Diagnostic performance of long head of biceps tendon tears on MRI: systematic review and meta-analysis.

OBJECTIVES: The purpose of this meta-analysis was to determine the diagnostic performance of conventional MRI and MR arthrography for tendinosis, and partial and complete tears of the long head of the biceps tendon (LHBT) using arthroscopy as the reference standard. MATERIALS AND METHODS: A systematic review was performed using predefined data fields in PubMed, and all articles published from January 2000 up to April 2022 were retrospectively pooled and reviewed. Six MRI studies on complete tear (n = 555) and ten studies on partial tear/tendinosis (n = 2487) were included in the analysis. Two of the included studies in each group investigated the use of MR arthrography. The data sets were analyzed using a univariate approach with the DerSimonian and Laird random effects model and the proportional hazards model. RESULTS: MRI shows high specificities in diagnosing complete tears of the LHBT ranging from 93.0 to 99.0%. Diagnostic sensitivity was more heterogeneous ranging from 55.9 to 90.0%. The overall negative likelihood ratio was 0.29 (95% CI: 0.17-0.50) and the overall positive likelihood ratio was 37.3 (95% CI: 11.9-117.4). The mean sensitivity in diagnosing partial tear/tendinosis of the LHBT was 67.8% (95% CI: 54.3-78.9%) and the specificity was 75.9% (95% CI: 63.6-85.0%), resulting in a balanced accuracy of 71.9%. The overall negative likelihood ratio was 0.44 (95% CI: 0.32-0.59) and the overall positive likelihood ratio was 2.64 (95% CI: 1.91-3.65). CONCLUSION: MRI is highly specific for the diagnosis of complete tears of the LHBT, whereas diagnostic sensitivity was more heterogeneous. The diagnosis of partial tears and/or tendinosis of the LHBT remains challenging on MRI, which may warrant complementary clinical examination or other imaging modalities to increase diagnostic confidence in equivocal cases. CLINICAL RELEVANCE STATEMENT: Conventional MRI and MR arthrography have high diagnostic performance for complete tendon tear when compared to arthroscopy. The diagnosis of tendinosis/partial tears remains challenging and may require comparison with clinical tests and other imaging modalities. KEY POINTS: •There is no clear consensus regarding the primary imaging modality for the evaluation of LHBT disorders. •Conventional MRI and MR arthrography are highly specific in diagnosing complete tears of the LHBT. •Diagnosis of partial tears/tendinosis of the LHBT on conventional MRI and MR arthrography remains a diagnostic challenge.

Prospective evaluation of ultrasound features of magnesium-based bioabsorbable screw resorption in pediatric fractures.

OBJECTIVE: Bioabsorbable magnesium-based alloy screws release gas upon resorption. The resulting findings in the adjacent soft tissues and joints may mimic infection. The aim of the study was to evaluate the ultrasound (US) findings in soft tissues and joints during screw resorption. METHODS: Prospectively acquired US studies from pediatric patients treated with magnesium screws were evaluated for screw head visibility, posterior acoustic shadowing, twinkling artifact, foreign body granuloma, gas (soft tissue, intra-articular), alterations of the skin and subcutaneous fat, perifascial fluid, localized fluid collections, hypervascularization, and joint effusion. RESULTS: Sixty-six US studies of 28 pediatric patients (nfemale = 9, nmale = 19) were included. The mean age of the patients at the time of surgery was 10.84 years; the mean time between surgery and ultrasound was 128.3 days (range = 6-468 days). The screw head and posterior acoustic shadowing were visible in 100% of the studies, twinkling artifact in 6.1%, foreign body granuloma in 92.4%, gas locules in soft tissue in 100% and intra-articular in 18.2%, hyperechogenicity of the subcutaneous fat in 90.9%, cobblestoning of the subcutaneous fat in 24.2%, loss of normal differentiation between the epidermis/dermis and the subcutaneous fat in 57.6%, localized fluid collection in 9.9%, perifascial fluid in 12.1%, hypervascularization in 27.3%, and joint effusion in 18.2%. CONCLUSION: US findings in pediatric patients treated with magnesium screws strongly resemble infection, but are normal findings in the setting of screw resorption. CLINICAL RELEVANCE STATEMENT: Bioabsorbable magnesium-based alloy screws release gas during resorption. The resulting US findings in the adjacent soft tissues and joints in pediatric patients may mimic infection, but are normal findings. KEY POINTS: • Bioabsorbable magnesium-based alloy screws release gas upon resorption. • The resulting ultrasound findings in children's soft tissues and joints closely resemble those of soft tissue infection or osteosynthesis-associated infection. • Be familiar with these ultrasound findings in order to avoid inadvertently misdiagnosing a soft tissue infection or osteosynthesis-associated infection.

