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OBJECTIVE Mild traumatic brain injury (mTBI) is a major cause of emergency room (ER) admission. Thirty percent of mTBI patients have postconcussion syndrome (PCS), and 15% have symptoms for over a year. This population is underdiagnosed and does not receive appropriate care. The authors proposed a fast and inexpensive fluorometric measurement of circulating cell-free DNA (cfDNA) as a biomarker for PCS. cfDNA is a proven, useful marker of a variety of acute pathological conditions such as trauma and acute illness. METHODS Thirty mTBI patients were recruited for this prospective single-center trial. At admission, patients completed questionnaires and blood was drawn to obtain cfDNA. At 3–4 months after injury, 18 patients returned for cognitive assessments with questionnaires and the Color Trails Test (CTT). The fast SYBR Gold assay was used to measure cfDNA. RESULTS Seventeen men and 13 women participated in this trial. The mean ± SD age was 50.9 ± 13.9 years. Of the 18 patients who returned for cognitive assessment, one-third reported working fewer hours, 4 (22.2%) changed their driving patterns, and 5 (27.7%) reduced or stopped performing physical activity. The median cfDNA level of the mTBI group was greater than that of the matched healthy control group (730.5 vs 521.5 ng/ml, p = 0.0395). Admission cfDNA concentration was negatively correlated with performance on the CTT1 and CTT2 standardized tests (r = −0.559 and −0.599), meaning that greater cfDNA level was correlated with decreased cognitive performance status. The performance of the patients with normal cfDNA level included in the mTBI group was similar to that of the healthy participants. In contrast, the increased cfDNA group (> 800 ng/ml) had lower scores on the CTT tests than the normal cfDNA group (p < 0.001). Furthermore, patients with moderate/severe cognitive impairment according to CTT1 results had a greater median cfDNA level than the patients with scores indicating mild impairment or normal function (1186 vs 473.5 ng/ml, p = 0.0441, area under the receiver operating characteristic curve = 0.8393). CONCLUSIONS The data from this pilot study show the potential to use cfDNA, as measured with a fast test, as a biomarker to screen for PCS in the ER. A large-scale study is required to establish the value of cfDNA as an early predictor of PCS.

Approaches to manage nonalcoholic fatty liver disease (NAFLD) are limited by an incomplete understanding of disease pathogenesis. The aim of this study was to identify hepatic gene-expression patterns associated with different patterns of liver injury in a high-risk cohort of adults with obesity. Using the NanoString Technologies (Seattle, WA) nCounter assay, we quantified expression of 795 genes, hypothesized to be involved in hepatic fibrosis, inflammation, and steatosis, in liver tissue from 318 adults with obesity. Liver specimens were categorized into four distinct NAFLD phenotypes: normal liver histology (NLH), steatosis only (steatosis), nonalcoholic steatohepatitis without fibrosis (NASH F0), and NASH with fibrosis stage 1-4 (NASH F1-F4). One hundred twenty-five genes were significantly increasing or decreasing as NAFLD pathology progressed. Compared with NLH, NASH F0 was characterized by increased inflammatory gene expression, such as gamma-interferon-inducible lysosomal thiol reductase (IFI30) and chemokine (C-X-C motif) ligand 9 (CXCL9), while complement and coagulation related genes, such as C9 and complement component 4 binding protein beta (C4BPB), were reduced. In the presence of NASH F1-F4, extracellular matrix degrading proteinases and profibrotic/scar deposition genes, such as collagens and transforming growth factor beta 1 (TGFB1), were simultaneously increased, suggesting a dynamic state of tissue remodeling. Conclusion: In adults with obesity, distinct states of NAFLD are associated with intrahepatic perturbations in genes related to inflammation, complement and coagulation pathways, and tissue remodeling. These data provide insights into the dynamic pathogenesis of NAFLD in high-risk individuals.

PurposeThe present study investigates superficial in vivo dosimetry (IVD) by means of a previously proposed electron paramagnetic resonance (EPR) dosimetry system aiming at measuring and verifying total doses delivered by complex radiotherapy treatments. In view of novel regulatory requirements in Germany, differences between measured and planned total doses to the EPR dosimeters are analyzed and compared to reporting thresholds for significant occurrences.MethodsEPR dosimeters, each consisting of one lithium formate monohydrate (LFM) and one polycrystalline l-alanine (ALA) pellet, were attached to the surface of an anthropomorphic head phantom. Three head and neck treatments with total target doses ranging from 30 to 64 Gy were fully delivered to the phantom by helical tomotherapy. During each treatment, eight EPR dosimeters were placed at distinct spots: (i) within or next to the planning target volume (PTV), (ii) near to organs at risk including the parotids and the lenses, (iii) at the thyroid lying out-of-field. EPR read out was always performed after all fractions were delivered. EPR results were compared to thermoluminescence dosimeter (TLD) measurements and to the planned total doses derived from the treatment planning system (TPS). Planned total doses to the EPR dosimeters ranged from about 2 to 64 Gy.ResultsBy taking uncertainties into account, the measured and planned doses were in good agreement. Exceptions occurred mainly at the thyroid (out-of-field) and lenses (extreme sparing). The maximum total dose difference between EPR results and corresponding planned doses was 1.3 Gy occurring at the lenses. Remarkably, each LFM and ALA pellet placed within or next to the PTV provided dose values that were within ±4% of the planned dose. Dose deviations from planned dose values were comparable for EPR and TLD measurements.ConclusionThe results of this proof of principle study suggests that superficial EPR-IVD is applicable in a wide dose range and in various irradiation conditions – being a valuable tool for monitoring cumulative total doses delivered by complex IMRT treatments. EPR-IVD in combination with helical tomotherapy is suitable to reliably detect local dose deviations at superficial dosimeter spots in the order of current national reporting thresholds for significant occurrences (i.e. 10%/4 Gy). published

Introduction Psoriatic arthritis (PsA) has a major impact on health-related quality of life (HRQOL) and other patient-reported outcomes (PROs), important components in the assessment of therapeutic efficacy. We evaluated the impact of upadacitinib on PROs in PsA patients with inadequate responses or intolerance to biologic disease-modifying anti-rheumatic drugs (bDMARD-IR). Methods Patients enrolled in the phase 3 SELECT-PsA 2 randomized controlled trial (RCT) received 56 weeks of oral upadacitinib 15 mg QD, upadacitinib 30 mg QD, or placebo switched to either dose of upadacitinib at week 24. PROs included patient global assessment of disease activity (PtGA), pain, physical function (HAQ-DI), health-related quality of life (SF-36 physical (PCS) and mental (MCS) component summary and domain scores), fatigue (FACIT-F), psoriasis symptom severity (SAPS), and work productivity (WPAI). Mean changes from baseline in PROs, improvements ≥ minimum clinically important differences (MCID) and scores ≥ normative values, and maintenance of improvements were assessed. Results At weeks 12 and 24, patients treated with either upadacitinib dose reported statistically and nominally significant improvements from baseline across all PROs versus placebo (p ≤ 0.05), except the WPAI absenteeism domain, which were maintained or further improved to week 56. A significantly greater proportion of patients receiving either upadacitinib dose reported improvements ≥ MCID and scores ≥ normative values versus placebo (nominal p ≤ 0.01) in most PROs at weeks 12 and 24, with clinically meaningful improvements continuing to week 56. Improvements ≥ MCID were reported as early as week 2 in PtGA, pain, and HAQ-DI. Conclusions Upadacitinib provides rapid, clinically meaningful, and sustained improvements in PROs reported by bDMARD-IR PsA patients. SELECT-PsA 2 ClinicalTrials.gov number, NCT03104374. Supplementary Information The online version contains supplementary material available at 10.1007/s40744-021-00377-x.

