Cardiac MRI in Patients with Prolonged Cardiorespiratory Symptoms after Mild to Moderate COVID-19.

Background Myocardial injury and inflammation at cardiac MRI in patients with COVID-19 have been described in recent publications. Concurrently, a chronic COVID-19 syndrome (CCS) after SARS-CoV-2 infection has been observed and manifests with symptoms such as fatigue and exertional dyspnea. Purpose To explore the relationship between CCS and myocardial injury and inflammation as an underlying cause of the persistent complaints in previously healthy individuals. Materials and Methods In this prospective study from January 2021 to April 2021, study participants without known cardiac or pulmonary diseases prior to SARS-CoV-2 infection who had persistent CCS symptoms such as fatigue or exertional dyspnea after convalescence and healthy control participants underwent cardiac MRI. The cardiac MRI protocol included evaluating the T1 and T2 relaxation times, extracellular volume, T2 signal intensity ratio, and late gadolinium enhancement (LGE). Student t tests, Mann-Whitney U tests, and χ2 tests were used for statistical analysis. Results Forty-one participants with CCS (mean age, 39 years ± 13 [standard deviation]; 18 men) and 42 control participants (mean age, 39 years ± 16; 26 men) were evaluated. The median time between the initial incidence of mild to moderate COVID-19 not requiring hospitalization and undergoing cardiac MRI was 103 days (interquartile range, 88-158 days). Troponin T levels were normal. Parameters indicating myocardial inflammation and edema were comparable between participants with CCS and control participants (T1 relaxation times: 978 msec ± 23 vs 971 msec ± 25 [P = .17]; T2 relaxation times: 53 msec ± 2 vs 52 msec ± 2 [P = .47]; T2 signal intensity ratios: 1.6 ± 0.2 vs 1.6 ± 0.3 [P = .10]). Visible myocardial edema was present in none of the participants. Three of 41 (7%) participants with CCS demonstrated nonischemic LGE, whereas no participants in the control group demonstrated nonischemic LGE (0 of 42 [0%]; P = .07). None of the participants fulfilled the 2018 Lake Louise criteria for the diagnosis of myocarditis. Conclusion Individuals with chronic COVID-19 syndrome who did not undergo hospitalization for COVID-19 did not demonstrate signs of active myocardial injury or inflammation at cardiac MRI. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lima and Bluemke in this issue.

Thermal effects of various drill materials during implant site preparation-Ceramic vs. stainless steel drills: A comparative in vitro study in a standardised bovine bone model.

OBJECTIVES: The aim of this study was to evaluate thermal effects of ceramic and metal implant drills during implant site preparation using a standardised bovine model. MATERIAL AND METHODS: A total of 320 automated intermittent osteotomies of 10- and 16-mm drilling depths were performed using zirconium dioxide-based and stainless steel drills. Various drill diameters (2.0/ 2.2, 2.8, 3.5, 4.2 mm ∅) and different cooling methods (without/ with external saline irrigation) were investigated at room temperature (21 ± 1°C). Temperature changes were recorded in real time using two custom-built multichannel thermoprobes in 1- and 2-mm distance to the osteotomy site. For comparisons, a linear mixed model was estimated. RESULTS: Comparing thermal effects, significantly lower temperatures could be detected with steel-based drills in various drill diameters, regardless of drilling depth or irrigation method. Recorded temperatures for metal drills of all diameters and drilling depths using external irrigation were below the defined critical temperature threshold of 47°C, whereas ceramic drills of smaller diameters reached or exceeded the harmful temperature threshold at 16-mm drilling depths, regardless of whether irrigation was applied or not. The results of this study suggest that the highest temperature changes were not found at the deepest point of the osteotomy site but were observed at subcortical and deeper layers of bone, depending on drill material, drill diameter, drilling depth and irrigation method. CONCLUSIONS: This standardised investigation revealed drill material and geometry to have a substantial impact on heat generation, as well as external irrigation, drilling depth and drill diameter.