Chemical biology and medicinal chemistry of RNA methyltransferases.

RNA methyltransferases (MTases) are ubiquitous enzymes whose hitherto low profile in medicinal chemistry, contrasts with the surging interest in RNA methylation, the arguably most important aspect of the new field of epitranscriptomics. As MTases become validated as drug targets in all major fields of biomedicine, the development of small molecule compounds as tools and inhibitors is picking up considerable momentum, in academia as well as in biotech. Here we discuss the development of small molecules for two related aspects of chemical biology. Firstly, derivates of the ubiquitous cofactor S-adenosyl-l-methionine (SAM) are being developed as bioconjugation tools for targeted transfer of functional groups and labels to increasingly visible targets. Secondly, SAM-derived compounds are being investigated for their ability to act as inhibitors of RNA MTases. Drug development is moving from derivatives of cosubstrates towards higher generation compounds that may address allosteric sites in addition to the catalytic centre. Progress in assay development and screening techniques from medicinal chemistry have led to recent breakthroughs, e.g. in addressing human enzymes targeted for their role in cancer. Spurred by the current pandemic, new inhibitors against coronaviral MTases have emerged at a spectacular rate, including a repurposed drug which is now in clinical trial.

Prospective measurement of the width of cerebrospinal fluid spaces by cranial ultrasound in neurologically healthy children aged 0-19 months.

BACKGROUND: Ultrasound (US) is often the first method used to look for brain or cerebrospinal fluid (CSF) space pathologies. Knowledge of normal CSF width values is essential. Most of the available US normative values were established over 20 years ago, were obtained with older equipment, and cover only part of the age spectrum that can be examined by cranial US. This prospective study aimed to determine the normative values of the widths of the subarachnoid and internal CSF spaces (craniocortical, minimal and maximal interhemispheric, interventricular, and frontal horn) for high-resolution linear US probes in neurologically healthy infants and children aged 0-19 months and assess whether subdural fluid collections can be delineated. METHODS: Two radiologists measured the width of the CSF spaces with a conventional linear probe and an ultralight hockey-stick probe in neurologically healthy children not referred for cranial or spinal US. RESULTS: This study included 359 neurologically healthy children (nboys = 178, 49.6%; ngirls = 181, 50.4%) with a median age of 46.0 days and a range of 1-599 days. We constructed prediction plots, including the 5th, 50th, and 95th percentiles, and an interactive spreadsheet to calculate normative values for individual patients. The measurements of the two probes and the left and right sides did not differ, eliminating the need for separate normative values. No subdural fluid collection was detected. CONCLUSION: Normative values for the widths of the subarachnoid space and the internal CSF spaces are useful for evaluating intracranial pathology, especially when determining whether an increase in the subarachnoid space width is abnormal.

Diagnostic imaging strategies of acute intracerebral hemorrhage in European academic hospitals-a decision-making analysis.

PURPOSE: To evaluate and compare which factors are relevant to the diagnostic decision-making and imaging workup of intracerebral hemorrhages in large, specialized European centers. METHODS: Expert neuroradiologists from ten large, specialized centers (where endovascular stroke treatment is routinely performed) in nine European countries were selected in cooperation with the European Society of Neuroradiology (ESNR). The experts were asked to describe how and when they would investigate specific causes in a patient who presented with an acute, atraumatic, intracerebral hemorrhage for two given locations: (1) basal ganglia, thalamus, pons or cerebellum; (2) lobar hemorrhage. Answers were collected, and decision trees were compared. RESULTS: Criteria that were considered relevant for decision-making reflect recommendations from current guidelines and were similar in all participating centers. CT Angiography or MR angiography was considered essential by the majority of centers regardless of other factors. Imaging in clinical practice tended to surpass guideline recommendations and was heterogeneous among different centers, e.g., in a scenario suggestive of typical hypertensive hemorrhage, recommendations ranged from no further follow-up imaging to CT angiography and MR angiography. In no case was a consensus above 60% achieved. CONCLUSION: In European clinical practices, existing guidelines for diagnostic imaging strategies in ICH evaluation are followed as a basis but in most cases, additional imaging investigation is undertaken. Significant differences in imaging workup were observed among the centers. Results suggest a high level of awareness and caution regarding potentially underlying pathology other than hypertensive disease.