Low back pain is a common health concern. The development of myofascial trigger points due to low back pain can cause debilitating pain and loss of functional movement in patients. Dry needling is a minimally invasive procedure that has shown to be useful in the treatment of myofascial trigger points when used with other forms of treatment. However, the literature surrounding dry needling and myofascial trigger points in patients with low back pain is lacking. The guiding systematic review and meta-analysis sought to analyze the effectiveness of dry needling for patients with low back pain. The review utilized eight databases for randomized controlled trials and selected 11 of 784 articles for analysis based on inclusion and exclusion criteria. A 6-subgroup meta-analysis was conducted on these studies, and 6 of the 11 studies were found to have high risk of bias. The included studies used both pain measurements and functional measurements including the visual analogue scale (VAS), Oswestry Disability Index (ODI), and the Roland-Morris Disability Questionnaire (RDQ). The studies did not include objective functional measurements. Overall researchers found a clinically meaningful decrease in outcome scores in the short-term, but there were no significant differences in pain or functional outcomes through long-term follow-up. This seems to correlate with the current literature on dry needling and its inflammatory effects on the body, suggesting that dry needling alone does not provide any long-term effect on myofascial trigger points in patients with low back pain. Dry needling should be combined with other treatments and high-quality rehabilitation to provide longer-lasting results and better treatment outcomes for patients with low back pain.

Osteonecrosis of the femoral head (ONFH) is an intractable disease occurring at a relatively young age. The characteristic finding of ONFH – the femoral head collapse with severe hip pain – is observed in many cases, which frequently leads to further joint destruction, requiring surgical treatment. Among the associated factors of ONFH, majority of patients who require high-dose corticosteroid are still challenging due to inevitable therapeutic option regardless of poor prognosis. As a pathological mechanism, ONFH is defined as tissue necrosis in the femoral head region due to occlusion of the nutrient vessels; but the detailed micro-level processes leading to blood flow failure remains unclear. The elucidation of ONFH and the establishment of preventive therapy is desirable for these patients. Here, we discuss the etiology and pathogenesis of corticosteroid-associated ONFH by reviewing current literature.

Significance: Osteonecrosis (ON) is characterized by bone tissue death due to disturbance of the nutrient artery. The detailed process leading to the necrotic changes has not been fully elucidated....

Ankylosierte Zahne sind eine grose Herausforderung im Rahmen einer kieferorthopadischen Behandlung. Neben der Extraktion, der Transplantation, dem konventionellen Einordnungsversuch nach Lockerung, sowie der ossaren Distraktion stellt die parodontale Distraktion (PDL-Distraktion) eine sehr effektive Methode zur Einordnung ankylosierter Zahne dar. Auch bei unsicherer langfristiger Prognose von Zahnen mit Defekten kann mittels PDL-Distraktion Knochen sowie Weichgewebe in der oft defizitaren Region generiert werden. Neue CAD-CAM-Techniken wie Insertionsguides und Metalldruck mittels Lasersintering optimieren das Verfahren der PDL-Distraktion. Ankylosed teeth are a major challenge in orthodontic treatment. In addition to extraction, transplantation, conventional alignment after tooth loosening, and osseous distraction, periodontal distraction (PDL distraction) is a very effective method for aligning ankylosed teeth. Even when the long-term prognosis of deficient teeth is uncertain, PDL distraction can be used to generate bone as well as soft tissue in the often deficient region. New CAD-CAM techniques such as insertion guides and metal printing by laser sintering optimize the PDL distraction procedure.

Background: Syrian refugees and asylum seekers (SRAs) face multiple stressors after flight, which may vary due to different geographic, economic, cultural and socio-political contexts in the host countries. Past research has recognised the importance of participants’ own perspectives. The aims of this multi-country study were to identify and compare self-reported problems of SRAs between various settings. Methods: a semi-structured client-generated outcome measurement was used to collect data among adult SRAs in Jordan (N = 61), Turkey (N = 46) and Switzerland (N = 57) between September 2018 and November 2019. Answers were analysed following thematic analysis. Results: over half of the participants reported practical problems with an emphasis on camp-related problems (Jordan), finances (Turkey), employment (Jordan and Switzerland) and government regulations (Switzerland), followed by psychological, and social issues. Conclusion: this study highlights the impact of local contextual factors on wellbeing. The findings emphasise that planning preventative procedures and mental health care services for SRAs need to consider local challenges affecting the population in specific countries., Swiss State Secretariat for Education, Research and Innovation (SERI); National Health and Medical Research Council-European Union Grant; European Union (EU); Horizon 2020; Research and Innovation Pro Innovation Programme Societal Challenges

BACKGROUND Acute respiratory failure is among the sequelae of complications that can develop in response to severe sepsis. Research into sepsis-related respiratory failure has focused on ARDS and invasive mechanical ventilation. We studied the factors associated with success and failure of noninvasive ventilation (NIV) in the treatment of sepsis-related acute respiratory failure. METHODS This retrospective study included 136 subjects with a diagnosis of acute respiratory failure and intrapulmonary or extrapulmonary sepsis who were placed on NIV. Subjects were divided into 2 groups based on the need for intubation from NIV: NIV failure (n = 70) and NIV success (n = 66). Demographic, clinical, and outcome data were collected and compared between groups, with the development of multivariate models to predict NIV failure and mortality. RESULTS The overall NIV failure rate in subjects with a diagnosis of sepsis was 51%. There were no between-group differences in demographic or baseline characteristics. However, there were significant differences in clinical variables, with higher SOFA scores (NIV failure: 6.4 [± 3.0] vs NIV success: 4.9 [± 2.1]; P = .002), 2nd lactate levels (NIV failure: 2.6 [1.7 - 4.3] vs NIV success: 1.9 [1.4 - 2.6] mmol/L; P = .007), and initial NIV [Formula: see text] settings (NIV failure: 0.50 [0.40 - 0.70] vs NIV failure: 0.40 [0.35 - 0.50]; P = .003) in subjects who failed NIV. There were also more subjects in the NIV failure group who had a lactate ≥ 4 mmol/L prior to NIV start compared to those who succeeded on NIV (33% vs 15%, P = .02). At NIV start, subjects in the NIV failure group had lower mean arterial pressure (85 mm Hg [IQR 74-96] vs 91.7 mm Hg [IQR 78-108], P = .042) and Glasgow coma scale scores (14 [IQR 13-15] vs 15 [IQR 14-15], P < .002), while fewer subjects in the NIV failure group received a fluid bolus in the 24 h prior to NIV start (33% vs 53%, P = .02) or had signs of volume overload (36% vs 64%, P < .001). Multivariate analysis indicated that age (odds ratio 1.05 [95% CI 1.01-1.09], P = .02), SOFA score (odds ratio 1.49 [95% CI 1.15-1.94], P = .002), first systolic blood pressure (odds ratio 0.97 [95% CI 0.95-0.99], P = .02), signs of volume overload (odds ratio 0.23 [95% CI 0.07-0.68], P = .008], fluids prior to NIV (odds ratio 0.08 [95% CI 0.02-0.31], P < .001), and initial [Formula: see text] on NIV (odds ratio 1.04 [95% CI 1.01-1.08, P = .002) independently predicted NIV failure with an area under the curve of 0.88. Only NIV failure independently predicted death in multivariate analysis (area under the curve = 0.70). CONCLUSIONS NIV failure in sepsis-related acute respiratory failure was independently predicted by patient acuity, first systolic blood pressure after sepsis alert, initial [Formula: see text] settings on NIV, fluid resuscitation, and signs of volume overload. However, only NIV failure independently predicted death in this cohort of subjects.