Guided Lateral Sinus Lift Procedure Using 3-Dimensionally Printed Templates for a Safe Surgical Approach: A Proof-of-Concept Case Report.

The purpose of this article was to present a guided lateral window sinus lift procedure with the aid of a fully digital workflow using surgical templates for window osteotomy preparation and implant placement. A 22-year-old patient with insufficient residual bone height in the posterior maxilla was treated with a maxillary sinus augmentation procedure with a lateral window technique and simultaneous implant installation using 3-dimensionally printed surgical guides. The surgical guides, used for the preparation of both the lateral window and the implant site according to the optimal prosthodontic and anatomic position, were based on a fully digital workflow and virtual pre-planning with modified implant-planning software. Successful functional and esthetic rehabilitation of the patient was accomplished using standard surgical techniques and instruments but an innovative method for the production and application of surgical templates ensured a precise and safe approach for the lateral window osteotomy preparation. This guided lateral window sinus lift technique may reduce the incidence of surgical complications and failures and enhance patient-related outcomes.

Myocardial maladaptation to pressure overload in CB2 receptor-deficient mice.

BACKGROUND: Adaptation to aortic valve stenosis leads to myocardial hypertrophy, which has been associated with inflammation, fibrosis and activation of the endocannabinoid system. Since the endocannabinoid system and the CB2 receptor provide cardioprotection and modulate immune response in experimental ischemia, we investigated the role of CB2 in a mouse model of cardiac pressure overload. METHODS: Transverse aortic constriction was performed in CB2 receptor-deficient (Cnr2-/-) mice and their wild-type littermates (Cnr2+/+). After echocardiography and Millar left heart catheter hemodynamic evaluation hearts were processed for histological, cellular and molecular analyses. RESULTS: The endocannabinoid system showed significantly higher anandamide production and CB2 receptor expression in Cnr2+/+ mice. Histology showed non-confluent, interstitial fibrosis with rare small areas of cardiomyocyte loss in Cnr2+/+ mice. In contrast, extensive cardiomyocyte loss and confluent scar formation were found in Cnr2-/- mice accompanied by significantly increased apoptosis and left ventricular dysfunction when compared with Cnr2+/+ mice. The underlying cardiac maladaptation in Cnr2-/- mice was associated with significantly reduced expression of myosin heavy chain isoform beta and less production of heme oxygenase-1. Cnr2-/- hearts presented after 7 days with stronger proinflammatory response including significantly higher TNF-alpha expression and macrophage density, but lower density of CD4+ and B220+ cells. At the same time, we found increased apoptosis of macrophages and adaptive immune cells. Higher myofibroblast accumulation and imbalance in MMP/TIMP-regulation indicated adverse remodeling in Cnr2-/- mice. CONCLUSIONS: Our study provides mechanistic evidence for the role of the endocannabinoid system in myocardial adaptation to pressure overload in mice. The underlying mechanisms include production of anandamide, adaptation of contractile elements and antioxidative enzymes, and selective modulation of immune cells action and apoptosis in order to prevent the loss of cardiomyocytes.

Impact of androgen deprivation therapy on apparent diffusion coefficient and T2w MRI for histogram and texture analysis with respect to focal radiotherapy of prostate cancer.