Chemical Space Virtual Screening against Hard-to-Drug RNA Methyltransferases DNMT2 and NSUN6.

Targeting RNA methyltransferases with small molecules as inhibitors or tool compounds is an emerging field of interest in epitranscriptomics and medicinal chemistry. For two challenging RNA methyltransferases that introduce the 5-methylcytosine (m5C) modification in different tRNAs, namely DNMT2 and NSUN6, an ultra-large commercially available chemical space was virtually screened by physicochemical property filtering, molecular docking, and clustering to identify new ligands for those enzymes. Novel chemotypes binding to DNMT2 and NSUN6 with affinities down to KD,app = 37 µM and KD,app = 12 µM, respectively, were identified using a microscale thermophoresis (MST) binding assay. These compounds represent the first molecules with a distinct structure from the cofactor SAM and have the potential to be developed into activity-based probes for these enzymes. Additionally, the challenges and strategies of chemical space docking screens with special emphasis on library focusing and diversification are discussed.

Diffusion-Weighted Imaging Distinguishes Between Osteomyelitis, Bone Marrow Edema, and Healthy Bone on Forefoot Magnetic Resonance Imaging.

BACKGROUND: Diagnosis of osteomyelitis by imaging can be challenging. The feasibility of diffusion-weighted imaging (DWI) as ancillary sequence was evaluated in this study. PURPOSE: To evaluate DWI for differentiation between osteomyelitis, bone marrow edema, and healthy bone on forefoot magnetic resonance imaging (MRI). STUDY TYPE: Prospective. SUBJECTS: A total of 60 consecutive patients undergoing forefoot MRI divided into three study groups (20 subjects each): osteomyelitis, bone marrow edema, and healthy bone. FIELD STRENGTH/SEQUENCE: A 1.5T and 3T MRI scanners; readout-segmented multishot echo planar DWI. ASSESSMENT: Two independent radiologists measured apparent diffusion coefficient (ADC) values within abnormal or healthy bone. STATISTICAL TESTS: ADC values were compared between groups (pairwise t-test with Bonferroni-Holm correction for multiple testing). Intraclass correlation coefficient (ICC) was calculated to assess inter-reader agreement. Threshold ADC values were determined as the cutoffs that maximized the sum of sensitivity and specificity. Receiver operating characteristic (ROC) analysis was performed with statistical threshold of P < 0.05. RESULTS: Inter-reader agreement was 0.92 in the healthy bone group and 0.78 in both the edema and osteomyelitis groups. Average ADC values were significantly different between groups: 1432 ± 222 × 10-6  mm2 /sec (osteomyelitis), 1071 ± 196 × 10-6  mm2 /sec (bone marrow edema), and 277 ± 89 × 10-6  mm2 /sec (healthy bone). A threshold ADC value of 534 × 10-6  mm2 /sec distinguishes between healthy and abnormal bone with specificity and sensitivity of 100% each. For distinction between osteomyelitis and bone marrow edema, two cutoff values were determined: a 95%-specificity cutoff indicating osteomyelitis (>1320 × 10-6  mm2 /sec) and a 95%-sensitivity cutoff indicating bone marrow edema (<1155 × 10-6  mm2 /sec). Diagnostic accuracy of 95% was achieved for 73% (29/40) of the subjects. DATA CONCLUSION: DWI with ADC maps distinguishes between healthy and abnormal bone on forefoot MRI. Calculated cutoff values allow confirmation or exclusion of osteomyelitis in a high proportion of subjects. EVIDENCE LEVEL: 2 TECHNICAL EFFICACY: Stage 2.

Protein-Based Virtual Screening Tools Applied for RNA-Ligand Docking Identify New Binders of the preQ1-Riboswitch.