Purpose: To evaluate the microsphere outflow dynamics and residual Ho-166 activity during and after transarterial radioembolization planning and treatment procedures, and to assess the distribution and predilection sites of residual activity in the proprietary delivery set and the microcatheter. Materials and Methods: Fifteen planning and 12 therapeutic radioembolization procedures were performed with poly-l-lactic acid microspheres loaded with Ho-166. The amount and distribution of residual activity was assessed by dose calibrator measurements and SPECT imaging. The activity flow profile from the microcatheter was assessed dynamically. For planning procedures, different injection methods were evaluated in order to attempt to decrease the residual activity. Results: The median residual activities for planning and treatment procedures using standard injection methods were 31.2% (range 17.3%–44.1%) and 4.3% (range 3.5%–6.9%), respectively. Planning residual activities could be decreased significantly with 2 injection methods similar to treatment procedures, to 17.5% and 10.9%, respectively ( P = 0.002). Main predilection sites of residual microspheres were the 3-way stopcock and the outflow needle connector. During treatment procedures, more than 80% of the injected activity is transferred during the first 3 injection cycles. Conclusion: After treatment procedures with holmium-loaded microspheres, mean residual activity in the delivery set is reproducibly low and between reported values for glass and resin microspheres. The majority of microspheres is transferred to the patient during the second and third injection cycle. An estimated residual waste of 3% to 4% may be included in the treatment activity calculation. For planning procedures, a modified injection technique should be used to avoid high residual activities.

Extreme-ultraviolet (XUV) sources including high-harmonic generation (HHG), free-electron lasers (FELs), soft-X-ray lasers and laser-driven plasmas are widely used for applications ranging from femtochemistry and attosecond science to coherent diffractive imaging and EUV (or XUV) lithography. The bandwidth of the XUV light emitted by these sources reflects the XUV generation process used. Whereas light from soft-X-ray lasers1 and seeded XUV FELs2 typically has a relatively narrow bandwidth, plasma sources and HHG sources often emit broadband XUV pulses3. Since these characteristic properties of a given source impose limitations on applications, techniques enabling modification of the bandwidth are highly desirable. Here we introduce a concept for efficient spectral compression by four-wave mixing (FWM), exploiting a phase-matching scheme based on closely-spaced resonances. We demonstrate the compression of broadband radiation in the 145–130 nm wavelength range into a narrow-bandwidth XUV pulse at 100.3 nm wavelength in the presence of a broadband near-infrared (NIR) pulse in a krypton gas jet. Our concept provides new possibilities for tailoring the spectral bandwidth of XUV beams. Through a dense krypton gas jet in the presence of a broadband near-infrared pulse, spectral compression of broadband XUV radiation between 145 and 130 nm wavelengths into a narrow-bandwidth XUV pulse at 100.3 nm wavelength by four-wave mixing is demonstrated.

GOAL The aim was to assess proactive specialized inflammatory bowel diseases (IBD) emergency department (ED) consultation and multidisciplinary IBD team (IBD-MDT) intervention on IBD-related patient outcomes after discharge. BACKGROUND Despite advances in patient care, IBD-related ED visits have increased and substantially contribute to the IBD burden. METHODS Consecutive patients with IBD (below 50 y) who visited the ED during November 2017 to April 2018 (intervention group) were compared with patients with IBD that visited the same ED during 2014 to 2017 (standard-care group). The primary outcomes were hospitalization and ED revisits at 30, 90, and 180 days. RESULTS The intervention group (45 patients, mean age 32.43±8.6 y, 57.8% male) and the standard-care group (237 patients) had comparable baseline characteristics, including age, sex, and IBD type, and similar rates of hospital admissions from the ED (46.7% vs. 38.8%, P=0.32). The intervention group more frequently underwent computed tomography (40% vs. 8%, P

Purpose Cardiovascular regulation during exercise, described using time series analysis, is expected to be attenuated after bed rest (BR) and this effect will be dampened by a reactive jumps countermeasure. Methods Twenty subjects (29 ± 6 years, 23.6 ± 1.7 kg m−2) were tested on a cycle ergometer 9 days (BDC-9) before the beginning of BR as well as 2 (R + 2) and 13 days (R + 13) after the end of BR, applying moderate pseudo-random binary (PRBS) work rate changes. Heart rate (HR) and mean arterial blood pressure (mBP) were measured beat-to-beat and interpolated to 1 s intervals. HR and mBP were cross-correlated [CCF(HR-mBP)] during the PRBS. Eleven subjects participated in a reactive jump countermeasure (JUMP) during the BR period, the other part of the group served as control group (CTRL). Results In the CTRL group, significantly lower CCF(HR-mBP) values during BDC-9 were observed compared to R + 2 during the lags 20–25 s and significantly higher values during the lags − 39 s to − 35 s. In the JUMP group, significantly lower CCFs were only observed at R + 2 compared with BDC-9 during the lags 23 s and 24 s, whereas the CCFs for BDC-9 were significantly higher at several lags compared with R + 13. Conclusion Attenuations in the regulation of the cardiovascular system during cycling exercise after BR were found in the CTRL group of the RSL study. Cardiovascular regulation in the JUMP group was improved compared to values before the beginning of BR, suggesting the effectiveness of the reactive jumps countermeasure to mitigate the deleterious effects of prolonged BR.

Early detection of ovarian cancer remains an important unmet medical need. Effective screening could reduce mortality by 10%–30%. Used individually, neither serum CA125 nor transvaginal sonography (TVS) is sufficiently sensitive or specific. Two-stage strategies have proven more effective, where a significant rise above a woman's baseline CA125 prompts TVS and an abnormal sonogram prompts surgery. Two major screening trials have documented that this strategy has adequate specificity, but sensitivity for early-stage (I–II) disease must improve to have a greater impact on mortality. To improve the first stage, different panels of protein biomarkers have detected cases missed by CA125. Autoantibodies against TP53 have detected 20% of early-stage ovarian cancers 8 months before elevation of CA125 and 22 months before clinical diagnosis. Panels of autoantibodies and antigen–autoantibody complexes are being evaluated with the goal of detecting >90% of early-stage ovarian cancers, alone or in combination with CA125, while maintaining 98% specificity in control subjects. Other biomarkers, including micro-RNAs, ctDNA, methylated DNA, and combinations of ctDNA alterations, are being tested to provide an optimal first-stage test. New technologies are also being developed with greater sensitivity than TVS to image small volumes of tumor. See all articles in this CEBP Focus section, “NCI Early Detection Research Network: Making Cancer Detection Possible.”

Greater than 80% of all cancer cases are carcinomas, formed by the malignant transformation of epithelial cells. One of the key features of epithelial tumors is the presence of intercellular junctions, which link cells to one another and act as barriers to the penetration of molecules. This study assessed the expression of desmoglein-2, an epithelial junction protein, as a prognostic and diagnostic biomarker for ovarian cancer. Ovarian cancer sections were stained for DSG2 and signal intensity was correlated to cancer type and grade. DSG2 immunohistochemistry signals and mRNA levels were analyzed in chemo-resistant and chemo-sensitive cases. Ovarian cancer patient serum levels of shed DSG2 were correlated to disease-free and overall survival. Primary ovarian cancer cells were used to study DSG2 levels as they changed in response to cisplatin treatment. DSG2 expression was found to be positively correlated with cancer grade. Ovarian cancer patients with high serum levels of shed DSG2 fared significantly worse in both progression-free survival (median survival of 16 months vs. 26 months, p = .0023) and general survival (median survival of 37 months vs. undefined, p

Purpose To evaluate the microsphere flow dynamics and residual yttrium-90 (90Y) activity during and after transarterial radioembolization with glass microspheres and to assess the distribution and predilection sites of residual activity in the administration devices. Materials and Methods In this laboratory investigation, after 18 consecutive clinical transarterial radioembolization and 4 ex vivo experimental procedures with 90Y glass microspheres, the distribution of residual activity in the administration devices was assessed by activimeter and positron emission tomography (PET)/CT measurements. During ex vivo procedures, microsphere outflow from the administration device was assessed by dynamic scintigraphic measurements. Results Mean residual activity was 3.4% ± 1.7 (range, 0.9%–8.8%). Calculations showed a negative correlation between relative residual activity and prescribed activity (r = −0.4258, P = .0486) and a positive correlation between absolute residual activity and prescribed activity (r = 0.5345, P = .0104). The main predilection site was the Luer-Lok microcatheter connector. Lower activities were detected in the dose vial. Flow measurements showed that more than 98% of the final injected activity was transferred to the patient with the first 20 mL of saline solution. Conclusions Residual activity in the standard administration device for glass microsphere radioembolization is considered to be low compared with similar procedures, but is variable. The microsphere flow profile shows an initial peak, resulting in a rapid activity transfer at the beginning of the injection process. The findings may have implications for safe handling of the administration device and for dose calculation of 90Y glass microspheres.