PURPOSE: Accurate prostate cancer (PCa) detection is essential for planning focal external beam radiotherapy (EBRT). While biparametric MRI (bpMRI) including T2-weighted (T2w) and diffusion-weighted images (DWI) is an accurate tool to localize PCa, its value is less clear in the case of additional androgen deprivation therapy (ADT). The aim of this study was to investigate the value of a textural feature (TF) approach on bpMRI analysis in prostate cancer patients with and without neoadjuvant ADT with respect to future dose-painting applications. METHODS: 28 PCa patients (54-80 years) with (n = 14) and without (n = 14) ADT who underwent bpMRI with T2w and DWI were analyzed retrospectively. Lesions, central gland (CG), and peripheral zone (PZ) were delineated by an experienced urogenital radiologist based on localized pre-therapeutic histopathology. Histogram parameters and 20 Haralick TF were calculated. Regional differences (i. e., tumor vs. PZ, tumor vs. CG) were analyzed for all imaging parameters. Receiver-operating characteristic (ROC) analysis was performed to measure diagnostic performance to distinguish PCa from benign prostate tissue and to identify the features with best discriminative power in both patient groups. RESULTS: The obtained sensitivities were equivalent or superior when utilizing the TF in the no-ADT group, while specificity was higher for the histogram parameters. However, in the ADT group, TF outperformed the conventional histogram parameters in both specificity and sensitivity. Rule-in and rule-out criteria for ADT patients could exclusively be defined with the aid of TF. CONCLUSIONS: The TF approach has the potential for quantitative image-assisted boost volume delineation in PCa patients even if they are undergoing neoadjuvant ADT.

Image guidance: past and future of radiotherapy.

Image guidance has been playing a decisive role throughout the history of radiotherapy, but developments in 3D-and 4D imaging data acquisition using computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) have significantly boosted the precision of conformal radiotherapy. An overarching aim of radiotherapy is conforming the treatment dose to the tumor in order to optimally limit a high radiation dose outside the target. Stereotactic, intensity modulated, and adaptive radiotherapy are all largely based on appropriately using imaging information both before and during treatment delivery using on-board imaging devices. While pretreatment imaging for planning has reached a very high level in the past two decades, the next step will be to further refine and accelerate imaging during treatment delivery, resulting in adaptation of the dose fluence during a patient's treatment in various scenarios, some of which are discussed in this article.

Impacted and transmigrated mandibular canines: an analysis of 3D radiographic imaging data.

OBJECTIVES: Impacted and transmigrated mandibular canines differ greatly in incidence, etiopathology, associated anomalies, and treatment prospects, when compared to their maxillary counterparts. The aim of this study was to provide a detailed analysis of 3D radiographic imaging data of impacted mandibular canines. MATERIALS AND METHODS: In a retrospective cross-sectional study, CT/CBCT data of 88 patients with a total of 94 impacted mandibular canines were analysed. Evaluated parameters included location, morphology, neighbouring structures, associated anomalies, the influence of those factors on mandibular canine transmigration, as well as applied treatment. RESULTS: Transmigration was found to occur in 40.4% of impacted mandibular canines. Transmigrated canines were located significantly more basally and horizontally angulated. Further, transmigration was significantly associated with a lack of contact to adjacent teeth and the canine's apex not contacting the mandibular cortical bone. The overall incidence of root resorptions of adjacent teeth related to impacted mandibular canines was 7.3% and was more likely, if the canine was lingually impacted. While about half of the non-transmigrated impacted canines were orthodontically aligned, half of the transmigrated canines were surgically removed. Monitoring was the second most applied treatment strategy for both groups, and no canines were autotransplantated. CONCLUSIONS: Root resorption of adjacent teeth and transmigration are commonly occurring phenomena related to impacted mandibular canines. CLINICAL RELEVANCE: Treatment often entails the surgical removal of the canine-especially in cases of transmigration. The findings emphasise the importance of early diagnosis and CT/CBCT imaging for further diagnostics and future research of impacted mandibular canines.

Multiple Perforations of the Sinus Floor During Maxillary Sinus Floor Augmentation to Provide Access to the Bone Marrow Space: A Technical Report.