Targeting RNA with small molecules is an emerging field. While several ligands for different RNA targets are reported, structure-based virtual screenings (VSs) against RNAs are still rare. Here, we elucidated the general capabilities of protein-based docking programs to reproduce native binding modes of small-molecule RNA ligands and to discriminate known binders from decoys by the scoring function. The programs were found to perform similar compared to the RNA-based docking tool rDOCK, and the challenges faced during docking, namely, protomer and tautomer selection, target dynamics, and explicit solvent, do not largely differ from challenges in conventional protein-ligand docking. A prospective VS with the Bacillus subtilis preQ1-riboswitch aptamer domain performed with FRED, HYBRID, and FlexX followed by microscale thermophoresis assays identified six active compounds out of 23 tested VS hits with potencies between 29.5 nM and 11.0 µM. The hits were selected not solely based on their docking score but for resembling key interactions of the native ligand. Therefore, this study demonstrates the general feasibility to perform structure-based VSs against RNA targets, while at the same time it highlights pitfalls and their potential solutions when executing RNA-ligand docking.

MRI findings of ischiofemoral impingement after total hip arthroplasty are associated with increased femoral antetorsion.

BACKGROUND: Ischiofemoral impingement (IFI) is a known complication after total hip arthroplasty (THA). PURPOSE: To assess if increased postoperative (FA) is associated with magnetic resonance imaging (MRI) findings of IFI. MATERIAL AND METHODS: In 221 patients with THA, two independent readers measured FA, ischiofemoral space (IFS), quadratus femoris space (QFS), edema, and fatty infiltration of quadratus femoris muscle. Three sets of IFI-imaging features were defined: acute IFI (set 1): IFS ≤15 mm or QFS ≤10 mm and edema in the quadratus femoris muscle; chronic IFI (set 2): IFS ≤15 mm or QFS ≤10 mm and fatty infiltration of quadratus femoris muscle Goutallier grade ≥2; acute and chronic IFI (set 3) with both criteria applicable. For each set, FA angles were compared between positive findings of IFI and negative findings of IFI. The t-test for independent samples tested statistical significance. RESULTS: In 7.2% (16/221) of patients, findings of IFI (IFS ≤15 mm or QFS ≤10 mm and edema, n = 1; fatty infiltration, n = 9; or both, n = 6) were observed. In women, 11.4% (14/123) exhibited findings of IFI compared to 2.0% (2/98) in men. Comparison in set 1 (n = 7): mean antetorsion of 23.9° ± 9.8° (findings of acute IFI) compared to 14.4° ± 9.7° (P = 0.01). Comparison in set 2 (n = 15): mean antetorsion of 16.2° ± 6.3° (findings of chronic IFI) compared to 14.5° ± 9.9° (P = 0.49). Comparison in set 3 (n = 6): mean antetorsion of 20.4° ± 3.8° (findings of acute and chronic IFI) compared to 14.5° ± 9.9° (P = 0.01). CONCLUSION: After THA, high postoperative FA is associated with MRI findings of acute as well as acute and chronic IFI. Findings of IFI were commonly seen in women.

Retrospective evaluation of routine in-hospital observation in 433 patients after CT-guided biopsies.

BACKGROUND: After computed tomography (CT)-guided interventions, routine in-hospital observation is recommended by the Cardiovascular and Interventional Radiological Society of Europe. PURPOSE: To evaluate the frequency of delayed major complications or hospitalizations after CT-guided biopsies in patients with initially no or minor complications and to assess whether routine in-hospital observation is justified. MATERIAL AND METHODS: This retrospective study included 433 outpatients after CT-guided biopsy of the thoracic (n = 176), abdominal (n = 129), or musculoskeletal (n = 128) region with subsequent in-hospital observation. Complications were graded according to the current Society of Interventional Radiology recommendations and grouped into minor or major. A complication that occurred during in-hospital observation was defined as delayed complication. A delayed major complication was a newly developed major complication or a progression from an initially minor to a major complication. Hospitalization frequencies were evaluated similarly. Occurrence, 95% confidence intervals (CI), and P values for significant differences between the three organ groups were calculated. If delayed major complications were more frequent than 1%, routine in-hospital observation was considered justified. RESULTS: Delayed, major complication frequencies were: thoracic, 8.2% (95% CI 4.6-13.4); abdominal, 0.0% (95% CI 0.0-2.9); and musculoskeletal, 0.0% (95% CI 0.0-2.9) (P < 0.001). Delayed hospitalization frequencies were: thoracic, 8.8% (95% CI 5.0-14.2); abdominal, 1.6% (95% CI 0.2-5.6); and musculoskeletal, 0.0% (95% CI 0.0-2.9) (P < 0.001). CONCLUSION: After thoracic interventions, routine observation is considered justified for patient safety whereas routine observation may be omitted after musculoskeletal interventions. In the abdominal group, no delayed complications were observed, but delayed hospitalization occurred. Thus, in-hospital observation could be justified in a safe patient environment, but remains an individual decision.