Background and Purpose: Intracranial dural arteriovenous fistulas (DAVFs) are abnormal shunts between dural arteries and dural venous sinus or cortical veins. We report our experience with endovascular therapy of primary complex DAVFs using modern embolic agents. Methods: This is a retrospective analysis of patients with DAVFs treated between 2015 and 2019. Patient demographics and technical aspects including the use of embolic agent, access to the fistula, number of treatments, occlusion rates, and complications were addressed. Angiographic treatment success was defined as complete occlusion (CO) of the DAVF. Results: Fifty patients were treated endovascularly. Median age was 61 years and 66% were men. The most common symptom was pulsatile tinnitus in 17 patients (34%). The most frequent location of the DAVF was the transverse-sigmoid sinus (40%). Thirty-six fistulas (72%) had cortical venous reflux. Nonadhesive and adhesive liquid agents were used in 92% as a single material or in combination. CO was achieved in 48 patients (96%). In 28 individuals (56%), only 1 procedure was necessary. Nonadhesive liquid agents were exclusively used in 14 patients (28%) with CO attained in every case. For CO of tentorial DAVFs, multiple sessions were more often required than at the other locations (55 vs. 14%, p = 0.0051). Among 93 procedures, the overall complication rate was 3%. The procedure-related mortality rate was 0%. Conclusion: Endovascular treatment of intracranial DAVFs is feasible, safe, and effective with high rates of CO. In more than half of the patients, the DAVF was completely occluded after a single procedure. However, in tentorial DAVFs, multiple sessions were more often required.

A variety of dietary nonalcoholic steatohepatitis (NASH) mouse models are available, and choosing the appropriate mouse model is one of the most important steps in the design of NASH studies. In addition to the histopathological and metabolic findings of NASH, a sufficient mouse model should guarantee a robust clinical status and good animal welfare. Three different NASH diets, a high-fat diet (HFD60), a western diet (WD), and a cafeteria diet (CAFD), were fed for 12 or 16 weeks. Metabolic assessment was conducted at baseline and before scheduled sacrifice, and liver inflammation was analyzed via fluorescence-associated cell sorting and histopathological examination. Clinical health conditions were scored weekly to assess the impact on animal welfare. The HFD60 and WD were identified as suitable NASH mouse models without a significant strain on animal welfare. Furthermore, the progression of inflammation and liver fibrosis was associated with a decreased proportion of CD3+ NK1.1+ cells. The WD represents a model of advanced-stage NASH, and the HFD60 is a strong model of nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome. However, the CAFD should not be considered a NASH model.

Background There is no consensus regarding the best route of intranasal delivery of corticosteroids in the treatment of chronic rhinosinusitis (CRS). The study objective of this work was to compare the impact of mometasone furoate nasal spray (MFNS) vs mometasone nasal irrigation in the management of CRS patients who have not undergone sinus surgery. Methods A double-blind, placebo-controlled, randomized clinical trial was conducted in adults with CRS. Individuals with nasal polyps and/or history of sinus surgery were excluded. Patients were randomized to receive 8 weeks of either MFNS or mometasone nasal irrigation. The primary outcome measure was change in the 22-item Sino-Nasal Outcome Test (SNOT-22) score between the 2 groups. Secondary outcome measures included patient global response to treatment and Lund-Kennedy endoscopy scores. Results A total of 43 participants completed the study (n = 22, MFNS; n = 21,mometasone nasal irrigation). Fourteen (64%) participants in the MFNS group and 17 (81%) in the mometasone lavage group had a clinically meaningful improvement in SNOT-22 scores with a proportion difference of 17% (95% confidence interval [CI], -9% to 44%). The least-squares (LS) mean difference between the 2 groups for SNOT-22 was -8.6 (95% CI, -17.7 to 0.58; p = 0.07), whereas the LS mean difference between the 2 groups for Lund-Kennedy endoscopy scores was 0.16 (95% CI, -0.84 to 1.15; p = 0.75). No adverse events were associated with the study. Conclusion Both MFNS and mometasone nasal irrigations are beneficial in symptom management of CRS. Our study suggests that patients who perform mometasone lavage do better in a clinically meaningful way, but our results are not definitive and further studies are warranted.

OBJECTIVE. The aim of this study was to evaluate the amount of free radioactivity in renal and intestinal excretions during the first 48 hours after transarterial radioembolization (TARE) procedure...

Background The Association Research Circulation Osseous (ARCO) presents the 2019 revised staging system of osteonecrosis of the femoral head (ONFH) based on the 1994 ARCO classification. Methods In October 2018, ARCO established a task force to revise the staging system of ONFH. The task force involved 29 experts who used a web-based survey for international collaboration. Content validity ratios for each answer were calculated to identify the levels of agreement. For the rating queries, a consensus was defined when more than 70% of the panel members scored a 4 or 5 rating on a 5-point scale. Results Response rates were 93.1%-100%, and through the 4-round Delphi study, the 1994 ARCO classification for ONFH was successfully revised. The final consensus resulted in the following 4-staged system: stage I—X-ray is normal, but either magnetic resonance imaging or bone scan is positive; stage II—X-ray is abnormal (subtle signs of osteosclerosis, focal osteoporosis, or cystic change in the femoral head) but without any evidence of subchondral fracture, fracture in the necrotic portion, or flattening of the femoral head; stage III—fracture in the subchondral or necrotic zone as seen on X-ray or computed tomography scans. This stage is further divided into stage IIIA (early, femoral head depression ≤2 mm) and stage IIIB (late, femoral head depression >2 mm); and stage IV—X-ray evidence of osteoarthritis with accompanying joint space narrowing, acetabular changes, and/or joint destruction. This revised staging system does not incorporate the previous subclassification or quantitation parameters, but the panels agreed on the future development of a separate grading system for predicting disease progression. Conclusion A staging system has been developed to revise the 1994 ARCO classification for ONFH by an expert panel-based Delphi survey. ARCO approved and recommends this revised system as a universal staging of ONFH.

Supra-erupted maxillary molar teeth pose a major restorative challenge when attempting to prosthetically rehabilitate a partially edentulous mandibular dental arch. Traditional approaches with conventional tooth-borne appliances usually entail undesirable side-effects, including extrusion of adjacent teeth. Temporary anchorage devices (TADs), often inserted in the alveolar process, should help to minimize this phenomenon. The interradicular placement of mini-implants positioned between the roots of the maxillary molars has a number of inherent disadvantages and limitations. The preferred site for insertion of mini-implants is the anterior palate, which ensures a low risk of failure and mini-implant fracture. The ‘Mousetrap’ appliance is comprised of two mini-implants in the anterior palate, with attached lever arms for molar intrusion and a transpalatal arch (TPA) to avoid unwanted palatal tipping of the molar to be intruded. The ‘Mini-Mousetrap’ appliance was designed as a pared-down version without a TPA. If a TPA is not used, molar movement must be closely monitored, and the line of force action may need modification in order to minimize unwanted molar tipping.