INTRODUCTION: Sinus floor augmentation is a routinely used surgical technique for increasing the bone height/volume of the atrophic posterior maxilla. Optimal integration of the implanted augmentation material within the newly formed bone will-at least partly-depend on adequate vascularization to ensure sufficient recruitment of osteoblast and osteoclast precursor cells. METHODS: The present technical note describes a modification intended to facilitate increased blood inflow into the augmented space. After preparation of the lateral window and elevation of the Schneiderian membrane, the cortical bone of the sinus floor is perforated several times either by using a piezoelectric device or a microsurgical handpiece with the corresponding tip or bur; these perforations should extend into the trabecular bone. RESULTS AND CONCLUSION: The experiences with this modified technique after 12 patients are presented and discussed. It is expected that by means of this relatively simple technique, increased blood and cell inflow into the augmented space is achieved. This may, in turn, enhance new bone formation and improve the integration of the augmentation material.

Metallothioneins 1 and 2 Modulate Inflammation and Support Remodeling in Ischemic Cardiomyopathy in Mice.

Aims. Repetitive brief ischemia and reperfusion (I/R) is associated with left ventricular dysfunction during development of ischemic cardiomyopathy. We investigated the role of zinc-donor proteins metallothionein MT1 and MT2 in a closed-chest murine model of I/R. Methods. Daily 15-minute LAD-occlusion was performed for 1, 3, and 7 days in SV129 (WT)- and MT1/2 knockout (MT(-/-))-mice (n = 8-10/group). Hearts were examined with M-mode echocardiography and processed for histological and mRNA studies. Results. Expression of MT1/2 mRNA was transiently induced during repetitive I/R in WT-mice, accompanied by a transient inflammation, leading to interstitial fibrosis with left ventricular dysfunction without infarction. In contrast, MT(-/-)-hearts presented with enhanced apoptosis and small infarctions leading to impaired global and regional pump function. Molecular analysis revealed maladaptation of myosin heavy chain isoforms and antioxidative enzymes in MT1/2(-/-)-hearts. Despite their postponed chemokine induction we found a higher total neutrophil density and macrophage infiltration in small infarctions in MT(-/-)-hearts. Subsequently, higher expression of osteopontin 1 and tenascin C was associated with increased myofibroblast density resulting in predominately nonreversible fibrosis and adverse remodeling in MT1/2(-/-)-hearts. Conclusion. Cardioprotective effects of MT1/2 seem to be exerted via modulation of contractile elements, antioxidative enzymes, inflammatory response, and myocardial remodeling.

[Treatment planning with functional MRI]. / Strahlentherapieplanung mit der funktionellen MRT.

CLINICAL/METHODICAL ISSUE: The aim of magnetic resonance imaging (MRI) guided radiotherapy is high precision in treatment delivery. With new developments it is possible to focus the high dose irradiation on the tumor while sparing the surrounding tissue. The achievements in precision of the treatment planning and delivery warrant equally precise tumor definition. STANDARD RADIOLOGICAL METHODS: In conventional radiation therapy it is necessary to carry out a planning computed tomography (CT). For many tumors there is also need for an additional morphological MRI because of more accurate tumor definition. In standard radiotherapy the tumor volume is irradiated with a homogeneous dose. METHODICAL INNOVATIONS: The aim of functional multiparametric MRI is to visualize and quantify biological, physiological and pathological processes at the cellular and molecular levels. Based on this information it is possible to elucidate tumor biology and identify subvolumes of more aggressive behavior. They are often radiotherapy-resistant, leading to tumor recurrence thus requiring further dose escalation. The concept of inhomogeneous tumor irradiation according to its biological behavior is called dose painting. PERFORMANCE: Dose painting is technically feasible. The expected clinical benefit is motivated by selective treatment adaptations based on biological tumor characteristics. Tumors show variable response to therapy underlining the need for individual treatment plans. This approach may lead not only to higher local control but also to better sparing of normal surrounding tissue. ACHIEVEMENTS: With the clinical implementation of dose painting, improvements in the therapeutic outcome can be expected. PRACTICAL RECOMMENDATIONS: Due to the existing technical challenges, extensive collaboration between radiation oncologists, radiologists, medical physicists and radiation biologists is needed.