Radiographic features of magnesium-based bioabsorbable screw resorption in paediatric fractures.

BACKGROUND: Resorption of magnesium-based alloy bioabsorbable screws produces hydrogen gas, which can be mistaken as a sign of infection and may affect the physis or fixed bone fragment. OBJECTIVE: We evaluated the temporal and spatial occurrence of gas and the occurrence of a breakage of the fixed bone fragment or screw following magnesium screw fixation. MATERIALS AND METHODS: Radiographs of paediatric patients treated with magnesium screws were retrospectively reviewed. Temporal occurrence and distribution of gas in the bone, the physis and soft tissues, breakage of the screw or fixed bone fragment and joint effusion were assessed. RESULTS: One hundred and three radiographs in 35 paediatric patients were reviewed (mean age: 10.6 years). Follow-up ranged from 1 to 730 days. Gas in the bone increases up to week 5, remains constant up to week 16 and then decreases. Gas in soft tissues, intra-articular gas and joint effusions gradually reduce over time. In 1/23 (4.3%) patients with an open physis, gas intrusion into the physis occurred. Breakage of the bone fragment fixated by the screw was observed in 4/35 (11.4%) patients within the first 6 weeks. Screw breakage was observed in 16/35 (45.7%) patients, with a median time to first detection of 300 days. CONCLUSION: Gas bubbles in bone and soft tissue are normal findings in the context of screw resorption and should not be confused with soft-tissue infection or osteomyelitis. Gas is rarely visible in the physis. Breakage of the fixed bone fragment and/or screw can occur.

Organ-based tube current modulation and bismuth eye shielding in pediatric head computed tomography.

BACKGROUND: Exposure of the eye lens to ionizing radiation results in cataract. Several dose optimization techniques to protect the lens are available for computed tomography (CT). OBJECTIVE: The radiation dose to the eye lens, volume CT dose index (CTDIvol) and image quality of various methods of dose optimization were evaluated for pediatric head CT: automated tube current modulation (ATCM), automated tube voltage selection (ATVS), organ-based tube current modulation (OBTCM) and bismuth shielding. MATERIALS AND METHODS: An anthropomorphic phantom of a 5-year-old child was scanned with nine protocols: no dose optimization technique and then adding different dose optimization techniques alone and in combination. Dose to the eye, thyroid and breast were estimated using metal oxide semiconductor field effect transistor (MOSFET) dosimetry. CTDIvol, influence of timing of shield placement, image noise and attenuation values in 13 regions of interest of the head and subjective image quality were compared. RESULTS: The eye shield significantly reduced the eye lens dose when used alone, to a similar degree as when using all software-based techniques together. When used in combination with software-based techniques, the shield reduced the eye lens dose by up to 45% compared to the no dose optimization technique. Noise was significantly increased by the shield, most pronounced in the anterior portion of the eye. CONCLUSION: The combination of ATCM, ATVS, OBTCM and a bismuth shield, with the shield placed after acquiring the localizer image, should be considered to reduce the radiation dose to the eye lens in pediatric head CT.

Short tau inversion recovery (STIR) after intravenous contrast agent administration obscures bone marrow edema-like signal on forefoot MRI.