Osteonecrosis of the femoral head (ONFH) is a common and refractory disease in orthopaedic clinics. The number of patients with ONFH is increasing worldwide every year. There are an estimated 8.12 million patients with nontraumatic osteonecrosis in China alone. Treatment of nontraumatic osteonecrosis has always been a clinical challenge for orthopaedic surgeons. To further standardize diagnosis and treatment of ONFH, these guidelines provide not only basic diagnosis, treatment, and evaluation systems for ONFH but also expert advice and standards in many aspects, including epidemiology, aetiology, diagnostic criteria, pathological staging, prevention and treatment options, and postoperative rehabilitation. The aetiological factors of ONFH can currently be divided into two major categories: traumatic and nontraumatic; however, the specific pathological mechanism of ONFH is not completely clear. Currently, the staging system of ONFH formulated by the Association Research Circulation Osseous is widely used in clinical practice. Based on the changes in the intraosseous blood supply at different stages, the corresponding nonsurgical and surgical treatments are recommended, and when there are risk factors for possible ONFH, certain preventive measures to avoid the occurrence of osteonecrosis are recommended. These guidelines provide brief classification criteria and treatment regimen for osteonecrosis. Specification of the aetiology, treatment plan based on comprehensive consideration of the different stages of osteonecrosis, hip function, age, and occupation of the patients are important steps in diagnosis and developing treatment strategies. Translational potential of this article: New advances in the epidemiology, etiology, pathophysiology, imaging, diagnosis and treatment of ONFH have been renewed in this revision. This guideline can be used for reference by orthopedic professionals and researchers, and for standardized diagnosis and treatment management under the clinical guidance, which is conducive to the prevention, treatment and further research of ONFH, improving the diagnosis and treatment level, making patients' symptoms under good control, and improving their quality of life. Keywords: Diagnosis, Guideline, Osteonecrosis of the femoral head (ONFH), Treatment

Background Fecal occult blood testing (FOBT) was developed to detect microscopic bleeding caused by colorectal neoplasms. The role of FOBT in the emergency department (ED) is typically used for 5 different clinical workups: trauma, anemia, syncope, hypotension, and before the administration of systemic anticoagulants or thrombolytics. Objective We scrutinized the literature to assess the utility of FOBT for its 5 most common applications in the emergent setting. Discussion Logic and clinical evidence advocating for FOBT usage in the aforementioned situations are lacking. The test itself requires specific drug and dietary restrictions that are often violated or never met when patients present to the ED with acute pathologies. In addition, the poor sensitivity and specificity of the test in these scenarios dictate that neither a negative nor positive FOBT should change the subsequent clinical workup of patients presenting to the ED. Conclusion Clinical decision making should seldom be predicated on the results of a FOBT in the ED setting.

Volumetric quantitative analyses of bone micromorphometry changes following orthodontic tooth movements are hardly standardizable. The present study aimed at validating and applying a novel microcomputed tomography (CT)-based approach that enables the segmentation of teeth and definition of a standardized volume of interest (VOI) around the roots to assess local bone micromorphometry.The jaws of 3 untreated and 14 orthodontically treated mice (protraction of the upper right molar for 11 days with 0.5 N; untreated left upper molar) were scanned with a micro-CT. The first molars and the alveolar bone were segmented, and a standardized VOI was defined around the teeth. The bone volume per total volume (BV/TV) was assessed within the VOI, and BV/TV values were compared between contralateral sites in both untreated (method validation) and treated animals (method application).The intraclass correlation coefficient of 0.99 revealed high reliability of the method. In the untreated animals, Bland-Altman analysis confirmed comparable BV/TV fractions (mean difference: -1.93, critical difference: 1.91, Wilcoxon: p = 0.03). In the orthodontically treated animals, BV/TV values were significantly lower at the test compared to the control site (test: 33.23% ± 5.74%, control: 41.33% ± 4.91%, Wilcoxon: p 0.001).Within the limits of the study, the novel approach demonstrated the applicability to evaluate bone micromorphometry around teeth subjected to orthodontic treatment.HINTERGRUND: Volumetrische quantitative Analysen von Veränderungen der Knochenmikrostruktur nach kieferorthopädischen Zahnbewegungen sind schwer standardisierbar. Ziel der vorliegenden Studie war die Validierung und Anwendung eines neuartigen mikro-computertomographie(µ-CT)-basierten Ansatzes, der die Segmentierung von Zähnen und die Definition eines standardisierten „volume of interest“ (VOI) um die Wurzeln herum ermöglicht, um die lokale Knochenmikrostruktur zu beurteilen.Die Kiefer von 3 unbehandelten und 14 kieferorthopädisch behandelten Mäusen (Protraktion des oberen rechten Molaren für 11 Tage mit 0,5 N; unbehandelter linker oberer Molar) wurden mit einem Mikro-CT gescannt. Die ersten Molaren und der Alveolarknochen wurden segmentiert und ein standardisiertes VOI um die Zähne definiert. Das Knochenvolumen pro Gesamtvolumen (BV/TV) wurde innerhalb des VOIs bestimmt. Die BV/TV-Werte wurden zwischen den kontralateralen Seiten sowohl bei unbehandelten (Methodenvalidierung) als auch bei kieferorthopädisch behandelten Tieren (Methodenanwendung) verglichen.Der Intraklassenkorrelationskoeffizient von 0,99 zeigte eine hohe Reliabilität der Methode. Bei den unbehandelten Tieren bestätigte die Bland-Altman-Analyse vergleichbare BV/TV-Werte (mittlere Differenz: −1,93, kritische Differenz: 1,91, Wilcoxon-Test: p = 0,03). Bei den kieferorthopädisch behandelten Tieren waren die BV/TV-Werte in der Test- im Vergleich zur Kontrollgruppe signifikant niedriger (Test: 33,23 % ± 5,74 %, Kontrolle: 41,33 % ± 4,91 %, Wilcoxon-Test: p 0,001).Im Rahmen der Studie zeigte der neuartige Ansatz die Anwendbarkeit zur Bewertung der Knochenmikrostruktur um Zahnwurzeln von Molaren, die einer kieferorthopädischen Behandlung unterzogen wurden.

Introduction YLB113 is a biosimilar of the reference product (RP), etanercept, under development for treatment of patients with moderate-to-severe rheumatoid arthritis (RA) and other approved indications. A phase 3 study was conducted in Europe, Japan, and India to compare the efficacy, safety, and immunogenicity of YLB113 with the RP over a treatment period of 52 weeks. Methods Overall, 528 patients with moderate-to-severe RA receiving concomitant methotrexate were randomized to receive a once-weekly, subcutaneous dose of 50 mg YLB113 or the RP. The primary endpoint was ACR20 response rate at week 24, with similarity confirmed if the 95% confidence interval (CI) for YLB113 and the RP was within the range of − 15 to 15%. Safety and immunogenicity endpoints were assessed to week 52. Results Based on the European analysis, in the full analysis set, ACR20 response at week 24 was 83.3% and 88.5% for YLB113 and the RP, respectively. Responses were within the predefined clinical equivalence margin. The sensitivity analysis in the per protocol set revealed a similar proportion of subjects exhibiting ACR20 response at week 24 between groups, with a difference of − 5.1% (95% CI − 11.07 to 0.81). The incidence of treatment-emergent adverse events was comparable between groups, and the incidence of antidrug antibody development to week 24 favored YLB113 (0.8 vs. 8.3%). Conclusions This study demonstrated biosimilarity of YLB113 to the RP regarding efficacy, safety, and immunogenicity in patients with moderate-to-severe RA. Based on the same mechanism of action, biosimilarity could be extrapolated to other therapeutic indications approved for etanercept. Trial registration EudraCT Number: 2015-002,809-12. Electronic Supplementary Material The online version of this article (10.1007/s40744-019-00186-3) contains supplementary material, which is available to authorized users.