The endocannabinoid-CB2 receptor axis protects the ischemic heart at the early stage of cardiomyopathy.

Ischemic heart disease is associated with inflammation, interstitial fibrosis and ventricular dysfunction prior to the development of heart failure. Endocannabinoids and the cannabinoid receptor CB2 have been claimed to be involved, but their potential role in cardioprotection is not well understood. We therefore explored the role of the cannabinoid receptor CB2 during the initial phase of ischemic cardiomyopathy development prior to the onset of ventricular dysfunction or infarction. Wild type and CB2-deficient mice underwent daily brief, repetitive ischemia and reperfusion (I/R) episodes leading to ischemic cardiomyopathy. The relevance of the endocannabinoid-CB2 receptor axis was underscored by the finding that CB2 was upregulated in ischemic wild type cardiomyocytes and that anandamide level was transiently increased during I/R. CB2-deficient mice showed an increased rate of apoptosis, irreversible loss of cardiomyocytes and persistent left ventricular dysfunction 60 days after the injury, whereas wild type mice presented neither morphological nor functional defects. These defects were due to lack of cardiomyocyte protection mechanisms, as CB2-deficient hearts were in contrast to controls unable to induce switch in myosin heavy chain isoforms, antioxidative enzymes and chemokine CCL2 during repetitive I/R. In addition, a prolonged inflammatory response and adverse myocardial remodeling were found in CB2-deficient hearts because of postponed activation of the M2a macrophage subpopulation. Therefore, the endocannabinoid-CB2 receptor axis plays a key role in cardioprotection during the initial phase of ischemic cardiomyopathy development.

A novel standardized bone model for thermal evaluation of bone osteotomies with various irrigation methods.

OBJECTIVES: Based on a novel standardized bovine specimen, the aim of this study was to investigate thermal effects of different irrigation methods during intermittent and graduated drilling. MATERIAL AND METHODS: Temperature changes during implant osteotomies (n = 320) of 10 and 16 mm drilling depths with various irrigation methods were investigated on manufactured uniform bone samples providing homogenous cortical and cancellous areas and analogous thermal conductivity comparable to human bone. Automated sequences were performed with surgical twist drills of 2 mm ∅ and conical drills of 3.5, 4.3 and 5 mm ∅. Real-time recording of temperature increase was done using two custom-built multichannel thermoprobes with 14 temperature sensors at a predefined distance of 1 and 2 mm to the final osteotomy. The effects of drilling depth, drilling diameter and irrigation methods on temperature changes were investigated by a linear mixed model. RESULTS: Using this uniform bone specimen, the greatest temperature rise was observed without any coolant supply with 29.87°C, followed by external with 28.47°C and then internal with 25.86°C and combined irrigation with 25.68°C. Significant differences (P ≤ 0.0156) between drill depths of 10 vs. 16 mm could be observed with all irrigation methods evaluated. With each of the irrigation methods, significantly higher temperature changes (P < 0.0001) during osteotomies could be observed between twist drills of 2 mm ∅ and conical drills of 3.5, 4.3 and 5 mm ∅. During 10 and 16 mm drilling osteotomies, external irrigation showed significantly higher temperatures (P < 0.05) for all conical drills compared with internal or combined irrigation, respectively. Significantly lower temperatures (P < 0.05) could be detected with internal or combined irrigation for the use of conical drills with various diameters and drilling depths. CONCLUSIONS: This fully standardized bone model provides optimized comparability for the evaluation of bone osteotomies and resulting temperature changes. As regards the efficiency of the various irrigation methods, it could be demonstrated that internal and combined irrigation appears to be more beneficial than external irrigation.

Thermal effects of a combined irrigation method during implant site drilling. A standardized in vitro study using a bovine rib model.