OBJECTIVE: Short tau or short TI inversion recovery (STIR) MRI sequences are considered a robust fat suppression technique. However, STIR also suppresses signals from other tissues with similar T1 relaxation times. This study investigates the in vivo effect of intravenous gadolinium-based T1-shortening contrast agent on STIR signal. MATERIALS AND METHODS: Institutional board approval and informed consent was obtained. MRI examinations (1.5-T or 3-T) of 31 prospectively included patients were analyzed by two readers. Signal intensity of degenerative bone marrow edema-like signal at the Lisfranc joint on precontrast STIR images and on STIR images acquired after intravenous contrast agent administration (gadoteric acid, gadolinium: 0.5 mmol/ml, 15 ml) was measured. The medial cuneiform bone without observable bone marrow edema-like signal was considered a healthy tissue and served as a reference. Relative changes in signal intensity between precontrast and postcontrast images were calculated for the two tissues. Wilcoxon signed-rank test served for statistical analyses. RESULTS: In bone marrow edema-like signal, both readers observed a median signal change of -35% (interquartile range (IQR) 24) and -34% (IQR 21), respectively, on postcontrast STIR images compared to precontrast STIR. In healthy tissue, the signal remained constant on postcontrast STIR images (median change -2%, IQR 15, and 0%, IQR 17) respectively. For both readers, postcontrast signal change in bone marrow edema-like signal differed from that in healthy tissue (p < 0.001). CONCLUSION: Intravenous gadolinium-based contrast agent causes a significant reduction of signal intensity in bone marrow edema-like signal on routine STIR images. Thus, pathological MRI findings may be obscured.

Limitations of Accelerated Stability Model Based on the Arrhenius Equation for Shelf Life Estimation of In Vitro Diagnostic Products.

BACKGROUND: An accelerated stability model based on the Arrhenius Equation can be used to estimate stability of diagnostic reagents. Here we review 3 examples in which the model does not accurately predict the stability of diagnostic reagents. METHODS: We prepared several pilot lots of quality controls materials containing fructosamine, BNP, and HbA1c in human whole blood and serum matrices and performed accelerated stability studies at increased temperatures (5 °C to 35 °C) and real-time stability studies at the recommended storage temperature (-10 °C to -20 °C) for several analytes in quality control materials. RESULTS: We observed that the stability predictions obtained from the accelerated stability studies were longer in 2 instances and much shorter in another than those observed from the real-time stability studies. CONCLUSIONS: Due to discrepancies between the stability results from accelerated stability studies and those from the real-time stability studies, we stress the need for caution when reagent manufacturers use the Arrhenius model and recommend that the technical groups and committees assigned to revise CLSI and ISO stability documents highlight the limitations of the accelerated stability model and include more guidance and direction on how and when to use the accelerated stability model.

Wallerian degeneration in cervical spinal cord tracts is commonly seen in routine T2-weighted MRI after traumatic spinal cord injury and is associated with impairment in a retrospective study.

OBJECTIVES: Wallerian degeneration (WD) is a well-known process after nerve injury. In this study, occurrence of remote intramedullary signal changes, consistent with WD, and its correlation with clinical and neurophysiological impairment were assessed after traumatic spinal cord injury (tSCI). METHODS: In 35 patients with tSCI, WD was evaluated by two radiologists on T2-weighted images of serial routine MRI examinations of the cervical spine. Dorsal column (DC), lateral corticospinal tract (CS), and lateral spinothalamic tract (ST) were the analyzed anatomical regions. Impairment scoring according to the American Spinal Injury Association Impairment Scale (AIS, A-D) as well as a scoring system (0-4 points) for motor evoked potential (MEP) and sensory evoked potential (SEP) was included. Mann-Whitney U test was used to test for differences. RESULTS: WD in the DC occurred in 71.4% (n = 25), in the CS in 57.1% (n = 20), and in 37.1% (n = 13) in the ST. With WD present, AIS grades were worse for all tracts. DC: median AIS B vs D, p < 0.001; CS: B vs D, p = 0.016; and ST: B vs D, p = 0.015. More pathological MEP scores correlated with WD in the DC (median score 0 vs 3, p < 0.001) and in the CS (0 vs 2, p = 0.032). SEP scores were lower with WD in the DC only (1 vs 2, p = 0.031). CONCLUSIONS: WD can be detected on T2-weighted scans in the majority of cervical spinal cord injury patients and should be considered as a direct effect of the trauma. When observed, it is associated with higher degree of impairment. KEY POINTS: • Wallerian degeneration is commonly seen in routine MRI after traumatic spinal cord injury. • Wallerian degeneration is visible in the anatomical regions of the dorsal column, the lateral corticospinal tract, and the lateral spinothalamic tract. • Presence of Wallerian degeneration is associated with higher degree of impairment.