Transient receptor potential vanilloid family member 4 (TRPV4) transcript and protein expression increased in the urinary bladder and lumbosacral dorsal root ganglia of transgenic mice with chronic urothelial overexpression of nerve growth factor (NGF-OE). We evaluated the functional role of TRPV4 in bladder function with open-outlet cystometry, void spot assays, and natural voiding (Urovoid) assays with the TRPV4 antagonist HC-067047 (1 μM) or vehicle in NGF-OE and littermate wild-type (WT) mice. Blockade of TRPV4 at the level of the urinary bladder significantly ( P ≤ 0.01) increased the intercontraction interval (2.2-fold) and void volume (2.6-fold) and decreased nonvoiding contractions (3.0-fold) in NGF-OE mice, with lesser effects (1.3-fold increase in the intercontraction interval and 1.3-fold increase in the void volume) in WT mice. Similar effects of TRPV4 blockade on bladder function in NGF-OE mice were demonstrated with natural voiding assays. Intravesical administration of HC-067047 (1 µM) significantly ( P ≤ 0.01) reduced pelvic sensitivity in NGF-OE mice but was without effect in littermate WT mice. Blockade of urinary bladder TRPV4 or intravesical infusion of brefeldin A significantly ( P ≤ 0.01) reduced (2-fold) luminal ATP release from the urinary bladder in NGF-OE and littermate WT mice. The results of the present study suggest that TRPV4 contributes to luminal ATP release from the urinary bladder and increased voiding frequency and pelvic sensitivity in NGF-OE mice.

Health disparities in the sexual minority population may be exacerbated by the loneliness experienced due to minority stress. Using a minority stress framework, this study examined minority stress, protective variables, and mental health as correlates of loneliness in sexual minority individuals in a small metropolitan area in the southeastern United States. Participants (n = 273) were a subsample of sexual minority individuals from a broader sample of LGBTQ adults in the Central Savannah River area who completed a health needs assessment. Bivariate correlations were calculated to assess for degree of significant relationships between loneliness and barriers to health care, minority stress, and mental health. Hierarchical linear regression was conducted to examine the relative importance of the study variables' associations with loneliness. A multiple regression model found household income, assault victimization, depressive symptoms, and sense of community to be significant correlates of loneliness. Interventions to decrease loneliness in this population will need to consider these interconnected, multi-level influences.

Our goal is to overcome treatment resistance in ovarian cancer patients which occurs in most cases after an initial positive response to chemotherapy. A central resistance mechanism is the maintenance of desmoglein-2 (DSG2) positive tight junctions between malignant cells that prevents drug penetration into the tumor. We have generated JO4, a recombinant protein that binds to DSG2 resulting in the transient opening of junctions in epithelial tumors. Here we present studies toward the clinical translation of c-JO4 in combination with PEGylated liposomal doxorubicin/Doxil for ovarian cancer therapy. A manufacturing process for cGMP compliant production of JO4 was developed resulting in c-JO4. GLP toxicology studies using material from this process in DSG2 transgenic mice and cynomolgus macaques showed no treatment-related toxicities after intravenous injection at doses reaching 24 mg/kg. Multiple cycles of intravenous c-JO4 plus Doxil (four cycles, 4 weeks apart, simulating the treatment regimen in the clinical trial) elicited antibodies against c-JO4 that increased with each cycle and were accompanied by elevation of pro-inflammatory cytokines IL-6 and TNFα. Pretreatment with steroids and cyclophosphamide reduced anti-c-JO4 antibody response and blunted cytokine release. Our data indicate acceptable safety of our new treatment approach if immune reactions are monitored and counteracted with appropriate immune suppression.

BackgroundNecrotizing soft tissue infection (NSTI) is a life-threatening infection associated with high morbidity and mortality. Treatment consists of surgery and antibiotics. Many studies have addressed NSTI and its subtypes, but few have reviewed the clinical, radiological, and pathological differences between the polymicrobial and monomicrobial diseases. The objective of our study was to evaluate the clinical, radiological, and pathological features of patients with polymicrobial (NSTI I) and monomicrobial (NSTI II) infections and their association with outcome.MethodsThe cohort consisted of patients hospitalized with NSTI at a tertiary medical center in 2002–2019. The medical charts were reviewed for clinical, radiological, and pathological features. Findings were compared between patients in whom blood/tissue bacterial cultures yielded one or more than one pathological isolate. The primary clinical outcome measure of the study was all-cause mortality at 90 days. Secondary outcomes were duration of hospitalization, intensive care unit (ICU) admission, score on the LRINEC (Laboratory Risk Indicator for Necrotizing Fasciitis), and need for vasopressor treatment.ResultsA total of 81 patients met the inclusion criteria: 54 (66.6%) with monomicrobial NSTI and 27 (33.3%) with polymicrobial NSTI. There were no significant between-group differences in in-hospital and 90-day mortality. On multivariate analysis, the monomicrobial disease group had a significantly higher 90-day mortality rate in addition to higher rates of in-hospital mortality, ICU admission, and vasopressor use than the polymicrobial disease group.ConclusionOur study is the first to compare the clinical, radiological, and pathological differences between the two most common types of NSTI. The results demonstrate better prognosis for polymicrobial NSTI, with minimal ICU stay, lower mortality, and lower use of vasopressors.Level of evidencePrognostic and epidemiological, level III.

Background Tumor recurrence is the leading cause of death after liver transplantation in patients with hepatocellular carcinoma. There is an ongoing debate as to whether metabolic indices such as tumor to liver standardized uptake value ratio in 18F-fluorodeoxyglucose positron emission tomography/computed tomography of the primary tumor can identify patients outside the Milan criteria with as low recurrence rates as patients inside Milan and thus should be added to the established prognostic factors. Methods This retrospective study analyzes 103 consecutive patients who underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography before liver transplantation for hepatocellular carcinoma using data of clinical tumor registry. Primary endpoints were overall survival and 10-year cumulative recurrence rates. Results Tumor to liver standardized uptake value ratio of the primary tumor was statistically significant higher in Milan out tumors, “up-to-seven” out tumors, grade 3 tumors, α- fetoprotein level >400 ng/ml and lesions > 5cm in diameter. Factors with statistically significant influence on the 10- year overall survival in the univariate analysis were Milan, up-to-seven” criteria, number of lesions and pT-category. COX regression analysis did not show independently statistically significant factors for 10-year overall survival. Milan, “up-to-seven” criteria, grade, pV, number of lesions, size of lesion, pT-category, tumor to liver standardized uptake value ratio influenced 10-year cumulative recurrence rates statistically significant. Tumor to liver standardized uptake value ratio, grade and pT-category proved to be independently statistically significant factors for 10-year cumulative recurrence rates. Conclusions Our study suggests that tumor to liver standardized uptake value standardized uptake value ratio in 18F-fluorodeoxyglucose positron emission tomography/computed tomography is an independent prognostic factor in transplanted patients with hepatocellular carcinoma. If we focus on preoperative findings, such as tumor size, tumor number and AFP value adding the information given by TLR of 18F-FDG PET/CT allows to estimate the risk of tumor recurrence more accurate than the established classifications Milan and UTS. Therefore, it may add valuable information to other preoperative findings, such as tumor size, tumor number and AFP level.

Background In-vivo dosimetry (IVD) is a patient specific measure of quality control and safety during radiotherapy. With regard to current reporting thresholds for significant occurrences in radiotherapy defined by German regulatory authorities, the present study examines the clinical feasibility of superficial electron paramagnetic resonance (EPR) IVD of cumulative total doses applied to breast cancer patients treated with helical intensity-modulated radiotherapy (tomotherapy). Methods In total, 10 female patients with left- or right-sided breast cancer were enrolled in this prospective IVD study. Each patient received a hypofractionated whole breast irradiation. A total median dose of 42.4 Gy in 16 fractions (5 fractions per week) was prescribed to the planning target volume. The treatments were completely delivered using helical tomotherapy and daily image guidance via megavoltage CT (MVCT). For each patient, three EPR dosimeters were prepared and placed at distinct locations on the patient’s skin during the delivery of all fractions. Two dosimeters were placed next to the ipsilateral and contralateral mammilla and one dosimeter was placed ventrally to the thyroid (out-of-primary-beam). The total doses delivered to the dosimeters were readout after all fractions had been administered. The measured total dose values were compared to the planned dose values derived from the treatment planning system (TPS). Daily positional variations (displacement vectors) of the ipsilateral mammilla and of the respective dosimeter were analyzed with respect to the planned positions using the daily registered MVCT image. Results Averaged over all patients, the mean absolute dose differences between measured and planned total dose values (± standard deviation (SD)) were: 0.49 ± 0.85 Gy for the ipsilateral dosimeter, 0.17 ± 0.49 Gy for the contralateral dosimeter and -0.12 ± 0.30 Gy for the thyroid dosimeter. The mean lengths of the ipsilateral displacement vectors (± SD) averaged over all patients and fractions were: 10 ± 7 mm for the dosimeter and 8 ± 4 mm for the mammilla. Conclusion Superficial EPR IVD is suitable as additional safeguard for dose delivery during helical tomotherapy of breast cancer. Despite positional uncertainties in clinical routine, the observed dose deviations at the ipsilateral breast were on average small compared to national reporting thresholds for total dose deviations (i.e. 10%/4 Gy). EPR IVD may allow for the detection of critical dose errors during whole breast irradiations.