OBJECTIVES: The purpose of this study was to evaluate the temperature changes during implant osteotomies with a combined irrigation system as compared to the commonly used external and internal irrigation under standardized conditions. MATERIAL AND METHODS: Drilling procedures were performed on VII bovine ribs using a computer-aided surgical system that ensured automated intermittent drilling cycles to simulate clinical conditions. A total of 320 drilling osteotomies were performed with twist (2 mm) and conical implant drills (3.5/4.3/5 mm) at various drilling depths (10/16 mm) and with different saline irrigation (50 ml/min) methods (without/external/internal/combined). Temperature changes were recorded in real time by two custom-built thermoprobes with 14 temperature sensors (7 sensors/thermoprobe) at defined measuring depths. RESULTS: The highest temperature increase during osteotomies was observed without any coolant irrigation (median, 8.01°C), followed by commonly used external saline irrigation (median, 2.60°C), combined irrigation (median, 1.51°C) and ultimately with internal saline irrigation (median, 1.48°C). Temperature increase with different drill diameters showed significant differences (P < 0.05) regarding drill depth, confirming drill depth and time of drilling as influencing factors of heat generation. Internal saline irrigation showed a significantly smaller temperature increase (P < 0.05) compared with combined and external irrigation. A combined irrigation procedure appears to be preferable (P < 0.05) to an external irrigation method primarily with higher osteotomy depths. CONCLUSIONS: Combined irrigation provides sufficient reduction in temperature changes during drilling, and it may be more beneficial in deeper site osteotomies. Further studies to optimize the effects of a combined irrigation are needed.

Automation of ePROMs in radiation oncology and its impact on patient response and bias.

PURPOSE: This study evaluates the impact of integrating a novel, in-house developed electronic Patient-Reported Outcome Measures (ePROMs) tool with a commercial Oncology Information System (OIS) on patient response rates and potential biases in real-world data science applications. MATERIALS AND METHODS: We designed an ePROMs tool using the NodeJS web application framework, automatically sending e-mail questionnaires to patients based on their treatment schedules in the OIS. The tool is used across various treatment sites to collect PROMs data in a real-world setting. This research examined the effects of increasing automation levels on both recruitment and response rates, as well as potential biases across different patient cohorts. Automation was implemented in three escalating levels, from telephone reminders for missing reports to minimal intervention from study nurses. RESULTS: From August 2020 to December 2023, 1,944 patients participated in the PROMs study. Our findings indicate that automating the workflows substantially reduced the patient management workload. However, higher levels of automation led to lower response rates, particularly in collecting late-phase symptoms in breast and head-and-neck cancer cohorts. Additionally, email-based PROMs introduced an age bias when recruiting new patients for the ePROMs study. Nevertheless, age was not a significant predictor of early dropout or missing symptom reports among patients participating. Notably, increased automation was significantly correlated with lower response rates in breast (p = 0.026) and head-and-neck cancer patients (p < 0.001). CONCLUSION: Integrating ePROMs within the OIS can significantly reduce workload and personnel resources. However, this efficiency may compromise patient responses in certain groups. A balance must be achieved between workload, resource allocation, and the sensitivity needed to detect clinically significant effects. This may necessitate customized automation levels tailored to specific cancer groups, highlighting a fundamental trade-off between operational efficiency and data quality.

Node-positive left-sided breast cancer: does VMAT improve treatment plan quality with respect to IMRT?