Golimumab improves work productivity in patients suffering from moderate to severe ulcerative colitis: results of a prospective study over 24 months.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory bowel disease with recurrent episodes of debilitating symptoms negatively affecting work productivity and health-related quality of life (HRQoL). The use of biologics in UC treatment improves work and HRQoL but prospective long-term data concerning the treatment with TNFα inhibitor golimumab in UC patients are still rare. Therefore, our study aimed to evaluate the change in work productivity, capacity for daily activities and HRQoL in UC patients treated with golimumab in Germany. METHODS: Using the Work Productivity and Activity Impairment questionnaire, the change in work productivity and in capacity for daily activities after 3 months and over the whole observational period of 24 months were assessed (both primary endpoints). Disease-specific and health-related quality of life (QoL) were analyzed with the Inflammatory Bowel Disease Questionnaire (IBDQ), the Short-Form 12 Health Survey Questionnaire (SF-12), and the Partial Mayo Score (secondary endpoints). Further, disease-related hospitalization rates were assessed. RESULTS: This prospective non-interventional study included 286 patients. Thereof, 212 patients were employed at baseline (modified intention to treat analysis set employed at baseline, mITTe). 61.3% of the mITTe patients had moderate and 17.0% had severe UC. Three months after initiation of golimumab therapy, total work productivity impairment (TWPI) score and activity impairment score improved significantly from baseline with a mean change of - 17.3% (p < 0.0001) and - 14.4% (p < 0.0001), respectively. Results persisted over 24 months (mean change TWPI score: - 24.5%, mean change activity impairment score: - 30.0%). Disease- and health-related QoL also improved significantly under golimumab treatment as indicated by increased IBDQ [mean change: 28.0 (SD: ± 36.1, month 3), 42.1 (SD: ± 39.5, month 24)] and SF-12 scores [PCS-12: 45.9 (SD: ± 8.5), MCS-12: 4.9 (SD: ± 10.6, month 3), PCS-12: 5.9 (SD: ± 9.0), MCS-12: 6.4 (SD: ± 11.1, month 24)]. Disease-related hospitalization rate decreased from 16.0% (BL) to 4.3% at month 24 and the mean number of missed working days due to UC decreased from 8.2 (SD: 17.6, BL) to 0.7 (SD: 2.1) after golimumab induction. CONCLUSIONS: Golimumab leads to notable long-term improvements in work productivity, daily activity, HRQoL, and disease-related hospitalization rates in patients with moderate to severe UC. TRIAL REGISTRATION: PEI (Paul-Ehrlich-Institute, Langen, Germany) Registration Nr: NIS#255 ( https://www.pei.de/SharedDocs/awb/nis-0201-0300/0255.html ).

Pinna-Imitating Microphone Directionality Improves Sound Localization and Discrimination in Bilateral Cochlear Implant Users.

OBJECTIVES: To compare the sound-source localization, discrimination, and tracking performance of bilateral cochlear implant users with omnidirectional (OMNI) and pinna-imitating (PI) microphone directionality modes. DESIGN: Twelve experienced bilateral cochlear implant users participated in the study. Their audio processors were fitted with two different programs featuring either the OMNI or PI mode. Each subject performed static and dynamic sound field spatial hearing tests in the horizontal plane. The static tests consisted of an absolute sound localization test and a minimum audible angle test, which was measured at eight azimuth directions. Dynamic sound tracking ability was evaluated by the subject correctly indicating the direction of a moving stimulus along two circular paths around the subject. RESULTS: PI mode led to statistically significant sound localization and discrimination improvements. For static sound localization, the greatest benefit was a reduction in the number of front-back confusions. The front-back confusion rate was reduced from 47% with OMNI mode to 35% with PI mode (p = 0.03). The ability to discriminate sound sources straight to the sides (90° and 270° angle) was only possible with PI mode. The averaged minimum audible angle value for the 90° and 270° angle positions decreased from a 75.5° to a 37.7° angle when PI mode was used (p < 0.001). Furthermore, a non-significant trend towards an improvement in the ability to track moving sound sources was observed for both trajectories tested (p = 0.34 and p = 0.27). CONCLUSIONS: Our results demonstrate that PI mode can lead to improved spatial hearing performance in bilateral cochlear implant users, mainly as a consequence of improved front-back discrimination with PI mode.

Normal sonographic liver and spleen dimensions in a central European pediatric population.