Altered lipid metabolism has emerged as an important feature of ovarian cancer (OC), yet the translational potential of lipid metabolites to aid in diagnosis and triage remains unproven. We conducted a multi-level interrogation of lipid metabolic phenotypes in patients with adnexal masses, integrating quantitative lipidomics profiling of plasma and ascites with publicly-available tumor transcriptome data. Using Sciex Lipidyzer, we assessed concentrations of > 500 plasma lipids in two patient cohorts—(i) a pilot set of 100 women with OC (50) or benign tumor (50), and (ii) an independent set of 118 women with malignant (60) or benign (58) adnexal mass. 249 lipid species and several lipid classes were significantly reduced in cases versus controls in both cohorts (FDR –5). Certain lipids exhibited greater alterations in early- (diacylglycerols) or late-stage (lysophospholipids) cases, and multiple lipids in plasma and ascites were positively correlated. Lipoprotein receptor gene expression differed markedly in OC versus benign tumors. Importantly, several plasma lipid species, such as DAG(16:1/18:1), improved the accuracy of CA125 in differentiating early-stage OC cases from benign controls, and conferred a 15–20% increase in specificity at 90% sensitivity in multivariate models adjusted for age and BMI. This study provides novel insight into systemic and local lipid metabolic differences between OC and benign disease, further implicating altered lipid uptake in OC biology, and advancing plasma lipid metabolites as a complementary class of circulating biomarkers for OC diagnosis and triage.

INTRODUCTION AND OBJECTIVE:The utilization of Lumenis Pulse™ 120W MOSES™ holmium laser has been associated with improved operative times for treatment of urolithiasis through retrograde ureteroscop...

Background Electric bikes (E-bikes) and powered scooters (P-scooters) have become increasingly popular modes of public transportation, but they have been associated with injuries of all kinds, including dental trauma. Helmet use is promoted as a means of reducing injuries in accidents involving motorized and unmotorized vehicles. The aim of the study was to evaluate the impact of helmet use on the number and severity of oral and maxillofacial injuries caused by E-bikes and P-scooters. Methods A retrospective cross-sectional study design was used. The cohort included all patients referred to the emergency department of a tertiary medical center in 2014–2020 with oral and maxillofacial injuries involving E-bikes or P-scooters. Data were collected from the medical files on demographics, types of injuries, circumstances of occurrence, work-up, treatment, and outcome. Use of a helmet was recorded in each case. Results Of the total 1417 patients referred to the emergency department for E-bike and P-scooter-related trauma, 62 had oral and maxillofacial injuries, including 57 riders and 5 pedestrians. All had hard- or soft-tissue injuries; 20 (32.2%) had head injuries and 22 (35.5%) had dentoalveolar injuries. Eleven riders had worn a helmet at the time of injury (17.7%). Helmet use was associated with time of injury (weekday/weekend, daytime/night-time), type of motorized vehicle (E-bike or P-scooter), head injury, and number of bone fractures. Head injuries occurred more often on the weekend (57.9%) than during the week (20.9%) and were more likely to occur in riders who were not protected by a helmet (37.3% vs 18.2%). Patients who used helmets also had a lower rate of fractured bones (18.2%) and dentoalveolar injuries (23.7%) than patients who did not (68.8 and 37.3%, respectively). Interestingly, helmet use had no protective effect on soft-tissue injuries. Conclusions Helmet use by E-bike and P-scooter riders decreased the probability of head injury and of hard tissue and dentoalveolar injuries. These results may provide guidance for effective legislation and regulation of helmet use and improved treatment protocols for general and dental physicians.

The design of a velocity map imaging (VMI) spectrometer is presented with a novel gas capillary integrated into the repeller electrode. The capillary is made of semiconductive lead glass, which replicates the electrostatic field of the VMI lenses. Thus, the target gas can be directly supplied to the interaction zone without degrading the VMI resolution. With this design, a high gas density and a large free aperture to focus long wavelength radiation into the VMI spectrometer have been achieved, which facilitates time resolved experiments with intense terahertz (THz)-light fields. The performance of the VMI spectrometer is demonstrated with momentum maps of electrons from multiphoton ionization of xenon and a first extreme ultraviolet-THz-streak experiment.

Tinnitus is a common symptom with an incidence of 4–20%. Pulsatile tinnitus represents a minor subgroup of less than 10% of all patients suffering from tinnitus. Pulsatile tinnitus – different from permanent mostly idiopathic tinnitus is mainly caused by physical sources related to vascular pathologies resulting in a change in blood volume and pressure or an alteration of the vessel lumen. Differential diagnosis for pulsatile tinnitus include dural arteriovenous fistulas, glomus tumors of the jugular foramen and the middle ear or atherosclerotic diseases of the carotid artery in the petrous or cavernous segment. Anomalies of the dural sinuses and the jugular bulb have been described as rare sources of synchronized tinnitus. The Woven EndoBridge (WEB, Microvention, Tustin, CA) is an intraaneurysmal flow diverter for the treatment of broad-based arterial aneurysms with a high safety and effectiveness profile. The initial version of the WEB with a dual layer structure evolved to a single layer structure in two different versions (WEB SL, WEB SLS). The WEB system does not require a concomitant antiplatelet therapy compared to other intraluminal devices as extra-aneurysmal flow-diverters or intracranial stents. Here we describe a case of an aneurysmatic diverticulum of the jugular bulb in a patient with ipsilateral pulsatile tinnitus treated with a WEB device.

Summary Objective This study aimed to assess oral health-related quality of life (OHRQoL) in relation to associated covariates in orthodontic patients of different age groups (children, adolescents, and adults) in a cross-sectional study. Methods A total of 898 subjects (50.6% females, 49.4% males; mean age 16.89 years) undergoing orthodontic treatment anonymously completed the German version of the Oral Health Impact Profile (OHIP-G14) to assess OHRQoL in addition to completing 23 other items. Descriptive, exploratory statistical analysis and multiple linear regression modelling were performed. Results The mean score of the OHIP-G14 was 8.3 for the 6- to 11-year olds, 8.9 for the 12- to 17-year olds, and 12.6 for adults. Physical pain (Subscale 2) was the highest factor in all groups. Additionally, a relevant factor was Subscale 3 (psychological discomfort). A linear regression model showed that, in the adolescent group, aesthetics in combination with pain had a significant negative influence on OHRQoL, whereas, in the adult group, function in combination with pain showed the same significant negative influence. Second, except for the children, fixed appliances had a significant negative effect on OHRQoL compared to removable appliances. Conclusions Our study showed that the majority of the 6- to 11-year olds and 12- to 17-year olds reported a good OHRQoL. Nevertheless, adolescents and adults who reported aesthetic/pain and function/pain problems, respectively, as reasons for orthodontic treatment showed a significant occurrence for reduced OHRQoL. Fixed appliances, in comparison with removable appliances, also resulted in a significant reduction in OHRQoL for both groups.

Updated therapeutic guidelines for inflammatory bowel disease call for effective disease assessment, early intervention, and personalized patient care using a treat-to-target (T2T) approach. The ongoing, intensive monitoring of a T2T strategy is best facilitated by a multidisciplinary team, but the increased demand on health care systems impedes implementation. Therefore, advanced practice providers have a growing role in bridging the gap between T2T recommendations and clinical practice. Advanced practice providers can effectively facilitate patient-care team communication, deliver patient education, perform in-clinic and remote monitoring of symptoms and treatment response, and assist patients with self-management.