PURPOSE: The aim of the present work was to explore plan quality and dosimetric accuracy of intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) for lymph node-positive left-sided breast cancer. METHODS: VMAT and IMRT plans were generated with the Pinnacle(3) V9.0 treatment planning system for 10 lymph node-positive left-sided breast cancer patients. VMAT plans were created using a single arc and IMRT was performed with 4 beams using 6, 10, and 15 MV photon energy, respectively. Plans were evaluated both manually and automatically using ArtiView™. Dosimetric plan verification was performed with a 2D ionization chamber array placed in a full scatter phantom. RESULTS: Photon energy had no significant influence on plan quality for both VMAT and IMRT. Large variability in low doses to the heart was found due to patient anatomy (range V(5 Gy) 26.5-95 %). Slightly more normal tissue dose was found for VMAT (e.g., V(Tissue30%) = 22 %) than in IMRT (V(Tissue30%) = 18 %). The manual and ArtiView™ plan evaluation coincided very accurately for most dose metrics (difference < 1 %). In VMAT, 96.7 % of detector points passed the 3 %/3 mm gamma criterion; marginally better accuracy was found in IMRT (98.3 %). CONCLUSION: VMAT for node-positive left-sided breast cancer retains target homogeneity and coverage when compared to IMRT and allows maximum doses to organs at risk to be reduced. ArtiView™ enables fast and accurate plan evaluation.

Can treatment of pediatric Hodgkin's lymphoma be improved by PET imaging and proton therapy?

BACKGROUND AND PURPOSE: To explore a new positron emission tomography (PET)-based target concept for pediatric Hodgkin's lymphoma (PHL). PATIENTS AND METHODS: For 10 patients, the planning target volume PTV1 was based on initial CT tumor extension and PTV2 on anatomy-related PET-positive lymph node levels after chemotherapy. The treatment techniques investigated (prescribed dose 19.8 Gy) comprised opposed-field (2F), intensity-modulated photon (IMXT), and single-field (PS) proton techniques. Treatment concepts were compared concerning dose-volume histogram (DVH) parameters and organ-equivalent doses (OED). RESULTS: The median PTV1 and PTV2 were 902 ± 555 cm(3) and 281 ± 228 cm(3). When using PTV2 instead of PTV1 for all techniques, the D(2%) of the heart was reduced from 14 to 9 Gy and the D(mean) of the thyroid from 16.6 to 2.7 Gy. Low- (20%), median- (50%), and high-dose volumes (80%) were reduced by 60% for the heart and bones using PTV2. PS reduced the high-dose volume of the lungs and the heart by up to 60%. IMXT increased the low-dose volumes and OED. PTV2 reduced OED by 54 ± 10% for all organs at risk. CONCLUSION: PTV2 has a high impact on the treated volume and on sparing of organs at risk. The combination of an adaptive target volume definition with protons could contribute to future PHL treatment concepts.

Time course of late rectal- and urinary bladder side effects after MRI-guided adaptive brachytherapy for cervical cancer.

BACKGROUND AND PURPOSE: To analyze the time course of late rectal- and urinary bladder complications after brachytherapy for cervical cancer and to compare the incidence- and prevalence rates thereof. PATIENTS AND METHODS: A total of 225 patients were treated with external-beam radiotherapy (EBRT) and magnetic resonance imaging (MRI)-guided brachytherapy with or without chemotherapy. Late side effects were assessed prospectively using the Late Effects in Normal Tissue--Subjective, Objective, Management and Analytic (LENT/SOMA) scale. The parameters analyzed were time to onset, duration, actuarial incidence- (occurrence of new side effects during a defined time period) and prevalence rates (side effects existing at a defined time point). RESULTS: Median follow-up was 44 months. Side effects (grade 1-4) in rectum and bladder were present in 31 and 49 patients, 14 and 27 months (mean time to onset) after treatment, respectively. All rectal and 76 % of bladder side effects occurred within 3 years after radiotherapy. Mean duration of rectal events was 19 months; 81 % resolved within 3 years of their initial diagnosis. Mean duration of bladder side effects was 20 months; 61 % resolved within 3 years. The 3- and 5-year actuarial complication rates were 16 and 19 % in rectum and 18 and 28 % in bladder, respectively. The corresponding prevalence rates were 9 and 2 % (rectum) and 18 and 21 % (bladder), respectively. CONCLUSION: Late side effects after cervical cancer radiotherapy are partially reversible, but their time course is organ-dependent. The combined presentation of incidence- and prevalence rates provides the most comprehensive information.