BACKGROUND: Organ size is influenced by a number of factors. Age, height, weight, and ethnicity are known influencing factors. Pediatric populations have changed over time, puberty beginning earlier resulting in a changing growth pattern of their organs. Hence, contemporary charts using local data are considered the most appropriate for a given population. Sonographic charts for liver size for a predominantly Caucasian population are limited, which has implications for clinical practice. The aim of this study was to define a contemporary normative range of liver and spleen sizes for a healthy, predominantly Caucasian population and for all pediatric age groups (0-18 years) and to investigate whether there is a size difference between genders and ethnicities. METHODS: Retrospective study including children with normal sonographic findings and no evidence of liver or splenic disease clinically. Craniocaudal and anteroposterior dimensions are measured for the right and left lobe of the liver, and craniocaudal dimension for the spleen. Relationship of the liver and spleen dimensions with age, body length, body surface area, weight, and gender were investigated. Charts of normal values were established. Values were compared to studies involving other ethnicities and to one study carried out in 1983 involving the same ethnicity. RESULTS: Seven hundred thirty-six children (371 boys, 365 girls) aged 1 day - 18.4 years were included. From the second year of life, the craniocaudal dimension of the right lobe of the liver is 1-2 cm larger in the Central European population compared with non-Caucasian populations at a given age. Liver size of Central European children in 2020 is greater compared to a similar population almost 40 years ago. The craniocaudal dimension of the spleen of Central European, US-American and Turkish children is similar. The difference between genders is statistically significant for both the liver and the spleen, being larger in boys. CONCLUSION: Contemporary and ethnically appropriate reference charts for liver and spleen measurements should be used, especially for liver size. The effect of ethnicity is reduced if patient height rather than age is referenced.

Impact of stem design and cementation on postoperative femoral antetorsion in 227 patients with total hip arthroplasty (THA).

OBJECTIVE: In total hip arthroplasty (THA), surgeons attempt to achieve a physiological antetorsion. However, postoperative antetorsion of the femoral stem is known to show large variabilities. The purpose of this study was to assess whether postoperative antetorsion is influenced by stem design or cementation. MATERIALS AND METHODS: This retrospective study included 227 patients with a hip prosthesis with five different stem designs (S1: short curved, S2 and S3: standard straight, S4: standard straight collared, S5: cemented straight), who had metal suppressed 1.5T-MRI of the hip between February 2015 and October 2019. Measurement of femoral antetorsion was done independently by two fellowship-trained radiologists on axial images by measuring the angle between the long axis of the femoral neck and the posterior condylar tangent of the knee. Measured angles in the different groups were compared using the t test for independent samples. RESULTS: The cementless collared stem S4 showed the highest antetorsion with 18.1° (± 10.5°; range -10°-45°), which was significantly higher than the antetorsion of the collarless S3 with 13.3° (± 8.4°; - 4°-29°) and the cemented S5 with 12.7° (± 7.7°; - 3°-27°) with p = 0.012 and p = 0.007, respectively. S1 and S2 showed an antetorsion of 14.8° (± 10.0°; 1°-37°) and 14.1° (± 12.2°; - 20°-41°). The torsional variability of the cementless stems (S1-4) was significantly higher compared with that of the cemented S5 with a combined standard deviation of 10.5° and 7.7° (p = 0.019). CONCLUSION: Prosthesis design impacts the postoperative femoral antetorsion, with the cementless collared stem showing the highest antetorsion. Cemented stems demonstrated significantly lower variability, suggesting the lowest rate of inadvertent malrotation.

Discovery of novel dual inhibitors of receptor tyrosine kinases EGFR and PDGFR-ß related to anticancer drug resistance.

With ongoing resistance problems against the marketed EGFR inhibitors having a quinazoline core scaffold there is a need for the development of novel inhibitors having a modified scaffold and, thus, expected lower EGFR resistance problems. An additional problem concerning EGFR inhibitor resistance is an observed heterodimerization of EGFR with PDGFR-ß that neutralises the sole inhibitor activity towards EGFR. We developed novel pyrimido[4,5-b]indoles with varied substitution patterns at the 4-anilino residue to evaluate their EGFR and PDGFR-ß inhibiting properties. We identified dual inhibitors of both EGFR and PDGFR-ß in the nanomolar range which have been initially screened in cancer cell lines to prove a benefit of both EGFR and PDGFR-ß inhibition.