Analysis of the structure of the fractures of opposite hinge (FOH) after angle-stable closed-wedge (CW) and open-wedge (OW) high tibial osteotomy (HTO), and their influence on the development of tibial pseudarthrosis. 187 CW and 94 OWHTOs were analyzed retrospectively. The FOHs in the OWHTO were classified according to Takeuchi, and in the CWHTO—according to the own classification with two types (depending on the direction of FOH). FOHs in both techniques were also subdivided into three subtypes according to displacement (A—non-displaced, B—primarily displaced, C—secondarily displaced). The statistical analysis included correlation analysis and logistic regression. FOHs were found in 81 (43.3%) CW and 39 (41.2%) OWHTOs. The stable type 1 fractures predominated in OWHTO (76.9 vs. 42%, p

Purpose To evaluate the infusion dynamics and residual yttrium-90 activity during and after resin microsphere radioembolization with different injection techniques and initial activities. To assess the distribution of residual activity in the administration systems to allow optimization of the procedure and the equipment. Materials and Methods In a setup similar to that in standard clinical practice, radioembolization procedures were performed ex vivo. The influence of different injection techniques was assessed by comparing pulsatile and continuous injections. The influence of the absolute amount of activity to the residual activity was assessed by comparing pulsatile 0.5-GBq- with 1.0-GBq-procedures. Continuous dose rate measurements were performed. Activity distribution was determined by positron-emission tomography (PET)/CT. Results Fifteen procedures were performed: 5 pulsatile 0.5-GBq-, 5 continuous 0.5-GBq-, and 5 pulsatile 1.0-GBq-procedures. Mean residual activity was 4.0% ± 1.7% (range 1.2%–6.6%), without statistically significant differences between injection techniques (P = .841) or between prescribed activities (P = .222). Dose-rate measurements revealed an exponential decrease of the activities in the vials with high variability. Activity fell rapidly to 32% ± 7.9% (range 23%–55%) after injection of 4 of 20 mL 5% dextrose solution. Residual activity accumulations were identified at the 3-way stopcock (100% of procedures), in the C-line (80%), at the microcatheter connector (20%), and in the A-line (6.7%), but not in the vials. Conclusions Residual activity in a commercial administration system for resin microsphere radioembolization is variable and does not systematically depend on initial yttrium-90 activity or on injection technique. Predilection sites for residual activity were identified, which should receive special attention when performing resin transarterial radioembolization procedures, and for further administration system developments.

Adoptive T-cell therapy using high-affinity T-cell receptors (TCR) to target tumor antigens has potential for improving outcomes in high-grade serous ovarian cancer (HGSOC) patients. Ovarian tumors develop a hostile, multicomponent tumor microenvironment containing suppressive cells, inhibitory ligands, and soluble factors that facilitate evasion of antitumor immune responses. Developing and validating an immunocompetent mouse model of metastatic ovarian cancer that shares antigenic and immunosuppressive qualities of human disease would facilitate establishing effective T-cell therapies. We used deep transcriptome profiling and IHC analysis of human HGSOC tumors and disseminated mouse ID8VEGF tumors to compare immunologic features. We then evaluated the ability of CD8 T cells engineered to express a high-affinity TCR specific for mesothelin, an ovarian cancer antigen, to infiltrate advanced ID8VEGF murine ovarian tumors and control tumor growth. Human CD8 T cells engineered to target mesothelin were also evaluated for ability to kill HLA-A2+ HGSOC lines. IHC and gene-expression profiling revealed striking similarities between tumors of both species, including processing/presentation of a leading candidate target antigen, suppressive immune cell infiltration, and expression of molecules that inhibit T-cell function. Engineered T cells targeting mesothelin infiltrated mouse tumors but became progressively dysfunctional and failed to persist. Treatment with repeated doses of T cells maintained functional activity, significantly prolonging survival of mice harboring late-stage disease at treatment onset. Human CD8 T cells engineered to target mesothelin were tumoricidal for three HGSOC lines. Treatment with engineered T cells may have clinical applicability in patients with advanced-stage HGSOC.

SIRT is an established treatment option for liver malignancies. Metabolic information can provide additional knowledge about tumoral characteristics and treatment response. FDG-PET/CT was shown to be advantageous for pre-/post-SIRT evaluation. However, whole-body PET/CT is an elaborate procedure. The aim of the study was to optimize clinical efficacy assessment after SIRT with a low-dose, low-cost protocol for focused diagnostic work-up. An abdomen-only minimal-activity FDG-PET/CT protocol (MA-PET) was established as an alternative for clinically indicated whole-body PET/CT scans. After administering 40 MBq of F-18-FDG one bed position was scanned for 15 minutes. Scans were acquired before (initial scan), one month after (interim scan) and three months after SIRT (follow-up scan). Metabolic tumor activity was evaluated and was compared to standard CT follow-up results. 50 lobar SIRT procedures in 37 patients were analysed. HCC (28), hepatic metastases (15) and CCC (7) were treated. In 18 liver lobes initial MA-PET did not show hypermetabolic lesions, 32 liver lobes underwent interim and follow-up MA-PET. All 114 MA-PET were technically feasible. Mean radiation dose was 1.9 mSv. 64 % of HCC presented low metabolism at baseline, whereas metastases and CCC were all clearly PET-positive. Majority of radiated liver tumors showed at least partial metabolic response. PET/CT results diverged from follow-up CT in 63 % of cases. Minimal-Activity FDG-PET/CT of the liver is a feasible tool for efficacy assessment after SIRT with low financial and radiation burden. It provides additional information to morphologic imaging modalities, which can be helpful in response appraisal and treatment planning.ZIEL: Die FDG-PET/CT erwies sich im Rahmen der SIRT als gewinnbringend für die prä- und posttherapeutische Diagnostik. Dennoch wird diese aufgrund des hohen Aufwands häufig nicht angewendet. Ziel unserer Untersuchung war die Optimierung der Therapiekontrolle nach SIRT mittels eines fokussierten, kostensparenden Niedrigdosis-PET-Protokolls. Ein Oberbauch-zentriertes, Minimal-Aktivitäts-FDG-PET/CT-Protokoll (MA-PET) wurde für klinisch indizierte Untersuchungen etabliert. Nach Injektion von 40 MBq F-18-FDG wurde eine Bettposition über 15 Minuten akquiriert. Die MA-PET wurden einen Tag vor, einen Monat nach und drei Monate nach SIRT durchgeführt. Das metabolische Therapieansprechen wurde ermittelt und mit der CT-Verlaufskontrolle verglichen. 50 lobäre SIRT-Prozeduren, darunter 28 HCC, 15 hepatische Metastasen und 7 CCC, wurden betrachtet. Von 37 eingeschlossenen Patienten erhielten 13 eine zusätzliche SIRT der Gegenseite. Alle Metastasen und CCC waren PET-positiv, 64 % der HCC hingegen initial PET-negativ. 32 Leberlappen mit initial hypermetabolen Läsionen wurden mittels MA-PET verlaufskontrolliert. Alle 114 MA-PET waren technisch durchführbar. Die mittlere Strahlenbelastung pro Untersuchung lag bei 1,9 mSv. Die Mehrheit der Lebertumoren zeigte mindestens ein partielles Therapieansprechen, wobei sich die MA-PET-Ergebnisse in 63 % der Fälle von denen der Standard-CT unterschieden. MA-PET der Leber ist ein zuverlässiges und geeignetes Verfahren zur Beurteilung der SIRT-Wirksamkeit, mit welchem Strahlenbelastung und Kosten eingespart werden können. Im Vergleich zur morphologischen Bildgebung werden auch mit dem neu etablierten Protokoll zusätzliche Informationen gewonnen, die für Verlaufskontrolle und Therapieplanung nützlich sein können.