Toll-like receptor 9 promotes cardiac inflammation and heart failure during polymicrobial sepsis.

BACKGROUND: Aim was to elucidate the role of toll-like receptor 9 (TLR9) in cardiac inflammation and septic heart failure in a murine model of polymicrobial sepsis. METHODS: Sepsis was induced via colon ascendens stent peritonitis (CASP) in C57BL/6 wild-type (WT) and TLR9-deficient (TLR9-D) mice. Bacterial load in the peritoneal cavity and cardiac expression of inflammatory mediators were determined at 6, 12, 18, 24, and 36 h. Eighteen hours after CASP cardiac function was monitored in vivo. Sarcomere length of isolated cardiomyocytes was measured at 0.5 to 10 Hz after incubation with heat-inactivated bacteria. RESULTS: CASP led to continuous release of bacteria into the peritoneal cavity, an increase of cytokines, and differential regulation of receptors of innate immunity in the heart. Eighteen hours after CASP WT mice developed septic heart failure characterised by reduction of end-systolic pressure, stroke volume, cardiac output, and parameters of contractility. This coincided with reduced cardiomyocyte sarcomere shortening. TLR9 deficiency resulted in significant reduction of cardiac inflammation and a sustained heart function. This was consistent with reduced mortality in TLR9-D compared to WT mice. CONCLUSIONS: In polymicrobial sepsis TLR9 signalling is pivotal to cardiac inflammation and septic heart failure.

The prevalence of root resorption of maxillary incisors caused by impacted maxillary canines.

OBJECTIVES: The aim of this study was to evaluate the prevalence of root resorption of maxillary incisors caused by impacted maxillary canines using low-dose dental computed tomography and to gain additional knowledge of the underlying aetiology and the progression of root resorption. MATERIALS AND METHODS: A total of 440 patients (mean age, 24.7 years) with 557 impacted maxillary canines were examined regarding their location and the occurrence of root resorption of maxillary incisors. RESULTS: The frequency of root resorption was 2 % of central and 7.7 % of lateral maxillary incisors. The location of the 557 impacted canines within the dental arch was palatal in 67.5 %, buccal in 15.4 % and central in 17.1 %. No significant differences could be shown with respect to the width and the shape of the dental follicle of the impacted maxillary canines and the presence of root resorption of incisors. The presence of root resorption of central (p < 0.0001) and lateral (p < 0.023) maxillary incisors was significantly correlated with an existing contact relationship of the impacted maxillary canines. CONCLUSIONS: Our investigation confirms the theory of prior reports comprising a much larger patient population, hypothesising that the dental follicle of impacted maxillary canines does not cause resorption of adjacent maxillary incisors per se. CLINICAL RELEVANCE: Root resorption of maxillary incisors is correlated with effects of contact of the impacted maxillary canines, and these findings should be considered in treatment planning. Our findings are consistent with other reports and may develop new treatment approaches for the treatment of this sequela.

Does choice change preferences? An incentivized test of the mere choice effect.

Widespread evidence from psychology and neuroscience documents that previous choices unconditionally increase the later desirability of chosen objects, even if those choices were uninformative. This is problematic for economists who use choice data to estimate latent preferences, demand functions, and social welfare. The evidence on this mere choice effect, however, exhibits serious shortcomings which prevent evaluating its possible relevance for economics. In this paper, we present a novel, parsimonious experimental design to test for the economic validity of the mere choice effect addressing these shortcomings. Our design uses well-defined, monetary lotteries, all decisions are incentivized, and we effectively randomize participants' initial choices without relying on deception. Results from a large, pre-registered online experiment find no support for the mere choice effect. Our results challenge conventional wisdom outside economics. The mere choice effect does not seem to be a concern for economics, at least in the domain of decision making under risk. Supplementary Information: The online version contains supplementary material available at 10.1007/s10683-021-09728-5.