ in responders versus non-responders to anti-PD-1 immune checkpoint inhibitors in patients with advanced and metastatic head and neck squamous cell carcinoma.

BACKGROUND: Biomarkers for response prediction to anti-programmed cell death 1 (PD-1) immune checkpoint inhibitors (ICI) in patients with head and neck squamous cell carcinoma (HNSCC) are urgently needed for a personalized therapy approach. We investigated the predictive potential of inflammatory parameters and DNA methylation profiling in patients with HNSCC treated with anti-PD-1 ICI. METHODS: We identified patients with HNSCC that were treated with anti-PD-1 ICI therapy in the recurrent or metastatic setting after progression to platinum-based chemotherapy in two independent centers. We analyzed DNA methylation profiles of >850.000 CpG sites in tumor specimens of these patients by Infinium MethylationEPIC microarrays, immune cell density in the tumor microenvironment (CD8, CD3, CD45RO, forkhead box P3 (FOXP3), CD68), PD-1 and programmed cell death ligand 1 (PD-L1) expression by immunohistochemistry, and blood inflammation markers (platelet-to-lymphocyte ratio, leucocyte-to-lymphocyte ratio, monocyte-to-lymphocyte ratio, neutrophil-to-lymphocyte ratio). DNA methylation profiles and immunological markers were bioinformatically and statistically correlated with radiological response to anti-PD-1 ICI. RESULTS: 37 patients with HNSCC (median age of 62 years; range 49-83; 8 (21.6%) women, 29 (78.4%) men) were included (Center 1 N=26, 70.3%; Center 2 N=11, 29.7%). Median number of prior systemic therapies was 1 (range 1-4). Five out of 37 (13.5%) patients achieved an objective response to ICI. Median progression-free survival and median overall survival times were 3.7 months (range 0-22.9) and 9.0 months (range 0-38.8), respectively. Microarray analyses revealed a methylation signature including both hypomethylation and hypermethylation which was predictive for response to ICI and included several genes involved in cancer-related molecular pathways. Over-represented differentially methylated genes between responders and non-responders were associated with 'Axon guidance', 'Hippo signaling', 'Pathways in cancer' and 'MAPK signaling'. A statistically significant correlation of PD-L1 expression and response was present (p=0.0498). CONCLUSIONS: Our findings suggest that tumor DNA methylation profiling may be useful to predict response to ICI in patients with HNSCC.

MRI versus radiography of acromioclavicular joint dislocation.

OBJECTIVE: Acromioclavicular joint injuries are usually diagnosed by clinical and radiographic assessment with the Rockwood classification, which is crucial for treatment planning. In view of the implementation of MRI for visualization of the acromioclavicular joint, the purpose of this study was to describe the MRI findings of acromioclavicular joint dislocation in comparison with the radiographic findings. SUBJECTS AND METHODS: Forty-four patients with suspected unilateral acromioclavicular joint dislocation after acute trauma were enrolled in this prospective study. All patients underwent digital radiography and 1-T MRI with a surface phased-array coil. MRI included coronal proton density-weighted turbo spin-echo and coronal 3D T1-weighted fast field-echo water-selective sequences. The Rockwood classification was used to assess acromioclavicular joint injuries at radiography and MRI. An adapted Rockwood classification was used for MRI evaluation of the acromioclavicular joint ligaments. The classifications of acromioclavicular joint dislocations diagnosed with radiography and MRI were compared. RESULTS: Among 44 patients with Rockwood type I-IV injuries on radiographs, classification on radiographs and MR images was concordant in 23 (52.2%) patients. At MRI, the injury was reclassified to a less severe type in 16 (36.4%) patients and to a more severe type in five (11.4%) patients. Compared with the findings according to the original Rockwood system, with the adapted system that included MRI findings, additional ligamentous lesions were found in 11 (25%) patients. CONCLUSION: In a considerable number of patients, the MRI findings change the Rockwood type determined with radiography. In addition to clinical assessment and radiography, MRI may yield important findings on ligaments that may influence management.